Treatment of ARDS With Prone Positioning.

PubMed

Scholten, Eric L; Beitler, Jeremy R; Prisk, G Kim; Malhotra, Atul

2017-01-01

Prone positioning was first proposed in the 1970s as a method to improve gas exchange in ARDS. Subsequent observations of dramatic improvement in oxygenation with simple patient rotation motivated the next several decades of research. This work elucidated the physiological mechanisms underlying changes in gas exchange and respiratory mechanics with prone ventilation. However, translating physiological improvements into a clinical benefit has proved challenging; several contemporary trials showed no major clinical benefits with prone positioning. By optimizing patient selection and treatment protocols, the recent Proning Severe ARDS Patients (PROSEVA) trial demonstrated a significant mortality benefit with prone ventilation. This trial, and subsequent meta-analyses, support the role of prone positioning as an effective therapy to reduce mortality in severe ARDS, particularly when applied early with other lung-protective strategies. This review discusses the physiological principles, clinical evidence, and practical application of prone ventilation in ARDS. Copyright © 2016 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.

High-Frequency Oscillatory Ventilation Use and Severe Pediatric ARDS in the Pediatric Hematopoietic Cell Transplant Recipient.

PubMed

Rowan, Courtney M; Loomis, Ashley; McArthur, Jennifer; Smith, Lincoln S; Gertz, Shira J; Fitzgerald, Julie C; Nitu, Mara E; Moser, Elizabeth As; Hsing, Deyin D; Duncan, Christine N; Mahadeo, Kris M; Moffet, Jerelyn; Hall, Mark W; Pinos, Emily L; Tamburro, Robert F; Cheifetz, Ira M

2018-04-01

The effectiveness of high-frequency oscillatory ventilation (HFOV) in the pediatric hematopoietic cell transplant patient has not been established. We sought to identify current practice patterns of HFOV, investigate parameters during HFOV and their association with mortality, and compare the use of HFOV to conventional mechanical ventilation in severe pediatric ARDS. This is a retrospective analysis of a multi-center database of pediatric and young adult allogeneic hematopoietic cell transplant subjects requiring invasive mechanical ventilation for critical illness from 2009 through 2014. Twelve United States pediatric centers contributed data. Continuous variables were compared using a Wilcoxon rank-sum test or a Kruskal-Wallis analysis. For categorical variables, univariate analysis with logistic regression was performed. The database contains 222 patients, of which 85 subjects were managed with HFOV. Of this HFOV cohort, the overall pediatric ICU survival was 23.5% ( n = 20). HFOV survivors were transitioned to HFOV at a lower oxygenation index than nonsurvivors (25.6, interquartile range 21.1-36.8, vs 37.2, interquartile range 26.5-52.2, P = .046). Survivors were transitioned to HFOV earlier in the course of mechanical ventilation, (day 0 vs day 2, P = .002). No subject survived who was transitioned to HFOV after 1 week of invasive mechanical ventilation. We compared subjects with severe pediatric ARDS treated only with conventional mechanical ventilation versus early HFOV (within 2 d of invasive mechanical ventilation) versus late HFOV. There was a trend toward difference in survival (conventional mechanical ventilation 24%, early HFOV 30%, and late HFOV 9%, P = .08). In this large database of pediatric allogeneic hematopoietic cell transplant subjects who had acute respiratory failure requiring invasive mechanical ventilation for critical illness with severe pediatric ARDS, early use of HFOV was associated with improved survival compared to late implementation of HFOV, and the subjects had outcomes similar to those treated only with conventional mechanical ventilation. Copyright © 2018 by Daedalus Enterprises.

High-frequency oscillatory ventilation in ALI/ARDS.

PubMed

Ali, Sammy; Ferguson, Niall D

2011-07-01

In the last 2 decades, our goals for mechanical ventilatory support in patients with acute respiratory distress syndrome (ARDS) or acute lung injury (ALI) have changed dramatically. Several randomized controlled trials have built on a substantial body of preclinical work to demonstrate that the way in which we employ mechanical ventilation has an impact on important patient outcomes. Avoiding ventilator-induced lung injury (VILI) is now a major focus when clinicians are considering which ventilatory strategy to employ in patients with ALI/ARDS. Physicians are searching for methods that may further limit VILI, while still achieving adequate gas exchange. Copyright © 2011 Elsevier Inc. All rights reserved.

Contemporary ventilator management in patients with and at risk of ALI/ARDS.

PubMed

Chang, Steven Y; Dabbagh, Ousama; Gajic, Ognen; Patrawalla, Amee; Elie, Marie-Carmelle; Talmor, Daniel S; Malhotra, Atul; Adesanya, Adebola; Anderson, Harry L; Blum, James M; Park, Pauline K; Gong, Michelle Ng

2013-04-01

Ventilator practices in patients at risk for acute lung injury (ALI) and ARDS are unclear. We examined factors associated with choice of set tidal volumes (VT), and whether VT < 8 mL/kg predicted body weight (PBW) relates to the development of ALI/ARDS. We performed a secondary analysis of a multicenter cohort of adult subjects at risk of lung injury with and without ALI/ARDS at onset of invasive ventilation. Descriptive statistics were used to describe ventilator practices in specific settings and ALI/ARDS risk groups. Logistic regression analysis was used to determine the factors associated with the use of VT < 8 mL/kg PBW and the relationship of VT to ALI/ARDS development and outcome. Of 829 mechanically ventilated patients, 107 met the criteria for ALI/ARDS at time of intubation, and 161 developed ALI/ARDS after intubation (post-intubation ALI/ARDS). There was significant intercenter variability in initial ventilator settings, and in the incidence of ALI/ARDS and post-intubation ALI/ARDS. The median VT was 7.96 (IQR 7.14-8.94) mL/kg PBW in ALI/ARDS subjects, and 8.45 (IQR 7.50-9.55) mL/kg PBW in subjects without ALI/ARDS (P = .004). VT decreased from 8.40 (IQR 7.38-9.37) mL/kg PBW to 7.97 (IQR 6.90-9.23) mL/kg PBW (P < .001) in those developing post-intubation ALI/ARDS. Among subjects without ALI/ARDS, VT ≥ 8 mL/kg PBW was associated with shorter height and higher body mass index, while subjects with pneumonia were less likely to get ≥ 8 mL/kg PBW. Initial VT ≥ 8 mL/kg PBW was not associated with the post-intubation ALI/ARDS (adjusted odds ratio 1.30, 95% CI 0.74-2.29) or worse outcomes. Post-intubation ALI/ARDS subjects had mortality similar to subjects intubated with ALI/ARDS. Clinicians seem to respond to ALI/ARDS with lower initial VT. Initial VT, however, was not associated with the development of post-intubation ALI/ARDS or other outcomes.

Effect of prone positioning during mechanical ventilation on mortality among patients with acute respiratory distress syndrome: a systematic review and meta-analysis.

PubMed

Sud, Sachin; Friedrich, Jan O; Adhikari, Neill K J; Taccone, Paolo; Mancebo, Jordi; Polli, Federico; Latini, Roberto; Pesenti, Antonio; Curley, Martha A Q; Fernandez, Rafael; Chan, Ming-Cheng; Beuret, Pascal; Voggenreiter, Gregor; Sud, Maneesh; Tognoni, Gianni; Gattinoni, Luciano; Guérin, Claude

2014-07-08

Mechanical ventilation in the prone position is used to improve oxygenation and to mitigate the harmful effects of mechanical ventilation in patients with acute respiratory distress syndrome (ARDS). We sought to determine the effect of prone positioning on mortality among patients with ARDS receiving protective lung ventilation. We searched electronic databases and conference proceedings to identify relevant randomized controlled trials (RCTs) published through August 2013. We included RCTs that compared prone and supine positioning during mechanical ventilation in patients with ARDS. We assessed risk of bias and obtained data on all-cause mortality (determined at hospital discharge or, if unavailable, after longest follow-up period). We used random-effects models for the pooled analyses. We identified 11 RCTs (n=2341) that met our inclusion criteria. In the 6 trials (n=1016) that used a protective ventilation strategy with reduced tidal volumes, prone positioning significantly reduced mortality (risk ratio 0.74, 95% confidence interval 0.59-0.95; I2=29%) compared with supine positioning. The mortality benefit remained in several sensitivity analyses. The overall quality of evidence was high. The risk of bias was low in all of the trials except one, which was small. Statistical heterogeneity was low (I2<50%) for most of the clinical and physiologic outcomes. Our analysis of high-quality evidence showed that use of the prone position during mechanical ventilation improved survival among patients with ARDS who received protective lung ventilation. © 2014 Canadian Medical Association or its licensors.

Effect of prone positioning during mechanical ventilation on mortality among patients with acute respiratory distress syndrome: a systematic review and meta-analysis

PubMed Central

Sud, Sachin; Friedrich, Jan O.; Adhikari, Neill K. J.; Taccone, Paolo; Mancebo, Jordi; Polli, Federico; Latini, Roberto; Pesenti, Antonio; Curley, Martha A.Q.; Fernandez, Rafael; Chan, Ming-Cheng; Beuret, Pascal; Voggenreiter, Gregor; Sud, Maneesh; Tognoni, Gianni; Gattinoni, Luciano; Guérin, Claude

2014-01-01

Background: Mechanical ventilation in the prone position is used to improve oxygenation and to mitigate the harmful effects of mechanical ventilation in patients with acute respiratory distress syndrome (ARDS). We sought to determine the effect of prone positioning on mortality among patients with ARDS receiving protective lung ventilation. Methods: We searched electronic databases and conference proceedings to identify relevant randomized controlled trials (RCTs) published through August 2013. We included RCTs that compared prone and supine positioning during mechanical ventilation in patients with ARDS. We assessed risk of bias and obtained data on all-cause mortality (determined at hospital discharge or, if unavailable, after longest follow-up period). We used random-effects models for the pooled analyses. Results: We identified 11 RCTs (n = 2341) that met our inclusion criteria. In the 6 trials (n = 1016) that used a protective ventilation strategy with reduced tidal volumes, prone positioning significantly reduced mortality (risk ratio 0.74, 95% confidence interval 0.59–0.95; I2 = 29%) compared with supine positioning. The mortality benefit remained in several sensitivity analyses. The overall quality of evidence was high. The risk of bias was low in all of the trials except one, which was small. Statistical heterogeneity was low (I2 < 50%) for most of the clinical and physiologic outcomes. Interpretation: Our analysis of high-quality evidence showed that use of the prone position during mechanical ventilation improved survival among patients with ARDS who received protective lung ventilation. PMID:24863923

Physiology in Medicine: Understanding dynamic alveolar physiology to minimize ventilator-induced lung injury.

PubMed

Nieman, Gary F; Satalin, Josh; Kollisch-Singule, Michaela; Andrews, Penny; Aiash, Hani; Habashi, Nader M; Gatto, Louis A

2017-06-01

Acute respiratory distress syndrome (ARDS) remains a serious clinical problem with the main treatment being supportive in the form of mechanical ventilation. However, mechanical ventilation can be a double-edged sword: if set improperly, it can exacerbate the tissue damage caused by ARDS; this is known as ventilator-induced lung injury (VILI). To minimize VILI, we must understand the pathophysiologic mechanisms of tissue damage at the alveolar level. In this Physiology in Medicine paper, the dynamic physiology of alveolar inflation and deflation during mechanical ventilation will be reviewed. In addition, the pathophysiologic mechanisms of VILI will be reviewed, and this knowledge will be used to suggest an optimal mechanical breath profile (MB P : all airway pressures, volumes, flows, rates, and the duration that they are applied at both inspiration and expiration) necessary to minimize VILI. Our review suggests that the current protective ventilation strategy, known as the "open lung strategy," would be the optimal lung-protective approach. However, the viscoelastic behavior of dynamic alveolar inflation and deflation has not yet been incorporated into protective mechanical ventilation strategies. Using our knowledge of dynamic alveolar mechanics (i.e., the dynamic change in alveolar and alveolar duct size and shape during tidal ventilation) to modify the MB P so as to minimize VILI will reduce the morbidity and mortality associated with ARDS. Copyright © 2017 the American Physiological Society.

Recurrent Spontaneous Pneumothorax during the Recovery Phase of ARDS Due to H1N1 Infection.

PubMed

Bor, Canan; Demirağ, Kubilay; Uyar, Mehmet; Cankayalı, Ilkin; Moral, Ali Reşat

2013-03-01

The pregnant patients are prone to influenza A (H1N1) virus infection, which may rapidly progress to lower respiratory tract infection and subsequent respiratory failure and acute respiratory distress syndrome (ARDS). Pneumothorax might develop in ARDS under mechanical ventilation. But post-ARDS pneumothorax in spontaneously breathing patient has not been reported in the literature. We report a 31-year old pregnant woman infected with influenza A (H1N1) virus and progressed to ARDS. Mechanical ventilation with high PEEP improved patient's gas exchange parameters within 3 weeks. However spontaneous pneumothorax was developed one week after she weaned off the ventilator. After successful drainage therapy, the patient was discharged. However she re-admitted to the hospital because of a recurrent pneumothorax one week later. She was discharged in good health after being treated with negative continuous pleural aspiration for 10 days. Influenza might cause severe pulmonary infection and death. In addition to diffuse alveolar damage, sub-pleural and intrapulmonary air cysts might occur in influenza-related ARDS and may lead to spontaneous pneumothorax. This complication should always be considered during the recovery period of ARDS and a long-term close follow-up is necessary.

Respiratory system mechanics in acute respiratory distress syndrome.

PubMed

Kallet, Richard H; Katz, Jeffrey A

2003-09-01

Respiratory mechanics research is important to the advancement of ARDS management. Twenty-eight years ago, research on the effects of PEEP and VT indicated that the lungs of ARDS patients did not behave in a manner consistent with homogenously distributed lung injury. Both Suter and colleagues] and Katz and colleagues reported that oxygenation continued to improve as PEEP increased (suggesting lung recruitment), even though static Crs decreased and dead-space ventilation increased (suggesting concurrent lung overdistension). This research strongly suggested that without VT reduction, the favorable effects of PEEP on lung recruitment are offset by lung overdistension at end-inspiration. The implications of these studies were not fully appreciated at that time, in part because the concept of ventilator-associated lung injury was in its nascent state. Ten years later. Gattinoni and colleagues compared measurements of static pressure-volume curves with FRC and CT scans of the chest in ARDS. They found that although PEEP recruits collapsed (primarily dorsal) lung segments, it simultaneously causes overdistension of non-dependent, inflated lung regions. Furthermore, the specific compliance of the aerated, residually healthy lung tissue is essentially normal. The main implication of these findings is that traditional mechanical ventilation practice was injecting excessive volumes of gas into functionally small lungs. Therefore, the emblematic low static Crs measured in ARDS reflects not only surface tension phenomena and recruitment of collapsed airspaces but also overdistension of the remaining healthy lung. The studies reviewed in this article support the concept that lung injury in ARDS is heterogeneously distributed, with resulting disparate mechanical stresses, and indicate the additional complexity from alterations in chest wall mechanics. Most of these studies, however, were published before lung-protective ventilation. Therefore, further studies are needed to refine the understanding of the mechanical effects of lung-protective ventilation. Although low-VT ventilation is becoming a standard of care for ARDS patients, many issues remain unresolved; among them are the role of PEEP and recruitment maneuvers in either preventing or promoting lung injury and the effects of respiratory rate and graded VT reduction on mechanical stress in the lungs. The authors believe that advances in mechanical ventilation that may further improve patient outcomes are likely to come from more sophisticated monitoring capabilities (ie, the ability to measure P1 or perhaps Cslice) than from the creation of new modes of ventilatory support.

Lower Respiratory Tract Infection and Short-Term Outcome in Patients With Acute Respiratory Distress Syndrome.

PubMed

Zampieri, Fernando G; Póvoa, Pedro; Salluh, Jorge I; Rodriguez, Alejandro; Valade, Sandrine; Andrade Gomes, José; Reignier, Jean; Molinos, Elena; Almirall, Jordi; Boussekey, Nicolas; Socias, Lorenzo; Ramirez, Paula; Viana, William N; Rouzé, Anahita; Nseir, Saad; Martin-Loeches, Ignacio

2018-01-01

To assess whether ventilator-associated lower respiratory tract infections (VA-LRTIs) are associated with mortality in critically ill patients with acute respiratory distress syndrome (ARDS). Post hoc analysis of prospective cohort study including mechanically ventilated patients from a multicenter prospective observational study (TAVeM study); VA-LRTI was defined as either ventilator-associated tracheobronchitis (VAT) or ventilator-associated pneumonia (VAP) based on clinical criteria and microbiological confirmation. Association between intensive care unit (ICU) mortality in patients having ARDS with and without VA-LRTI was assessed through logistic regression controlling for relevant confounders. Association between VA-LRTI and duration of mechanical ventilation and ICU stay was assessed through competing risk analysis. Contribution of VA-LRTI to a mortality model over time was assessed through sequential random forest models. The cohort included 2960 patients of which 524 fulfilled criteria for ARDS; 21% had VA-LRTI (VAT = 10.3% and VAP = 10.7%). After controlling for illness severity and baseline health status, we could not find an association between VA-LRTI and ICU mortality (odds ratio: 1.07; 95% confidence interval: 0.62-1.83; P = .796); VA-LRTI was also not associated with prolonged ICU length of stay or duration of mechanical ventilation. The relative contribution of VA-LRTI to the random forest mortality model remained constant during time. The attributable VA-LRTI mortality for ARDS was higher than the attributable mortality for VA-LRTI alone. After controlling for relevant confounders, we could not find an association between occurrence of VA-LRTI and ICU mortality in patients with ARDS.

Respiratory mechanics to understand ARDS and guide mechanical ventilation.

PubMed

Mauri, Tommaso; Lazzeri, Marta; Bellani, Giacomo; Zanella, Alberto; Grasselli, Giacomo

2017-11-30

As precision medicine is becoming a standard of care in selecting tailored rather than average treatments, physiological measurements might represent the first step in applying personalized therapy in the intensive care unit (ICU). A systematic assessment of respiratory mechanics in patients with the acute respiratory distress syndrome (ARDS) could represent a step in this direction, for two main reasons. Approach and Main results: On the one hand, respiratory mechanics are a powerful physiological method to understand the severity of this syndrome in each single patient. Decreased respiratory system compliance, for example, is associated with low end expiratory lung volume and more severe lung injury. On the other hand, respiratory mechanics might guide protective mechanical ventilation settings. Improved gravitationally dependent regional lung compliance could support the selection of positive end-expiratory pressure and maximize alveolar recruitment. Moreover, the association between driving airway pressure and mortality in ARDS patients potentially underlines the importance of sizing tidal volume on respiratory system compliance rather than on predicted body weight. The present review article aims to describe the main alterations of respiratory mechanics in ARDS as a potent bedside tool to understand severity and guide mechanical ventilation settings, thus representing a readily available clinical resource for ICU physicians.

EARLY STABILIZING ALVEOLAR VENTILATION PREVENTS ARDS- A NOVEL TIMING-BASED VENTILATORY INTERVENTION TO AVERT LUNG INJURY

PubMed Central

Roy, Shreyas; Sadowitz, Benjamin; Andrews, Penny; Gatto, Louis; Marx, William; Ge, Lin; Wang, Guirong; Lin, Xin; Dean, David A.; Kuhn, Michael; Ghosh, Auyon; Satalin, Joshua; Snyder, Kathy; Vodovotz, Yoram; Nieman, Gary; Habashi, Nader

2012-01-01

Background Established ARDS is often refractory to treatment. Clinical trials have demonstrated modest treatment effects, and mortality remains high. Ventilator strategies must be developed to prevent ARDS. Hypothesis Early ventilatory intervention will block progression to ARDS if the ventilator mode: 1) maintains alveolar stability and 2) reduces pulmonary edema formation. Methods Yorkshire Pigs (38–45kg) were anaesthetized and subjected to "2-hit" Ischemia-Reperfusion and Peritoneal Sepsis. Following injury, animals were randomized into two groups: Early Preventative Ventilation (Airway Pressure Release Ventilation- APRV) vs. Non-Preventative Ventilation (NPV) and followed for 48hr. All animals received anesthesia, antibiotics, and fluid/vasopressor therapy per Surviving Sepsis Campaign. Ventilation parameters: 1) NPV Group - Tidal volume (Vt): 10cc/kg + PEEP- 5 cm/H2O volume-cycled mode, 2) APRV Group - Vt: 10–15 cc/kg; Phigh, Plow, Thigh, Tlow were titrated for optimal alveolar stability. Physiologic data and plasma were collected throughout the 48hr study period, followed by BAL and necropsy. Results APRV prevented development of ARDS (p<0.001 vs NPV) by PaO2/FiO2 ratio. Quantitative histological scoring showed APRV prevented lung tissue injury (p<0.001 vs. NPV). BALF showed APRV lowered total protein and IL-6, while preserving surfactant proteins A & B (p<0.05 vs. NPV). APRV significantly lowered lung water (p<0.001 vs. NPV). Plasma IL-6 concentrations were similar between groups. Conclusions Early preventative mechanical ventilation with APRV blocked ARDS development, preserved surfactant proteins, and reduced pulmonary inflammation and edema, despite systemic inflammation similar to NPV. These data suggest early preventative ventilation strategies stabilizing alveoli and reducing pulmonary edema can attenuate ARDS after ischemia-reperfusion-sepsis. PMID:22846945

[Treatment of acute respiratory distress syndrome using pressure and volume controlled ventilation with lung protective strategy].

PubMed

Ge, Ying; Wan, Yong; Wang, Da-qing; Su, Xiao-lin; Li, Jun-ying; Chen, Jing

2004-07-01

To investigate the significance and effect of pressure controlled ventilation (PCV) as well as volume controlled ventilation (VCV) by lung protective strategy on respiratory mechanics, blood gas analysis and hemodynamics in patients with acute respiratory distress syndrome (ARDS). Fifty patients with ARDS were randomly divided into PCV and VCV groups with permissive hypercapnia and open lung strategy. Changes in respiratory mechanics, blood gas analysis and hemodynamics were compared between two groups. Peak inspiration pressure (PIP) in PCV group was significantly lower than that in VCV group, while mean pressure of airway (MPaw) was significantly higher than that in VCV after 24 hours mechanical ventilation. After 24 hours mechanical ventilation, there were higher central venous pressure (CVP) and slower heart rate (HR) in two groups, CVP was significantly higher in VCV compared with PCV, and PCV group had slower HR than VCV group, the two groups had no differences in mean blood pressure (MBP) at various intervals. All patients showed no ventilator-induced lung injury. Arterial blood oxygenations were obviously improved in two groups after 24 hours mechanical ventilation, PCV group had better partial pressure of oxygen in artery (PaO2) than VCV group. Both PCV and VCV can improve arterial blood oxygenations, prevent ventilator-induced lung injury, and have less disturbance in hemodynamic parameters. PCV with lung protective ventilatory strategy should be early use for patients with ARDS.

Mechanical ventilation in acute respiratory distress syndrome: The open lung revisited.

PubMed

Amado-Rodríguez, L; Del Busto, C; García-Prieto, E; Albaiceta, G M

2017-12-01

Acute respiratory distress syndrome (ARDS) is still related to high mortality and morbidity rates. Most patients with ARDS will require ventilatory support. This treatment has a direct impact upon patient outcome and is associated to major side effects. In this regard, ventilator-associated lung injury (VALI) is the main concern when this technique is used. The ultimate mechanisms of VALI and its management are under constant evolution. The present review describes the classical mechanisms of VALI and how they have evolved with recent findings from physiopathological and clinical studies, with the aim of analyzing the clinical implications derived from them. Lastly, a series of knowledge-based recommendations are proposed that can be helpful for the ventilator assisted management of ARDS at the patient bedside. Copyright © 2017 Elsevier España, S.L.U. y SEMICYUC. All rights reserved.

Rationale and Description of Right Ventricle-Protective Ventilation in ARDS.

PubMed

Paternot, Alexis; Repessé, Xavier; Vieillard-Baron, Antoine

2016-10-01

Pulmonary vascular dysfunction is associated with ARDS and leads to increased right-ventricular afterload and eventually right-ventricular failure, also called acute cor pulmonale. Interest in acute cor pulmonale and its negative impact on outcome in patients with ARDS has grown in recent years. Right-ventricular function in these patients should be closely monitored, and this is helped by the widespread use of echocardiography in intensive care units. Because mechanical ventilation may worsen right-ventricular failure, the interaction between the lungs and the right ventricle appears to be a key factor in the ventilation strategy. In this review, a rationale for a right ventricle-protective ventilation approach is provided, and such a strategy is described, including the reduction of lung stress (ie, the limitation of plateau pressure and driving pressure), the reduction of PaCO2 , and the improvement of oxygenation. Prone positioning seems to be a crucial part of this strategy by protecting both the lungs and the right ventricle, resulting in increased survival of patients with ARDS. Further studies are required to validate the positive impact on prognosis of right ventricle-protective mechanical ventilation. Copyright © 2016 by Daedalus Enterprises.

Epidemiological characteristics, practice of ventilation, and clinical outcome in patients at risk of acute respiratory distress syndrome in intensive care units from 16 countries (PRoVENT): an international, multicentre, prospective study.

PubMed

Neto, Ary Serpa; Barbas, Carmen S V; Simonis, Fabienne D; Artigas-Raventós, Antonio; Canet, Jaume; Determann, Rogier M; Anstey, James; Hedenstierna, Goran; Hemmes, Sabrine N T; Hermans, Greet; Hiesmayr, Michael; Hollmann, Markus W; Jaber, Samir; Martin-Loeches, Ignacio; Mills, Gary H; Pearse, Rupert M; Putensen, Christian; Schmid, Werner; Severgnini, Paolo; Smith, Roger; Treschan, Tanja A; Tschernko, Edda M; Melo, Marcos F V; Wrigge, Hermann; de Abreu, Marcelo Gama; Pelosi, Paolo; Schultz, Marcus J

2016-11-01

Scant information exists about the epidemiological characteristics and outcome of patients in the intensive care unit (ICU) at risk of acute respiratory distress syndrome (ARDS) and how ventilation is managed in these individuals. We aimed to establish the epidemiological characteristics of patients at risk of ARDS, describe ventilation management in this population, and assess outcomes compared with people at no risk of ARDS. PRoVENT (PRactice of VENTilation in critically ill patients without ARDS at onset of ventilation) is an international, multicentre, prospective study undertaken at 119 ICUs in 16 countries worldwide. All patients aged 18 years or older who were receiving mechanical ventilation in participating ICUs during a 1-week period between January, 2014, and January, 2015, were enrolled into the study. The Lung Injury Prediction Score (LIPS) was used to stratify risk of ARDS, with a score of 4 or higher defining those at risk of ARDS. The primary outcome was the proportion of patients at risk of ARDS. Secondary outcomes included ventilatory management (including tidal volume [V T ] expressed as mL/kg predicted bodyweight [PBW], and positive end-expiratory pressure [PEEP] expressed as cm H 2 O), development of pulmonary complications, and clinical outcomes. The PRoVENT study is registered at ClinicalTrials.gov, NCT01868321. The study has been completed. Of 3023 patients screened for the study, 935 individuals fulfilled the inclusion criteria. Of these critically ill patients, 282 were at risk of ARDS (30%, 95% CI 27-33), representing 0·14 cases per ICU bed over a 1-week period. V T was similar for patients at risk and not at risk of ARDS (median 7·6 mL/kg PBW [IQR 6·7-9·1] vs 7·9 mL/kg PBW [6·8-9·1]; p=0·346). PEEP was higher in patients at risk of ARDS compared with those not at risk (median 6·0 cm H 2 O [IQR 5·0-8·0] vs 5·0 cm H 2 O [5·0-7·0]; p<0·0001). The prevalence of ARDS in patients at risk of ARDS was higher than in individuals not at risk of ARDS (19/260 [7%] vs 17/556 [3%]; p=0·004). Compared with individuals not at risk of ARDS, patients at risk of ARDS had higher in-hospital mortality (86/543 [16%] vs 74/232 [32%]; p<0·0001), ICU mortality (62/533 [12%] vs 66/227 [29%]; p<0·0001), and 90-day mortality (109/653 [17%] vs 88/282 [31%]; p<0·0001). V T did not differ between patients who did and did not develop ARDS (p=0·471 for those at risk of ARDS; p=0·323 for those not at risk). Around a third of patients receiving mechanical ventilation in the ICU were at risk of ARDS. Pulmonary complications occur frequently in patients at risk of ARDS and their clinical outcome is worse compared with those not at risk of ARDS. There is potential for improvement in the management of patients without ARDS. Further refinements are needed for prediction of ARDS. None. Copyright © 2016 Elsevier Ltd. All rights reserved.

Acute respiratory distress syndrome in wartime military burns: application of the Berlin criteria.

PubMed

Belenkiy, Slava M; Buel, Allison R; Cannon, Jeremy W; Sine, Christy R; Aden, James K; Henderson, Jonathan L; Liu, Nehemiah T; Lundy, Jonathan B; Renz, Evan M; Batchinsky, Andriy I; Cancio, Leopoldo C; Chung, Kevin K

2014-03-01

Acute respiratory distress syndrome (ARDS) prevalence and related outcomes in burned military casualties from Iraq and Afghanistan have not been described previously. The objective of this article was to report ARDS prevalence and its associated in-hospital mortality in military burn patients. Demographic and physiologic data were collected retrospectively on mechanically ventilated military casualties admitted to our burn intensive care unit from January 2003 to December 2011. Patients with ARDS were identified in accordance with the new Berlin definition of ARDS. Subjects were categorized as having mild, moderate, or severe ARDS. Multivariate logistic regression identified independent risk factors for developing moderate-to-severe ARDS. The main outcome measure was the prevalence of ARDS in a cohort of patients burned as a result of recent combat operations. A total of 876 burned military casualties presented during the study period, of whom 291 (33.2%) required mechanical ventilation. Prevalence of ARDS in this cohort was 32.6%, with a crude overall mortality of 16.5%. Mortality increased significantly with ARDS severity: mild (11.1%), moderate (36.1%), and severe (43.8%) compared with no ARDS (8.7%) (p < 0.001). Predictors for the development of moderate or severe ARDS were inhalation injury (odds ratio [OR], 1.90; 95% confidence interval [CI], 1.01-3.54; p = 0.046), Injury Severity Score (ISS) (OR, 1.04; 95% CI, 1.01-1.07; p = 0.0021), pneumonia (OR, 198; 95% CI, 1.07-3.66; p = 0.03), and transfusion of fresh frozen plasma (OR, 1.32; 95% CI, 1.01-1.72; p = 0.04). Size of burn was associated with moderate or severe ARDS by univariate analysis but was not an independent predictor of ARDS by multivariate logistic regression (p > 0.05). Age, size of burn, and moderate or severe ARDS were independent predictors of mortality. In this cohort of military casualties with thermal injuries, nearly a third required mechanical ventilation; of those, nearly one third developed ARDS, and nearly one third of patients with ARDS did not survive. Moderate and severe ARDS increased the odds of death by more than fourfold and ninefold, respectively. Epidemiologic/prognostic study, level III.

Lung Metabolic Activation as an Early Biomarker of the Acute Respiratory Distress Syndrome and Local Gene Expression Heterogeneity

PubMed Central

Wellman, Tyler J.; de Prost, Nicolas; Tucci, Mauro; Winkler, Tilo; Baron, Rebecca M.; Filipczak, Piotr; Raby, Benjamin; Chu, Jen-hwa; Harris, R. Scott; Musch, Guido; dos Reis Falcao, Luiz F.; Capelozzi, Vera; Venegas, Jose; Melo, Marcos F. Vidal

2016-01-01

Background The acute respiratory distress syndrome (ARDS) is an inflammatory condition comprising diffuse lung edema and alveolar damage. ARDS frequently results from regional injury mechanisms. However, it is unknown whether detectable inflammation precedes lung edema and opacification, and whether topographically differential gene expression consistent with heterogeneous injury occurs in early ARDS. We aimed to determine the temporal relationship between pulmonary metabolic activation and density in a large animal model of early ARDS, and to assess gene expression in differentially activated regions. Methods We produced ARDS in sheep with intravenous LPS (10ng/kg/h) and mechanical ventilation for 20h. Using positron emission tomography, we assessed regional cellular metabolic activation with 2-deoxy-2-[(18)F]fluoro-D-glucose, perfusion and ventilation with 13NN-saline, and aeration using transmission scans. Species-specific micro-array technology was used to assess regional gene expression. Results Metabolic activation preceded detectable increases in lung density (as required for clinical diagnosis) and correlated with subsequent histological injury, suggesting its predictive value for severity of disease progression. Local time-courses of metabolic activation varied, with highly perfused and less aerated dependent lung regions activated earlier than non-dependent regions. These regions of distinct metabolic trajectories demonstrated differential gene expression for known and potential novel candidates for ARDS pathogenesis. Conclusions Heterogeneous lung metabolic activation precedes increases in lung density in the development of ARDS due to endotoxemia and mechanical ventilation. Local differential gene expression occurs in these early stages and reveals molecular pathways relevant to ARDS biology and of potential use as treatment targets. PMID:27611185

Bayesian inference of the lung alveolar spatial model for the identification of alveolar mechanics associated with acute respiratory distress syndrome

NASA Astrophysics Data System (ADS)

Christley, Scott; Emr, Bryanna; Ghosh, Auyon; Satalin, Josh; Gatto, Louis; Vodovotz, Yoram; Nieman, Gary F.; An, Gary

2013-06-01

Acute respiratory distress syndrome (ARDS) is acute lung failure secondary to severe systemic inflammation, resulting in a derangement of alveolar mechanics (i.e. the dynamic change in alveolar size and shape during tidal ventilation), leading to alveolar instability that can cause further damage to the pulmonary parenchyma. Mechanical ventilation is a mainstay in the treatment of ARDS, but may induce mechano-physical stresses on unstable alveoli, which can paradoxically propagate the cellular and molecular processes exacerbating ARDS pathology. This phenomenon is called ventilator induced lung injury (VILI), and plays a significant role in morbidity and mortality associated with ARDS. In order to identify optimal ventilation strategies to limit VILI and treat ARDS, it is necessary to understand the complex interplay between biological and physical mechanisms of VILI, first at the alveolar level, and then in aggregate at the whole-lung level. Since there is no current consensus about the underlying dynamics of alveolar mechanics, as an initial step we investigate the ventilatory dynamics of an alveolar sac (AS) with the lung alveolar spatial model (LASM), a 3D spatial biomechanical representation of the AS and its interaction with airflow pressure and the surface tension effects of pulmonary surfactant. We use the LASM to identify the mechanical ramifications of alveolar dynamics associated with ARDS. Using graphical processing unit parallel algorithms, we perform Bayesian inference on the model parameters using experimental data from rat lung under control and Tween-induced ARDS conditions. Our results provide two plausible models that recapitulate two fundamental hypotheses about volume change at the alveolar level: (1) increase in alveolar size through isotropic volume change, or (2) minimal change in AS radius with primary expansion of the mouth of the AS, with the implication that the majority of change in lung volume during the respiratory cycle occurs in the alveolar ducts. These two model solutions correspond to significantly different mechanical properties of the tissue, and we discuss the implications of these different properties and the requirements for new experimental data to discriminate between the hypotheses.

Regional physiology of ARDS.

PubMed

Gattinoni, Luciano; Tonetti, Tommaso; Quintel, Michael

2017-12-28

The acute respiratory distress (ARDS) lung is usually characterized by a high degree of inhomogeneity. Indeed, the same lung may show a wide spectrum of aeration alterations, ranging from completely gasless regions, up to hyperinflated areas. This inhomogeneity is normally caused by the presence of lung edema and/or anatomical variations, and is deeply influenced by the gravitational forces.For any given airway pressure generated by the ventilator, the pressure acting directly on the lung (i.e., the transpulmonary pressure or lung stress) is determined by two main factors: 1) the ratio between lung elastance and the total elastance of the respiratory system (which has been shown to vary widely in ARDS patients, between 0.2 and 0.8); and 2) the lung size. In severe ARDS, the ventilatable parenchyma is strongly reduced in size ('baby lung'); its resting volume could be as low as 300 mL, and the total inspiratory capacity could be reached with a tidal volume of 750-900 mL, thus generating lethal stress and strain in the lung. Although this is possible in theory, it does not explain the occurrence of ventilator-induced lung injury (VILI) in lungs ventilated with much lower tidal volumes. In fact, the ARDS lung contains areas acting as local stress multipliers and they could multiply the stress by a factor ~ 2, meaning that in those regions the transpulmonary pressure could be double that present in other parts of the same lung. These 'stress raisers' widely correspond to the inhomogenous areas of the ARDS lung and can be present in up to 40% of the lung.Although most of the literature on VILI concentrates on the possible dangers of tidal volume, mechanical ventilation in fact delivers mechanical power (i.e., energy per unit of time) to the lung parenchyma, which reacts to it according to its anatomical structure and pathophysiological status. The determinants of mechanical power are not only the tidal volume, but also respiratory rate, inspiratory flow, and positive end-expiratory pressure (PEEP). In the end, decreasing mechanical power, increasing lung homogeneity, and avoiding reaching the anatomical limits of the 'baby lung' should be the goals for safe ventilation in ARDS.

What Is Acute Respiratory Distress Syndrome?

MedlinePlus

... used for ARDS include: ■■ Breathing support from a mechanical ventilator combined with oxygen therapy (See ATS fact sheets on Mechanical Ventilation and Oxygen Therapy at www. thoracic.org/ ...

Low-Flow Extracorporeal Carbon Dioxide Removal Using the Hemolung Respiratory Dialysis System® to Facilitate Lung-Protective Mechanical Ventilation in Acute Respiratory Distress Syndrome.

PubMed

Akkanti, Bindu; Rajagopal, Keshava; Patel, Kirti P; Aravind, Sangeeta; Nunez-Centanu, Emmanuel; Hussain, Rahat; Shabari, Farshad Raissi; Hofstetter, Wayne L; Vaporciyan, Ara A; Banjac, Igor S; Kar, Biswajit; Gregoric, Igor D; Loyalka, Pranav

2017-06-01

Extracorporeal carbon dioxide removal (ECCO 2 R) permits reductions in alveolar ventilation requirements that the lungs would otherwise have to provide. This concept was applied to a case of hypercapnia refractory to high-level invasive mechanical ventilator support. We present a case of an 18-year-old man who developed post-pneumonectomy acute respiratory distress syndrome (ARDS) after resection of a mediastinal germ cell tumor involving the left lung hilum. Hypercapnia and hypoxemia persisted despite ventilator support even at traumatic levels. ECCO 2 R using a miniaturized system was instituted and provided effective carbon dioxide elimination. This facilitated establishment of lung-protective ventilator settings and lung function recovery. Extracorporeal lung support increasingly is being applied to treat ARDS. However, conventional extracorporeal membrane oxygenation (ECMO) generally involves using large cannulae capable of carrying high flow rates. A subset of patients with ARDS has mixed hypercapnia and hypoxemia despite high-level ventilator support. In the absence of profound hypoxemia, ECCO 2 R may be used to reduce ventilator support requirements to lung-protective levels, while avoiding risks associated with conventional ECMO.

Abdominal Muscle Activity during Mechanical Ventilation Increases Lung Injury in Severe Acute Respiratory Distress Syndrome.

PubMed

Zhang, Xianming; Wu, Weiliang; Zhu, Yongcheng; Jiang, Ying; Du, Juan; Chen, Rongchang

2016-01-01

It has proved that muscle paralysis was more protective for injured lung in severe acute respiratory distress syndrome (ARDS), but the precise mechanism is not clear. The purpose of this study was to test the hypothesis that abdominal muscle activity during mechanically ventilation increases lung injury in severe ARDS. Eighteen male Beagles were studied under mechanical ventilation with anesthesia. Severe ARDS was induced by repetitive oleic acid infusion. After lung injury, Beagles were randomly assigned into spontaneous breathing group (BIPAPSB) and abdominal muscle paralysis group (BIPAPAP). All groups were ventilated with BIPAP model for 8h, and the high pressure titrated to reached a tidal volume of 6ml/kg, the low pressure was set at 10 cmH2O, with I:E ratio 1:1, and respiratory rate adjusted to a PaCO2 of 35-60 mmHg. Six Beagles without ventilator support comprised the control group. Respiratory variables, end-expiratory volume (EELV) and gas exchange were assessed during mechanical ventilation. The levels of Interleukin (IL)-6, IL-8 in lung tissue and plasma were measured by qRT-PCR and ELISA respectively. Lung injury scores were determined at end of the experiment. For the comparable ventilator setting, as compared with BIPAPSB group, the BIPAPAP group presented higher EELV (427±47 vs. 366±38 ml) and oxygenation index (293±36 vs. 226±31 mmHg), lower levels of IL-6(216.6±48.0 vs. 297.5±71.2 pg/ml) and IL-8(246.8±78.2 vs. 357.5±69.3 pg/ml) in plasma, and lower express levels of IL-6 mRNA (15.0±3.8 vs. 21.2±3.7) and IL-8 mRNA (18.9±6.8 vs. 29.5±7.9) in lung tissues. In addition, less lung histopathology injury were revealed in the BIPAPAP group (22.5±2.0 vs. 25.2±2.1). Abdominal muscle activity during mechanically ventilation is one of the injurious factors in severe ARDS, so abdominal muscle paralysis might be an effective strategy to minimize ventilator-induce lung injury.

A quasi-experimental, before-after trial examining the impact of an emergency department mechanical ventilator protocol on clinical outcomes and lung-protective ventilation in acute respiratory distress syndrome

PubMed Central

Fuller, Brian M.; Ferguson, Ian T.; Mohr, Nicholas M.; Drewry, Anne M.; Palmer, Christopher; Wessman, Brian T.; Ablordeppey, Enyo; Keeperman, Jacob; Stephens, Robert J.; Briscoe, Cristopher C.; Kolomiets, Angelina A.; Hotchkiss, Richard S.; Kollef, Marin H.

2017-01-01

Objective To evaluate the impact of an emergency department (ED) mechanical ventilation protocol on clinical outcomes and adherence to lung-protective ventilation in patients with acute respiratory distress syndrome (ARDS). Design Quasi-experimental, before-after trial. Setting ED and intensive care units (ICU) of an academic center. Patients Mechanically ventilated ED patients experiencing ARDS while in the ED or after admission to the ICU. Interventions An ED ventilator protocol which targeted parameters in need of quality improvement, as identified by prior work: 1) lung-protective tidal volume; 2) appropriate setting of positive end-expiratory pressure (PEEP); 3) oxygen weaning; and 4) head-of-bed elevation. Measurements and Main Results A total of 229 patients (186 pre-intervention group, 43 intervention group) were studied. In the ED, the intervention was associated with significant changes (P < 0.01 for all) in tidal volume, PEEP, respiratory rate, oxygen administration, and head-of-bed elevation. There was a reduction in ED tidal volume from 8.1 mL/kg PBW (7.0 – 9.1) to 6.4 mL/kg PBW (6.1 – 6.7), and an increase in lung-protective ventilation from 11.1% to 61.5%, P < 0.01. The intervention was associated with a reduction in mortality from 54.8% to 39.5% (OR 0.38, 95% CI 0.17 – 0.83, P = 0.02), and a 3.9 day increase in ventilator-free days, P = 0.01. Conclusions This before-after study of mechanically ventilated patients with ARDS demonstrates that implementing a mechanical ventilator protocol in the ED is feasible, and associated with improved clinical outcomes. PMID:28157140

Mechanical Ventilation in Patients with the Acute Respiratory Distress Syndrome and Treated with Extracorporeal Membrane Oxygenation: Impact on Hospital and 30 Day Postdischarge Survival.

PubMed

Modrykamien, Ariel M; Hernandez, Omar O; Im, Yunhee; Walters, Ryan W; Schrader, Caleb L; Smith, Lauren E; Lima, Brian

2016-01-01

Mechanical ventilation support for acute respiratory distress syndrome (ARDS) patients involves the use of low tidal volumes and positive end-expiratory pressure. Nevertheless, the optimal ventilator strategy for ARDS patients undergoing extracorporeal membrane oxygenation (ECMO) therapy remains unknown. A retrospective analysis of a consecutive series of adult ARDS patients treated with V-V ECMO from October 2012 to May 2015 was performed. Mechanical ventilation data, as well as demographic and clinical data, were collected. We assessed the association between ventilator data and outcomes of interest. The primary outcome was hospital survival. Secondary outcome was 30 day survival posthospital discharge. Sixty-four ARDS patients were treated with ECMO. Univariate analysis showed that plateau pressure was independently associated with hospital survival. Tidal volume, positive end-expiratory pressure (PEEP), and plateau were independently associated with 30 day survival. Multivariate analysis, after controlling for covariates, revealed that a 1 unit increase in plateau pressure was associated with a 21% decrease in the odds of hospital survival (95% confidence interval [CI] = 6.39-33.42%, p = 0.007). In regards to 30 day survival postdischarge, a 1 unit increase in plateau pressure was associated with a 14.4% decrease in the odds of achieving the aforementioned outcome (95% CI = 1.75-25.4%, p = 0.027). Also, a 1 unit increase in PEEP was associated with a 36.2% decrease in the odds of 30 day survival (95% CI = 10.8-54.4%, p = 0.009). Among ARDS patients undergoing ECMO therapy, only plateau pressure is associated with hospital survival. Plateau pressure and PEEP are both associated with 30 day survival posthospital discharge.

Definition and epidemiology of acute respiratory distress syndrome

PubMed Central

Rezoagli, Emanuele; Fumagalli, Roberto

2017-01-01

Fifty years ago, Ashbaugh and colleagues defined for the first time the acute respiratory distress syndrome (ARDS), one among the most challenging clinical condition of the critical care medicine. The scientific community worked over the years to generate a unified definition of ARDS, which saw its revisited version in the Berlin definition, in 2014. Epidemiologic information about ARDS is limited in the era of the new Berlin definition, and wide differences are reported among countries all over the world. Despite decades of study in the field of lung injury, ARDS is still so far under-recognized, with 2 out of 5 cases missed by clinicians. Furthermore, although advances of ventilator strategies in the management of ARDS associated with outcome improvements—such as protective mechanical ventilation, lower driving pressure, higher PEEP levels and prone positioning—ARDS appears to be undertreated and mortality remains elevated up to 40%. In this review, we cover the history that led to the current worldwide accepted Berlin definition of ARDS and we summarize the recent data regarding ARDS epidemiology. PMID:28828357

Effect of type II diabetes mellitus on outcomes in patients with acute respiratory distress syndrome.

PubMed

Singla, Abhishek; Turner, Paul; Pendurthi, Madhu Kalyan; Agrawal, Vrinda; Modrykamien, Ariel

2014-02-01

The acute respiratory distress syndrome (ARDS) is a life-threatening condition, whereas the presence of diabetes has been shown to be protective in its development. We undertook this study to assess the association of type II diabetes mellitus with clinical outcomes in patients with ARDS. We retrospectively examined the medical records of consecutive series of patients with ARDS requiring mechanical ventilation from January 2008 to March 2011. Patients with type I diabetes were excluded from the study. Clinical outcomes such as ventilator-free days, mortality, length of stay in the hospital and intensive care unit (ICU), and reintubations were compared based on the presence of diabetes. Multivariate regression model was used to find if the presence of type II diabetes mellitus predicts ventilator-free days at day 28. Two hundred forty-nine patients with ARDS were admitted to the ICU during the study period. Fifty (20%) subjects had type II diabetes mellitus. Differences in ventilator-free days, in-hospital mortality, reintubation rate, and length of stay in the hospital or ICU were not statistically significant between diabetic and nondiabetic patients with ARDS. Acute Physiologic and Chronic Health Evaluation II, ICU specialty, use of vasopressors, and the need for reintubation were predictors of ventilator-free days at day 28. The presence of type II diabetes mellitus and its adjustment by body mass index did not show association with ventilator-free days at day 28. The presence of type II diabetes mellitus is not associated with clinical outcomes in ARDS, even when its presence is adjusted by body mass index. © 2013.

[Role of noninvasive mechanical ventilation in patients with severe avian influenza A (H7N9) complicated with acute respiratory distress syndrome].

PubMed

Luo, Haili; Wang, Shaohong; Shen, Feng; Yuan, Tongmei; Pan, Xianguo; Liu, Jingtao; Yao, Ling; Wu, Juncheng; Long, Xuemei

2018-05-01

Human infection with avian influenza A (H7N9) is an acute contagious respiratory disease. Acute respiratory distress syndrome (ARDS) is a common complication in patients with severe avian influenza A (H7N9), for whom mechanical ventilation (MV) is an important supportive method. A patient, suffered from severe avian influenza A (H7N9) and complicated with ARDS, was admitted to the Second Affiliated Hospital of Guizhou Medical University in January 2017. With very intensive care for oxygenation, respiration and consciousness, and monitoring, she was successfully cured by comprehensive managements, among which noninvasive mechanical ventilation (NIV) was the major respiratory support method. The result demonstrate that, in patients with conscious state, satisfied expectoration ability and relatively good cooperation, and with close observation of oxygenation and respiratory rate, NIV may be accepted as an effective method for patient with ARDS caused by severe avian influenza A (H7N9).

Early stabilizing alveolar ventilation prevents acute respiratory distress syndrome: a novel timing-based ventilatory intervention to avert lung injury.

PubMed

Roy, Shreyas; Sadowitz, Benjamin; Andrews, Penny; Gatto, Louis A; Marx, William; Ge, Lin; Wang, Guirong; Lin, Xin; Dean, David A; Kuhn, Michael; Ghosh, Auyon; Satalin, Joshua; Snyder, Kathy; Vodovotz, Yoram; Nieman, Gary; Habashi, Nader

2012-08-01

Established acute respiratory distress syndrome (ARDS) is often refractory to treatment. Clinical trials have demonstrated modest treatment effects, and mortality remains high. Ventilator strategies must be developed to prevent ARDS. Early ventilatory intervention will block progression to ARDS if the ventilator mode (1) maintains alveolar stability and (2) reduces pulmonary edema formation. Yorkshire pigs (38-45 kg) were anesthetized and subjected to a "two-hit" ischemia-reperfusion and peritoneal sepsis. After injury, animals were randomized into two groups: early preventative ventilation (airway pressure release ventilation [APRV]) versus nonpreventative ventilation (NPV) and followed for 48 hours. All animals received anesthesia, antibiotics, and fluid or vasopressor therapy as per the Surviving Sepsis Campaign. Titrated for optimal alveolar stability were the following ventilation parameters: (1) NPV group--tidal volume, 10 mL/kg + positive end-expiratory pressure - 5 cm/H2O volume-cycled mode; (2) APRV group--tidal volume, 10 to 15 mL/kg; high pressure, low pressure, time duration of inspiration (Thigh), and time duration of release phase (Tlow). Physiological data and plasma were collected throughout the 48-hour study period, followed by BAL and necropsy. APRV prevented the development of ARDS (p < 0.001 vs. NPV) by PaO₂/FIO₂ ratio. Quantitative histological scoring showed that APRV prevented lung tissue injury (p < 0.001 vs. NPV). Bronchoalveolar lavage fluid showed that APRV lowered total protein and interleukin 6 while preserving surfactant proteins A and B (p < 0.05 vs. NPV). APRV significantly lowered lung water (p < 0.001 vs. NPV). Plasma interleukin 6 concentrations were similar between groups. Early preventative mechanical ventilation with APRV blocked ARDS development, preserved surfactant proteins, and reduced pulmonary inflammation and edema despite systemic inflammation similar to NPV. These data suggest that early preventative ventilation strategies stabilizing alveoli and reducing pulmonary edema can attenuate ARDS after ischemia-reperfusion and sepsis.

Variability of Tidal Volume in Patient-Triggered Mechanical Ventilation in ARDS.

PubMed

Perinel-Ragey, Sophie; Baboi, Loredana; Guérin, Claude

2017-11-01

Limiting tidal volume (V T ) in patients with ARDS may not be achieved once patient-triggered breaths occur. Furthermore, ICU ventilators offer numerous patient-triggered modes that work differently across brands. We systematically investigated, using a bench model, the effect of patient-triggered modes on the size and variability of V T at different breathing frequencies (f), patient effort, and ARDS severity. We used a V500 Infinity ICU ventilator connected to an ASL 5000 lung model whose compliance was mimicking mild, moderate, and severe ARDS. Thirteen patient-triggered modes were tested, falling into 3 categories, namely volume control ventilation with mandatory minute ventilation; pressure control ventilation, including airway pressure release ventilation (APRV); and pressure support ventilation. Two levels of f and effort were tested for each ARDS severity in each mode. Median (first-third quartiles) V T was compared across modes using non-parametric tests. The probability of V T > 6 mL/kg ideal body weight was assessed by binomial regression and expressed as the odds ratio (OR) with 95% CI. V T variability was measured from the coefficient of variation. V T distribution over all f, effort, and ARDS categories significantly differed across modes ( P < .001, Kruskal-Wallis test). V T was significantly greater with pressure support (OR 420 mL, 95% CI 332-527 mL) than with any other mode except for variable pressure support level. Risk for V T to be > 6 mL/kg was significantly increased with spontaneous breaths patient-triggered by pressure support (OR 19.36, 95% CI 12.37-30.65) and significantly reduced in APRV (OR 0.44, 95% CI 0.26-0.72) and pressure support with guaranteed volume mode. The risk increased with increasing effort and decreasing f. Coefficient of variation of V T was greater for low f and volume control-mandatory minute ventilation and pressure control modes. APRV had the greatest within-mode variability. Risk of V T > 6 mL/kg was significantly reduced in APRV and pressure support with guaranteed volume mode. APRV had the highest variability. Pressure support with guaranteed volume could be tested in patients with ARDS. Copyright © 2017 by Daedalus Enterprises.

Extracorporeal Life Support for Severe Acute Respiratory Distress Syndrome in Adults

PubMed Central

Hemmila, Mark R.; Rowe, Stephen A.; Boules, Tamer N.; Miskulin, Judiann; McGillicuddy, John W.; Schuerer, Douglas J.; Haft, Jonathan W.; Swaniker, Fresca; Arbabi, Saman; Hirschl, Ronald B.; Bartlett, Robert H.

2004-01-01

Objective: Severe acute respiratory distress syndrome (ARDS) is associated with a high level of mortality. Extracorporeal life support (ECLS) during severe ARDS maintains oxygen and carbon dioxide gas exchange while providing an optimal environment for recovery of pulmonary function. Since 1989, we have used a protocol-driven algorithm for treatment of severe ARDS, which includes the use of ECLS when standard therapy fails. The objective of this study was to evaluate our experience with ECLS in adult patients with severe ARDS with respect to mortality and morbidity. Methods: We reviewed our complete experience with ELCS in adults from January 1, 1989, through December 31, 2003. Severe ARDS was defined as acute onset pulmonary failure, with bilateral infiltrates on chest x-ray, and PaO2/fraction of inspired oxygen (FiO2) ratio ≤100 or A-aDO2 >600 mm Hg despite maximal ventilator settings. The indication for ECLS was acute severe ARDS unresponsive to optimal conventional treatment. The technique of ECLS included veno-venous or veno-arterial vascular access, lung “rest” at low FiO2 and inspiratory pressure, minimal anticoagulation, and optimization of systemic oxygen delivery. Results: During the study period, ECLS was used for 405 adult patients age 17 or older. Of these 405 patients, 255 were placed on ECLS for severe ARDS refractory to all other treatment. Sixty-seven percent were weaned off ECLS, and 52% survived to hospital discharge. Multivariate logistic regression analysis identified the following pre-ELCS variables as significant independent predictors of survival: (1) age (P = 0.01); (2) gender (P = 0.048); (3) pH ≤7.10 (P = 0.01); (4) PaO2/FiO2 ratio (P = 0.03); and (5) days of mechanical ventilation (P < 0.001). None of the patients who survived required permanent mechanical ventilation or supplemental oxygen therapy. Conclusion: Extracorporeal life support for severe ARDS in adults is a successful therapeutic option in those patients who do not respond to conventional mechanical ventilator strategies. PMID:15383787

The Effect of ARDS on Survival: Do Patients Die From ARDS or With ARDS?

PubMed

Fuchs, Lior; Feng, Mengling; Novack, Victor; Lee, Joon; Taylor, Jonathan; Scott, Daniel; Howell, Michael; Celi, Leo; Talmor, Daniel

2017-01-01

To investigate the contribution of acute respiratory distress syndrome (ARDS) in of itself to mortality among ventilated patients. A longitudinal retrospective study of ventilated intensive care unit (ICU) patients. The analysis included patients ventilated for more than 48 hours. Patients were classified as having ARDS on admission (early-onset ARDS), late-onset ARDS (ARDS not present during the first 24 hours of admission), or no ARDS. Primary outcomes were mortality at 28 days, and secondary outcomes were 2-year mortality rate from ICU admission. A total of 1411 ventilated patients were enrolled: 41% had ARDS on admission, 28.5% developed ARDS during their ICU stay, and 30.5% did not meet the ARDS criteria prior to ICU discharge or death. The non-ARDS group was used as the control. We also divided the cohort based on the severity of ARDS. After adjusting for covariates, mortality risk at 28 days was not significantly different among the different groups. Both early- and late-onset ARDS as well as the severity of ARDS were found to be significant risk factors for 2 years from ICU survival. Among patients who were ventilated on ICU admission, neither the presence, the severity, or the timing of ARDS contribute independently to the short-term mortality risk. However, acute respiratory distress syndrome does contribute significantly to 2-year mortality risk. This suggests that patients may not die acutely from ARDS itself but rather from the primary disease, and during the acute phase of ARDS, clinicians should focus on improving treatment strategies for the diseases that led to ARDS.

Single-Center Experience With Venovenous ECMO for Influenza-Related ARDS.

PubMed

Buchner, Jessica; Mazzeffi, Michael; Kon, Zachary; Menaker, Jay; Rubinson, Lewis; Bittle, Gregory; Pasrija, Chetan; Herr, Daniel

2018-06-01

This study was designed to determine whether venovenous extracorporeal membrane oxygenation (VV ECMO) reduced mortality in patients with influenza-related acute respiratory distress syndrome (ARDS). A retrospective cohort study was performed. Baseline characteristics of participants were compared and Kaplan-Meier survival analysis was used to compare survival at last medical center follow-up. Cox proportional hazards modeling also was performed to test for univariate associations between salient variables and mortality. A single-center ECMO referral university hospital. All patients admitted with influenza-related ARDS during the 2015 to 2016 influenza season. Mechanical ventilation alone versus mechanical ventilation and ECMO cannulation. A total of 26 patients with influenza-related ARDS were included in the cohort. Thirteen patients were treated with VV ECMO while 13 were not. Twelve of the ECMO patients and 8 of the non-ECMO patients were transferred from outside hospitals. Patients treated with ECMO were younger and had less hypertension and diabetes mellitus. There was no difference in baseline sequential organ failure assessment score between the 2 groups. In-hospital mortality for ECMO patients was 15.4% versus 46.7% for patients not treated with ECMO. Survival at last medical center follow-up was better in patients treated with ECMO (p = 0.02). Age, highest blood carbon dioxide level, and treatment without ECMO were all associated with increased mortality. Influenza-related ARDS has a high mortality rate and patients treated only with mechanical ventilation have worse outcome than those managed with VV ECMO. More liberal use of ECMO should be considered in patients with influenza-related ARDS. Copyright © 2017 Elsevier Inc. All rights reserved.

A unified approach for EIT imaging of regional overdistension and atelectasis in acute lung injury.

PubMed

Gómez-Laberge, Camille; Arnold, John H; Wolf, Gerhard K

2012-03-01

Patients with acute lung injury or acute respiratory distress syndrome (ALI/ARDS) are vulnerable to ventilator-induced lung injury. Although this syndrome affects the lung heterogeneously, mechanical ventilation is not guided by regional indicators of potential lung injury. We used electrical impedance tomography (EIT) to estimate the extent of regional lung overdistension and atelectasis during mechanical ventilation. Techniques for tidal breath detection, lung identification, and regional compliance estimation were combined with the Graz consensus on EIT lung imaging (GREIT) algorithm. Nine ALI/ARDS patients were monitored during stepwise increases and decreases in airway pressure. Our method detected individual breaths with 96.0% sensitivity and 97.6% specificity. The duration and volume of tidal breaths erred on average by 0.2 s and 5%, respectively. Respiratory system compliance from EIT and ventilator measurements had a correlation coefficient of 0.80. Stepwise increases in pressure could reverse atelectasis in 17% of the lung. At the highest pressures, 73% of the lung became overdistended. During stepwise decreases in pressure, previously-atelectatic regions remained open at sub-baseline pressures. We recommend that the proposed approach be used in collaborative research of EIT-guided ventilation strategies for ALI/ARDS.

Personalized Medicine for ARDS: The 2035 Research Agenda

PubMed Central

Beitler, Jeremy R.; Goligher, Ewan C.; Schmidt, Matthieu; Spieth, Peter M.; Zanella, Alberto; Martin-Loeches, Ignacio; Calfee, Carolyn S.; Cavalcanti, Alexandre B.

2016-01-01

Survival from ARDS has increased substantially in the last twenty years as a result of key advances in lung-protective ventilation and resuscitation. Similarly, clinical practice improvements have contributed to an impressive decline in nosocomial ARDS incidence. Personalizing mechanical ventilation for further lung protection is a top research priority for the years ahead. However, the ARDS research agenda must be broader in scope. The clinical syndrome of ARDS includes a heterogeneous assemblage of pathophysiological processes leading to lung injury. Further understanding of these varied, complex biological underpinnings of ARDS pathogenesis is needed to inform therapeutic discovery and tailor management strategy to the individual patient. While some therapies may be applicable broadly to all ARDS patients, others may benefit only certain biologically distinct subsets. The twenty-year ARDSne(x)t research agenda calls for bringing personalized medicine to ARDS, asking simultaneously both whether a treatment affords clinically meaningful benefit and for whom. This expanded scope necessitates acquisition of highly granular biological, physiological, and clinical data as the new standard across studies. Tremendous investment in research infrastructure and global collaboration will be vital to fulfilling this agenda. PMID:27040103

Abdominal Muscle Activity during Mechanical Ventilation Increases Lung Injury in Severe Acute Respiratory Distress Syndrome

PubMed Central

Zhang, Xianming; Wu, Weiliang; Zhu, Yongcheng; Jiang, Ying; Du, Juan; Chen, Rongchang

2016-01-01

Objective It has proved that muscle paralysis was more protective for injured lung in severe acute respiratory distress syndrome (ARDS), but the precise mechanism is not clear. The purpose of this study was to test the hypothesis that abdominal muscle activity during mechanically ventilation increases lung injury in severe ARDS. Methods Eighteen male Beagles were studied under mechanical ventilation with anesthesia. Severe ARDS was induced by repetitive oleic acid infusion. After lung injury, Beagles were randomly assigned into spontaneous breathing group (BIPAPSB) and abdominal muscle paralysis group (BIPAPAP). All groups were ventilated with BIPAP model for 8h, and the high pressure titrated to reached a tidal volume of 6ml/kg, the low pressure was set at 10 cmH2O, with I:E ratio 1:1, and respiratory rate adjusted to a PaCO2 of 35–60 mmHg. Six Beagles without ventilator support comprised the control group. Respiratory variables, end-expiratory volume (EELV) and gas exchange were assessed during mechanical ventilation. The levels of Interleukin (IL)-6, IL-8 in lung tissue and plasma were measured by qRT-PCR and ELISA respectively. Lung injury scores were determined at end of the experiment. Results For the comparable ventilator setting, as compared with BIPAPSB group, the BIPAPAP group presented higher EELV (427±47 vs. 366±38 ml) and oxygenation index (293±36 vs. 226±31 mmHg), lower levels of IL-6(216.6±48.0 vs. 297.5±71.2 pg/ml) and IL-8(246.8±78.2 vs. 357.5±69.3 pg/ml) in plasma, and lower express levels of IL-6 mRNA (15.0±3.8 vs. 21.2±3.7) and IL-8 mRNA (18.9±6.8 vs. 29.5±7.9) in lung tissues. In addition, less lung histopathology injury were revealed in the BIPAPAP group (22.5±2.0 vs. 25.2±2.1). Conclusion Abdominal muscle activity during mechanically ventilation is one of the injurious factors in severe ARDS, so abdominal muscle paralysis might be an effective strategy to minimize ventilator-induce lung injury. PMID:26745868

Epidemiology, Patterns of Care, and Mortality for Patients With Acute Respiratory Distress Syndrome in Intensive Care Units in 50 Countries.

PubMed

Bellani, Giacomo; Laffey, John G; Pham, Tài; Fan, Eddy; Brochard, Laurent; Esteban, Andres; Gattinoni, Luciano; van Haren, Frank; Larsson, Anders; McAuley, Daniel F; Ranieri, Marco; Rubenfeld, Gordon; Thompson, B Taylor; Wrigge, Hermann; Slutsky, Arthur S; Pesenti, Antonio

2016-02-23

Limited information exists about the epidemiology, recognition, management, and outcomes of patients with the acute respiratory distress syndrome (ARDS). To evaluate intensive care unit (ICU) incidence and outcome of ARDS and to assess clinician recognition, ventilation management, and use of adjuncts-for example prone positioning-in routine clinical practice for patients fulfilling the ARDS Berlin Definition. The Large Observational Study to Understand the Global Impact of Severe Acute Respiratory Failure (LUNG SAFE) was an international, multicenter, prospective cohort study of patients undergoing invasive or noninvasive ventilation, conducted during 4 consecutive weeks in the winter of 2014 in a convenience sample of 459 ICUs from 50 countries across 5 continents. Acute respiratory distress syndrome. The primary outcome was ICU incidence of ARDS. Secondary outcomes included assessment of clinician recognition of ARDS, the application of ventilatory management, the use of adjunctive interventions in routine clinical practice, and clinical outcomes from ARDS. Of 29,144 patients admitted to participating ICUs, 3022 (10.4%) fulfilled ARDS criteria. Of these, 2377 patients developed ARDS in the first 48 hours and whose respiratory failure was managed with invasive mechanical ventilation. The period prevalence of mild ARDS was 30.0% (95% CI, 28.2%-31.9%); of moderate ARDS, 46.6% (95% CI, 44.5%-48.6%); and of severe ARDS, 23.4% (95% CI, 21.7%-25.2%). ARDS represented 0.42 cases per ICU bed over 4 weeks and represented 10.4% (95% CI, 10.0%-10.7%) of ICU admissions and 23.4% of patients requiring mechanical ventilation. Clinical recognition of ARDS ranged from 51.3% (95% CI, 47.5%-55.0%) in mild to 78.5% (95% CI, 74.8%-81.8%) in severe ARDS. Less than two-thirds of patients with ARDS received a tidal volume 8 of mL/kg or less of predicted body weight. Plateau pressure was measured in 40.1% (95% CI, 38.2-42.1), whereas 82.6% (95% CI, 81.0%-84.1%) received a positive end-expository pressure (PEEP) of less than 12 cm H2O. Prone positioning was used in 16.3% (95% CI, 13.7%-19.2%) of patients with severe ARDS. Clinician recognition of ARDS was associated with higher PEEP, greater use of neuromuscular blockade, and prone positioning. Hospital mortality was 34.9% (95% CI, 31.4%-38.5%) for those with mild, 40.3% (95% CI, 37.4%-43.3%) for those with moderate, and 46.1% (95% CI, 41.9%-50.4%) for those with severe ARDS. Among ICUs in 50 countries, the period prevalence of ARDS was 10.4% of ICU admissions. This syndrome appeared to be underrecognized and undertreated and associated with a high mortality rate. These findings indicate the potential for improvement in the management of patients with ARDS. clinicaltrials.gov Identifier: NCT02010073.

Mechanical ventilation in patients subjected to extracorporeal membrane oxygenation (ECMO).

PubMed

López Sanchez, M

2017-11-01

Mechanical ventilation (MV) is a crucial element in the management of acute respiratory distress syndrome (ARDS), because there is high level evidence that a low tidal volume of 6ml/kg (protective ventilation) improves survival. In these patients with refractory respiratory insufficiency, venovenous extracorporeal membrane oxygenation (ECMO) can be used. This salvage technique improves oxygenation, promotes CO 2 clearance, and facilitates protective and ultraprotective MV, potentially minimizing ventilation-induced lung injury. Although numerous trials have investigated different ventilation strategies in patients with ARDS, consensus is lacking on the optimal MV settings during venovenous ECMO. Although the concept of "lung rest" was introduced years ago, there are no evidence-based guidelines on its use in application to MV in patients supported by ECMO. How MV in ECMO patients can promote lung recovery and weaning from ventilation is not clear. The purpose of this review is to describe the ventilation strategies used during venovenous ECMO in clinical practice. Copyright © 2017 Elsevier España, S.L.U. y SEMICYUC. All rights reserved.

Factors among patients receiving prone positioning for the acute respiratory distress syndrome found useful for predicting mortality in the intensive care unit.

PubMed

Modrykamien, Ariel M; Daoud, Yahya

2018-01-01

Optimal mechanical ventilation management in patients with the acute respiratory distress syndrome (ARDS) involves the use of low tidal volumes and limited plateau pressure. Refractory hypoxemia may not respond to this strategy, requiring other interventions. The use of prone positioning in severe ARDS resulted in improvement in 28-day survival. To determine whether mechanical ventilation strategies or other parameters affected survival in patients undergoing prone positioning, a retrospective analysis was conducted of a consecutive series of patients with severe ARDS treated with prone positioning. Demographic and clinical information involving mechanical ventilation strategies, as well as other variables associated with prone positioning, was collected. The rate of in-hospital mortality was obtained, and previously described parameters were compared between survivors and nonsurvivors. Forty-three patients with severe ARDS were treated with prone positioning, and 27 (63%) died in the intensive care unit. Only three parameters were significant predictors of survival: APACHE II score ( P = 0.03), plateau pressure ( P = 0.02), and driving pressure ( P = 0.04). The ability of each of these parameters to predict mortality was assessed with receiver operating characteristic curves. The area under the curve values for APACHE II, plateau pressure, and driving pressure were 0.74, 0.69, and 0.67, respectively. In conclusion, in a group of patients with severe ARDS treated with prone positioning, only APACHE II, plateau pressure, and driving pressure were associated with mortality in the intensive care unit.

The ALIEN study: incidence and outcome of acute respiratory distress syndrome in the era of lung protective ventilation.

PubMed

Villar, Jesús; Blanco, Jesús; Añón, José Manuel; Santos-Bouza, Antonio; Blanch, Lluís; Ambrós, Alfonso; Gandía, Francisco; Carriedo, Demetrio; Mosteiro, Fernando; Basaldúa, Santiago; Fernández, Rosa Lidia; Kacmarek, Robert M

2011-12-01

While our understanding of the pathogenesis and management of acute respiratory distress syndrome (ARDS) has improved over the past decade, estimates of its incidence have been controversial. The goal of this study was to examine ARDS incidence and outcome under current lung protective ventilatory support practices before and after the diagnosis of ARDS. This was a 1-year prospective, multicenter, observational study in 13 geographical areas of Spain (serving a population of 3.55 million at least 18 years of age) between November 2008 and October 2009. Subjects comprised all consecutive patients meeting American-European Consensus Criteria for ARDS. Data on ventilatory management, gas exchange, hemodynamics, and organ dysfunction were collected. A total of 255 mechanically ventilated patients fulfilled the ARDS definition, representing an incidence of 7.2/100,000 population/year. Pneumonia and sepsis were the most common causes of ARDS. At the time of meeting ARDS criteria, mean PaO(2)/FiO(2) was 114 ± 40 mmHg, mean tidal volume was 7.2 ± 1.1 ml/kg predicted body weight, mean plateau pressure was 26 ± 5 cmH(2)O, and mean positive end-expiratory pressure (PEEP) was 9.3 ± 2.4 cmH(2)O. Overall ARDS intensive care unit (ICU) and hospital mortality was 42.7% (95%CI 37.7-47.8) and 47.8% (95%CI 42.8-53.0), respectively. This is the first study to prospectively estimate the ARDS incidence during the routine application of lung protective ventilation. Our findings support previous estimates in Europe and are an order of magnitude lower than those reported in the USA and Australia. Despite use of lung protective ventilation, overall ICU and hospital mortality of ARDS patients is still higher than 40%.

Mechanical ventilation strategies for intensive care unit patients without acute lung injury or acute respiratory distress syndrome: a systematic review and network meta-analysis.

PubMed

Guo, Lei; Wang, Weiwei; Zhao, Nana; Guo, Libo; Chi, Chunjie; Hou, Wei; Wu, Anqi; Tong, Hongshuang; Wang, Yue; Wang, Changsong; Li, Enyou

2016-07-22

It has been shown that the application of a lung-protective mechanical ventilation strategy can improve the prognosis of patients with acute lung injury (ALI) or acute respiratory distress syndrome (ARDS). However, the optimal mechanical ventilation strategy for intensive care unit (ICU) patients without ALI or ARDS is uncertain. Therefore, we performed a network meta-analysis to identify the optimal mechanical ventilation strategy for these patients. We searched the Cochrane Central Register of Controlled Trials (CENTRAL) in the Cochrane Library, EMBASE, MEDLINE, CINAHL, and Web of Science for studies published up to July 2015 in which pulmonary compliance or the partial pressure of arterial oxygen/fraction of inspired oxygen (PaO2/FIO2) ratio was assessed in ICU patients without ALI or ARDS, who received mechanical ventilation via different strategies. The data for study characteristics, methods, and outcomes were extracted. We assessed the studies for eligibility, extracted the data, pooled the data, and used a Bayesian fixed-effects model to combine direct comparisons with indirect evidence. Seventeen randomized controlled trials including a total of 575 patients who received one of six ventilation strategies were included for network meta-analysis. Among ICU patients without ALI or ARDS, strategy C (lower tidal volume (VT) + higher positive end-expiratory pressure (PEEP)) resulted in the highest PaO2/FIO2 ratio; strategy B (higher VT + lower PEEP) was associated with the highest pulmonary compliance; strategy A (lower VT + lower PEEP) was associated with a shorter length of ICU stay; and strategy D (lower VT + zero end-expiratory pressure (ZEEP)) was associated with the lowest PaO2/FiO2 ratio and pulmonary compliance. For ICU patients without ALI or ARDS, strategy C (lower VT + higher PEEP) was associated with the highest PaO2/FiO2 ratio. Strategy B (higher VT + lower PEEP) was superior to the other strategies in improving pulmonary compliance. Strategy A (lower VT + lower PEEP) was associated with a shorter length of ICU stay, whereas strategy D (lower VT + ZEEP) was associated with the lowest PaO2/FiO2 ratio and pulmonary compliance.

Lessons to learn from epidemiologic studies in ARDS.

PubMed

McNicholas, Bairbre A; Rooney, Grainne M; Laffey, John G

2018-02-01

Recent advances in our understanding of the epidemiology of ARDS has generated key insights into the incidence, risk factors, demographics, management and outcomes from this devastating clinical syndrome. ARDS occurs in 10% of all ICU patients, in 23% of all mechanically ventilated patients, with 5.5 cases per ICU bed each year. Although some regional variation exists regarding ARDS incidence, this may be less than previously thought. Subphenotypes are increasingly identified within the ARDS cohort, with studies identifying a 'hyperinflammatory' or 'reactive' subgroup that has a higher mortality, and may respond differently to therapeutic interventions. Demographic factors, such as race, may also affect the therapeutic response. Although mortality in ARDS is decreasing in clinical trials, it remains unchanged at approximately 40% in major observational studies. Modifiable ventilatory management factors, including PEEP, airway pressures, and respiratory rate are associated with mortality in ARDS. Hospital and ICU organizational factors play a role in outcome, whereas socioeconomic status is independently associated with survival in patients with ARDS. The Kigali adaptation of the Berlin ARDS definition may provide useful insights into the burden of ARDS in the developing world. ARDS exerts a substantial disease burden, with 40% of patients dying in hospital. Diverse factors, including patient-related factors such as age and illness severity, country level socioeconomic status, and ventilator management and ICU organizational factors each contribute to outcome from ARDS. Addressing these issues provides opportunities to improve outcome in patients with ARDS.

Effects of lung protective mechanical ventilation associated with permissive respiratory acidosis on regional extra-pulmonary blood flow in experimental ARDS.

PubMed

Hering, Rudolf; Kreyer, Stefan; Putensen, Christian

2017-10-27

Lung protective mechanical ventilation with limited peak inspiratory pressure has been shown to affect cardiac output in patients with ARDS. However, little is known about the impact of lung protective mechanical ventilation on regional perfusion, especially when associated with moderate permissive respiratory acidosis. We hypothesized that lung protective mechanical ventilation with limited peak inspiratory pressure and moderate respiratory acidosis results in an increased cardiac output but unequal distribution of blood flow to the different organs of pigs with oleic-acid induced ARDS. Twelve pigs were enrolled, 3 died during instrumentation and induction of lung injury. Thus, 9 animals received pressure controlled mechanical ventilation with a PEEP of 5 cmH 2 O and limited peak inspiratory pressure (17 ± 4 cmH 2 O) versus increased peak inspiratory pressure (23 ± 6 cmH 2 O) in a crossover-randomized design and were analyzed. The sequence of limited versus increased peak inspiratory pressure was randomized using sealed envelopes. Systemic and regional hemodynamics were determined by double indicator dilution technique and colored microspheres, respectively. The paired student t-test and the Wilcoxon test were used to compare normally and not normally distributed data, respectively. Mechanical ventilation with limited inspiratory pressure resulted in moderate hypercapnia and respiratory acidosis (PaCO 2 71 ± 12 vs. 46 ± 9 mmHg, and pH 7.27 ± 0.05 vs. 7.38 ± 0.04, p < 0.001, respectively), increased cardiac output (140 ± 32 vs. 110 ± 22 ml/min/kg, p<0.05) and regional blood flow in the myocardium, brain and spinal cord, adrenal and thyroid glands, the mucosal layers of the esophagus and jejunum, the muscularis layers of the esophagus and duodenum, and the gall and urinary bladders. Perfusion of kidneys, pancreas, spleen, hepatic arterial bed, and the mucosal and muscularis blood flow to the other evaluated intestinal regions remained unchanged. In this porcine model of ARDS mechanical ventilation with limited peak inspiratory pressure resulting in moderate respiratory acidosis was associated with an increase in cardiac output. However, the better systemic blood flow was not uniformly directed to the different organs. This observation may be of clinical interest in patients, e.g. with cardiac, renal and cerebral pathologies.

Implementation of a Goal-Directed Mechanical Ventilation Order Set Driven by Respiratory Therapists Improves Compliance With Best Practices for Mechanical Ventilation.

PubMed

Radosevich, Misty A; Wanta, Brendan T; Meyer, Todd J; Weber, Verlin W; Brown, Daniel R; Smischney, Nathan J; Diedrich, Daniel A

2017-01-01

Data regarding best practices for ventilator management strategies that improve outcomes in acute respiratory distress syndrome (ARDS) are readily available. However, little is known regarding processes to ensure compliance with these strategies. We developed a goal-directed mechanical ventilation order set that included physician-specified lung-protective ventilation and oxygenation goals to be implemented by respiratory therapists (RTs). We sought as a primary outcome to determine whether an RT-driven order set with predefined oxygenation and ventilation goals could be implemented and associated with improved adherence with best practice. We evaluated 1302 patients undergoing invasive mechanical ventilation (1693 separate episodes of invasive mechanical ventilation) prior to and after institution of a standardized, goal-directed mechanical ventilation order set using a controlled before-and-after study design. Patient-specific goals for oxygenation partial pressure of oxygen in arterial blood (Pao 2 ), ARDS Network [Net] positive end-expiratory pressure [PEEP]/fraction of inspired oxygen [Fio 2 ] table use) and ventilation (pH, partial pressure of carbon dioxide) were selected by prescribers and implemented by RTs. Compliance with the new mechanical ventilation order set was high: 88.2% compliance versus 3.8% before implementation of the order set ( P < .001). Adherence to the PEEP/Fio 2 table after implementation of the order set was significantly greater (86.0% after vs 82.9% before, P = .02). There was no difference in duration of mechanical ventilation, intensive care unit (ICU) length of stay, and in-hospital or ICU mortality. A standardized best practice mechanical ventilation order set can be implemented by a multidisciplinary team and is associated with improved compliance to written orders and adherence to the ARDSNet PEEP/Fio 2 table.

Fifty Years of Research in ARDS. Is Extracorporeal Circulation the Future of Acute Respiratory Distress Syndrome Management?

PubMed

Combes, Alain; Pesenti, Antonio; Ranieri, V Marco

2017-05-01

Mechanical ventilation (MV) remains the cornerstone of acute respiratory distress syndrome (ARDS) management. It guarantees sufficient alveolar ventilation, high Fi O 2 concentration, and high positive end-expiratory pressure levels. However, experimental and clinical studies have accumulated, demonstrating that MV also contributes to the high mortality observed in patients with ARDS by creating ventilator-induced lung injury. Under these circumstances, extracorporeal lung support (ECLS) may be beneficial in two distinct clinical settings: to rescue patients from the high risk for death associated with severe hypoxemia, hypercapnia, or both not responding to maximized conventional MV, and to replace MV and minimize/abolish the harmful effects of ventilator-induced lung injury. High extracorporeal blood flow venovenous extracorporeal membrane oxygenation (ECMO) may therefore rescue the sickest patients with ARDS from the high risk for death associated with severe hypoxemia, hypercapnia, or both not responding to maximized conventional MV. Successful venovenous ECMO treatment in patients with extremely severe H1N1-associated ARDS and positive results of the CESAR trial have led to an exponential use of the technology in recent years. Alternatively, lower-flow extracorporeal CO 2 removal devices may be used to reduce the intensity of MV (by reducing Vt from 6 to 3-4 ml/kg) and to minimize or even abolish the harmful effects of ventilator-induced lung injury if used as an alternative to conventional MV in nonintubated, nonsedated, and spontaneously breathing patients. Although conceptually very attractive, the use of ECLS in patients with ARDS remains controversial, and high-quality research is needed to further advance our knowledge in the field.

Effects of tidal volume on work of breathing during lung-protective ventilation in patients with acute lung injury and acute respiratory distress syndrome.

PubMed

Kallet, Richard H; Campbell, Andre R; Dicker, Rochelle A; Katz, Jeffrey A; Mackersie, Robert C

2006-01-01

To assess the effects of step-changes in tidal volume on work of breathing during lung-protective ventilation in patients with acute lung injury (ALI) or the acute respiratory distress syndrome (ARDS). Prospective, nonconsecutive patients with ALI/ARDS. Adult surgical, trauma, and medical intensive care units at a major inner-city, university-affiliated hospital. Ten patients with ALI/ARDS managed clinically with lung-protective ventilation. Five patients were ventilated at a progressively smaller tidal volume in 1 mL/kg steps between 8 and 5 mL/kg; five other patients were ventilated at a progressively larger tidal volume from 5 to 8 mL/kg. The volume mode was used with a flow rate of 75 L/min. Minute ventilation was maintained constant at each tidal volume setting. Afterward, patients were placed on continuous positive airway pressure for 1-2 mins to measure their spontaneous tidal volume. Work of breathing and other variables were measured with a pulmonary mechanics monitor (Bicore CP-100). Work of breathing progressively increased (0.86 +/- 0.32, 1.05 +/- 0.40, 1.22 +/- 0.36, and 1.57 +/- 0.43 J/L) at a tidal volume of 8, 7, 6, and 5 mL/kg, respectively. In nine of ten patients there was a strong negative correlation between work of breathing and the ventilator-to-patient tidal volume difference (R = -.75 to -.998). : The ventilator-delivered tidal volume exerts an independent influence on work of breathing during lung-protective ventilation in patients with ALI/ARDS. Patient work of breathing is inversely related to the difference between the ventilator-delivered tidal volume and patient-generated tidal volume during a brief trial of unassisted breathing.

Combination of Extracorporeal Life Support and Mesenchymal Stem Cell Therapy for Treatment of ARDS in Combat Casualties and Evacuation of Service Members with ARDS

DTIC Science & Technology

2017-10-01

invasiveness of mechanical ventilation and inflammatory mediators as well as improvement in oxygenation and functional outcome. 4 Keywords Acute...The Clark system is allowing us to measure the mitochondrial activity by the oxygen consumption during activation. Because the LPS-induced injury we... Ventilation • Tidal Volume • Respiratory Rate • Peak inspiratory Pressure • Positive End Expiratory Pressure (PEEP) • Fraction of inspired oxygen

Protective mechanical ventilation, why use it?

PubMed

Seiberlich, Emerson; Santana, Jonas Alves; Chaves, Renata de Andrade; Seiberlich, Raquel Carvalho

2011-01-01

Mechanical ventilation (MV) strategies have been modified over the last decades with a tendency for increasingly lower tidal volumes (VT). However, in patients without acute lung injury (ALI) or acute respiratory distress syndrome (ARDS) the use of high VTs is still very common. Retrospective studies suggest that this practice can be related to mechanical ventilation-associated ALI. The objective of this review is to search for evidence to guide protective MV in patients with healthy lungs and to suggest strategies to properly ventilate lungs with ALI/ARDS. A review based on the main articles that focus on the use of strategies of mechanical ventilation was performed. Consistent studies to determine which would be the best way to ventilate a patient with healthy lungs are lacking. Expert recommendations and current evidence presented in this article indicate that the use of a VT lower than 10 mL.kg(-1), associated with positive end-expiratory pressure (PEEP) ≥ 5 cmH(2)O without exceeding a pressure plateau of 15 to 20 cmH(2)O could minimize alveolar stretching at the end of inspiration and avoid possible inflammation or alveolar collapse. Copyright © 2011 Elsevier Editora Ltda. All rights reserved.

Optimizing PEEP by Electrical Impedance Tomography in a Porcine Animal Model of ARDS.

PubMed

Hochhausen, Nadine; Biener, Ingeborg; Rossaint, Rolf; Follmann, Andreas; Bleilevens, Christian; Braunschweig, Till; Leonhardt, Steffen; Czaplik, Michael

2017-03-01

Mechanical ventilation is necessary in diverse clinical circumstances. Especially in the context of ARDS, so-called protective ventilation strategies must be followed. It is already known that PEEP might enhance oxygenation in ARDS. However, determining the optimal PEEP settings in clinical routines is challenging. Electrical impedance tomography (EIT) is a promising technique with which to adjust ventilator settings. We investigated whether the combination of different EIT parameters, namely the global inhomogeneity and hyperdistension indices, may lead to a feasible and safe PEEP setting. ARDS was induced by a double-hit approach in 18 pigs weighing, on average, 34.8 ± 3.97 kg. First, a surfactant washout was conducted; second, the tidal volume was increased to 20 mL/kg body weight, triggering a ventilator-induced lung injury. Subsequently, pigs were randomized to either the EIT or control groups, followed by an observation time of 24 h. In the control group, PEEP was set according to the ARDS network table. In the EIT group, a PEEP trial was conducted to determine an appropriate PEEP. At defined time points, hemodynamic measures, ventilation parameters, and EIT recordings, as well as blood samples, were taken. After euthanization, lungs were removed for subsequent histopathological and cytological examination. The combination of PEEP and F IO 2 differed between groups, although respiratory compliance, gas exchange, and histopathological examinations, as well as hemodynamics, did not show any statistical differences between the EIT and control groups. However, in the control group, the PEEP/F IO 2 settings followed the given coupling; in the EIT group, divergent individual combinations of PEEP and F IO 2 ranges occurred. PEEP setting by EIT facilitates a more individual ventilation therapy. However, in our relatively short ARDS observation period of 24 h, no significant differences appeared in common clinical parameters compared with a control group. Copyright © 2017 by Daedalus Enterprises.

Fifty Years of Research in ARDS. Gas Exchange in Acute Respiratory Distress Syndrome.

PubMed

Radermacher, Peter; Maggiore, Salvatore Maurizio; Mercat, Alain

2017-10-15

Acute respiratory distress syndrome (ARDS) is characterized by severe impairment of gas exchange. Hypoxemia is mainly due to intrapulmonary shunt, whereas increased alveolar dead space explains the alteration of CO 2 clearance. Assessment of the severity of gas exchange impairment is a requisite for the characterization of the syndrome and the evaluation of its severity. Confounding factors linked to hemodynamic status can greatly influence the relationship between the severity of lung injury and the degree of hypoxemia and/or the effects of ventilator settings on gas exchange. Apart from situations of rescue treatment, targeting optimal gas exchange in ARDS has become less of a priority compared with prevention of injury. A complex question for clinicians is to understand when improvement in oxygenation and alveolar ventilation is related to a lower degree or risk of injury for the lungs. In this regard, a full understanding of gas exchange mechanism in ARDS is imperative for individualized symptomatic support of patients with ARDS.

Lung protective mechanical ventilation strategies in cardiothoracic critical care: a retrospective study.

PubMed

Zochios, Vasileios; Hague, Matthew; Giraud, Kimberly; Jones, Nicola

2016-01-01

A body of evidence supports the use of low tidal volumes in ventilated patients without lung pathology to slow progress to acute respiratory distress syndrome (ARDS) due to ventilator associated lung injury. We undertook a retrospective chart review and tested the hypothesis that tidal volume is a predictor of mortality in cardiothoracic (medical and surgical) critical care patients receiving invasive mechanical ventilation. Independent predictors of mortality in our study included: type of surgery, albumin, H + , bilirubin, and fluid balance. In particular, it is important to note that cardiac, thoracic, and transplant surgical patients were associated with lower mortality. However, our study did not sample equally from The Berlin Definition of ARDS severity categories (mild, moderate, and severe hypoxemia). Although our study was not adequately powered to detect a difference in mortality between these groups, it will inform the development of a large prospective cohort study exploring the role of low tidal volume ventilation in cardiothoracic critically ill patients.

Lung-protective ventilation initiated in the emergency department (LOV-ED): a study protocol for a quasi-experimental, before-after trial aimed at reducing pulmonary complications.

PubMed

Fuller, Brian M; Ferguson, Ian; Mohr, Nicholas M; Stephens, Robert J; Briscoe, Cristopher C; Kolomiets, Angelina A; Hotchkiss, Richard S; Kollef, Marin H

2016-04-11

In critically ill patients, acute respiratory distress syndrome (ARDS) and ventilator-associated conditions (VACs) are associated with increased mortality, survivor morbidity and healthcare resource utilisation. Studies conclusively demonstrate that initial ventilator settings in patients with ARDS, and at risk for it, impact outcome. No studies have been conducted in the emergency department (ED) to determine if lung-protective ventilation in patients at risk for ARDS can reduce its incidence. Since the ED is the entry point to the intensive care unit for hundreds of thousands of mechanically ventilated patients annually in the USA, this represents a knowledge gap in this arena. A lung-protective ventilation strategy was instituted in our ED in 2014. It aims to address the parameters in need of quality improvement, as demonstrated by our previous research: (1) prevention of volutrauma; (2) appropriate positive end-expiratory pressure setting; (3) prevention of hyperoxia; and (4) aspiration precautions. The lung-protective ventilation initiated in the emergency department (LOV-ED) trial is a single-centre, quasi-experimental before-after study testing the hypothesis that lung-protective ventilation, initiated in the ED, is associated with reduced pulmonary complications. An intervention cohort of 513 mechanically ventilated adult ED patients will be compared with over 1000 preintervention control patients. The primary outcome is a composite outcome of pulmonary complications after admission (ARDS and VACs). Multivariable logistic regression with propensity score adjustment will test the hypothesis that ED lung-protective ventilation decreases the incidence of pulmonary complications. Approval of the study was obtained prior to data collection on the first patient. As the study is a before-after observational study, examining the effect of treatment changes over time, it is being conducted with waiver of informed consent. This work will be disseminated by publication of full-length manuscripts, presentation in abstract form at major scientific meetings and data sharing with other investigators through academically established means. NCT02543554. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Protective lung ventilation in operating room: a systematic review.

PubMed

Futier, E; Constantin, J M; Jaber, S

2014-06-01

Postoperative pulmonary and extrapulmonary complications adversely affect clinical outcomes and healthcare utilization, so that prevention has become a measure of the quality of perioperative care. Mechanical ventilation is an essential support therapy to maintain adequate gas exchange during general anesthesia for surgery. Mechanical ventilation using high tidal volume (VT) (between 10 and 15 mL/kg) has been historically encouraged to prevent hypoxemia and atelectasis formation in anesthetized patients undergoing abdominal and thoracic surgery. However, there is accumulating evidence from both experimental and clinical studies that mechanical ventilation, especially the use of high VT and plateau pressure, may potentially aggravate or even initiate lung injury. Ventilator-associated lung injury can result from cyclic alveolar overdistension of non-dependent lung tissue, and repetitive opening and closing of dependent lung tissue resulting in ultrastructural damage at the junction of closed and open alveoli. Lung-protective ventilation, which refers to the use of lower VT and limited plateau pressure to minimize overdistension, and positive end-expiratory pressure to prevent alveolar collapse at end-expiration, was shown to improve outcome in critically ill patients with acute respiratory distress syndrome (ARDS). It has been recently suggested that this approach might also be beneficial in a broader population, especially in critically ill patients without ARDS at the onset of mechanical ventilation. There is, however, little evidence regarding a potential beneficial effect of lung protective ventilation during surgery, especially in patients with healthy lungs. Although surgical patients are frequently exposed to much shorter periods of mechanical ventilation, this is an important gap in knowledge given the number of patients receiving mechanical ventilation in the operating room. This review developed the benefits of lung protective ventilation during surgery and general anesthesia and offers some recommendations for mechanical ventilation in the surgical context.

Rationale, study design, and analysis plan of the Alveolar Recruitment for ARDS Trial (ART): study protocol for a randomized controlled trial.

PubMed

2012-08-28

Acute respiratory distress syndrome (ARDS) is associated with high in-hospital mortality. Alveolar recruitment followed by ventilation at optimal titrated PEEP may reduce ventilator-induced lung injury and improve oxygenation in patients with ARDS, but the effects on mortality and other clinical outcomes remain unknown. This article reports the rationale, study design, and analysis plan of the Alveolar Recruitment for ARDS Trial (ART). ART is a pragmatic, multicenter, randomized (concealed), controlled trial, which aims to determine if maximum stepwise alveolar recruitment associated with PEEP titration is able to increase 28-day survival in patients with ARDS compared to conventional treatment (ARDSNet strategy). We will enroll adult patients with ARDS of less than 72 h duration. The intervention group will receive an alveolar recruitment maneuver, with stepwise increases of PEEP achieving 45 cmH2O and peak pressure of 60 cmH2O, followed by ventilation with optimal PEEP titrated according to the static compliance of the respiratory system. In the control group, mechanical ventilation will follow a conventional protocol (ARDSNet). In both groups, we will use controlled volume mode with low tidal volumes (4 to 6 mL/kg of predicted body weight) and targeting plateau pressure ≤30 cmH2O. The primary outcome is 28-day survival, and the secondary outcomes are: length of ICU stay; length of hospital stay; pneumothorax requiring chest tube during first 7 days; barotrauma during first 7 days; mechanical ventilation-free days from days 1 to 28; ICU, in-hospital, and 6-month survival. ART is an event-guided trial planned to last until 520 events (deaths within 28 days) are observed. These events allow detection of a hazard ratio of 0.75, with 90% power and two-tailed type I error of 5%. All analysis will follow the intention-to-treat principle. If the ART strategy with maximum recruitment and PEEP titration improves 28-day survival, this will represent a notable advance to the care of ARDS patients. Conversely, if the ART strategy is similar or inferior to the current evidence-based strategy (ARDSNet), this should also change current practice as many institutions routinely employ recruitment maneuvers and set PEEP levels according to some titration method. ClinicalTrials.gov Identifier: NCT01374022.

Rationale, study design, and analysis plan of the Alveolar Recruitment for ARDS Trial (ART): Study protocol for a randomized controlled trial

PubMed Central

2012-01-01

Background Acute respiratory distress syndrome (ARDS) is associated with high in-hospital mortality. Alveolar recruitment followed by ventilation at optimal titrated PEEP may reduce ventilator-induced lung injury and improve oxygenation in patients with ARDS, but the effects on mortality and other clinical outcomes remain unknown. This article reports the rationale, study design, and analysis plan of the Alveolar Recruitment for ARDS Trial (ART). Methods/Design ART is a pragmatic, multicenter, randomized (concealed), controlled trial, which aims to determine if maximum stepwise alveolar recruitment associated with PEEP titration is able to increase 28-day survival in patients with ARDS compared to conventional treatment (ARDSNet strategy). We will enroll adult patients with ARDS of less than 72 h duration. The intervention group will receive an alveolar recruitment maneuver, with stepwise increases of PEEP achieving 45 cmH2O and peak pressure of 60 cmH2O, followed by ventilation with optimal PEEP titrated according to the static compliance of the respiratory system. In the control group, mechanical ventilation will follow a conventional protocol (ARDSNet). In both groups, we will use controlled volume mode with low tidal volumes (4 to 6 mL/kg of predicted body weight) and targeting plateau pressure ≤30 cmH2O. The primary outcome is 28-day survival, and the secondary outcomes are: length of ICU stay; length of hospital stay; pneumothorax requiring chest tube during first 7 days; barotrauma during first 7 days; mechanical ventilation-free days from days 1 to 28; ICU, in-hospital, and 6-month survival. ART is an event-guided trial planned to last until 520 events (deaths within 28 days) are observed. These events allow detection of a hazard ratio of 0.75, with 90% power and two-tailed type I error of 5%. All analysis will follow the intention-to-treat principle. Discussion If the ART strategy with maximum recruitment and PEEP titration improves 28-day survival, this will represent a notable advance to the care of ARDS patients. Conversely, if the ART strategy is similar or inferior to the current evidence-based strategy (ARDSNet), this should also change current practice as many institutions routinely employ recruitment maneuvers and set PEEP levels according to some titration method. Trial registration ClinicalTrials.gov Identifier: NCT01374022 PMID:22929542

Early application of airway pressure release ventilation may reduce the duration of mechanical ventilation in acute respiratory distress syndrome.

PubMed

Zhou, Yongfang; Jin, Xiaodong; Lv, Yinxia; Wang, Peng; Yang, Yunqing; Liang, Guopeng; Wang, Bo; Kang, Yan

2017-11-01

Experimental animal models of acute respiratory distress syndrome (ARDS) have shown that the updated airway pressure release ventilation (APRV) methodologies may significantly improve oxygenation, maximize lung recruitment, and attenuate lung injury, without circulatory depression. This led us to hypothesize that early application of APRV in patients with ARDS would allow pulmonary function to recover faster and would reduce the duration of mechanical ventilation as compared with low tidal volume lung protective ventilation (LTV). A total of 138 patients with ARDS who received mechanical ventilation for <48 h between May 2015 to October 2016 while in the critical care medicine unit (ICU) of the West China Hospital of Sichuan University were enrolled in the study. Patients were randomly assigned to receive APRV (n = 71) or LTV (n = 67). The settings for APRV were: high airway pressure (P high ) set at the last plateau airway pressure (P plat ), not to exceed 30 cmH 2 O) and low airway pressure ( P low ) set at 5 cmH 2 O; the release phase (T low ) setting adjusted to terminate the peak expiratory flow rate to ≥ 50%; release frequency of 10-14 cycles/min. The settings for LTV were: target tidal volume of 6 mL/kg of predicted body weight; P plat not exceeding 30 cmH 2 O; positive end-expiratory pressure (PEEP) guided by the PEEP-FiO 2 table according to the ARDSnet protocol. The primary outcome was the number of days without mechanical ventilation from enrollment to day 28. The secondary endpoints included oxygenation, P plat , respiratory system compliance, and patient outcomes. Compared with the LTV group, patients in the APRV group had a higher median number of ventilator-free days {19 [interquartile range (IQR) 8-22] vs. 2 (IQR 0-15); P < 0.001}. This finding was independent of the coexisting differences in chronic disease. The APRV group had a shorter stay in the ICU (P = 0.003). The ICU mortality rate was 19.7% in the APRV group versus 34.3% in the LTV group (P = 0.053) and was associated with better oxygenation and respiratory system compliance, lower P plat , and less sedation requirement during the first week following enrollment (P < 0.05, repeated-measures analysis of variance). Compared with LTV, early application of APRV in patients with ARDS improved oxygenation and respiratory system compliance, decreased P plat and reduced the duration of both mechanical ventilation and ICU stay.

Interaction between peri-operative blood transfusion, tidal volume, airway pressure and postoperative ARDS: an individual patient data meta-analysis

PubMed Central

Juffermans, Nicole P.; Hemmes, Sabrine N. T.; Barbas, Carmen S. V.; Beiderlinden, Martin; Biehl, Michelle; Fernandez-Bustamante, Ana; Futier, Emmanuel; Gajic, Ognjen; Jaber, Samir; Kozian, Alf; Licker, Marc; Lin, Wen-Qian; Memtsoudis, Stavros G.; Miranda, Dinis Reis; Moine, Pierre; Paparella, Domenico; Ranieri, Marco; Scavonetto, Federica; Schilling, Thomas; Selmo, Gabriele; Severgnini, Paolo; Sprung, Juraj; Sundar, Sugantha; Talmor, Daniel; Treschan, Tanja; Unzueta, Carmen; Weingarten, Toby N.; Wolthuis, Esther K.; Wrigge, Hermann; de Abreu, Marcelo Gama; Pelosi, Paolo; Schultz, Marcus J.

2018-01-01

Background Transfusion of blood products and mechanical ventilation with injurious settings are considered risk factors for postoperative lung injury in surgical Patients. Methods A systematic review and individual patient data meta-analysis was done to determine the independent effects of peri-operative transfusion of blood products, intra-operative tidal volume and airway pressure in adult patients undergoing mechanical ventilation for general surgery, as well as their interactions on the occurrence of postoperative acute respiratory distress syndrome (ARDS). Observational studies and randomized trials were identified by a systematic search of MEDLINE, CINAHL, Web of Science, and CENTRAL and screened for inclusion into a meta-analysis. Individual patient data were obtained from the corresponding authors. Patients were stratified according to whether they received transfusion in the peri-operative period [red blood cell concentrates (RBC) and/or fresh frozen plasma (FFP)], tidal volume size [≤7 mL/kg predicted body weight (PBW), 7–10 and >10 mL/kg PBW] and airway pressure level used during surgery (≤15, 15–20 and >20 cmH2O). The primary outcome was development of postoperative ARDS. Results Seventeen investigations were included (3,659 patients). Postoperative ARDS occurred in 40 (7.2%) patients who received at least one blood product compared to 40 patients (2.5%) who did not [adjusted hazard ratio (HR), 2.32; 95% confidence interval (CI), 1.25–4.33; P=0.008]. Incidence of postoperative ARDS was highest in patients ventilated with tidal volumes of >10 mL/kg PBW and having airway pressures of >20 cmH2O receiving both RBC and FFP, and lowest in patients ventilated with tidal volume of ≤7 mL/kg PBW and having airway pressures of ≤15 cmH2O with no transfusion. There was a significant interaction between transfusion and airway pressure level (P=0.002) on the risk of postoperative ARDS. Conclusions Peri-operative transfusion of blood products is associated with an increased risk of postoperative ARDS, which seems more dependent on airway pressure than tidal volume size. PMID:29430440

Interaction between peri-operative blood transfusion, tidal volume, airway pressure and postoperative ARDS: an individual patient data meta-analysis.

PubMed

Serpa Neto, Ary; Juffermans, Nicole P; Hemmes, Sabrine N T; Barbas, Carmen S V; Beiderlinden, Martin; Biehl, Michelle; Fernandez-Bustamante, Ana; Futier, Emmanuel; Gajic, Ognjen; Jaber, Samir; Kozian, Alf; Licker, Marc; Lin, Wen-Qian; Memtsoudis, Stavros G; Miranda, Dinis Reis; Moine, Pierre; Paparella, Domenico; Ranieri, Marco; Scavonetto, Federica; Schilling, Thomas; Selmo, Gabriele; Severgnini, Paolo; Sprung, Juraj; Sundar, Sugantha; Talmor, Daniel; Treschan, Tanja; Unzueta, Carmen; Weingarten, Toby N; Wolthuis, Esther K; Wrigge, Hermann; de Abreu, Marcelo Gama; Pelosi, Paolo; Schultz, Marcus J

2018-01-01

Transfusion of blood products and mechanical ventilation with injurious settings are considered risk factors for postoperative lung injury in surgical Patients. A systematic review and individual patient data meta-analysis was done to determine the independent effects of peri-operative transfusion of blood products, intra-operative tidal volume and airway pressure in adult patients undergoing mechanical ventilation for general surgery, as well as their interactions on the occurrence of postoperative acute respiratory distress syndrome (ARDS). Observational studies and randomized trials were identified by a systematic search of MEDLINE, CINAHL, Web of Science, and CENTRAL and screened for inclusion into a meta-analysis. Individual patient data were obtained from the corresponding authors. Patients were stratified according to whether they received transfusion in the peri-operative period [red blood cell concentrates (RBC) and/or fresh frozen plasma (FFP)], tidal volume size [≤7 mL/kg predicted body weight (PBW), 7-10 and >10 mL/kg PBW] and airway pressure level used during surgery (≤15, 15-20 and >20 cmH 2 O). The primary outcome was development of postoperative ARDS. Seventeen investigations were included (3,659 patients). Postoperative ARDS occurred in 40 (7.2%) patients who received at least one blood product compared to 40 patients (2.5%) who did not [adjusted hazard ratio (HR), 2.32; 95% confidence interval (CI), 1.25-4.33; P=0.008]. Incidence of postoperative ARDS was highest in patients ventilated with tidal volumes of >10 mL/kg PBW and having airway pressures of >20 cmH 2 O receiving both RBC and FFP, and lowest in patients ventilated with tidal volume of ≤7 mL/kg PBW and having airway pressures of ≤15 cmH 2 O with no transfusion. There was a significant interaction between transfusion and airway pressure level (P=0.002) on the risk of postoperative ARDS. Peri-operative transfusion of blood products is associated with an increased risk of postoperative ARDS, which seems more dependent on airway pressure than tidal volume size.

Update on the Role of Extracorporeal CO2 Removal as an Adjunct to Mechanical Ventilation in ARDS

DTIC Science & Technology

2015-03-16

alveoli, atelectotrauma, and increased in- flammatory mediator levels [7]. The ARDSNet study re- ported a reduction in mortality with a ventilation... mortality rates [6]. Impaired RV function in early stage ARDS may be under- diagnosed and yet it might be the harbinger of a down- ward spiral in the ...them according to the ARDSNet protocol for 72 h, at which point the tidal volume was reduced from 6 to 4 ml/kg in all patients (n = 10) who had a plateau

Outcome of Concurrent Occult Hemothorax and Pneumothorax in Trauma Patients Who Required Assisted Ventilation

PubMed Central

Mahmood, Ismail; Tawfeek, Zainab; El-Menyar, Ayman; Zarour, Ahmad; Afifi, Ibrahim; Kumar, Suresh; Latifi, Rifat; Al-Thani, Hassan

2015-01-01

Background. The management and outcomes of occult hemopneumothorax in blunt trauma patients who required mechanical ventilation are not well studied. We aimed to study patients with occult hemopneumothorax on mechanical ventilation who could be carefully managed without tube thoracostomy. Methods. Chest trauma patients with occult hemopneumothorax who were on mechanical ventilation were prospectively evaluated. The presence of hemopneumothorax was confirmed by CT scanning. Hospital length of stay, complications, and outcome were recorded. Results. A total of 56 chest trauma patients with occult hemopneumothorax who were on ventilatory support were included with a mean age of 36 ± 13 years. Hemopneumothorax was managed conservatively in 72% cases and 28% underwent tube thoracostomy as indicated. 29% of patients developed pneumonia, 16% had Acute Respiratory Distress Syndrome (ARDS), and 7% died. Thickness of hemothorax, duration of mechanical ventilation, and development of ARDS were significantly associated with tube thoracostomy in comparison to no-chest tube group. Conclusions. The majority of occult hemopneumothorax can be carefully managed without tube thoracostomy in patients who required positive pressure ventilation. Tube thoracotomy could be restricted to those who had evidence of increase in the size of the hemothorax or pneumothorax on follow-up chest radiographs or developed respiratory compromise. PMID:25785199

Obstructive Sleep Apnea, Obesity, and the Development of Acute Respiratory Distress Syndrome

PubMed Central

Karnatovskaia, Lioudmila V.; Lee, Augustine S.; Bender, S. Patrick; Talmor, Daniel; Festic, Emir

2014-01-01

Background: Obstructive sleep apnea (OSA) may increase the risk of respiratory complications and acute respiratory distress syndrome (ARDS) among surgical patients. OSA is more prevalent among obese individuals; obesity can predispose to ARDS. Hypothesis: It is unclear whether OSA independently contributes towards the risk of ARDS among hospitalized patients. Methods: This is a pre-planned retrospective subgroup analysis of the prospectively identified cohort of 5,584 patients across 22 hospitals with at least one risk factor for ARDS at the time of hospitalization from a trial by the US Critical Illness and Injury Trials Group designed to validate the Lung Injury Prediction Score. A total of 252 patients (4.5%) had a diagnosis of OSA at the time of hospitalization; of those, 66% were obese. Following multivariate adjustment in the logistic regression model, there was no significant relationship between OSA and development of ARDS (OR = 0.65, 95%CI = 0.32-1.22). However, body mass index (BMI) was associated with subsequent ARDS development (OR = 1.02, 95%CI = 1.00-1.04, p = 0.03). Neither OSA nor BMI affected mechanical ventilation requirement or mortality. Conclusions: Prior diagnosis of OSA did not independently affect development of ARDS among patients with at least one predisposing condition, nor the need for mechanical ventilation or hospital mortality. Obesity appeared to independently increase the risk of ARDS. Citation: Karnatovskaia LV, Lee AS, Bender SP, Talmor D, Festic E. Obstructive sleep apnea, obesity, and the development of acute respiratory distress syndrome. J Clin Sleep Med 2014;10(6):657-662. PMID:24932146

Novel analysis of 4DCT imaging quantifies progressive increases in anatomic dead space during mechanical ventilation in mice.

PubMed

Kim, Elizabeth H; Preissner, Melissa; Carnibella, Richard P; Samarage, Chaminda R; Bennett, Ellen; Diniz, Marcio A; Fouras, Andreas; Zosky, Graeme R; Jones, Heather D

2017-09-01

Increased dead space is an important prognostic marker in early acute respiratory distress syndrome (ARDS) that correlates with mortality. The cause of increased dead space in ARDS has largely been attributed to increased alveolar dead space due to ventilation/perfusion mismatching and shunt. We sought to determine whether anatomic dead space also increases in response to mechanical ventilation. Mice received intratracheal lipopolysaccharide (LPS) or saline and mechanical ventilation (MV). Four-dimensional computed tomography (4DCT) scans were performed at onset of MV and after 5 h of MV. Detailed measurements of airway volumes and lung tidal volumes were performed using image analysis software. The forced oscillation technique was used to obtain measures of airway resistance, tissue damping, and tissue elastance. The ratio of airway volumes to total tidal volume increased significantly in response to 5 h of mechanical ventilation, regardless of LPS exposure, and airways demonstrated significant variation in volumes over the respiratory cycle. These findings were associated with an increase in tissue elastance (decreased lung compliance) but without changes in tidal volumes. Airway volumes increased over time with exposure to mechanical ventilation without a concomitant increase in tidal volumes. These findings suggest that anatomic dead space fraction increases progressively with exposure to positive pressure ventilation and may represent a pathological process. NEW & NOTEWORTHY We demonstrate that anatomic dead space ventilation increases significantly over time in mice in response to mechanical ventilation. The novel functional lung-imaging techniques applied here yield sensitive measures of airway volumes that may have wide applications. Copyright © 2017 the American Physiological Society.

Neutrophil apoptosis: a marker of disease severity in sepsis and sepsis-induced acute respiratory distress syndrome

PubMed Central

Fialkow, Léa; Fochesatto Filho, Luciano; Bozzetti, Mary C; Milani, Adriana R; Rodrigues Filho, Edison M; Ladniuk, Roberta M; Pierozan, Paula; de Moura, Rafaela M; Prolla, João C; Vachon, Eric; Downey, Gregory P

2006-01-01

Introduction Apoptosis of neutrophils (polymorphonuclear neutrophils [PMNs]) may limit inflammatory injury in sepsis and acute respiratory distress syndrome (ARDS), but the relationship between the severity of sepsis and extent of PMN apoptosis and the effect of superimposed ARDS is unknown. The objective of this study was to correlate neutrophil apoptosis with the severity of sepsis and sepsis-induced ARDS. Methods A prospective cohort study was conducted in intensive care units of three tertiary hospitals in Porto Alegre, southern Brazil. Fifty-seven patients with sepsis (uncomplicated sepsis, septic shock, and sepsis-induced ARDS) and 64 controls were enrolled. Venous peripheral blood was collected from patients with sepsis within 24 hours of diagnosis. All surgical groups, including controls, had their blood drawn 24 hours after surgery. Control patients on mechanical ventilation had blood collected within 24 hours of initiation of mechanical ventilation. Healthy controls were blood donors. Neutrophils were isolated, and incubated ex vivo, and apoptosis was determined by light microscopy on cytospun preparations. The differences among groups were assessed by analysis of variance with Tukeys. Results In medical patients, the mean percentage of neutrophil apoptosis (± standard error of the mean [SEM]) was lower in sepsis-induced ARDS (28% ± 3.3%; n = 9) when compared with uncomplicated sepsis (57% ± 3.2%; n = 8; p < 0.001), mechanical ventilation without infection, sepsis, or ARDS (53% ± 3.0%; n = 11; p < 0.001) and healthy controls (69% ± 1.1%; n = 33; p < 0.001) but did not differ from septic shock (38% ± 3.7%; n = 12; p = 0.13). In surgical patients with sepsis, the percentage of neutrophil apoptosis was lower for all groups when compared with surgical controls (52% ± 3.6%; n = 11; p < 0.001). Conclusion In medical patients with sepsis, neutrophil apoptosis is inversely proportional to the severity of sepsis and thus may be a marker of the severity of sepsis in this population. PMID:17092345

Predictors of survival in critically ill patients with acute respiratory distress syndrome (ARDS): an observational study.

PubMed

Balzer, Felix; Menk, Mario; Ziegler, Jannis; Pille, Christian; Wernecke, Klaus-Dieter; Spies, Claudia; Schmidt, Maren; Weber-Carstens, Steffen; Deja, Maria

2016-11-08

Currently there is no ARDS definition or classification system that allows optimal prediction of mortality in ARDS patients. This study aimed to examine the predictive values of the AECC and Berlin definitions, as well as clinical and respiratory parameters obtained at onset of ARDS and in the course of the first seven consecutive days. The observational study was conducted at a 14-bed intensive care unit specialized on treatment of ARDS. Predictive validity of the AECC and Berlin definitions as well as P a O 2 /F i O 2 and F i O 2 /P a O 2 *P mean (oxygenation index) on mortality of ARDS patients was assessed and statistically compared. Four hundred forty two critically-ill patients admitted for ARDS were analysed. Multivariate Cox regression indicated that the oxygenation index was the most accurate parameter for mortality prediction. The third day after ARDS criteria were met at our hospital was found to represent the best compromise between earliness and accuracy of prognosis of mortality regarding the time of assessment. An oxygenation index of 15 or greater was associated with higher mortality, longer length of stay in ICU and hospital and longer duration of mechanical ventilation. In addition, non-survivors had a significantly longer length of stay and duration of mechanical ventilation in referring hospitals before admitted to the national reference centre than survivors. The oxygenation index is suggested to be the most suitable parameter to predict mortality in ARDS, preferably assessed on day 3 after admission to a specialized centre. Patients might benefit when transferred to specialized ICU centres as soon as possible for further treatment.

The Ratio of Partial Pressure Arterial Oxygen and Fraction of Inspired Oxygen 1 Day After Acute Respiratory Distress Syndrome Onset Can Predict the Outcomes of Involving Patients.

PubMed

Lai, Chih-Cheng; Sung, Mei-I; Liu, Hsiao-Hua; Chen, Chin-Ming; Chiang, Shyh-Ren; Liu, Wei-Lun; Chao, Chien-Ming; Ho, Chung-Han; Weng, Shih-Feng; Hsing, Shu-Chen; Cheng, Kuo-Chen

2016-04-01

The initial hypoxemic level of acute respiratory distress syndrome (ARDS) defined according to Berlin definition might not be the optimal predictor for prognosis. We aimed to determine the predictive validity of the stabilized ratio of partial pressure arterial oxygen and fraction of inspired oxygen (PaO2/FiO2 ratio) following standard ventilator setting in the prognosis of patients with ARDS.This prospective observational study was conducted in a single tertiary medical center in Taiwan and compared the stabilized PaO2/FiO2 ratio (Day 1) following standard ventilator settings and the PaO2/FiO2 ratio on the day patients met ARDS Berlin criteria (Day 0). Patients admitted to intensive care units and in accordance with the Berlin criteria for ARDS were collected between December 1, 2012 and May 31, 2015. Main outcome was 28-day mortality. Arterial blood gas and ventilator setting on Days 0 and 1 were obtained.A total of 238 patients met the Berlin criteria for ARDS were enrolled, and they were classified as mild (n = 50), moderate (n = 125), and severe (n = 63) ARDS, respectively. Twelve (5%) patients who originally were classified as ARDS did not continually meet the Berlin definition, and a total of 134 (56%) patients had the changes regarding the severity of ARDS from Day 0 to Day 1. The 28-day mortality rate was 49.1%, and multivariate analysis identified age, PaO2/FiO2 on Day 1, number of organ failures, and positive fluid balance within 5 days as significant risk factors of death. Moreover, the area under receiver-operating curve for mortality prediction using PaO2/FiO2 on Day 1 was significant higher than that on Day 0 (P = 0.016).PaO2/FiO2 ratio on Day 1 after applying mechanical ventilator is a better predictor of outcomes in patients with ARDS than those on Day 0.

The Ratio of Partial Pressure Arterial Oxygen and Fraction of Inspired Oxygen 1 Day After Acute Respiratory Distress Syndrome Onset Can Predict the Outcomes of Involving Patients

PubMed Central

Lai, Chih-Cheng; Sung, Mei-I; Liu, Hsiao-Hua; Chen, Chin-Ming; Chiang, Shyh-Ren; Liu, Wei-Lun; Chao, Chien-Ming; Ho, Chung-Han; Weng, Shih-Feng; Hsing, Shu-Chen; Cheng, Kuo-Chen

2016-01-01

Abstract The initial hypoxemic level of acute respiratory distress syndrome (ARDS) defined according to Berlin definition might not be the optimal predictor for prognosis. We aimed to determine the predictive validity of the stabilized ratio of partial pressure arterial oxygen and fraction of inspired oxygen (PaO2/FiO2 ratio) following standard ventilator setting in the prognosis of patients with ARDS. This prospective observational study was conducted in a single tertiary medical center in Taiwan and compared the stabilized PaO2/FiO2 ratio (Day 1) following standard ventilator settings and the PaO2/FiO2 ratio on the day patients met ARDS Berlin criteria (Day 0). Patients admitted to intensive care units and in accordance with the Berlin criteria for ARDS were collected between December 1, 2012 and May 31, 2015. Main outcome was 28-day mortality. Arterial blood gas and ventilator setting on Days 0 and 1 were obtained. A total of 238 patients met the Berlin criteria for ARDS were enrolled, and they were classified as mild (n = 50), moderate (n = 125), and severe (n = 63) ARDS, respectively. Twelve (5%) patients who originally were classified as ARDS did not continually meet the Berlin definition, and a total of 134 (56%) patients had the changes regarding the severity of ARDS from Day 0 to Day 1. The 28-day mortality rate was 49.1%, and multivariate analysis identified age, PaO2/FiO2 on Day 1, number of organ failures, and positive fluid balance within 5 days as significant risk factors of death. Moreover, the area under receiver-operating curve for mortality prediction using PaO2/FiO2 on Day 1 was significant higher than that on Day 0 (P = 0.016). PaO2/FiO2 ratio on Day 1 after applying mechanical ventilator is a better predictor of outcomes in patients with ARDS than those on Day 0. PMID:27057912

Acute respiratory distress syndrome: frequency, clinical course, and costs of care.

PubMed

Valta, P; Uusaro, A; Nunes, S; Ruokonen, E; Takala, J

1999-11-01

To define the occurrence rate of acute respiratory distress syndrome (ARDS) using established criteria in a well-defined general patient population, to study the clinical course of ARDS when patients were ventilated using a "lung-protective" strategy, and to define the total costs of care. A 3-yr (1993 through 1995) retrospective descriptive analysis of all patients with ARDS treated in Kuopio University Hospital. Intensive care unit in the university hospital. Fifty-nine patients fulfilled the definition of ARDS: Pao2/Fio2 <200 mm Hg (33.3 kPa) during mechanical ventilation and bilateral infiltrates on chest radiograph. None. With a patient data management system, the day-by-day data of hemodynamics, ventilation, respiratory mechanics, gas exchange, and organ failures were collected during the period that Pao2/Fio2 ratio was <200 mm Hg (33.3 kPa). The frequency of ARDS was 4.9 cases/100,000 inhabitants/yr. Pneumonia and sepsis were the most common causes of ARDS. Mean age was 43+/-2 yrs. At the time of lowest Pao2/Fio2, the nonsurvivors had lower arterial and venous oxygen saturations and higher arterial lactate than survivors, whereas there were no differences between the groups in other parameters. Multiple organ dysfunction preceded the worst oxygenation in both the survivors and nonsurvivors. The intensive care mortality was 37%; hospital mortality and mortality after a minimum 8 months of follow-up was 42%. The most frequent cause of death was multiple organ failure. The effective costs of intensive care per survivor were US $73,000. The outcome of ARDS is unpredictable at the time of onset and also at the time of the worst oxygenation. Keeping the inspiratory pressures low (30-35 cm H2O [2.94 to 3.43 kPa]) reduces the frequency of pneumothorax, and might lower the mortality. Most patients are young, and therefore the costs per saved year of life are low.

Comparison of the Berlin definition with the American European consensus definition for acute respiratory distress syndrome in burn patients.

PubMed

Bordes, Julien; Lacroix, Guillaume; Esnault, Pierre; Goutorbe, Philippe; Cotte, Jean; Dantzer, Eric; Meaudre, Eric

2014-06-01

Acute respiratory distress syndrome (ARDS) is a leading cause of mortality in burn patients. Smoke inhalation, pneumonia and inflammation process are the major causes of ARDS in burn patients. The American European Consensus Conference (AECC) definition proposed in 1994 has recently been revised by the Berlin definition. Our objective was to describe the epidemiology of ARDS comparing the Berlin definition with the AECC definition in a retrospective cohort of burn patients. We reviewed admitted burn adult patients for a two year period, and investigated patient who received mechanical ventilation for more than 48 h and in whom pneumonia was diagnosed. 40 patients were analyzed. According to the AECC definition, 11 patients met criteria for ALI (27.5%), and 29 patients for ARDS (72.5%). According to the Berlin definition, all patients met criteria for ARDS: 4 (10%) for a severe ARDS, 25 (62.5%) for a moderate ARDS, 11 (27.5%) for a mild ARDS. Inhalation injury was diagnosed in 10 patients (25%). Categorizing patients with the Berlin definition showed statistically significative difference of mortality within the three groups, but not with the AECC definition. The Berlin definition seems to be more accurate than the AECC definition to assess the severity of ARDS in term of outcome in burn patients. This definition may facilitate prompt recognition of ARDS in burn patients, and promote protective ventilation strategy to a larger number of patients. Copyright © 2014 Elsevier Ltd and ISBI. All rights reserved.

Association between use of lung-protective ventilation with lower tidal volumes and clinical outcomes among patients without acute respiratory distress syndrome: a meta-analysis.

PubMed

Serpa Neto, Ary; Cardoso, Sérgio Oliveira; Manetta, José Antônio; Pereira, Victor Galvão Moura; Espósito, Daniel Crepaldi; Pasqualucci, Manoela de Oliveira Prado; Damasceno, Maria Cecília Toledo; Schultz, Marcus J

2012-10-24

Lung-protective mechanical ventilation with the use of lower tidal volumes has been found to improve outcomes of patients with acute respiratory distress syndrome (ARDS). It has been suggested that use of lower tidal volumes also benefits patients who do not have ARDS. To determine whether use of lower tidal volumes is associated with improved outcomes of patients receiving ventilation who do not have ARDS. MEDLINE, CINAHL, Web of Science, and Cochrane Central Register of Controlled Trials up to August 2012. Eligible studies evaluated use of lower vs higher tidal volumes in patients without ARDS at onset of mechanical ventilation and reported lung injury development, overall mortality, pulmonary infection, atelectasis, and biochemical alterations. Three reviewers extracted data on study characteristics, methods, and outcomes. Disagreement was resolved by consensus. Twenty articles (2822 participants) were included. Meta-analysis using a fixed-effects model showed a decrease in lung injury development (risk ratio [RR], 0.33; 95% CI, 0.23 to 0.47; I2, 0%; number needed to treat [NNT], 11), and mortality (RR, 0.64; 95% CI, 0.46 to 0.89; I2, 0%; NNT, 23) in patients receiving ventilation with lower tidal volumes. The results of lung injury development were similar when stratified by the type of study (randomized vs nonrandomized) and were significant only in randomized trials for pulmonary infection and only in nonrandomized trials for mortality. Meta-analysis using a random-effects model showed, in protective ventilation groups, a lower incidence of pulmonary infection (RR, 0.45; 95% CI, 0.22 to 0.92; I2, 32%; NNT, 26), lower mean (SD) hospital length of stay (6.91 [2.36] vs 8.87 [2.93] days, respectively; standardized mean difference [SMD], 0.51; 95% CI, 0.20 to 0.82; I2, 75%), higher mean (SD) PaCO2 levels (41.05 [3.79] vs 37.90 [4.19] mm Hg, respectively; SMD, -0.51; 95% CI, -0.70 to -0.32; I2, 54%), and lower mean (SD) pH values (7.37 [0.03] vs 7.40 [0.04], respectively; SMD, 1.16; 95% CI, 0.31 to 2.02; I2, 96%) but similar mean (SD) ratios of PaO2 to fraction of inspired oxygen (304.40 [65.7] vs 312.97 [68.13], respectively; SMD, 0.11; 95% CI, -0.06 to 0.27; I2, 60%). Tidal volume gradients between the 2 groups did not influence significantly the final results. Among patients without ARDS, protective ventilation with lower tidal volumes was associated with better clinical outcomes. Some of the limitations of the meta-analysis were the mixed setting of mechanical ventilation (intensive care unit or operating room) and the duration of mechanical ventilation.

Setting ventilation parameters guided by electrical impedance tomography in an animal trial of acute respiratory distress syndrome

NASA Astrophysics Data System (ADS)

Czaplik, Michael; Biener, Ingeborg; Leonhardt, Steffen; Rossaint, Rolf

2014-03-01

Since mechanical ventilation can cause harm to lung tissue it should be as protective as possible. Whereas numerous options exist to set ventilator parameters, an adequate monitoring is lacking up to date. The Electrical Impedance Tomography (EIT) provides a non-invasive visualization of ventilation which is relatively easy to apply and commercially available. Although there are a number of published measures and parameters derived from EIT, it is not clear how to use EIT to improve clinical outcome of e.g. patients suffering from acute respiratory distress syndrome (ARDS), a severe disease with a high mortality rate. On the one hand, parameters should be easy to obtain, on the other hand clinical algorithms should consider them to optimize ventilator settings. The so called Global inhomogeneity (GI) index bases on the fact that ARDS is characterized by an inhomogeneous injury pattern. By applying positive endexpiratory pressures (PEEP), homogeneity should be attained. In this study, ARDS was induced by a double hit procedure in six pigs. They were randomly assigned to either the EIT or the control group. Whereas in the control group the ARDS network table was used to set the PEEP according to the current inspiratory oxygen fraction, in the EIT group the GI index was calculated during a decremental PEEP trial. PEEP was kept when GI index was lowest. Interestingly, PEEP was significantly higher in the EIT group. Additionally, two of these animals died ahead of the schedule. Obviously, not only homogeneity of ventilation distribution matters but also limitation of over-distension.

Retrospective evaluation of the prevalence, risk factors, management, outcome, and necropsy findings of acute lung injury and acute respiratory distress syndrome in dogs and cats: 29 cases (2011-2013).

PubMed

Balakrishnan, Anusha; Drobatz, Kenneth J; Silverstein, Deborah C

2017-11-01

To determine the prevalence and risk factors for veterinary acute lung injury (VetALI) and veterinary acute respiratory distress syndrome (VetARDS), assess mechanical ventilation settings and patient outcomes, and to evaluate the relationship of clinical diagnoses with necropsy findings. Retrospective study. University teaching hospital. Twenty-four dogs and 5 cats with a clinical diagnosis of VetALI or VetARDS. Control population includes 24 dogs and 5 cats with a clinical diagnosis of respiratory disease other than VetALI or VetARDS. None. VetALI and VetARDS were diagnosed in 3.2% of dogs and 1.3% of cats presenting to the ICU. Systemic inflammatory response syndrome was the most common inciting condition (16/24 dogs, 2/5 cats), followed by vomiting and subsequent aspiration of gastric contents (9/24 dogs), sepsis (5/24 dogs, 3/5 cats), multiple transfusions (4/24 dogs), trauma (3/24 dogs), and adverse drug reactions (1/24 dogs, 1/5 cats).  None of these conditions were found to be significantly associated with a risk of development of VetALI or VetARDS when compared to controls. Twelve dogs (50%) and 4 cats (80%) underwent mechanical ventilation for a median duration of 18 hours in dogs (range: 6-174 h) and 15.5 hours in cats (range: 6-91 h). Overall, 3/29 patients survived to discharge including 2/24 dogs and 1/5 cats. Necropsy results were available for 8/22 dogs and 3/4 cats. A total of 6/8 dogs (75%) dogs and 3/3 (100%) cats met the histopathologic criteria for diagnosis of VetALI or VetARDS. VetALI and VetARDS can cause life-threatening respiratory distress in dogs and cats necessitating mechanical ventilation in 50% of dogs and 80% of cats in this study. These diseases are associated with a poor clinical outcome and a high rate of humane euthanasia. © Veterinary Emergency and Critical Care Society 2017.

Associations between ventilator settings during extracorporeal membrane oxygenation for refractory hypoxemia and outcome in patients with acute respiratory distress syndrome: a pooled individual patient data analysis : Mechanical ventilation during ECMO.

PubMed

Serpa Neto, Ary; Schmidt, Matthieu; Azevedo, Luciano C P; Bein, Thomas; Brochard, Laurent; Beutel, Gernot; Combes, Alain; Costa, Eduardo L V; Hodgson, Carol; Lindskov, Christian; Lubnow, Matthias; Lueck, Catherina; Michaels, Andrew J; Paiva, Jose-Artur; Park, Marcelo; Pesenti, Antonio; Pham, Tài; Quintel, Michael; Marco Ranieri, V; Ried, Michael; Roncon-Albuquerque, Roberto; Slutsky, Arthur S; Takeda, Shinhiro; Terragni, Pier Paolo; Vejen, Marie; Weber-Carstens, Steffen; Welte, Tobias; Gama de Abreu, Marcelo; Pelosi, Paolo; Schultz, Marcus J

2016-11-01

Extracorporeal membrane oxygenation (ECMO) is a rescue therapy for patients with acute respiratory distress syndrome (ARDS). The aim of this study was to evaluate associations between ventilatory settings during ECMO for refractory hypoxemia and outcome in ARDS patients. In this individual patient data meta-analysis of observational studies in adult ARDS patients receiving ECMO for refractory hypoxemia, a time-dependent frailty model was used to determine which ventilator settings in the first 3 days of ECMO had an independent association with in-hospital mortality. Nine studies including 545 patients were included. Initiation of ECMO was accompanied by significant decreases in tidal volume size, positive end-expiratory pressure (PEEP), plateau pressure, and driving pressure (plateau pressure - PEEP) levels, and respiratory rate and minute ventilation, and resulted in higher PaO 2 /FiO 2 , higher arterial pH and lower PaCO 2 levels. Higher age, male gender and lower body mass index were independently associated with mortality. Driving pressure was the only ventilatory parameter during ECMO that showed an independent association with in-hospital mortality [adjusted HR, 1.06 (95 % CI, 1.03-1.10)]. In this series of ARDS patients receiving ECMO for refractory hypoxemia, driving pressure during ECMO was the only ventilator setting that showed an independent association with in-hospital mortality.

Lung Injury Prediction Score Is Useful in Predicting Acute Respiratory Distress Syndrome and Mortality in Surgical Critical Care Patients

PubMed Central

Bauman, Zachary M.; Gassner, Marika Y.; Coughlin, Megan A.; Mahan, Meredith; Watras, Jill

2015-01-01

Background. Lung injury prediction score (LIPS) is valuable for early recognition of ventilated patients at high risk for developing acute respiratory distress syndrome (ARDS). This study analyzes the value of LIPS in predicting ARDS and mortality among ventilated surgical patients. Methods. IRB approved, prospective observational study including all ventilated patients admitted to the surgical intensive care unit at a single tertiary center over 6 months. ARDS was defined using the Berlin criteria. LIPS were calculated for all patients and analyzed. Logistic regression models evaluated the ability of LIPS to predict development of ARDS and mortality. A receiver operator characteristic (ROC) curve demonstrated the optimal LIPS value to statistically predict development of ARDS. Results. 268 ventilated patients were observed; 141 developed ARDS and 127 did not. The average LIPS for patients who developed ARDS was 8.8 ± 2.8 versus 5.4 ± 2.8 for those who did not (p < 0.001). An ROC area under the curve of 0.79 demonstrates LIPS is statistically powerful for predicting ARDS development. Furthermore, for every 1-unit increase in LIPS, the odds of developing ARDS increase by 1.50 (p < 0.001) and odds of ICU mortality increase by 1.22 (p < 0.001). Conclusion. LIPS is reliable for predicting development of ARDS and predicting mortality in critically ill surgical patients. PMID:26301105

Extracorporeal membrane oxygenation (ECMO) as a treatment strategy for severe acute respiratory distress syndrome (ARDS) in the low tidal volume era: A systematic review.

PubMed

Tillmann, Bourke W; Klingel, Michelle L; Iansavichene, Alla E; Ball, Ian M; Nagpal, A Dave

2017-10-01

To evaluate the hospital survival in patients with severe ARDS managed with ECMO and low tidal volume ventilation as compared to patients managed with low tidal volume ventilation alone. Electronic databases were searched for studies of at least 10 adult patients with severe ARDS comparing the use of ECMO with low tidal volume ventilation to mechanical ventilation with a low tidal volume alone. Only studies reporting hospital or ICU survival were included. All identified studies were assessed independently by two reviewers. Of 1782 citations, 27 studies (n=1674) met inclusion criteria. Hospital survival for ECMO patients ranged from 33.3 to 86%, while survival with conventional therapy ranged from 36.3 to 71.2%. Five studies were identified with appropriate control groups allowing comparison, but due to the high degree of variability between studies (I 2 =63%), their results could not be pooled. Two of these studies demonstrated a significant difference, both favouring ECMO over conventional therapy. Given the lack of studies with appropriate control groups, our confidence in a difference in outcome between the two therapies remains weak. Future studies on the use of ECMO for severe ARDS are needed to clarify the role of ECMO in this disease. Copyright © 2017 Elsevier Inc. All rights reserved.

Bronchoalveolar lavage with diluted porcine surfactant in mechanically ventilated term infants with meconium aspiration syndrome.

PubMed

Lista, Gianluca; Bianchi, Silvia; Castoldi, Francesca; Fontana, Paola; Cavigioli, Francesco

2006-01-01

To evaluate the efficacy and safety of bronchoalveolar lavage (BAL) with diluted porcine surfactant in mechanically ventilated term infants with severe acute respiratory distress syndrome (ARDS) due to meconium aspiration syndrome (MAS). Eight consecutive mechanically ventilated term infants with severe ARDS due to MAS underwent BAL with 15 mL/kg of diluted (5.3mg phospholipid/mL) surfactant saline suspension (porcine surfactant [Curosurf]). Treatment was administered slowly in aliquots of 2.5 mL. The mean age of neonates at treatment was 3.5 (range 1-8) hours. Heart rate, systemic blood pressure and oxygen saturation were monitored continuously. Arterial blood gases were measured immediately before treatment, and again at 3 and 6 hours post-treatment. Chest x-rays were taken 6 and 24 hours after treatment. Radiological improvement was evident in all eight patients 6 hours post-treatment. Compared with pre-BAL values, significant improvements (p < 0.05) in mean values for partial pressure of oxygen in arterial blood, partial pressure of carbon dioxide in arterial blood, pH, arterial/alveolar O2 ratio and oxygenation index were documented at 3 and 6 hours after BAL. In all patients, tracheal fluids that had been meconium-stained prior to BAL were clear of meconium after BAL. Only one patient required nitric oxide therapy for transient pulmonary hypertension. No adverse sequelae of treatment occurred during the study. BAL with dilute porcine surfactant administered slowly in 2.5 mL aliquots improved oxygenation and chest x-ray findings, without causing major adverse effects, in mechanically ventilated term infants with ARDS due to MAS.

Ventilator-associated pneumonia and ICU mortality in severe ARDS patients ventilated according to a lung-protective strategy

PubMed Central

2012-01-01

Introduction Ventilator-associated pneumonia (VAP) may contribute to the mortality associated with acute respiratory distress syndrome (ARDS). We aimed to determine the incidence, outcome, and risk factors of bacterial VAP complicating severe ARDS in patients ventilated by using a strictly standardized lung-protective strategy. Methods This prospective epidemiologic study was done in all the 339 patients with severe ARDS included in a multicenter randomized, placebo-controlled double-blind trial of cisatracurium besylate in severe ARDS patients. Patients with suspected VAP underwent bronchoalveolar lavage to confirm the diagnosis. Results Ninety-eight (28.9%) patients had at least one episode of microbiologically documented bacterial VAP, including 41 (41.8%) who died in the ICU, compared with 74 (30.7%) of the 241 patients without VAP (P = 0.05). After adjustment, age and severity at baseline, but not VAP, were associated with ICU death. Cisatracurium besylate therapy within 2 days of ARDS onset decreased the risk of ICU death. Factors independently associated with an increased risk to develop a VAP were male sex and worse admission Glasgow Coma Scale score. Tracheostomy, enteral nutrition, and the use of a subglottic secretion-drainage device were protective. Conclusions In patients with severe ARDS receiving lung-protective ventilation, VAP was associated with an increased crude ICU mortality which did not remain significant after adjustment. PMID:22524447

High tidal volume decreases adult respiratory distress syndrome, atelectasis, and ventilator days compared with low tidal volume in pediatric burned patients with inhalation injury.

PubMed

Sousse, Linda E; Herndon, David N; Andersen, Clark R; Ali, Arham; Benjamin, Nicole C; Granchi, Thomas; Suman, Oscar E; Mlcak, Ronald P

2015-04-01

Inhalation injury, which is among the causes of acute lung injury and acute respiratory distress syndrome (ARDS), continues to represent a significant source of mortality in burned patients. Inhalation injury often requires mechanical ventilation, but the ideal tidal volume strategy is not clearly defined in burned pediatric patients. The aim of this study was to determine the effects of low and high tidal volume on the number of ventilator days, ventilation pressures, and incidence of atelectasis, pneumonia, and ARDS in pediatric burned patients with inhalation injury within 1 year post burn injury. From 1986 to 2014, inhalation injury was diagnosed by bronchoscopy in pediatric burned patients (n = 932). Patients were divided into 3 groups: unventilated (n = 241), high tidal volume (HTV, 15 ± 3 mL/kg, n = 190), and low tidal volume (LTV, 9 ± 3 mL/kg, n = 501). High tidal volume was associated with significantly decreased ventilator days (p < 0.005) and maximum positive end expiratory pressure (p < 0.0001) and significantly increased maximum peak inspiratory pressure (p < 0.02) and plateau pressure (p < 0.02) compared with those in patients with LTV. The incidence of atelectasis (p < 0.0001) and ARDS (p < 0.02) was significantly decreased with HTV compared with LTV. However, the incidence of pneumothorax was significantly increased in the HTV group compared with the LTV group (p < 0.03). High tidal volume significantly decreases ventilator days and the incidence of both atelectasis and ARDS compared with low tidal volume in pediatric burned patients with inhalation injury. Therefore, the use of HTV may interrupt sequences leading to lung injury in our patient population. Copyright © 2015 American College of Surgeons. Published by Elsevier Inc. All rights reserved.

Convexity, Jensen's inequality, and benefits of noisy or biologically variable life support (Keynote Address)

NASA Astrophysics Data System (ADS)

Mutch, W. Alan C.

2005-05-01

Life support with a mechanical ventilator is used to manage patients with a variety of lung diseases including acute respiratory distress syndrome (ARDS). Recently, management of ARDS has concentrated on ventilating at lower airway pressure using lower tidal volume. A large international study demonstrated a 22% reduction in mortality with the low tidal volume approach. The potential advantages of adding physiologic noise with fractal characteristics to the respiratory rate and tidal volume as delivered by a mechanical ventilator are discussed. A so-called biologically variable ventilator (BVV), incorporating such noise, has been developed. Here we show that the benefits of noisy ventilation - at lower tidal volumes - can be deduced from a simple probabilistic result known as Jensen"s Inequality. Using the local convexity of the pressure-volume relationship in the lung we demonstrate that the addition of noise results in higher mean tidal volume or lower mean airway pressure. The consequence is enhanced gas exchange or less stress on the lungs, both clinically desirable. Jensen"s Inequality has important considerations in engineering, information theory and thermodynamics. Here is an example of the concept applied to medicine that may have important considerations for the clinical management of critically ill patients. Life support devices, such as mechanical ventilators, are of vital use in critical care units and operating rooms. These devices usually have monotonous output. Improving mechanical ventilators and other life support devices may be as simple as adding noise to their output signals.

Titration of Ideal Positive End-expiratory Pressure in Acute Respiratory Distress Syndrome: Comparison between Lower Inflection Point and Esophageal Pressure Method Using Volumetric Capnography.

PubMed

Baikunje, Nandakishore; Sehgal, Inderpaul Singh; Dhooria, Sahajal; Prasad, Kuruswamy Thurai; Agarwal, Ritesh

2017-05-01

The tenets of mechanical ventilation in acute respiratory distress syndrome (ARDS) include the utilization of low tidal volume and optimal application of positive end-expiratory pressure (PEEP). Optimal PEEP in ARDS is characterized by reduction in alveolar dead space along with improvement in the lung compliance and resultant betterment in oxygenation. There are various methods of setting PEEP in ARDS. Herein, we report a patient of ARDS, wherein we employed measurement of dead space using volumetric capnography to compare two different PEEP strategies, namely, the lower inflection point and transpulmonary pressure monitoring.

Effect of ARDS Severity and Etiology on Short-Term Outcomes.

PubMed

El-Haddad, Haitham; Jang, Hyejeong; Chen, Wei; Soubani, Ayman O

2017-09-01

We evaluated the outcome of subjects with ARDS in relation to etiology and severity in a retrospective cohort study of the ARDS Network randomized controlled trials. The primary outcome was 28-d mortality. The secondary outcomes were 60-d mortality and ventilator- and ICU-free days. For severity of ARDS, subjects were stratified according to P aO2 /F IO2 . The etiology of ARDS was classified into sepsis, pneumonia, aspiration, trauma, and others. A total of 2,914 subjects were included in these trials. Outcomes were modeled with multivariable regressions adjusted for baseline covariates, age, sex, race, Acute Physiology and Chronic Health Evaluation III (APACHE III), vasopressor use, modified lung injury score, diabetes mellitus, cancer status, body mass index, pre-ICU location, ICU location, and study. There was no statistically significant difference in 28-d mortality in relation to ARDS severity. Subjects with trauma, compared with other etiologies of ARDS, had significantly lower mortality at 28 d (odds ratio [OR] = 0.47, 95% CI 0.26-0.83, P = .01). Sixty-day mortality was significantly lower for trauma subjects and those with severe ARDS group (OR = 0.5, 95% CI 0.3-0.85, P = .01 and OR = 0.71, 95% CI 0.52-0.98, P = .034, respectively). There were statistically significantly more ICU-free days and ventilator-free days for the aspiration group (OR = 1.09, 95% CI 1.02-1.17, P = .01 and OR = 1.09, 95% CI 1.02-1.16, P = .01, respectively). There was no statistically significant difference in ICU-free days or ventilator-free days in relation to severity of ARDS. Severity of ARDS based on P aO2 /F IO2 did not impact 28-d mortality, ventilator-free days, or ICU-free days. Among the etiologies of ARDS, trauma subjects had the lowest 28- and 60-d mortality, whereas subjects with aspiration had more ICU-free days and ventilator-free days. Copyright © 2017 by Daedalus Enterprises.

Severe acute respiratory distress syndrome caused by unintentional sewing machine lubricant ingestion: A case report.

PubMed

Kishore, Sunil; Chandelia, Sudha; Patharia, Neha; Swarnim

2016-11-01

Sewing machine oil ingestion is rare but is possible due to its availability at home. Chemically, it belongs to hydrocarbon family which is toxic if aspirated, owing to their physical properties such as high volatility and low viscosity. On the contrary, sewing machine lubricant has high viscosity and low volatility which makes it aspiration less likely. The main danger of hydrocarbon ingestion is chemical pneumonitis which may be as severe as acute respiratory distress syndrome (ARDS). We report a case of a 5-year-old girl with accidental ingestion of sewing machine lubricant oil, who subsequently developed ARDS refractory to mechanical ventilation. There was much improvement with airway pressure release ventilation mode of ventilation, but the child succumbed to death due to pulmonary hemorrhage.

Severe acute respiratory distress syndrome caused by unintentional sewing machine lubricant ingestion: A case report

PubMed Central

Kishore, Sunil; Chandelia, Sudha; Patharia, Neha; Swarnim

2016-01-01

Sewing machine oil ingestion is rare but is possible due to its availability at home. Chemically, it belongs to hydrocarbon family which is toxic if aspirated, owing to their physical properties such as high volatility and low viscosity. On the contrary, sewing machine lubricant has high viscosity and low volatility which makes it aspiration less likely. The main danger of hydrocarbon ingestion is chemical pneumonitis which may be as severe as acute respiratory distress syndrome (ARDS). We report a case of a 5-year-old girl with accidental ingestion of sewing machine lubricant oil, who subsequently developed ARDS refractory to mechanical ventilation. There was much improvement with airway pressure release ventilation mode of ventilation, but the child succumbed to death due to pulmonary hemorrhage. PMID:27994384

Optimal ventilator strategies for trauma-related ARDS.

PubMed

Goatly, Giles; Guidozzi, N; Khan, M

2018-03-29

Acute respiratory distress syndrome (ARDS) was first described in the 1960s and has become a major area of research due to the mortality and morbidity associated with it. ARDS is currently defined using the Berlin Consensus; however, this is not wholly applicable for trauma-related ARDS. A systematic review of the literature was undertaken using the Preferred Reporting for Systematic Reviews and Meta Analyses methodology. The Ovid Medline, Web of Science and PubMed online databases were interrogated for papers published between 1 January 1995 and 31 December 2017. The literature search yielded a total of 64 papers that fulfilled the search criteria. Despite decades of dedicated research into different treatment modalities, ARDS continues to carry a high burden of mortality. The ARDS definitions laid out in the Berlin consensus are not entirely suited to trauma. While trauma-related ARDS represents a small portion of the available research, the evidence continues to favour low tidal volume ventilation as the benchmark for current practice. Positive end expiratory ventilation and airway pressure release ventilation in trauma cohorts may be beneficial; however, the evidence to date does not show this. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Effect of driving pressure on mortality in ARDS patients during lung protective mechanical ventilation in two randomized controlled trials.

PubMed

Guérin, Claude; Papazian, Laurent; Reignier, Jean; Ayzac, Louis; Loundou, Anderson; Forel, Jean-Marie

2016-11-29

Driving pressure (ΔPrs) across the respiratory system is suggested as the strongest predictor of hospital mortality in patients with acute respiratory distress syndrome (ARDS). We wonder whether this result is related to the range of tidal volume (V T ). Therefore, we investigated ΔPrs in two trials in which strict lung-protective mechanical ventilation was applied in ARDS. Our working hypothesis was that ΔPrs is a risk factor for mortality just like compliance (Crs) or plateau pressure (Pplat,rs) of the respiratory system. We performed secondary analysis of data from 787 ARDS patients enrolled in two independent randomized controlled trials evaluating distinct adjunctive techniques while they were ventilated as in the low V T arm of the ARDSnet trial. For this study, we used V T , positive end-expiratory pressure (PEEP), Pplat,rs, Crs, ΔPrs, and respiratory rate recorded 24 hours after randomization, and compared them between survivors and nonsurvivors at day 90. Patients were followed for 90 days after inclusion. Cox proportional hazard modeling was used for mortality at day 90. If colinearity between ΔPrs, Crs, and Pplat,rs was verified, specific Cox models were used for each of them. Both trials enrolled 805 patients of whom 787 had day-1 data available, and 533 of these survived. In the univariate analysis, ΔPrs averaged 13.7 ± 3.7 and 12.8 ± 3.7 cmH 2 O (P = 0.002) in nonsurvivors and survivors, respectively. Colinearity between ΔPrs, Crs and Pplat,rs, which was expected as these variables are mathematically coupled, was statistically significant. Hazard ratios from the Cox models for day-90 mortality were 1.05 (1.02-1.08) (P = 0.005), 1.05 (1.01-1.08) (P = 0.008) and 0.985 (0.972-0.985) (P = 0.029) for ΔPrs, Pplat,rs and Crs, respectively. PEEP and V T were not associated with death in any model. When ventilating patients with low V T , ΔPrs is a risk factor for death in ARDS patients, as is Pplat,rs or Crs. As our data originated from trials from which most ARDS patients were excluded due to strict inclusion and exclusion criteria, these findings must be validated in independent observational studies in patients ventilated with a lung protective strategy. Clinicaltrials.gov NCT00299650 . Registered 6 March 2006 for the Acurasys trial. Clinicaltrials.gov NCT00527813 . Registered 10 September 2007 for the Proseva trial.

The clinical practice guideline for the management of ARDS in Japan.

PubMed

Hashimoto, Satoru; Sanui, Masamitsu; Egi, Moritoki; Ohshimo, Shinichiro; Shiotsuka, Junji; Seo, Ryutaro; Tanaka, Ryoma; Tanaka, Yu; Norisue, Yasuhiro; Hayashi, Yoshiro; Nango, Eishu

2017-01-01

The Japanese Society of Respiratory Care Medicine and the Japanese Society of Intensive Care Medicine provide here a clinical practice guideline for the management of adult patients with ARDS in the ICU. The guideline was developed applying the GRADE system for performing robust systematic reviews with plausible recommendations. The guideline consists of 13 clinical questions mainly regarding ventilator settings and drug therapies (the last question includes 11 medications that are not approved for clinical use in Japan). The recommendations for adult patients with ARDS include: we suggest against early tracheostomy (GRADE 2C), we suggest using NPPV for early respiratory management (GRADE 2C), we recommend the use of low tidal volumes at 6-8 mL/kg (GRADE 1B), we suggest setting the plateau pressure at 30cmH 2 0 or less (GRADE2B), we suggest using PEEP within the range of plateau pressures less than or equal to 30cmH 2 O, without compromising hemodynamics (Grade 2B), and using higher PEEP levels in patients with moderate to severe ARDS (Grade 2B), we suggest using protocolized methods for liberation from mechanical ventilation (Grade 2D), we suggest prone positioning especially in patients with moderate to severe respiratory dysfunction (GRADE 2C), we suggest against the use of high frequency oscillation (GRADE 2C), we suggest the use of neuromuscular blocking agents in patients requiring mechanical ventilation under certain circumstances (GRADE 2B), we suggest fluid restriction in the management of ARDS (GRADE 2A), we do not suggest the use of neutrophil elastase inhibitors (GRADE 2D), we suggest the administration of steroids, equivalent to methylprednisolone 1-2mg/kg/ day (GRADE 2A), and we do not recommend other medications for the treatment of adult patients with ARDS (GRADE1B; inhaled/intravenous β2 stimulants, prostaglandin E 1 , activated protein C, ketoconazole, and lisofylline, GRADE 1C; inhaled nitric oxide, GRADE 1D; surfactant, GRADE 2B; granulocyte macrophage colony-stimulating factor, N-acetylcysteine, GRADE 2C; Statin.). This article was translated from the Japanese version originally published as the ARDS clinical practice guidelines 2016 by the committee of ARDS clinical practice guideline (Tokyo, 2016, 293p, available from http://www.jsicm.org/ARDSGL/ARDSGL2016.pdf). The original article, written for Japanese healthcare providers, provides points of view that are different from those in other countries.

Budesonide Attenuates Ventilator-induced Lung Injury in a Rat Model of Inflammatory Acute Respiratory Distress Syndrome.

PubMed

Gao, Wei; Ju, Ying-Nan

2016-05-01

Patients with acute respiratory distress syndrome (ARDS) are particularly susceptible to ventilator-induced lung injury (VILI). This study investigated the effect of budesonide on VILI in a rat model of inflammatory ARDS. Forty eight rats were randomized into three groups (n = 16 each): sham group (S), endotoxin/ventilation group (LV), endotoxin/ventilation/budesonide group (LVB). Rats in the S group received anesthesia only. Rats in the LV and LVB groups received endotoxin to simulate ARDS and were mechanically ventilated for 4 h (tidal volume 30 mL/kg). Rats in the LVB group received budesonide 1 mg, and rats in the LV group received saline in airway. PaO2/FiO2, lung wet-to-dry weight ratios, inflammatory factors in serum and bronchoalveolar lavage fluid (BALF), histopathologic analysis of lung tissue, and survival were examined. PaO2/FiO2 was significantly increased in rats in the LVB group compared to the LV group. Total cell count, macrophages, and neutrophils in BALF, and levels of intercellular adhesion molecule (ICAM)-1, tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-8 in BALF and serum were significantly decreased in rats in the LVB group compared to the LV group, whereas levels of IL-10 in BALF and serum were significantly increased. Histopathological changes of lung injury and apoptosis were reduced, and survival was increased in rats in the LVB group compared to the LV group. Budesonide ameliorated VILI in a rat model of inflammatory ARDS. Copyright © 2016 IMSS. Published by Elsevier Inc. All rights reserved.

Physiologic effects of alveolar recruitment and inspiratory pauses during moderately-high-frequency ventilation delivered by a conventional ventilator in a severe lung injury model

PubMed Central

Costa, Eduardo Leite Vieira; Azevedo, Luciano Cesar Pontes; Gomes, Susimeire; Amato, Marcelo Britto Passos; Park, Marcelo

2017-01-01

Background and aims To investigate whether performing alveolar recruitment or adding inspiratory pauses could promote physiologic benefits (VT) during moderately-high-frequency positive pressure ventilation (MHFPPV) delivered by a conventional ventilator in a porcine model of severe acute respiratory distress syndrome (ARDS). Methods Prospective experimental laboratory study with eight pigs. Induction of acute lung injury with sequential pulmonary lavages and injurious ventilation was initially performed. Then, animals were ventilated on a conventional mechanical ventilator with a respiratory rate (RR) = 60 breaths/minute and PEEP titrated according to ARDS Network table. The first two steps consisted of a randomized order of inspiratory pauses of 10 and 30% of inspiratory time. In final step, we removed the inspiratory pause and titrated PEEP, after lung recruitment, with the aid of electrical impedance tomography. At each step, PaCO2 was allowed to stabilize between 57–63 mmHg for 30 minutes. Results The step with RR of 60 after lung recruitment had the highest PEEP when compared with all other steps (17 [16,19] vs 14 [10, 17]cmH2O), but had lower driving pressures (13 [13,11] vs 16 [14, 17]cmH2O), higher P/F ratios (212 [191,243] vs 141 [105, 184] mmHg), lower shunt (23 [20, 23] vs 32 [27, 49]%), lower dead space ventilation (10 [0, 15] vs 30 [20, 37]%), and a more homogeneous alveolar ventilation distribution. There were no detrimental effects in terms of lung mechanics, hemodynamics, or gas exchange. Neither the addition of inspiratory pauses or the alveolar recruitment maneuver followed by decremental PEEP titration resulted in further reductions in VT. Conclusions During MHFPPV set with RR of 60 bpm delivered by a conventional ventilator in severe ARDS swine model, neither the inspiratory pauses or PEEP titration after recruitment maneuver allowed reduction of VT significantly, however the last strategy decreased driving pressures and improved both shunt and dead space. PMID:28961282

Implementing a bedside assessment of respiratory mechanics in patients with acute respiratory distress syndrome.

PubMed

Chen, Lu; Chen, Guang-Qiang; Shore, Kevin; Shklar, Orest; Martins, Concetta; Devenyi, Brian; Lindsay, Paul; McPhail, Heather; Lanys, Ashley; Soliman, Ibrahim; Tuma, Mazin; Kim, Michael; Porretta, Kerri; Greco, Pamela; Every, Hilary; Hayes, Chris; Baker, Andrew; Friedrich, Jan O; Brochard, Laurent

2017-04-04

Despite their potential interest for clinical management, measurements of respiratory mechanics in patients with acute respiratory distress syndrome (ARDS) are seldom performed in routine practice. We introduced a systematic assessment of respiratory mechanics in our clinical practice. After the first year of clinical use, we retrospectively assessed whether these measurements had any influence on clinical management and physiological parameters associated with clinical outcomes by comparing their value before and after performing the test. The respiratory mechanics assessment constituted a set of bedside measurements to determine passive lung and chest wall mechanics, response to positive end-expiratory pressure, and alveolar derecruitment. It was obtained early after ARDS diagnosis. The results were provided to the clinical team to be used at their own discretion. We compared ventilator settings and physiological variables before and after the test. The physiological endpoints were oxygenation index, dead space, and plateau and driving pressures. Sixty-one consecutive patients with ARDS were enrolled. Esophageal pressure was measured in 53 patients (86.9%). In 41 patients (67.2%), ventilator settings were changed after the measurements, often by reducing positive end-expiratory pressure or by switching pressure-targeted mode to volume-targeted mode. Following changes, the oxygenation index, airway plateau, and driving pressures were significantly improved, whereas the dead-space fraction remained unchanged. The oxygenation index continued to improve in the next 48 h. Implementing a systematic respiratory mechanics test leads to frequent individual adaptations of ventilator settings and allows improvement in oxygenation indexes and reduction of the risk of overdistention at the same time. The present study involves data from our ongoing registry for respiratory mechanics (ClinicalTrials.gov identifier: NCT02623192 . Registered 30 July 2015).

Optimizing Ventilation Distribution and Gas Exchange in Combat-Related Lung Injury Using Multifrequency Oscillation

DTIC Science & Technology

2017-10-01

gas exchange in the acute respiratory distress syndrome (ARDS) and other forms of combat-related lung injury, while simultaneously preserving mechanical...civilian populations with ARDS. 15. SUBJECT TERMS Acute lung injury, Acute respiratory distress syndrome , Blast lung injury, Combat-related lung injury...REFERENCES 18 10.0 APPENDICES 19 Page 4 1.0 INTRODUCTION Respiratory failure from acute lung injury, now termed the acute respiratory distress syndrome

Moderately high frequency ventilation with a conventional ventilator allows reduction of tidal volume without increasing mean airway pressure.

PubMed

Cordioli, Ricardo Luiz; Park, Marcelo; Costa, Eduardo Leite Vieira; Gomes, Susimeire; Brochard, Laurent; Amato, Marcelo Britto Passos; Azevedo, Luciano Cesar Pontes

2014-12-01

The aim of this study was to explore if positive-pressure ventilation delivered by a conventional ICU ventilator at a moderately high frequency (HFPPV) allows a safe reduction of tidal volume (V T) below 6 mL/kg in a porcine model of severe acute respiratory distress syndrome (ARDS) and at a lower mean airway pressure than high-frequency oscillatory ventilation (HFOV). This is a prospective study. In eight pigs (median weight 34 [29,36] kg), ARDS was induced by pulmonary lavage and injurious ventilation. The animals were ventilated with a randomized sequence of respiratory rates: 30, 60, 90, 120, 150, followed by HFOV at 5 Hz. At each step, V T was adjusted to allow partial pressure of arterial carbon dioxide (PaCO2) to stabilize between 57 and 63 mmHg. Data are shown as median [P25th,P75th]. After lung injury, the PaO2/FiO2 (P/F) ratio was 92 [63,118] mmHg, pulmonary shunt 26 [17,31]%, and static compliance 11 [8,14] mL/cmH2O. Positive end-expiratory pressure (PEEP) was 14 [10,17] cmH2O. At 30 breaths/min, V T was higher than 6 (7.5 [6.8,10.2]) mL/kg, but at all higher frequencies, V T could be reduced and PaCO2 maintained, leading to reductions in plateau pressures and driving pressures. For frequencies of 60 to 150/min, V T progressively fell from 5.2 [5.1,5.9] to 3.8 [3.7,4.2] mL/kg (p < 0.001). There were no detrimental effects in terms of lung mechanics, auto-PEEP generation, hemodynamics, or gas exchange. Mean airway pressure was maintained constant and was increased only during HFOV. During protective mechanical ventilation, HFPPV delivered by a conventional ventilator in a severe ARDS swine model safely allows further tidal volume reductions. This strategy also allowed decreasing airway pressures while maintaining stable PaCO2 levels.

Pulmonary vascular dysfunction in ARDS

PubMed Central

2014-01-01

Acute respiratory distress syndrome (ARDS) is characterised by diffuse alveolar damage and is frequently complicated by pulmonary hypertension (PH). Multiple factors may contribute to the development of PH in this setting. In this review, we report the results of a systematic search of the available peer-reviewed literature for papers that measured indices of pulmonary haemodynamics in patients with ARDS and reported on mortality in the period 1977 to 2010. There were marked differences between studies, with some reporting strong associations between elevated pulmonary arterial pressure or elevated pulmonary vascular resistance and mortality, whereas others found no such association. In order to discuss the potential reasons for these discrepancies, we review the physiological concepts underlying the measurement of pulmonary haemodynamics and highlight key differences between the concepts of resistance in the pulmonary and systemic circulations. We consider the factors that influence pulmonary arterial pressure, both in normal lungs and in the presence of ARDS, including the important effects of mechanical ventilation. Pulmonary arterial pressure, pulmonary vascular resistance and transpulmonary gradient (TPG) depend not alone on the intrinsic properties of the pulmonary vascular bed but are also strongly influenced by cardiac output, airway pressures and lung volumes. The great variability in management strategies within and between studies means that no unified analysis of these papers was possible. Uniquely, Bull et al. (Am J Respir Crit Care Med 182:1123–1128, 2010) have recently reported that elevated pulmonary vascular resistance (PVR) and TPG were independently associated with increased mortality in ARDS, in a large trial with protocol-defined management strategies and using lung-protective ventilation. We then considered the existing literature to determine whether the relationship between PVR/TPG and outcome might be causal. Although we could identify potential mechanisms for such a link, the existing evidence does not allow firm conclusions to be drawn. Nonetheless, abnormally elevated PVR/TPG may provide a useful index of disease severity and progression. Further studies are required to understand the role and importance of pulmonary vascular dysfunction in ARDS in the era of lung-protective ventilation. PMID:25593744

Low-tidal volume mechanical ventilation in patients with acute respiratory distress syndrome caused by pandemic influenza A/H1N1 infection.

PubMed

Oh, Dong Kyu; Lee, Myung Goo; Choi, Eun Young; Lim, Jaemin; Lee, Hyun-Kyung; Kim, Seok Chan; Lim, Chae-Man; Koh, Younsuck; Hong, Sang-Bum

2013-08-01

Low-tidal volume (TV) mechanical ventilation is an important manipulation in managing patients with acute respiratory distress syndrome (ARDS). However, there is no definite evidence to support the use of this intervention in patients with viral etiologies. A retrospective observational study of 104 patients with ARDS caused by pandemic influenza A/H1N1 infection admitted to 28 intensive care units (ICUs) in Korea was performed. Patients were categorized into 3 groups according to the TV they received: TV less than or equal to 7 mL/kg, TV greater than 7 mL/kg but less than or equal to 9 mL/kg, or TV greater than 9 mL/kg. The mean age was 55.1 years, and 55.8% were male (n = 58). Patients with TV greater than 9 mL/kg showed higher 28-day ICU mortality than the 2 other groups (vs TV < 7 mL/kg, P = .007 and vs 7 mL/kg < TV ≤ 9 mL/kg, P = .004, respectively). Patients with TV less than or equal to 7 mL/kg required ventilators, ICU admissions, and hospitalizations for fewer days than those with TV greater than 7 mL/kg (11.4 vs 6.1 days for 28-day ventilator-free days, 9.7 vs 4.9 days for 28-day ICU-free days, and 5.2 vs 2.4 days for 28-day hospital-free days, respectively). Tidal volume greater than 9 mL/kg (hazard rate, 2.459; P = .003) and Sequential Organ Failure Assessment score (hazard rate, 1.158; P = .014) were significant predictors of 28-day ICU mortality. Low-TV mechanical ventilation still benefits patients with ARDS caused by viral pneumonia. Copyright © 2013 Elsevier Inc. All rights reserved.

High-frequency oscillatory ventilation for cardiac surgery children with severe acute respiratory distress syndrome.

PubMed

Li, Shengli; Wang, Xu; Li, Shoujun; Yan, Jun

2013-08-01

Acute respiratory distress syndrome (ARDS) in children after open heart surgery, although uncommon, can be a significant source of morbidity. Because high-frequency oscillatory ventilation (HFOV) had been used successfully with pediatric patients who had no congenital heart defects, this therapy was used in our unit. This report aims to describe a single-center experience with HFOV in the management of ARDS after open heart surgery with respect to mortality. This retrospective clinical study was conducted in a pediatric intensive care unit. From October 2008 to August 2012, 64 of 10,843 patients with refractory ARDS who underwent corrective surgery at our institution were ventilated with HFOV. Patients with significant uncorrected residual lesions were not included. No interventions were performed. The patients were followed up until hospital discharge. The main outcome measure was survival to hospital discharge. Severe ARDS was defined as acute-onset pulmonary failure with bilateral pulmonary infiltrates and an oxygenation index (OI) higher than 13 despite maximal ventilator settings. The indication for HFOV was acute severe ARDS unresponsive to optimal conventional treatment. The variables recorded and subjected to multivariate analysis were patient demographics, underlying disease, clinical data, and ventilator parameters and their association with hospital mortality. Nearly 10,843 patients underwent surgery during the study period, and the ARDS incidence rate was 0.76 % (83/10,843), with 64 patients (77 %, 64/83) receiving HFOV. No significant changes in systemic or central venous pressure were associated with initiation and maintenance of HFOV. The complications during HFOV included pneumothorax for 22 patients. The overall in-hospital mortality rate was 39 % (25/64). Multiple regression analyses indicated that pulmonary hypertension and recurrent respiratory tract infections (RRTIs) before surgery were independent predictors of in-hospital mortality. The findings show that HFOV is an effective and safe method for ventilating severe ARDS patients after corrective cardiac surgery. Pulmonary hypertension and RRTIs before surgery were risk factors for in-hospital mortality.

Quantification of asymmetric lung pathophysiology as a guide to the use of simultaneous independent lung ventilation in posttraumatic and septic adult respiratory distress syndrome.

PubMed Central

Siegel, J H; Stoklosa, J C; Borg, U; Wiles, C E; Sganga, G; Geisler, F H; Belzberg, H; Wedel, S; Blevins, S; Goh, K C

1985-01-01

The management of impaired respiratory gas exchange in patients with nonuniform posttraumatic and septic adult respiratory distress syndrome (ARDS) contains its own therapeutic paradox, since the need for volume-controlled ventilation and PEEP in the lung with the most reduced compliance increases pulmonary barotrauma to the better lung. A computer-based system has been developed by which respiratory pressure-flow-volume relations and gas exchange characteristics can be obtained and respiratory dynamic and static compliance curves computed and displayed for each lung, as a means of evaluating the effectiveness of ventilation therapy in ARDS. Using these techniques, eight patients with asymmetrical posttraumatic or septic ARDS, or both, have been managed using simultaneous independent lung ventilation (SILV). The computer assessment technique allows quantification of the nonuniform ARDS pattern between the two lungs. This enabled SILV to be utilized using two synchronized servo-ventilators at different pressure-flow-volumes, inspiratory/expiratory ratios, and PEEP settings to optimize the ventilatory volumes and gas exchange of each lung, without inducing excess barotrauma in the better lung. In the patients with nonuniform ARDS, conventional ventilation was not effective in reducing shunt (QS/QT) or in permitting a lower FIO2 to be used for maintenance of an acceptable PaO2. SILV reduced per cent v-a shunt and permitted a higher PaO2 at lower FIO2. Also, there was x-ray evidence of ARDS improvement in the poorer lung. While the ultimate outcome was largely dependent on the patient's injury and the adequacy of the septic host defense, by utilizing the SILV technique to match the quantitative aspects of respiratory dysfunction in each lung at specific times in the clinical course, it was possible to optimize gas exchange, to reduce barotrauma, and often to reverse apparently fixed ARDS changes. In some instances, this type of physiologically directed ventilatory therapy appeared to contribute to a successful recovery. Images FIG. 10. PMID:3901940

[Lung protective ventilation - pathophysiology and diagnostics].

PubMed

Uhlig, Stefan; Frerichs, Inéz

2008-06-01

Mechanical ventilation may lead to lung injury depending on the ventilatory settings (e.g. pressure amplitudes, endexpiratory pressures, frequency) and the length of mechanical ventilation. Particularly in the inhomogeneously injured lungs of ARDS patients, alveolar overextension results in volutrauma, cyclic opening and closure of alveolar units in atelectrauma. Particularly important appears to be the fact that these processes may also cause biotrauma, i.e. the ventilator-induced hyperactivation of inflammatory responses in the lung. These side effects are reduced, but not eliminated with the currently recommended ventilation strategy with a tidal volume of 6 ml/kg idealized body weight. It is our hope that in the future optimization of ventilator settings will be facilated by bedside monitoring of novel indices of respiratory mechanics such as the stress index or the Slice technique, and by innovative real-time imaging technologies such as electrical impedance tomography.

Association between Hyperglycaemia with Neurological Outcomes Following Severe Head Trauma.

PubMed

Khajavikhan, Javaher; Vasigh, Aminolah; Kokhazade, Taleb; Khani, Ali

2016-04-01

Head Trauma (HT) is a major cause of death, disability and important public health problem. HT is also the main cause of hyperglycaemia that can increase mortality. The aim of this study was to assess the correlation between hyperglycaemia with neurological outcomes following severe Traumatic Brain Injury (TBI). This is a descriptive and correlation study that was carried out at the Imam Khomeini Hospital affiliated with Ilam University of Medical Sciences, Ilam, IR, during March 2014-March 2015 on patients with severe TBI. Data were collected from the patient records on mortality, Intensive Care Unit (ICU) length of stay, hospital length of stay, admission GCS score, Injury Severity Score (ISS), mechanical ventilation, Ventilation Associated Pneumonia (VAP) and Acute Respiratory Distress Syndrome (ARDS). Random Blood Sugar (RBS) level on admission was recorded. Patients with diabetes mellitus (to minimize the overlap between acute stress hyperglycaemia and diabetic hyperglycaemia) were excluded. About 34(40%) of patients were admitted with hyperglycaemia (RBS ≥ 200 mg/dl) over the study period. The mortality rate, length of ICU stay, hospital stay, ISS and VAP & ARDS in patients with RBS levels ≥ 200 mg was significantly higher than patients with RBS levels below ≤ 200mg (p<0.05, p<0.001). A significant correlation was found between RBS with GCS arrival, length of ICU stay, length of hospital stay, ISS, mechanical ventilation and VAP & ARDS (p<0.05, p< 0.001). RBS is a predicate factor for ISS (p <0.05, OR : 1.36), GCS (p <0.001, OR : 1.69), mechanical ventilation (p< 0.05, OR : 1.27), VAP & ARDS (p <0.001, OR : 1.68), length of ICU stay (p <0.001, OR : 1.87) and length of hospital stay (p <0.05, OR : 1.24). Hyperglycaemia after severe TBI (RBS ≥ 200) is associated with poor outcome. It can be a predictive factor for mortality rate, ICU stay, GCS arrival, VAP & RDS, hospital stay and ISS. Management of hyperglycaemia with insulin protocol in cases with value >200mg/dl, is critical in improving the outcome of patients with TBI.

Rationale, study design and analysis plan of the lung imaging morphology for ventilator settings in acute respiratory distress syndrome study (LIVE study): Study protocol for a randomised controlled trial.

PubMed

Jabaudon, Matthieu; Godet, Thomas; Futier, Emmanuel; Bazin, Jean-Étienne; Sapin, Vincent; Roszyk, Laurence; Pereira, Bruno; Constantin, Jean-Michel

2017-10-01

Different acute respiratory distress syndrome (ARDS) phenotypes may explain controversial results in clinical trials. Lung-morphology is one of the ARDS-phenotypes and physiological studies suggest different responses in terms of positive-end-expiratory-pressure (PEEP) and recruitment-manoeuvres (RM) according to loss of aeration. To evaluate whether tailored ventilator regimens may impact ARDS outcomes, our group has designed a randomised-clinical-trial of ventilator settings according to lung morphology in moderate-to-severe ARDS (LIVE study). Patients will be enrolled within the first 12hours of ARDS onset. In both groups, volume-controlled ventilation with low tidal-volumes (Vt) will be used to target a plateau pressure≤30 cmH 2 O. In the control group, the PEEP level and inspired fraction of oxygen (FiO 2 ) will be set using the ARDSNet table; a Vt of 6 mL/kg of predicted body weight (PBW) will be set and prone position (PP) will be applied. In the intervention arm, the ventilator will be set according to lung morphology (focal/non-focal) that will be assessed according to CT-scan±chest x-ray+lung echography. For focal ARDS patients, a Vt of 8 mL/kg PBW will be used along with low PEEP and PP. For non-focal ARDS patients, a Vt of 6 mL/kg PBW will be used with RM and PEEP to reach a plateau pressure≤30 cmH 2 O. The primary outcome is all-cause 90-day mortality and the secondary outcomes are: in-hospital mortality, mortality at day 28, 60, 180 and 365; ventilator-free days at day 30, quality of life at one year; ventilator-associated pneumonia rate; barotrauma; ICU and hospital length of stay. This RCT is registered on Clinicaltrials.gov under identifier NCT02149589. Copyright © 2017 Société française d'anesthésie et de réanimation (Sfar). Published by Elsevier Masson SAS. All rights reserved.

Should PEEP Titration Be Based on Chest Mechanics in Patients With ARDS?

PubMed

Kallet, Richard H

2016-06-01

Functional residual capacity (FRC) is essentially the alveolar volume and a determinant of both oxygenation and respiratory system compliance (CRS). ARDS decreases FRC, and sufficient PEEP restores FRC; thus, assessments of PEEP by its impact on oxygenation and CRS are intimately linked. PEEP also can ameliorate or aggravate ventilator-induced lung injury. Therefore, it can be argued that PEEP should be titrated primarily by its impact on CRS The pro position argues that the heterogeneous nature of lung injury and its unique presentation in individual patients results in an uncoupling between oxygenation and CRS Therefore, relying upon oxygenation alone may enhance lung injury and mortality risk, particularly in those with severe ARDS. The con argument is that the preponderance of preclinical and clinical evidence suggests that a relatively narrow range of PEEP is required to manage all but the most severe cases of ARDS. In addition, pathological alterations in chest wall compliance confuse the interpretation of chest mechanics. Moreover, ambiguities and technical limitations in advanced techniques, such as esophageal manometry and pressure-volume curves, add a layer of complexity that renders its broader application in all ARDS patients both impractical and unnecessary. Whether sophisticated monitoring of chest mechanics in severe ARDS might improve outcomes further is open to question and should be studied further. However, it is highly improbable that we will ever discover a PEEP strategy that optimizes all aspects of cardiorespiratory function and chest mechanics for individual patients suffering from ARDS. Copyright © 2016 by Daedalus Enterprises.

Fifty Years of Research in ARDS. Respiratory Mechanics in Acute Respiratory Distress Syndrome.

PubMed

Henderson, William R; Chen, Lu; Amato, Marcelo B P; Brochard, Laurent J

2017-10-01

Acute respiratory distress syndrome is a multifactorial lung injury that continues to be associated with high levels of morbidity and mortality. Mechanical ventilation, although lifesaving, is associated with new iatrogenic injury. Current best practice involves the use of small Vt, low plateau and driving pressures, and high levels of positive end-expiratory pressure. Collectively, these interventions are termed "lung-protective ventilation." Recent investigations suggest that individualized measurements of pulmonary mechanical variables rather than population-based ventilation prescriptions may be used to set the ventilator with the potential to improve outcomes beyond those achieved with standard lung protective ventilation. This review outlines the measurement and application of clinically applicable pulmonary mechanical concepts, such as plateau pressures, driving pressure, transpulmonary pressures, stress index, and measurement of strain. In addition, the concept of the "baby lung" and the utility of dynamic in addition to static measures of pulmonary mechanical variables are discussed.

A Multicenter Retrospective Review of Prone Position Ventilation (PPV) in Treatment of Severe Human H7N9 Avian Flu

PubMed Central

Han, Yun; Zhou, Lixin; He, Weiqun; Chen, Sibei; Nong, Lingbo; Huang, Huang; Zhang, Yan; Yu, Tieou; Li, Yimin; Liu, Xiaoqing

2015-01-01

Background Patients with H7N9 avian flu concurrent with severe acute respiratory distress syndrome (ARDS) usually have a poor clinical outcome. Prone position ventilation (PPV) has been shown to improve the prognosis of patients with severe ARDS. This study explored the effects of PPV on the respiratory and circulatory mechanics of H7N9-infected patients with severe ARDS. Methods Individuals admitted to four hospitals designated for H7N9 patients in Guangdong province were treated with PPV, and their clinical data were recorded before and after receiving PPV. Results Six of 20 critically ill patients in the ICU received PPV. After treatment with 35 PPV sessions, the oxygenation index (OI) values of the six patients when measured post-PPV and post-supine position ventilation (SPV) were significantly higher than those measured pre-PPV (P < 0.05).The six patients showed no significant differences in their values for respiratory rate (RR), peak inspiratory pressure (PIP), tidal volume (TV) or arterial partial pressure of carbon dioxide (PaCO2) when compared pre-PPV, post-PPV, and post-SPV. Additionally, there were no significant differences in the mean values for arterial pressure (MAP), cardiac index (CI), central venous pressure (CVP), heart rate (HR), lactic acid (LAC) levels or the doses of norepinephrine (NE) administered when compared pre-PPV, post-PPV, and post-SPV. Conclusion PPV provided improved oxygenation that was sustained after returning to a supine position, and resulted in decreased carbon dioxide retention. PPV can thus serve as an alternative lung protective ventilation strategy for use in patients with H7N9 avian flu concurrent with severe ARDS. PMID:26317621

A Multicenter Retrospective Review of Prone Position Ventilation (PPV) in Treatment of Severe Human H7N9 Avian Flu.

PubMed

Xu, Yuanda; Deng, Xilong; Han, Yun; Zhou, Lixin; He, Weiqun; Chen, Sibei; Nong, Lingbo; Huang, Huang; Zhang, Yan; Yu, Tieou; Li, Yimin; Liu, Xiaoqing

2015-01-01

Patients with H7N9 avian flu concurrent with severe acute respiratory distress syndrome (ARDS) usually have a poor clinical outcome. Prone position ventilation (PPV) has been shown to improve the prognosis of patients with severe ARDS. This study explored the effects of PPV on the respiratory and circulatory mechanics of H7N9-infected patients with severe ARDS. Individuals admitted to four hospitals designated for H7N9 patients in Guangdong province were treated with PPV, and their clinical data were recorded before and after receiving PPV. Six of 20 critically ill patients in the ICU received PPV. After treatment with 35 PPV sessions, the oxygenation index (OI) values of the six patients when measured post-PPV and post-supine position ventilation (SPV) were significantly higher than those measured pre-PPV (P < 0.05).The six patients showed no significant differences in their values for respiratory rate (RR), peak inspiratory pressure (PIP), tidal volume (TV) or arterial partial pressure of carbon dioxide (PaCO2) when compared pre-PPV, post-PPV, and post-SPV. Additionally, there were no significant differences in the mean values for arterial pressure (MAP), cardiac index (CI), central venous pressure (CVP), heart rate (HR), lactic acid (LAC) levels or the doses of norepinephrine (NE) administered when compared pre-PPV, post-PPV, and post-SPV. PPV provided improved oxygenation that was sustained after returning to a supine position, and resulted in decreased carbon dioxide retention. PPV can thus serve as an alternative lung protective ventilation strategy for use in patients with H7N9 avian flu concurrent with severe ARDS.

Incidence Proportion of Acute Cor Pulmonale in Patients with Acute Respiratory Distress Syndrome Subjected to Lung Protective Ventilation: A Systematic Review and Meta-analysis.

PubMed

Das, Saurabh Kumar; Choupoo, Nang Sujali; Saikia, Priyam; Lahkar, Amitabh

2017-06-01

Reported incidence of acute cor pulmonale (ACP) in patients with acute respiratory distress syndrome (ARDS) varies from 10% to 84%, despite being subjected to lung protective ventilation according to the current guidelines. The objective of this review is to find pooled cumulative incidence of ACP in patients with ARDS undergoing lung protective ventilation. We searched MEDLINE, EMBASE, Cochrane Library, KoreaMed, LILACS, and WHO Clinical Trial Registry. Cross-sectional or cohort studies were included if they reported or provided data that could be used to calculate the incidence proportion of ACP. Inverse variance heterogeneity (IVhet) and random effect model were used for the main outcome and measures. We included 16 studies encompassing 1661 patients. The cumulative incidence of ACP using IVhet analysis was 23% (95% confidence interval [CI] = 18%-28%) over 3 days of lung protective ventilation. Random effect analysis of 7 studies (1250 patients) revealed pooled odd ratio of mortality of 1.16 (95% CI = 0.80-1.67, P = 0.44) due to ACP. Patients with ARDS have a 23% risk of developing ACP with lung protective ventilation. Findings of this review indicate the need of updating existing guidelines for ventilating ARDS patients to incorporate right ventricle protective strategy.

Prone positioning ventilation for treatment of acute lung injury and acute respiratory distress syndrome.

PubMed

Lan, Mei-juan; He, Xiao-di

2009-08-01

Patients who are diagnosed with acute lung injury/acute respiratory distress syndrome (ALI/ARDS) usually have ventilation-perfusion mismatch, severe decrease in lung capacity, and gas exchange abnormalities. Health care workers have implemented various strategies in an attempt to compensate for these pathological alterations. By rotating patients with ALI/ARDS between the supine and prone position, it is possible to achieve a significant improvement in PaO2/FiO2, decrease shunting and therefore improve oxygenation without use of expensive, invasive and experimental procedures. Prone positioning is a safe and effective way to improve ventilation when conventional strategies fail to initiate a patient response. Because a specific cure for ARDS is not available, the goal is to support the patients with therapies that cause the least amount of injury while the lungs have an opportunity to heal. Based on current data, a trial of prone positioning ventilation should be offered to the patients who have ALI/ARDS in the early course of the disease. Published studies exhibit substantial heterogeneity in clinical results, suggesting that an adequately sized study optimizing the duration of proning ventilation strategy is warranted to enable definitive conclusions to be drawn.

Prediction of high airway pressure using a non-linear autoregressive model of pulmonary mechanics.

PubMed

Langdon, Ruby; Docherty, Paul D; Schranz, Christoph; Chase, J Geoffrey

2017-11-02

For mechanically ventilated patients with acute respiratory distress syndrome (ARDS), suboptimal PEEP levels can cause ventilator induced lung injury (VILI). In particular, high PEEP and high peak inspiratory pressures (PIP) can cause over distension of alveoli that is associated with VILI. However, PEEP must also be sufficient to maintain recruitment in ARDS lungs. A lung model that accurately and precisely predicts the outcome of an increase in PEEP may allow dangerous high PIP to be avoided, and reduce the incidence of VILI. Sixteen pressure-flow data sets were collected from nine mechanically ventilated ARDs patients that underwent one or more recruitment manoeuvres. A nonlinear autoregressive (NARX) model was identified on one or more adjacent PEEP steps, and extrapolated to predict PIP at 2, 4, and 6 cmH 2 O PEEP horizons. The analysis considered whether the predicted and measured PIP exceeded a threshold of 40 cmH 2 O. A direct comparison of the method was made using the first order model of pulmonary mechanics (FOM(I)). Additionally, a further, more clinically appropriate method for the FOM was tested, in which the FOM was trained on a single PEEP prior to prediction (FOM(II)). The NARX model exhibited very high sensitivity (> 0.96) in all cases, and a high specificity (> 0.88). While both FOM methods had a high specificity (> 0.96), the sensitivity was much lower, with a mean of 0.68 for FOM(I), and 0.82 for FOM(II). Clinically, false negatives are more harmful than false positives, as a high PIP may result in distension and VILI. Thus, the NARX model may be more effective than the FOM in allowing clinicians to reduce the risk of applying a PEEP that results in dangerously high airway pressures.

Hyperpolarized gas diffusion MRI for the study of atelectasis and acute respiratory distress syndrome.

PubMed

Cereda, Maurizio; Xin, Yi; Kadlecek, Stephen; Hamedani, Hooman; Rajaei, Jennia; Clapp, Justin; Rizi, Rahim R

2014-12-01

Considerable uncertainty remains about the best ventilator strategies for the mitigation of atelectasis and associated airspace stretch in patients with acute respiratory distress syndrome (ARDS). In addition to several immediate physiological effects, atelectasis increases the risk of ventilator-associated lung injury, which has been shown to significantly worsen ARDS outcomes. A number of lung imaging techniques have made substantial headway in clarifying the mechanisms of atelectasis. This paper reviews the contributions of computed tomography, positron emission tomography, and conventional MRI to understanding this phenomenon. In doing so, it also reveals several important shortcomings inherent to each of these approaches. Once these shortcomings have been made apparent, we describe how hyperpolarized (HP) gas MRI--a technique that is uniquely able to assess responses to mechanical ventilation and lung injury in peripheral airspaces--is poised to fill several of these knowledge gaps. The HP-MRI-derived apparent diffusion coefficient (ADC) quantifies the restriction of (3) He diffusion by peripheral airspaces, thereby obtaining pulmonary structural information at an extremely small scale. Lastly, this paper reports the results of a series of experiments that measured ADC in mechanically ventilated rats in order to investigate (i) the effect of atelectasis on ventilated airspaces, (ii) the relationship between positive end-expiratory pressure (PEEP), hysteresis, and the dimensions of peripheral airspaces, and (iii) the ability of PEEP and surfactant to reduce airspace dimensions after lung injury. An increase in ADC was found to be a marker of atelectasis-induced overdistension. With recruitment, higher airway pressures were shown to reduce stretch rather than worsen it. Moving forward, HP MRI has significant potential to shed further light on the atelectatic processes that occur during mechanical ventilation. Copyright © 2014 John Wiley & Sons, Ltd.

Hyperpolarized Gas Diffusion MRI for the Study of Atelectasis and Acute Respiratory Distress Syndrome

PubMed Central

Cereda, Maurizio; Xin, Yi; Kadlecek, Stephen; Hamedani, Hooman; Rajaei, Jennia; Clapp, Justin; Rizi, Rahim R.

2014-01-01

Considerable uncertainty remains about the best ventilator strategies for the mitigation of atelectasis and associated airspace stretch in patients with acute respiratory distress syndrome (ARDS). In addition to several immediate physiological effects, atelectasis increases the risk of ventilator-associated lung injury (VALI), which has been shown to significantly worsen ARDS outcomes. A number of lung imaging techniques have made substantial headway in clarifying the mechanisms of atelectasis. This paper reviews the contributions of CT, PET, and conventional MRI to understanding this phenomenon. In doing so, it also reveals several important shortcomings inherent to each of these approaches. Once these shortcomings have been made apparent, we describe how hyperpolarized gas magnetic resonance imaging (HP MRI)—a technique that is uniquely able to assess responses to mechanical ventilation and lung injury in peripheral airspaces—is poised to fill several of these knowledge gaps. The HP-MRI-derived apparent diffusion coefficient (ADC) quantifies the restriction of 3He diffusion by peripheral airspaces, thereby obtaining pulmonary structural information at an extremely small scale. Lastly, this paper reports the results of a series of experiments that measured ADC in mechanically ventilated rats in order to investigate (i) the effect of atelectasis on ventilated airspaces; (ii) the relationship between positive end-expiratory pressure (PEEP), hysteresis, and the dimensions of peripheral airspaces; and (iii) the ability of PEEP and surfactant to reduce airspace dimensions after lung injury. An increase in ADC was found to be a marker of atelectasis-induced overdistension. With recruitment, higher airway pressures were shown to reduce stretch rather than worsen it. Moving forward, HP MRI has significant potential to shed further light on the atelectatic processes that occur during mechanical ventilation. PMID:24920074

Lower tidal volume strategy (≈3 ml/kg) combined with extracorporeal CO2 removal versus 'conventional' protective ventilation (6 ml/kg) in severe ARDS: the prospective randomized Xtravent-study.

PubMed

Bein, Thomas; Weber-Carstens, Steffen; Goldmann, Anton; Müller, Thomas; Staudinger, Thomas; Brederlau, Jörg; Muellenbach, Ralf; Dembinski, Rolf; Graf, Bernhard M; Wewalka, Marlene; Philipp, Alois; Wernecke, Klaus-Dieter; Lubnow, Matthias; Slutsky, Arthur S

2013-05-01

Acute respiratory distress syndrome is characterized by damage to the lung caused by various insults, including ventilation itself, and tidal hyperinflation can lead to ventilator induced lung injury (VILI). We investigated the effects of a low tidal volume (V(T)) strategy (V(T) ≈ 3 ml/kg/predicted body weight [PBW]) using pumpless extracorporeal lung assist in established ARDS. Seventy-nine patients were enrolled after a 'stabilization period' (24 h with optimized therapy and high PEEP). They were randomly assigned to receive a low V(T) ventilation (≈3 ml/kg) combined with extracorporeal CO2 elimination, or to a ARDSNet strategy (≈6 ml/kg) without the extracorporeal device. The primary outcome was the 28-days and 60-days ventilator-free days (VFD). Secondary outcome parameters were respiratory mechanics, gas exchange, analgesic/sedation use, complications and hospital mortality. Ventilation with very low V(T)'s was easy to implement with extracorporeal CO2-removal. VFD's within 60 days were not different between the study group (33.2 ± 20) and the control group (29.2 ± 21, p = 0.469), but in more hypoxemic patients (PaO2/FIO2 ≤150) a post hoc analysis demonstrated significant improved VFD-60 in study patients (40.9 ± 12.8) compared to control (28.2 ± 16.4, p = 0.033). The mortality rate was low (16.5%) and did not differ between groups. The use of very low V(T) combined with extracorporeal CO2 removal has the potential to further reduce VILI compared with a 'normal' lung protective management. Whether this strategy will improve survival in ARDS patients remains to be determined (Clinical trials NCT 00538928).

Effects of Interventions on Survival in Acute Respiratory Distress Syndrome: an Umbrella Review of 159 Published Randomized Trials and 29 Meta-analyses

PubMed Central

Tonelli, Adriano R.; Zein, Joe; Adams, Jacob; Ioannidis, John P.A.

2014-01-01

Purpose Multiple interventions have been tested in acute respiratory distress syndrome (ARDS). We examined the entire agenda of published randomized controlled trials (RCTs) in ARDS that reported on mortality and of respective meta-analyses. Methods We searched PubMed, the Cochrane Library and Web of Knowledge until July 2013. We included RCTs in ARDS published in English. We excluded trials of newborns and children; and those on short-term interventions, ARDS prevention or post-traumatic lung injury. We also reviewed all meta-analyses of RCTs in this field that addressed mortality. Treatment modalities were grouped in five categories: mechanical ventilation strategies and respiratory care, enteral or parenteral therapies, inhaled / intratracheal medications, nutritional support and hemodynamic monitoring. Results We identified 159 published RCTs of which 93 had overall mortality reported (n= 20,671 patients) - 44 trials (14,426 patients) reported mortality as a primary outcome. A statistically significant survival benefit was observed in 8 trials (7 interventions) and two trials reported an adverse effect on survival. Among RTCs with >50 deaths in at least 1 treatment arm (n=21), 2 showed a statistically significant mortality benefit of the intervention (lower tidal volumes and prone positioning), 1 showed a statistically significant mortality benefit only in adjusted analyses (cisatracurium) and 1 (high-frequency oscillatory ventilation) showed a significant detrimental effect. Across 29 meta-analyses, the most consistent evidence was seen for low tidal volumes and prone positioning in severe ARDS. Conclusions There is limited supportive evidence that specific interventions can decrease mortality in ARDS. While low tidal volumes and prone positioning in severe ARDS seem effective, most sporadic findings of interventions suggesting reduced mortality are not corroborated consistently in large-scale evidence including meta-analyses. PMID:24667919

Reabsorption atelectasis in a porcine model of ARDS: regional and temporal effects of airway closure, oxygen, and distending pressure.

PubMed

Derosa, Savino; Borges, João Batista; Segelsjö, Monica; Tannoia, Angela; Pellegrini, Mariangela; Larsson, Anders; Perchiazzi, Gaetano; Hedenstierna, Göran

2013-11-01

Little is known about the small airways dysfunction in acute respiratory distress syndrome (ARDS). By computed tomography (CT) imaging in a porcine experimental model of early ARDS, we aimed at studying the location and magnitude of peripheral airway closure and alveolar collapse under high and low distending pressures and high and low inspiratory oxygen fraction (FIO2). Six piglets were mechanically ventilated under anesthesia and muscle relaxation. Four animals underwent saline-washout lung injury, and two served as healthy controls. Beyond the site of assumed airway closure, gas was expected to be trapped in the injured lungs, promoting alveolar collapse. This was tested by ventilation with an FIO2 of 0.25 and 1 in sequence during low and high distending pressures. In the most dependent regions, the gas/tissue ratio of end-expiratory CT, after previous ventilation with FIO2 0.25 low-driving pressure, was significantly higher than after ventilation with FIO2 1; with high-driving pressure, this difference disappeared. Also, significant reduction in poorly aerated tissue and a correlated increase in nonaerated tissue in end-expiratory CT with FIO2 1 low-driving pressure were seen. When high-driving pressure was applied or after previous ventilation with FIO2 0.25 and low-driving pressure, this pattern disappeared. The findings suggest that low distending pressures produce widespread dependent airway closure and with high FIO2, subsequent absorption atelectasis. Low FIO2 prevented alveolar collapse during the study period because of slow absorption of gas behind closed airways.

Resolved versus confirmed ARDS after 24 h: insights from the LUNG SAFE study.

PubMed

Madotto, Fabiana; Pham, Tài; Bellani, Giacomo; Bos, Lieuwe D; Simonis, Fabienne D; Fan, Eddy; Artigas, Antonio; Brochard, Laurent; Schultz, Marcus J; Laffey, John G

2018-04-09

To evaluate patients with resolved versus confirmed ARDS, identify subgroups with substantial mortality risk, and to determine the utility of day 2 ARDS reclassification. Our primary objective, in this secondary LUNG SAFE analysis, was to compare outcome in patients with resolved versus confirmed ARDS after 24 h. Secondary objectives included identifying factors associated with ARDS persistence and mortality, and the utility of day 2 ARDS reclassification. Of 2377 patients fulfilling the ARDS definition on the first day of ARDS (day 1) and receiving invasive mechanical ventilation, 503 (24%) no longer fulfilled the ARDS definition the next day, 52% of whom initially had moderate or severe ARDS. Higher tidal volume on day 1 of ARDS was associated with confirmed ARDS [OR 1.07 (CI 1.01-1.13), P = 0.035]. Hospital mortality was 38% overall, ranging from 31% in resolved ARDS to 41% in confirmed ARDS, and 57% in confirmed severe ARDS at day 2. In both resolved and confirmed ARDS, age, non-respiratory SOFA score, lower PEEP and P/F ratio, higher peak pressure and respiratory rate were each associated with mortality. In confirmed ARDS, pH and the presence of immunosuppression or neoplasm were also associated with mortality. The increase in area under the receiver operating curve for ARDS reclassification on day 2 was marginal. ARDS, whether resolved or confirmed at day 2, has a high mortality rate. ARDS reclassification at day 2 has limited predictive value for mortality. The substantial mortality risk in severe confirmed ARDS suggests that complex interventions might best be tested in this population. ClinicalTrials.gov NCT02010073.

Acute exacerbation of idiopathic pulmonary fibrosis: lessons learned from acute respiratory distress syndrome?

PubMed

Marchioni, Alessandro; Tonelli, Roberto; Ball, Lorenzo; Fantini, Riccardo; Castaniere, Ivana; Cerri, Stefania; Luppi, Fabrizio; Malerba, Mario; Pelosi, Paolo; Clini, Enrico

2018-03-23

Idiopathic pulmonary fibrosis (IPF) is a fibrotic lung disease characterized by progressive loss of lung function and poor prognosis. The so-called acute exacerbation of IPF (AE-IPF) may lead to severe hypoxemia requiring mechanical ventilation in the intensive care unit (ICU). AE-IPF shares several pathophysiological features with acute respiratory distress syndrome (ARDS), a very severe condition commonly treated in this setting.A review of the literature has been conducted to underline similarities and differences in the management of patients with AE-IPF and ARDS.During AE-IPF, diffuse alveolar damage and massive loss of aeration occurs, similar to what is observed in patients with ARDS. Differently from ARDS, no studies have yet concluded on the optimal ventilatory strategy and management in AE-IPF patients admitted to the ICU. Notwithstanding, a protective ventilation strategy with low tidal volume and low driving pressure could be recommended similarly to ARDS. The beneficial effect of high levels of positive end-expiratory pressure and prone positioning has still to be elucidated in AE-IPF patients, as well as the precise role of other types of respiratory assistance (e.g., extracorporeal membrane oxygenation) or innovative therapies (e.g., polymyxin-B direct hemoperfusion). The use of systemic drugs such as steroids or immunosuppressive agents in AE-IPF is controversial and potentially associated with an increased risk of serious adverse reactions.Common pathophysiological abnormalities and similar clinical needs suggest translating to AE-IPF the lessons learned from the management of ARDS patients. Studies focused on specific therapeutic strategies during AE-IPF are warranted.

Health Care Utilization and the Cost of Post-Traumatic ARDS Care.

PubMed

Robles, Anamaria J; Kornblith, Lucy Z; Hendrickson, Carolyn M; Howard, Benjamin M; Conroy, Amanda S; Moazed, Farzad; Calfee, Carolyn S; Cohen, Mitchell J; Callcut, Rachael A

2018-04-02

Post-traumatic acute respiratory distress syndrome (ARDS) is associated with prolonged mechanical ventilation and longer hospitalizations. The relationship between post-traumatic ARDS severity and financial burden has not been previously studied. We hypothesized that increasing severity is associated with incrementally higher health care costs. Adults arriving as the highest level of trauma activation were enrolled in an ongoing prospective cohort study. Patients who survived ≥6 hours are included in the analysis. Blinded review of chest radiographs was performed by two independent physicians for any intubated patient with PaO2:FiO2 ratio (P/F) ≤300mgHg during the first 8 days of admission. The severity of ARDS was classified by the Berlin criteria. Hospital charge data was utilized to perform standard costing analysis. ARDS occurred in 13% (203/1586). The distribution of disease severity was 33% mild, 42% moderate, and 25% severe. Patients with ARDS were older (41 vs 35 years, p<0.01), had higher median ISS (30 vs 10, p<0.01), more chest injury (AIS≥3: 51% vs 21%, p<0.01), and blunt mechanisms (85% vs 53%, p<0.01). By ARDS severity, there was no significant difference in age, mechanism, or rate of traumatic brain injury. Increasing ARDS severity was associated with higher ISS and higher mortality rates. Standardized total hospital charges were four-fold higher for patients who developed ARDS compared to those who did not develop ARDS ($434K vs $96K, p<0.01). Furthermore, the daily hospital charges significantly increased across categories of worsening ARDS severity (mild $20,451; moderate $23,994; severe $33,316, p<0.01). The development of post-traumatic ARDS is associated with higher health care costs. Among trauma patients who develop ARDS, total hospital charges per day increase with worsening severity of disease. Prevention, early recognition, and treatment of ARDS after trauma are potentially important objectives for efforts to control health care costs in this population. IV STUDY TYPE: Economic and Value-based Evaluations.

Multivariable fractional polynomial interaction to investigate continuous effect modifiers in a meta-analysis on higher versus lower PEEP for patients with ARDS.

PubMed

Kasenda, Benjamin; Sauerbrei, Willi; Royston, Patrick; Mercat, Alain; Slutsky, Arthur S; Cook, Deborah; Guyatt, Gordon H; Brochard, Laurent; Richard, Jean-Christophe M; Stewart, Thomas E; Meade, Maureen; Briel, Matthias

2016-09-08

A recent individual patient data (IPD) meta-analysis suggested that patients with moderate or severe acute respiratory distress syndrome (ARDS) benefit from higher positive end-expiratory pressure (PEEP) ventilation strategies. However, thresholds for continuous variables (eg, hypoxaemia) are often arbitrary and linearity assumptions in regression approaches may not hold; the multivariable fractional polynomial interaction (MFPI) approach can address both problems. The objective of this study was to apply the MFPI approach to investigate interactions between four continuous patient baseline variables and higher versus lower PEEP on clinical outcomes. Pooled data from three randomised trials in intensive care identified by a systematic review. 2299 patients with acute lung injury requiring mechanical ventilation. Higher (N=1136) versus lower PEEP (N=1163) ventilation strategy. Prespecified outcomes included mortality, time to death and time-to-unassisted breathing. We examined the following continuous baseline characteristics as potential effect modifiers using MFPI: PaO2/FiO2 (arterial partial oxygen pressure/ fraction of inspired oxygen), oxygenation index, respiratory system compliance (tidal volume/(inspiratory plateau pressure-PEEP)) and body mass index (BMI). We found that for patients with PaO2/FiO2 below 150 mm Hg, but above 100 mm Hg or an oxygenation index above 12 (moderate ARDS), higher PEEP reduces hospital mortality, but the beneficial effect appears to level off for patients with very severe ARDS. Patients with mild ARDS (PaO2/FiO2 above 200 mm Hg or an oxygenation index below 10) do not seem to benefit from higher PEEP and might even be harmed. For patients with a respiratory system compliance above 40 mL/cm H2O or patients with a BMI above 35 kg/m(2), we found a trend towards reduced mortality with higher PEEP, but there is very weak statistical confidence in these findings. MFPI analyses suggest a nonlinear effect modification of higher PEEP ventilation by PaO2/FiO2 and oxygenation index with reduced mortality for some patients suffering from moderate ARDS. CRD42012003129. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Respirator triggering of electron beam computed tomography (EBCT): evaluation of dynamic changes during mechanical expiration in the traumatized patient

NASA Astrophysics Data System (ADS)

Recheis, Wolfgang A.; Kleinsasser, Axel; Hatschenberger, Robert; Knapp, Rudolf; zur Nedden, Dieter; Hoermann, Christoph

1999-05-01

The purpose of this project is to evaluate the dynamic changes during expiration at different levels of positive end- expiratory pressure (PEEP) in the ventilated patient. We wanted to discriminate between normal lung function and acute respiratory distress syndrome (ARDS). After approval by the local Ethic Committee we studied two ventilated patients: (1) with normal lung function; (2) ARDS). We used the 50 ms scan mode of the EBCT. The beam was positioned 1 cm above the diaphragm. The table position remained unchanged. An electronic trigger was developed, that utilizes the respirators synchronizing signal to start the EBCT at the onset of expiration. During controlled mechanical expiration at two levels of PEEP (0 and 15 cm H2O), pulmonary aeration was rated as: well-aerated (-900HU/-500HU), poorly- aerated (-500HU/-100HU) and non-aerated (-100HU/+100HU). Pathological and normal lung function showed different dynamic changes (FIG.4-12). The different PEEP levels resulted in a significant change of pulmonary aeration in the same patient. Although we studied only a very limited number of patients, respirator triggered EBCT may be accurate in discriminating pathological changes due to the abnormal lung function in the mechanically ventilated patient.

Noninvasive Ventilation of Patients with Acute Respiratory Distress Syndrome. Insights from the LUNG SAFE Study.

PubMed

Bellani, Giacomo; Laffey, John G; Pham, Tài; Madotto, Fabiana; Fan, Eddy; Brochard, Laurent; Esteban, Andres; Gattinoni, Luciano; Bumbasirevic, Vesna; Piquilloud, Lise; van Haren, Frank; Larsson, Anders; McAuley, Daniel F; Bauer, Philippe R; Arabi, Yaseen M; Ranieri, Marco; Antonelli, Massimo; Rubenfeld, Gordon D; Thompson, B Taylor; Wrigge, Hermann; Slutsky, Arthur S; Pesenti, Antonio

2017-01-01

Noninvasive ventilation (NIV) is increasingly used in patients with acute respiratory distress syndrome (ARDS). The evidence supporting NIV use in patients with ARDS remains relatively sparse. To determine whether, during NIV, the categorization of ARDS severity based on the Pa O 2 /Fi O 2 Berlin criteria is useful. The LUNG SAFE (Large Observational Study to Understand the Global Impact of Severe Acute Respiratory Failure) study described the management of patients with ARDS. This substudy examines the current practice of NIV use in ARDS, the utility of the Pa O 2 /Fi O 2 ratio in classifying patients receiving NIV, and the impact of NIV on outcome. Of 2,813 patients with ARDS, 436 (15.5%) were managed with NIV on Days 1 and 2 following fulfillment of diagnostic criteria. Classification of ARDS severity based on Pa O 2 /Fi O 2 ratio was associated with an increase in intensity of ventilatory support, NIV failure, and intensive care unit (ICU) mortality. NIV failure occurred in 22.2% of mild, 42.3% of moderate, and 47.1% of patients with severe ARDS. Hospital mortality in patients with NIV success and failure was 16.1% and 45.4%, respectively. NIV use was independently associated with increased ICU (hazard ratio, 1.446 [95% confidence interval, 1.159-1.805]), but not hospital, mortality. In a propensity matched analysis, ICU mortality was higher in NIV than invasively ventilated patients with a Pa O 2 /Fi O 2 lower than 150 mm Hg. NIV was used in 15% of patients with ARDS, irrespective of severity category. NIV seems to be associated with higher ICU mortality in patients with a Pa O 2 /Fi O 2 lower than 150 mm Hg. Clinical trial registered with www.clinicaltrials.gov (NCT 02010073).

Use of the PiCCO system in critically ill patients with septic shock and acute respiratory distress syndrome: a study protocol for a randomized controlled trial.

PubMed

Zhang, Zhongheng; Xu, Xiao; Yao, Min; Chen, Huilan; Ni, Hongying; Fan, Haozhe

2013-02-01

Hemodynamic monitoring is very important in critically ill patients with shock or acute respiratory distress syndrome(ARDS). The PiCCO (Pulse index Contour Continuous Cardiac Output, Pulsion Medical Systems, Germany) system has been developed and used in critical care settings for several years. However, its impact on clinical outcomes remains unknown. The study is a randomized controlled multi-center trial. A total of 708 patients with ARDS, septic shock or both will be included from January 2012 to January 2014. Subjects will be randomized to receive PiCCO monitoring or not. Our primary end point is 30-day mortality, and secondary outcome measures include ICU length of stay, days on mechanical ventilation, days of vasoactive agent support, ICU-free survival days during a 30-day period, mechanical-ventilation-free survival days during a 30-day period, and maximum SOFA score during the first 7 days. We investigate whether the use of PiCCO monitoring will improve patient outcomes in critically ill patients with ARDS or septic shock. This will provide additional data on hemodynamic monitoring and help clinicians to make decisions on the use of PiCCO. http://www.clinicaltrials.gov NCT01526382.

Effects of pleural effusion drainage on oxygenation, respiratory mechanics, and hemodynamics in mechanically ventilated patients.

PubMed

Razazi, Keyvan; Thille, Arnaud W; Carteaux, Guillaume; Beji, Olfa; Brun-Buisson, Christian; Brochard, Laurent; Mekontso Dessap, Armand

2014-09-01

In mechanically ventilated patients, the effect of draining pleural effusion on oxygenation is controversial. We investigated the effect of large pleural effusion drainage on oxygenation, respiratory function (including lung volumes), and hemodynamics in mechanically ventilated patients after ultrasound-guided drainage. Arterial blood gases, respiratory mechanics (airway, pleural and transpulmonary pressures, end-expiratory lung volume, respiratory system compliance and resistance), and hemodynamics (blood pressure, heart rate, and cardiac output) were recorded before and at 3 and 24 hours (H24) after pleural drainage. The respiratory settings were kept identical during the study period. The mean volume of effusion drained was 1,579 ± 684 ml at H24. Uncomplicated pneumothorax occurred in two patients. Respiratory mechanics significantly improved after drainage, with a decrease in plateau pressure and a large increase in end-expiratory transpulmonary pressure. Respiratory system compliance, end-expiratory lung volume, and PaO2/FiO2 ratio all improved. Hemodynamics were not influenced by drainage. Improvement in the PaO2/FiO2 ratio from baseline to H24 was positively correlated with the increase in end-expiratory lung volume during the same time frame (r = 0.52, P = 0.033), but not with drained volume. A high value of pleural pressure or a highly negative transpulmonary pressure at baseline predicted limited lung expansion following effusion drainage. A lesser improvement in oxygenation occurred in patients with ARDS. Drainage of large (≥500 ml) pleural effusion in mechanically ventilated patients improves oxygenation and end-expiratory lung volume. Oxygenation improvement correlated with an increase in lung volume and a decrease in transpulmonary pressure, but was less so in patients with ARDS.

Using Optical Tweezers to Study Cell Mechanics during Airway Reopening

NASA Astrophysics Data System (ADS)

Yalcin, Huseyin; Wang, Jing; Ghadiali, Samir; Ou-Yang, H. Daniel

2006-03-01

Patients suffering from the acute respiratory distress syndrome (ARDS) must be mechanically ventilated in order to survive. However, these ventilation protocols may generate injurious hydrodynamic stresses especially during low tidal volume (VT) ventilation when the flow of micron-sized air bubbles displace the surrounding liquid. In-vitro studies in our lab revealed that microbubble flows can severally damage lung epithelial cells (EC). The degree of injury was elevated for sub-confluent monolayers in small channel heights. Under these conditions, the micromechanics of individual EC may influence the degree of cellular injury. To investigate the role of cell mechanics, we used an oscillating Optical Tweezers (OT) technique to measure the intrinsic mechanical properties of EC before and after the flow of microbubbles. Knowledge of how the EC's micromechanical properties influence cell viability may lead to the development of novel treatment therapies that enhance the EC's ability to withstand injurious hydrodynamic stresses during ventilation treatment.

Biomarkers in Pediatric ARDS: Future Directions.

PubMed

Orwoll, Benjamin E; Sapru, Anil

2016-01-01

Acute respiratory distress syndrome (ARDS) is common among mechanically ventilated children and accompanies up to 30% of all pediatric intensive care unit deaths. Though ARDS diagnosis is based on clinical criteria, biological markers of acute lung damage have been extensively studied in adults and children. Biomarkers of inflammation, alveolar epithelial and capillary endothelial disruption, disordered coagulation, and associated derangements measured in the circulation and other body fluids, such as bronchoalveolar lavage, have improved our understanding of pathobiology of ARDS. The biochemical signature of ARDS has been increasingly well described in adult populations, and this has led to the identification of molecular phenotypes to augment clinical classifications. However, there is a paucity of data from pediatric ARDS (pARDS) patients. Biomarkers and molecular phenotypes have the potential to identify patients at high risk of poor outcomes, and perhaps inform the development of targeted therapies for specific groups of patients. Additionally, because of the lower incidence of and mortality from ARDS in pediatric patients relative to adults and lack of robust clinical predictors of outcome, there is an ongoing interest in biological markers as surrogate outcome measures. The recent definition of pARDS provides additional impetus for the measurement of established and novel biomarkers in future pediatric studies in order to further characterize this disease process. This chapter will review the currently available literature and discuss potential future directions for investigation into biomarkers in ARDS among children.

Biomarkers in Pediatric ARDS: Future Directions

PubMed Central

Orwoll, Benjamin E.; Sapru, Anil

2016-01-01

Acute respiratory distress syndrome (ARDS) is common among mechanically ventilated children and accompanies up to 30% of all pediatric intensive care unit deaths. Though ARDS diagnosis is based on clinical criteria, biological markers of acute lung damage have been extensively studied in adults and children. Biomarkers of inflammation, alveolar epithelial and capillary endothelial disruption, disordered coagulation, and associated derangements measured in the circulation and other body fluids, such as bronchoalveolar lavage, have improved our understanding of pathobiology of ARDS. The biochemical signature of ARDS has been increasingly well described in adult populations, and this has led to the identification of molecular phenotypes to augment clinical classifications. However, there is a paucity of data from pediatric ARDS (pARDS) patients. Biomarkers and molecular phenotypes have the potential to identify patients at high risk of poor outcomes, and perhaps inform the development of targeted therapies for specific groups of patients. Additionally, because of the lower incidence of and mortality from ARDS in pediatric patients relative to adults and lack of robust clinical predictors of outcome, there is an ongoing interest in biological markers as surrogate outcome measures. The recent definition of pARDS provides additional impetus for the measurement of established and novel biomarkers in future pediatric studies in order to further characterize this disease process. This chapter will review the currently available literature and discuss potential future directions for investigation into biomarkers in ARDS among children. PMID:27313995

A risk tertiles model for predicting mortality in patients with acute respiratory distress syndrome: age, plateau pressure, and P(aO(2))/F(IO(2)) at ARDS onset can predict mortality.

PubMed

Villar, Jesús; Pérez-Méndez, Lina; Basaldúa, Santiago; Blanco, Jesús; Aguilar, Gerardo; Toral, Darío; Zavala, Elizabeth; Romera, Miguel A; González-Díaz, Gumersindo; Nogal, Frutos Del; Santos-Bouza, Antonio; Ramos, Luís; Macías, Santiago; Kacmarek, Robert M

2011-04-01

Predicting mortality has become a necessary step for selecting patients for clinical trials and defining outcomes. We examined whether stratification by tertiles of respiratory and ventilatory variables at the onset of acute respiratory distress syndrome (ARDS) identifies patients with different risks of death in the intensive care unit. We performed a secondary analysis of data from 220 patients included in 2 multicenter prospective independent trials of ARDS patients mechanically ventilated with a lung-protective strategy. Using demographic, pulmonary, and ventilation data collected at ARDS onset, we derived and validated a simple prediction model based on a population-based stratification of variable values into low, middle, and high tertiles. The derivation cohort included 170 patients (all from one trial) and the validation cohort included 50 patients (all from a second trial). Tertile distribution for age, plateau airway pressure (P(plat)), and P(aO(2))/F(IO(2)) at ARDS onset identified subgroups with different mortalities, particularly for the highest-risk tertiles: age (> 62 years), P(plat) (> 29 cm H(2)O), and P(aO(2))/F(IO(2)) (< 112 mm Hg). Risk was defined by the number of coexisting high-risk tertiles: patients with no high-risk tertiles had a mortality of 12%, whereas patients with 3 high-risk tertiles had 90% mortality (P < .001). A prediction model based on tertiles of patient age, P(plat), and P(aO(2))/F(IO(2)) at the time the patient meets ARDS criteria identifies patients with the lowest and highest risk of intensive care unit death.

[Concepts and monitoring of pulmonary mechanic in patients under ventilatory support in intensive care unit].

PubMed

Faustino, Eduardo Antonio

2007-06-01

In mechanical ventilation, invasive and noninvasive, the knowledge of respiratory mechanic physiology is indispensable to take decisions and into the efficient management of modern ventilators. Monitoring of pulmonary mechanic parameters is been recommended from all the review works and clinical research. The objective of this study was review concepts of pulmonary mechanic and the methods used to obtain measures in the bed side, preparing a rational sequence to obtain this data. It was obtained bibliographic review through data bank LILACS, MedLine and PubMed, from the last ten years. This review approaches parameters of resistance, pulmonary compliance and intrinsic PEEP as primordial into comprehension of acute respiratory failure and mechanic ventilatory support, mainly in acute respiratory distress syndrome (ARDS) and in chronic obstructive pulmonary disease (COPD). Monitoring pulmonary mechanics in patients under mechanical ventilation in intensive care units gives relevant informations and should be implemented in a rational and systematic way.

Low Tidal Volume Ventilation in Patients without Acute Respiratory Distress Syndrome: A Paradigm Shift in Mechanical Ventilation

PubMed Central

Lipes, Jed; Bojmehrani, Azadeh; Lellouche, Francois

2012-01-01

Protective ventilation with low tidal volume has been shown to reduce morbidity and mortality in patients suffering from acute lung injury (ALI) and acute respiratory distress syndrome (ARDS). Low tidal volume ventilation is associated with particular clinical challenges and is therefore often underutilized as a therapeutic option in clinical practice. Despite some potential difficulties, data have been published examining the application of protective ventilation in patients without lung injury. We will briefly review the physiologic rationale for low tidal volume ventilation and explore the current evidence for protective ventilation in patients without lung injury. In addition, we will explore some of the potential reasons for its underuse and provide strategies to overcome some of the associated clinical challenges. PMID:22536499

Protective Lung Ventilation and Morbidity After Pulmonary Resection: A Propensity Score-Matched Analysis.

PubMed

Amar, David; Zhang, Hao; Pedoto, Alessia; Desiderio, Dawn P; Shi, Weiji; Tan, Kay See

2017-07-01

Protective lung ventilation (PLV) during one-lung ventilation (OLV) for thoracic surgery is frequently recommended to reduce pulmonary complications. However, limited outcome data exist on whether PLV use during OLV is associated with less clinically relevant pulmonary morbidity after lung resection. Intraoperative data were prospectively collected in 1080 patients undergoing pulmonary resection with OLV, intentional crystalloid restriction, and mechanical ventilation to maintain inspiratory peak airway pressure <30 cm H2O. Other ventilator settings and all aspects of anesthetic management were at the discretion of the anesthesia care team. We defined PLV and non-PLV as <8 or ≥8 mL/kg (predicted body weight) mean tidal volume. The primary outcome was the occurrence of pneumonia and/or acute respiratory distress syndrome (ARDS). Propensity score matching was used to generate PLV and non-PLV groups with comparable characteristics. Associations between outcomes and PLV status were analyzed by exact logistic regression, with matching as cluster in the anatomic and nonanatomic lung resection cohorts. In the propensity score-matched analysis, the incidence of pneumonia and/or ARDS among patients who had an anatomic lung resection was 9/172 (5.2%) in the non-PLV compared to the PLV group 7/172 (4.1%; odds ratio, 1.29; 95% confidence interval, 0.48-3.45, P= .62). The incidence of pneumonia and/or ARDS in patients who underwent nonanatomic resection was 3/118 (2.5%) in the non-PLV compared to the PLV group, 1/118 (0.9%; odds ratio, 3.00; 95% confidence interval, 0.31-28.84, P= .34). In this prospective observational study, we found no differences in the incidence of pneumonia and/or ARDS between patients undergoing lung resection with tidal volumes <8 or ≥8 mL/kg. Our data suggest that when fluid restriction and peak airway pressures are limited, the clinical impact of PLV in this patient population is small. Future randomized trials are needed to better understand the benefits of a small tidal volume strategy during OLV on clinically important outcomes.

Liver Cirrhosis is Independently Associated With 90-Day Mortality in ARDS Patients.

PubMed

Gacouin, Arnaud; Locufier, Maxime; Uhel, Fabrice; Letheulle, Julien; Bouju, Pierre; Fillatre, Pierre; Le Tulzo, Yves; Tadié, Jean Marc

2016-01-01

In a few studies, cirrhosis has been associated with increased mortality in patients with acute respiratory distress syndrome (ARDS). These studies were, however, conducted mostly before 2000. Over the last 15 years, the prognosis of cirrhotic patients admitted to the intensive care unit (ICU) seems to have improved and major changes in the management of mechanical ventilation (MV) of ARDS have appeared. The aim of this study was to determine whether cirrhosis remains a factor for poor prognosis despite improvements in MV techniques and supportive therapies for ARDS. Retrospective analysis of data recorded from 232 patients (42 with cirrhosis and 290 without cirrhosis) who received lung-protective ventilation for ARDS defined according to American-European Consensus Conference criteria and admitted from 2006 to 2013. Alcohol was the most common aetiology of the cirrhosis. The end point was mortality at day-90 from the diagnosis of ARDS, survival was calculated using the Kaplan-Meier method, and we used a Cox-proportional hazard model to determine whether cirrhosis remained independently associated with mortality after adjustment for other prognostic variables for ARDS described previously. Organ dysfunctions were assessed based on the Sequential Organ Failure Assessment (SOFA) criteria, pulmonary and nonpulmonary dysfunctions were distinguished and compared between cirrhotic and non-cirrhotic patients on the first 3 days of VM. Comparison of survival curves showed that cirrhotic patients had a poorer 90-day prognosis than non-cirrhotic patients (P = 0.03 by the log-rank test). After adjusted analysis, cirrhosis remained independently associated with mortality at day 90 (adjusted hazard ratio 2.09, 95% CI, 1.27-3.45, P = 0.004). Non-pulmonary SOFA scores were significantly higher in cirrhotic patients than in non-cirrhotic patients on day 1 (P < 0.001), day 2 (P = 0.003), and day 3 (P = 0.002) of MV for ARDS whereas pulmonary SOFA scores did not differ significantly. Despite improvements in the management of cirrhotic patients admitted to the ICU and in the management of MV for the treatment of ARDS, cirrhosis remained associated with a poorer prognosis in ARDS patients. The prognosis of cirrhotic patients with ARDS appears related to extrapulmonary organ dysfunctions rather than pulmonary dysfunction.

[Ventilatory strategy for ARDS].

PubMed

Yoshida, Takeshi; Takegawa, Ryousuke; Ogura, Hiroshi

2016-02-01

Fifteen years have passed since lung protective strategy to the patients with acute respiratory distress syndrome (ARDS) established. Recently, the new Berlin Definition of ARDS has been developed and this classified ARDS into three stages (mild, moderate, and severe ARDS), depending on the PaO2/FiO2. After this new definition of ARDS, each treatment to the patients with ARDS should be considered, depending on the severity of lung injury, such as prone position to the patients with severe ARDS, muscle paralysis to the patients with severe ARDS. In this review article, we review the history of lung protective strategy and ARDS definition, discuss the novel physiological approaches to minimizing ventilator-induced lung injury, and highlight a numbers of experimental/clinical studies to support these concepts.

Parecoxib reduced ventilation induced lung injury in acute respiratory distress syndrome.

PubMed

Meng, Fan-You; Gao, Wei; Ju, Ying-Nan

2017-03-29

Cyclooxygenase-2 (COX-2) contributes to ventilation induced lung injury (VILI) and acute respiratory distress syndrome (ARDS). The objective of present study was to observe the therapeutic effect of parecoxib on VILI in ARDS. In this parallel controlled study performed at Harbin Medical University, China between January 2016 and March 2016, 24 rats were randomly allocated into sham group (S), volume ventilation group/ARDS (VA), parecoxib/volume ventilation group/ARDS (PVA). Rats in the S group only received anesthesia; rats in the VA and PVA group received intravenous injection of endotoxin to induce ARDS, and then received ventilation. Rats in the VA and PVA groups were treated with intravenous injection of saline or parecoxib. The ratio of arterial oxygen pressure to fractional inspired oxygen (PaO 2 /FiO 2 ), the wet to dry weight ratio of lung tissue, inflammatory factors in serum and bronchoalveolar lavage fluid (BALF), and histopathologic analyses of lung tissue were examined. In addition, survival was calculated at 24 h after VILI. Compared to the VA group, in the PVA group, PaO 2 /FiO 2 was significantly increased; lung tissue wet to dry weight ratio; macrophage and neutrophil counts, total protein and neutrophil elastase levels in BALF; tumor necrosis factor-α, interleukin-1β, and prostaglandin E 2 levels in BALF and serum; and myeloperoxidase (MPO) activity, malondialdehyde levels, and Bax and COX-2 protein levels in lung tissue were significantly decreased, while Bcl-2 protein levels were significantly increased. Lung histopathogical changes and apoptosis were reduced by parecpxib in the PVA group. Survival was increased in the PVA group. Parecoxib improves gas exchange and epithelial permeability, decreases edema, reduces local and systemic inflammation, ameliorates lung injury and apoptosis, and increases survival in a rat model of VILI.

Mechanical ventilation drives pneumococcal pneumonia into lung injury and sepsis in mice: protection by adrenomedullin.

PubMed

Müller-Redetzky, Holger C; Will, Daniel; Hellwig, Katharina; Kummer, Wolfgang; Tschernig, Thomas; Pfeil, Uwe; Paddenberg, Renate; Menger, Michael D; Kershaw, Olivia; Gruber, Achim D; Weissmann, Norbert; Hippenstiel, Stefan; Suttorp, Norbert; Witzenrath, Martin

2014-04-14

Ventilator-induced lung injury (VILI) contributes to morbidity and mortality in acute respiratory distress syndrome (ARDS). Particularly pre-injured lungs are susceptible to VILI despite protective ventilation. In a previous study, the endogenous peptide adrenomedullin (AM) protected murine lungs from VILI. We hypothesized that mechanical ventilation (MV) contributes to lung injury and sepsis in pneumonia, and that AM may reduce lung injury and multiple organ failure in ventilated mice with pneumococcal pneumonia. We analyzed in mice the impact of MV in established pneumonia on lung injury, inflammation, bacterial burden, hemodynamics and extrapulmonary organ injury, and assessed the therapeutic potential of AM by starting treatment at intubation. In pneumococcal pneumonia, MV increased lung permeability, and worsened lung mechanics and oxygenation failure. MV dramatically increased lung and blood cytokines but not lung leukocyte counts in pneumonia. MV induced systemic leukocytopenia and liver, gut and kidney injury in mice with pneumonia. Lung and blood bacterial burden was not affected by MV pneumonia and MV increased lung AM expression, whereas receptor activity modifying protein (RAMP) 1-3 expression was increased in pneumonia and reduced by MV. Infusion of AM protected against MV-induced lung injury (66% reduction of pulmonary permeability p < 0.01; prevention of pulmonary restriction) and against VILI-induced liver and gut injury in pneumonia (91% reduction of AST levels p < 0.05, 96% reduction of alanine aminotransaminase (ALT) levels p < 0.05, abrogation of histopathological changes and parenchymal apoptosis in liver and gut). MV paved the way for the progression of pneumonia towards ARDS and sepsis by aggravating lung injury and systemic hyperinflammation leading to liver, kidney and gut injury. AM may be a promising therapeutic option to protect against development of lung injury, sepsis and extrapulmonary organ injury in mechanically ventilated individuals with severe pneumonia.

Acute Respiratory Distress Syndrome in Burn Patients: A Comparison of the Berlin and American-European Definitions.

PubMed

Sine, Christy R; Belenkiy, Slava M; Buel, Allison R; Waters, J Alan; Lundy, Jonathan B; Henderson, Jonathan L; Stewart, Ian J; Aden, James K; Liu, Nehemiah T; Batchinsky, Andriy; Cannon, Jeremy W; Cancio, Leopoldo C; Chung, Kevin K

2016-01-01

The purpose of this study was to compare the Berlin definition to the American-European Consensus Conference (AECC) definition in determining the prevalence of acute respiratory distress syndrome (ARDS) and associated mortality in the critically ill burn population. Consecutive patients admitted to our institution with burn injury that required mechanical ventilation for more than 24 hours were included for analysis. Included patients (N = 891) were classified by both definitions. The median age, % TBSA burn, and injury severity score (interquartile ranges) were 35 (24-51), 25 (11-45), and 18 (9-26), respectively. Inhalation injury was present in 35.5%. The prevalence of ARDS was 34% using the Berlin definition and 30.5% using the AECC definition (combined acute lung injury and ARDS), with associated mortality rates of 40.9 and 42.9%, respectively. Under the Berlin definition, mortality rose with increased ARDS severity (14.6% no ARDS; 16.7% mild; 44% moderate; and 59.7% severe, P < 0.001). By contrast, under the AECC definition increased mortality was seen only for ARDS category (14.7% no ARDS; 15.1% acute lung injury; and 46.0% ARDS, P < 0.001). The mortality of the 22 subjects meeting the AECC, but not the Berlin definition was not different from patients without ARDS (P = .91). The Berlin definition better stratifies ARDS in terms of severity and correctly excludes those with minimal disease previously captured by the AECC.

[Effects of lung protective ventilation strategy combined with lung recruitment maneuver on patients with severe burn complicated with acute respiratory distress syndrome].

PubMed

Li, Xiaojian; Zhong, Xiaomin; Deng, Zhongyuan; Zhang Xuhui; Zhang, Zhi; Zhang, Tao; Tang, Wenbin; Chen, Bib; Liu, Changling; Cao, Wenjuan

2014-08-01

To investigate the effects of lung protective ventilation strategy combined with lung recruitment maneuver on ARDS complicating patients with severe burn. Clinical data of 15 severely burned patients with ARDS admitted to our burn ICU from September 2011 to September 2013 and conforming to the study criteria were analyzed. Right after the diagnosis of acute lung injury/ARDS, patients received mechanical ventilation with lung protective ventilation strategy. When the oxygenation index (OI) was below or equal to 200 mmHg (1 mmHg = 0. 133 kPa), lung recruitment maneuver was performed combining incremental positive end-expiratory pressure. When OI was above 200 mmHg, lung recruitment maneuver was stopped and ventilation with lung protective ventilation strategy was continued. When OI was above 300 mmHg, mechanical ventilation was stopped. Before combining lung recruitment maneuver, 24 h after combining lung recruitment maneuver, and at the end of combining lung recruitment maneuver, variables of blood gas analysis (pH, PaO2, and PaCO2) were obtained by blood gas analyzer, and the OI values were calculated; hemodynamic parameters including heart rate, mean arterial pressure (MAP), central venous pressure (CVP) of all patients and the cardiac output (CO), extravascular lung water index (EVLWI) of 4 patients who received pulse contour cardiac output (PiCCO) monitoring were monitored. Treatment measures and outcome of patients were recorded. Data were processed with analysis of variance of repeated measurement of a single group and LSD test. (1) Before combining lung recruitment maneuver, 24 h after combining lung recruitment maneuver, and at the end of combining lung recruitment maneuver, the levels of PaO2 and OI of patients were respectively (77 ± 8), (113 ± 5), (142 ± 6) mmHg, and (128 ± 12), (188 ± 8), (237 ± 10) mmHg. As a whole, levels of PaO2 and OI changed significantly at different time points (with F values respectively 860. 96 and 842. 09, P values below 0. 01); levels of pH and PaCO2 showed no obvious changes (with F values respectively 0.35 and 3.13, P values above 0.05). (2) Levels of heart rate, MAP, CVP of all patients and CO of 4 patients who received PiCCO monitoring showed no significant changes at different time points (with F values from 0. 13 to 4. 26, P values above 0.05). Before combining lung recruitment maneuver, 24 h after combining lung recruitment maneuver, and at the end of combining lung recruitment maneuver, the EVLWI values of 4 patients who received PiCCO monitoring were respectively (13.5 ± 1.3), (10.2 ± 1.0), (7.0 ± 0.8) mL/kg ( F =117.00, P <0.01). (3) The patients received mechanical ventilation at 2 to 72 h after burn, lasting for 14-32 (21 ± 13) d. At post injury day 3-14 (7 ± 5) d, lung recruitment maneuver was applied for 2-5 (3.0 ± 2.0) d. All 15 patients recovered without other complications. Lung protective ventilation strategy combining lung recruitment maneuver can significantly improve the oxygenation in patients with severe burn complicated with ARDS and may therefore improve the prognosis.

Plasma Biomarker Analysis in Pediatric ARDS: Generating Future Framework from a Pilot Randomized Control Trial of Methylprednisolone: A Framework for Identifying Plasma Biomarkers Related to Clinical Outcomes in Pediatric ARDS.

PubMed

Kimura, Dai; Saravia, Jordy; Rovnaghi, Cynthia R; Meduri, Gianfranco Umberto; Schwingshackl, Andreas; Cormier, Stephania A; Anand, Kanwaljeet J

2016-01-01

Lung injury activates multiple pro-inflammatory pathways, including neutrophils, epithelial, and endothelial injury, and coagulation factors leading to acute respiratory distress syndrome (ARDS). Low-dose methylprednisolone therapy (MPT) improved oxygenation and ventilation in early pediatric ARDS without altering duration of mechanical ventilation or mortality. We evaluated the effects of MPT on biomarkers of endothelial [Ang-2 and soluble intercellular adhesion molecule-1 (sICAM-1)] or epithelial [soluble receptor for activated glycation end products (sRAGE)] injury, neutrophil activation [matrix metalloproteinase-8 (MMP-8)], and coagulation (plasminogen activator inhibitor-1). Double-blind, placebo-controlled randomized trial. Tertiary-care pediatric intensive care unit (ICU). Mechanically ventilated children (0-18 years) with early ARDS. Blood samples were collected on days 0 (before MPT), 7, and 14 during low-dose MPT (n = 17) vs. placebo (n = 18) therapy. The MPT group received a 2-mg/kg loading dose followed by 1 mg/kg/day continuous infusions from days 1 to 7, tapered off over 7 days; placebo group received equivalent amounts of 0.9% saline. We analyzed plasma samples using a multiplex assay for five biomarkers of ARDS. Multiple regression models were constructed to predict associations between changes in biomarkers and the clinical outcomes reported earlier, including P/F ratio on days 8 and 9, plateau pressure on days 1 and 2, PaCO2 on days 2 and 3, racemic epinephrine following extubation, and supplemental oxygen at ICU discharge. No differences occurred in biomarker concentrations between the groups on day 0. On day 7, reduction in MMP-8 levels (p = 0.0016) occurred in the MPT group, whereas increases in sICAM-1 levels (p = 0.0005) occurred in the placebo group (no increases in sICAM-1 in the MPT group). sRAGE levels decreased in both MPT and placebo groups (p < 0.0001) from day 0 to day 7. On day 7, sRAGE levels were positively correlated with MPT group PaO2/FiO2 ratios on day 8 (r = 0.93, p = 0.024). O2 requirements at ICU transfer positively correlated with day 7 MMP-8 (r = 0.85, p = 0.016) and Ang-2 levels (r = 0.79, p = 0.036) in the placebo group and inversely correlated with day 7 sICAM-1 levels (r = -0.91, p = 0.005) in the MPT group. Biomarkers selected from endothelial, epithelial, or intravascular factors can be correlated with clinical endpoints in pediatric ARDS. For example, MPT could reduce neutrophil activation (⇓MMP-8), decrease endothelial injury (⇔sICAM-1), and allow epithelial recovery (⇓sRAGE). Large ARDS clinical trials should develop similar frameworks. https://clinicaltrials.gov, NCT01274260.

Hypothermic total liquid ventilation after experimental aspiration-associated acute respiratory distress syndrome.

PubMed

Rambaud, Jérôme; Lidouren, Fanny; Sage, Michaël; Kohlhauer, Matthias; Nadeau, Mathieu; Fortin-Pellerin, Étienne; Micheau, Philippe; Zilberstein, Luca; Mongardon, Nicolas; Ricard, Jean-Damien; Terada, Megumi; Bruneval, Patrick; Berdeaux, Alain; Ghaleh, Bijan; Walti, Hervé; Tissier, Renaud

2018-05-02

Ultrafast cooling by total liquid ventilation (TLV) provides potent cardio- and neuroprotection after experimental cardiac arrest. However, this was evaluated in animals with no initial lung injury, whereas out-of-hospital cardiac arrest is frequently associated with early-onset pneumonia, which may lead to acute respiratory distress syndrome (ARDS). Here, our objective was to determine whether hypothermic TLV could be safe or even beneficial in an aspiration-associated ARDS animal model. ARDS was induced in anesthetized rabbits through a two-hits model including the intra-tracheal administration of a pH = 1 solution mimicking gastric content and subsequent gaseous non-protective ventilation during 90 min (tidal volume [Vt] = 10 ml/kg with positive end-expiration pressure [PEEP] = 0 cmH 2 O). After this initial period, animals either received lung protective gas ventilation (LPV; Vt = 8 ml/kg and PEEP = 5 cmH 2 O) under normothermic conditions, or hypothermic TLV (TLV; Vt = 8 ml/kg and end-expiratory volume = 15 ml/kg). Both strategies were applied for 120 min with a continuous monitoring of respiratory and cardiovascular parameters. Animals were then euthanized for pulmonary histological analyses. Eight rabbits were included in each group. Before randomization, all animals elicited ARDS with arterial oxygen partial pressure over inhaled oxygen fraction ratios (PaO 2 /FiO 2 ) below 100 mmHg, as well as decreased lung compliance. After randomization, body temperature rapidly decreased in TLV versus LPV group (32.6 ± 0.6 vs. 38.2 ± 0.4 °C after 15 min). Static lung compliance and gas exchanges were not significantly different in the TLV versus LPV group (PaO 2 /FiO 2  = 62 ± 4 vs. 52 ± 8 mmHg at the end of the procedure, respectively). Mean arterial pressure and arterial bicarbonates levels were significantly higher in TLV versus LPV. Histological analysis also showed significantly lower inflammation in TLV versus LPV group (median histological score = 3 vs. 4.5/5, respectively; p = 0.03). Hypothermic TLV can be safely induced in rabbits during aspiration-associated ARDS. It modified neither gas exchanges nor respiratory mechanics but reduced lung inflammation and hemodynamic failure in comparison with LPV. Since hypothermic TLV was previously shown to provide neuro- and cardio protective effects after cardiac arrest, these findings suggest a possible use of TLV in the settings of cardiac arrest-associated ARDS.

Lung Recruitment Maneuvers for Adult Patients with Acute Respiratory Distress Syndrome. A Systematic Review and Meta-Analysis.

PubMed

Goligher, Ewan C; Hodgson, Carol L; Adhikari, Neill K J; Meade, Maureen O; Wunsch, Hannah; Uleryk, Elizabeth; Gajic, Ognjen; Amato, Marcelo P B; Ferguson, Niall D; Rubenfeld, Gordon D; Fan, Eddy

2017-10-01

In patients with acute respiratory distress syndrome (ARDS), lung recruitment maneuvers (LRMs) may prevent ventilator-induced lung injury and improve survival. To summarize the current evidence in support of the use of LRMs in adult patients with ARDS and to inform the recently published American Thoracic Society/European Society of Intensive Care Medicine/Society of Critical Care Medicine clinical practice guideline on mechanical ventilation in ARDS. We conducted a systematic review and meta-analysis of randomized trials comparing mechanical ventilation strategies with and without LRMs. Eligible trials were identified from among previously published systematic reviews and an updated literature search. Data on 28-day mortality, oxygenation, adverse events, and use of rescue therapy were collected, and results were pooled using random effects models weighted by inverse variance. Strength of evidence was assessed using the Grading of Recommendations Assessment, Development, and Evaluation methodology. We screened 430 citations and previous systematic reviews and found six trials eligible for inclusion (n = 1,423 patients in total). The type of LRM varied widely between trials, and five of the trials involved a cointervention with a higher positive end-expiratory pressure (PEEP) ventilation strategy. Risk of bias was deemed high in one trial. In the primary analysis, the only trial without a cointervention showed that LRMs were associated with reduced mortality (one trial; risk ratio [RR], 0.62; 95% confidence interval [CI], 0.39-0.98; evidence grade = low). Meta-analysis of all six trials also suggested a significant mortality reduction (six trials; RR, 0.81; 95% CI, 0.69-0.95; evidence grade = moderate), and the use of a higher PEEP cointervention did not significantly modify the mortality effect (P = 0.27 for heterogeneity). LRMs were also associated with improved oxygenation after 24 hours (six trials; mean increase, 52 mm Hg; 95% CI, 23-81 mm Hg) and less frequent requirement for rescue therapy (three trials; RR, 0.65; 95% CI, 0.45-0.94). LRMs were not associated with an increased rate of barotrauma (four trials; RR, 0.84; 95% CI, 0.46-1.55). The rate of hemodynamic compromise was not significantly increased with LRMs (three trials; RR, 1.30; 95% CI, 0.92-1.78). Randomized trials suggest that LRMs in combination with a higher PEEP ventilation strategy reduce mortality, but confidence in this finding is limited. Further trials are required to confirm benefit from LRMs in adults with ARDS.

Can fiberoptic bronchoscopy be applied to critically ill patients treated with noninvasive ventilation for acute respiratory distress syndrome? Prospective observational study.

PubMed

Korkmaz Ekren, Pervin; Basarik Aydogan, Burcu; Gurgun, Alev; Tasbakan, Mehmet Sezai; Bacakoglu, Feza; Nava, Stefano

2016-05-31

Noninvasive ventilation (NIV) is a cornerstone for the treatment of acute respiratory failure of various etiologies. Using NIV is discussed in mild-to-moderate acute respiratory distress syndrome (ARDS) patients (PaO2/FiO2 > 150). These patients often have comorbidities that increase the risk for bronchoscopy related complications. The primary outcome of this prospective observational study was to evaluate the feasibility, safety and contribution in diagnosis and/or modification of the ongoing treatment of fiberoptic bronchoscopy (FOB) in patients with ARDS treated with NIV. ARDS patients treated with NIV and who require FOB as the diagnostic or therapeutic procedure were included the study. Intensive care ventilators or other dedicated NIV ventilators were used. NIV was applied via simple oro-nasal mask or full-face mask. Pressure support or inspiratory positive airway pressure (IPAP), external positive end expiratory pressure (PEEP) or expiratory positive airway pressure (EPAP) levels were titrated to achieve an expiratory tidal volume of 8 to 10 ml/kg according to ideal body weight, SpO2 > 90 % and respiratory rate below 25/min. Twenty eight subjects (mean age 63.3 ± 15.9 years, 15 men, 13 women, PaO2/FiO2 rate 145 ± 50.1 at admission) were included the study. Overall the procedure was well tolerated with only 5 (17.9 %) patients showing minor complications. There was no impairment in arterial blood gas and cardiopulmonary parameters after FOB. PaO2/FiO2 rate increased from 132.2 ± 49.8 to 172.9 ± 63.2 (p = 0.001). No patient was intubated within 2 h after the bronchoscopy. 10.7, 32.1 and 39.3 % of the patients required invasive mechanical ventilation after 8 h, 24 h and 48 h, respectively. Bronchoscopy provided diagnosis in 27 (96.4 %) patients. Appropriate treatment was decided according to the results of the bronchoscopic sampling in 20 (71.4 %) patients. FOB under NIV could be considered as a feasible tool for diagnosis and guide for treatment of patients with ARDS treated via NIV in intensive care units. However, FOB-correlated life-treathening complications in severe hypoxemia should not be forgotten. Furthermore, further controlled studies involving a larger series of homogeneous ARDS patients undergoing FOB under NIV are needed to confirm these preliminary findings.

Optimal support techniques when providing mechanical ventilation to patients with acute respiratory distress syndrome.

PubMed

Parissopoulos, Stelios; Mpouzika, Meropi DA; Timmins, Fiona

2017-01-01

Adult respiratory distress syndrome (ARDS) is a type of acute diffuse lung injury characterized by severe inflammation, increased pulmonary vascular permeability and a loss of aerated lung tissue. The effects of high fraction of inspired oxygen (FiO 2 ) include oxygen toxicity manifested by damage to the lung parenchyma in the acute phase of lung injury. There is still a high mortality rate among this group of patients, so clinically sensitive evidence-based interventions are paramount to maximize survival chances during critical care. The aim of this article is to explore the current opinion concerning optimal mechanical ventilation support techniques for patients with acute respiratory distress syndrome. A literature search of clinical trials and observation studies, reviews, discussion papers, meta-analyses and clinical guidelines written in English up to 2015, derived from the databases of Scopus, CINAHL, Cochrane Library databases and PubMed was conducted. Low tidal volume, pressure limitation and prone positioning in severe ARDS patients appear to be of some benefit. More research is required and further development and use of standardized protocols is an important strategy for reducing practice variations across disciplines, as well as giving clear guidelines to nurses practising in critical care. There is also evidence that this syndrome is under-diagnosed and the utilization of lung protective ventilation is still variable. It is important that nurses have underlying knowledge of both aetiology of ARDS and ventilation management, and that they monitor patients very closely. The adoption of a low tidal ventilation protocol, which is based on quality evidence guidelines, the value of rescue therapies and patient observation practices in the overall patient management, and the need to place emphasis on long-term patient outcomes, all these emerge as key factors for consideration and future research. However, there is also a need for more research that would explore the unique contribution of nurses in the management of this patient group, as it is difficult to discern this in the current literature. © 2015 British Association of Critical Care Nurses.

Diagnostic workup for ARDS patients.

PubMed

Papazian, Laurent; Calfee, Carolyn S; Chiumello, Davide; Luyt, Charles-Edouard; Meyer, Nuala J; Sekiguchi, Hiroshi; Matthay, Michael A; Meduri, Gianfranco Umberto

2016-05-01

Acute respiratory distress syndrome (ARDS) is defined by the association of bilateral infiltrates and hypoxaemia following an initial insult. Although a new definition has been recently proposed (Berlin definition), there are various forms of ARDS with potential differences regarding their management (ventilator settings, prone positioning use, corticosteroids). ARDS can be caused by various aetiologies, and the adequate treatment of the responsible cause is crucial to improve the outcome. It is of paramount importance to characterize the mechanisms causing lung injury to optimize both the aetiological treatment and the symptomatic treatment. If there is no obvious cause of ARDS or if a direct lung injury is suspected, bronchoalveolar lavage (BAL) should be strongly considered to identify microorganisms responsible for pneumonia. Blood samples can also help to identify microorganisms and to evaluate biomarkers of infection. If there is no infectious cause of ARDS or no other apparent aetiology is found, second-line examinations should include markers of immunologic diseases. In selected cases, open lung biopsy remains useful to identify the cause of ARDS when all other examinations remain inconclusive. CT scan is fundamental when there is a suspicion of intra-abdominal sepsis and in some cases of pneumonia. Ultrasonography is important not only in evaluating biventricular function but also in identifying pleural effusions and pneumothorax. The definition of ARDS remains clinical and the main objective of the diagnostic workup should be to be focused on identification of its aetiology, especially a treatable infection.

Role of Nrf2 and Autophagy in Acute Lung Injury

PubMed Central

Rojo de la Vega, Montserrat; Dodson, Matthew; Gross, Christine; Manzour, Heidi; Lantz, R. Clark; Chapman, Eli; Wang, Ting; Black, Stephen M.; Garcia, Joe G.N.; Zhang, Donna D.

2016-01-01

Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are the clinical manifestations of severe lung damage and respiratory failure. Characterized by severe inflammation and compromised lung function, ALI/ARDS result in very high mortality of affected individuals. Currently, there are no effective treatments for ALI/ARDS, and ironically, therapies intended to aid patients (specifically mechanical ventilation, MV) may aggravate the symptoms. Key events contributing to the development of ALI/ARDS are: increased oxidative and proteotoxic stresses, unresolved inflammation, and compromised alveolar-capillary barrier function. Since the airways and lung tissues are constantly exposed to gaseous oxygen and airborne toxicants, the bronchial and alveolar epithelial cells are under higher oxidative stress than other tissues. Cellular protection against oxidative stress and xenobiotics is mainly conferred by Nrf2, a transcription factor that promotes the expression of genes that regulate oxidative stress, xenobiotic metabolism and excretion, inflammation, apoptosis, autophagy, and cellular bioenergetics. Numerous studies have demonstrated the importance of Nrf2 activation in the protection against ALI/ARDS, as pharmacological activation of Nrf2 prevents the occurrence or mitigates the severity of ALI/ARDS. Another promising new therapeutic strategy in the prevention and treatment of ALI/ARDS is the activation of autophagy, a bulk protein and organelle degradation pathway. In this review, we will discuss the strategy of concerted activation of Nrf2 and autophagy as a preventive and therapeutic intervention to ameliorate ALI/ARDS. PMID:27313980

Is there still a role for the lung injury score in the era of the Berlin definition ARDS?

PubMed Central

2014-01-01

Background The Lung Injury Score (LIS) remains a commonly utilized measure of lung injury severity though the additive value of LIS to predict ARDS outcomes over the recent Berlin definition of ARDS, which incorporates severity, is not known. Methods We tested the association of LIS (in which scores range from 0 to 4, with higher scores indicating more severe lung injury) and its four components calculated on the day of ARDS diagnosis with ARDS morbidity and mortality in a large, multi-ICU cohort of patients with Berlin-defined ARDS. Receiver Operator Characteristic (ROC) curves were generated to compare the predictive validity of LIS for mortality to Berlin stages of severity (mild, moderate and severe). Results In 550 ARDS patients, a one-point increase in LIS was associated with 58% increased odds of in-hospital death (95% CI 14 to 219%, P = 0.006), a 7% reduction in ventilator-free days (95% CI 2 to 13%, P = 0.01), and, among patients surviving hospitalization, a 25% increase in days of mechanical ventilation (95% CI 9 to 43%, P = 0.001) and a 16% increase (95% CI 2 to 31%, P = 0.02) in the number of ICU days. However, the mean LIS was only 0.2 points higher (95% CI 0.1 to 0.3) among those who died compared to those who lived. Berlin stages of severity were highly correlated with LIS (Spearman’s rho 0.72, P < 0.0001) and were also significantly associated with ARDS mortality and similar morbidity measures. The predictive validity of LIS for mortality was similar to Berlin stages of severity with an area under the curve of 0.58 compared to 0.60, respectively (P-value 0.49). Conclusions In a large, multi-ICU cohort of patients with ARDS, both LIS and the Berlin definition severity stages were associated with increased in-hospital morbidity and mortality. However, predictive validity of both scores was marginal, and there was no additive value of LIS over Berlin. Although neither LIS nor the Berlin definition were designed to prognosticate outcomes, these findings suggest that the role of LIS in characterizing lung injury severity in the era of the Berlin definition ARDS may be limited. PMID:24533450

The EIT-based global inhomogeneity index is highly correlated with regional lung opening in patients with acute respiratory distress syndrome.

PubMed

Zhao, Zhanqi; Pulletz, Sven; Frerichs, Inéz; Müller-Lisse, Ullrich; Möller, Knut

2014-02-06

The electrical impedance tomography (EIT)-based global inhomogeneity (GI) index was introduced to quantify tidal volume distribution within the lung. Up to now, the GI index was evaluated for plausibility but the analysis of how it is influenced by various physiological factors is still missing. The aim of our study was to evaluate the influence of proportion of open lung regions measured by EIT on the GI index. A constant low-flow inflation maneuver was performed in 18 acute respiratory distress syndrome (ARDS) patients (58 ± 14 years, mean age ± SD) and 8 lung-healthy patients (41 ± 12 years) under controlled mechanical ventilation. EIT raw data were acquired at 25 scans/s and reconstructed offline. Recruited lung regions were identified as those image pixels of the lung regions within the EIT scans where local impedance amplitudes exceeded 10% of the maximum amplitude during the maneuver. A series of GI indices was calculated during mechanical lung inflation, based on the differential images obtained between different time points. Respiratory system elastance (Ers) values were calculated at 10 lung volume levels during low-flow maneuver. The GI index decreased during low-flow inflation, while the percentage of open lung regions increased. The values correlated highly in both ARDS (r2 = 0.88 ± 0.08, p < 0.01) and lung-healthy patients (r2 = 0.92 ± 0.05, p < 0.01). Ers and GI index were also significantly correlated in 16 out of 18 ARDS (r2 = 0.84 ± 0.13, p < 0.01) and in 6 out of 8 lung-healthy patients (r2 = 0.84 ± 0.07, p < 0.01). Significant differences were found in GI values between two groups (0.52 ± 0.21 for ARDS and 0.41 ± 0.04 for lung-healthy patients, p < 0.05) as well in Ers values (0.017 ± 0.008 cmH2O/ml for ARDS and 0.009 ± 0.001 cmH2O/ml for lung-healthy patients, p < 0.01). We conclude that the GI index is a reliable measure of ventilation heterogeneity highly correlated with lung recruitability measured with EIT. The GI index may prove to be a useful EIT-based index to guide ventilation therapy.

Study protocol: The Improving Care of Acute Lung Injury Patients (ICAP) study

PubMed Central

Needham, Dale M; Dennison, Cheryl R; Dowdy, David W; Mendez-Tellez, Pedro A; Ciesla, Nancy; Desai, Sanjay V; Sevransky, Jonathan; Shanholtz, Carl; Scharfstein, Daniel; Herridge, Margaret S; Pronovost, Peter J

2006-01-01

Introduction The short-term mortality benefit of lower tidal volume ventilation (LTVV) for patients with acute lung injury/acute respiratory distress syndrome (ALI/ARDS) has been demonstrated in a large, multi-center randomized trial. However, the impact of LTVV and other critical care therapies on the longer-term outcomes of ALI/ARDS survivors remains uncertain. The Improving Care of ALI Patients (ICAP) study is a multi-site, prospective cohort study that aims to evaluate the longer-term outcomes of ALI/ARDS survivors with a particular focus on the effect of LTVV and other critical care therapies. Methods Consecutive mechanically ventilated ALI/ARDS patients from 11 intensive care units (ICUs) at four hospitals in the city of Baltimore, MD, USA, will be enrolled in a prospective cohort study. Exposures (patient-based, clinical management, and ICU organizational) will be comprehensively collected both at baseline and throughout patients' ICU stay. Outcomes, including mortality, organ impairment, functional status, and quality of life, will be assessed with the use of standardized surveys and testing at 3, 6, 12, and 24 months after ALI/ARDS diagnosis. A multi-faceted retention strategy will be used to minimize participant loss to follow-up. Results On the basis of the historical incidence of ALI/ARDS at the study sites, we expect to enroll 520 patients over two years. This projected sample size is more than double that of any published study of long-term outcomes in ALI/ARDS survivors, providing 86% power to detect a relative mortality hazard of 0.70 in patients receiving higher versus lower exposure to LTVV. The projected sample size also provides sufficient power to evaluate the association between a variety of other exposure and outcome variables, including quality of life. Conclusion The ICAP study is a novel, prospective cohort study that will build on previous critical care research to improve our understanding of the longer-term impact of ALI/ARDS, LTVV and other aspects of critical care management. Given the paucity of information about the impact of interventions on long-term outcomes for survivors of critical illness, this study can provide important information to inform clinical practice. PMID:16420652

Protective ventilation in experimental acute respiratory distress syndrome after ventilator-induced lung injury: a randomized controlled trial.

PubMed

Uttman, L; Bitzén, U; De Robertis, E; Enoksson, J; Johansson, L; Jonson, B

2012-10-01

Low tidal volume (V(T)), PEEP, and low plateau pressure (P(PLAT)) are lung protective during acute respiratory distress syndrome (ARDS). This study tested the hypothesis that the aspiration of dead space (ASPIDS) together with computer simulation can help maintain gas exchange at these settings, thus promoting protection of the lungs. ARDS was induced in pigs using surfactant perturbation plus an injurious ventilation strategy. One group then underwent 24 h protective ventilation, while control groups were ventilated using a conventional ventilation strategy at either high or low pressure. Pressure-volume curves (P(el)/V), blood gases, and haemodynamics were studied at 0, 4, 8, 16, and 24 h after the induction of ARDS and lung histology was evaluated. The P(el)/V curves showed improvements in the protective strategy group and deterioration in both control groups. In the protective group, when respiratory rate (RR) was ≈ 60 bpm, better oxygenation and reduced shunt were found. Histological damage was significantly more severe in the high-pressure group. There were no differences in venous oxygen saturation and pulmonary vascular resistance between the groups. The protective ventilation strategy of adequate pH or PaCO2 with minimal V(T), and high/safe P(PLAT) resulting in high PEEP was based on the avoidance of known lung-damaging phenomena. The approach is based upon the optimization of V(T), RR, PEEP, I/E, and dead space. This study does not lend itself to conclusions about the independent role of each of these features. However, dead space reduction is fundamental for achieving minimal V(T) at high RR. Classical physiology is applicable at high RR. Computer simulation optimizes ventilation and limiting of dead space using ASPIDS. Inspiratory P(el)/V curves recorded from PEEP or, even better, expiratory P(el)/V curves allow monitoring in ARDS.

The effect of prone positioning in acute respiratory distress syndrome or acute lung injury: a meta-analysis. Areas of uncertainty and recommendations for research.

PubMed

Abroug, Fekri; Ouanes-Besbes, Lamia; Elatrous, Souheil; Brochard, Laurent

2008-06-01

To compare the effects of ventilation in prone and in supine position in patients with acute lung injury/acute respiratory distress syndrome (ALI/ARDS). Meta-analysis of randomised controlled trials. BioMedCentral, PubMed, CINAHL, and Embase (to November 2007), with additional information from authors. From selected randomised controlled trials comparing positioning in ALI/ARDS we extracted data concerning study design, disease severity, clinical outcomes, and adverse events. Five trials including 1,372 patients met the inclusion criteria for mortality analysis; one trial was added to assess the effects on acquisition of ventilator-associated pneumonia (VAP). The included trials were significantly underpowered and enrolled patients with varying severity. Prone positioning duration and mechanical ventilation strategy were not standardised across studies. Using a fixed-effects model, we did not find a significant effect of prone positioning (proning) on mortality (odds ratio 0.97, 95% confidence interval 0.77-1.22). The PaO(2)/FiO(2) ratio increased significantly more with proning (weighted means difference 25 mmHg, p < 0.00001). Proning was associated with a non-significant 23% reduction in the odds of VAP (p=0.09), and with no increase in major adverse airway complications: OR 1.01, 95% CI 0.71-1.43. Length of intensive care unit stay was marginally and not significantly increased by proning. Prone position is not associated with a significant reduction in mortality from ALI/ARDS despite a significant increase in PaO(2)/FiO(2), is safe, and tends to decrease VAP. Published studies exhibit substantial clinical heterogeneity, suggesting that an adequately sized study optimising the duration of proning and ventilation strategy is warranted to enable definitive conclusions to be drawn.

Preventing ARDS

PubMed Central

Beitler, Jeremy R.; Schoenfeld, David A.

2014-01-01

Advances in critical care practice have led to a substantial decline in the incidence of ARDS over the past several years. Low tidal volume ventilation, timely resuscitation and antimicrobial administration, restrictive transfusion practices, and primary prevention of aspiration and nosocomial pneumonia have likely contributed to this reduction. Despite decades of research, there is no proven pharmacologic treatment of ARDS, and mortality from ARDS remains high. Consequently, recent initiatives have broadened the scope of lung injury research to include targeted prevention of ARDS. Prediction scores have been developed to identify patients at risk for ARDS, and clinical trials testing aspirin and inhaled budesonide/formoterol for ARDS prevention are ongoing. Future trials aimed at preventing ARDS face several key challenges. ARDS has not been validated as an end point for pivotal clinical trials, and caution is needed when testing toxic therapies that may prevent ARDS yet potentially increase mortality. PMID:25288000

[Lung-brain interaction in the mechanically ventilated patient].

PubMed

López-Aguilar, J; Fernández-Gonzalo, M S; Turon, M; Quílez, M E; Gómez-Simón, V; Jódar, M M; Blanch, L

2013-10-01

Patients with acute lung injury or acute respiratory distress syndrome (ARDS) admitted to the ICU present neuropsychological alterations, which in most cases extend beyond the acute phase and have an important adverse effect upon quality of life. The aim of this review is to deepen in the analysis of the complex interaction between lung and brain in critically ill patients subjected to mechanical ventilation. This update first describes the neuropsychological alterations occurring both during the acute phase of ICU stay and at discharge, followed by an analysis of lung-brain interactions during mechanical ventilation, and finally explores the etiology and mechanisms leading to the neurological disorders observed in these patients. The management of critical patients requires an integral approach focused on minimizing the deleterious effects over the short, middle or long term. Copyright © 2012 Elsevier España, S.L. y SEMICYUC. All rights reserved.

Increasing the inspiratory time and I:E ratio during mechanical ventilation aggravates ventilator-induced lung injury in mice.

PubMed

Müller-Redetzky, Holger C; Felten, Matthias; Hellwig, Katharina; Wienhold, Sandra-Maria; Naujoks, Jan; Opitz, Bastian; Kershaw, Olivia; Gruber, Achim D; Suttorp, Norbert; Witzenrath, Martin

2015-01-28

Lung-protective ventilation reduced acute respiratory distress syndrome (ARDS) mortality. To minimize ventilator-induced lung injury (VILI), tidal volume is limited, high plateau pressures are avoided, and positive end-expiratory pressure (PEEP) is applied. However, the impact of specific ventilatory patterns on VILI is not well defined. Increasing inspiratory time and thereby the inspiratory/expiratory ratio (I:E ratio) may improve oxygenation, but may also be harmful as the absolute stress and strain over time increase. We thus hypothesized that increasing inspiratory time and I:E ratio aggravates VILI. VILI was induced in mice by high tidal-volume ventilation (HVT 34 ml/kg). Low tidal-volume ventilation (LVT 9 ml/kg) was used in control groups. PEEP was set to 2 cm H2O, FiO2 was 0.5 in all groups. HVT and LVT mice were ventilated with either I:E of 1:2 (LVT 1:2, HVT 1:2) or 1:1 (LVT 1:1, HVT 1:1) for 4 hours or until an alternative end point, defined as mean arterial blood pressure below 40 mm Hg. Dynamic hyperinflation due to the increased I:E ratio was excluded in a separate group of animals. Survival, lung compliance, oxygenation, pulmonary permeability, markers of pulmonary and systemic inflammation (leukocyte differentiation in lung and blood, analyses of pulmonary interleukin-6, interleukin-1β, keratinocyte-derived chemokine, monocyte chemoattractant protein-1), and histopathologic pulmonary changes were analyzed. LVT 1:2 or LVT 1:1 did not result in VILI, and all individuals survived the ventilation period. HVT 1:2 decreased lung compliance, increased pulmonary neutrophils and cytokine expression, and evoked marked histologic signs of lung injury. All animals survived. HVT 1:1 caused further significant worsening of oxygenation, compliance and increased pulmonary proinflammatory cytokine expression, and pulmonary and blood neutrophils. In the HVT 1:1 group, significant mortality during mechanical ventilation was observed. According to the "baby lung" concept, mechanical ventilation-associated stress and strain in overinflated regions of ARDS lungs was simulated by using high tidal-volume ventilation. Increase of inspiratory time and I:E ratio significantly aggravated VILI in mice, suggesting an impact of a "stress/strain × time product" for the pathogenesis of VILI. Thus increasing the inspiratory time and I:E ratio should be critically considered.

Preemptive antibiotic treatment based on gram staining reduced the incidence of ARDS in mechanically ventilated patients.

PubMed

Matsushima, Asako; Tasaki, Osamu; Shimizu, Kentaro; Tomono, Kazunori; Ogura, Hiroshi; Shimazu, Takeshi; Sugimoto, Hisashi

2008-08-01

Ventilator-associated pneumonia (VAP) is one of the major complications in the intensive care unit. VAP sometimes results in acute respiratory distress syndrome (ARDS), and the associated mortality is high. We hypothesized that preemptive antibiotic therapy based on results of bedside gram staining would reduce the incidence of VAP. Patients who were endotracheally intubated in our intensive care unit for more than 72 hours were included. Patients younger than 16 years of age or patients died because of brain death were excluded. The study was divided into two periods. During the first period, we used antibiotics according to the American Thoracic Society guidelines. During the second period, antibiotics were given according to the results of bedside gram staining even before radiographic infiltrate appeared. One hundred twenty-eight patients and 133 patients were included in the first and second periods, respectively. The incidence of VAP was significantly decreased in the second period (first period, 22%; second period, 9%, p < 0.01). The incidence of ARDS was also decreased significantly in the second period (first period, 11%; second period, 3%, p < 0.01). The duration and total amount of antibiotics administered did not increase in the second period. VAP associated mortality was significantly lower in the second period (first period, 5%; second period, 0.8%, p < 0.05). Early diagnosis and treatment of respiratory infection based on results of gram staining significantly reduced the incidences of VAP and ARDS without an increase in the use of antibiotics.

Acute respiratory distress syndrome mimickers lacking common risk factors of the Berlin definition.

PubMed

Gibelin, Aude; Parrot, Antoine; Maitre, Bernard; Brun-Buisson, Christian; Mekontso Dessap, Armand; Fartoukh, Muriel; de Prost, Nicolas

2016-02-01

Some patients presenting with acute respiratory failure and meeting the Berlin criteria for acute respiratory distress syndrome (ARDS) lack exposure to common risk factors (CRF). These so-called ARDS mimickers often lack histological diffuse alveolar damage. We aimed to describe such ARDS mimickers lacking CRF (ARDS CRF-) in comparison with others (ARDS CRF+). Retrospective study including all patients receiving invasive mechanical ventilation for ARDS admitted to the intensive care units (ICUs) of two tertiary care centers from January 2003 to December 2012. The prevalence of ARDS CRF- was 7.5 % (95 % CI [5.5-9.5]; n = 50/665). On the basis of medical history, bronchoalveolar lavage fluid cytology, and chest CT scan patterns, four etiological categories were identified: immune (n = 18; 36 %), drug-induced (n = 13; 26 %), malignant (n = 7; 14 %), and idiopathic (n = 12; 24 %). Although the ARDS CRF- patients had a lower logistic organ dysfunction score (4 [3-8] vs. 10 [6-13]; p < 0.0001) and less often shock upon ICU admission (44 vs. 80 %; p < 0.0001) than their counterparts, their overall ICU mortality rate was very high (66 % [46-74]), and the absence of CRF remained associated with ICU mortality by multivariable logistic regression analysis (adjusted OR = 2.06; 95 % CI [1.02-4.18]; p = 0.044). Among ARDS CRF- patients, the presence of potentially reversible lung lesions with corticosteroids (aOR = 0.14; 95 % CI [0.03-0.62]) was associated with ICU survival. The absence of CRF among patients with ARDS is common and associated with a higher risk of mortality. For such atypical ARDS, a complete diagnostic workup, including bronchoalveolar lavage fluid cytology and chest CT scan patterns, should be performed to identify those patients who might benefit from specific therapies, including corticosteroids.

Feasibility and safety of low-flow extracorporeal CO2 removal managed with a renal replacement platform to enhance lung-protective ventilation of patients with mild-to-moderate ARDS.

PubMed

Schmidt, Matthieu; Jaber, Samir; Zogheib, Elie; Godet, Thomas; Capellier, Gilles; Combes, Alain

2018-05-10

Extracorporeal carbon-dioxide removal (ECCO 2 R) might allow ultraprotective mechanical ventilation with lower tidal volume (VT) (< 6 ml/kg predicted body weight), plateau pressure (P plat ) (< 30 cmH 2 O), and driving pressure to limit ventilator-induced lung injury. This study was undertaken to assess the feasibility and safety of ECCO 2 R managed with a renal replacement therapy (RRT) platform to enable very low tidal volume ventilation of patients with mild-to-moderate acute respiratory distress syndrome (ARDS). Twenty patients with mild (n = 8) or moderate (n = 12) ARDS were included. VT was gradually lowered from 6 to 5, 4.5, and 4 ml/kg, and PEEP adjusted to reach 23 ≤ P plat  ≤ 25 cmH 2 O. Standalone ECCO 2 R (no hemofilter associated with the RRT platform) was initiated when arterial PaCO 2 increased by > 20% from its initial value. Ventilation parameters (VT, respiratory rate, PEEP), respiratory system compliance, P plat and driving pressure, arterial blood gases, and ECCO 2 R-system operational characteristics were collected during at least 24 h of very low tidal volume ventilation. Complications, day-28 mortality, need for adjuvant therapies, and data on weaning off ECCO 2 R and mechanical ventilation were also recorded. While VT was reduced from 6 to 4 ml/kg and P plat kept < 25 cmH 2 O, PEEP was significantly increased from 13.4 ± 3.6 cmH 2 O at baseline to 15.0 ± 3.4 cmH 2 O, and the driving pressure was significantly reduced from 13.0 ± 4.8 to 7.9 ± 3.2 cmH 2 O (both p < 0.05). The PaO 2 /FiO 2 ratio and respiratory-system compliance were not modified after VT reduction. Mild respiratory acidosis occurred, with mean PaCO 2 increasing from 43 ± 8 to 53 ± 9 mmHg and mean pH decreasing from 7.39 ± 0.1 to 7.32 ± 0.10 from baseline to 4 ml/kg VT, while the respiratory rate was not altered. Mean extracorporeal blood flow, sweep-gas flow, and CO 2 removal were 421 ± 40 ml/min, 10 ± 0.3 L/min, and 51 ± 26 ml/min, respectively. Mean treatment duration was 31 ± 22 h. Day-28 mortality was 15%. A low-flow ECCO 2 R device managed with an RRT platform easily and safely enabled very low tidal volume ventilation with moderate increase in PaCO 2 in patients with mild-to-moderate ARDS. ClinicalTrials.gov, NCT02606240. Registered on 17 November 2015.

Pharmacotherapy of Acute Lung Injury and Acute Respiratory Distress Syndrome

PubMed Central

Raghavendran, Krishnan; Pryhuber, Gloria S.; Chess, Patricia R.; Davidson, Bruce A.; Knight, Paul R.; Notter, Robert H.

2009-01-01

Acute lung injury (ALI) and the acute respiratory distress syndrome (ARDS) are characterized by rapid-onset respiratory failure following a variety of direct and indirect insults to the parenchyma or vasculature of the lungs. Mortality from ALI/ARDS is substantial, and current therapy primarily emphasizes mechanical ventilation and judicial fluid management plus standard treatment of the initiating insult and any known underlying disease. Current pharmacotherapy for ALI/ARDS is not optimal, and there is a significant need for more effective medicinal chemical agents for use in these severe and lethal lung injury syndromes. To facilitate future chemical-based drug discovery research on new agent development, this paper reviews present pharmacotherapy for ALI/ARDS in the context of biological and biochemical drug activities. The complex lung injury pathophysiology of ALI/ARDS offers an array of possible targets for drug therapy, including inflammation, cell and tissue injury, vascular dysfunction, surfactant dysfunction, and oxidant injury. Added targets for pharmacotherapy outside the lungs may also be present, since multiorgan or systemic pathology is common in ALI/ARDS. The biological and physiological complexity of ALI/ARDS requires the consideration of combined-agent treatments in addition to single-agent therapies. A number of pharmacologic agents have been studied individually in ALI/ARDS, with limited or minimal success in improving survival. However, many of these agents have complementary biological/biochemical activities with the potential for synergy or additivity in combination therapy as discussed in this article. PMID:18691048

Misclassification of acute respiratory distress syndrome after traumatic injury: The cost of less rigorous approaches.

PubMed

Hendrickson, Carolyn M; Dobbins, Sarah; Redick, Brittney J; Greenberg, Molly D; Calfee, Carolyn S; Cohen, Mitchell Jay

2015-09-01

Adherence to rigorous research protocols for identifying adult respiratory distress syndrome (ARDS) after trauma is variable. To examine how misclassification of ARDS may bias observational studies in trauma populations, we evaluated the agreement of two methods for adjudicating ARDS after trauma: the current gold standard, direct review of chest radiographs and review of dictated radiology reports, a commonly used alternative. This nested cohort study included 123 mechanically ventilated patients between 2005 and 2008, with at least one PaO2/FIO2 less than 300 within the first 8 days of admission. Two blinded physician investigators adjudicated ARDS by two methods. The investigators directly reviewed all chest radiographs to evaluate for bilateral infiltrates. Several months later, blinded to their previous assessments, they adjudicated ARDS using a standardized rubric to classify radiology reports. A κ statistics was calculated. Regression analyses quantified the association between established risk factors as well as important clinical outcomes and ARDS determined by the aforementioned methods as well as hypoxemia as a surrogate marker. The κ was 0.47 for the observed agreement between ARDS adjudicated by direct review of chest radiographs and ARDS adjudicated by review of radiology reports. Both the magnitude and direction of bias on the estimates of association between ARDS and established risk factors as well as clinical outcomes varied by method of adjudication. Classification of ARDS by review of dictated radiology reports had only moderate agreement with the current gold standard, ARDS adjudicated by direct review of chest radiographs. While the misclassification of ARDS had varied effects on the estimates of associations with established risk factors, it tended to weaken the association of ARDS with important clinical outcomes. A standardized approach to ARDS adjudication after trauma by direct review of chest radiographs will minimize misclassification bias in future observational studies. Diagnostic study, level II.

Tidal volume in acute respiratory distress syndrome: how best to select it.

PubMed

Umbrello, Michele; Marino, Antonella; Chiumello, Davide

2017-07-01

Mechanical ventilation is the type of organ support most widely provided in the intensive care unit. However, this form of support does not constitute a cure for acute respiratory distress syndrome (ARDS), as it mainly works by buying time for the lungs to heal while contributing to the maintenance of vital gas exchange. Moreover, it can further damage the lung, leading to the development of a particular form of lung injury named ventilator-induced lung injury (VILI). Experimental evidence accumulated over the last 30 years highlighted the factors associated with an injurious form of mechanical ventilation. The present paper illustrates the physiological effects of delivering a tidal volume to the lungs of patients with ARDS, and suggests an approach to tidal volume selection. The relationship between tidal volume and the development of VILI, the so called volotrauma, will be reviewed. The still actual suggestion of a lung-protective ventilatory strategy based on the use of low tidal volumes scaled to the predicted body weight (PBW) will be presented, together with newer strategies such as the use of airway driving pressure as a surrogate for the amount of ventilatable lung tissue or the concept of strain, i.e., the ratio between the tidal volume delivered relative to the resting condition, that is the functional residual capacity (FRC). An ultra-low tidal volume strategy with the use of extracorporeal carbon dioxide removal (ECCO 2 R) will be presented and discussed. Eventually, the role of other ventilator-related parameters in the generation of VILI will be considered (namely, plateau pressure, airway driving pressure, respiratory rate (RR), inspiratory flow), and the promising unifying framework of mechanical power will be presented.

Tidal volume in acute respiratory distress syndrome: how best to select it

PubMed Central

Umbrello, Michele; Marino, Antonella

2017-01-01

Mechanical ventilation is the type of organ support most widely provided in the intensive care unit. However, this form of support does not constitute a cure for acute respiratory distress syndrome (ARDS), as it mainly works by buying time for the lungs to heal while contributing to the maintenance of vital gas exchange. Moreover, it can further damage the lung, leading to the development of a particular form of lung injury named ventilator-induced lung injury (VILI). Experimental evidence accumulated over the last 30 years highlighted the factors associated with an injurious form of mechanical ventilation. The present paper illustrates the physiological effects of delivering a tidal volume to the lungs of patients with ARDS, and suggests an approach to tidal volume selection. The relationship between tidal volume and the development of VILI, the so called volotrauma, will be reviewed. The still actual suggestion of a lung-protective ventilatory strategy based on the use of low tidal volumes scaled to the predicted body weight (PBW) will be presented, together with newer strategies such as the use of airway driving pressure as a surrogate for the amount of ventilatable lung tissue or the concept of strain, i.e., the ratio between the tidal volume delivered relative to the resting condition, that is the functional residual capacity (FRC). An ultra-low tidal volume strategy with the use of extracorporeal carbon dioxide removal (ECCO2R) will be presented and discussed. Eventually, the role of other ventilator-related parameters in the generation of VILI will be considered (namely, plateau pressure, airway driving pressure, respiratory rate (RR), inspiratory flow), and the promising unifying framework of mechanical power will be presented. PMID:28828362

Intratidal Overdistention and Derecruitment in the Injured Lung: A Simulation Study.

PubMed

Amini, Reza; Herrmann, Jacob; Kaczka, David W

2017-03-01

Ventilated patients with the acute respiratory distress syndrome (ARDS) are predisposed to cyclic parenchymal overdistention and derecruitment, which may worsen existing injury. We hypothesized that intratidal variations in global mechanics, as assessed at the airway opening, would reflect such distributed processes. We developed a computational lung model for determining local instantaneous pressure distributions and mechanical impedances continuously during a breath. Based on these distributions and previous literature, we simulated the within-breath variability of airway segment dimensions, parenchymal viscoelasticity, and acinar recruitment in an injured canine lung for tidal volumes( V T ) of 10, 15, and 20 mL·kg -1 and positive end-expiratory pressures (PEEP) of 5, 10, and 15 cm H 2 O. Acini were allowed to transition between recruited and derecruited states when exposed to stochastically determined critical opening and closing pressures, respectively. For conditions of low V T and low PEEP, we observed small intratidal variations in global resistance and elastance, with a small number of cyclically recruited acini. However, with higher V T and PEEP, larger variations in resistance and elastance were observed, and the majority of acini remained open throughout the breath. Changes in intratidal resistance, elastance, and impedance followed well-defined parabolic trajectories with tracheal pressure, achieving minima near 12 to 16 cm H 2 O. Intratidal variations in lung mechanics may allow for optimization of ventilator settings in patients with ARDS, by balancing lung recruitment against parenchymal overdistention. Titration of airway pressures based on variations in intratidal mechanics may mitigate processes associated with injurious ventilation.

Pre-B-cell colony-enhancing factor gene polymorphisms and risk of acute respiratory distress syndrome.

PubMed

Bajwa, Ednan K; Yu, Chu-Ling; Gong, Michelle N; Thompson, B Taylor; Christiani, David C

2007-05-01

Pre-B-cell colony-enhancing factor (PBEF) levels are elevated in bronchoalveolar lavage fluid and serum of patients with acute lung injury. There are several suspected functional polymorphisms of the corresponding PBEF gene. We hypothesized that variations in PBEF gene polymorphisms alter the risk of developing acute respiratory distress syndrome (ARDS). Nested case-control study. Tertiary academic medical center. We studied 375 patients with ARDS and 787 at-risk controls genotyped for the PBEF T-1001G and C-1543T polymorphisms. None. Patients with the -1001G (variant) allele had significantly greater odds of developing ARDS than wild-type homozygotes (odds ratio, 1.35; 95% confidence interval, 1.02-1.78). Patients with the -1543T (variant) allele did not have significantly different odds of developing ARDS than wild-type homozygotes (odds ratio, 0.86; 95% confidence interval, 0.65-1.13). When analysis was stratified by ARDS risk factor, -1543T was associated with decreased odds of developing ARDS in septic shock patients (odds ratio, 0.66; 95% confidence interval, 0.45-0.97). Also, -1001G was associated with increased hazard of intensive care unit mortality, whereas -1543T was associated with decreased hazard of 28-day and 60-day ARDS mortality, as well as shorter duration of mechanical ventilation. Similar results were found in analyses of the related GC (-1001G:-1543C) and TT (-1001T:-1543T) haplotypes. The PBEFT-1001G variant allele and related haplotype are associated with increased odds of developing ARDS and increased hazard of intensive care unit mortality among at-risk patients, whereas the C-1543T variant allele and related haplotype are associated with decreased odds of ARDS among patients with septic shock and better outcomes among patients with ARDS.

Ventilator-associated pneumonia in ARDS patients: the impact of prone positioning. A secondary analysis of the PROSEVA trial.

PubMed

Ayzac, L; Girard, R; Baboi, L; Beuret, P; Rabilloud, M; Richard, J C; Guérin, C

2016-05-01

The goal of this study was to assess the impact of prone positioning on the incidence of ventilator-associated pneumonia (VAP) and the role of VAP in mortality in a recent multicenter trial performed on patients with severe ARDS. An ancillary study of a prospective multicenter randomized controlled trial on early prone positioning in patients with severe ARDS. In suspected cases of VAP the diagnosis was based on positive quantitative cultures of bronchoalveolar lavage fluid or tracheal aspirate at the 10(4) and 10(7) CFU/ml thresholds, respectively. The VAP cases were then subject to central, independent adjudication. The cumulative probabilities of VAP were estimated in each position group using the Aalen-Johansen estimator and compared using Gray's test. A univariate and a multivariate Cox model was performed to assess the impact of VAP, used as a time-dependent covariate for mortality hazard during the ICU stay. In the supine and prone position groups, the incidence rate for VAP was 1.18 (0.86-1.60) and 1.54 (1.15-2.02) per 100 days of invasive mechanical ventilation (p = 0.10), respectively. The cumulative probability of VAP at 90 days was estimated at 46.5 % (27-66) in the prone group and at 33.5 % (23-44) in the supine group. The difference between the two cumulative probability curves was not statistically significant (p = 0.11). In the univariate Cox model, VAP was associated with an increase in the mortality rate during the ICU stay [HR 1.65 (1.05-2.61), p = 0.03]. HR increased to 2.2 (1.39-3.52) (p < 0.001) after adjustment for position group, age, SOFA score, McCabe score, and immunodeficiency. In severe ARDS patients prone positioning did not reduce the incidence of VAP and VAP was associated with higher mortality.

The EIT-based global inhomogeneity index is highly correlated with regional lung opening in patients with acute respiratory distress syndrome

PubMed Central

2014-01-01

Background The electrical impedance tomography (EIT)-based global inhomogeneity (GI) index was introduced to quantify tidal volume distribution within the lung. Up to now, the GI index was evaluated for plausibility but the analysis of how it is influenced by various physiological factors is still missing. The aim of our study was to evaluate the influence of proportion of open lung regions measured by EIT on the GI index. Methods A constant low-flow inflation maneuver was performed in 18 acute respiratory distress syndrome (ARDS) patients (58 ± 14 years, mean age ± SD) and 8 lung-healthy patients (41 ± 12 years) under controlled mechanical ventilation. EIT raw data were acquired at 25 scans/s and reconstructed offline. Recruited lung regions were identified as those image pixels of the lung regions within the EIT scans where local impedance amplitudes exceeded 10% of the maximum amplitude during the maneuver. A series of GI indices was calculated during mechanical lung inflation, based on the differential images obtained between different time points. Respiratory system elastance (Ers) values were calculated at 10 lung volume levels during low-flow maneuver. Results The GI index decreased during low-flow inflation, while the percentage of open lung regions increased. The values correlated highly in both ARDS (r2 = 0.88 ± 0.08, p < 0.01) and lung-healthy patients (r2 = 0.92 ± 0.05, p < 0.01). Ers and GI index were also significantly correlated in 16 out of 18 ARDS (r2 = 0.84 ± 0.13, p < 0.01) and in 6 out of 8 lung-healthy patients (r2 = 0.84 ± 0.07, p < 0.01). Significant differences were found in GI values between two groups (0.52 ± 0.21 for ARDS and 0.41 ± 0.04 for lung-healthy patients, p < 0.05) as well in Ers values (0.017 ± 0.008 cmH2O/ml for ARDS and 0.009 ± 0.001 cmH2O/ml for lung-healthy patients, p < 0.01). Conclusions We conclude that the GI index is a reliable measure of ventilation heterogeneity highly correlated with lung recruitability measured with EIT. The GI index may prove to be a useful EIT-based index to guide ventilation therapy. PMID:24502320

Acute Respiratory Distress Syndrome after the Use of Gadolinium Contrast Media.

PubMed

Park, Jihye; Byun, Il Hwan; Park, Kyung Hee; Lee, Jae-Hyun; Nam, Eun Ji; Park, Jung-Won

2015-07-01

Acute respiratory distress syndrome (ARDS) is a medical emergency that threatens life. To this day, ARDS is very rarely reported by iodine contrast media, and there is no reported case of ARDS induced by gadolinium contrast media. Here, we present a case with ARDS after the use of gadobutrol (Gadovist) as a magnetic resonance imaging (MRI) contrast medium. A 26 years old female without any medical history, including allergic diseases and without current use of drugs, visited the emergency room for abdominal pain. Her abdominopelvic computed tomography with iodine contrast media showed a right ovarian cyst and possible infective colitis. Eighty-three hours later, she underwent pelvis MRI after injection of 7.5 mL (0.1 mL/kg body weight) of gadobutrol (Gadovist) to evaluate the ovarian cyst. She soon presented respiratory difficulty, edema of the lips, nausea, and vomiting, and we could hear wheezing upon auscultation. She was treated with dexamethasone, epinephrine, and norepinephrine. Her chest X-ray showed bilateral central bat-wing consolidative appearance. Managed with mechanical ventilation, she was extubated 3 days later and discharged without complications.

Immunocompromised patients with acute respiratory distress syndrome: secondary analysis of the LUNG SAFE database.

PubMed

Cortegiani, Andrea; Madotto, Fabiana; Gregoretti, Cesare; Bellani, Giacomo; Laffey, John G; Pham, Tai; Van Haren, Frank; Giarratano, Antonino; Antonelli, Massimo; Pesenti, Antonio; Grasselli, Giacomo

2018-06-12

The aim of this study was to describe data on epidemiology, ventilatory management, and outcome of acute respiratory distress syndrome (ARDS) in immunocompromised patients. We performed a post hoc analysis on the cohort of immunocompromised patients enrolled in the Large Observational Study to Understand the Global Impact of Severe Acute Respiratory Failure (LUNG SAFE) study. The LUNG SAFE study was an international, prospective study including hypoxemic patients in 459 ICUs from 50 countries across 5 continents. Of 2813 patients with ARDS, 584 (20.8%) were immunocompromised, 38.9% of whom had an unspecified cause. Pneumonia, nonpulmonary sepsis, and noncardiogenic shock were their most common risk factors for ARDS. Hospital mortality was higher in immunocompromised than in immunocompetent patients (52.4% vs 36.2%; p < 0.0001), despite similar severity of ARDS. Decisions regarding limiting life-sustaining measures were significantly more frequent in immunocompromised patients (27.1% vs 18.6%; p < 0.0001). Use of noninvasive ventilation (NIV) as first-line treatment was higher in immunocompromised patients (20.9% vs 15.9%; p = 0.0048), and immunodeficiency remained independently associated with the use of NIV after adjustment for confounders. Forty-eight percent of the patients treated with NIV were intubated, and their mortality was not different from that of the patients invasively ventilated ab initio. Immunosuppression is frequent in patients with ARDS, and infections are the main risk factors for ARDS in these immunocompromised patients. Their management differs from that of immunocompetent patients, particularly the greater use of NIV as first-line ventilation strategy. Compared with immunocompetent subjects, they have higher mortality regardless of ARDS severity as well as a higher frequency of limitation of life-sustaining measures. Nonetheless, nearly half of these patients survive to hospital discharge. ClinicalTrials.gov, NCT02010073 . Registered on 12 December 2013.

[Treatment of patients with different degree of acute respiratory distress syndrome caused by inhalation of white smoke].

PubMed

Yang, F W; Xin, H M; Zhu, J H; Feng, X Y; Jiang, X C; Gong, Z Y; Tong, Y L

2017-12-20

Objective: To summarize the treatment experience of patients with different degree of acute respiratory distress syndrome (ARDS) caused by inhalation of white smoke from burning smoke bomb. Methods: A batch of 13 patients with different degree of ARDS caused by inhalation of white smoke from burning smoke bomb, including 2 patients complicated by pulmonary fibrosis at the late stage, were admitted to our unit in February 2016. Patients were divided into mild (9 cases), moderate (2 cases), and serious (2 cases) degree according to the ARDS Berlin diagnostic criteria. Patients with mild and moderate ARDS were conventionally treated with glucocorticoid. Patients with severe ARDS were sequentially treated with glucocorticoid and pirfenidone, and ventilator-assisted breathing, etc. were applied. The vital signs, arterial oxygenation index, changes of lung imaging, pulmonary ventilation function, general condition, and the other important organs/systems function were timely monitored according to the condition of patients. The above indexes were also monitored during the follow-up time of 10-15 months post injury. Data were processed with SPSS 18.0 statistical software. Results: (1) The symptoms of respiratory system of patients with mild and moderate ARDS almost disappeared after 3 days' treatment. Their arterial oxygenation index was decreased from post injury day 1 to 4, which almost recovered on post injury day 7 and completely recovered one month post injury. The symptoms of respiratory system of patients with severe ARDS almost disappeared at tranquillization condition 1-3 month (s) post injury. Their arterial oxygenation index was decreased from post injury day 3 to 21, which gradually recovered 1-3 month (s) post injury and was normal 15 months post injury. (2) Within 24 hours post injury, there was no obvious abnormality or only a little texture enlargement of lung in image of chest CT or X-rays of patients with mild and moderate ARDS. One patient with moderate ARDS had diffuse patchy and ground-glass like increased density shadow (pulmonary exudation for short) at post injury hour 96. Chest iconography of all patients with mild and moderate ARDS showed no abnormalities 10 months post injury. Both lungs of each of the two patients with severe ARDS showed obvious pulmonary exudation at post injury hours 45 and 75, respectively. One patient with severe ARDS showed no abnormality in chest image 10 months post injury, but there was still a small mesh-like increased density shadow in double lobes with slight adhesion of pleura in the other patient with severe ARDS 15 months post injury. (3) All patients showed severe restrictive hypoventilation when admitted to hospital. Pulmonary ventilation function of patients with mild and moderate ARDS recovered to normal one month post injury, and they could do exercises like running, etc. Pulmonary ventilation function of one patient with severe ARDS recovered to normal 6 months post injury, and the patient could do exercises like running, etc. The other patient with severe ARDS showed mild restrictive hypoventilation 15 months post injury and could do exercises like rapid walking, etc. (4) The condition of all mild and one moderate ARDS patients was better on post injury day 3, and they were transferred to the local hospital for subsequent treatment and left hospital on post injury day 21. One patient with moderate ARDS healed and left hospital on post injury day 29. Patients with severe ARDS healed and left hospital on post injury day 81. During the follow-up time of 10-15 months post injury, the other important organs/systems of all patients showed no abnormality, and there was no adverse reaction of glucocorticoid like osteoporosis, femoral head necrosis, or metabolic disorder. Two patients with severe ARDS did not have any adverse reaction of pirfenidone like liver function damage, photosensitivity, anorexia, or lethargy. Conclusions: Early enough and uninterrupted application of glucocorticoid can significantly reduce the ARDS of patients caused by inhalation of white smoke from burning smoke bomb. Sequential application of glucocorticoid and pirfenidone can effectively treat pulmonary fibrosis at the late stage.

Genome-Wide Association Study in African Americans with Acute Respiratory Distress Syndrome Identifies the Selectin P Ligand Gene as a Risk Factor.

PubMed

Bime, Christian; Pouladi, Nima; Sammani, Saad; Batai, Ken; Casanova, Nancy; Zhou, Tong; Kempf, Carrie L; Sun, Xiaoguang; Camp, Sara M; Wang, Ting; Kittles, Rick A; Lussier, Yves A; Jones, Tiffanie K; Reilly, John P; Meyer, Nuala J; Christie, Jason D; Karnes, Jason H; Gonzalez-Garay, Manuel; Christiani, David C; Yates, Charles R; Wurfel, Mark M; Meduri, Gianfranco U; Garcia, Joe G N

2018-06-01

Genetic factors are involved in acute respiratory distress syndrome (ARDS) susceptibility. Identification of novel candidate genes associated with increased risk and severity will improve our understanding of ARDS pathophysiology and enhance efforts to develop novel preventive and therapeutic approaches. To identify genetic susceptibility targets for ARDS. A genome-wide association study was performed on 232 African American patients with ARDS and 162 at-risk control subjects. The Identify Candidate Causal SNPs and Pathways platform was used to infer the association of known gene sets with the top prioritized intragenic SNPs. Preclinical validation of SELPLG (selectin P ligand gene) was performed using mouse models of LPS- and ventilator-induced lung injury. Exonic variation within SELPLG distinguishing patients with ARDS from sepsis control subjects was confirmed in an independent cohort. Pathway prioritization analysis identified a nonsynonymous coding SNP (rs2228315) within SELPLG, encoding P-selectin glycoprotein ligand 1, to be associated with increased susceptibility. In an independent cohort, two exonic SELPLG SNPs were significantly associated with ARDS susceptibility. Additional support for SELPLG as an ARDS candidate gene was derived from preclinical ARDS models where SELPLG gene expression in lung tissues was significantly increased in both ventilator-induced (twofold increase) and LPS-induced (5.7-fold increase) murine lung injury models compared with controls. Furthermore, Selplg -/- mice exhibited significantly reduced LPS-induced inflammatory lung injury compared with wild-type C57/B6 mice. Finally, an antibody that neutralizes P-selectin glycoprotein ligand 1 significantly attenuated LPS-induced lung inflammation. These findings identify SELPLG as a novel ARDS susceptibility gene among individuals of European and African descent.

Lung ventilation strategies for acute respiratory distress syndrome: a systematic review and network meta-analysis

PubMed Central

Wang, Changsong; Wang, Xiaoyang; Chi, Chunjie; Guo, Libo; Guo, Lei; Zhao, Nana; Wang, Weiwei; Pi, Xin; Sun, Bo; Lian, Ailing; Shi, Jinghui; Li, Enyou

2016-01-01

To identify the best lung ventilation strategy for acute respiratory distress syndrome (ARDS), we performed a network meta-analysis. The Cochrane Central Register of Controlled Trials, EMBASE, MEDLINE, CINAHL, and the Web of Science were searched, and 36 eligible articles were included. Compared with higher tidal volumes with FiO2-guided lower positive end-expiratory pressure [PEEP], the hazard ratios (HRs) for mortality were 0.624 (95% confidence interval (CI) 0.419–0.98) for lower tidal volumes with FiO2-guided lower PEEP and prone positioning and 0.572 (0.34–0.968) for pressure-controlled ventilation with FiO2-guided lower PEEP. Lower tidal volumes with FiO2-guided higher PEEP and prone positioning had the greatest potential to reduce mortality, and the possibility of receiving the first ranking was 61.6%. Permissive hypercapnia, recruitment maneuver, and low airway pressures were most likely to be the worst in terms of all-cause mortality. Compared with higher tidal volumes with FiO2-guided lower PEEP, pressure-controlled ventilation with FiO2-guided lower PEEP and lower tidal volumes with FiO2-guided lower PEEP and prone positioning ventilation are associated with lower mortality in ARDS patients. Lower tidal volumes with FiO2-guided higher PEEP and prone positioning ventilation and lower tidal volumes with pressure-volume (P–V) static curve-guided individual PEEP are potential optimal strategies for ARDS patients. PMID:26955891

The Right Ventricle in ARDS.

PubMed

Zochios, Vasileios; Parhar, Ken; Tunnicliffe, William; Roscoe, Andrew; Gao, Fang

2017-07-01

ARDS is associated with poor clinical outcomes, with a pooled mortality rate of approximately 40% despite best standards of care. Current therapeutic strategies are based on improving oxygenation and pulmonary compliance while minimizing ventilator-induced lung injury. It has been demonstrated that relative hypoxemia can be well tolerated, and improvements in oxygenation do not necessarily translate into survival benefit. Cardiac failure, in particular right ventricular dysfunction (RVD), is commonly encountered in moderate to severe ARDS and is reported to be one of the major determinants of mortality. The prevalence rate of echocardiographically evident RVD in ARDS varies across studies, ranging from 22% to 50%. Although there is no definitive causal relationship between RVD and mortality, severe RVD is associated with increased mortality. Factors that can adversely affect RV function include hypoxic pulmonary vasoconstriction, hypercapnia, and invasive ventilation with high driving pressure. It might be expected that early diagnosis of RVD would be of benefit; however, echocardiographic markers (qualitative and quantitative) used to prospectively evaluate the right ventricle in ARDS have not been tested in adequately powered studies. In this review, we examine the prognostic implications and pathophysiology of RVD in ARDS and discuss available diagnostic modalities and treatment options. We aim to identify gaps in knowledge and directions for future research that could potentially improve clinical outcomes in this patient population. Copyright © 2017 American College of Chest Physicians. All rights reserved.

Lung Microbiota Is Related to Smoking Status and to Development of Acute Respiratory Distress Syndrome in Critically Ill Trauma Patients.

PubMed

Panzer, Ariane R; Lynch, Susan V; Langelier, Chaz; Christie, Jason D; McCauley, Kathryn; Nelson, Mary; Cheung, Christopher K; Benowitz, Neal L; Cohen, Mitchell J; Calfee, Carolyn S

2018-03-01

Cigarette smoking is associated with increased risk of acute respiratory distress syndrome (ARDS) in patients after severe trauma; however, the mechanisms underlying this association are unknown. To determine whether cigarette smoking contributes to ARDS development after trauma by altering community composition of the lung microbiota. We studied the lung microbiota of mechanically ventilated patients admitted to the ICU after severe blunt trauma. To do so, we used 16S ribosomal RNA gene amplicon sequencing of endotracheal aspirate samples obtained on ICU admission (n = 74) and at 48 hours after admission (n = 30). Cigarette smoke exposure (quantified using plasma cotinine), ARDS development, and other clinical parameters were correlated with lung microbiota composition. Smoking status was significantly associated with lung bacterial community composition at ICU admission (P = 0.007 by permutational multivariate ANOVA [PERMANOVA]) and at 48 hours (P = 0.03 by PERMANOVA), as well as with significant enrichment of potential pathogens, including Streptococcus, Fusobacterium, Prevotella, Haemophilus, and Treponema. ARDS development was associated with lung community composition at 48 hours (P = 0.04 by PERMANOVA) and was characterized by relative enrichment of Enterobacteriaceae and of specific taxa enriched at baseline in smokers, including Prevotella and Fusobacterium. After severe blunt trauma, a history of smoking is related to lung microbiota composition, both at the time of ICU admission and at 48 hours. ARDS development is also correlated with respiratory microbial community structure at 48 hours and with taxa that are relatively enriched in smokers at ICU admission. The data derived from this pilot study suggest that smoking-related changes in the lung microbiota could be related to ARDS development after severe trauma.

A universal definition of ARDS: the PaO2/FiO2 ratio under a standard ventilatory setting--a prospective, multicenter validation study.

PubMed

Villar, Jesús; Pérez-Méndez, Lina; Blanco, Jesús; Añón, José Manuel; Blanch, Lluís; Belda, Javier; Santos-Bouza, Antonio; Fernández, Rosa Lidia; Kacmarek, Robert M

2013-04-01

The PaO2/FiO2 is an integral part of the assessment of patients with acute respiratory distress syndrome (ARDS). The American-European Consensus Conference definition does not mandate any standardization procedure. We hypothesized that the use of PaO2/FiO2 calculated under a standard ventilatory setting within 24 h of ARDS diagnosis allows a more clinically relevant ARDS classification. We studied 452 ARDS patients enrolled prospectively in two independent, multicenter cohorts treated with protective mechanical ventilation. At the time of ARDS diagnosis, patients had a PaO2/FiO2 ≤ 200. In the derivation cohort (n = 170), we measured PaO2/FiO2 with two levels of positive end-expiratory pressure (PEEP) (≥ 5 and ≥ 10 cmH2O) and two levels of FiO2 (≥ 0.5 and 1.0) at ARDS onset and 24 h later. Dependent upon PaO2 response, patients were reclassified into three groups: mild (PaO2/FiO2 > 200), moderate (PaO2/FiO2 101-200), and severe (PaO2/FiO2 ≤ 100) ARDS. The primary outcome measure was ICU mortality. The standard ventilatory setting that reached the highest significance difference in mortality among these categories was tested in a separate cohort (n = 282). The only standard ventilatory setting that identified the three PaO2/FiO2 risk categories in the derivation cohort was PEEP ≥ 10 cmH2O and FiO2 ≥ 0.5 at 24 h after ARDS onset (p = 0.0001). Using this ventilatory setting, patients in the validation cohort were reclassified as having mild ARDS (n = 47, mortality 17 %), moderate ARDS (n = 149, mortality 40.9 %), and severe ARDS (n = 86, mortality 58.1 %) (p = 0.00001). Our method for assessing PaO2/FiO2 greatly improved risk stratification of ARDS and could be used for enrolling appropriate ARDS patients into therapeutic clinical trials.

National Trauma Institute: A National Coordinating Center for Trauma Research Funding

DTIC Science & Technology

2016-12-01

comparing the effectiveness of modern ventilator modalities upon patients with ARDS/ALI does not exist. Low-tidal volume ventilation (ARDSNet...associated with better oxygenation , less sedative usage, and less ventilator -associated pneumonia compared with other ventilator modes. However, questions...hypercoagulable at baseline, and that further investigations into the effects of platelet activation and obesity, time-to-enoxaparin administration, and

Effect of Noninvasive Ventilation Delivered by Helmet vs Face Mask on the Rate of Endotracheal Intubation in Patients With Acute Respiratory Distress Syndrome: A Randomized Clinical Trial.

PubMed

Patel, Bhakti K; Wolfe, Krysta S; Pohlman, Anne S; Hall, Jesse B; Kress, John P

2016-06-14

Noninvasive ventilation (NIV) with a face mask is relatively ineffective at preventing endotracheal intubation in patients with acute respiratory distress syndrome (ARDS). Delivery of NIV with a helmet may be a superior strategy for these patients. To determine whether NIV delivered by helmet improves intubation rate among patients with ARDS. Single-center randomized clinical trial of 83 patients with ARDS requiring NIV delivered by face mask for at least 8 hours while in the medical intensive care unit at the University of Chicago between October 3, 2012, through September 21, 2015. Patients were randomly assigned to continue face mask NIV or switch to a helmet for NIV support for a planned enrollment of 206 patients (103 patients per group). The helmet is a transparent hood that covers the entire head of the patient and has a rubber collar neck seal. Early trial termination resulted in 44 patients randomized to the helmet group and 39 to the face mask group. The primary outcome was the proportion of patients who required endotracheal intubation. Secondary outcomes included 28-day invasive ventilator-free days (ie, days alive without mechanical ventilation), duration of ICU and hospital length of stay, and hospital and 90-day mortality. Eighty-three patients (45% women; median age, 59 years; median Acute Physiology and Chronic Health Evaluation [APACHE] II score, 26) were included in the analysis after the trial was stopped early based on predefined criteria for efficacy. The intubation rate was 61.5% (n = 24) for the face mask group and 18.2% (n = 8) for the helmet group (absolute difference, -43.3%; 95% CI, -62.4% to -24.3%; P < .001). The number of ventilator-free days was significantly higher in the helmet group (28 vs 12.5, P < .001). At 90 days, 15 patients (34.1%) in the helmet group died compared with 22 patients (56.4%) in the face mask group (absolute difference, -22.3%; 95% CI, -43.3 to -1.4; P = .02). Adverse events included 3 interface-related skin ulcers for each group (ie, 7.6% in the face mask group had nose ulcers and 6.8% in the helmet group had neck ulcers). Among patients with ARDS, treatment with helmet NIV resulted in a significant reduction of intubation rates. There was also a statistically significant reduction in 90-day mortality with helmet NIV. Multicenter studies are needed to replicate these findings. clinicaltrials.gov Identifier: NCT01680783.

Optimal plateau pressure for patients with acute respiratory distress syndrome: a protocol for a systematic review and meta-analysis with meta-regression.

PubMed

Yasuda, Hideto; Nishimura, Tetsuro; Kamo, Tetsuro; Sanui, Masamitsu; Nango, Eishu; Abe, Takayuki; Takebayashi, Toru; Lefor, Alan Kawarai; Hashimoto, Satoru

2017-05-29

Lower tidal volume ventilation in patients with acute respiratory distress syndrome (ARDS) is a strategy to reduce the plateau pressure and driving pressure to limit ventilator-induced lung injury (VILI). Several randomised controlled trials (RCTs) and meta-analyses showed that limiting both the plateau pressure and the tidal volume decreased mortality, but the optimal plateau pressure to demonstrate a benefit is uncertain. The aim of this systematic review is to investigate the optimal upper limit of plateau pressure in patients with ARDS to prevent VILI and improve clinical outcomes using meta-analysis with and without meta-regression. RCTs comparing two mechanical ventilation strategies will be included, with lower plateau pressure and with higher plateau pressure, among patients with ARDS and acute lung injury. Data sources include MEDLINE via the NCBI Entrez system, Cochrane Central Register of Controlled Trials (CENTRAL), EMBASE and Ichushi, a database of papers in Japanese. Two of three physicians will independently screen trials obtained by search for eligibility, and extract data from included studies onto standardised data recording forms. For each included trial, the risk of bias and the quality of evidence will be evaluated using the Grading of Recommendation Assessment Development and Evaluation system. This study does not require ethical approval. The results of this systematic review and meta-analysis with and without meta-regression will be disseminated through conference presentation and publication in a peer-reviewed journal. CRD42016041924. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

A Markov computer simulation model of the economics of neuromuscular blockade in patients with acute respiratory distress syndrome

PubMed Central

Macario, Alex; Chow, John L; Dexter, Franklin

2006-01-01

Background Management of acute respiratory distress syndrome (ARDS) in the intensive care unit (ICU) is clinically challenging and costly. Neuromuscular blocking agents may facilitate mechanical ventilation and improve oxygenation, but may result in prolonged recovery of neuromuscular function and acute quadriplegic myopathy syndrome (AQMS). The goal of this study was to address a hypothetical question via computer modeling: Would a reduction in intubation time of 6 hours and/or a reduction in the incidence of AQMS from 25% to 21%, provide enough benefit to justify a drug with an additional expenditure of $267 (the difference in acquisition cost between a generic and brand name neuromuscular blocker)? Methods The base case was a 55 year-old man in the ICU with ARDS who receives neuromuscular blockade for 3.5 days. A Markov model was designed with hypothetical patients in 1 of 6 mutually exclusive health states: ICU-intubated, ICU-extubated, hospital ward, long-term care, home, or death, over a period of 6 months. The net monetary benefit was computed. Results Our computer simulation modeling predicted the mean cost for ARDS patients receiving standard care for 6 months to be $62,238 (5% – 95% percentiles $42,259 – $83,766), with an overall 6-month mortality of 39%. Assuming a ceiling ratio of $35,000, even if a drug (that cost $267 more) hypothetically reduced AQMS from 25% to 21% and decreased intubation time by 6 hours, the net monetary benefit would only equal $137. Conclusion ARDS patients receiving a neuromuscular blocker have a high mortality, and unpredictable outcome, which results in large variability in costs per case. If a patient dies, there is no benefit to any drug that reduces ventilation time or AQMS incidence. A prospective, randomized pharmacoeconomic study of neuromuscular blockers in the ICU to asses AQMS or intubation times is impractical because of the highly variable clinical course of patients with ARDS. PMID:16539706

Acute respiratory distress syndrome and acute lung injury.

PubMed

Dushianthan, A; Grocott, M P W; Postle, A D; Cusack, R

2011-09-01

Acute respiratory distress syndrome (ARDS) is a life threatening respiratory failure due to lung injury from a variety of precipitants. Pathologically ARDS is characterised by diffuse alveolar damage, alveolar capillary leakage, and protein rich pulmonary oedema leading to the clinical manifestation of poor lung compliance, severe hypoxaemia, and bilateral infiltrates on chest radiograph. Several aetiological factors associated with the development of ARDS are identified with sepsis, pneumonia, and trauma with multiple transfusions accounting for most cases. Despite the absence of a robust diagnostic definition, extensive epidemiological investigations suggest ARDS remains a significant health burden with substantial morbidity and mortality. Improvements in outcome following ARDS over the past decade are in part due to improved strategies of mechanical ventilation and advanced support of other failing organs. Optimal treatment involves judicious fluid management, protective lung ventilation with low tidal volumes and moderate positive end expiratory pressure, multi-organ support, and treatment where possible of the underlying cause. Moreover, advances in general supportive measures such as appropriate antimicrobial therapy, early enteral nutrition, prophylaxis against venous thromboembolism and gastrointestinal ulceration are likely contributory reasons for the improved outcomes. Although therapies such as corticosteroids, nitric oxide, prostacyclins, exogenous surfactants, ketoconazole and antioxidants have shown promising clinical effects in animal models, these have failed to translate positively in human studies. Most recently, clinical trials with β2 agonists aiding alveolar fluid clearance and immunonutrition with omega-3 fatty acids have also provided disappointing results. Despite these negative studies, mortality seems to be in decline due to advances in overall patient care. Future directions of research are likely to concentrate on identifying potential biomarkers or genetic markers to facilitate diagnosis, with phenotyping of patients to predict outcome and treatment response. Pharmacotherapies remain experimental and recent advances in the modulation of inflammation and novel cellular based therapies, such as mesenchymal stem cells, may reduce lung injury and facilitate repair.

Respiratory support in patients with acute respiratory distress syndrome: an expert opinion.

PubMed

Chiumello, Davide; Brochard, Laurent; Marini, John J; Slutsky, Arthur S; Mancebo, Jordi; Ranieri, V Marco; Thompson, B Taylor; Papazian, Laurent; Schultz, Marcus J; Amato, Marcelo; Gattinoni, Luciano; Mercat, Alain; Pesenti, Antonio; Talmor, Daniel; Vincent, Jean-Louis

2017-09-12

Acute respiratory distress syndrome (ARDS) is a common condition in intensive care unit patients and remains a major concern, with mortality rates of around 30-45% and considerable long-term morbidity. Respiratory support in these patients must be optimized to ensure adequate gas exchange while minimizing the risks of ventilator-induced lung injury. The aim of this expert opinion document is to review the available clinical evidence related to ventilator support and adjuvant therapies in order to provide evidence-based and experience-based clinical recommendations for the management of patients with ARDS.

Prehospital amiodarone may increase the incidence of acute respiratory distress syndrome among patients at risk.

PubMed

Karnatovskaia, Lioudmila V; Festic, Emir; Gajic, Ognjen; Carter, Rickey E; Lee, Augustine S

2012-10-01

Amiodarone has been implicated as a risk factor for acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) when used in the hospital. This study aims to estimate whether prehospital amiodarone also increases the risk of ALI/ARDS. Adult patients admitted to 22 centers with at least 1 risk factor for developing ALI were recruited. In a secondary analysis of this cohort, the prehospital use of amiodarone was documented on admission, and the patients followed for the primary outcome of ALI and secondary outcomes of ARDS, the need for invasive ventilation, and mortality. Dose/duration of amiodarone therapy was not available. Propensity matching was performed to account for imbalances in being assigned to amiodarone. The adjusted risk for ALI/ARDS was then estimated from a conditional logistic regression model of this propensity-matched set. Forty of 5584 patients were on amiodarone at the time of hospitalization; of those, 6 developed ALI, with 5 progressing to ARDS. In comparison, 371 patients not on amiodarone developed ALI, with 224 having ARDS. After propensity score matching, the prehospital use of amiodarone was not statistically associated with an increased risk for all ALI (odds ratio [OR], 1.8; 95% confidence interval [CI], 0.7-5.0; P = .25), invasive ventilation (OR, 1.9; 95% CI, 1.0-3.6; P = .059), or in-hospital mortality (OR, 1.2; 95% CI, 0.5-2.9; P = .75); but its use appeared to significantly increase the risk for ARDS (OR 3.8; 95% CI, 1.1-13.1; P = .036). Prehospital use of amiodarone may independently increase the risk for ARDS in patients who have at least 1 predisposing condition for ALI. Copyright © 2012 Elsevier Inc. All rights reserved.

Multiple organ failure with the adult respiratory distress syndrome in homicidal arsenic poisoning.

PubMed

Bolliger, C T; van Zijl, P; Louw, J A

1992-01-01

A 30-year-old man and a 39-year-old woman, who was 28 weeks pregnant, were simultaneously poisoned by eating chocolate containing arsenic trioxide. They developed a picture of multiple organ failure peaking around the 8th to 10th day after ingestion, with the development of life-threatening adult respiratory distress syndrome (ARDS) in both patients. This rarely reported complication of arsenic poisoning was managed successfully by intubation and mechanical ventilation with positive end expiratory pressure in both patients. Hemodynamic and laboratory data are presented supporting the clinical course. Arsenic toxicity further resulted in intrauterine fetal death. The effects of severe arsenic poisoning leading to early multiple organ failure with ARDS as well as to protracted, debilitating polyneuropathy are discussed.

Critically ill infants and children with influenza A (H1N1) in pediatric intensive care units in Argentina.

PubMed

Farias, Julio A; Fernández, Analía; Monteverde, Ezequiel; Vidal, Nilda; Arias, Pilar; Montes, María J; Rodríguez, Gabriela; Allasia, Mariela; Ratto, Maria E; Jaén, Roxana; Meregalli, Claudia; Fiquepron, Karina; Calvo, Ana R; Siaba, Alejandro; Albano, Lidia; Poterala, Rossana; Neira, Pablo; Esteban, Andrés

2010-06-01

To determine the epidemiological features, course, and outcomes of critically ill pediatric patients with Influenza A (H1N1) virus. Prospective cohort of children in pediatric intensive care units (PICUs) due to Influenza A (H1N1) virus infection. Seventeen medical-surgical PICUs in tertiary care hospital in Argentina. All consecutive patients admitted to the PICUs with influenza A (H1N1) viral infection from 15 June to 31 July 2009. Of 437 patients with acute lower respiratory infection in PICUs, 147 (34%) were diagnosed with influenza A (H1N1) related to critical illness. The median age of these patients was 10 months (IQR 3-59). Invasive mechanical ventilation was used in 117 (84%) on admission. The rate of acute respiratory distress syndrome (ARDS) was 80% (118 of 147 patients). Initial non-invasive ventilation failed in 19 of 22 attempts (86%). Mortality at 28 days was 39% (n = 57). Chronic complex conditions (CCCs), acute renal dysfunction (ARD) and ratio PaO(2)/FiO(2) at day 3 on MV were independently associated with a higher risk of mortality. The odds ratio (OR) for CCCs was 3.06, (CI 95% 1.36-6.84); OR for ARD, 3.38, (CI 95% 1.45-10.33); OR for PaO(2)/FiO(2), 4 (CI 95% 1.57-9.59). The administration of oseltamivir within 24 h after admission had a protective effect: OR 0.2 (CI 95% 0.07-0.54). In children with ARDS, H1N1 as an etiologic agent confers high mortality, and the presence of CCCs in such patients increases the risk of death.

Simvastatin in the acute respiratory distress syndrome.

PubMed

McAuley, Daniel F; Laffey, John G; O'Kane, Cecilia M; Perkins, Gavin D; Mullan, Brian; Trinder, T John; Johnston, Paul; Hopkins, Philip A; Johnston, Andrew J; McDowell, Cliona; McNally, Christine

2014-10-30

Studies in animals and in vitro and phase 2 studies in humans suggest that statins may be beneficial in the treatment of the acute respiratory distress syndrome (ARDS). This study tested the hypothesis that treatment with simvastatin would improve clinical outcomes in patients with ARDS. In this multicenter, double-blind clinical trial, we randomly assigned (in a 1:1 ratio) patients with an onset of ARDS within the previous 48 hours to receive enteral simvastatin at a dose of 80 mg or placebo once daily for a maximum of 28 days. The primary outcome was the number of ventilator-free days to day 28. Secondary outcomes included the number of days free of nonpulmonary organ failure to day 28, mortality at 28 days, and safety. The study recruited 540 patients, with 259 patients assigned to simvastatin and 281 to placebo. The groups were well matched with respect to demographic and baseline physiological variables. There was no significant difference between the study groups in the mean (±SD) number of ventilator-free days (12.6±9.9 with simvastatin and 11.5±10.4 with placebo, P=0.21) or days free of nonpulmonary organ failure (19.4±11.1 and 17.8±11.7, respectively; P=0.11) or in mortality at 28 days (22.0% and 26.8%, respectively; P=0.23). There was no significant difference between the two groups in the incidence of serious adverse events related to the study drug. Simvastatin therapy, although safe and associated with minimal adverse effects, did not improve clinical outcomes in patients with ARDS. (Funded by the U.K. National Institute for Health Research Efficacy and Mechanism Evaluation Programme and others; HARP-2 Current Controlled Trials number, ISRCTN88244364.).

Interstitial pneumonia with autoimmune features: an additional risk factor for ARDS?

PubMed

Grasselli, Giacomo; Vergnano, Beatrice; Pozzi, Maria Rosa; Sala, Vittoria; D'Andrea, Gabriele; Scaravilli, Vittorio; Mantero, Marco; Pesci, Alberto; Pesenti, Antonio

2017-09-18

Interstitial pneumonia with autoimmune features (IPAF) identifies a recently recognized autoimmune syndrome characterized by interstitial lung disease and autoantibodies positivity, but absence of a specific connective tissue disease diagnosis or alternative etiology. We retrospectively reviewed the clinical presentation, diagnostic workup and management of seven critically ill patients who met diagnostic criteria for IPAF. We compared baseline characteristics and clinical outcome of IPAF patients with those of the population of ARDS patients admitted in the same period. Seven consecutive patients with IPAF admitted to intensive care unit for acute respiratory distress syndrome (ARDS) were compared with 78 patients with ARDS secondary to a known risk factor and with eight ARDS patients without recognized risk factors. Five IPAF patients (71%) survived and were discharged alive from ICU: Their survival rate was equal to that of patients with a known risk factor (71%), while the subgroup of patients without risk factors had a markedly lower survival (38%). According to the Berlin definition criteria, ARDS was severe in four IPAF patients and moderate in the remaining three. All had multiple organ dysfunction at presentation. The most frequent autoantibody detected was anti-SSA/Ro52. All patients required prolonged mechanical ventilation (median duration 49 days, range 10-88); four received extracorporeal membrane oxygenation and one received low-flow extracorporeal CO 2 removal. All patients received immunosuppressive therapy. This is the first description of a cohort of critical patients meeting the diagnostic criteria for IPAF presenting with ARDS. This diagnosis should be considered in any critically ill patient with interstitial lung disease of unknown origin. While management is challenging and level of support high, survival appears to be good and comparable to that of patients with ARDS associated with a known clinical insult.

[Alveolar ventilation and recruitment under lung protective ventilation].

PubMed

Putensen, Christian; Muders, Thomas; Kreyer, Stefan; Wrigge, Hermann

2008-11-01

Goal of mechanical ventilation is to improve gas exchange and reduce work of breathing without contributing to further lung injury. Besides providing adequate EELV and thereby arterial oxygenation PEEP in addition to a reduction in tidal volume is required to prevent cyclic alveolar collapse and tidal recruitment and hence protective mechanical ventilation. Currently, there is no consensus if and if yes at which price alveolar recruitment with high airway pressures should be intended ("open up the lung"), or if it is more important to reduce the mechanical stress and strain to the lungs as much as possible ("keep the lung closed"). Potential of alveolar recruitment differs from patient to patient but also between lung regions. Potential for recruitment depends probably more on regional lung mechanics - especially on lung elastance - than on the underlying disease. Based on available data neither high PEEP nor other methods used for alveolar recruitment could demonstrate a survival benefit in patients with ARDS. These results may support an individualized titration of PEEP or other manoeuvres used for recruitment taking into consideration the regional effects. Bedside imaging techniques allowing titration of PEEP or other manoeuvres to prevent end-expiratory alveolar collapse (tidal recruitment) and inspiratory overinflation may be a promising development.

Diagnosing acute respiratory distress syndrome in resource limited settings: the Kigali modification of the Berlin definition.

PubMed

Riviello, Elisabeth D; Buregeya, Egide; Twagirumugabe, Theogene

2017-02-01

The acute respiratory distress syndrome (ARDS) was re-defined by a panel of experts in Berlin in 2012. Although the Berlin criteria improved upon the validity and reliability of the definition, it did not make diagnosis of ARDS in resource limited settings possible. Mechanical ventilation, arterial blood gas measurements, and chest radiographs are not feasible in many regions of the world. In 2014, we proposed and applied the Kigali modification of the Berlin definition in a hospital in Rwanda. This review synthesizes literature from the last 18 months relevant to the Kigali modification. In the last 18 months, the need for a universally applicable ARDS definition was reinforced by advances in supportive care that can be implemented in resource poor settings. Research demonstrating the variable impact of positive end expiratory pressure on hypoxemia, the validity of using pulse oximetry rather than arterial blood gas to categorize hypoxemia, and the accuracy of lung ultrasound support the use of the Kigali modification of the Berlin definition. Studies directly comparing the Berlin definition to the Kigali modification are needed. Ongoing clinical research on ARDS needs to include low-income countries.

Impact of Different Tidal Volume Levels at Low Mechanical Power on Ventilator-Induced Lung Injury in Rats.

PubMed

Moraes, Lillian; Silva, Pedro L; Thompson, Alessandra; Santos, Cintia L; Santos, Raquel S; Fernandes, Marcos V S; Morales, Marcelo M; Martins, Vanessa; Capelozzi, Vera L; de Abreu, Marcelo G; Pelosi, Paolo; Rocco, Patricia R M

2018-01-01

Tidal volume (V T ) has been considered the main determinant of ventilator-induced lung injury (VILI). Recently, experimental studies have suggested that mechanical power transferred from the ventilator to the lungs is the promoter of VILI. We hypothesized that, as long as mechanical power is kept below a safe threshold, high V T should not be injurious. The present study aimed to investigate the impact of different V T levels and respiratory rates (RR) on lung function, diffuse alveolar damage (DAD), alveolar ultrastructure, and expression of genes related to inflammation [interleukin (IL)-6], alveolar stretch (amphiregulin), epithelial [club cell secretory protein (CC)16] and endothelial [intercellular adhesion molecule (ICAM)-1] cell injury, and extracellular matrix damage [syndecan-1, decorin, and metalloproteinase (MMP)-9] in experimental acute respiratory distress syndrome (ARDS) under low-power mechanical ventilation. Twenty-eight Wistar rats received Escherichia coli lipopolysaccharide intratracheally. After 24 h, 21 animals were randomly assigned to ventilation (2 h) with low mechanical power at three different V T levels ( n = 7/group): (1) V T = 6 mL/kg and RR adjusted to normocapnia; (2) V T = 13 mL/kg; and 3) V T = 22 mL/kg. In the second and third groups, RR was adjusted to yield low mechanical power comparable to that of the first group. Mechanical power was calculated as [(Δ[Formula: see text]/Est, L )/2]× RR (ΔP, L = transpulmonary driving pressure, Est, L = static lung elastance). Seven rats were not mechanically ventilated (NV) and were used for molecular biology analysis. Mechanical power was comparable among groups, while V T gradually increased. ΔP, L and mechanical energy were higher in V T = 22 mL/kg than V T = 6 mL/kg and V T = 13 mL/kg ( p < 0.001 for both). Accordingly, DAD score increased in V T = 22 mL/kg compared to V T = 6 mL/kg and V T = 13 mL/kg [23(18.5-24.75) vs. 16(12-17.75) and 16(13.25-18), p < 0.05, respectively]. V T = 22 mL/kg was associated with higher IL-6, amphiregulin, CC16, MMP-9, and syndecan-1 mRNA expression and lower decorin expression than V T = 6 mL/kg. Multiple linear regression analyses indicated that V T was able to predict changes in IL-6 and CC16, whereas ΔP, L predicted pHa, oxygenation, amphiregulin, and syndecan-1 expression. In the model of ARDS used herein, even at low mechanical power, high V T resulted in VILI. V T control seems to be more important than RR control to mitigate VILI.

Efficacy of prone position in acute respiratory distress syndrome patients: A pathophysiology-based review

PubMed Central

Koulouras, Vasilios; Papathanakos, Georgios; Papathanasiou, Athanasios; Nakos, Georgios

2016-01-01

Acute respiratory distress syndrome (ARDS) is a syndrome with heterogeneous underlying pathological processes. It represents a common clinical problem in intensive care unit patients and it is characterized by high mortality. The mainstay of treatment for ARDS is lung protective ventilation with low tidal volumes and positive end-expiratory pressure sufficient for alveolar recruitment. Prone positioning is a supplementary strategy available in managing patients with ARDS. It was first described 40 years ago and it proves to be in alignment with two major ARDS pathophysiological lung models; the “sponge lung” - and the “shape matching” -model. Current evidence strongly supports that prone positioning has beneficial effects on gas exchange, respiratory mechanics, lung protection and hemodynamics as it redistributes transpulmonary pressure, stress and strain throughout the lung and unloads the right ventricle. The factors that individually influence the time course of alveolar recruitment and the improvement in oxygenation during prone positioning have not been well characterized. Although patients’ response to prone positioning is quite variable and hard to predict, large randomized trials and recent meta-analyses show that prone position in conjunction with a lung-protective strategy, when performed early and in sufficient duration, may improve survival in patients with ARDS. This pathophysiology-based review and recent clinical evidence strongly support the use of prone positioning in the early management of severe ARDS systematically and not as a rescue maneuver or a last-ditch effort. PMID:27152255

Effect of dobutamine on extravascular lung water index, ventilator function, and perfusion parameters in acute respiratory distress syndrome associated with septic shock.

PubMed

Zhou, Min; Dai, Ji; Du, Min; Wang, Wei; Guo, Changxing; Wang, Yi; Tang, Rui; Xu, Fengling; Rao, Zhuqing; Sun, Gengyun

2016-08-01

The role of dobutamine in the relief of pulmonary edema during septic shock-induced acute respiratory distress syndrome (ARDS) remains undetermined, due to a lack of controllable and quantitative clinical studies. Our objective was to assess the potential effects of dobutamine on extravascular lung water index (ELWI) in septic shock-induced ARDS, reflecting its importance in pulmonary edema. At the same time, ventilator function and perfusion parameters were evaluated. We designed a prospective, non-randomized, non-blinded, controlled study to compare the differences in PiCCO parameters after 6 h of constant dobutamine infusion (15 μg/kg/min), in the baseline parameters in 26 septic shock-related ARDS patients with cardiac index ≥ 2.5I/min/m(2) and hyperlactatemia. These patients (12 survivors/14 non-survivors) were monitored using the PiCCO catheter system within 48 h of onset of septic shock. The dynamic changes in ELWI, which is typically used for quantifying the extent of pulmonary edema, were evaluated, and the corresponding ventilator function and tissue perfusion parameters were also measured. Decreasing ELWI (p = 0.0376) was accompanied by significantly decreased SVRI (p < 0.0001). Despite a significant increase in cardiac output (p < 0.0001), no differences were found in ITBI or GEDI. Moreover, the required dose of norepinephrine was decreased (p = 0.0389), and urine output was increased (p = 0.0358), accompanied by stabilized lactacidemia and MAP. Additionally, airway pressure was moderately improved. During the early stage of septic shock-induced ARDS, dobutamine treatment demonstrated a beneficial effect by relieving pulmonary edema in patients, without a negative elevation in preload or hemodynamics, which might account for the improvements in ventilator function and tissue hypoperfusion.

Geo-economic variations in epidemiology, patterns of care, and outcomes in patients with acute respiratory distress syndrome: insights from the LUNG SAFE prospective cohort study.

PubMed

Laffey, John G; Madotto, Fabiana; Bellani, Giacomo; Pham, Tài; Fan, Eddy; Brochard, Laurent; Amin, Pravin; Arabi, Yaseen; Bajwa, Ednan K; Bruhn, Alejandro; Cerny, Vladimir; Clarkson, Kevin; Heunks, Leo; Kurahashi, Kiyoyasu; Laake, Jon Henrik; Lorente, Jose A; McNamee, Lia; Nin, Nicolas; Palo, Jose Emmanuel; Piquilloud, Lise; Qiu, Haibo; Jiménez, Juan Ignacio Silesky; Esteban, Andres; McAuley, Daniel F; van Haren, Frank; Ranieri, Marco; Rubenfeld, Gordon; Wrigge, Hermann; Slutsky, Arthur S; Pesenti, Antonio

2017-08-01

Little information is available about the geo-economic variations in demographics, management, and outcomes of patients with acute respiratory distress syndrome (ARDS). We aimed to characterise the effect of these geo-economic variations in patients enrolled in the Large Observational Study to Understand the Global Impact of Severe Acute Respiratory Failure (LUNG SAFE). LUNG SAFE was done during 4 consecutive weeks in winter, 2014, in a convenience sample of 459 intensive-care units in 50 countries across six continents. Inclusion criteria were admission to a participating intensive-care unit (including transfers) within the enrolment window and receipt of invasive or non-invasive ventilation. One of the trial's secondary aims was to characterise variations in the demographics, management, and outcome of patients with ARDS. We used the 2016 World Bank countries classification to define three major geo-economic groupings, namely European high-income countries (Europe-High), high-income countries in the rest of the world (rWORLD-High), and middle-income countries (Middle). We compared patient outcomes across these three groupings. LUNG SAFE is registered with ClinicalTrials.gov, number NCT02010073. Of the 2813 patients enrolled in LUNG SAFE who fulfilled ARDS criteria on day 1 or 2, 1521 (54%) were recruited from Europe-High, 746 (27%) from rWORLD-High, and 546 (19%) from Middle countries. We noted significant geographical variations in demographics, risk factors for ARDS, and comorbid diseases. The proportion of patients with severe ARDS or with ratios of the partial pressure of arterial oxygen (PaO 2 ) to the fractional concentration of oxygen in inspired air (F i O 2 ) less than 150 was significantly lower in rWORLD-High countries than in the two other regions. Use of prone positioning and neuromuscular blockade was significantly more common in Europe-High countries than in the other two regions. Adjusted duration of invasive mechanical ventilation and length of stay in the intensive-care unit were significantly shorter in patients in rWORLD-High countries than in Europe-High or Middle countries. High gross national income per person was associated with increased survival in ARDS; hospital survival was significantly lower in Middle countries than in Europe-High or rWORLD-High countries. Important geo-economic differences exist in the severity, clinician recognition, and management of ARDS, and in patients' outcomes. Income per person and outcomes in ARDS are independently associated. European Society of Intensive Care Medicine, St Michael's Hospital, University of Milan-Bicocca. Copyright © 2017 Elsevier Ltd. All rights reserved.

Variability in usual care mechanical ventilation for pediatric acute lung injury: the potential benefit of a lung protective computer protocol.

PubMed

Khemani, Robinder G; Sward, Katherine; Morris, Alan; Dean, J Michael; Newth, Christopher J L

2011-11-01

Although pediatric intensivists claim to embrace lung protective ventilation for acute lung injury (ALI), ventilator management is variable. We describe ventilator changes clinicians made for children with hypoxemic respiratory failure, and evaluate the potential acceptability of a pediatric ventilation protocol. This was a retrospective cohort study performed in a tertiary care pediatric intensive care unit (PICU). The study period was from January 2000 to July 2007. We included mechanically ventilated children with PaO(2)/FiO(2) (P/F) ratio less than 300. We assessed variability in ventilator management by evaluating actual changes to ventilator settings after an arterial blood gas (ABG). We evaluated the potential acceptability of a pediatric mechanical ventilation protocol we adapted from National Institutes of Health/National Heart, Lung, and Blood Institute (NIH/NHLBI) Acute Respiratory Distress Syndrome (ARDS) Network protocols by comparing actual practice changes in ventilator settings to changes that would have been recommended by the protocol. A total of 2,719 ABGs from 402 patients were associated with 6,017 ventilator settings. Clinicians infrequently decreased FiO(2), even when the PaO(2) was high (>68 mmHg). The protocol would have recommended more positive end expiratory pressure (PEEP) than was used in actual practice 42% of the time in the mid PaO(2) range (55-68 mmHg) and 67% of the time in the low PaO(2) range (<55 mmHg). Clinicians often made no change to either peak inspiratory pressure (PIP) or ventilator rate (VR) when the protocol would have recommended a change, even when the pH was greater than 7.45 with PIP at least 35 cmH(2)O. There may be lost opportunities to minimize potentially injurious ventilator settings for children with ALI. A reproducible pediatric mechanical ventilation protocol could prompt clinicians to make ventilator changes that are consistent with lung protective ventilation.

Noninvasive ventilation for patients with acute lung injury or acute respiratory distress syndrome.

PubMed

Nava, Stefano; Schreiber, Ania; Domenighetti, Guido

2011-10-01

Few studies have been performed on noninvasive ventilation (NIV) to treat hypoxic acute respiratory failure in patients with acute lung injury (ALI) or acute respiratory distress syndrome (ARDS). The outcomes of these patients, for whom endotracheal intubation is not mandatory, depend on the degree of hypoxia, the presence of comorbidities and complications, and their illness severity. The use of NIV as an alternative to invasive ventilation in severely hypoxemic patients with ARDS (ie, P(aO(2))/F(IO(2)) < 200) is not generally advisable and should be limited to hemodynamically stable patients who can be closely monitored in an intensive care unit by highly skilled staff. Early NIV application may be extremely helpful in immunocompromised patients with pulmonary infiltrates, in whom intubation dramatically increases the risk of infection, pneumonia, and death. The use of NIV in patients with severe acute respiratory syndrome and other airborne diseases has generated debate, despite encouraging clinical results, mainly because of safety issues. Overall, the high rate of NIV failure suggests a cautious approach to NIV use in patients with ALI/ARDS, including early initiation, intensive monitoring, and prompt intubation if signs of NIV failure emerge.

Ventilatory strategies and supportive care in acute respiratory distress syndrome.

PubMed

Luks, Andrew M

2013-11-01

While antiviral therapy is an important component of care in patients with the acute respiratory distress syndrome (ARDS) following influenza infection, it is not sufficient to ensure good outcomes, and additional measures are usually necessary. Patients usually receive high levels of supplemental oxygen to counteract the hypoxemia resulting from severe gas exchange abnormalities. Many patients also receive invasive mechanical ventilation for support for oxygenation, while in resource-poor settings, supplemental oxygen via face mask may be the only available intervention. Patients with ARDS receiving mechanical ventilation should receive lung-protective ventilation, whereby tidal volume is decreased to 6 ml/kg of their predicted weight and distending pressures are maintained ≤ 30 cm H2 O, as well as increased inspired oxygen concentrations and positive end-expiratory pressure (PEEP) to prevent atelectasis and support oxygenation. While these measures are sufficient in most patients, a minority develop refractory hypoxemia and may receive additional therapies, including prone positioning, inhaled vasodilators, extracorporeal membrane oxygenation, recruitment maneuvers followed by high PEEP, and neuromuscular blockade, although recent data suggest that this last option may be warranted earlier in the clinical course before development of refractory hypoxemia. Application of these "rescue strategies" is complicated by the lack of guidance in the literature regarding implementation. While much attention is devoted to these strategies, clinicians must not lose sight of simple interventions that affect patient outcomes including head of bed elevation, prophylaxis against venous thromboembolism and gastrointestinal bleeding, judicious use of fluids in the post-resuscitative phase, and a protocol-based approach to sedation and spontaneous breathing trials. © 2013 Blackwell Publishing Ltd.

Low-Tidal-Volume Ventilation in the Acute Respiratory Distress Syndrome

PubMed Central

Malhotra, Atul

2008-01-01

A 55-year-old man who is 178 cm tall and weighs 95 kg is hospitalized with community-acquired pneumonia and progressively severe dyspnea. His arterial oxygen saturation while breathing 100% oxygen through a face mask is 76%; a chest radiograph shows diffuse alveolar infiltrates with air bronchograms. He is intubated and receives mechanical ventilation; ventilator settings include a tidal volume of 1000 ml, a positive end-expiratory pressure (PEEP) of 5 cm of water, and a fraction of inspired oxygen (FiO2) of 0.8. With these settings, peak airway pressure is 50 to 60 cm of water, plateau airway pressure is 38 cm of water, partial pressure of arterial oxygen is 120 mm Hg, partial pressure of carbon dioxide is 37 mm Hg, and arterial blood pH is 7.47. The diagnosis of the acute respiratory distress syndrome (ARDS) is made. An intensive care specialist evaluates the patient and recommends changing the current ventilator settings and implementing a low-tidal-volume ventilation strategy. PMID:17855672

Difficulties in modelling ARDS (2017 Grover Conference Series).

PubMed

Uhlig, Stefan; Kuebler, Wolfgang M

2018-01-01

Fifty years after the first description of acute respiratory distress syndrome (ARDS), none of the many positive drug studies in animal models have been confirmed in clinical trials and translated into clinical practice. This bleak outcome of so many animal experiments shows how difficult it is to model ARDS. Lungs from patients are characterized by hyperinflammation, permeability edema, and hypoxemia; accordingly, this is what most models aim to reproduce. However, in animal models it is very easy to cause inflammation in the lungs, but difficult to cause hypoxemia. Often - and not unlike in patients - models with hypoxemia are accompanied by cardiovascular failure that necessitates fluid support and ventilation, raising the question as to the role of intensive care measures in models of ARDS. In our opinion, there are two major arguments in favor of modelling intensive care medicine in models of ARDS: (1) preventing death from shock; and (2) modelling ventilation and other ICU measures as a second hit. The preferable predictive endpoints in any model of ARDS remain unclear. At present, the best recommendation is to use endpoints that can be compared across studies (i.e. PaO 2 /FiO 2 ratio, compliance, wet-to-dry weight ratio) rather than percentage data. Another important and often overlooked issue is the fact that the thermoneutral environmental temperatures for mice and rats are 30℃ and 28℃, respectively; thus, at room temperature (20-22℃) they suffer from cold stress with the associated significant metabolic changes. While, by definition, any model is an abstraction, we suggest that clinically relevant models of ARDS will have to closer recapitulate important properties of the disease while taking into account species-specific confounders.

Clinical review: Exogenous surfactant therapy for acute lung injury/acute respiratory distress syndrome - where do we go from here?

PubMed Central

2012-01-01

Acute lung injury and acute respiratory distress syndrome (ARDS) are characterised by severe hypoxemic respiratory failure and poor lung compliance. Despite advances in clinical management, morbidity and mortality remains high. Supportive measures including protective lung ventilation confer a survival advantage in patients with ARDS, but management is otherwise limited by the lack of effective pharmacological therapies. Surfactant dysfunction with quantitative and qualitative abnormalities of both phospholipids and proteins are characteristic of patients with ARDS. Exogenous surfactant replacement in animal models of ARDS and neonatal respiratory distress syndrome shows consistent improvements in gas exchange and survival. However, whilst some adult studies have shown improved oxygenation, no survival benefit has been demonstrated to date. This lack of clinical efficacy may be related to disease heterogeneity (where treatment responders may be obscured by nonresponders), limited understanding of surfactant biology in patients or an absence of therapeutic effect in this population. Crucially, the mechanism of lung injury in neonates is different from that in ARDS: surfactant inhibition by plasma constituents is a typical feature of ARDS, whereas the primary pathology in neonates is the deficiency of surfactant material due to reduced synthesis. Absence of phenotypic characterisation of patients, the lack of an ideal natural surfactant material with adequate surfactant proteins, coupled with uncertainty about optimal timing, dosing and delivery method are some of the limitations of published surfactant replacement clinical trials. Recent advances in stable isotope labelling of surfactant phospholipids coupled with analytical methods using electrospray ionisation mass spectrometry enable highly specific molecular assessment of phospholipid subclasses and synthetic rates that can be utilised for phenotypic characterisation and individualisation of exogenous surfactant replacement therapy. Exploring the clinical benefit of such an approach should be a priority for future ARDS research. PMID:23171712

Temporal patterns of radiographic infiltration in severely traumatized patients with and without adult respiratory distress syndrome.

PubMed

Johnson, K S; Bishop, M H; Stephen, C M; Jorgens, J; Shoemaker, W C; Shori, S K; Ordog, G; Thadepalli, H; Appel, P L; Kram, H B

1994-05-01

We prospectively evaluated the patterns of pulmonary structural and functional changes in 100 consecutive surgical intensive care unit trauma patients who had (1) emergent major surgery, (2) a pelvic fracture, or (3) two or more major long bone fractures. For each patient, arterial blood gas measurements (ABGs), central venous pressure (CVP), pulmonary capillary occlusion pressure (PAOP), thoracic compliance, arterial oxygen tension/fraction of inspired oxygen (PAO2/FIO2), pulmonary venous admixture (Qs/Qt), and portable chest roentgenograms were sequentially tracked. The senior staff radiologist interpreted all chest roentgenograms. Pulmonary infiltration was quantitated in each of six fields using a scale ranging from 0 to 4, with 0 being no infiltration and 4 being the maximum. Adult respiratory distress syndrome (ARDS) was defined as follows: Qs/Qt > or = 20%, PAO2/FIO2 < 250 or both; dependence on mechanical ventilation for life support for > or = 24 hours; PAOP or CVP or both < 20 mm Hg; and thoracic compliance < 50 mL/cm H2O. Time zero (T0) the time of onset of ARDS, was defined as the time these criteria were met. Eighty-three of 100 study group patients had penetrating injuries, and 17 were admitted with blunt trauma. Fifty-one of 100 patients developed ARDS: 36 of 51 died. Only 4 of 49 (8%) patients without ARDS died. The injured lungs of patients with and without ARDS had similar amounts of infiltration over most measured time intervals. The noninjured lungs of the ARDS patients, however, had significantly greater infiltration than those without ARDS at T0 and over subsequent time intervals.(ABSTRACT TRUNCATED AT 250 WORDS)

Lung Injury Etiology and Other Factors Influencing the Relationship Between Dead-Space Fraction and Mortality in ARDS.

PubMed

Kallet, Richard H; Zhuo, Hanjing; Ho, Kelly; Lipnick, Michael S; Gomez, Antonio; Matthay, Michael A

2017-10-01

In ARDS, elevated pulmonary dead-space fraction (V D /V T ) is a particularly strong indicator of mortality risk. Whether the magnitude of V D /V T is modified by the underlying etiology of ARDS and whether this influences the strength of its association with mortality remains unknown. We sought to elucidate the impact of ARDS etiology on V D /V T and also to determine whether ARDS severity, as classified by the Berlin definition, has correspondence with changes in V D /V T . This single-center, retrospective, observational study (2010-2016) measured V D /V T in 685 subjects with ARDS as part of clinical management with lung-protective ventilation. Volumetric capnography was used to measure V D /V T with 99% of measurements occurring within 48 h of ARDS onset. Demographic information as well as illness severity scores and pulmonary mechanics data also were collected. Multivariate logistic regression modeling was done to assess the strength of association between V D /V T and mortality. V D /V T was elevated across etiologies, with aspiration and pneumonia having significantly higher V D /V T than non-pulmonary sepsis or trauma. Differences in the magnitude of V D /V T across etiologies did not necessarily correspond with mortality between etiologies. However, within each etiology grouping, V D /V T was significantly elevated in non-survivors versus survivors. The same results were found in both moderate and severe (but not mild) ARDS using the Berlin definition. In the final adjusted model, the strongest mortality risk was V D /V T , wherein the risk of death increased by 22% for every 0.05 increase in V D /V T . V D /V T magnitude varies by ARDS etiology, as does mortality. Only in mild ARDS does V D /V T fail to distinguish non-survivors from survivors. Nonetheless, V D /V T has the strongest association with mortality risk in those with ARDS. Copyright © 2017 by Daedalus Enterprises.

Worsening respiratory function in mechanically ventilated intensive care patients: feasibility and value of xenon-enhanced dual energy CT.

PubMed

Hoegl, Sandra; Meinel, Felix G; Thieme, Sven F; Johnson, Thorsten R C; Eickelberg, Oliver; Zwissler, Bernhard; Nikolaou, Konstantin

2013-03-01

To evaluate the feasibility and incremental diagnostic value of xenon-enhanced dual-energy CT in mechanically ventilated intensive care patients with worsening respiratory function. The study was performed in 13 mechanically ventilated patients with severe pulmonary conditions (acute respiratory distress syndrome (ARDS), n=5; status post lung transplantation, n=5; other, n=3) and declining respiratory function. CT scans were performed using a dual-source CT scanner at an expiratory xenon concentration of 30%. Both ventilation images (Xe-DECT) and standard CT images were reconstructed from a single CT scan. Findings were recorded for Xe-DECT and standard CT images separately. Ventilation defects on xenon images were matched to morphological findings on standard CT images and incremental diagnostic information of xenon ventilation images was recorded if present. Mean xenon consumption was 2.95 l per patient. No adverse events occurred under xenon inhalation. In the visual CT analysis, the Xe-DECT ventilation defects matched with pathologic changes in lung parenchyma seen in the standard CT images in all patients. Xe-DECT provided additional diagnostic findings in 4/13 patients. These included preserved ventilation despite early pneumonia (n=1), more confident discrimination between a large bulla and pneumothorax (n=1), detection of an airway-to-pneumothorax fistula (n=1) and exclusion of a suspected airway-to-mediastinum fistula (n=1). In all 4 patients, the additional findings had a substantial impact on patients' management. Xenon-enhanced DECT is safely feasible and can add relevant diagnostic information in mechanically ventilated intensive care patients with worsening respiratory function. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Continuous distending pressure effects on variables contributing to oxygenation in healthy and ARDS model pigs during HFOV

NASA Astrophysics Data System (ADS)

Laviola, Marianna; Hajny, Ondrej; Roubik, Karel

2014-10-01

High frequency oscillatory ventilation (HFOV) is an alternative mode of mechanical ventilation. HFOV has been shown to provide adequate ventilation and oxygenation in acute respiratory distress syndrome (ARDS) patients and may represent an effective lung-protective ventilation in patients where conventional ventilation is failing. The aim of this study is to evaluate effects of continuous distending pressure (CDP) on variables that contribute to the oxygenation in healthy and ARDS lung model pigs. Methods. In order to simulate a lung disease, lung injury was induced by lavage with normal saline with detergent in three pigs. HFOV ventilation was applied before and after the lung lavage. CDP was stepwise increased by 2 cmH2O, until the maximum CDP (before the lung lavage 32 cmH2O and after the lung lavage 42 cmH2O) and then it was stepwise decreased by 2 cmH2O to the initial value. In this paper we analyzed the following parameters acquired during our experiments: partial pressure of oxygen in arterial blood (PaO2), cardiac output (CO) and mixed venous blood oxygen saturation (SvO2). In order to find how both PaO2 and CO affected SvO2 during the increase of CDP before and after lavage, a nonlinear regression fitting of the response in SvO2 on the predictors (PaO2 and CO) was implemented. Results. Before the lavage, with increasing of CDP, PaO2 remained constant, CO strongly decreased and SvO2 slightly decreased. After the lavage, with increasing of CDP, PaO2 strongly increased, CO decreased and SvO2 increased. So, development of SvO2 followed the PaO2 and CO trends. Changes in PaO2 and CO occur at decisive CDP step and it was much higher after the lung lavage compared to the healthy lungs. The implemented nonlinear model gives a good goodness of fitting in all three pigs. The values of PaO2 and CO estimated coefficients changed at the same decisive step of CDP identified by the trends. Also the algorithm identified a CDP step much higher after the lung lavage. Conclusions. The novelty of this study consists of the implementing of a model that allows to predict how PaO2 and CO affect SvO2. It is possible to identify a certain level of CDP (higher in ARDS model pigs) at which the contribution of PaO2 and CO to SvO2 course changes their weights. Above this value, PaO2 plays a major role in SvO2 developments. This is in concordance with the clinical experience that HFOV is suitable for patient with more severe lung diseases when much higher CDP levels are required to assure an adequate oxygenation.

Characteristics and outcome of mechanically ventilated patients with 2009 H1N1 influenza in Bosnia and Herzegovina and Serbia: impact of newly established multidisciplinary intensive care units.

PubMed

Kojicić, Marija; Kovacević, Pedja; Bajramović, Nermina; Batranović, Uros; Vidović, Jadranka; Aganović, Kenana; Gavrilović, Srdjan; Zlojutro, Biljana; Thiery, Guillaume

2012-12-01

To describe characteristics and outcome of mechanically ventilated patients admitted to three newly established intensive care units (ICU) in Bosnia-Herzegovina and Serbia for 2009 H1N1 influenza infection. The retrospective observational study included all mechanically ventilated adult patients of three university-affiliated hospitals between November 1, 2009 and March 1 2010 who had 2009 H1N1 influenza infection confirmed by real-time reverse transcriptase-polymerase-chain-reaction (RT-PCR) from nasopharyngeal swab specimens and respiratory secretions. The study included 50 patients, 31 male (62%), aged 43±13 years. Median time from hospital to ICU admission was 1 day (range 1-2). Sixteen patients (30%) presented with one or more chronic medical condition: 8 (16%) with chronic lung disease, 5 (10%) with chronic heart failure, and 3 (6%) with diabetes mellitus. Thirty-two (64%) were obese. Forty-eight patients (96%) experienced acute respiratory distress syndrome (ARDS), 28 (56%) septic shock, and 27 (54%) multiorgan failure. Forty-five patients (90%) were intubated and mechanically ventilated, 5 received non-invasive mechanical ventilation, 7 (14%) high-frequency oscillatory ventilation, and 7 (14%) renal replacement therapy. The median duration of mechanical ventilation was 7 (4-14) days. Hospital mortality was 52%. Influenza 2009 H1N1 infection in three southeast European ICUs affected predominantly healthy young patients and was associated with rapid deterioration after hospital admission and severe respiratory and multiorgan failure. These emerging ICUs provided contemporary ICU services, resulting in case-fatality rate comparable to reports from well-established ICU settings.

Clinical resolution in patients with suspicion of ventilator-associated pneumonia: a cohort study comparing patients with and without acute respiratory distress syndrome.

PubMed

Vidaur, Loreto; Gualis, Belen; Rodriguez, Alejandro; Ramírez, Rafael; Sandiumenge, Alberto; Sirgo, Gonzalo; Diaz, Emili; Rello, Jordi

2005-06-01

To determine the pattern of resolution of classic infectious and respiratory variables in patients with ventilator-associated pneumonia (VAP) and appropriate empirical therapy, depending on the presence of acute respiratory distress syndrome (ARDS). A secondary objective was to identify clinical variables that might be useful for monitoring response to therapy. Prospective, observational cohort study. Medical-surgical intensive care unit. Seventy-five episodes of VAP without ARDS were identified and compared with 20 episodes with ARDS at VAP onset. Six episodes were excluded due to in vitro resistance to the initial antibiotic choice and six due to death in the first 72 hrs. None. Resolution of fever, Pao2/Fio2 >250 mm Hg, and white blood cell count in episodes of VAP were present in 73.3%, 74.7%, and 53.3% of patients after 3 days of therapy. Indeed, >50% of episodes with the absence of ARDS presented resolution of fever and Pao2/Fio2 >250 within the first day of therapy. In contrast, resolution of radiologic opacities and clearance of secretions (median of 14 and 6 days of resolution) were late events. In patients with ARDS, resolution of fever remained the earliest variable. However, similar to Pao2/Fio2 250 and white blood cell count, fever showed a significantly worse pattern after 3 days of therapy: 45%, 15% and 25%, respectively. Radiologic resolution was an extremely poor indicator, being present in only 10% of ARDS patients after 15 days of follow-up. Failure to improve after 48 hrs of therapy was documented in 65% of ARDS patients and 14.7% of controls (p < .05). Measures of oxygenation and core temperature can help physicians to individualize and shorten the duration of antibiotic therapy in VAP episodes. ARDS patients with VAP take twice as long to resolve fever, whereas hypoxemia should be ignored in defining resolution in this subset.

Raised protein levels and altered cellular expression of factor VII activating protease (FSAP) in the lungs of patients with acute respiratory distress syndrome (ARDS)

PubMed Central

Wygrecka, Malgorzata; Markart, Philipp; Fink, Ludger; Guenther, Andreas; Preissner, Klaus T

2007-01-01

Background The acute respiratory distress syndrome (ARDS) is characterised by inflammation of the lung parenchyma and changes in alveolar haemostasis with extravascular fibrin deposition. Factor VII activating protease (FSAP) is a recently described serine protease in plasma and tissues known to be involved in haemostasis, cell proliferation and migration. Methods The level of FSAP protein expression was examined by western blotting/ELISA/immunohistochemistry and its activity was investigated by coagulation/fibrinolysis assays in plasma, bronchoalveolar lavage (BAL) fluid and lung tissue of mechanically ventilated patients with early ARDS and compared with patients with cardiogenic pulmonary oedema and healthy controls. Cell culture experiments were performed to assess the influence of different inflammatory stimuli on FSAP expression by various cell populations of the lung. Results FSAP protein level and activity were markedly increased in the plasma and BAL fluid of patients with ARDS with a significant contribution to the increased alveolar procoagulant activity. Immunoreactivity for FSAP was observed in alveolar macrophages, bronchial epithelial and endothelial cells of lungs of patients with ARDS, while in controls the immunoreactivity for FSAP was restricted to alveolar macrophages. Only a low basal level of FSAP expression was detected in these cell populations. However, FSAP‐specific mRNA expression was induced by lipopolysaccharide and interleukin‐8 in human lung microvascular endothelial cells and in bronchial epithelial cells. FSAP was also found to be taken up by alveolar macrophages and degraded within the lysosomal compartment. Conclusions Increased levels of FSAP and an altered cellular expression pattern are found in the lungs of patients with ARDS. This may represent a novel pathological mechanism which contributes to pulmonary extravascular fibrin deposition and may also modulate inflammation in the acutely injured lung via haemostasis‐independent cellular activities of FSAP. PMID:17483138

Analysis of discrete and continuous distributions of ventilatory time constants from dynamic computed tomography

NASA Astrophysics Data System (ADS)

Doebrich, Marcus; Markstaller, Klaus; Karmrodt, Jens; Kauczor, Hans-Ulrich; Eberle, Balthasar; Weiler, Norbert; Thelen, Manfred; Schreiber, Wolfgang G.

2005-04-01

In this study, an algorithm was developed to measure the distribution of pulmonary time constants (TCs) from dynamic computed tomography (CT) data sets during a sudden airway pressure step up. Simulations with synthetic data were performed to test the methodology as well as the influence of experimental noise. Furthermore the algorithm was applied to in vivo data. In five pigs sudden changes in airway pressure were imposed during dynamic CT acquisition in healthy lungs and in a saline lavage ARDS model. The fractional gas content in the imaged slice (FGC) was calculated by density measurements for each CT image. Temporal variations of the FGC were analysed assuming a model with a continuous distribution of exponentially decaying time constants. The simulations proved the feasibility of the method. The influence of experimental noise could be well evaluated. Analysis of the in vivo data showed that in healthy lungs ventilation processes can be more likely characterized by discrete TCs whereas in ARDS lungs continuous distributions of TCs are observed. The temporal behaviour of lung inflation and deflation can be characterized objectively using the described new methodology. This study indicates that continuous distributions of TCs reflect lung ventilation mechanics more accurately compared to discrete TCs.

Acute respiratory distress syndrome and septic shock in a cat with disseminated toxoplasmosis.

PubMed

Evans, Natashia A; Walker, Julie M; Manchester, Alison C; Bach, Jonathan F

2017-07-01

To describe acute respiratory distress syndrome (ARDS) and septic shock in a cat with disseminated toxoplasmosis. A 2-year-old neutered male domestic shorthair cat was presented for acute respiratory distress. At the time of presentation it had been receiving cyclosporine for treatment of eosinophilic dermatitis. Thoracic radiographs revealed severe mixed nodular interstitial and alveolar patterns. An endotracheal wash was performed, which confirmed a diagnosis of pulmonary toxoplasmosis. Despite initial treatment with oxygen supplementation and intravenous clindamycin, the cat developed refractory hypoxemia and hypotension requiring mechanical ventilation and vasopressor support within 24 hours of hospital admission. Cardiac arrest occurred 56 hours after admission. Necropsy was performed and histopathology revealed protozoal organisms disseminated throughout the heart, lungs, liver, and brain. The clinical and necropsy findings presented here are consistent with ARDS secondary to disseminated toxoplasmosis in a cat. This is the first detailed report of ARDS in a cat. Toxoplasma titer testing and antimicrobial prophylaxis should be considered in cats prior to immunosuppressive treatment with cyclosporine. © Veterinary Emergency and Critical Care Society 2017.

Low-flow CO₂ removal integrated into a renal-replacement circuit can reduce acidosis and decrease vasopressor requirements.

PubMed

Forster, Christian; Schriewer, Jens; John, Stefan; Eckardt, Kai-Uwe; Willam, Carsten

2013-07-24

Lung-protective ventilation in patients with ARDS and multiorgan failure, including renal failure, is often paralleled with a combined respiratory and metabolic acidosis. We assessed the effectiveness of a hollow-fiber gas exchanger integrated into a conventional renal-replacement circuit on CO₂ removal, acidosis, and hemodynamics. In ten ventilated critically ill patients with ARDS and AKI undergoing renal- and respiratory-replacement therapy, effects of low-flow CO₂ removal on respiratory acidosis compensation were tested by using a hollow-fiber gas exchanger added to the renal-replacement circuit. This was an observational study on safety, CO₂-removal capacity, effects on pH, ventilator settings, and hemodynamics. CO₂ elimination in the low-flow circuit was safe and was well tolerated by all patients. After 4 hours of treatment, a mean reduction of 17.3 mm Hg (-28.1%) pCO₂ was observed, in line with an increase in pH. In hemodynamically instable patients, low-flow CO₂ elimination was paralleled by hemodynamic improvement, with an average reduction of vasopressors of 65% in five of six catecholamine-dependent patients during the first 24 hours. Because no further catheters are needed, besides those for renal replacement, the implementation of a hollow-fiber gas exchanger in a renal circuit could be an attractive therapeutic tool with only a little additional trauma for patients with mild to moderate ARDS undergoing invasive ventilation with concomitant respiratory acidosis, as long as no severe oxygenation defects indicate ECMO therapy.

Respiratory Dialysis: Reduction in Dependence on Mechanical Ventilation by Venovenous Extracorporeal CO2 Removal

DTIC Science & Technology

2011-06-01

deaths in the United States (1). Acute lung injury and ARDS are also sig- nificant combat casualty care problems stemming from trauma and resuscitation ...the respiratory function of the natural lung. ECMO was introduced for treatment of neonatal respiratory failure (39). ECMO is currently used in adults...Toomasian J, et al: Extracorporeal membrane oxygenation (ECMO) in neonatal respiratory failure. 100 cases. Ann Surg 1986; 204:236–245 40. Peek GJ

An attempt to validate the modification of the American-European consensus definition of acute lung injury/acute respiratory distress syndrome by the Berlin definition in a university hospital.

PubMed

Hernu, R; Wallet, F; Thiollière, F; Martin, O; Richard, J C; Schmitt, Z; Wallon, G; Delannoy, B; Rimmelé, T; Démaret, C; Magnin, C; Vallin, H; Lepape, A; Baboi, L; Argaud, L; Piriou, V; Allaouchiche, B; Aubrun, F; Bastien, O; Lehot, J J; Ayzac, L; Guérin, C

2013-12-01

The Berlin definition for acute respiratory distress syndrome (ARDS) is a new proposal for changing the American-European consensus definition but has not been assessed prospectively as yet. In the present study, we aimed to determine (1) the prevalence and incidence of ARDS with both definitions, and (2) the initial characteristics of patients with ARDS and 28-day mortality with the Berlin definition. We performed a 6-month prospective observational study in the ten adult ICUs affiliated to the Public University Hospital in Lyon, France, from March to September 2012. Patients under invasive or noninvasive mechanical ventilation, with PaO2/FiO2 <300 mmHg regardless of the positive end-expiratory pressure (PEEP) level, and acute onset of new or increased bilateral infiltrates or opacities on chest X-ray were screened from ICU admission up to discharge. Patients with cardiogenic pulmonary edema were excluded. Patients were further classified into specific categories by using the American-European Consensus Conference and the Berlin definition criteria. The complete data set was measured at the time of inclusion. Patient outcome was measured at day 28 after inclusion. During the study period 3,504 patients were admitted and 278 fulfilled the American-European Consensus Conference criteria. Among them, 18 (6.5 %) did not comply with the Berlin criterion PEEP ≥ 5 cmH2O and 20 (7.2 %) had PaO2/FiO2 ratio ≤200 while on noninvasive ventilation. By using the Berlin definition in the remaining 240 patients (n = 42 mild, n = 123 moderate, n = 75 severe), the overall prevalence was 6.85 % and it was 1.20, 3.51, and 2.14 % for mild, moderate, and severe ARDS, respectively (P > 0.05 between the three groups). The incidence of ARDS amounted to 32 per 100,000 population per year, with values for mild, moderate, and severe ARDS of 5.6, 16.3, and 10 per 100,000 population per year, respectively (P < 0.05 between the three groups). The 28-day mortality was 35.0 %. It amounted to 30.9 % in mild, 27.9 % in moderate, and 49.3 % in severe categories (P < 0.01 between mild or moderate and severe, P = 0.70 between mild and moderate). In the Cox proportional hazard regression analysis ARDS stage was not significantly associated with patient death at day 28. The present study did not validate the Berlin definition of ARDS. Neither the stratification by severity nor the PaO2/FiO2 at study entry was independently associated with mortality.

Alveolar fibrin formation caused by enhanced procoagulant and depressed fibrinolytic capacities in severe pneumonia. Comparison with the acute respiratory distress syndrome.

PubMed

Günther, A; Mosavi, P; Heinemann, S; Ruppert, C; Muth, H; Markart, P; Grimminger, F; Walmrath, D; Temmesfeld-Wollbrück, B; Seeger, W

2000-02-01

Changes in the alveolar hemostatic balance in severe pneumonia were compared with those in the acute respiratory distress syndrome (ARDS). Analysis was performed in bronchoalveolar lavage fluids (BALF) of patients with ARDS triggered by nonpulmonary underlying events in the absence of lung infection (ARDS; n = 25), pneumonia demanding mechanical ventilation (PNEU-vent; n = 114), spontaneously breathing patients with pneumonia (PNEU-spon; n = 40), and ARDS in combination with lung infection (ARDS+PNEU; n = 43); comparison with healthy control subjects (n = 35) was performed. In all groups of patients, BALF total procoagulant activity was increased by nearly two orders of magnitude, being largely attributable to the tissue factor pathway of coagulation. Concomitantly, markedly reduced overall fibrinolytic capacity (fibrin plate assay) was noted in the lavage fluids of all patients. BALF levels of urokinase-type plasminogen activator were significantly reduced throughout, whereas the lavage concentrations of tissue-type plasminogen activator did not differ from those in control subjects. In addition, markedly enhanced levels of plasminogen activator- inhibitor I and alpha(2)-antiplasmin were noted in ARDS, ARDS+PNEU, and PNEU-vent, but not in PNEU-spon. In all groups of patients, the changes in the lavage enzymatic activities were paralleled by manifold increased BALF concentrations of fibrinopeptide A and D-dimer, reflecting in vivo coagulation processes. Within the overall number of patients with pneumonia, changes in the alveolar hemostatic balance were more prominent in alveolar and interstitial pneumonia than in bronchopneumonia. Acute inflammatory lung injury, whether triggered by nonpulmonary systemic events or primary lung infection, is thus consistently characterized by both enhanced procoagulant and depressed fibrinolytic activities in the alveolar lining layer, with the appearance of fibrin formation in this compartment. Profile and extent of changes in severe pneumonia demanding respirator therapy are virtually identical to those in ARDS, whereas somewhat less prominent alterations of the alveolar hemostatic balance are noted in spontaneously breathing patients with pneumonia.

Lower airways inflammation in patients with ARDS measured using endotracheal aspirates: a pilot study.

PubMed

Spadaro, Savino; Kozhevnikova, Iryna; Casolari, Paolo; Ruggeri, Paolo; Bellini, Tiziana; Ragazzi, Riccardo; Barbieri, Federica; Marangoni, Elisabetta; Caramori, Gaetano; Volta, Carlo Alberto

2017-01-01

Our knowledge of acute respiratory distress syndrome (ARDS) pathogenesis is incomplete. The goal of this pilot study is to investigate the feasibility of measuring lower airways inflammation in patients with ARDS using repeated endotracheal aspirates (ETAs). ETAs were obtained within 24 hours by intensive care unit admission from 25 mechanically ventilated patients with ARDS and 10 of them underwent a second ETA within 96 hours after the first sampling. In each sample, cell viability was assessed using trypan blue exclusion method and the total and differential cell counts were measured using Neubauer-improved cell counting chamber and cytospins stained with Diff-Quik. The median cell viability was 89 (IQR 80-93)%, with a median total cell count of 305 (IQR 130-1270)×10 3 /mL and a median macrophage, neutrophil, lymphocyte and eosinophil count, respectively, of 19.8 (IQR 5.4-71.6)×10 3 /mL; 279 (IQR 109-1213)×10 3 /mL; 0 (IQR 0-0.188)×10 3 /mL; 0 (IQR 0-1.050)×10 3 /mL. Eosinophil count in the ETA correlated with the number of blood eosinophils (r=0.4840, p=0.0142). Cell viability and total and differential cell counts were neither significantly different in the second ETA compared with the first ETA nor were unaffected by the presence or absence of bacteria in the blood and/or ETA, or by the ARDS aetiology, apart from the macrophage count which was significantly increased in patients with ARDS associated with acute pancreatitis compared with those associated with pneumonia (p=0.0143). ETA can be used to investigate the cellularity of the lower airways in patients with ARDS and it is an easy-to-perform and non-invasive procedure. Eosinophil counts in ETA and blood are significantly correlated. The number of macrophages in ETA may be affected by the aetiology of the ARDS.

Clinical Characteristics and Outcomes Are Similar in ARDS Diagnosed by Oxygen Saturation/Fio2 Ratio Compared With Pao2/Fio2 Ratio

PubMed Central

Janz, David R.; Shaver, Ciara M.; Bernard, Gordon R.; Bastarache, Julie A.; Ware, Lorraine B.

2015-01-01

BACKGROUND: Oxygen saturation as measured by pulse oximetry/Fio2 (SF) ratio is highly correlated with the Pao2/Fio2 (PF) ratio in patients with ARDS. However, it remains uncertain whether SF ratio can be substituted for PF ratio for diagnosis of ARDS and whether SF ratio might identify patients who are systemically different from patients diagnosed by PF ratio. METHODS: We conducted a secondary analysis of a large observational prospective cohort study. Patients were eligible if they were admitted to the medical ICU and fulfilled the Berlin definition of ARDS with hypoxemia criteria using either the standard PF threshold (PF ratio ≤ 300) or a previously published SF threshold (SF ratio ≤ 315). RESULTS: Of 362 patients with ARDS, 238 (66%) received a diagnosis by PF ratio and 124 (34%) by SF ratio. In a small group of patients who received diagnoses of ARDS by SF ratio who had arterial blood gas measurements on the same day (n = 10), the PF ratio did not meet ARDS criteria. There were no major differences in clinical characteristics or comorbidities between groups with the exception of APACHE (Acute Physiology and Chronic Health Evaluation) II scores, which were higher in the group diagnosed by PF ratio. However, this difference was no longer apparent when arterial blood gas-dependent variables (pH, Pao2) were removed from the APACHE II score. There were also no differences in clinical outcomes including duration of mechanical ventilation (mean, 7 days in both groups; P = .25), duration of ICU stay (mean, 10 days vs 9 days in PF ratio vs SF ratio; P = .26), or hospital mortality (36% in both groups, P = .9). CONCLUSIONS: Patients with ARDS diagnosed by SF ratio have very similar clinical characteristics and outcomes compared with patients diagnosed by PF ratio. These findings suggest that SF ratio could be considered as a diagnostic tool for early enrollment into clinical trials. PMID:26271028

Effect of enteral feeding with eicosapentaenoic acid, gamma-linolenic acid, and antioxidants in patients with acute respiratory distress syndrome. Enteral Nutrition in ARDS Study Group.

PubMed

Gadek, J E; DeMichele, S J; Karlstad, M D; Pacht, E R; Donahoe, M; Albertson, T E; Van Hoozen, C; Wennberg, A K; Nelson, J L; Noursalehi, M

1999-08-01

Recent studies in animal models of sepsis-induced acute respiratory distress syndrome (ARDS) have shown that a low-carbohydrate, high-fat diet combining the anti-inflammatory and vasodilatory properties of eicosapentaenoic acid (EPA; fish oil), gamma-linolenic acid (GLA; borage oil) (EPA+GLA), and antioxidants improves lung microvascular permeability, oxygenation, and cardiopulmonary function and reduces proinflammatory eicosanoid synthesis and lung inflammation. These findings suggest that enteral nutrition with EPA+GLA and antioxidants may reduce pulmonary inflammation and may improve oxygenation and clinical outcomes in patients with ARDS. Prospective, multicentered, double-blind, randomized controlled trial. Intensive care units of five academic and teaching hospitals in the United States. We enrolled 146 patients with ARDS (as defined by the American-European Consensus Conference) caused by sepsis/pneumonia, trauma, or aspiration injury in the study. Patients meeting entry criteria were randomized and continuously tube-fed either EPA+GLA or an isonitrogenous, isocaloric standard diet at a minimum caloric delivery of 75% of basal energy expenditure x 1.3 for at least 4-7 days. Arterial blood gases were measured, and ventilator settings were recorded at baseline and study days 4 and 7 to enable calculation of PaO2/FIO2, a measure of gas exchange. Pulmonary neutrophil recruitment was assessed by measuring the number of neutrophils and the total cell count in bronchoalveolar lavage fluid at the same time points. Clinical outcomes were recorded. Baseline characteristics of 98 evaluable patients revealed that key demographic, physiologic, and ventilatory variables were similar at entry between both groups. Multiple bronchoalveolar lavages revealed significant decreases (approximately 2.5-fold) in the number of total cells and neutrophils per mL of recovered lavage fluid during the study with EPA+GLA compared with patients fed the control diet. Significant improvements in oxygenation (PaO2/FIO2) from baseline to study days 4 and 7 with lower ventilation variables (FIO2, positive end-expiratory pressure, and minute ventilation) occurred in patients fed EPA+GLA compared with controls. Patients fed EPA+GLA required significantly fewer days of ventilatory support (11 vs. 16.3 days; p = .011), and had a decreased length of stay in the intensive care unit (12.8 vs. 17.5 days; p = .016) compared with controls. Only four of 51 (8%) patients fed EPA+GLA vs. 13 of 47 (28%) control patients developed a new organ failure during the study (p = .015). The beneficial effects of the EPA+GLA diet on pulmonary neutrophil recruitment, gas exchange, requirement for mechanical ventilation, length of intensive care unit stay, and the reduction of new organ failures suggest that this enteral nutrition formula would be a useful adjuvant therapy in the clinical management of patients with or at risk of developing ARDS.

Assessment of the optimal operating parameters during extracorporeal CO2 removal with the Abylcap® system.

PubMed

Eloot, Sunny; Peperstraete, Harlinde; De Somer, Filip; Hoste, Eric

2017-01-13

Lung protective ventilation is recommended in patients with acute respiratory distress syndrome (ARDS) needing mechanical ventilation. This can however be associated with hypercapnia and respiratory acidosis, such that extracorporeal CO2 removal (ECCO2R) can be applied. The aim of this study was to derive optimal operating parameters for the ECCO2R Abylcap® system (Bellco, Italy). We included 4 ARDS patients with a partial arterial oxygen tension over the fraction of inspired oxygen (PaO2/FiO2) lower than 150 mmHg, receiving lung-protective ventilation and treated with the Abylcap® via a double lumen 13.5-Fr dialysis catheter in the femoral vein. Every 24 hours during 5 consecutive days, blood was sampled at the Abylcap® inlet and outlet for different blood flows (QB:200-300-400 mL/min) with 100% O2 gas flow (QG) of 7 L/min, and for different QG (QG: 0.5-1-1.5-3-6-8 L/min) with QB400 mL/min. CO2 and O2 transfer remained constant over 5 days for a fixed QB. We found that, for a fixed QG of 7 L/min, CO2 transfer linearly and significantly increased with QB (i.e. from 58 ± 8 to 98 ± 16 mL/min for QB 200 to 400 mL/min). For a fixed QB of 400 mL/min, CO2 transfer non-linearly increased with QG (i.e. from 39 ± 9 to 98 ± 16 mL/min for QG 0.5 to 8 L/min) reaching a plateau at QG of 6 L/min. Hence, when using the Abylcap® ECCO2R in the treatment of ARDS patients the O2 flow should be at least 6 L/min while QB should be set at its maximum.

[The clinical effect of airway pressure release ventilation for acute lung injury/acute respiratory distress syndrome].

PubMed

Song, Shaohua; Tian, Huiyu; Yang, Xiufen; Hu, Zhenjie

2016-01-01

To evaluate the effect of airway pressure release ventilation (APRV) in patients with acute lung injury/acute respiratory distress syndrome (ALI/ARDS), to evaluate the extent of ventilator-induced lung injury (VILI), and to explore its possible mechanism. A prospective study was conducted in the Department of Critical Care Medicine of the First Hospital of Hebei Medical University from December 2010 to February 2012. The patients with ALI/ARDS were enrolled. They were randomly divided into two groups. The patients in APRV group were given APRV pattern, while those in control group were given lung protection ventilation, synchronized intermittent mandatory ventilation with positive end-expiratory pressure (SIMV+PEEP). All patients were treated with AVEA ventilator. The parameters such as airway peak pressure (Ppeak), mean airway pressure (Pmean), pulse oxygen saturation (SpO2), mean arterial pressure (MAP), heart rate (HR), central venous pressure (CVP), arterial blood gas, urine output (UO), the usage of sedation and muscle relaxation drugs were recorded. AVEA ventilator "turning point (Pflex) operation" was used to describe the quasi-static pressure volume curve (P-V curve). High and low inflection point (UIP, LIP) and triangular Pflex volume (Vdelta) were automatically measured and calculated. The ventilation parameters were set, and the 24-hour P-V curve was recorded again in order to be compared with subsequent results. Venous blood was collected before treatment, 24 hours and 48 hours after ventilation to measure lung surfactant protein D (SP-D) and large molecular mucus in saliva (KL-6) by enzyme linked immunosorbent assay (ELISA), and the correlation between the above two parameters and prognosis on 28 days was analyzed by multinomial logistic regression. Twenty-six patients with ALI/ARDS were enrolled, and 22 of them completed the test with 10 in APRV group and 12 in control group. The basic parameters and P-V curves between two groups were similar before the test. After 24 hours and 48 hours, mechanical ventilation was given in both groups. The patients' oxygenation was improved significantly, though there were no significant changes in hemodynamic parameters. The Pmean (cmH2O, 1 cmH2O = 0.098 kPa) in APRV group was significantly higher than that in control group (24 hours: 24.20±4.59 vs. 17.50±3.48, P < 0.01; 48 hours: 18.10±4.30 vs. 15.00±2.59, P < 0.05). After ventilation for 24 hours, the ratio of patients with increased Vdelta in APRV group was higher than that in control group (90% vs. 75%), but without statistical difference (P > 0.05). The SP-D level (μg/L) in serum in APRV group showed a tendency of increase (increased from 19.70±7.34 to 27.61±10.21, P < 0.05), in contrast there was a tendency of decrease in control group (decreased from 21.83±7.31 to 16.58±2.90, P > 0.05), the difference between the two groups was statistically significant (P < 0.05). After 48-hour ventilation, SP-D in APRV group was decreased, but no change was found in control group, and no significant difference was found as compared with that of the control group (16.45±8.17 vs. 17.20±4.59, P > 0.05). There was no significant difference in serum KL-6 between the two groups before and after ventilation. The SP-D and KL-6 levels in serum were unrelated with 28-day survival rate of the patients. The odds ratio (OR) of SP-D were 0.900 [95% confidence interval (95%CI) = 0.719-1.125], 1.054 (95%CI = 0.878-1.266), 1.143 (95%CI = 0.957-1.365), and the OR of KL-6 were 1.356 (95%CI = 0.668-2.754), 0.658 (95%CI = 0.161-2.685), 0.915 (95%CI = 0.350-2.394) before the test, 24 hours and 48 hours after ventilation (all P > 0.05). APRV was similar to lung protective ventilation strategy in oxygenation and improvements in the lung mechanics parameters. APRV with a higher Pmean can recruit alveolar more effectively, and it had no impact on hemo-dynamics, but might exacerbate VILI.

Clinical course of ICU patients with severe pandemic 2009 influenza A (H1N1) pneumonia: single center experience with proning and pressure release ventilation.

PubMed

Sundar, Krishna M; Thaut, Phillip; Nielsen, David B; Alward, William T; Pearce, Michael J

2012-01-01

A number of different modalities have been employed in addition to conventional ventilation to improve oxygenation in patients with severe 2009 pandemic influenza A (H1N1) pneumonia. Outcomes with ventilatory and rescue therapies for H1N1 influenza-related acute respiratory distress syndrome (ARDS) have been varied. A single intensive care unit (ICU) experience with management of laboratory-confirmed 2009 pandemic influenza A (H1N1) ARDS with a combination of proning and airway pressure release ventilation (APRV) is described. A retrospective review of medical records of ICU patients seen at Utah Valley Regional Medical Center during the first and second waves of the H1N1 influenza pandemic was done. Fourteen ICU patients were managed with invasive ventilation for 2009 pandemic influenza A (H1N1)-related ARDS. Hypoxemia refractory to conventional ventilation was noted in 11 of 14 patients despite application of APRV. Following proning in patients on APRV, improvement of hypoxemia and hemodynamic status was achieved. Only 2 of 11 patients on APRV and proning required continuous dialysis. Mortality in intubated patients receiving a combination of proning and APRV was 27.3% (3/11) with 2 of these dying during the first wave of the H1N1 influenza pandemic. In all, 3 of 11 patients on proning and APRV underwent tracheostomy, with 2 of these undergoing tube thoracostomy. ARDSnet fluid-conservative protocol was safely tolerated in 8 of 11 of the intubated patients following initiation of proning and APRV. Proning in combination with APRV provides improvement of hypoxemia with limitation of end-organ dysfunction and thereby facilitates recovery from severe 2009 pandemic influenza A (H1N1).

Corticosteroids and ARDS: A review of treatment and prevention evidence

PubMed Central

Khilnani, G.C.; Hadda, Vijay

2011-01-01

To systematically review the role of corticosteroids in prevention of acute respiratory distress syndrome (ARDS) in high-risk patients, and in treatment of established ARDS. Primary articles were identified by English-language Pubmed/MEDLINE, Cochrane central register of controlled trials, and Cochrane systemic review database search (1960–June 2009) using the MeSH headings: ARDS, adult respiratory distress syndrome, ARDS, corticosteroids, and methylprednisolone (MP). The identified studies were reviewed and information regarding role of corticosteroids in prevention and treatment of ARDS was evaluated. Nine trials have evaluated the role of corticosteroid drugs in management of ARDS at various stages. Of the 9, 4 trials evaluated role of corticosteroids in prevention of ARDS, while other 5 trials were focused on treatment after variable periods of onset of ARDS. Trials with preventive corticosteroids, mostly using high doses of MP, showed negative results with patients in treatment arm, showing higher mortality and rate of ARDS development. While trials of corticosteroids in early ARDS showed variable results, somewhat, favoring use of these agents to reduce associated morbidities. In late stage of ARDS, these drugs have no benefits and are associated with adverse outcome. Use of corticosteroids in patients with early ARDS showed equivocal results in decreasing mortality; however, there is evidence that these drugs reduce organ dysfunction score, lung injury score, ventilator requirement, and intensive care unit stay. However, most of these trials are small, having a significant heterogeneity regarding study design, etiology of ARDS, and dosage of corticosteroids. Further research involving large-scale trials on relatively homogeneous cohort is necessary to establish the role of corticosteroids for this condition. PMID:21712921

Assessment of PaO2/FiO2 for stratification of patients with moderate and severe acute respiratory distress syndrome

PubMed Central

Villar, Jesús; Blanco, Jesús; del Campo, Rafael; Andaluz-Ojeda, David; Díaz-Domínguez, Francisco J; Muriel, Arturo; Córcoles, Virgilio; Suárez-Sipmann, Fernando; Tarancón, Concepción; González-Higueras, Elena; López, Julia; Blanch, Lluis; Pérez-Méndez, Lina; Fernández, Rosa Lidia; Kacmarek, Robert M

2015-01-01

Objectives A recent update of the definition of acute respiratory distress syndrome (ARDS) proposed an empirical classification based on ratio of arterial partial pressure of oxygen to fraction of inspired oxygen (PaO2/FiO2) at ARDS onset. Since the proposal did not mandate PaO2/FiO2 calculation under standardised ventilator settings (SVS), we hypothesised that a stratification based on baseline PaO2/FiO2 would not provide accurate assessment of lung injury severity. Design A prospective, multicentre, observational study. Setting A network of teaching hospitals. Participants 478 patients with eligible criteria for moderate (100300). Primary and secondary outcomes Group severity and hospital mortality. Results At ARDS onset, 173 patients had a PaO2/FiO2≤100 but only 38.7% met criteria for severe ARDS at 24 h under SVS. When assessed under SVS, 61.3% of patients with severe ARDS were reclassified as moderate, mild and non-ARDS, while lung severity and hospital mortality changed markedly with every PaO2/FiO2 category (p<0.000001). Our model of risk stratification outperformed the stratification using baseline PaO2/FiO2 and non-standardised PaO2/FiO2 at 24 h, when analysed by the predictive receiver operating characteristic (ROC) curve: area under the ROC curve for stratification at baseline was 0.583 (95% CI 0.525 to 0.636), 0.605 (95% CI 0.552 to 0.658) at 24 h without SVS and 0.693 (95% CI 0.645 to 0.742) at 24 h under SVS (p<0.000001). Conclusions Our findings support the need for patient assessment under SVS at 24 h after ARDS onset to assess disease severity, and have implications for the diagnosis and management of ARDS patients. Trial registration numbers NCT00435110 and NCT00736892. PMID:25818272

Assessment of PaO₂/FiO₂ for stratification of patients with moderate and severe acute respiratory distress syndrome.

PubMed

Villar, Jesús; Blanco, Jesús; del Campo, Rafael; Andaluz-Ojeda, David; Díaz-Domínguez, Francisco J; Muriel, Arturo; Córcoles, Virgilio; Suárez-Sipmann, Fernando; Tarancón, Concepción; González-Higueras, Elena; López, Julia; Blanch, Lluis; Pérez-Méndez, Lina; Fernández, Rosa Lidia; Kacmarek, Robert M

2015-03-27

A recent update of the definition of acute respiratory distress syndrome (ARDS) proposed an empirical classification based on ratio of arterial partial pressure of oxygen to fraction of inspired oxygen (PaO₂/FiO₂) at ARDS onset. Since the proposal did not mandate PaO₂/FiO₂ calculation under standardised ventilator settings (SVS), we hypothesised that a stratification based on baseline PaO₂/FiOv would not provide accurate assessment of lung injury severity. A prospective, multicentre, observational study. A network of teaching hospitals. 478 patients with eligible criteria for moderate (100300). Group severity and hospital mortality. At ARDS onset, 173 patients had a PaO₂/FiO₂≤100 but only 38.7% met criteria for severe ARDS at 24 h under SVS. When assessed under SVS, 61.3% of patients with severe ARDS were reclassified as moderate, mild and non-ARDS, while lung severity and hospital mortality changed markedly with every PaO₂/FiO₂ category (p<0.000001). Our model of risk stratification outperformed the stratification using baseline PaO₂/FiO₂ and non-standardised PaO₂/FiO₂ at 24 h, when analysed by the predictive receiver operating characteristic (ROC) curve: area under the ROC curve for stratification at baseline was 0.583 (95% CI 0.525 to 0.636), 0.605 (95% CI 0.552 to 0.658) at 24 h without SVS and 0.693 (95% CI 0.645 to 0.742) at 24 h under SVS (p<0.000001). Our findings support the need for patient assessment under SVS at 24 h after ARDS onset to assess disease severity, and have implications for the diagnosis and management of ARDS patients. NCT00435110 and NCT00736892. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Mechanisms of decreased left ventricular preload during continuous positive pressure ventilation in ARDS

DOE Office of Scientific and Technical Information (OSTI.GOV)

Dhainaut, J.F.; Devaux, J.Y.; Monsallier, J.F.

1986-07-01

Continuous positive pressure ventilation is associated with a reduction in left ventricular preload and cardiac output, but the mechanisms responsible are controversial. The decrease in left ventricular preload may result exclusively from a decreased systemic venous return due to increased pleural pressure, or from an additional effect such as decreased left ventricular compliance. To determine the mechanisms responsible, we studied the changes in cardiac output induced by continuous positive pressure ventilation in eight patients with the adult respiratory distress syndrome. We measured cardiac output by thermodilution, and biventricular ejection fraction by equilibrium gated blood pool scintigraphy. Biventricular end-diastolic volumes weremore » then calculated by dividing stroke volume by ejection fraction. As positive end-expiratory pressure increased from 0 to 20 cm H/sub 2/O, stroke volume and biventricular end-diastolic volumes fell about 25 percent, and biventricular ejection fraction remained unchanged. At 20 cm H/sub 2/O positive end-expiratory pressure, volume expansion for normalizing cardiac output restored biventricular end-diastolic volumes without markedly changing biventricular end-diastolic transmural pressures. The primary cause of the reduction in left ventricular preload with continuous positive pressure ventilation appears to be a fall in venous return and hence in right ventricular stroke volume, without evidence of change in left ventricular diastolic compliance.« less

Extracorporeal Gas Exchange and Spontaneous Breathing for the Treatment of Acute Respiratory Distress Syndrome: An Alternative to Mechanical Ventilation?

DTIC Science & Technology

2014-03-01

Milano, Milan , Italy. 3National Research Council, National Academies, Washington, DC. 4School of Medicine, Università degli Studi di Milano, Milan ...Policlinico di Milano, Milan , Italy. This work was performed at the Comprehensive Intensive Care Research Task Area, US Army Institute of Surgical Research... Schultz HD, et al: Stimulation of pulmo- nary vagal afferent C-fibers by lung edema in dogs. Circ Res 1986; 58:512–522 45. Schuster DP: ARDS: Clinical

High-frequency oscillation and tracheal gas insufflation in patients with severe acute respiratory distress syndrome and traumatic brain injury: an interventional physiological study

PubMed Central

2013-01-01

Introduction In acute respiratory distress syndrome (ARDS), combined high-frequency oscillation (HFO) and tracheal gas insufflation (TGI) improves gas exchange compared with conventional mechanical ventilation (CMV). We evaluated the effect of HFO-TGI on PaO2/fractional inspired O2 (FiO2) and PaCO2, systemic hemodynamics, intracranial pressure (ICP), and cerebral perfusion pressure (CPP) in patients with traumatic brain injury (TBI) and concurrent severe ARDS. Methods We studied 13 TBI/ARDS patients requiring anesthesia, hyperosmolar therapy, and ventilation with moderate-to-high CMV-tidal volumes for ICP control. Patients had PaO2/FiO2 <100 mm Hg at end-expiratory pressure ≥10 cm H2O. Patients received consecutive, daily, 12-hour rescue sessions of HFO-TGI interspersed with 12-hour periods of CMV. HFO-TGI was discontinued when the post-HFO-TGI PaO2/FiO2 exceeded 100 mm Hg for >12 hours. Arterial/central-venous blood gases, hemodynamics, and ICP were recorded before, during (every 4 hours), and after HFO-TGI, and were analyzed by using repeated measures analysis of variance. Respiratory mechanics were assessed before and after HFO-TGI. Results Each patient received three to four HFO-TGI sessions (total sessions, n = 43). Pre-HFO-TGI PaO2/FiO2 (mean ± standard deviation (SD): 83.2 ± 15.5 mm Hg) increased on average by approximately 130% to163% during HFO-TGI (P < 0.01) and remained improved by approximately 73% after HFO-TGI (P < 0.01). Pre-HFO-TGI CMV plateau pressure (30.4 ± 4.5 cm H2O) and respiratory compliance (37.8 ± 9.2 ml/cm H2O), respectively, improved on average by approximately 7.5% and 20% after HFO-TGI (P < 0.01 for both). During HFO-TGI, systemic hemodynamics remained unchanged. Transient improvements were observed after 4 hours of HFO-TGI versus pre-HFO-TGI CMV in PaCO2 (37.7 ± 9.9 versus 41.2 ± 10.8 mm Hg; P < 0.01), ICP (17.2 ± 5.4 versus 19.7 ± 5.9 mm Hg; P < 0.05), and CPP (77.2 ± 14.6 versus 71.9 ± 14.8 mm Hg; P < 0.05). Conclusions In TBI/ARDS patients, HFO-TGI may improve oxygenation and respiratory mechanics, without adversely affecting PaCO2, hemodynamics, or ICP. These findings support the use of HFO-TGI as a rescue ventilatory strategy in patients with severe TBI and imminent oxygenation failure due to severe ARDS. PMID:23844839

SpO2/FiO2 ratio on hospital admission is an indicator of early acute respiratory distress syndrome development among patients at risk.

PubMed

Festic, Emir; Bansal, Vikas; Kor, Daryl J; Gajic, Ognjen

2015-05-01

Oxygen saturation to fraction of inspired oxygen ratio (SpO(2)/FiO(2)) has been validated as a surrogate marker for partial pressure of oxygen to fraction of inspired oxygen ratio among mechanically ventilated patients with acute respiratory distress syndrome (ARDS). The validity of SpO(2)/FiO(2) measurements in predicting ARDS has not been studied. Recently, a Lung Injury Prediction Score (LIPS) has been developed to help identify patients at risk of developing ARDS. This was a secondary analysis of the LIPS-1 cohort. A multivariate logistic regression included all established variables for LIPS, Acute Physiology and Chronic Health Evaluation 2, age, and comorbid conditions that could affect SpO(2)/FiO(2). The primary outcome was development of ARDS in the hospital. The secondary outcomes included hospital mortality, hospital day of ARDS development, and hospital day of death. Of the 5584 patients, we evaluated all 4646 with recorded SpO(2)/FiO(2) values. Median SpO(2)/FiO(2) in those who did and did not develop ARDS was 254 (100, 438) and 452 (329, 467), respectively. There was a significant association between SpO(2)/FiO(2) and ARDS (P ≤ .001). The SpO(2)/FiO(2) was found to be an independent predictor of ARDS in a "dose-dependent" manner; for SpO(2)/FiO(2) < 100--odds ratios (OR) 2.49 (1.69-3.64, P < .001), for SpO(2)/FiO(2) 100 < 200--OR 1.75 (1.16-2.58, P = .007), and for SpO(2)/FiO(2) 200 < 300--OR 1.62 (1.06-2.42, P = .025). The discriminatory characteristics of the multivariable model and SpO2/FiO2 as a single variable demonstrated area under the curve (AUC) of 0.81 and AUC of 0.74, respectively. The SpO2/FiO2, measured within the first 6 hours after hospital admission, is an independent indicator of ARDS development among patients at risk. © The Author(s) 2013.

Feasibility and safety of low-flow extracorporeal carbon dioxide removal to facilitate ultra-protective ventilation in patients with moderate acute respiratory distress sindrome.

PubMed

Fanelli, Vito; Ranieri, Marco V; Mancebo, Jordi; Moerer, Onnen; Quintel, Michael; Morley, Scott; Moran, Indalecio; Parrilla, Francisco; Costamagna, Andrea; Gaudiosi, Marco; Combes, Alain

2016-02-10

Mechanical ventilation with a tidal volume (VT) of 6 mL/kg/predicted body weight (PBW), to maintain plateau pressure (Pplat) lower than 30 cmH2O, does not completely avoid the risk of ventilator induced lung injury (VILI). The aim of this study was to evaluate safety and feasibility of a ventilation strategy consisting of very low VT combined with extracorporeal carbon dioxide removal (ECCO2R). In fifteen patients with moderate ARDS, VT was reduced from baseline to 4 mL/kg PBW while PEEP was increased to target a plateau pressure--(Pplat) between 23 and 25 cmH2O. Low-flow ECCO2R was initiated when respiratory acidosis developed (pH < 7.25, PaCO2 > 60 mmHg). Ventilation parameters (VT, respiratory rate, PEEP), respiratory compliance (CRS), driving pressure (DeltaP = VT/CRS), arterial blood gases, and ECCO2R system operational characteristics were collected during the period of ultra-protective ventilation. Patients were weaned from ECCO2R when PaO2/FiO2 was higher than 200 and could tolerate conventional ventilation settings. Complications, mortality at day 28, need for prone positioning and extracorporeal membrane oxygenation, and data on weaning from both MV and ECCO2R were also collected. During the 2 h run in phase, VT reduction from baseline (6.2 mL/kg PBW) to approximately 4 mL/kg PBW caused respiratory acidosis (pH < 7.25) in all fifteen patients. At steady state, ECCO2R with an average blood flow of 435 mL/min and sweep gas flow of 10 L/min was effective at correcting pH and PaCO2 to within 10 % of baseline values. PEEP values tended to increase at VT of 4 mL/kg from 12.2 to 14.5 cmH2O, but this change was not statistically significant. Driving pressure was significantly reduced during the first two days compared to baseline (from 13.9 to 11.6 cmH2O; p < 0.05) and there were no significant differences in the values of respiratory system compliance. Rescue therapies for life threatening hypoxemia such as prone position and ECMO were necessary in four and two patients, respectively. Only two study-related adverse events were observed (intravascular hemolysis and femoral catheter kinking). The low-flow ECCO2R system safely facilitates a low volume, low pressure ultra-protective mechanical ventilation strategy in patients with moderate ARDS.

Manual muscle testing: a method of measuring extremity muscle strength applied to critically ill patients.

PubMed

Ciesla, Nancy; Dinglas, Victor; Fan, Eddy; Kho, Michelle; Kuramoto, Jill; Needham, Dale

2011-04-12

Survivors of acute respiratory distress syndrome (ARDS) and other causes of critical illness often have generalized weakness, reduced exercise tolerance, and persistent nerve and muscle impairments after hospital discharge. Using an explicit protocol with a structured approach to training and quality assurance of research staff, manual muscle testing (MMT) is a highly reliable method for assessing strength, using a standardized clinical examination, for patients following ARDS, and can be completed with mechanically ventilated patients who can tolerate sitting upright in bed and are able to follow two-step commands. (7, 8) This video demonstrates a protocol for MMT, which has been taught to ≥ 43 research staff who have performed >800 assessments on >280 ARDS survivors. Modifications for the bedridden patient are included. Each muscle is tested with specific techniques for positioning, stabilization, resistance, and palpation for each score of the 6-point ordinal Medical Research Council scale. Three upper and three lower extremity muscles are graded in this protocol: shoulder abduction, elbow flexion, wrist extension, hip flexion, knee extension, and ankle dorsiflexion. These muscles were chosen based on the standard approach for evaluating patients for ICU-acquired weakness used in prior publications. (1,2).

Applying Precision Medicine to Trial Design Using Physiology. Extracorporeal CO2 Removal for Acute Respiratory Distress Syndrome.

PubMed

Goligher, Ewan C; Amato, Marcelo B P; Slutsky, Arthur S

2017-09-01

In clinical trials of therapies for acute respiratory distress syndrome (ARDS), the average treatment effect in the study population may be attenuated because individual patient responses vary widely. This inflates sample size requirements and increases the cost and difficulty of conducting successful clinical trials. One solution is to enrich the study population with patients most likely to benefit, based on predicted patient response to treatment (predictive enrichment). In this perspective, we apply the precision medicine paradigm to the emerging use of extracorporeal CO 2 removal (ECCO 2 R) for ultraprotective ventilation in ARDS. ECCO 2 R enables reductions in tidal volume and driving pressure, key determinants of ventilator-induced lung injury. Using basic physiological concepts, we demonstrate that dead space and static compliance determine the effect of ECCO 2 R on driving pressure and mechanical power. This framework might enable prediction of individual treatment responses to ECCO 2 R. Enriching clinical trials by selectively enrolling patients with a significant predicted treatment response can increase treatment effect size and statistical power more efficiently than conventional enrichment strategies that restrict enrollment according to the baseline risk of death. To support this claim, we simulated the predicted effect of ECCO 2 R on driving pressure and mortality in a preexisting cohort of patients with ARDS. Our computations suggest that restricting enrollment to patients in whom ECCO 2 R allows driving pressure to be decreased by 5 cm H 2 O or more can reduce sample size requirement by more than 50% without increasing the total number of patients to be screened. We discuss potential implications for trial design based on this framework.

Pumpless extracorporeal interventional lung assist in patients with acute respiratory distress syndrome: a prospective pilot study.

PubMed

Zimmermann, Markus; Bein, Thomas; Arlt, Matthias; Philipp, Alois; Rupprecht, Leopold; Mueller, Thomas; Lubnow, Matthias; Graf, Bernhard M; Schlitt, Hans J

2009-01-01

Pumpless interventional lung assist (iLA) is used in patients with acute respiratory distress syndrome (ARDS) aimed at improving extracorporeal gas exchange with a membrane integrated in a passive arteriovenous shunt. In previous studies, feasibility and safety of the iLA system was demonstrated, but no survival benefit was observed. In the present pilot study we tested the hypothesis that timely initiation of iLA using clear algorithms and an improved cannulation technique will positively influence complication rates and management of lung protective ventilation. iLA was implemented in 51 patients from multiple aetiologies meeting ARDS-criteria (American-European Consensus) for more than 12 hours. Initiation of iLA followed an algorithm for screening, careful evaluation and insertion technique. Patients with cardiac insufficiency or severe peripheral vascular disease were not considered suitable for iLA. Arterial and venous cannulae were inserted using a new strategy (ultrasound evaluation of vessels by an experienced team, using cannulae of reduced diameter). The incidence of complications and the effects on tidal volumes and inspiratory plateau pressures were primary outcome parameters, while oxygenation improvement and carbon dioxide removal capabilities were secondary study parameters. Initiation of iLA resulted in a marked removal in arterial carbon dioxide allowing a rapid reduction in tidal volume (

[Analysis of the risk factors of acute respiratory distress syndrome of Berlin new definition in patients with sepsis in emergency department].

PubMed

Qiao, Liang; Liu, Zhi

2015-07-01

To discuss the risk factors of acute respiratory distress syndrome (ARDS) in patients with sepsis in emergency department. 312 patients with sepsis admitted to Department of Emergency of China Medical University Affiliated First Hospital were retrospectively analyzed, and they were divided into two groups according to development of ARDS, which was defined according to the Berlin new definition. The age, gender, vital signs, laboratory results, underlying disease, the mortality in emergency department sepsis (MEDS) score and lung injury prediction score (LIPS) were collected. Univariate analysis was done for each parameter. Statistical significance results were evaluated by multivariate logistic regression analysis. Receiver operating characteristic (ROC) curve was plotted to analyze the predictive value of the parameter for ARDS. The incidence of sepsis-related ARDS was 11.2% (35/312). Within 35 cases of ARDS, there were 10 cases of mild ARDS, 18 cases of moderate ARDS, and 7 cases of severe ARDS. Univariate analysis showed that age (t=-2.134, P=0.035), oxygenation index (t=-4.245, P=0.001), arterial lactate (Lac, t=6.245, P<0.001), drugs for vascular diseases (χ2=4.261, P=0.026), shock (χ2=4.386, P=0.021), MEDS (t=4.021, P=0.045), LIPS (t=5.569, P<0.001), lung infections (χ2=4.289, P=0.025), and mechanical ventilation (χ2=6.245, P=0.001) were related to ARDS. The incidence of ARDS was different in different levels of Lac, which was 5.00% (3/16) at low level of Lac (<2.0 mmol/L), 9.46% (14/148) at middle level of Lac (2.0-3.9 mmol/L) and 17.31% (18/104) at high level of Lac (≥4.0 mmol/L). It was shown by multivariate logistic regression analysis that LIPS [ odds ratio (OR)=5.124, 95% confidence interval (95%CI)=3.642-10.153, P=0.002], Lac (OR=18.180, 95%CI=7.677-32.989, P<0.001) were independent risk factors for ARDS. It was shown by area under ROC (AUC) that the predictive value of LIPS and Lac in ARDS occurrence was significant. AUC of LIPS was 0.725, the cut-off value was 7, when LIPS≥7, the sensitivity was 71.0%, specificity was 75.6%. AUC of Lac was 0.793, the cut-off value was 4.2 mmol/L, when Lac≥4.2 mmol/L, the sensitivity was 72.1%, and specificity was 81.9%. LIPS and Lac are independent risk factors of ARDS in patients with sepsis in emergency department, which may be a reference for the early clinical diagnosis of ARDS.

Evaluation of ventilators used during transport of critically ill patients: a bench study.

PubMed

Boussen, Salah; Gainnier, Marc; Michelet, Pierre

2013-11-01

To evaluate the most recent transport ventilators' operational performance regarding volume delivery in controlled mode, trigger function, and the quality of pressurization in pressure support mode. Eight recent transport ventilators were included in a bench study in order to evaluate their accuracy to deliver a set tidal volume under normal resistance and compliance conditions, ARDS conditions, and obstructive conditions. The performance of the triggering system was assessed by the measure of the decrease in pressure and the time delay required to open the inspiratory valve. The quality of pressurization was obtained by computing the integral of the pressure-time curve for the first 300 ms and 500 ms after the onset of inspiration. For the targeted tidal volumes of 300, 500, and 800 mL the errors ranged from -3% to 48%, -7% to 18%, and -5% to 25% in the normal conditions, -4% to 27%, -2% to 35%, and -3% to 35% in the ARDS conditions, and -4% to 53%, -6% to 30%, and -30% to 28% in the obstructive conditions. In pressure support mode the pressure drop range was 0.4-1.7 cm H2O, the trigger delay range was 68-198 ms, and the pressurization performance (percent of ideal pressurization, as measured by pressure-time product at 300 ms and 500 ms) ranges were -9% to 44% at 300 ms and 6%-66% at 500 ms (P < .01). There were important differences in the performance of the tested ventilators. The most recent turbine ventilators outperformed the pneumatic ventilators. The best performers among the turbine ventilators proved comparable to modern ICU ventilators.

Clinical review: Lung imaging in acute respiratory distress syndrome patients - an update

PubMed Central

2013-01-01

Over the past 30 years lung imaging has greatly contributed to the current understanding of the pathophysiology and the management of acute respiratory distress syndrome (ARDS). In the past few years, in addition to chest X-ray and lung computed tomography, newer functional lung imaging techniques, such as lung ultrasound, positron emission tomography, electrical impedance tomography and magnetic resonance, have been gaining a role as diagnostic tools to optimize lung assessment and ventilator management in ARDS patients. Here we provide an updated clinical review of lung imaging in ARDS over the past few years to offer an overview of the literature on the available imaging techniques from a clinical perspective. PMID:24238477

Extracorporeal carbon dioxide removal for patients with acute respiratory failure secondary to the acute respiratory distress syndrome: a systematic review

PubMed Central

2014-01-01

Acute respiratory distress syndrome (ARDS) continues to have significant mortality and morbidity. The only intervention proven to reduce mortality is the use of lung-protective mechanical ventilation strategies, although such a strategy may lead to problematic hypercapnia. Extracorporeal carbon dioxide removal (ECCO2R) devices allow uncoupling of ventilation from oxygenation, thereby removing carbon dioxide and facilitating lower tidal volume ventilation. We performed a systematic review to assess efficacy, complication rates, and utility of ECCO2R devices. We included randomised controlled trials (RCTs), case–control studies and case series with 10 or more patients. We searched MEDLINE, Embase, LILACS (Literatura Latino Americana em Ciências da Saúde), and ISI Web of Science, in addition to grey literature and clinical trials registries. Data were independently extracted by two reviewers against predefined criteria and agreement was reached by consensus. Outcomes of interest included mortality, intensive care and hospital lengths of stay, respiratory parameters and complications. The review included 14 studies with 495 patients (two RCTs and 12 observational studies). Arteriovenous ECCO2R was used in seven studies, and venovenous ECCO2R in seven studies. Available evidence suggests no mortality benefit to ECCO2R, although post hoc analysis of data from the most recent RCT showed an improvement in ventilator-free days in more severe ARDS. Organ failure-free days or ICU stay have not been shown to decrease with ECCO2R. Carbon dioxide removal was widely demonstrated as feasible, facilitating the use of lower tidal volume ventilation. Complication rates varied greatly across the included studies, representing technological advances. There was a general paucity of high-quality data and significant variation in both practice and technology used among studies, which confounded analysis. ECCO2R is a rapidly evolving technology and is an efficacious treatment to enable protective lung ventilation. Evidence for a positive effect on mortality and other important clinical outcomes is lacking. Rapid technological advances have led to major changes in these devices and together with variation in study design have limited applicability of analysis. Further well-designed adequately powered RCTs are needed. PMID:25033302

Comparison of Cisatracurium Versus Atracurium in Early ARDS.

PubMed

Moore, Leanne; Kramer, Charles Joseph; Delcoix-Lopes, Sophie; Modrykamien, Ariel M

2017-07-01

Administration of cisatracurium in severe ARDS decreases in-hospital mortality. Whether clinical outcomes are cisatracurium-specific or related with all neuromuscular blockers is unknown. This study aimed to compare outcomes in severe ARDS patients treated with cisatracurium versus atracurium. Patients admitted in ICUs with a diagnosis of severe ARDS and treated with neuromuscular blocking agents within 72 h of diagnosis were included. Subjects treated with cisatracurium versus atracurium were compared. The primary outcome was improvement in oxygenation, defined as the difference of P aO 2 /F IO 2 at 72 h post-initiation of neuromuscular blocking agents. Secondary outcomes were ventilator-free days at day 28, ICU and hospital lengths of stay, and hospital mortality. Seventy-six subjects with ARDS were included in the study. Eighteen subjects (24%) were treated with atracurium, whereas 58 (76%) were treated with cisatracurium. Equivalent dosages of sedation and analgesia as well as use of brain function monitoring technology were similar between both groups. There were no differences in clinical outcomes. Specifically, improvement of P aO 2 /F IO 2 was a median (interquartile range [IQR]) of 65 (25-162) in the atracurium group and 66 (IQR 16-147) in the cisatracurium group ( P = .65). Ventilator-free days at day 28 were 13 d (IQR 0-22 d) and 15 d (IQR 8-21 d) in the atracurium and cisatracurium groups, respectively ( P = .72). ICU length or stay was 18 d (IQR 8-34 d) in the atracurium group and 15 d (IQR 9-22 d) in the cisatracurium group ( P = .34). In-hospital mortality was 50% for the atracurium population and 62% for the cisatracurium group ( P = .42) CONCLUSIONS: Among subjects with early severe ARDS, the utilization of atracurium versus cisatracurium within 72 h of admission was not associated with significant differences in clinical outcomes. Copyright © 2017 by Daedalus Enterprises.

Metabolomics based predictive biomarker model of ARDS: A systemic measure of clinical hypoxemia

PubMed Central

Viswan, Akhila; Singh, Chandan; Rai, Ratan Kumar; Azim, Afzal; Baronia, Arvind Kumar

2017-01-01

Despite advancements in ventilator technologies, lung supportive and rescue therapies, the outcome and prognostication in acute respiratory distress syndrome (ARDS) remains incremental and ambiguous. Metabolomics is a potential insightful measure to the diagnostic approaches practiced in critical disease settings. In our study patients diagnosed with mild and moderate/severe ARDS clinically governed by hypoxemic P/F ratio between 100–300 but with indistinct molecular phenotype were discriminated employing nuclear magnetic resonance (NMR) based metabolomics of mini bronchoalveolar lavage fluid (mBALF). Resulting biomarker prototype comprising six metabolites was substantiated highlighting ARDS susceptibility/recovery. Both the groups (mild and moderate/severe ARDS) showed distinct biochemical profile based on 83.3% classification by discriminant function analysis and cross validated accuracy of 91% using partial least squares discriminant analysis as major classifier. The predictive performance of narrowed down six metabolites were found analogous with chemometrics. The proposed biomarker model consisting of six metabolites proline, lysine/arginine, taurine, threonine and glutamate were found characteristic of ARDS sub-stages with aberrant metabolism observed mainly in arginine, proline metabolism, lysine synthesis and so forth correlating to diseased metabotype. Thus NMR based metabolomics has provided new insight into ARDS sub-stages and conclusively a precise biomarker model proposed, reflecting underlying metabolic dysfunction aiding prior clinical decision making. PMID:29095932

Metabolomics based predictive biomarker model of ARDS: A systemic measure of clinical hypoxemia.

PubMed

Viswan, Akhila; Singh, Chandan; Rai, Ratan Kumar; Azim, Afzal; Sinha, Neeraj; Baronia, Arvind Kumar

2017-01-01

Despite advancements in ventilator technologies, lung supportive and rescue therapies, the outcome and prognostication in acute respiratory distress syndrome (ARDS) remains incremental and ambiguous. Metabolomics is a potential insightful measure to the diagnostic approaches practiced in critical disease settings. In our study patients diagnosed with mild and moderate/severe ARDS clinically governed by hypoxemic P/F ratio between 100-300 but with indistinct molecular phenotype were discriminated employing nuclear magnetic resonance (NMR) based metabolomics of mini bronchoalveolar lavage fluid (mBALF). Resulting biomarker prototype comprising six metabolites was substantiated highlighting ARDS susceptibility/recovery. Both the groups (mild and moderate/severe ARDS) showed distinct biochemical profile based on 83.3% classification by discriminant function analysis and cross validated accuracy of 91% using partial least squares discriminant analysis as major classifier. The predictive performance of narrowed down six metabolites were found analogous with chemometrics. The proposed biomarker model consisting of six metabolites proline, lysine/arginine, taurine, threonine and glutamate were found characteristic of ARDS sub-stages with aberrant metabolism observed mainly in arginine, proline metabolism, lysine synthesis and so forth correlating to diseased metabotype. Thus NMR based metabolomics has provided new insight into ARDS sub-stages and conclusively a precise biomarker model proposed, reflecting underlying metabolic dysfunction aiding prior clinical decision making.

Intravenous immunoglobulin fails to improve ARDS in patients undergoing ECMO therapy.

PubMed

Prohaska, Stefanie; Schirner, Andrea; Bashota, Albina; Körner, Andreas; Blumenstock, Gunnar; Haeberle, Helene A

2018-01-01

Acute respiratory distress syndrome (ARDS) is associated with high mortality rates. ARDS patients suffer from severe hypoxemia, and extracorporeal membrane oxygenation (ECMO) therapy may be necessary to ensure oxygenation. ARDS has various etiologies, including trauma, ischemia-reperfusion injury or infections of various origins, and the associated immunological responses may vary. To support the immunological response in this patient collective, we used intravenous IgM immunoglobulin therapy to enhance the likelihood of pulmonary recovery. ARDS patients admitted to the intensive care unit (ICU) who were placed on ECMO and treated with (IVIG group; n  = 29) or without (control group; n  = 28) intravenous IgM-enriched immunoglobulins for 3 days in the initial stages of ARDS were analyzed retrospectively. The baseline characteristics did not differ between the groups, although the IVIG group showed a significantly reduced oxygenation index compared to the control group. We found no differences in the length of ICU stay or ventilation parameters. We did not find a significant difference between the groups for the extent of inflammation or for overall survival. We conclude that administration of IgM-enriched immunoglobulins as an additional therapy did not have a beneficial effect in patients with severe ARDS requiring ECMO support. Clinical Trials: NCT02961166; retrospectively registered.

Clinical Characteristics and Outcomes of Sepsis-Related vs Non-Sepsis-Related ARDS

PubMed Central

Sheu, Chau-Chyun; Gong, Michelle N.; Zhai, Rihong; Chen, Feng; Bajwa, Ednan K.; Clardy, Peter F.; Gallagher, Diana C.; Thompson, B. Taylor

2010-01-01

Background: ARDS may occur after either septic or nonseptic injuries. Sepsis is the major cause of ARDS, but little is known about the differences between sepsis-related and non-sepsis-related ARDS. Methods: A total of 2,786 patients with ARDS-predisposing conditions were enrolled consecutively into a prospective cohort, of which 736 patients developed ARDS. We defined sepsis-related ARDS as ARDS developing in patients with sepsis and non-sepsis-related ARDS as ARDS developing after nonseptic injuries, such as trauma, aspiration, and multiple transfusions. Patients with both septic and nonseptic risks were excluded from analysis. Results: Compared with patients with non-sepsis-related ARDS (n = 62), patients with sepsis-related ARDS (n = 524) were more likely to be women and to have diabetes, less likely to have preceding surgery, and had longer pre-ICU hospital stays and higher APACHE III (Acute Physiology and Chronic Health Evaluation III) scores (median, 78 vs 65, P < .0001). There were no differences in lung injury score, blood pH, Pao2/Fio2 ratio, and Paco2 on ARDS diagnosis. However, patients with sepsis-related ARDS had significantly lower Pao2/Fio2 ratios than patients with non-sepsis-related ARDS patients on ARDS day 3 (P = .018), day 7 (P = .004), and day 14 (P = .004) (repeated-measures analysis, P = .011). Compared with patients with non-sepsis-related ARDS, those with sepsis-related had a higher 60-day mortality (38.2% vs 22.6%; P = .016), a lower successful extubation rate (53.6% vs 72.6%; P = .005), and fewer ICU-free days (P = .0001) and ventilator-free days (P = .003). In multivariate analysis, age, APACHE III score, liver cirrhosis, metastatic cancer, admission serum bilirubin and glucose levels, and treatment with activated protein C were independently associated with 60-day ARDS mortality. After adjustment, sepsis-related ARDS was no longer associated with higher 60-day mortality (hazard ratio, 1.26; 95% CI, 0.71-2.22). Conclusion: Sepsis-related ARDS has a higher overall disease severity, poorer recovery from lung injury, lower successful extubation rate, and higher mortality than non-sepsis-related ARDS. Worse clinical outcomes in sepsis-related ARDS appear to be driven by disease severity and comorbidities. PMID:20507948

[Effect of transpulmonary pressure-directed mechanical ventilation on respiration in severe acute pancreatitis patient with intraabdominal hypertension].

PubMed

Wu, Xiaoyan; Zheng, Ruiqiang; Lin, Hua; Zhuang, Zhiqing; Zhang, Min; Yan, Peixia

2015-10-20

To assess the effect of mehanical ventilation (MV) guided by transpulmonary pressure (Ptp) on respiratory mechanics and gas exchange in severe acute pancreatitis patient with intraabdominal hypertension. Twelve severe acute pancreatitis patient with intraabdominal hypertension and acute respiratory distress syndrome(ARDS) underwent mechanical ventilation were involved from Jan to Dec 2013. PEEP levels were set to achieve a Ptp of 0 to 10 cm of water at end expiration. We also limited tidal volume to keep Ptp at less than 25 cm of water at end inspiration. Respiratory mechanics and gas-exchange were measured. Plat pressure (Pplat) increased and the compliance of chest wall (Ccw) decreased when intraabdominal pressure (IAP) increased. Pplat correlated with IAP positively (r2=0.741 9, P<0.05) and Ccw correlated with IAP negtively (r2=0.722 2, P<0.05), respectively.There were not corrletions between IAP and end-expiratory Ptp (Ptp-e) and end-inspiratory Ptp (Ptp-i) (P>0.05). Compared with baseline, after guiding MV with Ptp, the Level of PEEP (14.6±4.2) cmH2O vs (8.3±2.0) cmH2O, and Ptp-e (1.5±0.5) cmH2O vs (-2.3±1.4) cmH2O increased (P<0.05) and Ptp-i did not increase significantly (P>0.05). Ptp-e correlated with PEEP (r2=0.549, P<0.05) and end-expiratory esophageal pressure (Pes-e) (r2=0.260, P<0.05). Ptp-i correlated with Pplat (r2=0.523, P<0.05) and end-inspiratory esophageal pressure (Pes-i) (r2=0.231, P<0.05), but did not correlate with Tidal volume(VT) (r2=0.052 4, P>0.05). Compared with baseline, lung compliance (CL) (48.1±10.3) cmH2O vs (25.7±6.4) cmH2O and oxygenation index (PaO2/FiO2) (235±48) mmHg vs (160±35) mmHg improved obviously (P<0.05), dead space fraction (VD/VT) (0.48±0.07) vs (0.59±0.06) decreased (P<0.05), but Ccw and respiratory compliance(Cr) didn't improve (P>0.05). Transpulmonary pressure-directed mechanical ventilation in ARDS secondary to severe acute pancreatitis patient with intraabdominal hypertension could not only recruit the collapsed alveoli, improve lung compliance, increase oxygenation index and decrease dead space ventilation but also monitor lung stress to avoid alveoli overinflation, which might be lung protective.

The Predictive Value of Coefficient of PCT × BG for Anastomotic Leak in Esophageal Carcinoma Patients With ARDS After Esophagectomy.

PubMed

Li, Huan; Wang, Daofeng; Wei, Wenxiao; Ouyang, Lamei; Lou, Ning

2017-01-01

Anastomotic leak was a potentially severe life-threatening complication of esophagectomy, which drew attention in consequence of progressive dyspnea until acute respiratory distress syndrome (ARDS) due to the early asymptomatic presentation. Respiratory failure, caused by ARDS as the severe presentation of anastomotic leak, is the most common organ failure. CRP (C-reactive protein), procalcitonin (PCT), and Blood G (BG) test are the sensitivity markers for inflammatory, sepsis, and fungemia, respectively. Early recognition and intervention treatment of anastomotic leak may alleviate complication and improve outcome. We retrospectively analyzed 71 patients, accepting mechanical ventilation support because of ARDS as the complication after radical resection of esophagus cancer. Clinical data were collected from the patients' electronic medical records, including their clinically hematological examination, drainage fluid cultures, and sputum culture. Accord to appearance of anastomotic leak or not, all patients were divided into 2 groups, leak group and no-leak group. Inflammatory markers, such as CRP, PCT, and the coefficient of BG and PCT, were significantly different between the 2 groups. Respiratory index, white blood cell, hemoglobin (HBG), platelet (PLT), and other clinical factors were not significantly different between the 2 groups. Receiver operating characteristic curves were constructed to calculate the sensitivity, specificity, positive predictive value, negative predictive value, and area under the curve for various cutoff levels of several factors. Blood G tests presented the better predicting value for anastomotic leak. Blood G tests and PCT should be tested after esophagectomy. The coefficient of PCT and BG (>260) is of great significance, and clinical value to predict anastomotic leak for patients with postesophagectomy ARDS, early PCT and BG test, and especially, dynamic variation may alleviate complication and improve outcome.

The association between the Th-17 immune response and pulmonary complications in a trauma ICU population.

PubMed

Holloway, Travis L; Rani, Meenakshi; Cap, Andrew P; Stewart, Ronald M; Schwacha, Martin G

2015-12-01

The overall immunopathology of the T-helper cell (Th)-17 immune response has been implicated in various inflammatory diseases including pulmonary inflammation; however its potential role in acute respiratory distress syndrome (ARDS) is not defined. This study aimed to evaluate the Th-17 response in bronchoalveolar lavage fluid (BALF) and blood and from trauma patients with pulmonary complications. A total of 21 severely injured intensive care unit (ICU) subjects, who were mechanically ventilated and undergoing bronchoscopy, were enrolled. BALF and blood were collected and analyzed for Th-1 (interferon [IFN]γ), Th-2 (interleukin [IL]-4, -10), Th-17 (IL-17A, -17F, -22, 23) and pro-inflammatory (IL-1β, IL-6, tumor necrosis factor [TNF]α) cytokine levels. Significant levels of the Th-17 cytokines IL-17A, -17F and -21 and IL-6 (which can be classified as a Th-17 cytokine) were observed in the BALF of all subjects. There were no significant differences in Th-17 cytokines between those subjects with ARDS and those without, with the exception of plasma and BALF IL-6, which was markedly greater in ARDS subjects, as compared with controls and non-ARDS subjects. Trauma patients with pulmonary complications exhibited a significant Th-17 response in the lung and blood, suggesting that this pro-inflammatory milieu may be a contributing factor to such complications. Copyright © 2015 Elsevier Ltd. All rights reserved.

Perceptions of diagnosis and management of patients with acute respiratory distress syndrome: a survey of United Kingdom intensive care physicians.

PubMed

Dushianthan, Ahilanandan; Cusack, Rebecca; Chee, Nigel; Dunn, John-Oliver; Grocott, Michael P W

2014-01-01

Acute respiratory distress syndrome (ARDS) is a potentially devastating refractory hypoxemic illness with multi-organ involvement. Although several randomised controlled trials into ventilator and fluid management strategies have provided level 1 evidence to guide supportive therapy, there are few, established guidelines on how to manage patients with ARDS. In addition, and despite their continued use, pharmacotherapies for ARDS disease modulation have no proven benefit in improving mortality. Little is known however about the variability in diagnostic and treatment practices across the United Kingdom (UK). The aim of this survey, therefore, was to assess the use of diagnostic criteria and treatment strategies for ARDS in critical care units across the UK. The survey questionnaire was developed and internally piloted at University Hospital Southampton NHS Foundation Trust. Following ethical approval from University of Southampton Ethics and Research Committee, a link to an online survey engine (Survey Monkey) was then placed on the Intensive Care Society (UK) website. Fellows of The Intensive Care Society were subsequently personally approached via e-mail to encourage participation. The survey was conducted over a period of 3 months. The survey received 191 responses from 125 critical care units, accounting for 11% of all registered intensive care physicians at The Intensive Care Society. The majority of the responses were from physicians managing general intensive care units (82%) and 34% of respondents preferred the American European Consensus Criteria for ARDS. There was a perceived decline in both incidence and mortality in ARDS. Primary ventilation strategies were based on ARDSnet protocols, though frequent deviations from ARDSnet positive end expiratory pressure (PEEP) recommendations (51%) were described. The majority of respondents set permissive blood gas targets (hypoxia (92%), hypercapnia (58%) and pH (90%)). The routine use of pharmacological agents is rare. Neuromuscular blockers and corticosteroids are considered occasionally and on a case-by-case basis. Routine (58%) or late (64%) tracheostomy was preferred to early tracheostomy insertion. Few centres offered routine follow-up or dedicated rehabilitation programmes following hospital discharge. There is substantial variation in the diagnostic and management strategies employed for patients with ARDS across the UK. National and/or international guidelines may help to improve standardisation in the management of ARDS.

Nutrition: A Primary Therapy in Pediatric Acute Respiratory Distress Syndrome

PubMed Central

Wilson, Bryan; Typpo, Katri

2016-01-01

Appropriate nutrition is an essential component of intensive care management of children with acute respiratory distress syndrome (ARDS) and is linked to patient outcomes. One out of every two children in the pediatric intensive care unit (PICU) will develop malnutrition or have worsening of baseline malnutrition and present with specific micronutrient deficiencies. Early and adequate enteral nutrition (EN) is associated with improved 60-day survival after pediatric critical illness, and, yet, despite early EN guidelines, critically ill children receive on average only 55% of goal calories by PICU day 10. Inadequate delivery of EN is due to perceived feeding intolerance, reluctance to enterally feed children with hemodynamic instability, and fluid restriction. Underlying each of these factors is large practice variation between providers and across institutions for initiation, advancement, and maintenance of EN. Strategies to improve early initiation and advancement and to maintain delivery of EN are needed to improve morbidity and mortality from pediatric ARDS. Both, over and underfeeding, prolong duration of mechanical ventilation in children and worsen other organ function such that precise calorie goals are needed. The gut is thought to act as a “motor” of organ dysfunction, and emerging data regarding the role of intestinal barrier functions and the intestinal microbiome on organ dysfunction and outcomes of critical illness present exciting opportunities to improve patient outcomes. Nutrition should be considered a primary rather than supportive therapy for pediatric ARDS. Precise nutritional therapies, which are titrated and targeted to preservation of intestinal barrier function, prevention of intestinal dysbiosis, preservation of lean body mass, and blunting of the systemic inflammatory response, offer great potential for improving outcomes of pediatric ARDS. In this review, we examine the current evidence regarding dose, route, and timing of nutrition, current recommendations for provision of nutrition to children with ARDS, and the current literature for immune-modulating diets for pediatric ARDS. We will examine emerging data regarding the role of the intestinal microbiome in modulating the response to critical illness. PMID:27790606

Bacterial respiratory tract infections are promoted by systemic hyperglycemia after severe burn injury in pediatric patients.

PubMed

Kraft, Robert; Herndon, David N; Mlcak, Ronald P; Finnerty, Celeste C; Cox, Robert A; Williams, Felicia N; Jeschke, Marc G

2014-05-01

Burns are associated with hyperglycemia leading to increased incidence of infections with pneumonia being one of the most prominent and adverse complications. Recently, various studies in critically ill patients indicated that increased pulmonary glucose levels with airway/blood glucose threshold over 150 mg/dl lead to an overwhelming growth of bacteria in the broncho-pulmonary system, subsequently resulting in an increased risk of pulmonary infections. The aim of the present study was to determine whether a similar cutoff value exists for severely burned pediatric patients. One-hundred six severely burned pediatric patients were enrolled in the study. Patients were divided in two groups: high (H) defined as daily average glucose levels >75% of LOS >150 mg/dl), and low (L) with daily average glucose levels >75% of the LOS <150 mg/dl). Incidences of pneumonia, atelectasis, and acute respiratory distress syndrome (ARDS) were assessed. Incidence of infections, sepsis, and respiratory parameters were recorded. Blood was analyzed for glucose and insulin levels. Statistical analysis was performed using Student's t-test and chi-square test. Significance was set at p<0.05. Patient groups were similar in demographics and injury characteristics. Pneumonia in patients on the mechanical ventilation (L: 21%, H: 32%) and off mechanical ventilation (L: 5%, H: 15%), as well as ARDS were significantly higher in the high group (L: 3%, H: 19%), p<0.05, while atelectasis was not different. Patients in the high group required significantly longer ventilation compared to low patients (p<0.05). Furthermore, incidence of infection and sepsis were significantly higher in the high group, p<0.05. Our results indicate that systemic glucose levels over 150 mg/dl are associated with a higher incidence of pneumonia confirming the previous studies in critically ill patients. Copyright © 2013 Elsevier Ltd and ISBI. All rights reserved.

Bacterial Respiratory Tract Infections are Promoted by Systemic Hyperglycemia after Severe Burn Injury in Pediatric Patients

PubMed Central

Kraft, Robert; Herndon, David N; Mlcak, Ronald P; Finnerty, Celeste C; Cox, Robert A; Williams, Felicia N; Jeschke, Marc G

2014-01-01

Background Burn injuries are associated with hyperglycemia leading to increased incidence of infections with pneumonia being one of the most prominent and adverse complication. Recently, various studies in critically ill patients indicated that increased pulmonary glucose levels with airway/blood glucose threshold over 150 mg/dl lead to an overwhelming growth of bacteria in the broncho-pulmonary system, subsequently resulting in an increased risk of pulmonary infections. The aim of the present study was to determine whether a similar cutoff value exists for severely burned pediatric patients. Methods One-hundred six severely burned pediatric patients were enrolled in the study. Patients were divided in two groups: high (H) defined as daily average glucose levels >75% of LOS >150 mg/dl), and low (L) with daily average glucose levels >75% of the LOS <150 mg/dl). Incidences of pneumonia, atelectasis, and acute respiratory distress syndrome (ARDS) were assessed. Incidence of infections, sepsis, and respiratory parameters were recorded. Blood was analyzed for glucose and insulin levels. Statistical analysis was performed using Student’s t-test and chi-square test. Significance was set at p<0.05. Results Patient groups were similar in demographics and injury characteristics. Pneumonia in patients on the mechanical ventilation (L: 21% H: 32%) and off mechanical ventilation (L: 5% H: 15%), as well as ARDS were significantly higher in the high group (L: 3% H: 19%), p<0.05, while atelectasis was not different. Patients in the high group required significantly longer ventilation compared to low patients (p<0.05). Furthermore, incidence of infection and sepsis were significantly higher in the high group, p<0.05. Conclusion Our results indicate that systemic glucose levels over 150 mg/dl are associated with a higher incidence of pneumonia confirming the previous studies in critically ill patients. PMID:24074819

Respiratory Management of Perioperative Obese Patients.

PubMed

Imber, David Ae; Pirrone, Massimiliano; Zhang, Changsheng; Fisher, Daniel F; Kacmarek, Robert M; Berra, Lorenzo

2016-12-01

With a rising incidence of obesity in the United States, anesthesiologists are faced with a larger volume of obese patients coming to the operating room as well as obese patients with ever-larger body mass indices (BMIs). While there are many cardiovascular and endocrine issues that clinicians must take into account when caring for the obese patient, one of the most prominent concerns of the anesthesiologist in the perioperative setting should be the status of the lung. Because the pathophysiology of reduced lung volumes in the obese patient differs from that of the ARDS patient, the best approach to keeping the obese patient's lung open and adequately ventilated during mechanical ventilation is unique. Although strong evidence and research are lacking regarding how to best ventilate the obese surgical patient, we aim with this review to provide an assessment of the small amount of research that has been conducted and the pathophysiology we believe influences the apparent results. We will provide a basic overview of the anatomy and pathophysiology of the obese respiratory system and review studies concerning pre-, intra-, and postoperative respiratory care. Our focus in this review centers on the best approach to keeping the lung recruited through the prevention of compression atelectasis and the maintaining of physiological lung volumes. We recommend the use of PEEP via noninvasive ventilation (NIV) before induction and endotracheal intubation, the use of both PEEP and periodic recruitment maneuvers during mechanical ventilation, and the use of PEEP via NIV after extubation. It is our hope that by studying the underlying mechanisms that make ventilating obese patients so difficult, future research can be better tailored to address this increasingly important challenge to the field of anesthesia. Copyright © 2016 by Daedalus Enterprises.

Imatinib attenuates inflammation and vascular leak in a clinically relevant two-hit model of acute lung injury.

PubMed

Rizzo, Alicia N; Sammani, Saad; Esquinca, Adilene E; Jacobson, Jeffrey R; Garcia, Joe G N; Letsiou, Eleftheria; Dudek, Steven M

2015-12-01

Acute lung injury/acute respiratory distress syndrome (ALI/ARDS), an illness characterized by life-threatening vascular leak, is a significant cause of morbidity and mortality in critically ill patients. Recent preclinical studies and clinical observations have suggested a potential role for the chemotherapeutic agent imatinib in restoring vascular integrity. Our prior work demonstrates differential effects of imatinib in mouse models of ALI, namely attenuation of LPS-induced lung injury but exacerbation of ventilator-induced lung injury (VILI). Because of the critical role of mechanical ventilation in the care of patients with ARDS, in the present study we pursued an assessment of the effectiveness of imatinib in a "two-hit" model of ALI caused by combined LPS and VILI. Imatinib significantly decreased bronchoalveolar lavage protein, total cells, neutrophils, and TNF-α levels in mice exposed to LPS plus VILI, indicating that it attenuates ALI in this clinically relevant model. In subsequent experiments focusing on its protective role in LPS-induced lung injury, imatinib attenuated ALI when given 4 h after LPS, suggesting potential therapeutic effectiveness when given after the onset of injury. Mechanistic studies in mouse lung tissue and human lung endothelial cells revealed that imatinib inhibits LPS-induced NF-κB expression and activation. Overall, these results further characterize the therapeutic potential of imatinib against inflammatory vascular leak. Copyright © 2015 the American Physiological Society.

Clinical practice of acute respiratory distress syndrome in Japan: A nationwide survey and scientific evidences.

PubMed

Tasaka, Sadatomo; Tatsumi, Koichiro

2017-07-01

There has been limited information about epidemiology and clinical practice of acute respiratory distress syndrome (ARDS) in Japan. An invitation letter to the web-based survey was mailed to all 871 board certified hospitals of the Japanese Respiratory Society. The questionnaires were designed to collect data on epidemiology and clinical practice of ARDS, including diagnostic measures and therapeutics. Within 4 months of the survey period, valid responses were obtained from 296 (34%) hospitals. The incidence of ARDS was estimated to be 3.13 cases/100 hospital beds or 1.91 cases/ICU bed per year. The most frequent underlying disease was pneumonia (34%), followed by sepsis (29%). In hospitals with fewer ICU beds, pulmonologists tended to be in charge of management of ARDS patients. Routine diagnostic measures included computed tomography of the chest (69.6% of the hospitals) and Swan-Ganz catheterization was rarely performed for diagnosis. In 87.4% of the hospitals, non-invasive ventilation was applied to management of ARDS patients, especially those with mild disease. Prone positioning and extracorporeal membrane oxygenation (ECMO) for ARDS patients was more widely adopted in hospitals with larger numbers of ICU beds and intensivists. In 58.2% of the responding hospitals, corticosteroid was considered as a treatment option for ARDS, among which pulse therapy was routinely introduced to ARDS patients in 35.4%. The incidence of ARDS in Japan was estimated to be lower than that in the recent international study. The scale and equipment of hospitals and the number of intensivists might influence clinical practice of ARDS. Copyright © 2017 The Japanese Respiratory Society. Published by Elsevier B.V. All rights reserved.

Acute respiratory distress syndrome without identifiable risk factors: A secondary analysis of the ARDS network trials.

PubMed

Harrington, John S; Schenck, Edward J; Oromendia, Clara; Choi, Augustine M K; Siempos, Ilias I

2018-06-02

We examined whether patients with acute respiratory distress syndrome (ARDS) lacking risk factors are enrolled in therapeutic trials and assessed their clinical characteristics and outcomes. We performed a secondary analysis of patient-level data pooled from the ARMA, ALVEOLI, FACTT, ALTA and EDEN ARDSNet randomized controlled trials obtained from the Biologic Specimen and Data Repository Information Coordinating Center of the National Heart, Lung and Blood Institute. We compared baseline characteristics and clinical outcomes (before and after adjustment using Poisson regression model) of ARDS patients with versus without risk factors. Of 3733 patients with ARDS, 81 (2.2%) did not have an identifiable risk factor. Patients without risk factors were younger, had lower baseline severity of illness, were more likely to have the ARDS resolve rapidly (i.e., within 24 h) (p < 0.001) and they had more ventilator-free days (median 21; p = 0.003), more intensive care unit-free days (18; p = 0.010), and more non-pulmonary organ failure-free days (24; p < 0.001) than comparators (17, 14 and 18, respectively). Differences persisted after adjustment for potential confounders. Patients with ARDS without identifiable risk factors are enrolled in therapeutic trials and may have better outcomes, including a higher proportion of rapidly resolving ARDS, than those with risk factors. Copyright © 2018. Published by Elsevier Inc.

Clinical outcomes of patients requiring ventilatory support in Brazilian intensive care units: a multicenter, prospective, cohort study

PubMed Central

2013-01-01

Introduction Contemporary information on mechanical ventilation (MV) use in emerging countries is limited. Moreover, most epidemiological studies on ventilatory support were carried out before significant developments, such as lung protective ventilation or broader application of non-invasive ventilation (NIV). We aimed to evaluate the clinical characteristics, outcomes and risk factors for hospital mortality and failure of NIV in patients requiring ventilatory support in Brazilian intensive care units (ICU). Methods In a multicenter, prospective, cohort study, a total of 773 adult patients admitted to 45 ICUs over a two-month period requiring invasive ventilation or NIV for more than 24 hours were evaluated. Causes of ventilatory support, prior chronic health status and physiological data were assessed. Multivariate analysis was used to identifiy variables associated with hospital mortality and NIV failure. Results Invasive MV and NIV were used as initial ventilatory support in 622 (80%) and 151 (20%) patients. Failure with subsequent intubation occurred in 54% of NIV patients. The main reasons for ventilatory support were pneumonia (27%), neurologic disorders (19%) and non-pulmonary sepsis (12%). ICU and hospital mortality rates were 34% and 42%. Using the Berlin definition, acute respiratory distress syndrome (ARDS) was diagnosed in 31% of the patients with a hospital mortality of 52%. In the multivariate analysis, age (odds ratio (OR), 1.03; 95% confidence interval (CI), 1.01 to 1.03), comorbidities (OR, 2.30; 95% CI, 1.28 to 3.17), associated organ failures (OR, 1.12; 95% CI, 1.05 to 1.20), moderate (OR, 1.92; 95% CI, 1.10 to 3.35) to severe ARDS (OR, 2.12; 95% CI, 1.01 to 4.41), cumulative fluid balance over the first 72 h of ICU (OR, 2.44; 95% CI, 1.39 to 4.28), higher lactate (OR, 1.78; 95% CI, 1.27 to 2.50), invasive MV (OR, 2.67; 95% CI, 1.32 to 5.39) and NIV failure (OR, 3.95; 95% CI, 1.74 to 8.99) were independently associated with hospital mortality. The predictors of NIV failure were the severity of associated organ dysfunctions (OR, 1.20; 95% CI, 1.05 to 1.34), ARDS (OR, 2.31; 95% CI, 1.10 to 4.82) and positive fluid balance (OR, 2.09; 95% CI, 1.02 to 4.30). Conclusions Current mortality of ventilated patients in Brazil is elevated. Implementation of judicious fluid therapy and a watchful use and monitoring of NIV patients are potential targets to improve outcomes in this setting. Trial registration ClinicalTrials.gov NCT01268410. PMID:23557378

Predicted body weight relationships for protective ventilation - unisex proposals from pre-term through to adult.

PubMed

Martin, Dion C; Richards, Glenn N

2017-05-23

The lung-protective ventilation bundle has been shown to reduce mortality in adult acute respiratory distress syndrome (ARDS). This concept has expanded to other areas of acute adult ventilation and is recommended for pediatric ventilation. A component of lung-protective ventilation relies on a prediction of lean body weight from height. The predicted body weight (PBW) relationship employed in the ARDS Network trial is considered valid only for adults, with a dedicated formula required for each sex. No agreed PBW formula applies to smaller body sizes. This analysis investigated whether it might be practical to derive a unisex PBW formula spanning all body sizes, while retaining relevance to established adult protective ventilation practice. Historic population-based growth charts were adopted as a reference for lean body weight, from pre-term infant through to adult median weight. The traditional ARDSNet PBW formulae acted as the reference for prevailing protective ventilation practice. Error limits for derived PBW models were relative to these references. The ARDSNet PBW formulae typically predict weights heavier than the population median, therefore no single relationship could satisfy both references. Four alternate piecewise-linear lean body-weight predictive formulae were presented for consideration, each with different balance between the objectives. The 'PBWuf + MBW' model is proposed as an appropriate compromise between prevailing practice and simplification, while also better representing lean adult body-weight. This model applies the ARDSNet 'female' formula to both adult sexes, while providing a tight fit to median body weight at smaller statures down to pre-term. The 'PBWmf + MBW' model retains consistency with current practice over the adult range, while adding prediction for small statures.

Driving pressure and survival in the acute respiratory distress syndrome.

PubMed

Amato, Marcelo B P; Meade, Maureen O; Slutsky, Arthur S; Brochard, Laurent; Costa, Eduardo L V; Schoenfeld, David A; Stewart, Thomas E; Briel, Matthias; Talmor, Daniel; Mercat, Alain; Richard, Jean-Christophe M; Carvalho, Carlos R R; Brower, Roy G

2015-02-19

Mechanical-ventilation strategies that use lower end-inspiratory (plateau) airway pressures, lower tidal volumes (VT), and higher positive end-expiratory pressures (PEEPs) can improve survival in patients with the acute respiratory distress syndrome (ARDS), but the relative importance of each of these components is uncertain. Because respiratory-system compliance (CRS) is strongly related to the volume of aerated remaining functional lung during disease (termed functional lung size), we hypothesized that driving pressure (ΔP=VT/CRS), in which VT is intrinsically normalized to functional lung size (instead of predicted lung size in healthy persons), would be an index more strongly associated with survival than VT or PEEP in patients who are not actively breathing. Using a statistical tool known as multilevel mediation analysis to analyze individual data from 3562 patients with ARDS enrolled in nine previously reported randomized trials, we examined ΔP as an independent variable associated with survival. In the mediation analysis, we estimated the isolated effects of changes in ΔP resulting from randomized ventilator settings while minimizing confounding due to the baseline severity of lung disease. Among ventilation variables, ΔP was most strongly associated with survival. A 1-SD increment in ΔP (approximately 7 cm of water) was associated with increased mortality (relative risk, 1.41; 95% confidence interval [CI], 1.31 to 1.51; P<0.001), even in patients receiving "protective" plateau pressures and VT (relative risk, 1.36; 95% CI, 1.17 to 1.58; P<0.001). Individual changes in VT or PEEP after randomization were not independently associated with survival; they were associated only if they were among the changes that led to reductions in ΔP (mediation effects of ΔP, P=0.004 and P=0.001, respectively). We found that ΔP was the ventilation variable that best stratified risk. Decreases in ΔP owing to changes in ventilator settings were strongly associated with increased survival. (Funded by Fundação de Amparo e Pesquisa do Estado de São Paulo and others.).

Acute respiratory failure requiring mechanical ventilation in severe chronic obstructive pulmonary disease (COPD)

PubMed Central

Gadre, Shruti K.; Duggal, Abhijit; Mireles-Cabodevila, Eduardo; Krishnan, Sudhir; Wang, Xiao-Feng; Zell, Katrina; Guzman, Jorge

2018-01-01

Abstract There are limited data on the epidemiology of acute respiratory failure necessitating mechanical ventilation in patients with severe chronic obstructive pulmonary disease (COPD). The prognosis of acute respiratory failure requiring invasive mechanical ventilation is believed to be grim in this population. The purpose of this study was to illustrate the epidemiologic characteristics and outcomes of patients with underlying severe COPD requiring mechanical ventilation. A retrospective study of patients admitted to a quaternary referral medical intensive care unit (ICU) between January 2008 and December 2012 with a diagnosis of severe COPD and requiring invasive mechanical ventilation for acute respiratory failure. We evaluated 670 patients with an established diagnosis of severe COPD requiring mechanical ventilation for acute respiratory failure of whom 47% were male with a mean age of 63.7 ± 12.4 years and Acute physiology and chronic health evaluation (APACHE) III score of 76.3 ± 27.2. Only seventy-nine (12%) were admitted with a COPD exacerbation, 27(4%) had acute respiratory distress syndrome (ARDS), 78 (12%) had pneumonia, 78 (12%) had sepsis, and 312 (47%) had other causes of respiratory failure, including pulmonary embolism, pneumothorax, etc. Eighteen percent of the patients received a trial of noninvasive positive pressure ventilation. The median duration of mechanical ventilation was 3 days (interquartile range IQR 2–7); the median duration for ICU length of stay (LOS) was 5 (IQR 2–9) days and the median duration of hospital LOS was 12 (IQR 7–22) days. The overall ICU mortality was 25%. Patients with COPD exacerbation had a shorter median duration of mechanical ventilation (2 vs 4 days; P = .04), ICU (3 vs 5 days; P = .01), and hospital stay (10 vs 13 days; P = .01). The ICU mortality (9% vs 27%; P < .001), and the hospital mortality (17% vs 32%; P = .004) for mechanically ventilated patients with an acute exacerbation of severe COPD were lower than those with other etiologies of acute respiratory failure. A 1-unit increase in the APACHE III score was associated with a 1% decrease and having an active cancer was associated with a 45% decrease in ICU survival (P < .001). A discharge home at the time of index admission was associated an increased overall survival compared with any other discharge location (P < .001). We report good early outcomes, but significant long-term morbidity in patients with severe COPD requiring invasive mechanical ventilation for acute respiratory failure. A higher APACHE score and presence of active malignancy are associated with a decrease in ICU survival, whereas a discharge home is associated with an increase in the overall survival. PMID:29703009

Acute respiratory failure requiring mechanical ventilation in severe chronic obstructive pulmonary disease (COPD).

PubMed

Gadre, Shruti K; Duggal, Abhijit; Mireles-Cabodevila, Eduardo; Krishnan, Sudhir; Wang, Xiao-Feng; Zell, Katrina; Guzman, Jorge

2018-04-01

There are limited data on the epidemiology of acute respiratory failure necessitating mechanical ventilation in patients with severe chronic obstructive pulmonary disease (COPD). The prognosis of acute respiratory failure requiring invasive mechanical ventilation is believed to be grim in this population. The purpose of this study was to illustrate the epidemiologic characteristics and outcomes of patients with underlying severe COPD requiring mechanical ventilation.A retrospective study of patients admitted to a quaternary referral medical intensive care unit (ICU) between January 2008 and December 2012 with a diagnosis of severe COPD and requiring invasive mechanical ventilation for acute respiratory failure.We evaluated 670 patients with an established diagnosis of severe COPD requiring mechanical ventilation for acute respiratory failure of whom 47% were male with a mean age of 63.7 ± 12.4 years and Acute physiology and chronic health evaluation (APACHE) III score of 76.3 ± 27.2. Only seventy-nine (12%) were admitted with a COPD exacerbation, 27(4%) had acute respiratory distress syndrome (ARDS), 78 (12%) had pneumonia, 78 (12%) had sepsis, and 312 (47%) had other causes of respiratory failure, including pulmonary embolism, pneumothorax, etc. Eighteen percent of the patients received a trial of noninvasive positive pressure ventilation. The median duration of mechanical ventilation was 3 days (interquartile range IQR 2-7); the median duration for ICU length of stay (LOS) was 5 (IQR 2-9) days and the median duration of hospital LOS was 12 (IQR 7-22) days. The overall ICU mortality was 25%. Patients with COPD exacerbation had a shorter median duration of mechanical ventilation (2 vs 4 days; P = .04), ICU (3 vs 5 days; P = .01), and hospital stay (10 vs 13 days; P = .01). The ICU mortality (9% vs 27%; P < .001), and the hospital mortality (17% vs 32%; P = .004) for mechanically ventilated patients with an acute exacerbation of severe COPD were lower than those with other etiologies of acute respiratory failure. A 1-unit increase in the APACHE III score was associated with a 1% decrease and having an active cancer was associated with a 45% decrease in ICU survival (P < .001). A discharge home at the time of index admission was associated an increased overall survival compared with any other discharge location (P < .001).We report good early outcomes, but significant long-term morbidity in patients with severe COPD requiring invasive mechanical ventilation for acute respiratory failure. A higher APACHE score and presence of active malignancy are associated with a decrease in ICU survival, whereas a discharge home is associated with an increase in the overall survival.

[A comparison of leak compensation in six acute care ventilators during non-invasive ventilation].

PubMed

Hu, X S; Wang, Y; Wang, Z T; Yan, P; Zhang, X G; Zhao, S F; Xie, F; Gu, H J; Xie, L X

2017-02-12

Objective: To compare the ability of leak compensation in 6 medical ventilators during non-invasive ventilation. Methods: Six medical ventilators were selected, including 3 non-invasive ventilators (V60, Flexo and Stellar150), and 3 invasive ventilators(Avea, Servo I and BellaVist). Using a lung simulator, the ability of leak compensation was evaluated during triggering and cycling in 2 respiratory mechanics conditions (high airway resistance condition and high elastance resistance condition), and each condition was performed under 2 PEEP levels (4, and 8 cmH(2)O, 1 mmHg=0.098 kPa) at 4 air leak level conditions (L0: 2-3 L/min, L1: 8-10 L/min, L2: 22-27 L/min, L3: 35-40 L/min). Results: In the high elastance resistance condition (L2, L3)with different leak levels, the number of auto-triggering and miss-triggering of the non-invasive ventilator Flexo was significantly less than those of the others (L2: 1, 1; L3: 1.67, 1.33, P <0.01), and had better synchronization (L2: 2.33, 2.33; L3: 3.33, 3.33, P <0.01). In the high airway resistance condition with PEEP 4 cmH(2)O, V60 had less number of auto-triggering than other ventilators ( P <0.01), while in the high airway resistance condition with PEEP 8 cmH(2)O, Stellar150 had less number of miss-triggering than other ventilators (1, 0.67, 0, P <0.01). Flexo had a shorter trigger delay time than other ventilators in both high airway resistance and high elastance resistance conditions with L0 and L1 leak levels and PEEP levels [ARDS, PEEP=4: (109.8±1.8) ms, (112.0±0.6) ms; ARDS, PEEP=8: (103.1±0.7) ms, (109.7±0.7) ms; COPD, PEEP=4: (207.3±1.1) ms, (220.8±1.1) ms; COPD, PEEP=8: (195.6±6.7) ms, (200.0±1.2) ms , P <0.01]. Stellar150 had the shortest trigger delay time in high airway resistance condition with PEEP 4 cmH(2)O and high leak level L3[(262.8±0.8) ms , P <0.01]. V60 had a good performance on trigger delay time in high elastance resistance condition with PEEP 4 and 8 cmH(2)O, and also was most stable in increasing leak levels. Conclusion: In high airway resistance and high elastance resistance conditions with different PEEP levels and leak levels, V60, Stellar150, Flexo and BellaVista ventilators could be synchronized, among which V60, Stellar150 and Flexo presented a good performance features in specific conditions.

Plasma membrane wounding and repair in pulmonary diseases.

PubMed

Cong, Xiaofei; Hubmayr, Rolf D; Li, Changgong; Zhao, Xiaoli

2017-03-01

Various pathophysiological conditions such as surfactant dysfunction, mechanical ventilation, inflammation, pathogen products, environmental exposures, and gastric acid aspiration stress lung cells, and the compromise of plasma membranes occurs as a result. The mechanisms necessary for cells to repair plasma membrane defects have been extensively investigated in the last two decades, and some of these key repair mechanisms are also shown to occur following lung cell injury. Because it was theorized that lung wounding and repair are involved in the pathogenesis of acute respiratory distress syndrome (ARDS) and idiopathic pulmonary fibrosis (IPF), in this review, we summarized the experimental evidence of lung cell injury in these two devastating syndromes and discuss relevant genetic, physical, and biological injury mechanisms, as well as mechanisms used by lung cells for cell survival and membrane repair. Finally, we discuss relevant signaling pathways that may be activated by chronic or repeated lung cell injury as an extension of our cell injury and repair focus in this review. We hope that a holistic view of injurious stimuli relevant for ARDS and IPF could lead to updated experimental models. In addition, parallel discussion of membrane repair mechanisms in lung cells and injury-activated signaling pathways would encourage research to bridge gaps in current knowledge. Indeed, deep understanding of lung cell wounding and repair, and discovery of relevant repair moieties for lung cells, should inspire the development of new therapies that are likely preventive and broadly effective for targeting injurious pulmonary diseases. Copyright © 2017 the American Physiological Society.

Impact and safety of open lung biopsy in patients with acute respiratory distress syndrome (ARDS).

PubMed

Ortiz, G; Garay, M; Mendoza, D; Cardinal-Fernández, P

2018-02-28

Acute respiratory distress syndrome (ARDS) is an inflammatory lung disorder, and its pathological hallmark is diffuse alveolar damage (DAD). Given that open lung biopsy (OLB) can sometimes result in severe side effects, it is rarely performed in patients with ARDS. The aims of this study were to describe: (a) the rate of treatment change associated with the histological result; and (b) the incidence of side effects induced by OLB. A retrospective, single-center, descriptive observational study was carried out in Hospital Santa Clara (Bogotá, Colombia) from February 2007 to January 2014. Critically ill patients over 18 years of age, undergoing invasive mechanical ventilation, diagnosed with ARDS of unknown etiology, and with OLB performed at the bedside. ARDS was diagnosed according to the Berlin definition. DAD was defined by the presence of a hyaline membrane plus at least one of the following: intra-alveolar edema, alveolar type I cell necrosis, alveolar type II cell (cuboidal cells) proliferation progressively covering the denuded alveolar-capillary membrane, interstitial proliferation of fibroblasts and myofibroblasts, or organizing interstitial fibrosis. The rate of treatment change (RTC) was established according to whether the OLB pathology report resulted in: a) the prescription or discontinuation of an antimicrobial; b) the indication of new procedures; c) medical interconsultation; or d) limitation of therapeutic effort. Patients were followed-up until death or hospital discharge. This study was approved by the Ethics Committee. A total of 32 OLBs were performed during the study period; 17 were ruled out as they did not involve ARDS, and 15 were considered for further analysis. A histological diagnosis was reached in 14 of the 15 patients (12 DAD, one case of bronchiolitis obliterans organizing pneumonia and one case of Wegener's granulomatosis with alveolar hemorrhage). The RTC rate was 0.73. The most frequent intervention was discontinuation of antimicrobial or corticosteroid treatment. No deaths but four side effects (3 airway leaks and one hemothorax) were associated with the OLB procedure. All were resolved before ICU discharge. The information provided by OLB performed at the bedside in ARDS patients of unknown etiology could be relevant, as it may optimize treatment. The risk associated with OLB seems to be acceptable. Copyright © 2018 Elsevier España, S.L.U. y SEMICYUC. All rights reserved.

Diagnosis of acute respiratory distress syndrome by exhaled breath analysis

PubMed Central

2018-01-01

The acute respiratory distress syndrome (ARDS) is a complication of critical illness that is characterized by acute onset, protein rich, pulmonary edema. There is no treatment for ARDS, other than the reduction of additional ventilator induced lung injury. Prediction or earlier recognition of ARDS could result in preventive measurements and might decrease mortality and morbidity. Exhaled breath contains volatile organic compounds (VOCs), a collection of hundreds of small molecules linked to several physiological and pathophysiological processes. Analysis of exhaled breath through gas-chromatography and mass-spectrometry (GC-MS) has resulted in an accurate diagnosis of ARDS in several studies. Most identified markers are linked to lipid peroxidation. Octane is one of the few markers that was validated as a marker of ARDS and is pathophysiologically likely to be increased in ARDS. None of the currently studied breath analysis methods is directly applicable in clinical practice. Two steps have to be taken before any breath test can be allowed into the intensive care unit. External validation in a multi-center study is a prerequisite for any of the candidate breath markers and the breath test should outperform clinical prediction scores. Second, the technology for breath analysis should be adapted so that it is available at a decentralized lab inside the intensive care unit and can be operated by trained nurses, in order to reduce the analysis time. In conclusion, exhaled analysis might be used for the early diagnosis and prediction of ARDS in the near future but several obstacles have to be taken in the coming years. Most of the candidate markers can be linked to lipid peroxidation. Only octane has been validated in a temporal external validation cohort and is, at this moment, the top-ranking breath biomarker for ARDS. PMID:29430450

The coexistence of autoimmune rheumatic diseases and thymomas.

PubMed

Jiang, Ying; Dai, Xiaodan; Duan, Liping; Zhou, Yaou

2017-01-01

Autoimmune rheumatic diseases (ARDs), involving immune disturbances resulting from auto-inflammatory mechanisms, are a group of diseases characterized by autoimmunity and autoimmunemediated organ damage. Thymoma, whose mechanism is also associated with immune abnormalities, is the most common neoplasm of the anterior mediastinum. But thymoma with ARDs is relatively less frequent. The clinical characteristics of the coexistence of ARDs and thymomas are still not very clear. And the therapeutic strategy for ARDs combined with thymomas varies, with an uncertain outcome. The aim of this study was to investigate the clinical characteristics of the coexistence of ARDs and thymomas in order to speculate whether a thymectomy is effective for ARDs combined with thymomas, and to seek the proper therapeutic strategy for treating ARDs combined with thymomas. We presented 2 cases of the coexistence of ARDs and thymomas. Then, we summarized 20 cases (including our 2 cases) in which the ARD was diagnosed concurrently with, or prior to, the thymoma. Pure red cell aplastic anemia (PRCA) might be associated with an ARD and a thymoma, and a thymectomy may lead to the appearance, exacerbation, or remission of ARDs. Searching for a thymoma is necessitated if a patient with ARDs experiences PRCA and the effects of thymectomy in ARDs combined with thymomas may be associated with the onset sequence of ARDs and thymomas.

[Biochemical and biophysical investigation of liposome action in artificially induced ARDS in rabbit lungs].

PubMed

Petkova, D; Steneva, I; Iordanova, A; Khristova, E; Lalchev, Z

2007-01-01

The aim of this study is to evaluate the application of phospholipid liposomes in HCl--induced RDS in rabbits. Acute respiratory distress syndrome was induced by administration of 0.2 N HCl via intratracheal instillation for 45 min. After induced ARDS animals under artificial lung ventilation were retreated with liposomes for 60 min. Arterial blood gas analysis was performed at 30, 45 and 60 min after liposome application. Untreated animals were ventilated for the same time. Rabbits were killed with thiopental and bronhoalveolar lavage fluid biochemical and biophysical parameters were investigated. HCl- lung injury caused decrease of arterial oxygen pressure/ fraction of inspired oxygen ratio more than 50% compared to the control. We obtained high respiratory acidosis as well. The instillation of liposomes led to reversion of gas exchange at 60 min. after application almost to the control value. In order to characterize the rabbit lung tissue changes after HCl-treatment histological and ultra thin slices were obtained. Electron microscopic preparations demonstrate disappearance of surface active film in treated animals. Application of liposomes led to visualization of osmophilic material forming lamellae in lamellar bodies. On the basis of the results obtained we may assume that it is likely that the liposomes assessed in this study might be used for in vivo improvement of oxygenation in acid aspiration induced ARDS.

A clinical classification of the acute respiratory distress syndrome for predicting outcome and guiding medical therapy*.

PubMed

Villar, Jesús; Fernández, Rosa L; Ambrós, Alfonso; Parra, Laura; Blanco, Jesús; Domínguez-Berrot, Ana M; Gutiérrez, José M; Blanch, Lluís; Añón, José M; Martín, Carmen; Prieto, Francisca; Collado, Javier; Pérez-Méndez, Lina; Kacmarek, Robert M

2015-02-01

Current in-hospital mortality of the acute respiratory distress syndrome (ARDS) is above 40%. ARDS outcome depends on the lung injury severity within the first 24 hours of ARDS onset. We investigated whether two widely accepted cutoff values of PaO2/FIO2 and positive end-expiratory pressure (PEEP) would identify subsets of patients with ARDS for predicting outcome and guiding therapy. A 16-month (September 2008 to January 2010) prospective, multicenter, observational study. Seventeen multidisciplinary ICUs in Spain. We studied 300 consecutive, mechanically ventilated patients meeting American-European Consensus Conference criteria for ARDS (PaO2/FIO2 ≤ 200 mm Hg) on PEEP greater than or equal to 5 cm H2O, and followed up until hospital discharge. None. Based on threshold values for PaO2/FIO2 (150 mm Hg) and PEEP (10 cm H2O) at ARDS onset and at 24 hours, we assigned patients to four categories: group I (PaO2/FIO2 ≥ 150 on PEEP < 10), group II (PaO2/FIO2 ≥ 150 on PEEP ≥ 10), group III (PaO2/FIO2 < 150 on PEEP < 10), and group IV (PaO2/FIO2 < 150 on PEEP ≥ 10). The primary outcome was all-cause in-hospital mortality. Overall hospital mortality was 46.3%. Although at study entry, patients with PaO2/FIO2 less than 150 had a higher mortality than patients with a PaO2/FIO2 greater than or equal to 150 (p = 0.044), there was minimal variability in mortality among the four groups (p = 0.186). However, classification of patients in each group changed markedly after 24 hours of usual care. Group categorization at 24 hours provided a strong association with in-hospital mortality (p < 0.00001): group I had the lowest mortality (23.1%), whereas group IV had the highest mortality (60.3%). The degree of lung dysfunction established by a PaO2/FIO2 of 150 mm Hg and a PEEP of 10 cm H2O demonstrated that ARDS is not a homogeneous disorder. Rather, it is a series of four subsets that should be considered for enrollment in clinical trials and for guiding therapy. A major contribution of our study is the distinction between survival after 24 hours of care versus survival at the time of ARDS onset.

Acute respiratory distress syndrome: the Berlin Definition.

PubMed

Ranieri, V Marco; Rubenfeld, Gordon D; Thompson, B Taylor; Ferguson, Niall D; Caldwell, Ellen; Fan, Eddy; Camporota, Luigi; Slutsky, Arthur S

2012-06-20

The acute respiratory distress syndrome (ARDS) was defined in 1994 by the American-European Consensus Conference (AECC); since then, issues regarding the reliability and validity of this definition have emerged. Using a consensus process, a panel of experts convened in 2011 (an initiative of the European Society of Intensive Care Medicine endorsed by the American Thoracic Society and the Society of Critical Care Medicine) developed the Berlin Definition, focusing on feasibility, reliability, validity, and objective evaluation of its performance. A draft definition proposed 3 mutually exclusive categories of ARDS based on degree of hypoxemia: mild (200 mm Hg < PaO2/FIO2 ≤ 300 mm Hg), moderate (100 mm Hg < PaO2/FIO2 ≤ 200 mm Hg), and severe (PaO2/FIO2 ≤ 100 mm Hg) and 4 ancillary variables for severe ARDS: radiographic severity, respiratory system compliance (≤40 mL/cm H2O), positive end-expiratory pressure (≥10 cm H2O), and corrected expired volume per minute (≥10 L/min). The draft Berlin Definition was empirically evaluated using patient-level meta-analysis of 4188 patients with ARDS from 4 multicenter clinical data sets and 269 patients with ARDS from 3 single-center data sets containing physiologic information. The 4 ancillary variables did not contribute to the predictive validity of severe ARDS for mortality and were removed from the definition. Using the Berlin Definition, stages of mild, moderate, and severe ARDS were associated with increased mortality (27%; 95% CI, 24%-30%; 32%; 95% CI, 29%-34%; and 45%; 95% CI, 42%-48%, respectively; P < .001) and increased median duration of mechanical ventilation in survivors (5 days; interquartile [IQR], 2-11; 7 days; IQR, 4-14; and 9 days; IQR, 5-17, respectively; P < .001). Compared with the AECC definition, the final Berlin Definition had better predictive validity for mortality, with an area under the receiver operating curve of 0.577 (95% CI, 0.561-0.593) vs 0.536 (95% CI, 0.520-0.553; P < .001). This updated and revised Berlin Definition for ARDS addresses a number of the limitations of the AECC definition. The approach of combining consensus discussions with empirical evaluation may serve as a model to create more accurate, evidence-based, critical illness syndrome definitions and to better inform clinical care, research, and health services planning.

Analysis of risk factors for and the prognosis of postoperative acute respiratory distress syndrome in patients with Stanford type A aortic dissection.

PubMed

Chen, Mei-Fang; Chen, Liang-Wan; Cao, Hua; Lin, Yong

2016-10-01

To explore the risk factors for and the prognosis of postoperative acute respiratory distress syndrome (ARDS) in patients with Stanford type A aortic dissection (AD). This retrospective nested case-control study included 527 Stanford type A AD patients who were divided into ARDS groups and non-ARDS groups. The clinical features of the groups were examined. The fifty-nine patients in the ARDS group exhibited extended durations of cardiopulmonary bypass (CPB) (P=0.004), deep hypothermic circulatory arrest (DHCA) (P=0.000), ventilator support (P=0.013) and intensive care unit (ICU) stay (P=0.045), higher hospital costs (P=0.000), larger perioperative transfusions volumes [red blood cells (RBC): P=0.002, platelets (PLT): P=0.040, fresh frozen plasma (FFP): P=0.001], more frequent pulmonary infection (P=0.018) and multiple organ dysfunction syndrome (MODS) (P=0.040) and a higher rate of in-hospital mortality (P=0.020). The ARDS group exhibited worse statuses in terms of oxygenation index (OI) values (P=0.000) and Apache II scores (P=0.000). DHCA [P=0.000, odds ratio (OR) =2.589] and perioperative transfusion (RBC: P=0.000, OR =2.573; PLT: P=0.027, OR =1.571; FFP: P=0.002, OR =1.929) were independent risk factors for postoperative ARDS. The survival rates and median survival times after discharge were similar between the two groups (P=0.843). DHCA duration and perioperative transfusion volume were independent risk factors for postoperative ARDS which warrants greater attention by the cardiac surgeons.

Effect of PEEP and Tidal Volume on Ventilation Distribution and End-Expiratory Lung Volume: A Prospective Experimental Animal and Pilot Clinical Study

PubMed Central

Becher, Tobias; Schädler, Dirk; Pulletz, Sven; Freitag-Wolf, Sandra; Weiler, Norbert; Frerichs, Inéz

2013-01-01

Introduction Lung-protective ventilation aims at using low tidal volumes (VT) at optimum positive end-expiratory pressures (PEEP). Optimum PEEP should recruit atelectatic lung regions and avoid tidal recruitment and end-inspiratory overinflation. We examined the effect of VT and PEEP on ventilation distribution, regional respiratory system compliance (CRS), and end-expiratory lung volume (EELV) in an animal model of acute lung injury (ALI) and patients with ARDS by using electrical impedance tomography (EIT) with the aim to assess tidal recruitment and overinflation. Methods EIT examinations were performed in 10 anaesthetized pigs with normal lungs ventilated at 5 and 10 ml/kg body weight VT and 5 cmH2O PEEP. After ALI induction, 10 ml/kg VT and 10 cmH2O PEEP were applied. Afterwards, PEEP was set according to the pressure-volume curve. Animals were randomized to either low or high VT ventilation changed after 30 minutes in a crossover design. Ventilation distribution, regional CRS and changes in EELV were analyzed. The same measures were determined in five ARDS patients examined during low and high VT ventilation (6 and 10 (8) ml/kg) at three PEEP levels. Results In healthy animals, high compared to low VT increased CRS and ventilation in dependent lung regions implying tidal recruitment. ALI reduced CRS and EELV in all regions without changing ventilation distribution. Pressure-volume curve-derived PEEP of 21±4 cmH2O (mean±SD) resulted in comparable increase in CRS in dependent and decrease in non-dependent regions at both VT. This implied that tidal recruitment was avoided but end-inspiratory overinflation was present irrespective of VT. In patients, regional CRS differences between low and high VT revealed high degree of tidal recruitment and low overinflation at 3±1 cmH2O PEEP. Tidal recruitment decreased at 10±1 cmH2O and was further reduced at 15±2 cmH2O PEEP. Conclusions Tidal recruitment and end-inspiratory overinflation can be assessed by EIT-based analysis of regional CRS. PMID:23991138

[Effect of different transpulmonary pressures guided mechanical ventilation on respiratory and hemodynamics of patients with ARDS: a prospective randomized controlled trial].

PubMed

Li, Jianqiu; Luo, Zhihui; Li, Xiaolei; Huang, Zhongyi; Han, Jie; Li, Zifeng; Zhou, Zhaoxiong; Chen, Houwang

2017-01-01

To assess the effect of different transpulmonary pressures (Ptp) guided mechanical ventilation (MV) on respiratory function and hemodynamics parameters of patients with acute respiratory distress syndrome (ARDS), and to find out a more optimized Ptp. A prospective randomized controlled trial (RCT) was conducted. The ventilated patients with ARDS admitted to Department of Critical Care Medicine (ICU) of Shenzhen Shajing Affiliated Hospital of Guangzhou Medical University and Department of Emergency and Critical Care Medicine (EICU) of Shenzhen Hospital of South Medical University from February 2013 to August 2016 were enrolled. According to random number table method, all patients were divided into control group and observation group. The patients in observation group was subdivided into three subgroups according to the different setting of Ptp, namely Ptp 10, 15, 20 cmH 2 O (1 cmH 2 O = 0.098 kPa) subgroups. The patients in all groups received standard treatment in accordance with the international guidelines for ARDS. The patients in control group were ventilated by guidance of ARDSNet, and the patients in observation group were ventilated by guidance of different Ptp. After setting different Ptp at 1, 24, 48 hours in the process of MV, respiratory function parameters of patients in all groups were determined. The hemodynamic parameters were determined by using pulse indicating continuous cardiac output (PiCCO) technology. The duration of MV, length of ICU stay and 28-day mortality were recorded. A total of 67 patients with ARDS were enrolled, among whom 2 patients died within 48 hours, and 1 case was lost to follow-up. Finally, 64 patients completed the study, 43 patients in observation group, and 21 in control group. There were no significant differences in gender composition, age, oxygenation index (PaO 2 /FiO 2 ) within 4 hours after hospital admission and acute physiology and chronic health evaluation II (APACHE II) score between the two groups, which showed the baseline was equivalent and comparable. The respiratory function and hemodynamic parameters showed no obvious change in control group at different time points of MV; but with the extension of ventilation, the respiratory function was improved significantly in observation group, and the gradually rising of Ptp had obvious adverse effects on hemodynamics parameters. Compared with control group, at 48 hours of ventilation after setting Ptp, the respiratory function in Ptp 20 cmH 2 O subgroup was improved significantly, PaO 2 /FiO 2 , arterial partial pressure of carbon dioxide (PaCO 2 ), positive end-expiratory pressure (PEEP), airway platform pressure (Pplat), and lung compliance (Cst) were significantly increased [PaO 2 /FiO 2 (mmHg, 1 mmHg = 0.133 kPa): 220.9±30.8 vs. 178.5±42.9, PaCO 2 (mmHg): 55.1±7.6 vs. 38.6±4.8, PEEP (cmH 2 O): 24.7±4.8 vs. 6.6±2.2, Pplat (cmH 2 O): 34.4±3.7 vs. 20.7±3.5, Cst (mL/cmH 2 O): 23.8±3.6 vs. 13.1±4.6; all P < 0.05], and extravascular lung water index (ELWI) was significantly decreased (mL/kg: 6.8±1.7 vs. 10.8±2.6, P < 0.05), but mean artery pressure (MAP), cardiac index (CI), global end-diastolic volume index (GEDVI) such as hemodynamics parameters were also significantly reduced [MAP (mmHg): 58.8±6.7 vs. 69.7±4.7, CI (mL×s -1 ×m -2 ): 46.7±23.3 vs. 73.3±30.0, GEDVI (mL/m 2 ): 633.2±45.2 vs. 702.6±55.7; all P < 0.05]; the PaO 2 /FiO 2 , PEEP, Pplat, and Cst in Ptp 10 cmH 2 O subgroup were significantly increased [PaO 2 /FiO 2 (mmHg): 183.4±45.5 vs. 178.5±42.9, PEEP (cmH 2 O): 14.4±3.6 vs. 6.6±2.2, Pplat (cmH 2 O): 25.7±5.6 vs. 20.7±3.5, Cst (mL/cmH 2 O): 16.2±4.3 vs. 13.1±4.6; all P < 0.05], and ELWI was significantly reduced (mL/kg: 8.7±1.8 vs. 10.8±2.6, P < 0.05), but the MAP, CI and GEDVI showed no significant difference [MAP (mmHg): 65.8±4.6 vs. 69.7±4.7, CI (mL×s -1 ×m -2 ): 65.0±35.0 vs. 73.3±30.0, GEDVI (mL/m 2 ): 706.7±54.4 vs. 702.6±55.7; all P > 0.05]. The above illustrated that 10 cmH 2 O Ptp could act as the same as 20 cmH 2 O did to improve oxygenation and respiratory function, but had no obvious effect on hemodynamics. Compared with control group, the duration of MV and the length of ICU stay showed no significant differences in Ptp 10 cmH 2 O and 15 cmH 2 O subgroups, but those in 20 cmH 2 O subgroup were significantly shortened [duration of MV (days): 95.5±21.5 vs. 130.8±23.6, length of ICU stay (days): 8.1±2.2 vs. 12.8±2.8, both P > 0.05]. There was no significant difference in 28-day mortality among the groups. MV guided by Ptp of 10 cmH 2 O could improve oxygenation and respiratory mechanics, while has less hemodynamic influence. It was a safe and effective cardiopulmonary protection ventilation method.

Intensive care unit surveillance of influenza infection in France: the 2009/10 pandemic and the three subsequent seasons.

PubMed

Bonmarin, Isabelle; Belchior, Emmanuel; Bergounioux, Jean; Brun-Buisson, Christian; Mégarbane, Bruno; Chappert, Jean Loup; Hubert, Bruno; Le Strat, Yann; Lévy-Bruhl, Daniel

2015-01-01

During the 2009/10 pandemic, a national surveillance system for severe influenza cases was set up in France. We present results from the system's first four years. All severe influenza cases admitted to intensive care units (ICU) were reported to the Institut de Veille Sanitaire using a standardised form: data on demographics, immunisation and virological status, risk factors, severity (e.g. acute respiratory distress syndrome (ARDS) onset, mechanical ventilation, extracorporeal life support) and outcome. Multivariate analysis was performed to identify factors associated with ARDS and death. The number of confirmed influenza cases varied from 1,210 in 2009/10 to 321 in 2011/12. Most ICU patients were infected with A(H1N1)pdm09, except during the 2011/12 winter season when A(H3N2)-related infections predominated. Patients' characteristics varied according to the predominant strain. Based on multivariate analysis, risk factors associated with death were age ≥ 65 years, patients with any of the usual recommended indications for vaccination and clinical severity. ARDS occurred more frequently in patients who were middle-aged (36-55 years), pregnant, obese, or infected with A(H1N1)pdm09. Female sex and influenza vaccination were protective. These data confirm the persistent virulence of A(H1N1)pdm09 after the pandemic and the heterogeneity of influenza seasons, and reinforce the need for surveillance of severe influenza cases.

Stability of ARDS subphenotypes over time in two randomised controlled trials.

PubMed

Delucchi, Kevin; Famous, Katie R; Ware, Lorraine B; Parsons, Polly E; Thompson, B Taylor; Calfee, Carolyn S

2018-05-01

Two distinct acute respiratory distress syndrome (ARDS) subphenotypes have been identified using data obtained at time of enrolment in clinical trials; it remains unknown if these subphenotypes are durable over time. To determine the stability of ARDS subphenotypes over time. Secondary analysis of data from two randomised controlled trials in ARDS, the ARMA trial of lung protective ventilation (n=473; patients randomised to low tidal volumes only) and the ALVEOLI trial of low versus high positive end-expiratory pressure (n=549). Latent class analysis (LCA) and latent transition analysis (LTA) were applied to data from day 0 and day 3, independent of clinical outcomes. In ALVEOLI, LCA indicated strong evidence of two ARDS latent classes at days 0 and 3; in ARMA, evidence of two classes was stronger at day 0 than at day 3. The clinical and biological features of these two classes were similar to those in our prior work and were largely stable over time, though class 2 demonstrated evidence of progressive organ failures by day 3, compared with class 1. In both LCA and LTA models, the majority of patients (>94%) stayed in the same class from day 0 to day 3. Clinical outcomes were statistically significantly worse in class 2 than class 1 and were more strongly associated with day 3 class assignment. ARDS subphenotypes are largely stable over the first 3 days of enrolment in two ARDS Network trials, suggesting that subphenotype identification may be feasible in the context of clinical trials. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Omentin protects against LPS-induced ARDS through suppressing pulmonary inflammation and promoting endothelial barrier via an Akt/eNOS-dependent mechanism.

PubMed

Qi, Di; Tang, Xumao; He, Jing; Wang, Daoxin; Zhao, Yan; Deng, Wang; Deng, Xinyu; Zhou, Guoqi; Xia, Jing; Zhong, Xi; Pu, Shenglan

2016-09-08

Acute respiratory distress syndrome (ARDS) is characterized by increased pulmonary inflammation and endothelial barrier permeability. Omentin has been shown to benefit obesity-related systemic vascular diseases; however, its effects on ARDS are unknown. In the present study, the level of circulating omentin in patients with ARDS was assessed to appraise its clinical significance in ARDS. Mice were subjected to systemic administration of adenoviral vector expressing omentin (Ad-omentin) and one-shot treatment of recombinant human omentin (rh-omentin) to examine omentin's effects on lipopolysaccharide (LPS)-induced ARDS. Pulmonary endothelial cells (ECs) were treated with rh-omentin to further investigate its underlying mechanism. We found that a decreased level of circulating omentin negatively correlated with white blood cells and procalcitonin in patients with ARDS. Ad-omentin protected against LPS-induced ARDS by alleviating the pulmonary inflammatory response and endothelial barrier injury in mice, accompanied by Akt/eNOS pathway activation. Treatment of pulmonary ECs with rh-omentin attenuated inflammatory response and restored adherens junctions (AJs), and cytoskeleton organization promoted endothelial barrier after LPS insult. Moreover, the omentin-mediated enhancement of EC survival and differentiation was blocked by the Akt/eNOS pathway inactivation. Therapeutic rh-omentin treatment also effectively protected against LPS-induced ARDS via the Akt/eNOS pathway. Collectively, these data indicated that omentin protects against LPS-induced ARDS by suppressing inflammation and promoting the pulmonary endothelial barrier, at least partially, through an Akt/eNOS-dependent mechanism. Therapeutic strategies aiming to restore omentin levels may be valuable for the prevention or treatment of ARDS.

[Lung and kidney failure. Pathogenesis, interactions, and therapy].

PubMed

John, S; Willam, C

2015-09-01

The lungs and kidneys represent the most often affected organs (acute respiratory distress syndrome, ARDS or kidney failure) in multiple organ failure (MOF) due to shock, trauma, or sepsis with a still unacceptable high mortality for both organ failures. Although the exact pathophysiological mechanisms of MOF are not completely elucidated, it appears that the lungs and kidneys share several pathophysiologic pathways and have the potential to further harm each other (kidney-lung crosstalk). Inflammatory signals in both directions and volume overload with consecutive edema formation in both organs may play a key role in this crosstalk. The organ replacement therapies used in both organ failures have the potential to further injure the other organ (ventilator trauma, dialyte trauma). On the other hand, renal replacement therapy can have positive effects on lung injury by restoring volume and acid-base homeostasis. The new development of "low-flow" extracorporeal CO2 removal on renal replacement therapy platforms may further help to decrease ventilator trauma in the future.

[Choice of optimal respiratory support in acute parenchymatous respiratory failure].

PubMed

Cherniĭ, V I; Kuznetsova, I V; Kovalenko, V L

2005-01-01

The principal goals of respiratory therapy for acute respiratory failure are to correct gas exchange and to lower respiratory performance. In acute lung lesion syndrome (ALLS) and acute respiratory distress syndrome (ARDS), the oxygenation index (PaO2/FiO2) reflects the degree of alveolar-capillary membrane damage. The changes in PaO2/FiO2 between 400 to 300 at adequate ventilation can be interpreted as occult alveolar-capillary insufficiency. The principle of power saving in ALLS/ARDS is to choose a respiratory support regimen that may ensure oxygenation safety by eliminating the excess work of respiration. The ratio of PaO2/FiO2/VO2 is proposed to consider to be a criterion for the effectiveness of respiratory support in ALLS/ARDS and a marker of energy deficiency. It has been established that the function of the alveolar-capillary membrane is not impaired with the PaO2/FiO2 ratio of more than 1.5 and the ratio of less than 1.0 is typical of the severe course of the severe course of ARDS and suggests both alveolar-capillary membrane damage and energy deficiency.

Correlation of lung collapse and gas exchange - a computer tomographic study in sheep and pigs with atelectasis in otherwise normal lungs.

PubMed

Wolf, Samuel J; Reske, Alexander P; Hammermüller, Sören; Costa, Eduardo L V; Spieth, Peter M; Hepp, Pierre; Carvalho, Alysson R; Kraßler, Jens; Wrigge, Hermann; Amato, Marcelo B P; Reske, Andreas W

2015-01-01

Atelectasis can provoke pulmonary and non-pulmonary complications after general anaesthesia. Unfortunately, there is no instrument to estimate atelectasis and prompt changes of mechanical ventilation during general anaesthesia. Although arterial partial pressure of oxygen (PaO2) and intrapulmonary shunt have both been suggested to correlate with atelectasis, studies yielded inconsistent results. Therefore, we investigated these correlations. Shunt, PaO2 and atelectasis were measured in 11 sheep and 23 pigs with otherwise normal lungs. In pigs, contrasting measurements were available 12 hours after induction of acute respiratory distress syndrome (ARDS). Atelectasis was calculated by computed tomography relative to total lung mass (Mtotal). We logarithmically transformed PaO2 (lnPaO2) to linearize its relationships with shunt and atelectasis. Data are given as median (interquartile range). Mtotal was 768 (715-884) g in sheep and 543 (503-583) g in pigs. Atelectasis was 26 (16-47) % in sheep and 18 (13-23) % in pigs. PaO2 (FiO2 = 1.0) was 242 (106-414) mmHg in sheep and 480 (437-514) mmHg in pigs. Shunt was 39 (29-51) % in sheep and 15 (11-20) % in pigs. Atelectasis correlated closely with lnPaO2 (R2 = 0.78) and shunt (R2 = 0.79) in sheep (P-values<0.0001). The correlation of atelectasis with lnPaO2 (R2 = 0.63) and shunt (R2 = 0.34) was weaker in pigs, but R2 increased to 0.71 for lnPaO2 and 0.72 for shunt 12 hours after induction of ARDS. In both, sheep and pigs, changes in atelectasis correlated strongly with corresponding changes in lnPaO2 and shunt. In lung-healthy sheep, atelectasis correlates closely with lnPaO2 and shunt, when blood gases are measured during ventilation with pure oxygen. In lung-healthy pigs, these correlations were significantly weaker, likely because pigs have stronger hypoxic pulmonary vasoconstriction (HPV) than sheep and humans. Nevertheless, correlations improved also in pigs after blunting of HPV during ARDS. In humans, the observed relationships may aid in assessing anaesthesia-related atelectasis.

Effect of Aspirin on Development of ARDS in At-Risk Patients Presenting to the Emergency Department: The LIPS-A Randomized Clinical Trial.

PubMed

Kor, Daryl J; Carter, Rickey E; Park, Pauline K; Festic, Emir; Banner-Goodspeed, Valerie M; Hinds, Richard; Talmor, Daniel; Gajic, Ognjen; Ware, Lorraine B; Gong, Michelle Ng

2016-06-14

Management of acute respiratory distress syndrome (ARDS) remains largely supportive. Whether early intervention can prevent development of ARDS remains unclear. To evaluate the efficacy and safety of early aspirin administration for the prevention of ARDS. A multicenter, double-blind, placebo-controlled, randomized clinical trial conducted at 16 US academic hospitals. Between January 2, 2012, and November 17, 2014, 7673 patients at risk for ARDS (Lung Injury Prediction Score ≥4) in the emergency department were screened and 400 were randomized. Ten patients were excluded, leaving 390 in the final modified intention-to-treat analysis cohort. Administration of aspirin, 325-mg loading dose followed by 81 mg/d (n = 195) or placebo (n = 195) within 24 hours of emergency department presentation and continued to hospital day 7, discharge, or death. The primary outcome was the development of ARDS by study day 7. Secondary measures included ventilator-free days, hospital and intensive care unit length of stay, 28-day and 1-year survival, and change in serum biomarkers associated with ARDS. A final α level of .0737 (α = .10 overall) was required for statistical significance of the primary outcome. Among 390 analyzed patients (median age, 57 years; 187 [48%] women), the median (IQR) hospital length of stay was 6 3-10) days. Administration of aspirin, compared with placebo, did not significantly reduce the incidence of ARDS at 7 days (10.3% vs 8.7%, respectively; odds ratio, 1.24 [92.6% CI, 0.67 to 2.31], P = .53). No significant differences were seen in secondary outcomes: ventilator-free to day 28, mean (SD), 24.9 (7.4) days vs 25.2 (7.0) days (mean [90% CI] difference, -0.26 [-1.46 to 0.94] days; P = .72); ICU length of stay, mean (SD), 5.2 (7.0) days vs 5.4 (7.0) days (mean [90% CI] difference, -0.16 [-1.75 to 1.43] days; P = .87); hospital length of stay, mean (SD), 8.8 (10.3) days vs 9.0 (9.9) days (mean [90% CI] difference, -0.27 [-1.96 to 1.42] days; P = .79); or 28-day survival, 90% vs 90% (hazard ratio [90% CI], 1.03 [0.60 to 1.79]; P = .92) or 1-year survival, 73% vs 75% (hazard ratio [90% CI], 1.06 [0.75 to 1.50]; P = .79). Bleeding-related adverse events were infrequent in both groups (aspirin vs placebo, 5.6% vs 2.6%; odds ratio [90% CI], 2.27 [0.92 to 5.61]; P = .13). Among 390 analyzed patients (median age, 57 years; 187 [48%] women), median (IQR) hospital length of stay was 6 (3-10) days. Administration of aspirin, compared with placebo, did not significantly reduce the incidence of ARDS at 7 days (OR, 1.24; 92.6%CI, 0.67-2.31). No significant differences were seen in secondary outcomes or adverse events. [table: see text] Among at-risk patients presenting to the ED, the use of aspirin compared with placebo did not reduce the risk of ARDS at 7 days. The findings of this phase 2b trial do not support continuation to a larger phase 3 trial. clinicaltrials.gov Identifier: NCT01504867.

Aspirin reduces lipopolysaccharide-induced pulmonary inflammation in human models of ARDS.

PubMed

Hamid, U; Krasnodembskaya, A; Fitzgerald, M; Shyamsundar, M; Kissenpfennig, A; Scott, C; Lefrancais, E; Looney, M R; Verghis, R; Scott, J; Simpson, A J; McNamee, J; McAuley, D F; O'Kane, C M

2017-11-01

Platelets play an active role in the pathogenesis of acute respiratory distress syndrome (ARDS). Animal and observational studies have shown aspirin's antiplatelet and immunomodulatory effects may be beneficial in ARDS. To test the hypothesis that aspirin reduces inflammation in clinically relevant human models that recapitulate pathophysiological mechanisms implicated in the development of ARDS. Healthy volunteers were randomised to receive placebo or aspirin 75  or 1200 mg (1:1:1) for seven days prior to lipopolysaccharide (LPS) inhalation, in a double-blind, placebo-controlled, allocation-concealed study. Bronchoalveolar lavage (BAL) was performed 6 hours after inhaling 50 µg of LPS. The primary outcome measure was BAL IL-8. Secondary outcome measures included markers of alveolar inflammation (BAL neutrophils, cytokines, neutrophil proteases), alveolar epithelial cell injury, systemic inflammation (neutrophils and plasma C-reactive protein (CRP)) and platelet activation (thromboxane B2, TXB2). Human lungs, perfused and ventilated ex vivo (EVLP) were randomised to placebo or 24 mg aspirin and injured with LPS. BAL was carried out 4 hours later. Inflammation was assessed by BAL differential cell counts and histological changes. In the healthy volunteer (n=33) model, data for the aspirin groups were combined. Aspirin did not reduce BAL IL-8. However, aspirin reduced pulmonary neutrophilia and tissue damaging neutrophil proteases (Matrix Metalloproteinase (MMP)-8/-9), reduced BAL concentrations of tumour necrosis factor α and reduced systemic and pulmonary TXB2. There was no difference between high-dose and low-dose aspirin. In the EVLP model, aspirin reduced BAL neutrophilia and alveolar injury as measured by histological damage. These are the first prospective human data indicating that aspirin inhibits pulmonary neutrophilic inflammation, at both low and high doses. Further clinical studies are indicated to assess the role of aspirin in the prevention and treatment of ARDS. NCT01659307 Results. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Iterative integral parameter identification of a respiratory mechanics model.

PubMed

Schranz, Christoph; Docherty, Paul D; Chiew, Yeong Shiong; Möller, Knut; Chase, J Geoffrey

2012-07-18

Patient-specific respiratory mechanics models can support the evaluation of optimal lung protective ventilator settings during ventilation therapy. Clinical application requires that the individual's model parameter values must be identified with information available at the bedside. Multiple linear regression or gradient-based parameter identification methods are highly sensitive to noise and initial parameter estimates. Thus, they are difficult to apply at the bedside to support therapeutic decisions. An iterative integral parameter identification method is applied to a second order respiratory mechanics model. The method is compared to the commonly used regression methods and error-mapping approaches using simulated and clinical data. The clinical potential of the method was evaluated on data from 13 Acute Respiratory Distress Syndrome (ARDS) patients. The iterative integral method converged to error minima 350 times faster than the Simplex Search Method using simulation data sets and 50 times faster using clinical data sets. Established regression methods reported erroneous results due to sensitivity to noise. In contrast, the iterative integral method was effective independent of initial parameter estimations, and converged successfully in each case tested. These investigations reveal that the iterative integral method is beneficial with respect to computing time, operator independence and robustness, and thus applicable at the bedside for this clinical application.

WISP-3/CCN6 inhibits apoptosis by regulating caspase pathway after hyperoxia in lung epithelial cells.

PubMed

Wei, Shuquan; Wang, Kangwei; Zhao, Zhuxiang; Huang, Xiaomei; Tang, Wanna; Zhao, Ziwen

2018-06-16

Cell death is a normal phenomenon in the course of biological development, moreover, which is also a prominent feature in lung exposed to hyperoxia. Severe hypoxia occurs in ALI/ARDS patients, who generally require high concentration oxygen therapy assisted by mechanical ventilation. Nevertheless, high oxygen can cause excessive reactive oxygen species (ROS), leading to apoptosis in lung epithelial cells, which has been reported in our previous study. Herein, the correlation between increments of ROS and CCN6 expression was negative in CCN6-mediated the mitochondria dependent, intrinsic apoptotic pathway. Our latest research explained that CCN6 can inhibit caspase-8 mediated extrinsic apoptotic pathway to protect cells from hyperoxia-induced apoptosis. As demonstrated by Western Blot Analysis, Caspase 8 cleavage and Caspase 3 cleavage in CCN6-depleted cells exceeded the control group treated with high oxygen (48 h). And deletion of CCN6 enhanced caspase-8 activation after hyperoxia shown by Flow Cytometry. Although, it is unclear how CCN6 participated in the regulation of apoptotic pathways, the future targeted therapy drugs inhibiting CCN6 may be useful in the treatment of ALI/ARDS. Copyright © 2018. Published by Elsevier B.V.

Surgical strategies in polytraumatized patients with femoral shaft fractures - comparing a German and an Australian level I trauma centre.

PubMed

Andruszkow, Hagen; Dowrick, Adam S; Frink, Michael; Zeckey, Christian; Krettek, Christian; Hildebrand, Frank; Edwards, Elton R; Mommsen, Philipp

2013-08-01

Femoral shaft fractures are one of the most common injuries in multiple trauma patients. Due to their prognostic relevance, there is an ongoing controversial discussion as to the optimal treatment strategy in terms of Damage Control Orthopaedics (DCO) and Early Total Care (ETC). We aimed to describe the differences in fracture management and clinical outcome of multiple trauma patients with concomitant femoral shaft fractures treated at a German and an Australian level I trauma centre using the same inclusion criteria. Polytraumatized patients (ISS ≥ 16) with a femoral shaft fracture aged ≥ 16 years treated at a German and an Australian trauma centre between 2003 and 2007 were included. According to ETC and DCO management principles, we evaluated demographic parameters as well as posttraumatic complications and clinical outcome. Seventy-three patients were treated at the German and 134 patients at the Australian trauma centre. DCO was performed in case of increased injury severity in both hospitals. Prolonged mechanical ventilation time, and length of ICU and hospital stay were demonstrated in DCO treatment regardless of the trauma centre. No differences concerning posttraumatic complications and survival were found between both centres. Survival of patients after DCO was similar to those managed using ETC despite a greater severity of injury and lower probability of survival. There was no difference in the incidence of ARDS. DCO was, however, associated with a greatly increased length of time on mechanical ventilation and length of stay in the ICU. We found no differences concerning patient demographics or clinical outcomes in terms of incidence of ARDS, MODS, or mortality. As such, we propose that comparability between German and Australian trauma populations is justified. Despite a higher ISS in the DCO group, there were no differences in posttraumatic complications and survival depending on ETC or DCO treatment. Further research is required to confirm whether this is the case with other countries, too. Copyright © 2013 Elsevier Ltd. All rights reserved.

3D modelling of the human thorax for ventilation distribution measured through electrical impedance tomography

NASA Astrophysics Data System (ADS)

Fan, W. R.; Wang, H. X.

2010-11-01

Thoracic electrical impedance tomography (EIT) aims to reconstruct a cross-sectional image of the internal spatial distribution of conductivity from electrical measurements made by injecting small alternating currents via an electrode array placed on the surface of the thorax. It is a non-invasive, radiation-free monitoring technique. In this paper, true 3D thorax models with conductivity distribution or complex conductivity distribution under different ARDS conditions are built up in comparison with the 2.5D ones, and EIT-derived numeric indices are also employed for evaluation of the lung ventilation. The purpose of this paper is to study different effects of different thorax models with either conductivity or complex conductivity on the reconstructed images and ventilation indices.

Injection sclerotherapy for haemorrhoids causing adult respiratory distress syndrome.

PubMed

Rashid, Muhammad Misbah; Murtaza, Badar; Gondal, Zafar Iqbal; Mehmood, Arshad; Shah, Shahzad Saleem; Abbasi, Muhammad Hanif; Tamimy, Muhammad Sarmad; Kazmi, Syed Tahawwar Mujtaba

2006-05-01

A young lady with first-degree haemorrhoids was administered injection sclerotherapy with 5% phenol in almond oil. Soon after the injection, she developed syncope and later signs and symptoms of acute respiratory distress syndrome (ARDS). She was kept on ventilatory support for 4 days, made a smooth recovery and was successfully weaned off from the ventilator.

Lipopolysaccharide-induced endotoxemia in corn oil-preloaded mice causes an extended course of lung injury and repair and pulmonary fibrosis: A translational mouse model of acute respiratory distress syndrome.

PubMed

Wu, Chaomin; Evans, Colin E; Dai, Zhiyu; Huang, Xiaojia; Zhang, Xianming; Jin, Hua; Hu, Guochang; Song, Yuanlin; Zhao, You-Yang

2017-01-01

Acute respiratory distress syndrome (ARDS) is characterized by acute hypoxemia respiratory failure, bilateral pulmonary infiltrates, and pulmonary edema of non-cardiac origin. Effective treatments for ARDS patients may arise from experimental studies with translational mouse models of this disease that aim to delineate the mechanisms underlying the disease pathogenesis. Mouse models of ARDS, however, can be limited by their rapid progression from injured to recovery state, which is in contrast to the course of ARDS in humans. Furthermore, current mouse models of ARDS do not recapitulate certain prominent aspects of the pathogenesis of ARDS in humans. In this study, we developed an improved endotoxemic mouse model of ARDS resembling many features of clinical ARDS including extended courses of injury and recovery as well as development of fibrosis following i.p. injection of lipopolysaccharide (LPS) to corn oil-preloaded mice. Compared with mice receiving LPS alone, those receiving corn oil and LPS exhibited extended course of lung injury and repair that occurred over a period of >2 weeks instead of 3-5days. Importantly, LPS challenge of corn oil-preloaded mice resulted in pulmonary fibrosis during the repair phase as often seen in ARDS patients. In summary, this simple novel mouse model of ARDS could represent a valuable experimental tool to elucidate mechanisms that regulate lung injury and repair in ARDS patients.

A novel swine model of ricin-induced acute respiratory distress syndrome

PubMed Central

Katalan, Shahaf; Falach, Reut; Rosner, Amir; Goldvaser, Michael; Brosh-Nissimov, Tal; Dvir, Ayana; Mizrachi, Avi; Goren, Orr; Cohen, Barak; Gal, Yoav; Sapoznikov, Anita; Ehrlich, Sharon; Kronman, Chanoch

2017-01-01

ABSTRACT Pulmonary exposure to the plant toxin ricin leads to respiratory insufficiency and death. To date, in-depth study of acute respiratory distress syndrome (ARDS) following pulmonary exposure to toxins is hampered by the lack of an appropriate animal model. To this end, we established the pig as a large animal model for the comprehensive study of the multifarious clinical manifestations of pulmonary ricinosis. Here, we report for the first time, the monitoring of barometric whole body plethysmography for pulmonary function tests in non-anesthetized ricin-treated pigs. Up to 30 h post-exposure, as a result of progressing hypoxemia and to prevent carbon dioxide retention, animals exhibited a compensatory response of elevation in minute volume, attributed mainly to a large elevation in respiratory rate with minimal response in tidal volume. This response was followed by decompensation, manifested by a decrease in minute volume and severe hypoxemia, refractory to oxygen treatment. Radiological evaluation revealed evidence of early diffuse bilateral pulmonary infiltrates while hemodynamic parameters remained unchanged, excluding cardiac failure as an explanation for respiratory insufficiency. Ricin-intoxicated pigs suffered from increased lung permeability accompanied by cytokine storming. Histological studies revealed lung tissue insults that accumulated over time and led to diffuse alveolar damage. Charting the decline in PaO2/FiO2 ratio in a mechanically ventilated pig confirmed that ricin-induced respiratory damage complies with the accepted diagnostic criteria for ARDS. The establishment of this animal model of pulmonary ricinosis should help in the pursuit of efficient medical countermeasures specifically tailored to deal with the respiratory deficiencies stemming from ricin-induced ARDS. PMID:28067630

Lung recruitment maneuver effects on respiratory mechanics and extravascular lung water index in patients with acute respiratory distress syndrome.

PubMed

Zhang, Jian-Guo; Chen, Xiao-Juan; Liu, Fen; Zeng, Zhen-Guo; Qian, Ke-Jian

2011-01-01

Animal experiments showed that recruitment maneuver (RM) and protective ventilation strategy of the lung could improve oxygenation and reduce extravascular lung water. This study was to investigate the effects of RM on respiratory mechanics and extravascular lung water index (EVLWI) in patients with acute respiratory distress syndrome (ARDS). Thirty patients with ARDS were randomized into a RM group and a non-RM group. In the RM group, after basic mechanical ventilation stabilized for 30 minutes, RM was performed and repeated once every 12 hours for 3 days. In the non-RM group, lung protective strategy was conducted without RM. Oxygenation index (PaO2/FiO2), peak inspiratory pressure (PIP), Plateau pressure (Pplat), static pulmonary compliance (Cst) and EVLWI of patients before treatment and at 12, 24, 48, 72 hours after the treatment were measured and compared between the groups. Hemodynamic changes were observed before and after RM. One-way ANOVA, Student's t test and Fisher's exact test were used to process the data. The levels of PaO2/FiO2 and Cst increased after treatment in the two groups, but they were higher in the RM group than in the non-RM group (P<0.05). The PIP and Pplat decreased after treatment in the two groups, but they were lower in the RM group than in the non-RM group (P<0.05). The EVLWI in the two groups showed downward trend after treatment (P<0.05), and the differences were signifcant at all time points (P<0.01); the EVLWI in the RM group was lower than that in the non-RM group at 12, 24, 48 and 72 hours (P<0.05 or P<0.01). Compared with pre-RM, hemodynamics changes during RM were significantly different (P<0.01); compared with pre-RM, the changes were not significantly different at 120 seconds after the end of RM (P>0.05). RM could reduce EVLWI, increase oxygenation and lung compliance. The effect of RM on hemodynamics was transient.

Compliance-guided versus FiO2-driven positive-end expiratory pressure in patients with moderate or severe acute respiratory distress syndrome according to the Berlin definition.

PubMed

Pintado, M-C; de Pablo, R; Trascasa, M; Milicua, J-M; Sánchez-García, M

To study the effect of setting positive end-expiratory pressure (PEEP) in an individualized manner (based on highest static compliance) compared to setting PEEP according to FiO 2 upon mortality at 28 and 90 days, in patients with different severity acute respiratory distress syndrome (ARDS). A Spanish medical-surgical ICU. A post hoc analysis of a randomized controlled pilot study. Patients with ARDS. Ventilation with low tidal volumes and pressure limitation at 30cmH 2 O, randomized in two groups according to the method used to set PEEP: FiO 2 -guided PEEP group according to FiO 2 applied and compliance-guided group according to the highest compliance. Demographic data, risk factors and severity of ARDS, APACHE II and SOFA scores, daily Lung Injury Score, ventilatory measurements, ICU and hospital stay, organ failure and mortality at day 28 and 90 after inclusion. A total of 159 patients with ARDS were evaluated, but just 70 patients were included. Severe ARDS patients showed more organ dysfunction-free days at 28 days (12.83±10.70 versus 3.09±7.23; p=0.04) and at 90 days (6.73±22.31 vs. 54.17±42.14, p=0.03), and a trend toward lower 90-days mortality (33.3% vs. 90.9%, p=0.02), when PEEP was applied according to the best static compliance. Patients with moderate ARDS did not show these effects. In patients with severe ARDS, individualized PEEP selection based on the best static compliance was associated to lower mortality at 90 days, with an increase in organ dysfunction-free days at 28 and 90 days. Copyright © 2016 Elsevier España, S.L.U. y SEMICYUC. All rights reserved.

Endothelial glycocalyx degradation is more severe in patients with non-pulmonary sepsis compared to pulmonary sepsis and associates with risk of ARDS and other organ dysfunction.

PubMed

Murphy, Laura S; Wickersham, Nancy; McNeil, J Brennan; Shaver, Ciara M; May, Addison K; Bastarache, Julie A; Ware, Lorraine B

2017-10-06

Disruption of the endothelial glycocalyx contributes to acute lung injury in experimental sepsis but has not been well studied in humans. To study glycocalyx degradation in sepsis-induced ARDS, we measured plasma levels of syndecan-1, a marker for glycocalyx degradation. The present study is a retrospective observational study of 262 ventilated medical ICU patients at risk of ARDS due to severe sepsis and APACHE II ≥ 25. Plasma syndecan-1 was measured at study enrollment. Primary analysis focused on the association between syndecan-1 levels and the development of ARDS, other organ dysfunction (Brussels criteria), or in-hospital mortality. Overall, 135 (52%) patients developed ARDS. In patients with non-pulmonary sepsis, syndecan-1 levels were associated with ARDS (p = 0.05). Regardless of etiology of sepsis, higher syndecan-1 levels were associated with hepatic (p < 0.001), renal (p = 0.003), coagulation (p = 0.001), and circulatory (p = 0.02) failure as well as in-hospital mortality (p = 0.001), and there was a significant association between syndecan-1 levels and the number of vasopressors required in the first 24 h (p < 0.001). In addition, elevated syndecan levels were independently predictive of mortality in multivariable logistic regression adjusted for age and APACHE II score (odds ratio 1.85 per log increase in syndecan-1, 95% CI 1.056-3.241, p = 0.03). The extent of endothelial glycocalyx degradation is associated with non-pulmonary organ dysfunction in subjects with sepsis and is associated with ARDS but only in the subgroup with non-pulmonary sepsis. Measurement of syndecan-1 levels in sepsis patients might be useful for identifying patients at high risk of organ dysfunction and mortality as well as those who could benefit from therapies targeted at protecting or restoring the glycocalyx.

Does thorax EIT image analysis depend on the image reconstruction method?

NASA Astrophysics Data System (ADS)

Zhao, Zhanqi; Frerichs, Inéz; Pulletz, Sven; Müller-Lisse, Ullrich; Möller, Knut

2013-04-01

Different methods were proposed to analyze the resulting images of electrical impedance tomography (EIT) measurements during ventilation. The aim of our study was to examine if the analysis methods based on back-projection deliver the same results when applied on images based on other reconstruction algorithms. Seven mechanically ventilated patients with ARDS were examined by EIT. The thorax contours were determined from the routine CT images. EIT raw data was reconstructed offline with (1) filtered back-projection with circular forward model (BPC); (2) GREIT reconstruction method with circular forward model (GREITC) and (3) GREIT with individual thorax geometry (GREITT). Three parameters were calculated on the resulting images: linearity, global ventilation distribution and regional ventilation distribution. The results of linearity test are 5.03±2.45, 4.66±2.25 and 5.32±2.30 for BPC, GREITC and GREITT, respectively (median ±interquartile range). The differences among the three methods are not significant (p = 0.93, Kruskal-Wallis test). The proportions of ventilation in the right lung are 0.58±0.17, 0.59±0.20 and 0.59±0.25 for BPC, GREITC and GREITT, respectively (p = 0.98). The differences of the GI index based on different reconstruction methods (0.53±0.16, 0.51±0.25 and 0.54±0.16 for BPC, GREITC and GREITT, respectively) are also not significant (p = 0.93). We conclude that the parameters developed for images generated with GREITT are comparable with filtered back-projection and GREITC.

A new horizon for the use of non-invasive ventilation in patients with acute respiratory distress syndrome.

PubMed

Carron, Michele

2016-09-01

Non-invasive ventilation (NIV) has assumed an important role in the management of acute respiratory failure (ARF). NIV, compared with standard medical therapy, improves survival and reduces complications in selected patients with ARF. NIV represents the first-line intervention for some forms of ARF, such as chronic obstructive pulmonary disease (COPD) exacerbations and acute cardiogenic pulmonary edema. The use of NIV is also well supported for immunocompromised patients who are at high risk for infectious complications from endotracheal intubation. Selection of appropriate patients is crucial for optimizing NIV success rates. Appropriate ventilator settings, a well-fitting and comfortable interface, and a team skilled and experienced in managing NIV are key components to its success. In a recent issue of the Journal of the American Medical Association , Patel et al . reported the results of their single-center trial of 83 patients with acute respiratory distress syndrome (ARDS) who were randomly assigned to NIV delivered via a helmet or face mask. Patients assigned to the helmet group exhibited a significantly lower intubation rate and were more likely to survive through 90 days. This perspective reviews the findings of this trial in the context of current clinical practice and in light of data from the literature focused on the potential reasons for success of NIV delivered through a helmet compared to face mask. The implications for early management of patients with ARDS are likewise discussed.

Effects on lung stress of position and different doses of perfluorocarbon in a model of ARDS.

PubMed

López-Aguilar, Josefina; Lucangelo, Umberto; Albaiceta, Guillermo M; Nahum, Avi; Murias, Gastón; Cañizares, Rosario; Oliva, Joan Carles; Romero, Pablo V; Blanch, Lluís

2015-05-01

We determined whether the combination of low dose partial liquid ventilation (PLV) with perfluorocarbons (PFC) and prone positioning improved lung function while inducing minimal stress. Eighteen pigs with acute lung injury were assigned to conventional mechanical ventilation (CMV) or PLV (5 or 10 ml/kg of PFC). Positive end-expiratory pressure (PEEP) trials in supine and prone positions were performed. Data were analyzed by a multivariate polynomial regression model. The interplay between PLV and position depended on the PEEP level. In supine PLV dampened the stress induced by increased PEEP during the trial. The PFC dose of 5 ml/kg was more effective than the dose 10 ml/kg. This effect was not observed in prone. Oxygenation was significantly higher in prone than in supine position mainly at lower levels of PEEP. In conclusion, MV settings should take both gas exchange and stress/strain into account. When protective CMV fails, rescue strategies combining prone positioning and PLV with optimal PEEP should improve gas exchange with minimal stress. Copyright © 2015 Elsevier B.V. All rights reserved.

Airway driving pressure and lung stress in ARDS patients.

PubMed

Chiumello, Davide; Carlesso, Eleonora; Brioni, Matteo; Cressoni, Massimo

2016-08-22

Lung-protective ventilation strategy suggests the use of low tidal volume, depending on ideal body weight, and adequate levels of PEEP. However, reducing tidal volume according to ideal body weight does not always prevent overstress and overstrain. On the contrary, titrating mechanical ventilation on airway driving pressure, computed as airway pressure changes from PEEP to end-inspiratory plateau pressure, equivalent to the ratio between the tidal volume and compliance of respiratory system, should better reflect lung injury. However, possible changes in chest wall elastance could affect the reliability of airway driving pressure. The aim of this study was to evaluate if airway driving pressure could accurately predict lung stress (the pressure generated into the lung due to PEEP and tidal volume). One hundred and fifty ARDS patients were enrolled. At 5 and 15 cmH2O of PEEP, lung stress, driving pressure, lung and chest wall elastance were measured. The applied tidal volume (mL/kg of ideal body weight) was not related to lung gas volume (r (2) = 0.0005 p = 0.772). Patients were divided according to an airway driving pressure lower and equal/higher than 15 cmH2O (the lower and higher airway driving pressure groups). At both PEEP levels, the higher airway driving pressure group had a significantly higher lung stress, respiratory system and lung elastance compared to the lower airway driving pressure group. Airway driving pressure was significantly related to lung stress (r (2) = 0.581 p < 0.0001 and r (2) = 0.353 p < 0.0001 at 5 and 15 cmH2O of PEEP). For a lung stress of 24 and 26 cmH2O, the optimal cutoff value for the airway driving pressure were 15.0 cmH2O (ROC AUC 0.85, 95 % CI = 0.782-0.922); and 16.7 (ROC AUC 0.84, 95 % CI = 0.742-0.936). Airway driving pressure can detect lung overstress with an acceptable accuracy. However, further studies are needed to establish if these limits could be used for ventilator settings.

Oxygenation Saturation Index Predicts Clinical Outcomes in ARDS.

PubMed

DesPrez, Katherine; McNeil, J Brennan; Wang, Chunxue; Bastarache, Julie A; Shaver, Ciara M; Ware, Lorraine B

2017-12-01

Traditional measures of ARDS severity such as Pao 2 /Fio 2 may not reliably predict clinical outcomes. The oxygenation index (OI [Fio 2  × mean airway pressure × 100)/Pao 2 ]) may more accurately reflect ARDS severity but requires arterial blood gas measurement. We hypothesized that the oxygenation saturation index (OSI [Fio 2  × mean airway pressure × 100)/oxygen saturation by pulse oximetry (Spo 2 )]) is a reliable noninvasive surrogate for the OI that is associated with hospital mortality and ventilator-free days (VFDs) in patients with ARDS. Critically ill patients enrolled in a prospective cohort study were eligible if they developed ARDS (Berlin criteria) during the first 4 ICU days and had mean airway pressure, Spo 2 /Fio 2 , and Pao 2 /Fio 2 values recorded on the first day of ARDS (N = 329). The highest mean airway pressure and lowest Spo 2 /Fio 2 and Pao 2 /Fio 2 values were used to calculate OI and OSI. The association between OI or OSI and hospital mortality or VFD was analyzed by using logistic regression and linear regression, respectively. The area under the receiver-operating characteristic curve (AUC) for mortality was compared among OI, OSI, Spo 2 /Fio 2 , Pao 2 /Fio 2 , and Acute Physiology and Chronic Health Evaluation II scores. OI and OSI were strongly correlated (rho = 0.862; P < .001). OSI was independently associated with hospital mortality (OR per 5-point increase in OSI, 1.228 [95% CI, 1.056-1.429]; P = .008). OI and OSI were each associated with a reduction in VFD (OI, P = .023; OSI, P = .005). The AUC for mortality prediction was greatest for Acute Physiology and Chronic Health Evaluation II scores (AUC, 0.695; P < .005) and OSI (AUC, 0.602; P = .007). The AUC for OSI was substantially better in patients aged < 40 years (AUC, 0.779; P < .001). In patients with ARDS, the OSI was correlated with the OI. The OSI on the day of ARDS diagnosis was significantly associated with increased mortality and fewer VFDs. The findings suggest that OSI is a reliable surrogate for OI that can noninvasively provide prognostic information and assessment of ARDS severity. Copyright © 2017 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.

Western and Chinese antirheumatic drug-induced T cell apoptotic DNA damage uses different caspase cascades and is independent of Fas/Fas ligand interaction.

PubMed

Lai, J H; Ho, L J; Lu, K C; Chang, D M; Shaio, M F; Han, S H

2001-06-01

Spontaneous or therapeutic induction of T cell apoptosis plays a critical role in establishing transplantation tolerance and maintaining remission of autoimmune diseases. We investigated the mechanisms of apoptosis induced by Chinese and Western antirheumatic drugs (ARDs) in human T cells. We found that hydroxychloroquine, Tripterygium wilfordii hook F, and tetrandrine (Tet), but not methotrexate, at therapeutic concentrations can cause T cell death. In addition, Tet selectively killed T cells, especially activated T cells. Although ARD-induced cytotoxicity was mediated through apoptotic mechanisms, Fas/Fas ligand interaction was not required. We further demonstrated that the processes of phosphatidylserine externalization and DNA damage along the ARD-induced T cell apoptotic pathway could operate independently, and that selective inhibition of DNA damage by caspase inhibitors did not prevent T cells from undergoing cell death. Moreover, we found that Tet- and Tripterygium wilfordii hook F-induced T cell DNA damage required caspase-3 activity, and hydroxychloroquine-induced T cell DNA damage was mediated through a caspase-3- and caspase-8-independent, but Z-Asp-Glu-Val-Asp-fluomethyl ketone-sensitive, signaling pathway. Finally, the observation that ARD-induced activation of caspase-3 in both Fas-sensitive and Fas-resistant Jurkat T cells indicates that Fas/Fas ligand interaction plays no role in ARD-induced T cell apoptosis. Our observations provide new information about the complex apoptotic mechanisms of ARDs, and have implications for combining Western and Chinese ARDs that have different immunomodulatory mechanisms in the therapy of autoimmune diseases and transplantation rejection.

Cytokine Reduction in the Setting of an ARDS-Associated Inflammatory Response with Multiple Organ Failure.

PubMed

Träger, Karl; Schütz, Christian; Fischer, Günther; Schröder, Janpeter; Skrabal, Christian; Liebold, Andreas; Reinelt, Helmut

2016-01-01

A 45-year-old male was admitted to our hospital with a small bowel obstruction due to torsion and was immediately scheduled for surgical intervention. At anesthesia induction, the patient aspirated and subsequently developed a severe SIRS with ARDS and multiple organ failure requiring the use of ECMO, CRRT, antibiotics, and low dose steroids. Due to a rapid deterioration in clinical status and a concurrent surge in inflammatory biomarkers, an extracorporeal cytokine adsorber (CytoSorb) was added to the CRRT blood circuit. The combined treatment resulted in a rapid and significant reduction in the levels of circulating inflammatory mediators. This decrease was paralleled by marked clinical stabilization of the patient including a significant improvement in hemodynamic stability and a reduced need for norepinephrine and improved respiratory function as measured by PaO2/FIO2, ventilator parameters, lung mechanics, and indirect measures of capillary leak syndrome. The patient could be discharged to a respiratory weaning unit where successful respiratory weaning could be achieved later on. We attribute the clinical improvement to the rapid control of the hyperinflammatory response and the reduction of inflammatory mediators using a combination of CytoSorb and these other therapies. CytoSorb treatment was safe and well tolerated, with no device-related adverse effects observed.

Cytokine Reduction in the Setting of an ARDS-Associated Inflammatory Response with Multiple Organ Failure

PubMed Central

Träger, Karl; Schütz, Christian; Fischer, Günther; Schröder, Janpeter; Skrabal, Christian; Liebold, Andreas; Reinelt, Helmut

2016-01-01

A 45-year-old male was admitted to our hospital with a small bowel obstruction due to torsion and was immediately scheduled for surgical intervention. At anesthesia induction, the patient aspirated and subsequently developed a severe SIRS with ARDS and multiple organ failure requiring the use of ECMO, CRRT, antibiotics, and low dose steroids. Due to a rapid deterioration in clinical status and a concurrent surge in inflammatory biomarkers, an extracorporeal cytokine adsorber (CytoSorb) was added to the CRRT blood circuit. The combined treatment resulted in a rapid and significant reduction in the levels of circulating inflammatory mediators. This decrease was paralleled by marked clinical stabilization of the patient including a significant improvement in hemodynamic stability and a reduced need for norepinephrine and improved respiratory function as measured by PaO2/FIO2, ventilator parameters, lung mechanics, and indirect measures of capillary leak syndrome. The patient could be discharged to a respiratory weaning unit where successful respiratory weaning could be achieved later on. We attribute the clinical improvement to the rapid control of the hyperinflammatory response and the reduction of inflammatory mediators using a combination of CytoSorb and these other therapies. CytoSorb treatment was safe and well tolerated, with no device-related adverse effects observed. PMID:26885411

Hemodynamic profile of pulmonary hypertension (PH) in ARDS

PubMed Central

Calcaianu, Mihaela; Gschwend, Anthony; Canuet, Matthieu; Meziani, Ferhat; Kessler, Romain

2017-01-01

Acute respiratory distress syndrome (ARDS) is a diffuse lung injury that leads to a severe acute respiratory failure. Traditional diagnostic criteria for pulmonary hypertension (PH), in this situation, may be unreliable due to the effects of positive pressure ventilation and vasoactive agents. The aim of this study is to describe the hemodynamic characteristics of PH secondary to ARDS, in relation with respiratory parameters. We assessed the hemodynamic, respiratory function, and ventilator parameters in a cohort of 38 individuals with ARDS-associated PH defined by mean pulmonary arterial pressure (mPAP) ≥ 25 mmHg. Individual characteristics: PaO2/FiO2 = 110 ± 60 mmHg, alveolar-arterial oxygen gradient (A-aO2) = 549 ± 148.9 mmHg, positive end-expiratory pressure (PEEP) = 8.7 ± 3.5 cmH2O, pulmonary static compliance (Cstat) = 30 ± 12.1 L*cmH2O-1, mPAP = 35.4 ±6.6 mmHg, pulmonary artery wedge pressure (PAWP) = 15.6 ± 5.5 mmHg, cardiac index (CI) = 3.4 ± 1.2 L/min/m2, pulmonary vascular resistance (PVR) = 3.3 ± 1.6 Wood units (WU), right atrial pressure (RAP) = 13.4 ± 5.4 mmHg, diastolic pulmonary gradient (DPG) = 12.6 ± 6.5 mmHg, and trans-pulmonary gradient (TPG) = 19.7 ± 7.7 mmHg. The composite marker—DPG >7 mmHg and PVR > 3 WU—is associated with lower CI (P = 0.016), higher mPAP (P = 0.003), and lower pulmonary static compliance (P = 0.028). We confirmed a poor prognosis of ARDS associated with PH, with a 50% survival rate after 17 days. We observed that the survival rate at 28 days was better in the case of improvement in the PaO2/FiO2 ratio in the first 24 h (log rank P = 0.003). ARDS associated with PH is a severe condition with a very poor survival rate. The composite marker DPG > 7 mmHg and PVR > 3 WU seemed to better describe the hemodynamic and respiratory dysfunction. The improvement in PaO2/FiO2 ratio in the first 24 h defined a better survival in our cohort of patients. PMID:29283029

Hemodynamic profile of pulmonary hypertension (PH) in ARDS.

PubMed

Calcaianu, George; Calcaianu, Mihaela; Gschwend, Anthony; Canuet, Matthieu; Meziani, Ferhat; Kessler, Romain

2018-01-01

Acute respiratory distress syndrome (ARDS) is a diffuse lung injury that leads to a severe acute respiratory failure. Traditional diagnostic criteria for pulmonary hypertension (PH), in this situation, may be unreliable due to the effects of positive pressure ventilation and vasoactive agents. The aim of this study is to describe the hemodynamic characteristics of PH secondary to ARDS, in relation with respiratory parameters. We assessed the hemodynamic, respiratory function, and ventilator parameters in a cohort of 38 individuals with ARDS-associated PH defined by mean pulmonary arterial pressure (mPAP) ≥ 25 mmHg. Individual characteristics: PaO2/FiO2 = 110 ± 60 mmHg, alveolar-arterial oxygen gradient (A-aO2) = 549 ± 148.9 mmHg, positive end-expiratory pressure (PEEP) = 8.7 ± 3.5 cmH 2 O, pulmonary static compliance (Cstat) = 30 ± 12.1 L*cmH 2 O-1, mPAP = 35.4 ±6.6 mmHg, pulmonary artery wedge pressure (PAWP) = 15.6 ± 5.5 mmHg, cardiac index (CI) = 3.4 ± 1.2 L/min/m 2 , pulmonary vascular resistance (PVR) = 3.3 ± 1.6 Wood units (WU), right atrial pressure (RAP) = 13.4 ± 5.4 mmHg, diastolic pulmonary gradient (DPG) = 12.6 ± 6.5 mmHg, and trans-pulmonary gradient (TPG) = 19.7 ± 7.7 mmHg. The composite marker-DPG >7 mmHg and PVR > 3 WU-is associated with lower CI ( P = 0.016), higher mPAP ( P = 0.003), and lower pulmonary static compliance ( P = 0.028). We confirmed a poor prognosis of ARDS associated with PH, with a 50% survival rate after 17 days. We observed that the survival rate at 28 days was better in the case of improvement in the PaO2/FiO2 ratio in the first 24 h (log rank P = 0.003). ARDS associated with PH is a severe condition with a very poor survival rate. The composite marker DPG > 7 mmHg and PVR > 3 WU seemed to better describe the hemodynamic and respiratory dysfunction. The improvement in PaO2/FiO2 ratio in the first 24 h defined a better survival in our cohort of patients.

Correlation of Lung Collapse and Gas Exchange - A Computer Tomographic Study in Sheep and Pigs with Atelectasis in Otherwise Normal Lungs

PubMed Central

Hammermüller, Sören; Costa, Eduardo L. V.; Spieth, Peter M.; Hepp, Pierre; Carvalho, Alysson R.; Kraßler, Jens; Wrigge, Hermann; Amato, Marcelo B. P.; Reske, Andreas W.

2015-01-01

Background Atelectasis can provoke pulmonary and non-pulmonary complications after general anaesthesia. Unfortunately, there is no instrument to estimate atelectasis and prompt changes of mechanical ventilation during general anaesthesia. Although arterial partial pressure of oxygen (PaO2) and intrapulmonary shunt have both been suggested to correlate with atelectasis, studies yielded inconsistent results. Therefore, we investigated these correlations. Methods Shunt, PaO2 and atelectasis were measured in 11 sheep and 23 pigs with otherwise normal lungs. In pigs, contrasting measurements were available 12 hours after induction of acute respiratory distress syndrome (ARDS). Atelectasis was calculated by computed tomography relative to total lung mass (Mtotal). We logarithmically transformed PaO2 (lnPaO2) to linearize its relationships with shunt and atelectasis. Data are given as median (interquartile range). Results Mtotal was 768 (715–884) g in sheep and 543 (503–583) g in pigs. Atelectasis was 26 (16–47) % in sheep and 18 (13–23) % in pigs. PaO2 (FiO2 = 1.0) was 242 (106–414) mmHg in sheep and 480 (437–514) mmHg in pigs. Shunt was 39 (29–51) % in sheep and 15 (11–20) % in pigs. Atelectasis correlated closely with lnPaO2 (R2 = 0.78) and shunt (R2 = 0.79) in sheep (P-values<0.0001). The correlation of atelectasis with lnPaO2 (R2 = 0.63) and shunt (R2 = 0.34) was weaker in pigs, but R2 increased to 0.71 for lnPaO2 and 0.72 for shunt 12 hours after induction of ARDS. In both, sheep and pigs, changes in atelectasis correlated strongly with corresponding changes in lnPaO2 and shunt. Discussion and Conclusion In lung-healthy sheep, atelectasis correlates closely with lnPaO2 and shunt, when blood gases are measured during ventilation with pure oxygen. In lung-healthy pigs, these correlations were significantly weaker, likely because pigs have stronger hypoxic pulmonary vasoconstriction (HPV) than sheep and humans. Nevertheless, correlations improved also in pigs after blunting of HPV during ARDS. In humans, the observed relationships may aid in assessing anaesthesia-related atelectasis. PMID:26258686

The association between physiologic dead-space fraction and mortality in subjects with ARDS enrolled in a prospective multi-center clinical trial.

PubMed

Kallet, Richard H; Zhuo, Hanjing; Liu, Kathleen D; Calfee, Carolyn S; Matthay, Michael A

2014-11-01

We tested the association between pulmonary dead-space fraction (ratio of dead space to tidal volume [V(D)/V(T)]) and mortality in subjects with ARDS (Berlin definition, P(aO2)/F(IO2) ≤ 300 mm Hg; PEEP ≥ 5 cm H2O) enrolled into a clinical trial incorporating lung-protective ventilation. We conducted a prospective, multi-center study at medical-surgical ICUs in the United States. A total of 126 ALI subjects with acute lung injury were enrolled into a phase 3 randomized, placebo-controlled study of aerosolized albuterol. V(D)/V(T) and pulmonary mechanics were measured within 4 h of enrollment and repeated daily on study days 1 and 2 in subjects requiring arterial blood gases for clinical management. At baseline, non-survivors had a trend toward higher V(D)/V(T) compared with survivors (0.62 ± 0.11 vs 0.56 ± 0.11, respectively, P = .08). Differences in V(D)/V(T) between non-survivors and survivors became significant on study days 1 (0.64 ± 0.12 vs 0.55 ± 0.11, respectively, P = .01) and 2 (0.67 ± 0.12 vs 0.56 ± 0.11, respectively, P = .004). Likewise, the association between VD/VT and mortality was significant on study day 1 (odds ratio per 0.10 change in V(D)/V(T) [95% CI]: 6.84 [1.62-28.84] P = .01; and study day 2: 4.90 [1.28-18.73] P = .02) after adjusting for V(D)/V(T), P(aO2)/F(IO2), oxygenation index, vasopressor use, and the primary risk for ARDS. Using a Cox proportional hazard model, V(D)/V(T) was associated with a trend toward higher mortality (HR = 4.37 [CI 0.99-19.32], P = .052) that became significant when the analysis was adjusted for daily oxygenation index (HR = 1.74 [95% CI 1.12-3.35] P = .04). Markedly elevated V(D)/V(T) (≥ 0.60) in early ARDS is associated with higher mortality. Measuring V(D)/V(T) may be useful in identifying ARDS patients at increased risk of death who are enrolled into a therapeutic trial. Copyright © 2014 by Daedalus Enterprises.

A novel swine model of ricin-induced acute respiratory distress syndrome.

PubMed

Katalan, Shahaf; Falach, Reut; Rosner, Amir; Goldvaser, Michael; Brosh-Nissimov, Tal; Dvir, Ayana; Mizrachi, Avi; Goren, Orr; Cohen, Barak; Gal, Yoav; Sapoznikov, Anita; Ehrlich, Sharon; Sabo, Tamar; Kronman, Chanoch

2017-02-01

Pulmonary exposure to the plant toxin ricin leads to respiratory insufficiency and death. To date, in-depth study of acute respiratory distress syndrome (ARDS) following pulmonary exposure to toxins is hampered by the lack of an appropriate animal model. To this end, we established the pig as a large animal model for the comprehensive study of the multifarious clinical manifestations of pulmonary ricinosis. Here, we report for the first time, the monitoring of barometric whole body plethysmography for pulmonary function tests in non-anesthetized ricin-treated pigs. Up to 30 h post-exposure, as a result of progressing hypoxemia and to prevent carbon dioxide retention, animals exhibited a compensatory response of elevation in minute volume, attributed mainly to a large elevation in respiratory rate with minimal response in tidal volume. This response was followed by decompensation, manifested by a decrease in minute volume and severe hypoxemia, refractory to oxygen treatment. Radiological evaluation revealed evidence of early diffuse bilateral pulmonary infiltrates while hemodynamic parameters remained unchanged, excluding cardiac failure as an explanation for respiratory insufficiency. Ricin-intoxicated pigs suffered from increased lung permeability accompanied by cytokine storming. Histological studies revealed lung tissue insults that accumulated over time and led to diffuse alveolar damage. Charting the decline in PaO2/FiO2 ratio in a mechanically ventilated pig confirmed that ricin-induced respiratory damage complies with the accepted diagnostic criteria for ARDS. The establishment of this animal model of pulmonary ricinosis should help in the pursuit of efficient medical countermeasures specifically tailored to deal with the respiratory deficiencies stemming from ricin-induced ARDS. © 2017. Published by The Company of Biologists Ltd.

Airway pressure release ventilation: what do we know?

PubMed

Daoud, Ehab G; Farag, Hany L; Chatburn, Robert L

2012-02-01

Airway pressure release ventilation (APRV) is inverse ratio, pressure controlled, intermittent mandatory ventilation with unrestricted spontaneous breathing. It is based on the principle of open lung approach. It has many purported advantages over conventional ventilation, including alveolar recruitment, improved oxygenation, preservation of spontaneous breathing, improved hemodynamics, and potential lung-protective effects. It has many claimed disadvantages related to risks of volutrauma, increased work of breathing, and increased energy expenditure related to spontaneous breathing. APRV is used mainly as a rescue therapy for the difficult to oxygenate patients with acute respiratory distress syndrome (ARDS). There is confusion regarding this mode of ventilation, due to the different terminology used in the literature. APRV settings include the "P high," "T high," "P low," and "T low". Physicians and respiratory therapists should be aware of the different ways and the rationales for setting these variables on the ventilators. Also, they should be familiar with the differences between APRV, biphasic positive airway pressure (BIPAP), and other conventional and nonconventional modes of ventilation. There is no solid proof that APRV improves mortality; however, there are ongoing studies that may reveal further information about this mode of ventilation. This paper reviews the different methods proposed for APRV settings, and summarizes the different studies comparing APRV and BIPAP, and the potential benefits and pitfalls for APRV.

The role of high airway pressure and dynamic strain on ventilator-induced lung injury in a heterogeneous acute lung injury model.

PubMed

Jain, Sumeet V; Kollisch-Singule, Michaela; Satalin, Joshua; Searles, Quinn; Dombert, Luke; Abdel-Razek, Osama; Yepuri, Natesh; Leonard, Antony; Gruessner, Angelika; Andrews, Penny; Fazal, Fabeha; Meng, Qinghe; Wang, Guirong; Gatto, Louis A; Habashi, Nader M; Nieman, Gary F

2017-12-01

Acute respiratory distress syndrome causes a heterogeneous lung injury with normal and acutely injured lung tissue in the same lung. Improperly adjusted mechanical ventilation can exacerbate ARDS causing a secondary ventilator-induced lung injury (VILI). We hypothesized that a peak airway pressure of 40 cmH 2 O (static strain) alone would not cause additional injury in either the normal or acutely injured lung tissue unless combined with high tidal volume (dynamic strain). Pigs were anesthetized, and heterogeneous acute lung injury (ALI) was created by Tween instillation via a bronchoscope to both diaphragmatic lung lobes. Tissue in all other lobes was normal. Airway pressure release ventilation was used to precisely regulate time and pressure at both inspiration and expiration. Animals were separated into two groups: (1) over-distension + high dynamic strain (OD + H DS , n = 6) and (2) over-distension + low dynamic strain (OD + L DS , n = 6). OD was caused by setting the inspiratory pressure at 40 cmH 2 O and dynamic strain was modified by changing the expiratory duration, which varied the tidal volume. Animals were ventilated for 6 h recording hemodynamics, lung function, and inflammatory mediators followed by an extensive necropsy. In normal tissue (N T ), OD + L DS caused minimal histologic damage and a significant reduction in BALF total protein (p < 0.05) and MMP-9 activity (p < 0.05), as compared with OD + H DS . In acutely injured tissue (ALI T ), OD + L DS resulted in reduced histologic injury and pulmonary edema (p < 0.05), as compared with OD + H DS . Both N T and ALI T are resistant to VILI caused by OD alone, but when combined with a H DS , significant tissue injury develops.

Variation of poorly ventilated lung units (silent spaces) measured by electrical impedance tomography to dynamically assess recruitment.

PubMed

Spadaro, Savino; Mauri, Tommaso; Böhm, Stephan H; Scaramuzzo, Gaetano; Turrini, Cecilia; Waldmann, Andreas D; Ragazzi, Riccardo; Pesenti, Antonio; Volta, Carlo Alberto

2018-01-31

Assessing alveolar recruitment at different positive end-expiratory pressure (PEEP) levels is a major clinical and research interest because protective ventilation implies opening the lung without inducing overdistention. The pressure-volume (P-V) curve is a validated method of assessing recruitment but reflects global characteristics, and changes at the regional level may remain undetected. The aim of the present study was to compare, in intubated patients with acute hypoxemic respiratory failure (AHRF) and acute respiratory distress syndrome (ARDS), lung recruitment measured by P-V curve analysis, with dynamic changes in poorly ventilated units of the dorsal lung (dependent silent spaces [DSSs]) assessed by electrical impedance tomography (EIT). We hypothesized that DSSs might represent a dynamic bedside measure of recruitment. We carried out a prospective interventional study of 14 patients with AHRF and ARDS admitted to the intensive care unit undergoing mechanical ventilation. Each patient underwent an incremental/decremental PEEP trial that included five consecutive phases: PEEP 5 and 10 cmH 2 O, recruitment maneuver + PEEP 15 cmH 2 O, then PEEP 10 and 5 cmH 2 O again. We measured, at the end of each phase, recruitment from previous PEEP using the P-V curve method, and changes in DSS were continuously monitored by EIT. PEEP changes induced alveolar recruitment as assessed by the P-V curve method and changes in the amount of DSS (p < 0.001). Recruited volume measured by the P-V curves significantly correlated with the change in DSS (r s  = 0.734, p < 0.001). Regional compliance of the dependent lung increased significantly with rising PEEP (median PEEP 5 cmH 2 O = 11.9 [IQR 10.4-16.7] ml/cmH 2 O, PEEP 15 cmH 2 O = 19.1 [14.2-21.3] ml/cmH 2 O; p < 0.001), whereas regional compliance of the nondependent lung decreased from PEEP 5 cmH 2 O to PEEP 15 cmH 2 O (PEEP 5 cmH 2 O = 25.3 [21.3-30.4] ml/cmH 2 O, PEEP 15 cmH 2 O = 20.0 [16.6-22.8] ml/cmH 2 O; p <0.001). By increasing the PEEP level, the center of ventilation moved toward the dependent lung, returning to the nondependent lung during the decremental PEEP steps. The variation of DSSs dynamically measured by EIT correlates well with lung recruitment measured using the P-V curve technique. EIT might provide useful information to titrate personalized PEEP. ClinicalTrials.gov, NCT02907840 . Registered on 20 September 2016.

Statin therapy for acute respiratory distress syndrome: an individual patient data meta-analysis of randomised clinical trials.

PubMed

Nagendran, Myura; McAuley, Daniel F; Kruger, Peter S; Papazian, Laurent; Truwit, Jonathon D; Laffey, John G; Thompson, B Taylor; Clarke, Mike; Gordon, Anthony C

2017-05-01

We performed an individual patient data meta-analysis to assess the possible benefits and harms of statin therapy in adults with acute respiratory distress syndrome (ARDS) and to investigate effects in specific ARDS subgroups. We identified randomised clinical trials up to 31 October 2016 that had investigated statin therapy versus placebo in patients with ARDS. Individual patient data from each trial were compiled. Conventional two-stage meta-analyses were performed for primary and secondary outcomes, and one-stage regression models with single treatment-covariate interactions for subgroup analyses. Risk of bias was assessed using the Cochrane Risk of Bias Tool. Six trials with a total of 1755 patients were included. For the primary outcomes, there was no significant effect of statin therapy on 28-day mortality [relative risk (RR) 1.03, 95% CI 0.86-1.23], ventilator-free days (mean difference 0.34 days, 95% CI -0.68 to 1.36) or serious adverse events (RR 1.14, 95% CI 0.84-1.53). There was a significantly increased incidence of raised serum creatine kinase or transaminase levels with statin therapy (106/879; 12.1%) versus control (78/876; 8.9%) (RR 1.40, 95% CI 1.07-1.83, p = 0.015). There were no significant treatment-covariate interactions in the predefined subgroups investigated. We found no clinical benefit from initiation of statin therapy in adult patients with ARDS, either overall or in predefined subgroups. While there was an increased incidence of raised serum creatine kinase and transaminase levels, there was no difference in serious adverse events among groups. Therefore, we do not recommend initiation of statin therapy for the treatment of ARDS.

[ARDS and severe brain injury. Therapeutic strategies in conflict].

PubMed

Bein, T; Kuhr, L P; Metz, C; Woertgen, C; Philipp, A; Taeger, K

2002-07-01

The development of adult respiratory distress syndrome (ARDS) complicates the treatment of patients with severe head injury, since special therapeutic strategies for both conditions might lead to a "conflict of interest". We report on the intensive care treatment of a young man who suffered severe brain injury (Glasgow Coma Scale = 3) due to a traffic accident and simultaneously developed ARDS from the aspiration of gastric content. We performed extensive monitoring of cerebral hemodynamics and metabolism (intracranial pressure measurement, jugular bulb oxymetry, estimation of arterial-jugular bulb lactate concentration difference) to prevent cerebral hypoxia and to control cerebral hyperemia. The application of a "lung protective strategy" with "permissive hypercapnia" led to a conflict, since the development of cranial hyperemia combined with cranial hypertension a few days after trauma, warranted the concept of controlled, temporary hyperventilation. Therefore, we applied a pumpless extracorporeal lung assist to improve carbon dioxide elimination. Furthermore, we started the ventilation in the prone position, since arterial oxygenation continued to deteriorate, although there is a lack of data describing the effect of a prone position on acute cerebral injury. Positioning the patient prone, we observed a prompt increase in intracranial pressure, which resulted in pharmacological intervention (mannitol). Treating the patient by intermittent prone position, by continuous extracorporeal lung assist and aerosolized prostacyclin administration in the following period, lung function improved and ARDS was treated successfully. After withdrawing the analgo-sedation the patient's vigilance rose continuously. The patient was transferred to a rehabilitation ward 33 days after admission to the intensive care unit. The combination of ARDS and severe brain injury needs special treatment, which includes extensive monitoring techniques to find a solution for therapeutic conflicts.

Force control of endothelium permeability in mechanically stressed pulmonary micro-vascular endothelial cells.

PubMed

Wang, Bin; Caluch, Adam; Fodil, Redouane; Féréol, Sophie; Zadigue, Patricia; Pelle, Gabriel; Louis, Bruno; Isabey, Daniel

2012-01-01

Mechanical factors play a key role in the pathogenesis of Acute Respiratory Distress Syndrome (ARDS) and Ventilator-Induced Lung Injury (VILI) as contributing to alveolo-capillary barrier dysfunction. This study aims at elucidating the role of the cytoskeleton (CSK) and cell-matrix adhesion system in the stressed endothelium and more precisely in the loss of integrity of the endothelial barrier. We purposely develop a cellular model made of a monolayer of confluent Human Pulmonary Microvascular Endothelial Cells (HPMVECs) whose cytoskeleton (CSK) is directly exposed to sustained cyclic mechanical stress for 1 and 2 h. We used RGD-coated ferromagnetic beads and measured permeability before and after stress application. We find that endothelial permeability increases in the stressed endothelium, hence reflecting a loss of integrity. Structural and mechanical results suggest that this endothelial barrier alteration would be due to physically-founded discrepancies in latero-basal reinforcement of adhesion sites in response to the global increase in CSK stiffness or centripetal intracellular forces. Basal reinforcement of adhesion is presently evidenced by the marked redistribution of αvβ3 integrin with cluster formation in the stressed endothelium.

Surfactant Therapy of ALI and ARDS

PubMed Central

Raghavendran, K; Willson, D; Notter, RH

2011-01-01

This article examines exogenous lung surfactant replacement therapy and its utility in mitigating clinical acute lung injury (ALI) and the acute respiratory distress syndrome (ARDS). Biophysical research has documented that lung surfactant dysfunction can be reversed or mitigated by increasing surfactant concentration, and multiple studies in animals with ALI/ARDS have shown that respiratory function and pulmonary mechanics in vivo can be improved by exogenous surfactant administration. Exogenous surfactant therapy is a routine intervention in neonatal intensive care, and is life-saving in preventing or treating the neonatal respiratory distress syndrome (NRDS) in premature infants. In applications relevant for lung injury-related respiratory failure and ALI/ARDS, surfactant therapy has been shown to be beneficial in term infants with pneumonia and meconium aspiration lung injury, and in children up to age 21 with direct pulmonary forms of ALI/ARDS. However, extension of exogenous surfactant therapy to adults with respiratory failure and clinical ALI/ARDS remains a challenge. Coverage here reviews clinical studies of surfactant therapy in pediatric and adult patients with ALI/ARDS, particularly focusing on its potential advantages in patients with direct pulmonary forms of these syndromes. Also discussed is the rationale for mechanism-based therapies utilizing exogenous surfactant in combination with agents targeting other aspects of the multifaceted pathophysiology of inflammatory lung injury. Additional factors affecting the efficacy of exogenous surfactant therapy in ALI/ARDS are also described, including the difficulty of effectively delivering surfactants to injured lungs and the existence of activity differences between clinical surfactant drugs. PMID:21742216

Infusion of freshly isolated autologous bone marrow derived mononuclear cells prevents endotoxin-induced lung injury in an ex-vivo perfused swine model

PubMed Central

2013-01-01

Introduction The acute respiratory distress syndrome (ARDS), affects up to 150,000 patients per year in the United States. We and other groups have demonstrated that bone marrow derived mesenchymal stromal stem cells prevent ARDS induced by systemic and local administration of endotoxin (lipopolysaccharide (LPS)) in mice. Methods A study was undertaken to determine the effects of the diverse populations of bone marrow derived cells on the pathophysiology of ARDS, using a unique ex-vivo swine preparation, in which only the ventilated lung and the liver are perfused with autologous blood. Six experimental groups were designated as: 1) endotoxin alone, 2) endotoxin + total fresh whole bone marrow nuclear cells (BMC), 3) endotoxin + non-hematopoietic bone marrow cells (CD45 neg), 4) endotoxin + hematopoietic bone marrow cells (CD45 positive), 5) endotoxin + buffy coat and 6) endotoxin + in vitro expanded swine CD45 negative adherent allogeneic bone marrow cells (cultured CD45neg). We measured at different levels the biological consequences of the infusion of the different subsets of cells. The measured parameters were: pulmonary vascular resistance (PVR), gas exchange (PO2), lung edema (lung wet/dry weight), gene expression and serum concentrations of the pro-inflammatory cytokines IL-1β, TNF-α and IL-6. Results Infusion of freshly purified autologous total BMCs, as well as non-hematopoietic CD45(-) bone marrow cells significantly reduced endotoxin-induced pulmonary hypertension and hypoxemia and reduced the lung edema. Also, in the groups that received BMCs and cultured CD45neg we observed a decrease in the levels of IL-1β and TNF-α in plasma. Infusion of hematopoietic CD45(+) bone marrow cells or peripheral blood buffy coat cells did not protect against LPS-induced lung injury. Conclusions We conclude that infusion of freshly isolated autologous whole bone marrow cells and the subset of non-hematopoietic cells can suppress the acute humoral and physiologic responses induced by endotoxemia by modulating the inflammatory response, mechanisms that do not involve engraftment or trans-differentiation of the cells. These observations may have important implications for the design of future cell therapies for ARDS. PMID:23497755

Heat and moisture exchangers and heated humidifiers in acute lung injury/acute respiratory distress syndrome patients. Effects on respiratory mechanics and gas exchange.

PubMed

Morán, Indalecio; Bellapart, Judith; Vari, Alessandra; Mancebo, Jordi

2006-04-01

To compare, in acute lung injury/acute respiratory distress syndrome (ALI/ARDS) patients, the short-term effects of heat and moisture exchangers (HME) and heated humidifiers (HH) on gas exchange, and also on respiratory system mechanics when isocapnic conditions are met. Prospective open clinical study. Intensive Care Service. Seventeen invasively ventilated ALI/ARDS patients. The study was performed in three phases: (1) determinations were made during basal ventilatory settings with HME; (2) basal ventilatory settings were maintained and HME was replaced by an HH; (3) using the same HH, tidal volume (Vt) was decreased until basal PaCO2 levels were reached. FiO2, respiratory rate and PEEP were kept unchanged. Respiratory mechanics, Vdphys, gas exchange and hemodynamic parameters were obtained at each phase. By using HH instead of HME and without changing Vt, PaCO2 decreased from 46+/-9 to 40+/-8 mmHg (p<0.001) and Vdphys decreased from 352+/-63 to 310+/-74 ml (p<0.001). Comparing the first phase with the third, Vt decreased from 521+/-106 to 440+/-118 ml (p<0.001) without significant changes in PaCO2, Vd/Vt decreased from 0.69+/-0.11 to 0.62+/-0.12 (p<0.001), plateau airway pressure decreased from 25+/-6 to 21+/-6 cmH2O (p<0.001) and respiratory system compliance improved from 35+/-12 to 42+/-15 ml/cmH2O (p<0.001). PaO2 remained unchanged in the three phases. Reducing dead space with the use of HH decreases PaCO2 and more importantly, if isocapnic conditions are maintained by reducing Vt, this strategy improves respiratory system compliance and reduces plateau airway pressure.

A prospective international observational prevalence study on prone positioning of ARDS patients: the APRONET (ARDS Prone Position Network) study.

PubMed

Guérin, C; Beuret, P; Constantin, J M; Bellani, G; Garcia-Olivares, P; Roca, O; Meertens, J H; Maia, P Azevedo; Becher, T; Peterson, J; Larsson, A; Gurjar, M; Hajjej, Z; Kovari, F; Assiri, A H; Mainas, E; Hasan, M S; Morocho-Tutillo, D R; Baboi, L; Chrétien, J M; François, G; Ayzac, L; Chen, L; Brochard, L; Mercat, A

2018-01-01

While prone positioning (PP) has been shown to improve patient survival in moderate to severe acute respiratory distress syndrome (ARDS) patients, the rate of application of PP in clinical practice still appears low. This study aimed to determine the prevalence of use of PP in ARDS patients (primary endpoint), the physiological effects of PP, and the reasons for not using it (secondary endpoints). The APRONET study was a prospective international 1-day prevalence study performed four times in April, July, and October 2016 and January 2017. On each study day, investigators in each ICU had to screen every patient. For patients with ARDS, use of PP, gas exchange, ventilator settings and plateau pressure (Pplat) were recorded before and at the end of the PP session. Complications of PP and reasons for not using PP were also documented. Values are presented as median (1st-3rd quartiles). Over the study period, 6723 patients were screened in 141 ICUs from 20 countries (77% of the ICUs were European), of whom 735 had ARDS and were analyzed. Overall 101 ARDS patients had at least one session of PP (13.7%), with no differences among the 4 study days. The rate of PP use was 5.9% (11/187), 10.3% (41/399) and 32.9% (49/149) in mild, moderate and severe ARDS, respectively (P = 0.0001). The duration of the first PP session was 18 (16-23) hours. Measured with the patient in the supine position before and at the end of the first PP session, PaO 2 /F I O 2 increased from 101 (76-136) to 171 (118-220) mmHg (P = 0.0001) driving pressure decreased from 14 [11-17] to 13 [10-16] cmH 2 O (P = 0.001), and Pplat decreased from 26 [23-29] to 25 [23-28] cmH 2 O (P = 0.04). The most prevalent reason for not using PP (64.3%) was that hypoxemia was not considered sufficiently severe. Complications were reported in 12 patients (11.9%) in whom PP was used (pressure sores in five, hypoxemia in two, endotracheal tube-related in two ocular in two, and a transient increase in intracranial pressure in one). In conclusion, this prospective international prevalence study found that PP was used in 32.9% of patients with severe ARDS, and was associated with low complication rates, significant increase in oxygenation and a significant decrease in driving pressure.

Complement-mediated neutrophil activation in sepsis- and trauma-related adult respiratory distress syndrome. Clarification with radioaerosol lung scans

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tennenberg, S.D.; Jacobs, M.P.; Solomkin, J.S.

Complement-mediated neutrophil activation (CMNA) has been proposed as an important pathogenic mechanism causing acute microvascular lung injury in the adult respiratory distress syndrome (ARDS). To clarify the relationship between CMNA and evolving lung injury, we studied 26 patients with multiple trauma and sepsis within 24 hours of risk establishment for ARDS. Pulmonary alveolar-capillary permeability (PACP) was quantified as the clearance rate of a particulate radioaerosol. Seventeen patients (65%) had increased PACP (six developed ARDS) while nine (35%) had normal PACP (none developed ARDS; clearance rates of 3.4%/min and 1.5%/min, respectively). These patients, regardless of evidence of early lung injury, hadmore » elevated plasma C3adesArg levels and neutrophil chemotactic desensitization to C5a/C5adesArg. Plasma C3adesArg levels correlated weakly, but significantly, with PACP. Thus, CMNA may be a necessary, but not a sufficient, pathogenic mechanism in the evolution of ARDS.« less

Inflammation and growth factor expression in lung tissue of F344 rats exposed to Libby amphibole asbestos

EPA Science Inventory

Rationale: An increased incidence of asbestos-related diseases (ARD) in Libby, Montana has prompted toxicological investigations into the potential mechanism(s) of Libby amphibole (LA) asbestos that induce ARD. Asbestos exposure, in general, results in a potent pulmonary inflamma...

Deciphering potential mechanisms of anaerobic soil disinfestation (ASD)-mediated control of Pratylenchus penetrans

USDA-ARS?s Scientific Manuscript database

Pratylenchus penetrans is a component of the apple replant disease (ARD) causal pathogen complex. The potential role for biological mechanisms contributing to ASD-mediated suppression of P. penetrans was examined in greenhouse study using orchard soil with a history of ARD. Populations of P. penetra...

Effects of budesonide on the lung functions, inflammation and apoptosis in a saline-lavage model of acute lung injury.

PubMed

Mokra, D; Kosutova, P; Balentova, S; Adamkov, M; Mikolka, P; Mokry, J; Antosova, M; Calkovska, A

2016-12-01

Diffuse alveolar injury, edema, and inflammation are fundamental signs of acute lung injury (ALI) and acute respiratory distress syndrome (ARDS). Whereas the systemic administration of corticosteroids previously led to controversial results, this study evaluated if corticosteroids given intratracheally may improve lung functions and reduce edema formation, migration of cells into the lung and their activation in experimentally-induced ALI. In oxygen-ventilated rabbits, ALI was induced by repetitive saline lung lavage, until PaO2 decreased to < 26.7 kPa in FiO 2 1.0. Then, one group of animals was treated with corticosteroid budesonide (Pulmicort susp inh, AstraZeneca; 0.25 mg/kg) given intratracheally by means of inpulsion regime of high-frequency jet ventilation, while another group was non-treated, and both groups were oxygen-ventilated for following 5 hours. Another group of animals served as healthy controls. After sacrifice of animals, left lung was saline-lavaged and protein content was measured and cells in the lavage fluid were determined microscopically. Right lung tissue was used for estimation of edema formation (expressed as wet/dry weight ratio), for histomorphological investigation, immunohistochemical determination of apoptosis of lung cells, and for determination of markers of inflammation and lung injury (IL-1β, IL-6, IL-8, TNF-α, IFNγ, esRAGE, caspase-3) by ELISA methods. Levels of several cytokines were estimated also in plasma. Repetitive lung lavage worsened gas exchange, induced lung injury, inflammation and lung edema and increased apoptosis of lung epithelial cells. Budesonide reduced lung edema, cell infiltration into the lung and apoptosis of epithelial cells and decreased concentrations of proinflammatory markers in the lung and blood. These changes resulted in improved ventilation. Concluding, curative intratracheal treatment with budesonide alleviated lung injury, inflammation, apoptosis of lung epithelial cells and lung edema and improved lung functions in a lavage model of ALI. These findings suggest a potential of therapy with inhaled budesonide also for patients with ARDS.

Inhaled Nitric Oxide in Acute Lung Disease.

DTIC Science & Technology

1995-01-01

play a pivotal and central cellular, NO. combines with the heme molecules role in many of the clinical manifestations of ARDS, it present in...blood flow to trate anion (NO3), and b) reaction with 02 to form poorly ventilated lung segments and further compro- nitrite anion (NO2) (23, 24). It...is the most consistent feature of creases in methemoglobin levels (Table 1). Plasma NO- therapy. Theoretically, inhaled NO. vasodilates nitrite levels

The Montreux definition of neonatal ARDS: biological and clinical background behind the description of a new entity.

PubMed

De Luca, Daniele; van Kaam, Anton H; Tingay, David G; Courtney, Sherry E; Danhaive, Olivier; Carnielli, Virgilio P; Zimmermann, Luc J; Kneyber, Martin C J; Tissieres, Pierre; Brierley, Joe; Conti, Giorgio; Pillow, Jane J; Rimensberger, Peter C

2017-08-01

Acute respiratory distress syndrome (ARDS) is undefined in neonates, despite the long-standing existing formal recognition of ARDS syndrome in later life. We describe the Neonatal ARDS Project: an international, collaborative, multicentre, and multidisciplinary project which aimed to produce an ARDS consensus definition for neonates that is applicable from the perinatal period. The definition was created through discussions between five expert members of the European Society for Paediatric and Neonatal Intensive Care; four experts of the European Society for Paediatric Research; two independent experts from the USA and two from Australia. This Position Paper provides the first consensus definition for neonatal ARDS (called the Montreux definition). We also provide expert consensus that mechanisms causing ARDS in adults and older children-namely complex surfactant dysfunction, lung tissue inflammation, loss of lung volume, increased shunt, and diffuse alveolar damage-are also present in several critical neonatal respiratory disorders. Copyright © 2017 Elsevier Ltd. All rights reserved.

Effects of different concentrations of isoflurane pretreatment on respiratory mechanics, oxygenation and hemodynamics in LPS-induced acute respiratory distress syndrome model of juvenile piglets.

PubMed

Fu, Haibin; Sun, Minli; Miao, Changhong

2015-01-01

This study was prospectively designed to investigate the effects of different concentrations of isoflurane (ISO) pretreatment on respiratory mechanics, oxygenation, and hemodynamics in lipopolysaccharide (LPS)-induced acute respiratory distress syndrome (ARDS) model of juvenile piglets. Twenty-four piglets (9-14 kg, 5-6 weeks old) were randomly assigned to four groups (n = 6): LPS group, which was injected with LPS (20 μg/kg) to induce ARDS; 0.5 ISO-LPS, 1.0 ISO-LPS, and 1.3 ISO-LPS groups, which were pretreated with 0.5, 1.0, and 1.3 minimum alveolar concentrations (MAC) ISO for 30 min before immediate LPS infusion, respectively. After establishment of ARDS, respiratory mechanism, oxygenation and hemodynamics parameters were measured at baseline, and 0, 1, 2, 3, and 4 hours after induction of ARDS. After induction of ARDS, there were increases in alveolar-arterial oxygen difference (A-aDO2), oxygenation index (OI), mean airway pressure (MAP), dead space-to-tidal volume ratio, heart rate (HR), dP/dtmax, extravascular lung water index, pulmonary vascular permeability index, and PaCO2, and decreases in PaO2/FIO2, respiratory rate (RR), dynamic lung compliance (Cdyn), mean arterial blood pressure (MABP) and systemic vascular resistance (SVR) compared with baseline (P(time) < 0.05). Pretreatment with 1.0 and 1.3 MAC ISO alleviated changes in dP/dtmax and PaCO2 at ARDS 0-2 hours, SVR at 0-3 hours, PaO2/FIO2, RR, and MABP at 1-2 hours, HR at 2-3 hours, A-aDO2 at 3-4 hours, and OI at 4 hours (P(group) < 0.05). Pretreatment with 1.0 and 1.3 MAC ISO had protective effects on respiratory mechanics, oxygenation, and hemodynamics in piglets with LPS-induced ARDS.

Using the prone position for ventilated patients with respiratory failure: a review.

PubMed

Wright, Angie D; Flynn, Maria

2011-01-01

this review explored the evidence relating to prone positioning in ventilated patients diagnosed with respiratory failure, including acute lung injury (ALI) or adult respiratory distress syndrome (ARDS). mortality rates for ventilated patients with ALI or ARDS are high, and there is a growing body of evidence suggesting that the position these patients are nursed in may influence clinical outcomes. However, there are no guidelines to inform nursing practice in positioning these patients. Medline, Scopus, Cinahl and the Cochrane Library databases were searched for original research reports or systematic reviews of evidence between 2000 and 2009. Reference lists of retrieved papers were hand searched and included studies were analysed using the Critical Appraisal and Skills Programme framework. A narrative data synthesis considered the strengths and limitations of studies, and findings were collated and interpreted. Application of the search strategy identified a systematic review, currently underway, which has not yet reported and 14 relevant studies eligible for inclusion in this review. Analysis showed considerable variation in study design, but suggests that PaO(2) /FiO(2) ratio, incidence of VAP and mortality may be positively affected by prone positioning. evidence of the clinical benefits associated with prone positioning is inconclusive and provides little guidance for nursing practice. There is a need for further research into the clinical outcomes of prone positioning, and greater understanding of the practicalities of prone positioning critically ill patients is required. nurses have a central role to play in the continual assessment and management of this patient group, including the position they are nursed in, not only to ensure the best clinical outcomes but also to provide care and comfort to the patient and their family. It is therefore important that their nursing practice and interventions are informed by the best available evidence.

Receptor Interacting Protein 3-Mediated Necroptosis Promotes Lipopolysaccharide-Induced Inflammation and Acute Respiratory Distress Syndrome in Mice.

PubMed

Wang, Linlin; Wang, Tingting; Li, Haobo; Liu, Qing; Zhang, Zhongjun; Xie, Wanli; Feng, Yinglu; Socorburam, Tumenjavkhlan; Wu, Gui; Xia, Zhengyuan; Wu, Qingping

2016-01-01

Necrosis amplifies inflammation and plays important roles in acute respiratory distress syndrome (ARDS). Necroptosis is a newly identified programmed necrosis that is mediated by receptor interacting protein 3 (RIP3). However, the potential involvement and impact of necroptosis in lipopolysaccharide (LPS)-induced ARDS remains unknown. We therefore explored the role and mechanism of RIP3-mediated necroptosis in LPS-induced ARDS. Mice were instilled with increasing doses of LPS intratracheally to induce different degrees of ARDS. Lung tissues were harvested for histological and TUNEL staining and western blot for RIP3, p-RIP3, X-linked inhibitor of apoptosis protein (XIAP), mixed lineage kinase domain-like protein (MLKL), total and cleaved caspases-3/8. Then, wild-type and RIP3 knock-out mice were induced ARDS with 30 mg/kg LPS. Pulmonary cellular necrosis was labeled by the propidium Iodide (PI) staining. Levels of TNF-a, Interleukin (IL)-1β, IL-6, IL-1α, IL-10 and HMGB1, tissue myeloperoxidase (MPO) activity, neutrophil counts and total protein concentration were measured. Results showed that in high dose LPS (30mg/kg and 40mg/kg) -induced severe ARDS, RIP3 protein was increased significantly, accompanied by increases of p-RIP3 and MLKL, while in low dose LPS (10mg/kg and 20mg/kg) -induced mild ARDS, apoptosis was remarkably increased. In LPS-induced severe ARDS, RIP3 knock-out alleviated the hypothermia symptom, increased survival rate and ameliorated the lung tissue injury RIP3 depletion also attenuated LPS-induced increase in IL-1α/β, IL-6 and HMGB1 release, decreased tissue MPO activity, and reduced neutrophil influx and total protein concentration in BALF in severe ARDS. Further, RIP3 depletion reduced the necrotic cells in the lung and decreased the expression of MLKL, but had no impact on cleaved caspase-3 in LPS-induced ARDS. It is concluded that RIP3-mediated necroptosis is a major mechanism of enhanced inflammation and lung tissue injury in high dose LPS- induced severe ARDS in mice.

Receptor Interacting Protein 3-Mediated Necroptosis Promotes Lipopolysaccharide-Induced Inflammation and Acute Respiratory Distress Syndrome in Mice

PubMed Central

Li, Haobo; Liu, Qing; Zhang, Zhongjun; Xie, Wanli; Feng, Yinglu; Socorburam, Tumenjavkhlan; Wu, Gui; Xia, Zhengyuan; Wu, Qingping

2016-01-01

Necrosis amplifies inflammation and plays important roles in acute respiratory distress syndrome (ARDS). Necroptosis is a newly identified programmed necrosis that is mediated by receptor interacting protein 3 (RIP3). However, the potential involvement and impact of necroptosis in lipopolysaccharide (LPS)-induced ARDS remains unknown. We therefore explored the role and mechanism of RIP3-mediated necroptosis in LPS-induced ARDS. Mice were instilled with increasing doses of LPS intratracheally to induce different degrees of ARDS. Lung tissues were harvested for histological and TUNEL staining and western blot for RIP3, p-RIP3, X-linked inhibitor of apoptosis protein (XIAP), mixed lineage kinase domain-like protein (MLKL), total and cleaved caspases-3/8. Then, wild-type and RIP3 knock-out mice were induced ARDS with 30 mg/kg LPS. Pulmonary cellular necrosis was labeled by the propidium Iodide (PI) staining. Levels of TNF-a, Interleukin (IL)-1β, IL-6, IL-1α, IL-10 and HMGB1, tissue myeloperoxidase (MPO) activity, neutrophil counts and total protein concentration were measured. Results showed that in high dose LPS (30mg/kg and 40mg/kg) -induced severe ARDS, RIP3 protein was increased significantly, accompanied by increases of p-RIP3 and MLKL, while in low dose LPS (10mg/kg and 20mg/kg) -induced mild ARDS, apoptosis was remarkably increased. In LPS-induced severe ARDS, RIP3 knock-out alleviated the hypothermia symptom, increased survival rate and ameliorated the lung tissue injury RIP3 depletion also attenuated LPS-induced increase in IL-1α/β, IL-6 and HMGB1 release, decreased tissue MPO activity, and reduced neutrophil influx and total protein concentration in BALF in severe ARDS. Further, RIP3 depletion reduced the necrotic cells in the lung and decreased the expression of MLKL, but had no impact on cleaved caspase-3 in LPS-induced ARDS. It is concluded that RIP3-mediated necroptosis is a major mechanism of enhanced inflammation and lung tissue injury in high dose LPS- induced severe ARDS in mice. PMID:27195494

National review of use of extracorporeal membrane oxygenation as respiratory support in thoracic surgery excluding lung transplantation.

PubMed

Rinieri, Philippe; Peillon, Christophe; Bessou, Jean-Paul; Veber, Benoît; Falcoz, Pierre-Emmanuel; Melki, Jean; Baste, Jean-Marc

2015-01-01

Extracorporeal membrane oxygenation (ECMO) for respiratory support is increasingly used in intensive care units (ICU), but rarely during thoracic surgical procedures outside the transplantation setting. ECMO can be an alternative to cardiopulmonary bypass for major trachea-bronchial surgery and single-lung procedures without in-field ventilation. Our aim was to evaluate the intraoperative use of ECMO as respiratory support in thoracic surgery: benefits, indications and complications. This was a multicentre retrospective study (questionnaire) of use of ECMO as respiratory support during the thoracic surgical procedure. Lung transplantation and lung resection for tumour invading the great vessels and/or the left atrium were excluded, because they concern respiratory and circulatory support. From March 2009 to September 2012, 17 of the 34 centres in France applied ECMO within veno-venous (VV) (n=20) or veno-arterial (VA) (n=16) indications in 36 patients. Ten VA ECMO were performed with peripheral cannulation and 6 with central cannulation; all VV ECMO were achieved through peripheral cannulation. Group 1 (total respiratory support) was composed of 28 patients without mechanical ventilation, involving 23 tracheo-bronchial and 5 single-lung procedures. Group 2 (partial respiratory support) was made up of 5 patients with respiratory insufficiency. Group 3 was made up of 3 patients who underwent thoracic surgery in a setting of acute respiratory distress syndrome (ARDS) with preoperative ECMO. Mortality at 30 days in Groups 1, 2 and 3 was 7, 40 and 67%, respectively (P<0.05). In Group 1, ECMO was weaned intraoperatively or within 24 h in 75% of patients. In Group 2, ECMO was weaned in ICU over several days. In Group 1, 2 patients with VA support were converted to VV support for chronic respiratory indications. Bleeding was the major complication with 17% of patients requiring return to theatre for haemostasis. There were two cannulation-related complications (6%). VV or VA ECMO is a satisfactory alternative to in-field ventilation in complex tracheo-bronchial surgery or in single-lung surgery. ECMO should be considered and used in precarious postoperative respiratory conditions. Full respiratory support can be achieved with VV ECMO. Indications for and results of ECMO during surgery in patients with ARDS warrant further careful investigation. © The Author 2014. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.

Acetylation of androgen receptor by ARD1 promotes dissociation from HSP90 complex and prostate tumorigenesis

PubMed Central

Zhang, Guanyi; Qian, Chiping; Zhang, Haitao; Zabaleta, Jovanny; Liu, Wanguo

2016-01-01

Prostate cancer is an androgen receptor (AR)-driven disease and post-translational modification of AR is critical for AR activation. We previously reported that Arrest-defective protein 1 (ARD1) is an oncoprotein in prostate cancer. It acetylates and activates AR to promote prostate tumorigenesis. However, the ARD1-targeted residue within AR and the mechanisms of the acetylation event in prostate tumorigenesis remained unknown. In this study, we show that ARD1 acetylates AR at lysine 618 (K618) in vitro and in vivo. An AR construct with the charged lysine substitution by arginine (AR-618R) reduces RNA Pol II binding, AR transcriptional activity, prostate cancer cell growth, and xenograft tumor formation due to attenuation of AR nuclear translocation, whereas, construct mimicking neutral polar substitution acetylation at K618 by glutamine (AR-618Q) enhanced these effects beyond that of the wild-type AR. Mechanistically, ARD1 forms a ternary complex with AR and HSP90 in vitro and in vivo. Expression of ARD1 increases levels of AR acetylation and AR-HSP90 dissociation in a dose dependent manner. Moreover, the AR acetylation defective K618R mutant is unable to dissociate from HSP90 while the HSP90-dissociated AR is acetylated following ligand exposure. This work identifies a new mechanism for ligand-induced AR-HSP90 dissociation and AR activation. Targeting ARD1-mediated AR acetylation may be a potent intervention for AR-dependent prostate cancer therapy. PMID:27659526

Effective and Safe Use of Glucocorticosteroids for Rescue of Late ARDS

PubMed Central

Diana, Paolo; Money, Dustin T.; Gelvin, Michael G.

2017-01-01

We describe a case of severe refractory hypoxemia requiring prolonged extra corporeal membrane oxygenation (ECMO) support in a case of postpartum acute respiratory distress syndrome (ARDS). The clinical course was marked by persistently poor lung compliance and several complications of ECMO, that is, significant hemolysis, hemothorax, and intracranial bleeding. We report marked improvement of lung mechanics and respiratory function, leading to accelerated separation from ECMO, following rescue administration of low dose methylprednisolone 24 days after the onset of ARDS. Corticosteroid treatment was safe and well tolerated. In contrast with the conclusions of the 2006 ARDS Network trial, our report establishes a case in support of the use of low dose methylprednisolone as a safe and effective rescue treatment option in selected subsets of patients with nonresolving ARDS. PMID:28337348

Initial trophic vs full enteral feeding in patients with acute lung injury: the EDEN randomized trial.

PubMed

Rice, Todd W; Wheeler, Arthur P; Thompson, B Taylor; Steingrub, Jay; Hite, R Duncan; Moss, Marc; Morris, Alan; Dong, Ning; Rock, Peter

2012-02-22

The amount of enteral nutrition patients with acute lung injury need is unknown. To determine if initial lower-volume trophic enteral feeding would increase ventilator-free days and decrease gastrointestinal intolerances compared with initial full enteral feeding. The EDEN study, a randomized, open-label, multicenter trial conducted from January 2, 2008, through April 12, 2011. Participants were 1000 adults within 48 hours of developing acute lung injury requiring mechanical ventilation whose physicians intended to start enteral nutrition at 44 hospitals in the National Heart, Lung, and Blood Institute ARDS Clinical Trials Network. Participants were randomized to receive either trophic or full enteral feeding for the first 6 days. After day 6, the care of all patients who were still receiving mechanical ventilation was managed according to the full feeding protocol. Ventilator-free days to study day 28. Baseline characteristics were similar between the trophic-feeding (n = 508) and full-feeding (n = 492) groups. The full-feeding group received more enteral calories for the first 6 days, about 1300 kcal/d compared with 400 kcal/d (P < .001). Initial trophic feeding did not increase the number of ventilator-free days (14.9 [95% CI, 13.9 to 15.8] vs 15.0 [95% CI, 14.1 to 15.9]; difference, -0.1 [95% CI, -1.4 to 1.2]; P = .89) or reduce 60-day mortality (23.2% [95% CI, 19.6% to 26.9%] vs 22.2% [95% CI, 18.5% to 25.8%]; difference, 1.0% [95% CI, -4.1% to 6.3%]; P = .77) compared with full feeding. There were no differences in infectious complications between the groups. Despite receiving more prokinetic agents, the full-feeding group experienced more vomiting (2.2% vs 1.7% of patient feeding days; P = .05), elevated gastric residual volumes (4.9% vs 2.2% of feeding days; P < .001), and constipation (3.1% vs 2.1% of feeding days; P = .003). Mean plasma glucose values and average hourly insulin administration were both higher in the full-feeding group over the first 6 days. In patients with acute lung injury, compared with full enteral feeding, a strategy of initial trophic enteral feeding for up to 6 days did not improve ventilator-free days, 60-day mortality, or infectious complications but was associated with less gastrointestinal intolerance. clinicaltrials.gov Identifiers: NCT00609180 and NCT00883948.

High Positive End-Expiratory Pressure Renders Spontaneous Effort Noninjurious.

PubMed

Morais, Caio C A; Koyama, Yukiko; Yoshida, Takeshi; Plens, Glauco M; Gomes, Susimeire; Lima, Cristhiano A S; Ramos, Ozires P S; Pereira, Sérgio M; Kawaguchi, Naomasa; Yamamoto, Hirofumi; Uchiyama, Akinori; Borges, João B; Vidal Melo, Marcos F; Tucci, Mauro R; Amato, Marcelo B P; Kavanagh, Brian P; Costa, Eduardo L V; Fujino, Yuji

2018-05-15

In acute respiratory distress syndrome (ARDS), atelectatic solid-like lung tissue impairs transmission of negative swings in pleural pressure (Ppl) that result from diaphragmatic contraction. The localization of more negative Ppl proportionally increases dependent lung stretch by drawing gas either from other lung regions (e.g., nondependent lung [pendelluft]) or from the ventilator. Lowering the level of spontaneous effort and/or converting solid-like to fluid-like lung might render spontaneous effort noninjurious. To determine whether spontaneous effort increases dependent lung injury, and whether such injury would be reduced by recruiting atelectatic solid-like lung with positive end-expiratory pressure (PEEP). Established models of severe ARDS (rabbit, pig) were used. Regional histology (rabbit), inflammation (positron emission tomography; pig), regional inspiratory Ppl (intrabronchial balloon manometry), and stretch (electrical impedance tomography; pig) were measured. Respiratory drive was evaluated in 11 patients with ARDS. Although injury during muscle paralysis was predominantly in nondependent and middle lung regions at low (vs. high) PEEP, strong inspiratory effort increased injury (indicated by positron emission tomography and histology) in dependent lung. Stronger effort (vs. muscle paralysis) caused local overstretch and greater tidal recruitment in dependent lung, where more negative Ppl was localized and greater stretch was generated. In contrast, high PEEP minimized lung injury by more uniformly distributing negative Ppl, and lowering the magnitude of spontaneous effort (i.e., deflection in esophageal pressure observed in rabbits, pigs, and patients). Strong effort increased dependent lung injury, where higher local lung stress and stretch was generated; effort-dependent lung injury was minimized by high PEEP in severe ARDS, which may offset need for paralysis.

Eosinophilic pneumonia presenting as life-threatening ARDS.

PubMed

Maia, José Miguel; Guedes, Fernando; Aragão, Irene; Cardoso, Teresa

2015-07-06

We present a case of a 25-year-old woman with sudden onset of shortness of breath, cough and malaise, 24 h after discharge from a psychiatric hospital. She had been there for 2 weeks after a suicide attempt with lye, and started treatment with paroxetin, alprazolam and valproic acid. She also started smoking 20 cigarettes/day during that hospital admission. Brought to the emergency department, she evolved in the first 24 h with respiratory failure and shock needing intensive care unit (ICU) admission, with mechanical ventilation and vasopressor support. Empiric antibiotic therapy was started (piperacillin-tazobactam and azithromycin) suspecting healthcare-associated pneumonia. The patient's chest radiography progressed with bilateral infiltrates. Peripheral blood eosinophilia was seen on the second day. A bronchoalveolar lavage was performed and had 50% of eosinophils. She was started on treatment with steroids and the next day no longer needed vasopressors; 4 days later she was extubated. 2015 BMJ Publishing Group Ltd.

Recovery from Dysphagia Symptoms after Oral Endotracheal Intubation in Acute Respiratory Distress Syndrome Survivors. A 5-Year Longitudinal Study.

PubMed

Brodsky, Martin B; Huang, Minxuan; Shanholtz, Carl; Mendez-Tellez, Pedro A; Palmer, Jeffrey B; Colantuoni, Elizabeth; Needham, Dale M

2017-03-01

Nearly 60% of patients who are intubated in intensive care units (ICUs) experience dysphagia after extubation, and approximately 50% of them aspirate. Little is known about dysphagia recovery time after patients are discharged from the hospital. To determine factors associated with recovery from dysphagia symptoms after hospital discharge for acute respiratory distress syndrome (ARDS) survivors who received oral intubation with mechanical ventilation. This is a prospective, 5-year longitudinal cohort study involving 13 ICUs at four teaching hospitals in Baltimore, Maryland. The Sydney Swallowing Questionnaire (SSQ), a 17-item visual analog scale (range, 0-1,700), was used to quantify patient-perceived dysphagia symptoms at hospital discharge, and at 3, 6, 12, 24, 36, 48, and 60 months after ARDS. An SSQ score greater than or equal to 200 was used to indicate clinically important dysphagia symptoms at the time of hospital discharge. Recovery was defined as an SSQ score less than 200, with a decrease from hospital discharge greater than or equal to 119, the reliable change index for SSQ score. Fine and Gray proportional subdistribution hazards regression analysis was used to evaluate patient and ICU variables associated with time to recovery accounting for the competing risk of death. Thirty-seven (32%) of 115 patients had an SSQ score greater than or equal to 200 at hospital discharge; 3 died before recovery. All 34 remaining survivors recovered from dysphagia symptoms by 5-year follow-up, 7 (23%) after 6 months. ICU length of stay was independently associated with time to recovery, with a hazard ratio (95% confidence interval) of 0.96 (0.93-1.00) per day. One-third of orally intubated ARDS survivors have dysphagia symptoms that persist beyond hospital discharge. Patients with a longer ICU length of stay have slower recovery from dysphagia symptoms and should be carefully considered for swallowing assessment to help prevent complications related to dysphagia.

Therapeutic Effect of Intravenous Infusion of Perfluorocarbon Emulsion on LPS-Induced Acute Lung Injury in Rats

PubMed Central

Lv, Qi; Yin, Xiaofeng; Song, Jianqi; Landén, Ning Xu; Fan, Haojun

2014-01-01

Acute lung injury (ALI) and its more severe form, acute respiratory distress syndrome (ARDS) are the leading causes of death in critical care. Despite extensive efforts in research and clinical medicine, mortality remains high in these diseases. Perfluorocarbon (PFC), a chemical compound known as liquid ventilation medium, is capable of dissolving large amounts of physiologically important gases (mainly oxygen and carbon dioxide). In this study we aimed to investigate the effect of intravenous infusion of PFC emulsion on lipopolysaccharide (LPS) induced ALI in rats and elucidate its mechanism of action. Forty two Wistar rats were randomly divided into three groups: 6 rats were treated with saline solution by intratracheal instillation (control group), 18 rats were treated with LPS by intratracheal instillation (LPS group) and the other 18 rats received PFC through femoral vein prior to LPS instillation (LPS+PFC group). The rats in the control group were sacrificed 6 hours later after saline instillation. At 2, 4 and 6 hours of exposure to LPS, 6 rats in the LPS group and 6 rats in LPS+PFC group were sacrificed at each time point. By analyzing pulmonary pathology, partial pressure of oxygen in the blood (PaO2) and lung wet-dry weight ratio (W/D) of each rat, we found that intravenous infusion of PFC significantly alleviated acute lung injury induced by LPS. Moreover, we showed that the expression of pulmonary myeloperoxidase (MPO), intercellular adhesion molecule-1 (ICAM-1) of endothelial cells and CD11b of polymorphonuclear neutrophils (PMN) induced by LPS were significantly decreased by PFC treatment in vivo. Our results indicate that intravenous infusion of PFC inhibits the infiltration of PMNs into lung tissue, which has been shown as the core pathogenesis of ALI/ARDS. Thus, our study provides a theoretical foundation for using intravenous infusion of PFC to prevent and treat ALI/ARDS in clinical practice. PMID:24489970

Recovery from Dysphagia Symptoms after Oral Endotracheal Intubation in Acute Respiratory Distress Syndrome Survivors. A 5-Year Longitudinal Study

PubMed Central

Needham, Dale M.

2017-01-01

Rationale: Nearly 60% of patients who are intubated in intensive care units (ICUs) experience dysphagia after extubation, and approximately 50% of them aspirate. Little is known about dysphagia recovery time after patients are discharged from the hospital. Objectives: To determine factors associated with recovery from dysphagia symptoms after hospital discharge for acute respiratory distress syndrome (ARDS) survivors who received oral intubation with mechanical ventilation. Methods: This is a prospective, 5-year longitudinal cohort study involving 13 ICUs at four teaching hospitals in Baltimore, Maryland. The Sydney Swallowing Questionnaire (SSQ), a 17-item visual analog scale (range, 0–1,700), was used to quantify patient-perceived dysphagia symptoms at hospital discharge, and at 3, 6, 12, 24, 36, 48, and 60 months after ARDS. An SSQ score greater than or equal to 200 was used to indicate clinically important dysphagia symptoms at the time of hospital discharge. Recovery was defined as an SSQ score less than 200, with a decrease from hospital discharge greater than or equal to 119, the reliable change index for SSQ score. Fine and Gray proportional subdistribution hazards regression analysis was used to evaluate patient and ICU variables associated with time to recovery accounting for the competing risk of death. Measurements and Main Results: Thirty-seven (32%) of 115 patients had an SSQ score greater than or equal to 200 at hospital discharge; 3 died before recovery. All 34 remaining survivors recovered from dysphagia symptoms by 5-year follow-up, 7 (23%) after 6 months. ICU length of stay was independently associated with time to recovery, with a hazard ratio (95% confidence interval) of 0.96 (0.93–1.00) per day. Conclusions: One-third of orally intubated ARDS survivors have dysphagia symptoms that persist beyond hospital discharge. Patients with a longer ICU length of stay have slower recovery from dysphagia symptoms and should be carefully considered for swallowing assessment to help prevent complications related to dysphagia. PMID:27983872

How Useful is Extravascular Lung Water Measurement in Managing Lung Injury in Intensive Care Unit?

PubMed

Bhattacharjee, Anirban; Pradhan, Debasis; Bhattacharyya, Prithwis; Dey, Samarjit; Chhunthang, Daniala; Handique, Akash; Barman, Angkita; Yunus, Mohd

2017-08-01

The primary goal of septic shock management is optimization of organ perfusion, often at the risk of overloading the interstitium and causing pulmonary edema. The conventionally used end points of resuscitation do not generally include volumetric parameters such as extravascular lung water index (EVLWI) and pulmonary vascular permeability index (PVPI). This study aimed to assess the prognostic value of EVLWI and PVPI by calculating their correlation with the severity of lung injury. This prospective observational study included twenty mechanically ventilated critically ill patients with Acute Physiology and Chronic Health Evaluation score (APACHE II) >20. EVLWI and PVPI were measured using transpulmonary thermodilution, and simultaneously, PaO 2 :FiO 2 ratio, alveolar-arterial gradient of oxygen (AaDO 2 ), and chest radiograph scores from two radiologists were obtained. The correlation of EVLWI and PVPI with chest radiograph scores, PaO 2 :FiO 2 ratio, and AaDO 2 were calculated. The inter-observer agreement between the two radiologists was tested using kappa test. EVLWI and PVPI correlated modestly with PaO 2 :FiO 2 ( r = -0.32, P = 0.0004; r = -0.39, P = 0.0001). There was a better correlation of EVLWI and PVPI with PaO 2 :FiO 2 ratio ( r = -0.71, P < 0.0001; r = -0.58, P = 0.0001) in the acute respiratory distress syndrome (ARDS) subgroup. The EVLWI values correlated significantly with corresponding chest radiograph scores ( r = 0.71, P < 0.0001 for observer 1 and r = 0.68, P < 0.0001 for observer 2). EVLWI and PVPI may have a prognostic significance in the assessment of lung injury in septic shock patients with ARDS. Further research is required to reveal the usefulness of EVLWI as an end point of fluid resuscitation in the management of septic shock with ARDS.

Corticosteroid use in the intensive care unit: a survey of intensivists.

PubMed

Lamontagne, François; Quiroz Martinez, Hector; Adhikari, Neill K J; Cook, Deborah J; Koo, Karen K Y; Lauzier, François; Turgeon, Alexis F; Kho, Michelle E; Burns, Karen E A; Chant, Clarence; Fowler, Rob; Douglas, Ivor; Poulin, Yannick; Choong, Karen; Ferguson, Niall D; Meade, Maureen O

2013-07-01

The efficacy of systemic corticosteroids in many critical illnesses remains uncertain. Our primary objective was to survey intensivists in North America about their perceived use of corticosteroids in clinical practice. Self-administered paper survey. Intensivists in academic hospitals with clinical trial expertise in critical illness. We generated questionnaire items in focus groups and refined them after assessments of clinical sensibility and test-retest reliability and pilot testing. We administered the survey to experienced intensivists practicing in selected North American centres actively enrolling patients in the multicentre Oscillation for ARDS Treated Early (OSCILLATE) Trial (ISRCTN87124254). Respondents used a four-point scale to grade how frequently they would administer corticosteroids in 14 clinical settings. They also reported their opinions on 16 potential near-absolute indications or contraindications for the use of corticosteroids. Our response rate was 82% (103/125). Respondents were general internists (50%), respirologists (22%), anesthesiologists (21%), and surgeons (7%) who practiced in mixed medical-surgical units. A majority of respondents reported almost always prescribing corticosteroids in the setting of significant bronchospasm in a mechanically ventilated patient (94%), recent corticosteroid use and low blood pressure (93%), and vasopressor-refractory septic shock (52%). Although more than half of respondents stated they would almost never prescribe corticosteroids in severe community-acquired pneumonia (81%), acute lung injury (ALI, 76%), acute respiratory distress syndrome (ARDS, 65%), and severe ARDS (51%), variability increased with severity of acute lung injury. Near-absolute indications selected by most respondents included known adrenal insufficiency (99%) and suspicion of cryptogenic organizing pneumonia (89%), connective tissue disease (85%), or other potentially corticosteroid-responsive illnesses (85%). Respondents reported rarely prescribing corticosteroids for ALI, but accepted them for bronchospasm, suspected adrenal insufficiency due to previous corticosteroid use, and vasopressor-refractory septic shock. These competing indications will complicate the design and interpretation of any future large-scale trial of corticosteroids in critical illness.

Increased expression of neutrophil-related genes in patients with early sepsis-induced ARDS.

PubMed

Kangelaris, Kirsten Neudoerffer; Prakash, Arun; Liu, Kathleen D; Aouizerat, Bradley; Woodruff, Prescott G; Erle, David J; Rogers, Angela; Seeley, Eric J; Chu, Jeffrey; Liu, Tom; Osterberg-Deiss, Thomas; Zhuo, Hanjing; Matthay, Michael A; Calfee, Carolyn S

2015-06-01

The early sequence of events leading to the development of the acute respiratory distress syndrome (ARDS) in patients with sepsis remains inadequately understood. The purpose of this study was to identify changes in gene expression early in the course of illness, when mechanisms of injury may provide the most relevant treatment and prognostic targets. We collected whole blood RNA in critically ill patients admitted from the Emergency Department to the intensive care unit within 24 h of admission at a tertiary care center. Whole genome expression was compared in patients with sepsis and ARDS to patients with sepsis alone. We selected genes with >1 log2 fold change and false discovery rate <0.25, determined their significance in the literature, and performed pathway analysis. Several genes were upregulated in 29 patients with sepsis with ARDS compared with 28 patients with sepsis alone. The most differentially expressed genes included key mediators of the initial neutrophil response to infection: olfactomedin 4, lipocalin 2, CD24, and bactericidal/permeability-increasing protein. These gene expression differences withstood adjustment for age, sex, study batch, white blood cell count, and presence of pneumonia or aspiration. Pathway analysis demonstrated overrepresentation of genes involved in known respiratory and infection pathways. These data indicate that several neutrophil-related pathways may be involved in the early pathogenesis of sepsis-related ARDS. In addition, identifiable gene expression differences occurring early in the course of sepsis-related ARDS may further elucidate understanding of the neutrophil-related mechanisms in progression to ARDS. Copyright © 2015 the American Physiological Society.

Increased expression of neutrophil-related genes in patients with early sepsis-induced ARDS

PubMed Central

Prakash, Arun; Liu, Kathleen D.; Aouizerat, Bradley; Woodruff, Prescott G.; Erle, David J.; Rogers, Angela; Seeley, Eric J.; Chu, Jeffrey; Liu, Tom; Osterberg-Deiss, Thomas; Zhuo, Hanjing; Matthay, Michael A.; Calfee, Carolyn S.

2015-01-01

The early sequence of events leading to the development of the acute respiratory distress syndrome (ARDS) in patients with sepsis remains inadequately understood. The purpose of this study was to identify changes in gene expression early in the course of illness, when mechanisms of injury may provide the most relevant treatment and prognostic targets. We collected whole blood RNA in critically ill patients admitted from the Emergency Department to the intensive care unit within 24 h of admission at a tertiary care center. Whole genome expression was compared in patients with sepsis and ARDS to patients with sepsis alone. We selected genes with >1 log2 fold change and false discovery rate <0.25, determined their significance in the literature, and performed pathway analysis. Several genes were upregulated in 29 patients with sepsis with ARDS compared with 28 patients with sepsis alone. The most differentially expressed genes included key mediators of the initial neutrophil response to infection: olfactomedin 4, lipocalin 2, CD24, and bactericidal/permeability-increasing protein. These gene expression differences withstood adjustment for age, sex, study batch, white blood cell count, and presence of pneumonia or aspiration. Pathway analysis demonstrated overrepresentation of genes involved in known respiratory and infection pathways. These data indicate that several neutrophil-related pathways may be involved in the early pathogenesis of sepsis-related ARDS. In addition, identifiable gene expression differences occurring early in the course of sepsis-related ARDS may further elucidate understanding of the neutrophil-related mechanisms in progression to ARDS. PMID:25795726

Candidate genes and pathogenesis investigation for sepsis-related acute respiratory distress syndrome based on gene expression profile.

PubMed

Wang, Min; Yan, Jingjun; He, Xingxing; Zhong, Qiang; Zhan, Chengye; Li, Shusheng

2016-04-18

Acute respiratory distress syndrome (ARDS) is a potentially devastating form of acute inflammatory lung injury as well as a major cause of acute respiratory failure. Although researchers have made significant progresses in elucidating the pathophysiology of this complex syndrome over the years, the absence of a universal detail disease mechanism up until now has led to a series of practical problems for a definitive treatment. This study aimed to predict some genes or pathways associated with sepsis-related ARDS based on a public microarray dataset and to further explore the molecular mechanism of ARDS. A total of 122 up-regulated DEGs and 91 down-regulated differentially expressed genes (DEGs) were obtained. The up- and down-regulated DEGs were mainly involved in functions like mitotic cell cycle and pathway like cell cycle. Protein-protein interaction network of ARDS analysis revealed 20 hub genes including cyclin B1 (CCNB1), cyclin B2 (CCNB2) and topoisomerase II alpha (TOP2A). A total of seven transcription factors including forkhead box protein M1 (FOXM1) and 30 target genes were revealed in the transcription factor-target gene regulation network. Furthermore, co-cited genes including CCNB2-CCNB1 were revealed in literature mining for the relations ARDS related genes. Pathways like mitotic cell cycle were closed related with the development of ARDS. Genes including CCNB1, CCNB2 and TOP2A, as well as transcription factors like FOXM1 might be used as the novel gene therapy targets for sepsis related ARDS.

Outcome Prediction in Pneumonia Induced ALI/ARDS by Clinical Features and Peptide Patterns of BALF Determined by Mass Spectrometry

PubMed Central

Frenzel, Jochen; Gessner, Christian; Sandvoss, Torsten; Hammerschmidt, Stefan; Schellenberger, Wolfgang; Sack, Ulrich; Eschrich, Klaus; Wirtz, Hubert

2011-01-01

Background Peptide patterns of bronchoalveolar lavage fluid (BALF) were assumed to reflect the complex pathology of acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) better than clinical and inflammatory parameters and may be superior for outcome prediction. Methodology/Principal Findings A training group of patients suffering from ALI/ARDS was compiled from equal numbers of survivors and nonsurvivors. Clinical history, ventilation parameters, Murray's lung injury severity score (Murray's LISS) and interleukins in BALF were gathered. In addition, samples of bronchoalveolar lavage fluid were analyzed by means of hydrophobic chromatography and MALDI-ToF mass spectrometry (MALDI-ToF MS). Receiver operating characteristic (ROC) analysis for each clinical and cytokine parameter revealed interleukin-6>interleukin-8>diabetes mellitus>Murray's LISS as the best outcome predictors. Outcome predicted on the basis of BALF levels of interleukin-6 resulted in 79.4% accuracy, 82.7% sensitivity and 76.1% specificity (area under the ROC curve, AUC, 0.853). Both clinical parameters and cytokines as well as peptide patterns determined by MALDI-ToF MS were analyzed by classification and regression tree (CART) analysis and support vector machine (SVM) algorithms. CART analysis including Murray's LISS, interleukin-6 and interleukin-8 in combination was correct in 78.0%. MALDI-ToF MS of BALF peptides did not reveal a single identifiable biomarker for ARDS. However, classification of patients was successfully achieved based on the entire peptide pattern analyzed using SVM. This method resulted in 90% accuracy, 93.3% sensitivity and 86.7% specificity following a 10-fold cross validation (AUC = 0.953). Subsequent validation of the optimized SVM algorithm with a test group of patients with unknown prognosis yielded 87.5% accuracy, 83.3% sensitivity and 90.0% specificity. Conclusions/Significance MALDI-ToF MS peptide patterns of BALF, evaluated by appropriate mathematical methods can be of value in predicting outcome in pneumonia induced ALI/ARDS. PMID:21991318

Outcome prediction in pneumonia induced ALI/ARDS by clinical features and peptide patterns of BALF determined by mass spectrometry.

PubMed

Frenzel, Jochen; Gessner, Christian; Sandvoss, Torsten; Hammerschmidt, Stefan; Schellenberger, Wolfgang; Sack, Ulrich; Eschrich, Klaus; Wirtz, Hubert

2011-01-01

Peptide patterns of bronchoalveolar lavage fluid (BALF) were assumed to reflect the complex pathology of acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) better than clinical and inflammatory parameters and may be superior for outcome prediction. A training group of patients suffering from ALI/ARDS was compiled from equal numbers of survivors and nonsurvivors. Clinical history, ventilation parameters, Murray's lung injury severity score (Murray's LISS) and interleukins in BALF were gathered. In addition, samples of bronchoalveolar lavage fluid were analyzed by means of hydrophobic chromatography and MALDI-ToF mass spectrometry (MALDI-ToF MS). Receiver operating characteristic (ROC) analysis for each clinical and cytokine parameter revealed interleukin-6>interleukin-8>diabetes mellitus>Murray's LISS as the best outcome predictors. Outcome predicted on the basis of BALF levels of interleukin-6 resulted in 79.4% accuracy, 82.7% sensitivity and 76.1% specificity (area under the ROC curve, AUC, 0.853). Both clinical parameters and cytokines as well as peptide patterns determined by MALDI-ToF MS were analyzed by classification and regression tree (CART) analysis and support vector machine (SVM) algorithms. CART analysis including Murray's LISS, interleukin-6 and interleukin-8 in combination was correct in 78.0%. MALDI-ToF MS of BALF peptides did not reveal a single identifiable biomarker for ARDS. However, classification of patients was successfully achieved based on the entire peptide pattern analyzed using SVM. This method resulted in 90% accuracy, 93.3% sensitivity and 86.7% specificity following a 10-fold cross validation (AUC = 0.953). Subsequent validation of the optimized SVM algorithm with a test group of patients with unknown prognosis yielded 87.5% accuracy, 83.3% sensitivity and 90.0% specificity. MALDI-ToF MS peptide patterns of BALF, evaluated by appropriate mathematical methods can be of value in predicting outcome in pneumonia induced ALI/ARDS.

Structural and Biochemical Consequences of Disease-Causing Mutations in the Ankyrin Repeat Domain of the Human TRPV4 Channel

DOE Office of Scientific and Technical Information (OSTI.GOV)

Inada, Hitoshi; Procko, Erik; Sotomayor, Marcos

2012-10-23

The TRPV4 calcium-permeable cation channel plays important physiological roles in osmosensation, mechanosensation, cell barrier formation, and bone homeostasis. Recent studies reported that mutations in TRPV4, including some in its ankyrin repeat domain (ARD), are associated with human inherited diseases, including neuropathies and skeletal dysplasias, probably because of the increased constitutive activity of the channel. TRPV4 activity is regulated by the binding of calmodulin and small molecules such as ATP to the ARD at its cytoplasmic N-terminus. We determined structures of ATP-free and -bound forms of human TRPV4-ARD and compared them with available TRPV-ARD structures. The third inter-repeat loop region (Fingermore » 3 loop) is flexible and may act as a switch to regulate channel activity. Comparisons of TRPV-ARD structures also suggest an evolutionary link between ARD structure and ATP binding ability. Thermal stability analyses and molecular dynamics simulations suggest that ATP increases stability in TRPV-ARDs that can bind ATP. Biochemical analyses of a large panel of TRPV4-ARD mutations associated with human inherited diseases showed that some impaired thermal stability while others weakened ATP binding ability, suggesting molecular mechanisms for the diseases.« less

[Value of procalcitonin on predicting the severity and prognosis in patients with early ARDS: a prospective observation study].

PubMed

Yu, Zhixin; Ji, Musen; Hu, Xiulan; Yan, Jun; Jin, Zhaochen

2017-01-01

To investigate the value of procalcitonin (PCT) on predicting the severity and prognosis in patients with early acute respiratory distress syndrome (ARDS). A prospective observation study was conducted. A total of 113 patients with ARDS undergoing mechanical ventilation admitted to intensive care unit (ICU) of Affiliated People's Hospital of Jiangsu University from October 2012 to April 2016 were enrolled. Based on oxygenation index (PaO 2 /FiO 2 ), the patients were classified into mild, moderate, and severe groups according to Berlin Definition. Twenty-five healthy volunteers were served as controls. Demographics, acute physiology and chronic health evaluation II (APACHE II) score, and Murray lung injury score were recorded. Within 24 hours after diagnosis of ARDS, the serum levels of PCT and C-reactive protein (CRP) were determined by enzyme-linked fluorescence analysis (ELFA) and immune turbidimetric method, respectively. The patients were also divided into survival and non-survival groups according to clinical outcome within 28-day follow-up, and the clinical data were compared between the two groups. Spearman rank correlation was applied to determine the correlation between variables. The predictive value of the parameters on 28-day mortality was evaluated with receiver operating characteristic curve (ROC). Kaplan-Meier survival curve analysis was used to compare different PCT levels of patients with 28-day cumulative survival rate. After excluding patients who did not meet the inclusion criteria and loss to follow-up, the final 89 patients were enrolled in the analysis. Among 89 ARDS patients analyzed, 27 of them were mild, 34 moderate, and 28 severe ARDS. No significant differences were found in age and gender between ARDS and healthy control groups. Infection and trauma were the most common etiology of ARDS (55.1% and 34.8%, respectively). Compared with healthy control group, both CRP and PCT in serum of ARDS group were higher [CRP (mg/L): 146.32 (111.31, 168.49) vs. 6.08 (4.47, 7.89), PCT (μg/L): 3.46 (1.98, 5.56) vs. 0.02 (0.01, 0.04), both P < 0.01], and the two showed sustained upward trends with the ARDS course of disease. Compared with mild group, severe group had significantly higher APACHE II and Murray scores. Spearman rank correlation analysis showed that both serum PCT and CRP in patients with ARDS was correlated well with APACHE II score (r values were 0.669 and 0.601, respectively, both P < 0.001), while PCT was weakly but positively correlated with Murray score (r = 0.294, P = 0.005), but not the case of CRP (r = 0.203, P = 0.052). APACHE II score and serum PCT in non-survival group (n = 38) were significantly higher than those of the survival group [n = 51; APACHE II score: 26.00 (23.00, 28.50) vs. 21.00 (17.00, 25.00), PCT (μg/L): 6.38 (2.82, 9.49) vs. 3.09 (1.08, 3.57), both P < 0.01], but Murray score and CRP level were similar between survivors and non-survivors. The areas under ROC curve (AUC) of APACHE II score and PCT for predicting 28-day mortality were 0.781 and 0.793, respectively, which were better than those of AUC of Murray score and CRP (0.606 and 0.561, respectively, all P < 0.05). The AUC of APACHE II score combined with PCT was significantly higher than that of PCT (0.859 vs. 0.793, P = 0.048) or APACHE II score alone (0.859 vs. 0.781, P = 0.038). Using a PCT cut-off value of > 4.35 μg/L for predicting 28-day mortality, the sensitivity and specificity was 92.2% and 63.2%, respectively, and the positive and negative likelihood ratios were 2.50 and 0.12 respectively. Kaplan-Meier survival curve analysis indicated that the patients whose PCT more than 4.35 μg/L, had lower 28-day cummulative survival rate as compared with those with PCT ≤ 4.35 μg/L (log-rank test: χ 2 = 5.013, P = 0.025). The elevated serum PCT level in patients with ARDS seems to be correlated well with the severity of lung injury, and appears to be a useful prognostic marker of outcome in the early phases of ARDS.

Identification of Novel Single Nucleotide Polymorphisms Associated with Acute Respiratory Distress Syndrome by Exome-Seq

PubMed Central

Shortt, Katherine; Chaudhary, Suman; Grigoryev, Dmitry; Heruth, Daniel P.; Venkitachalam, Lakshmi; Zhang, Li Q.; Ye, Shui Q.

2014-01-01

Acute respiratory distress syndrome (ARDS) is a lung condition characterized by impaired gas exchange with systemic release of inflammatory mediators, causing pulmonary inflammation, vascular leak and hypoxemia. Existing biomarkers have limited effectiveness as diagnostic and therapeutic targets. To identify disease-associating variants in ARDS patients, whole-exome sequencing was performed on 96 ARDS patients, detecting 1,382,399 SNPs. By comparing these exome data to those of the 1000 Genomes Project, we identified a number of single nucleotide polymorphisms (SNP) which are potentially associated with ARDS. 50,190SNPs were found in all case subgroups and controls, of which89 SNPs were associated with susceptibility. We validated three SNPs (rs78142040, rs9605146 and rs3848719) in additional ARDS patients to substantiate their associations with susceptibility, severity and outcome of ARDS. rs78142040 (C>T) occurs within a histone mark (intron 6) of the Arylsulfatase D gene. rs9605146 (G>A) causes a deleterious coding change (proline to leucine) in the XK, Kell blood group complex subunit-related family, member 3 gene. rs3848719 (G>A) is a synonymous SNP in the Zinc-Finger/Leucine-Zipper Co-Transducer NIF1 gene. rs78142040, rs9605146, and rs3848719 are associated significantly with susceptibility to ARDS. rs3848719 is associated with APACHE II score quartile. rs78142040 is associated with 60-day mortality in the overall ARDS patient population. Exome-seq is a powerful tool to identify potential new biomarkers for ARDS. We selectively validated three SNPs which have not been previously associated with ARDS and represent potential new genetic biomarkers for ARDS. Additional validation in larger patient populations and further exploration of underlying molecular mechanisms are warranted. PMID:25372662

Elevated Plasma Levels of sRAGE Are Associated With Nonfocal CT-Based Lung Imaging in Patients With ARDS: A Prospective Multicenter Study.

PubMed

Mrozek, Segolene; Jabaudon, Matthieu; Jaber, Samir; Paugam-Burtz, Catherine; Lefrant, Jean-Yves; Rouby, Jean-Jacques; Asehnoune, Karim; Allaouchiche, Bernard; Baldesi, Olivier; Leone, Marc; Lu, Qin; Bazin, Jean-Etienne; Roszyk, Laurence; Sapin, Vincent; Futier, Emmanuel; Pereira, Bruno; Constantin, Jean-Michel

2016-11-01

During ARDS, CT can reveal two distinct lung imaging patterns, focal or nonfocal, with different responses to positive end-expiratory pressure, recruitment maneuvers, and prone position. Nevertheless, their association with plasma biomarkers and their distinct functional/pathobiological mechanisms are unknown. The objective of this study was to characterize focal and nonfocal patterns of lung CT-based imaging with plasma markers of lung injury. A prospective multicenter cohort study involving 119 consecutive patients with ARDS. Plasma biomarkers (soluble form of the receptor for advanced glycation end product [sRAGE], plasminogen activator inhibitor-1, soluble intercellular adhesion molecule-1, and surfactant protein-D) were measured within 24 h of ARDS onset. Lung CT scan was performed within the first 48 h to assess lung morphology. Thirty-two (27%) and 87 (73%) patients had focal and nonfocal ARDS, respectively. Plasma levels of sRAGE were significantly higher in nonfocal ARDS, compared with focal ARDS. A cut-off of 1,188 pg/mL differentiated focal from nonfocal ARDS with a sensitivity of 94% and a specificity of 84%. Nonfocal patterns were associated with higher 28- and 90-day mortality than focal patterns (31% vs 12%, P = .038 and 46% vs 21%, P = .026, respectively). Plasma levels of plasminogen activator inhibitor-1 were significantly higher in nonfocal ARDS. There was no difference in other biomarkers. Plasma sRAGE is associated with a nonfocal ARDS. Such novel findings may suggest a role for RAGE pathway in an underlying endotype of impaired alveolar fluid clearance and stimulate future research on the association between ARDS phenotypes and therapeutic responses. Copyright © 2016 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.

Low-dose CT for quantitative analysis in acute respiratory distress syndrome

PubMed Central

2013-01-01

Introduction The clinical use of serial quantitative computed tomography (CT) to characterize lung disease and guide the optimization of mechanical ventilation in patients with acute respiratory distress syndrome (ARDS) is limited by the risk of cumulative radiation exposure and by the difficulties and risks related to transferring patients to the CT room. We evaluated the effects of tube current-time product (mAs) variations on quantitative results in healthy lungs and in experimental ARDS in order to support the use of low-dose CT for quantitative analysis. Methods In 14 sheep chest CT was performed at baseline and after the induction of ARDS via intravenous oleic acid injection. For each CT session, two consecutive scans were obtained applying two different mAs: 60 mAs was paired with 140, 15 or 7.5 mAs. All other CT parameters were kept unaltered (tube voltage 120 kVp, collimation 32 × 0.5 mm, pitch 0.85, matrix 512 × 512, pixel size 0.625 × 0.625 mm). Quantitative results obtained at different mAs were compared via Bland-Altman analysis. Results Good agreement was observed between 60 mAs and 140 mAs and between 60 mAs and 15 mAs (all biases less than 1%). A further reduction of mAs to 7.5 mAs caused an increase in the bias of poorly aerated and nonaerated tissue (-2.9% and 2.4%, respectively) and determined a significant widening of the limits of agreement for the same compartments (-10.5% to 4.8% for poorly aerated tissue and -5.9% to 10.8% for nonaerated tissue). Estimated mean effective dose at 140, 60, 15 and 7.5 mAs corresponded to 17.8, 7.4, 2.0 and 0.9 mSv, respectively. Image noise of scans performed at 140, 60, 15 and 7.5 mAs corresponded to 10, 16, 38 and 74 Hounsfield units, respectively. Conclusions A reduction of effective dose up to 70% has been achieved with minimal effects on lung quantitative results. Low-dose computed tomography provides accurate quantitative results and could be used to characterize lung compartment distribution and possibly monitor time-course of ARDS with a lower risk of exposure to ionizing radiation. A further radiation dose reduction is associated with lower accuracy in quantitative results. PMID:24004842

Comparison of patients with avian influenza A (H7N9) and influenza A (H1N1) complicated by acute respiratory distress syndrome.

PubMed

Li, Hongyan; Weng, Heng; Lan, Changqing; Zhang, Hongying; Wang, Xinhang; Pan, Jianguang; Chen, Lulu; Huang, Jinbao

2018-03-01

The aim of this study was to compare the clinical features of patients with avian influenza A (H7N9) and influenza A (H1N1) complicated by acute respiratory distress syndrome (ARDS).The clinical data of 18 cases of H7N9 and 26 cases of H1N1 with ARDS were collected and compared in the respiratory intensive care unit (RICU) of Fuzhou Pulmonary Hospital of Fujian from March 2014 to December 2016.Patients with H7N9 had a higher acute physiology and chronic health evaluation-II score (P < .05) and lung injury score (P < .05). The rates of coexisting diabetes mellitus, hyperpyrexia, and bloody sputum production were significantly higher in the H7N9 group than in the H1N1 group (P < .05). The H7N9 group had a longer duration of viral shedding from the onset of illness (P < .05) and from the initiation of antiviral therapy (P < .05) to a negative viral test result than the H1N1 group. Patients with H7N9 had higher rates of invasive mechanical ventilation; serious complications, including alimentary tract hemorrhage, pneumothorax or septum emphysema, hospital-acquired pneumonia (HAP) and multiple organ dysfunction syndrome (MODS); and hospital mortality (P < .05). At the 6th month of follow-up, the rates of bronchiectasia, reticular opacities, fibrous stripes, and patchy opacities on chest computed tomography (CT) were significantly higher in the H7N9 group than in the H1N1 group (P < .05). Based on multiple logistic regression analysis, H7N9 influenza viral infection was associated with a higher risk of the presence of severe ARDS than H1N1 influenza viral infection (odds ratio 8.29, 95% confidence interval [CI] 1.53-44.94; P < .05).Compared to patients with H1N1, patients with H7N9 complicated by ARDS had much more severe disease. During long-term follow-up, more changes in pulmonary fibrosis were observed in patients with H7N9 than in patients with H1N1 during the convalescent stage.

Recent directions in personalised acute respiratory distress syndrome medicine.

PubMed

Jabaudon, Matthieu; Blondonnet, Raiko; Audard, Jules; Fournet, Marianne; Godet, Thomas; Sapin, Vincent; Constantin, Jean-Michel

2018-06-01

Acute respiratory distress syndrome (ARDS) is heterogeneous by definition and patient response varies depending on underlying biology and their severity of illness. Although ARDS subtypes have been identified with different prognoses in past studies, the concept of phenotypes or endotypes does not extend to the clinical definition of ARDS. This has possibly hampered the development of therapeutic interventions that target select biological mechanisms of ARDS. Recently, a major advance may have been achieved as it may now be possible to identify ARDS subtypes that may confer different responses to therapy. The aim of personalised medicine is to identify, select, and test therapies that are most likely to be associated with a favourable outcome in a specific patient. Several promising approaches to ARDS subtypes capable of predicting therapeutic response, and not just prognosis, are highlighted in this perspective paper. An overview is also provided of current and future directions regarding the provision of personalised ARDS medicine. The importance of delivering the right care, at the right time, to the right patient, is emphasised. Copyright © 2018 Société française d'anesthésie et de réanimation (Sfar). Published by Elsevier Masson SAS. All rights reserved.

Clinical Meaning of Early Oxygenation Improvement in Severe Acute Respiratory Distress Syndrome under Prolonged Prone Positioning

PubMed Central

Lee, Kwangha; Kim, Mi-Young; Yoo, Jung-Wan; Hong, Sang-Bum; Lim, Chae-Man

2010-01-01

Background/Aims Ventilating patients with acute respiratory distress syndrome (ARDS) in the prone position has been shown to improve arterial oxygenation, but prolonged prone positioning frequently requires continuous deep sedation, which may be harmful to patients. We evaluated the meaning of early gas exchange in patients with severe ARDS under prolonged (≥ 12 hours) prone positioning. Methods We retrospectively studied 96 patients (mean age, 60.1 ± 15.6 years; 75% men) with severe ARDS (PaO2/FiO2 ≤ 150 mmHg) admitted to a medical intensive care unit (MICU). The terms "PaO2 response" and "PaCO2 response" represented responses that resulted in increases in the PaO2/FiO2 ratio of ≥ 20 mmHg and decreases in PaCO2 of ≥ 1 mmHg, respectively, 8 to 12 hours after first placement in the prone position. Results The mean duration of prone positioning was 78.5 ± 61.2 hours, and the 28-day mortality rate after MICU admission was 56.3%. No significant difference in clinical characteristics was observed between PaO2 and PaCO2 responders and non-responders. The PaO2 responders after prone positioning showed an improved 28-day outcome, compared with non-responders by Kaplan-Meier survival estimates (p < 0.05 by the log-rank test), but the PaCO2 responders did not. Conclusions Our results suggest that the early oxygenation improvement after prone positioning might be associated with an improved 28-day outcome and may be an indicator to maintain prolonged prone positioning in patients with severe ARDS. PMID:20195404

Pleiotropic effects of interleukin-6 in a "two-hit" murine model of acute respiratory distress syndrome.

PubMed

Goldman, Julia L; Sammani, Saad; Kempf, Carrie; Saadat, Laleh; Letsiou, Eleftheria; Wang, Ting; Moreno-Vinasco, Liliana; Rizzo, Alicia N; Fortman, Jeffrey D; Garcia, Joe G N

2014-06-01

Patients with acute respiratory distress syndrome (ARDS) exhibit elevated levels of interleukin-6 (IL-6), which correlate with increased morbidity and mortality. The exact role of IL-6 in ARDS has proven difficult to study because it exhibits either pro- or anti-inflammatory actions in mouse models of lung injury, depending on the model utilized. In order to improve understanding of the role of this complex cytokine in ARDS, we evaluated IL-6 using the clinically relevant combination of lipopolysaccharide (LPS) and ventilator-induced lung injury (VILI) in IL-6(-/-) mice. Bronchoalveolar lavage fluid (BAL), whole-lung tissue, and histology were evaluated for inflammatory markers of injury. Transendothelial electrical resistance was used to evaluate the action of IL-6 on endothelial cells in vitro. In wild-type mice, the combination model showed a significant increase in lung injury compared to either LPS or VILI alone. IL-6(-/-) mice exhibited a statistically significant decrease in BAL cellular inflammation as well as lower histologic scores for lung injury, changes observed only in the combination model. A paradoxical increase in BAL total protein was observed in IL-6(-/-) mice exposed to LPS, suggesting that IL-6 provides protection from vascular leakage. However, in vitro data showed that IL-6, when combined with its soluble receptor, actually caused a significant increase in endothelial cell permeability, suggesting that the protection seen in vivo was likely due to complex interactions of IL-6 and other inflammatory mediators rather than to direct effects of IL-6. These studies suggest that a dual-injury model exhibits utility in evaluating the pleiotropic effects of IL-6 in ARDS on inflammatory cells and lung endothelium.

Total ginsenosides synergize with ulinastatin against septic acute lung injury and acute respir atory distress syndrome

PubMed Central

Sun, Rongju; Li, Yana; Chen, Wei; Zhang, Fei; Li, Tanshi

2015-01-01

Total ginsenosides synergize with ulinastatin (UTI) against septic acute lung injury (ALI) and acute respiratory distress syndrome (ARDS). We randomly divided 80 cases of severe sepsis-induced ALI and ARDS into a UTI group and a ginsenosides (GS)+UTI group. Continuous electrocardiac monitoring of pulse, respiratory rate, blood pressure, and heart rate; invasive hemodynamic monitoring; ventilator-assisted breathing and circulation support; and anti-infection as well as UTI treatment were given in the UTI group with GS treatment added for 7 consecutive days in the GS+UTI group. The indicators of pulmonary vascular permeability, pulmonary circulation, blood gases, and hemodynamics as well as APACHE II and ALI scores were detected on days 1, 3, and 7. The ALI score in the GS+UTI group was significantly decreased (P < 0.05) compared with that of the UTI group, and the indicators of pulmonary capillary permeability such as pulmonary vascular permeability index, extravascular lung water index, and oxygenation index, in the GS+UTI group improved significantly more than that of the UTI group. The indicators of hemodynamics and pulmonary circulation such as cardiac index, intrathoracic blood volume index, and central venous pressure improved significantly (P < 0.05), and the APACHE II score in the GS+UTI group was lower than that of the UTI group. GS can effectively collaborate with UTI against ALI and/or ARDS. PMID:26261640

Soluble programmed cell death receptor-1 (sPD-1): a potential biomarker with anti-inflammatory properties in human and experimental acute respiratory distress syndrome (ARDS).

PubMed

Monaghan, Sean F; Chung, Chun-Shiang; Chen, Yaping; Lomas-Neira, Joanne; Fairbrother, William G; Heffernan, Daithi S; Cioffi, William G; Ayala, Alfred

2016-11-11

Acute respiratory distress syndrome (ARDS) remains a common organ dysfunction in the critically ill patient. Mechanisms for its development have focused on immune mediated causes, aspects of our understanding are not complete, and we lack biomarkers. Blood and bronchial alveolar lavage fluid (BAL) from humans (n = 10-13) with ARDS and controls (n = 5-10) as well as a murine model of ARDS (n = 5-6) with controls (n = 6-7) were studied. ARDS was induced in mice by hemorrhagic shock (day 1) followed by poly-microbial sepsis (day 2). Samples were then collected on the third day after the animals were euthanized. Ex vivo experiments used splenocytes from animals with ARDS cultured with and without soluble programmed death receptor-1 (sPD-1). Levels of sPD-1 are increased in both the serum (11,429.3 pg/mL(SD 2133.3) vs. 8061.4(SD 4187.8), p = 0.036) and bronchial alveolar lavage (BAL) fluid (6,311.1 pg/mL(SD 3758.0) vs. 90.7 pg/mL(SD 202.8), p = 0.002) of humans with ARDS. Similar results are seen in the serum (9396.1 pg/mL(SD 1546.0) vs. 3464.5 pg/mL(SD 2511.8), p = 0.001) and BAL fluid (2891.7 pg/mL(SD 868.1) vs. 1385.9 pg/mL(SD 927.8), p = 0.012) of mice. sPD-1 levels in murine blood (AUC = 1(1-1), p = 0.006), murine BAL fluid (AUC = 0.905(0.717-1.093), p = 0.015), and human BAL (AUC = 1(1-1), p = 0.001) fluid predicted ARDS. To assess the importance of sPD-1 in ARDS, ex vivo experiments were undertaken. BAL fluid from mice with ARDS dampens the TNF-α production compared to cells cultured with BAL lacking sPD-1 (2.7 pg/mL(SD 3.8) vs. 52.38 pg/mL(SD 25.1), p = 0.002). This suggests sPD-1 is elevated in critical illness and may represent a potential biomarker for ARDS. In addition, sPD-1 has an anti-inflammatory mechanism in conditions of marked stress and aids in the resolution of severe inflammation. sPD-1 could be used to not only diagnose ARDS, but may be a potential therapy.

Metal-dependent function of a mammalian acireductone dioxygenase

PubMed Central

Deshpande, Aditi R.; Wagenpfeil, Karina; Pochapsky, Thomas C.; Petsko, Gregory A.; Ringe, Dagmar

2017-01-01

The two acireductone dioxygenase (ARD) isozymes from the methionine salvage pathway of Klebsiella oxytoca are the only known pair of naturally occurring metalloenzymes with distinct chemical and physical properties determined solely by the identity of the divalent transition metal ion (Fe2+ or Ni2+) in the active site. We now show that this dual chemistry can also occur in mammals. ARD from Mus musculus (MmARD) was studied to relate metal ion identity and three-dimensional structure to enzyme function. The iron-containing isozyme catalyzes the cleavage of 1,2-dihydroxy-3-keto-5-(thiomethyl)pent-1-ene (acireductone) by O2 to formate and the ketoacid precursor of methionine, the penultimate step in methionine salvage. The nickel bound form of ARD catalyzes an off-pathway reaction resulting in formate, carbon monoxide (CO) and 5-(thiomethyl) propionate. Recombinant MmARD was expressed and purified to obtain a homogeneous enzyme with a single transition metal ion bound. The Fe2+ bound protein, which shows about ten-fold higher activity than others, catalyzes on-pathway chemistry, whereas the Ni2+, Co2+ or Mn2+ forms exhibit off-pathway chemistry, as has been seen with ARD from Klebsiella. Thermal stability of the isozymes is strongly affected by metal ion identity, with Ni2+ bound MmARD being the most stable followed by Co2+ and Fe2+, and Mn2+-bound ARD being the least stable. Ni2+ and Co2+ bound MmARD were crystallized and the structures of the two proteins found to be similar. Enzyme-ligand complexes provide insight into substrate binding, metal coordination and catalytic mechanism. PMID:26858196

Surfactant Dysfunction in ARDS and Bronchiolitis is Repaired with Cyclodextrins.

PubMed

Al-Saiedy, Mustafa; Gunasekara, Lasantha; Green, Francis; Pratt, Ryan; Chiu, Andrea; Yang, Ailian; Dennis, John; Pieron, Cora; Bjornson, Candice; Winston, Brent; Amrein, Matthias

2018-03-01

Acute respiratory distress syndrome (ARDS) is caused by many factors including inhalation of toxicants, acute barotrauma, acid aspiration, and burns. Surfactant function is impaired in ARDS and acute airway injury resulting in high surface tension with alveolar and small airway collapse, edema, hypoxemia, and death. In this study, we explore the mechanisms whereby surfactant becomes dysfunctional in ARDS and bronchiolitis and its repair with a cyclodextrin drug that sequesters cholesterol. We used in vitro model systems, a mouse model of ARDS, and samples from patients with acute bronchiolitis. Surface tension was measured by captive bubble surfactometry. Patient samples showed severe surfactant inhibition even in the absence of elevated cholesterol levels. Surfactant was also impaired in ARDS mice where the cholesterol to phospholipid ratio (W/W%) was increased. Methyl-β-cyclodextrin (MβCD) restored surfactant function to normal in both human and animal samples. Model studies showed that the inhibition of surfactant was due to both elevated cholesterol and an interaction between cholesterol and oxidized phospholipids. MβCD was also shown to have anti-inflammatory effects. Inhaled cyclodextrins have potential for the treatment of ARDS. They could be delivered in a portable device carried in combat and used following exposure to toxic gases and fumes or shock secondary to hemorrhage and burns.

The 30-year evolution of airway pressure release ventilation (APRV).

PubMed

Jain, Sumeet V; Kollisch-Singule, Michaela; Sadowitz, Benjamin; Dombert, Luke; Satalin, Josh; Andrews, Penny; Gatto, Louis A; Nieman, Gary F; Habashi, Nader M

2016-12-01

Airway pressure release ventilation (APRV) was first described in 1987 and defined as continuous positive airway pressure (CPAP) with a brief release while allowing the patient to spontaneously breathe throughout the respiratory cycle. The current understanding of the optimal strategy to minimize ventilator-induced lung injury is to "open the lung and keep it open". APRV should be ideal for this strategy with the prolonged CPAP duration recruiting the lung and the minimal release duration preventing lung collapse. However, APRV is inconsistently defined with significant variation in the settings used in experimental studies and in clinical practice. The goal of this review was to analyze the published literature and determine APRV efficacy as a lung-protective strategy. We reviewed all original articles in which the authors stated that APRV was used. The primary analysis was to correlate APRV settings with physiologic and clinical outcomes. Results showed that there was tremendous variation in settings that were all defined as APRV, particularly CPAP and release phase duration and the parameters used to guide these settings. Thus, it was impossible to assess efficacy of a single strategy since almost none of the APRV settings were identical. Therefore, we divided all APRV studies divided into two basic categories: (1) fixed-setting APRV (F-APRV) in which the release phase is set and left constant; and (2) personalized-APRV (P-APRV) in which the release phase is set based on changes in lung mechanics using the slope of the expiratory flow curve. Results showed that in no study was there a statistically significant worse outcome with APRV, regardless of the settings (F-ARPV or P-APRV). Multiple studies demonstrated that P-APRV stabilizes alveoli and reduces the incidence of acute respiratory distress syndrome (ARDS) in clinically relevant animal models and in trauma patients. In conclusion, over the 30 years since the mode's inception there have been no strict criteria in defining a mechanical breath as being APRV. P-APRV has shown great promise as a highly lung-protective ventilation strategy.

Predicting Survival After Extracorporeal Membrane Oxygenation for ARDS: An External Validation of RESP and PRESERVE Scores.

PubMed

Brunet, Jennifer; Valette, Xavier; Buklas, Dimitrios; Lehoux, Philippe; Verrier, Pierre; Sauneuf, Bertrand; Ivascau, Calin; Dalibert, Yves; Seguin, Amélie; Terzi, Nicolas; Babatasi, Gérard; du Cheyron, Damien; Parienti, Jean-Jacques; Daubin, Cédric

2017-07-01

We aimed to test the performance of PRESERVE and RESP scores to predict death in patients with severe ARDS receiving extracorporeal membrane oxygenation (ECMO) with different case mixes. All consecutive patients treated with ECMO for refractory ARDS, regardless of cause, in the Caen University Hospital in northwestern France over the last decade were included in a retrospective cohort study. The receiver operating characteristic curves of each score were plotted, and the area under the curve was computed to assess their performance in predicting mortality (c-index). Forty-one subjects were included. Pre-ECMO ventilator settings were: mean V T , 6.1 ± 0.9 mL/kg; breathing frequency, 32 ± 4 breaths/min; PEEP, 11 ± 4 cm H 2 O; peak inspiratory pressure, 48 ± 9 cm H 2 O; plateau pressure, 30.4 ± 4.4 cm H 2 O. At ECMO initiation, blood gas results were: pH 7.22 ± 0.17, P aO 2 /F IO 2 = 63 ± 22 mm Hg; P aCO 2 = 56 ± 18 mm Hg; F IO 2 = 99 ± 2%. Pre-ECMO data were available in 35 and 27 subjects for calculation of the PRESERVE score and RESP score, respectively. Pre-ECMO scoring system results were: median PRESERVE score, 4 (interquartile range 2-5), and median RESP score, 0 (interquartile range -2 to 2). Twenty-three subjects (56%) died, including 19 receiving ECMO. In univariate analysis, plateau pressure ( P = .031), driving pressure ( P = <.001), and compliance ( P = .02) recorded at the time of ECMO initiation as well as the PRESERVE score ( P = .032) were significantly associated with mortality. With a c-index of 0.69 (95% CI 0.53-0.87), the PRESERVE score had better discrimination than the RESP score (c-index of 0.60 [95% CI 0.41-0.78]) for predicting mortality. The use of these scores in helping physicians to determine the patients with ARDS most likely to benefit from ECMO should be limited in clinical practice because of their relatively poor performance in predicting death in subjects with severe ARDS receiving ECMO support. Before widespread use is initiated, these scoring systems should be tested in large prospective studies of subjects with severe ARDS undergoing ECMO treatment. Copyright © 2017 by Daedalus Enterprises.

Plasma cytokines IL-6, IL-8, and IL-10 are associated with the development of acute respiratory distress syndrome in patients with severe traumatic brain injury.

PubMed

Aisiku, Imo P; Yamal, Jose-Miguel; Doshi, Pratik; Benoit, Julia S; Gopinath, Shankar; Goodman, Jerry C; Robertson, Claudia S

2016-09-15

Patients with severe traumatic brain injury (TBI) are at risk of the development of acute respiratory distress syndrome (ARDS). TBI and ARDS pathophysiologic mechanisms are known to independently involve significant inflammatory responses. The literature on the association between plasma inflammatory cytokines and ARDS in patients with TBI is sparse. The study was a secondary analysis of the safety of a randomized trial of erythropoietin and transfusion threshold in patients with severe TBI. Inflammatory markers within the first 24 hours after injury were compared in patients who developed ARDS and patients without ARDS, using Cox proportional hazards models. There were 200 patients enrolled in the study. The majority of plasma and cerebrospinal fluid (CSF) cytokine levels were obtained within 6 hours. Plasma proinflammatory markers IL-6 and IL-8 and anti-inflammatory marker IL-10 were associated with the development of ARDS (adjusted hazard ratio (HR) = 1.55, confidence interval (CI) = 1.14, 2.11, P = 0.005 for IL-6; adjusted HR = 1.32, CI = 1.10, 1.59, P = 0.003 for IL-8). Plasma markers of IL-6, IL-8, and IL-10 are associated with ARDS in patients with severe TBI. NCT00313716 registered 4/2006.

Prevention or treatment of ARDS with aspirin: a review of preclinical models and meta- analysis of clinical studies

PubMed Central

Panka, Bernardo Amisa; de Grooth, Harm-Jan; Spoelstra–de Man, Angeliquè; Looney, Mark; Tuinman, Pieter-Roel

2016-01-01

Background The acute respiratory distress syndrome (ARDS) is a life-threating disorder that contributes significantly to critical illness. No specific pharmacological interventions directed at lung injury itself, have proven effective in improving outcome of patients with ARDS. Platelet activation was identified as a key component in ARDS pathophysiology and may provide an opportunity for preventive and therapeutic strategies. We hypothesize that use of acetyl salicylic acid (ASA) may prevent and/or attenuate lung injury. Methods We conducted a systematic review of preclinical studies and meta-analysis of clinical studies investigating the efficacy of ASA in the setting of lung injury. MEDLINE, EMBASE AND COCHRANE databases were searched. Results The literature search yielded 1314 unique articles. Fifteen pre-clinical studies and eight clinical studies fulfilled the in- and exclusion criteria. In the animal studies, the overall effect of ASA was positive, e.g. ASA improved survival and attenuated inflammation and pulmonary edema. Mechanisms of actions involved, among others, are interference with the neutrophil-platelets interaction, reduction of leukotrienes, neutrophil extracellular traps and prostaglandins. High dose ASA may be the drug of choice. A meta-analysis of 3 clinical studies showed an association between ASA use and a reduced incidence of ARDS (OR 0.59, 95% CI 0.36–0.98), albeit with substantial between-study heterogeneity. All studies had their own shortcomings in methodological quality. Conclusion This systematic review of preclinical studies and meta-analysis of clinical studies suggests a beneficial role for ASA in ARDS prevention and treatment. However, the currently available data is insufficient to justify an indication for ASA in ARDS. The body of literature does support further studies in humans. We suggest clinical trials in which the mechanisms of action of ASA in lung injury models is being evaluated to guide optimal timing and dose, before prospective randomized trials. PMID:27984533

[Advance on human umbilical cord mesenchymal stem cells for treatment of ALI in severe burns].

PubMed

Wang, Yu; Hu, Xiaohong

2017-01-01

Severe burn is often accompanied by multiple organ damage. Acute lung injury (ALI) is one of the most common complications, and often occurs in the early stage of severe burns. If it is not treated in time, it will progress to acute respiratory distress syndrome (ARDS), which will be a serious threat to the lives of patients. At present, the treatment of ALI in patients with severe burn is still remained in some common ways, such as the liquid resuscitation, the primary wound treatment, ventilation support, and anti-infection. In recently, human umbilical cord mesenchymal stem cells (hUCMSCs) have been found having some good effects on ALI caused by various causes, but few reports on the efficacy of ALI caused by severe burns were reported. By reviewing the mechanism of stem cell therapy for ALI, therapeutic potential of hUCMSCs in the treatment of severe burns with ALI and a new approach for clinical treatment was provided.

[Legionella pneumonia--a case report].

PubMed

Marques, A S; Estrada, M H

2005-01-01

Legionella, as a cause of community-acquired pneumonia, is probably under-recognized because the diagnosis relies on the use of specific tests as well the existence of an in-numerous species and serogroups not easily identify by the tests available. In studies from Europe and North America, it ranged from 2 to 15 percent of all community-acquired pneumonias that required hospitalisation, in the first four causes when culture methods were done and the second cause of those admitted in the intensive care units. We do a case report of 43 year-old man with history of cigarette smoking and corticosteroid therapy for a ocular disease, that presents with a pneumonia complicated with a Acute Respiratory Distress Syndrome (ARDS), that leaded to his admission to an intensive care unit were he was mechanical ventilated. The epidemiological investigation identified Legionella pneumophila serogroup 1. The authors present this case doing a brief review of this disease and discussing the epidemiology, clinical features, laboratory diagnosis as well as therapeutic options.

Severe rhinovirus pneumonia in a young woman taking performance-enhancing drugs.

PubMed

Mayer, Kristina Nadine; Wyder, Daniel; Spasic, Danijela; Herren, Thomas

2016-01-06

A 22-year-old woman presented to the emergency room of a local hospital with pleuritic chest pain. She regularly worked out and admitted to taking performance-enhancing drugs (PEDs). Clinical findings and further diagnostic work up revealed a diagnosis of perimyocarditis, and adequate therapy was initiated. During the course of the first day, the patient had to be intubated and mechanically ventilated. A diagnosis of bilateral pneumonia and acute respiratory distress syndrome (ARDS) due to an infection by rhinovirus spp was made. A smoking habit, the intense physical training and the use of PED's may have exacerbated the course of the viral pneumonia. After 12 days the patient could be extubated. The length of stay in the intensive care unit was 16 days. After hospital discharge, the patient went to a pulmonary rehabilitation facility for 2 weeks. The outcome was favourable and the patient resumed her strength and endurance training. 2016 BMJ Publishing Group Ltd.

Development of regional extracorporeal life support system: The importance of innovative simulation training.

PubMed

Puślecki, Mateusz; Ligowski, Marcin; Dąbrowski, Marek; Stefaniak, Sebastian; Ładzińska, Małgorzata; Pawlak, Aleksander; Zieliński, Marcin; Szarpak, Łukasz; Perek, Bartłomiej; Jemielity, Marek

2018-04-18

Despite advances in mechanical ventilation, severe acute respiratory distress syndrome (ARDS) is associated with high morbidity and mortality rates ranging from 30% to 60%. Extracorporeal Membrane Oxygenation (ECMO) can be used as a "bridge to recovery". ECMO is a complex network that provides oxygenation and ventilation and allows the lungs to rest and recover from respiratory failure, while minimizing iatrogenic ventilator-induced lung injury. In the critical care settings, ECMO is shown to improve survival rates and outcomes in patients with severe ARDS. The primary objective was to present an innovative approach for using high-fidelity medical simulation before setting ECMO program for reversible respiratory failure (RRF) in Poland's first unique regional program "ECMO for Greater Poland", covering a total population of 3.5 million inhabitants in the Greater Poland region (Wielkopolska). Because this organizational model is complex and expensive, we use advanced high-fidelity medical simulation to prepare for the real-life implementation. The algorithm was proposed for respiratory treatment by veno-venous (VV) Extracorporeal Membrane Oxygenation (ECMO). The scenario includes all critical stages: hospital identification (Regional Department of Intensive Care) - inclusion and exclusion criteria matching using an authorship protocol; ECMO team transport; therapy confirmation; veno-venous cannulation of mannequin's artificial vessels and implementation of perfusion therapy and transport with ECMO to another hospital in a provincial city (Clinical Department of Intensive Care), where the VV ECMO therapy was performed in the next 48 h, as training platform. The total time, by definition, means the time from the first contact with the mannequin to the cannulation of artificial vessels and starting VV perfusion on ECMO, did not exceed 3 h - including 75 min of transport (the total time of simulation with first call from provincial hospital to admission to the Clinical Intensive Care department was 5 h). The next 48 h for perfusion simulation "in situ" generated a specific learning platform for intensive care personnel. Shortly after this simulation, we performed, the first in the region: ECMO used for RRF treatment. The transport was successful and exceeded 120 km. During first year of Program duration we performed 6 successful ECMO transports (5 adult and 1 paediatric) with 60% of adult patient survival of ECMO therapies. Three patients in good condition were discharged to home. Two years old patient was successfully disconnected from ECMO and in stabile condition is treated in Paediatric Department. We discovered the important role of medical simulation, not only as an examination for testing the medical professional's skills, but also as a mechanism for creating non-existent procedures. During debriefing, it was found that the previous simulation-based training allowed to build a successful procedural chain, to eliminate errors at the stage of identification, notification, transportation and providing ECMO perfusion therapy. Copyright © 2018. Published by Elsevier Inc.

OBESITY AND NUTRITION IN ARDS

PubMed Central

Stapleton, Renee D.; Suratt, Benjamin T.

2014-01-01

This chapter collectively discusses two important topics related to patients with ARDS: 1) obesity and its potential contribution to clinical outcomes through proposed biologic mechanisms and 2) current literature on provision of nutrition and micronutrients. The prevalence of obesity is rapidly increasing around the world, and more than one third of Americans are now obese. While obesity is associated with increased morbidity and mortality in the general population, recent literature suggests that among critically ill patients including those with ARDS, the relationship between obesity and outcomes is quite complex. Observational data demonstrate that obese patients may be at greater risk of developing ARDS and of having longer ICU and hospital lengths of stay compared to normal weight patients. However, obesity is also associated with improved survival. Therefore, in contrast to what might be assumed by clinicians, although obesity may confer greater ICU morbidity, it appears to simultaneously decrease mortality. The mechanisms for these findings are not yet clear, but recent biologic data may begin to provide an explanation. Critical illness, and more specifically the acute respiratory distress syndrome (ARDS), is a catabolic state where patients demonstrate a profound inflammatory response, multiple organ dysfunction, and hypermetabolism. This is often accompanied by malnutrition, which can lead to further impairment of immune function and increased morbidity and mortality in critically ill patients. Over the past decade or more, as we have come to better understand immunologic effects of nutrition in critical illness, nutrition has begun to be thought of as therapeutic, rather than purely supportive. Additionally, the concept of pharmaconutrition has emerged. Fortunately, several recent large studies about nutrition in critical care, with some investigations specifically in patients with ARDS, have provided valuable new evidence. PMID:25453416

Evaluation of lung recruitment maneuvers in acute respiratory distress syndrome using computer simulation.

PubMed

Das, Anup; Cole, Oana; Chikhani, Marc; Wang, Wenfei; Ali, Tayyba; Haque, Mainul; Bates, Declan G; Hardman, Jonathan G

2015-01-12

Direct comparison of the relative efficacy of different recruitment maneuvers (RMs) for patients with acute respiratory distress syndrome (ARDS) via clinical trials is difficult, due to the heterogeneity of patient populations and disease states, as well as a variety of practical issues. There is also significant uncertainty regarding the minimum values of positive end-expiratory pressure (PEEP) required to ensure maintenance of effective lung recruitment using RMs. We used patient-specific computational simulation to analyze how three different RMs act to improve physiological responses, and investigate how different levels of PEEP contribute to maintaining effective lung recruitment. We conducted experiments on five 'virtual' ARDS patients using a computational simulator that reproduces static and dynamic features of a multivariable clinical dataset on the responses of individual ARDS patients to a range of ventilator inputs. Three recruitment maneuvers (sustained inflation (SI), maximal recruitment strategy (MRS) followed by a titrated PEEP, and prolonged recruitment maneuver (PRM)) were implemented and evaluated for a range of different pressure settings. All maneuvers demonstrated improvements in gas exchange, but the extent and duration of improvement varied significantly, as did the observed mechanism of operation. Maintaining adequate post-RM levels of PEEP was seen to be crucial in avoiding cliff-edge type re-collapse of alveolar units for all maneuvers. For all five patients, the MRS exhibited the most prolonged improvement in oxygenation, and we found that a PEEP setting of 35 cm H2O with a fixed driving pressure of 15 cm H2O (above PEEP) was sufficient to achieve 95% recruitment. Subsequently, we found that PEEP titrated to a value of 16 cm H2O was able to maintain 95% recruitment in all five patients. There appears to be significant scope for reducing the peak levels of PEEP originally specified in the MRS and hence to avoid exposing the lung to unnecessarily high pressures. More generally, our study highlights the huge potential of computer simulation to assist in evaluating the efficacy of different recruitment maneuvers, in understanding their modes of operation, in optimizing RMs for individual patients, and in supporting clinicians in the rational design of improved treatment strategies.

Advantages and pitfalls of combining intravenous antithrombin with nebulized heparin and tissue plasminogen activator in acute respiratory distress syndrome.

PubMed

Rehberg, Sebastian; Yamamoto, Yusuke; Sousse, Linda E; Jonkam, Collette; Cox, Robert A; Prough, Donald S; Enkhbaatar, Perenlei

2014-01-01

Pulmonary coagulopathy has become an important therapeutic target in adult respiratory distress syndrome (ARDS). We hypothesized that combining intravenous recombinant human antithrombin (rhAT), nebulized heparin, and nebulized tissue plasminogen activator (TPA) more effectively improves pulmonary gas exchange compared with a single rhAT infusion, while maintaining the anti-inflammatory properties of rhAT in ARDS. Therefore, the present prospective, randomized experiment was conducted using an established ovine model. Following burn and smoke inhalation injury (40% of total body surface area, third-degree flame burn, and 4 × 12 breaths of cold cotton smoke), 18 chronically instrumented sheep were randomly assigned to receive intravenous saline plus saline nebulization (control), intravenous rhAT (6 IU/kg/h) started 1 hour after injury plus saline nebulization (AT i.v.) or intravenous rhAT combined with nebulized heparin (10,000 IU every 4 hours, started 2 hours after injury), and nebulized TPA (2 mg every 4 hours, started 4 hours after injury) (triple therapy, n = 6 each). All animals were mechanically ventilated and fluid resuscitated according to standard protocols during the 48-hour study period. Both treatment approaches attenuated ARDS compared with control animals. Notably, triple therapy was associated with an improved PaO2/FiO2 ratio (p = 0.007), attenuated pulmonary obstruction (p = 0.02) and shunting (p = 0.025), as well as reduced ventilatory pressures (p < 0.05 each) versus AT i.v. at 48 hours. However, the anti-inflammatory effects of sole AT i.v., namely, the inhibition of neutrophil activation (neutrophil count in the lymph and pulmonary polymorphonuclear cells, p < 0.05 vs. control each), pulmonary transvascular fluid flux (lymph flow, p = 0.004 vs. control), and systemic vascular leakage (cumulative net fluid balance, p < 0.001 vs. control), were abolished in the triple therapy group. Combining intravenous rhAT with nebulized heparin and nebulized TPA more effectively restores pulmonary gas exchange, but the anti-inflammatory effects of sole rhAT are abolished with the triple therapy. Interferences between the different anticoagulants may represent a potential explanation for these findings.

Protocols and Hospital Mortality in Critically ill Patients: The United States Critical Illness and Injury Trials Group Critical Illness Outcomes Study

PubMed Central

Sevransky, Jonathan E.; Checkley, William; Herrera, Phabiola; Pickering, Brian W.; Barr, Juliana; Brown, Samuel M; Chang, Steven Y; Chong, David; Kaufman, David; Fremont, Richard D; Girard, Timothy D; Hoag, Jeffrey; Johnson, Steven B; Kerlin, Mehta P; Liebler, Janice; O'Brien, James; O'Keefe, Terence; Park, Pauline K; Pastores, Stephen M; Patil, Namrata; Pietropaoli, Anthony P; Putman, Maryann; Rice, Todd W.; Rotello, Leo; Siner, Jonathan; Sajid, Sahul; Murphy, David J; Martin, Greg S

2015-01-01

Objective Clinical protocols may decrease unnecessary variation in care and improve compliance with desirable therapies. We evaluated whether highly protocolized intensive care units have superior patient outcomes compared with less highly protocolized intensive care units. Design Observational study in which participating intensive care units completed a general assessment and enrolled new patients one day each week. Setting and Patients 6179 critically ill patients across 59 intensive care units in the United States Critical Illness and Injury Trials Group Critical Illness Outcomes Study Interventions: None Measurements and Main Results The primary exposure was the number of intensive care unit protocols; the primary outcome was hospital mortality. 5809 participants were followed prospectively and 5454 patients in 57 intensive care units had complete outcome data. The median number of protocols per intensive care unit was 19 (IQR 15 to 21.5). In single variable analyses, there were no differences in intensive care unit and hospital mortality, length of stay, use of mechanical ventilation, vasopressors, or continuous sedation among individuals in intensive care units with a high vs. low number of protocols. The lack of association was confirmed in adjusted multivariable analysis (p=0.70). Protocol compliance with two ventilator management protocols was moderate and did not differ between intensive care units with high vs. low numbers of protocols for lung protective ventilation in ARDS (47% vs. 52%; p=0.28) and for spontaneous breathing trials (55% vs. 51%; p=0.27). Conclusions Clinical protocols are highly prevalent in United States intensive care units. The presence of a greater number of protocols was not associated with protocol compliance or patient mortality. PMID:26110488

Enteral omega-3 fatty acid, gamma-linolenic acid, and antioxidant supplementation in acute lung injury.

PubMed

Rice, Todd W; Wheeler, Arthur P; Thompson, B Taylor; deBoisblanc, Bennett P; Steingrub, Jay; Rock, Peter

2011-10-12

The omega-3 (n-3) fatty acids docosahexaenoic acid and eicosapentaenoic acid, along with γ-linolenic acid and antioxidants, may modulate systemic inflammatory response and improve oxygenation and outcomes in patients with acute lung injury. To determine if dietary supplementation of these substances to patients with acute lung injury would increase ventilator-free days to study day 28. The OMEGA study, a randomized, double-blind, placebo-controlled, multicenter trial conducted from January 2, 2008, through February 21, 2009. Participants were 272 adults within 48 hours of developing acute lung injury requiring mechanical ventilation whose physicians intended to start enteral nutrition at 44 hospitals in the National Heart, Lung, and Blood Institute ARDS Clinical Trials Network. All participants had complete follow-up. Twice-daily enteral supplementation of n-3 fatty acids, γ-linolenic acid, and antioxidants compared with an isocaloric control. Enteral nutrition, directed by a protocol, was delivered separately from the study supplement. Ventilator-free days to study day 28. The study was stopped early for futility after 143 and 129 patients were enrolled in the n-3 and control groups. Despite an 8-fold increase in plasma eicosapentaenoic acid levels, patients receiving the n-3 supplement had fewer ventilator-free days (14.0 vs 17.2; P = .02) (difference, -3.2 [95% CI, -5.8 to -0.7]) and intensive care unit-free days (14.0 vs 16.7; P = .04). Patients in the n-3 group also had fewer nonpulmonary organ failure-free days (12.3 vs 15.5; P = .02). Sixty-day hospital mortality was 26.6% in the n-3 group vs 16.3% in the control group (P = .054), and adjusted 60-day mortality was 25.1% and 17.6% in the n-3 and control groups, respectively (P = .11). Use of the n-3 supplement resulted in more days with diarrhea (29% vs 21%; P = .001). Twice-daily enteral supplementation of n-3 fatty acids, γ-linolenic acid, and antioxidants did not improve the primary end point of ventilator-free days or other clinical outcomes in patients with acute lung injury and may be harmful. clinicaltrials.gov Identifier: NCT00609180.

Comparison of Prevalence and Outcomes of Pediatric Acute Respiratory Distress Syndrome Using Pediatric Acute Lung Injury Consensus Conference Criteria and Berlin Definition.

PubMed

Gupta, Samriti; Sankar, Jhuma; Lodha, Rakesh; Kabra, Sushil K

2018-01-01

Our objective was to compare the prevalence and outcomes of pediatric acute respiratory distress syndrome using the Pediatric Acute Lung Injury Consensus Conference (PALICC) criteria and Berlin definitions. We screened case records of all children aged 1 month to 17 years of age admitted to the Pediatric Intensive Care Unit (PICU) over a 3-year period (2015-2017) for presence of any respiratory difficulty at admission or during PICU stay. We applied both PALICC and Berlin criteria to these patients. Data collection included definition and outcome related variables. Data were compared between the "PALICC only group" and the "Berlin with or without PALICC" group using Stata 11. Of a total of 615 admissions, 246 were identified as having respiratory difficulty at admission or during PICU stay. A total of 61 children (prevalence 9.9%; 95% CI: 7.8-12.4) fulfilled the definition of acute respiratory distress syndrome (ARDS) with either of the two criteria. While 60 children (98%) fulfilled PALICC criteria, only 26 children (43%) fulfilled Berlin definition. There was moderate agreement between the two definitions (Kappa: 0.51; 95% CI: 0.40-0.62; observed agreement 85%). Greater proportion of patients had severe ARDS in the "Berlin with or without PALICC group" as compared to the "PALICC only" group (50 vs. 19%). There was no difference between the groups with regard to key clinical outcomes such as duration of ventilation (7 vs. 8 days) or mortality [51.4 vs. 57.7%: RR (95% CI): 0.99 (0.64-1.5)]. In comparison to Berlin definition, the PALICC criteria identified more number of patients with ARDS. Proportion with severe ARDS and complications was greater in the "Berlin with or without PALICC" group as compared to the "PALICC only" group. There were no differences in clinical outcomes between the groups.

Pathophysiological Approaches of Acute Respiratory Distress syndrome: Novel Bases for Study of Lung Injury

PubMed Central

Castillo, R.L; Carrasco Loza, R; Romero-Dapueto, C

2015-01-01

Experimental approaches have been implemented to research the lung damage related-mechanism. These models show in animals pathophysiological events for acute respiratory distress syndrome (ARDS), such as neutrophil activation, reactive oxygen species burst, pulmonary vascular hypertension, exudative edema, and other events associated with organ dysfunction. Moreover, these approaches have not reproduced the clinical features of lung damage. Lung inflammation is a relevant event in the develop of ARDS as component of the host immune response to various stimuli, such as cytokines, antigens and endotoxins. In patients surviving at the local inflammatory states, transition from injury to resolution is an active mechanism regulated by the immuno-inflammatory signaling pathways. Indeed, inflammatory process is regulated by the dynamics of cell populations that migrate to the lung, such as neutrophils and on the other hand, the role of the modulation of transcription factors and reactive oxygen species (ROS) sources, such as nuclear factor kappaB and NADPH oxidase. These experimental animal models reproduce key components of the injury and resolution phases of human ALI/ARDS and provide a methodology to explore mechanisms and potential new therapies. PMID:26312099

Chickenpox: presentation and complications in adults.

PubMed

Abro, Ali Hassan; Ustadi, Abdulla Muhammed; Das, Kirpal; Abdou, Ahmed Muhammed Saleh; Hussaini, Hina Syeda; Chandra, Fatma Saifuddin

2009-12-01

To describe the clinical manifestations laboratory findings and frequency of complications in adult chickenpox patients admitted in the hospital. This was a hospital based descriptive study, conducted at the Infectious Diseases Unit, Rashid Hospital Dubai, UAE, from March 2005 to February 2008. The study was designed to include demographics (age, sex, nationality); clinical information, radiological and biochemical changes observed in each patient and data was entered into the proforma separately. Full blood count, urea, electrolytes and blood sugar were done for all the patients, whereas, other tests were carried out when and where it was indicated. Patients were treated according to the standard protocol for the management of Chickenpox and its complications. A total of 102 adult patients were entered into the study. The main presenting symptoms were itchy skin rash, fever, cough, sputum, breathlessness, throat pain, vomiting, abdominal pain, confusion and headache. Whereas, the most common complications observed were raised Alanine aminotransferases (ALT) levels (51.9%) and the levels were greater than 10-folds of normal value in 4.9%, thrombocytopenia (42.1%), varicella pneumonia (28.4%), skin infection (25.4%), septicaemia (10.7%), Encephalitis/Meningitis (8.8%), Acute Respiratory Distress Syndrome (ARDS) (6.8%), acute renal failure (2.9%) and acute hepatic failure (1.9%). The frequency of varicella pneumonia was noted to be higher in males, older age group (p < .005), smokers (p < .002) and patients with respiratory symptoms (p < .0001). Total five (4.9%) patients expired, whereas, mortality rate was 17.2% in varicella pneumonia patients and 45.5% in mechanically ventilated patients. Chickenpox in adults causes severe systemic manifestations leading to high frequency of complications with increased mortality rate, particularly in the older age group and in smokers who develops varicella pneumonia and require mechanical ventilation.

Scrub Typhus in a Tertiary Care Hospital in North India.

PubMed

Sharma, Navneet; Biswal, Manisha; Kumar, Abhay; Zaman, Kamran; Jain, Sanjay; Bhalla, Ashish

2016-08-03

Scrub typhus, a zoonotic disease caused by the bacterium Orientia tsutsugamushi, has become endemic in many parts of India. We studied the clinical profile of this infection in 228 patients that reported to this tertiary care center from July 2013 to December 2014. The median age of patients was 35 years (interquartile range = 24.5-48.5 years), and 111 were males and 117 females. A high-grade fever occurred in 85%, breathlessness in 42%, jaundice in 32%, abdominal pain in 28%, renal failure in 11%, diarrhea in 10%, rashes in 9%, and seizures in 7%. Common laboratory abnormalities at presentation were a deranged hepatic function in 61%, anemia in 54%, leukopenia in 15%, and thrombocytopenia in 90% of our patients. Acute kidney injury (32%), acute respiratory distress syndrome (ARDS) (25%), and disseminated intravascular coagulation (DIC) (16%) were the commonest complications. A hepatorenal syndrome was seen in 38% and multiple organ dysfunction syndrome (MODS) in 20% patients. The overall case fatality rate was 13.6%. In univariate analysis, ARDS requiring mechanical ventilation, acute kidney injury requiring hemodialysis, hypotension requiring inotropic support, central nervous system dysfunction at presentation, and MODS were inversely associated with survival. Survival was significantly higher in patients that presented with a duration of fever < 10 days compared with those that presented ≥ 12 days (P < 0.05) after onset. In conclusion, scrub typhus has become a leading infectious disease in north India and an important cause of infectious fever. An increasing awareness of this disease coupled with prompt management will go a long way in reducing both morbidity and mortality from this disease. © The American Society of Tropical Medicine and Hygiene.

Effectiveness of treatment based on PiCCO parameters in critically ill patients with septic shock and/or acute respiratory distress syndrome: a randomized controlled trial.

PubMed

Zhang, Zhongheng; Ni, Hongying; Qian, Zhixian

2015-03-01

To compare treatment based on either PiCCO-derived physiological values or central venous pressure (CVP) monitoring, we performed a prospective randomized controlled trial with group sequential analysis. Consecutive critically ill patients with septic shock and/or ARDS were included. The planned total sample size was 715. The primary outcome was 28-day mortality after randomization. Participants underwent stratified randomization according to the classification of ARDS and/or septic shock. Caregivers were not blinded to the intervention, but participants and outcome assessors were blinded to group assignment. The study was stopped early because of futility after enrollment of 350 patients including 168 in the PiCCO group and 182 in the control group. There was no loss to follow-up and data from all enrolled participants were analyzed. The result showed that treatment based on PiCCO-derived physiological values was not able to reduce the 28-day mortality risk (odds ratio 1.00, 95 % CI 0.66-1.52; p = 0.993). There was no difference between the two groups in secondary outcomes such as 14-day mortality (40.5 vs. 41.2 %; p = 0.889), ICU length of stay (median 9 vs. 7.5 days; p = 0.598), days free of vasopressors (median 14.5 vs. 19 days; p = 0.676), and days free of mechanical ventilation (median 3 vs. 6 days; p = 0.168). No severe adverse event was reported in both groups. On the basis of our study, PICCO-based fluid management does not improve outcome when compared to CVP-based fluid management.

Acute Respiratory Distress Syndrome after Onyx Embolization of Arteriovenous Malformation

PubMed Central

Tawil, Isaac; Carlson, Andrew P.; Taylor, Christopher L.

2011-01-01

Purpose. We report a case of a 60-year-old male who underwent sequential Onyx embolizations of a cerebral arteriovenous malformation (AVM) which we implicate as the most likely etiology of subsequent acute respiratory distress syndrome (ARDS). Methods. Case report and literature review. Results. Shortly after the second Onyx embolization procedure, the patient declined from respiratory failure secondary to pulmonary edema. Clinical entities typically responsible for pulmonary edema including cardiac failure, renal failure, iatrogenic volume overload, negative-pressure pulmonary edema, and infectious etiologies were evaluated and excluded. The patient required mechanical ventilatory support for several days, delaying operative resection. The patient met clinical and radiographic criteria for ARDS. After excluding other etiologies of ARDS, we postulate that ARDS developed as a result of Onyx administration. The Onyx copolymer is dissolved in dimethyl sulfoxide (DMSO), a solvent excreted through the lungs and has been implicated in transient pulmonary side effects. Additionally, a direct toxic effect of the Onyx copolymer is postulated. Conclusion. Onyx embolization and DMSO toxicity are implicated as the etiology of ARDS given the lack of other inciting factors and the close temporal relationship. A strong physiologic rationale provides further support. Clinicians should consider this uncommon but important complication. PMID:21687580

Enrichment of the lung microbiome with gut bacteria in sepsis and the acute respiratory distress syndrome.

PubMed

Dickson, Robert P; Singer, Benjamin H; Newstead, Michael W; Falkowski, Nicole R; Erb-Downward, John R; Standiford, Theodore J; Huffnagle, Gary B

2016-07-18

Sepsis and the acute respiratory distress syndrome (ARDS) are major causes of mortality without targeted therapies. Although many experimental and clinical observations have implicated gut microbiota in the pathogenesis of these diseases, culture-based studies have failed to demonstrate translocation of bacteria to the lungs in critically ill patients. Here, we report culture-independent evidence that the lung microbiome is enriched with gut bacteria both in a murine model of sepsis and in humans with established ARDS. Following experimental sepsis, lung communities were dominated by viable gut-associated bacteria. Ecological analysis identified the lower gastrointestinal tract, rather than the upper respiratory tract, as the likely source community of post-sepsis lung bacteria. In bronchoalveolar lavage fluid from humans with ARDS, gut-specific bacteria (Bacteroides spp.) were common and abundant, undetected by culture and correlated with the intensity of systemic inflammation. Alveolar TNF-α, a key mediator of alveolar inflammation in ARDS, was significantly correlated with altered lung microbiota. Our results demonstrate that the lung microbiome is enriched with gut-associated bacteria in sepsis and ARDS, potentially representing a shared mechanism of pathogenesis in these common and lethal diseases.

Extracorporeal membrane oxygenation support in a situation of diagnostic dilemma.

PubMed

Elahi, Maqsood M; Houng, Chew; Trahair, Toby; Ravindranathan, Hari; Grant, Peter W

2012-12-01

Severe acute respiratory distress syndrome (ARDS) in children carries a high morbidity and mortality. High frequency ventilation and extracorporeal membrane oxygenation (ECMO) are used as rescue modes of support in difficult situations. Malignancy may be considered to be a relative contraindication to ECMO support. We report a case where the decision was made to support the patient with ECMO for fulminant Epstein-Barr (EBV) infection while investigations were being done to exclude an underlying malignancy. Copyright © 2012 Australian and New Zealand Society of Cardiac and Thoracic Surgeons (ANZSCTS) and the Cardiac Society of Australia and New Zealand (CSANZ). All rights reserved.

Nur77 attenuates endothelin-1 expression via downregulation of NF-κB and p38 MAPK in A549 cells and in an ARDS rat model.

PubMed

Jiang, Yujie; Zeng, Yi; Huang, Xia; Qin, Yueqiu; Luo, Weigui; Xiang, Shulin; Sooranna, Suren R; Pinhu, Liao

2016-12-01

Acute respiratory distress syndrome (ARDS) is characterized by inflammatory injury to the alveolar and capillary barriers that results in impaired gas exchange and severe acute respiratory failure. Nuclear orphan receptor Nur77 has emerged as a regulator of gene expression in inflammation, and its role in the pathogenesis of ARDS is not clear. The objective of this study is to investigate the potential role of Nur77 and its underlying mechanism in the regulation of endothelin-1 (ET-1) expression in lipopolysaccharide (LPS)-induced A549 cells and an ARDS rat model. We demonstrate that LPS induced Nur77 expression and nuclear export in A549 cells. Overexpression of Nur77 markedly decreased basal and LPS-induced ET-1 expression in A549 cells, whereas knockdown of Nur77 increased the ET-1 expression. LPS-induced phosphorylation and nuclear translocation of NF-κB and p38 MAPK were blocked by Nur77 overexpression and augmented by Nur77 knockdown in A549 cells. In vivo, LPS induced Nur77 expression in lung in ARDS rats. Pharmacological activation of Nur77 by cytosporone B (CsnB) inhibited ET-1 expression in ARDS rats, decreased LPS-induced phosphorylation of NF-κB and p38 MAPK, and relieved lung, liver, and kidney injury. Pharmacological deactivation of Nur77 by 1,1-bis-(3'-indolyl)-1-(p-hydroxyphenyl)methane (DIM-C-pPhOH, C-DIM8) had no effect on ET-1 expression and lung injury. These results indicated that Nur77 decreases ET-1 expression by suppressing NF-κB and p38 MAPK in LPS-stimulated A549 cells in vitro, and, in an LPS-induced ARDS rat model, CsnB reduced ET-1 expression and lung injury in ARDS rats. Copyright © 2016 the American Physiological Society.

Identification of StARD3 as a lutein-binding protein in the macula of the primate retina.

PubMed

Li, Binxing; Vachali, Preejith; Frederick, Jeanne M; Bernstein, Paul S

2011-04-05

Lutein, zeaxanthin, and their metabolites are the xanthophyll carotenoids that form the macular pigment of the human retina. Epidemiological evidence suggests that high levels of these carotenoids in the diet, serum, and macula are associated with a decreased risk of age-related macular degeneration (AMD), and the AREDS2 study is prospectively testing this hypothesis. Understanding the biochemical mechanisms underlying the selective uptakes of lutein and zeaxanthin into the human macula may provide important insights into the physiology of the human macula in health and disease. GSTP1 is the macular zeaxanthin-binding protein, but the identity of the human macular lutein-binding protein has remained elusive. Prior identification of the silkworm lutein-binding protein (CBP) as a member of the steroidogenic acute regulatory domain (StARD) protein family and selective labeling of monkey photoreceptor inner segments with an anti-CBP antibody provided an important clue for identifying the primate retina lutein-binding protein. The homology of CBP with all 15 human StARD proteins was analyzed using database searches, Western blotting, and immunohistochemistry, and we here provide evidence to identify StARD3 (also known as MLN64) as a human retinal lutein-binding protein. Antibody to StARD3, N-62 StAR, localizes to all neurons of monkey macular retina and especially cone inner segments and axons, but does not colocalize with the Müller cell marker, glutamine synthetase. Further, recombinant StARD3 selectively binds lutein with high affinity (K(D) = 0.45 μM) when assessed by surface plasmon resonance (SPR) binding assays. Our results demonstrate previously unrecognized, specific interactions of StARD3 with lutein and provide novel avenues for exploring its roles in human macular physiology and disease.

Identification of StARD3 as a Lutein-binding Protein in the Macula of the Primate Retina†

PubMed Central

Li, Binxing; Vachali, Preejith; Frederick, Jeanne M.; Bernstein, Paul S.

2011-01-01

Lutein, zeaxanthin and their metabolites are the xanthophyll carotenoids that form the macular pigment of the human retina. Epidemiological evidence suggests that high levels of these carotenoids in the diet, serum and macula are associated with decreased risk of age-related macular degeneration (AMD), and the AREDS2 study is prospectively testing this hypothesis. Understanding the biochemical mechanisms underlying the selective uptakes of lutein and zeaxanthin into the human macula may provide important insights into the physiology of the human macula in health and disease. GSTP1 is the macular zeaxanthin-binding protein, but the identity of the human macular lutein-binding protein has remained elusive. Prior identification of the silkworm lutein-binding protein (CBP) as a member of the steroidogenic acute regulatory domain (StARD) protein family, and selective labeling of monkey photoreceptor inner segments by anti-CBP antibody provided an important clue toward identifying the primate retina lutein-binding protein. Homology of CBP to all 15 human StARD proteins was analyzed using database searches, western blotting and immunohistochemistry, and we here provide evidence to identify StARD3 (also known as MLN64) as a human retinal lutein-binding protein. Further, recombinant StARD3 selectively binds lutein with high affinity (KD = 0.45 micromolar) when assessed by surface plasmon resonance (SPR) binding assays. Our results demonstrate previously unrecognized, specific interactions of StARD3 with lutein and provide novel avenues to explore its roles in human macular physiology and disease. PMID:21322544

Inhibition of endotoxin-induced airway epithelial cell injury by a novel family of pyrrol derivates.

PubMed

Cabrera-Benítez, Nuria E; Pérez-Roth, Eduardo; Ramos-Nuez, Ángela; Sologuren, Ithaisa; Padrón, José M; Slutsky, Arthur S; Villar, Jesús

2016-06-01

Inflammation and apoptosis are crucial mechanisms for the development of the acute respiratory distress syndrome (ARDS). Currently, there is no specific pharmacological therapy for ARDS. We have evaluated the ability of a new family of 1,2,3,5-tetrasubstituted pyrrol compounds for attenuating lipopolysaccharide (LPS)-induced inflammation and apoptosis in an in vitro LPS-induced airway epithelial cell injury model based on the first steps of the development of sepsis-induced ARDS. Human alveolar A549 and human bronchial BEAS-2B cells were exposed to LPS, either alone or in combination with the pyrrol derivatives. Rhein and emodin, two representative compounds with proven activity against the effects of LPS, were used as reference compounds. The pyrrol compound that was termed DTA0118 had the strongest inhibitory activity and was selected as the lead compound to further explore its properties. Exposure to LPS caused an intense inflammatory response and apoptosis in both A549 and BEAS-2B cells. DTA0118 treatment downregulated Toll-like receptor-4 expression and upregulated nuclear factor-κB inhibitor-α expression in cells exposed to LPS. These anti-inflammatory effects were accompanied by a significantly lower secretion of interleukin-6 (IL-6), IL-8, and IL-1β. The observed antiapoptotic effect of DTA0118 was associated with the upregulation of antiapoptotic Bcl-2 and downregulation of proapoptotic Bax and active caspase-3 protein levels. Our findings demonstrate the potent anti-inflammatory and antiapoptotic properties of the pyrrol DTA0118 compound and suggest that it could be considered as a potential drug therapy for the acute phase of sepsis and septic ARDS. Further investigations are needed to examine and validate these mechanisms and effects in a clinically relevant animal model of sepsis and sepsis-induced ARDS.

Cloning, Characterization, and Expression Analysis of the Novel Acetyltransferase Retrogene Ard1b in the Mouse1

PubMed Central

Pang, Alan Lap-Yin; Peacock, Stephanie; Johnson, Warren; Bear, Deborah H.; Rennert, Owen M.; Chan, Wai-Yee

2009-01-01

N-alpha-terminal acetylation is a modification process that occurs cotranslationally on most eukaryotic proteins. The major enzyme responsible for this process, N-alpha-terminal acetyltransferase, is composed of the catalytic subunit ARD1A and the auxiliary subunit NAT1. We cloned, characterized, and studied the expression pattern of Ard1b (also known as Ard2), a novel homolog of the mouse Ard1a. Comparison of the genomic structures suggests that the autosomal Ard1b is a retroposed copy of the X-linked Ard1a. Expression analyses demonstrated a testis predominance of Ard1b. A reciprocal expression pattern between Ard1a and Ard1b is also observed during spermatogenesis, suggesting that Ard1b is expressed to compensate for the loss of Ard1a starting from meiosis. Both ARD1A and ARD1B can interact with NAT1 to constitute a functional N-alpha-terminal acetyltransferase in vitro. The expression of ARD1B protein can be detected in mouse testes but is delayed until the first appearance of round spermatids. In a cell culture model, the inclusion of the long 3′ untranslated region of Ard1b leads to reduction of luciferase reporter activity, which implicates its role in translational repression of Ard1b during spermatogenesis. Our results suggest that ARD1B may have an important role in the later course of the spermatogenic process. PMID:19246321

Cloning, characterization, and expression analysis of the novel acetyltransferase retrogene Ard1b in the mouse.

PubMed

Pang, Alan Lap-Yin; Peacock, Stephanie; Johnson, Warren; Bear, Deborah H; Rennert, Owen M; Chan, Wai-Yee

2009-08-01

N-alpha-terminal acetylation is a modification process that occurs cotranslationally on most eukaryotic proteins. The major enzyme responsible for this process, N-alpha-terminal acetyltransferase, is composed of the catalytic subunit ARD1A and the auxiliary subunit NAT1. We cloned, characterized, and studied the expression pattern of Ard1b (also known as Ard2), a novel homolog of the mouse Ard1a. Comparison of the genomic structures suggests that the autosomal Ard1b is a retroposed copy of the X-linked Ard1a. Expression analyses demonstrated a testis predominance of Ard1b. A reciprocal expression pattern between Ard1a and Ard1b is also observed during spermatogenesis, suggesting that Ard1b is expressed to compensate for the loss of Ard1a starting from meiosis. Both ARD1A and ARD1B can interact with NAT1 to constitute a functional N-alpha-terminal acetyltransferase in vitro. The expression of ARD1B protein can be detected in mouse testes but is delayed until the first appearance of round spermatids. In a cell culture model, the inclusion of the long 3' untranslated region of Ard1b leads to reduction of luciferase reporter activity, which implicates its role in translational repression of Ard1b during spermatogenesis. Our results suggest that ARD1B may have an important role in the later course of the spermatogenic process.

Lycium barbarum polysaccharide protects against LPS-induced ARDS by inhibiting apoptosis, oxidative stress, and inflammation in pulmonary endothelial cells.

PubMed

Chen, Lan; Li, Wen; Qi, Di; Wang, Daoxin

2018-04-01

Acute respiratory distress syndrome (ARDS) is a heterogenous syndrome characterised by diffuse alveolar damage, with an increase in lung endothelial and epithelial permeability. Lycium barbarum polysaccharide (LBP), the most biologically active fraction of wolfberry, possesses antiapoptotic and antioxidative effects in distinct situations. In the present study, the protective effects and potential molecular mechanisms of LBP against lipopolysaccharide (LPS)-induced ARDS were investigated in the mice and in the human pulmonary microvascular endothelial cells (HPMECs). The data indicated that pretreatment with LBP significantly attenuated LPS-induced lung inflammation and pulmonary oedema in vivo. LBP significantly reversed LPS-induced decrease in cell viability, increase in apoptosis and oxidative stress via inhibiting caspase-3 activation and intracellular reactive oxygen species (ROS) production in vitro. Moreover, the scratch assay verified that LBP restored the dysfunction of endothelial cells (ECs) migration induced by LPS stimulation. Furthermore, LBP also significantly suppressed LPS-induced NF-κB activation, and subsequently reversed the release of cytochrome c. These results showed the antiapoptosis and antioxidant LBP could partially protect against LPS-induced ARDS through promoting the ECs survival and scavenging ROS via inhibition of NF-κB signalling pathway. Thus, LBP could be potentially used for ARDS against pulmonary inflammation and pulmonary oedema.

ω-3 fatty acids, γ-linolenic acid, and antioxidants: immunomodulators or inert dietary supplements?

PubMed

Schott, Christopher K; Huang, David T

2012-11-23

The omega-3 (n-3) fatty acids docosahexaenoic acid and eicosapentaenoic acid, along with γ-linolenic acid and antioxidants, may modulate systemic inflammatory response and improve oxygenation and outcomes in patients with acute lung injury. Objective: To determine if dietary supplementation of these substances to patients with acute lung injury would increase ventilator-free days to study day 28. Design: The OMEGA study, a randomized, double-blind, placebo-controlled, multicenter trial conducted from January 2, 2008, through February 21, 2009. All participants had complete follow-up. Setting: This trial occurred at 44 hospitals in the National Heart, Lung, and Blood Institute ARDS Clinical Trials Network. Subjects: Participants were 272 adults within 48 hours of developing acute lung injury requiring mechanical ventilation whose physicians intended to start enteral nutrition. Intervention: Twice-daily enteral supplementation of n-3 fatty acids, γ -linolenic acid, and antioxidants compared with an isocaloric control. Enteral nutrition, directed by a protocol, was delivered separately from the study supplement. Outcomes: Ventilator-free days to study day 28. The study was stopped early for futility after 143 and 129 patients were enrolled in the n-3 and control groups. Despite an 8-fold increase in plasma eicosapentaenoic acid levels, patients receiving the n-3 supplement had fewer ventilator-free days (14.0 vs 17.2; P=.02) (difference, −3.2 [95% CI, −5.8 to −0.7]) and intensive care unit-free days (14.0 vs 16.7; P=.04). Patients in the n-3 group also had fewer nonpulmonary organ failure-free days (12.3 vs 15.5; P=.02). Sixty-day hospital mortality was 26.6% in the n 3 group vs 16.3% in the control group (P=.054), and adjusted 60-day mortality was 25.1% and 17.6% in the n-3 and control groups, respectively (P=.11). Use of the n-3 supplement resulted in more days with diarrhea (29% vs 21%; P=.001). Twice-daily enteral supplementation of n-3 fatty acids, γ-linolenic acid, and antioxidants did not improve the primary end point of ventilator-free days or other clinical outcomes in patients with acute lung injury and may be harmful.

Prone positioning reduces mortality from acute respiratory distress syndrome in the low tidal volume era: a meta-analysis

PubMed Central

Shaefi, Shahzad; Montesi, Sydney B.; Devlin, Amy; Loring, Stephen H.; Talmor, Daniel; Malhotra, Atul

2014-01-01

Purpose Prone positioning for ARDS has been performed for decades without definitive evidence of clinical benefit. A recent multicenter trial demonstrated for the first time significantly reduced mortality with prone positioning. This meta-analysis was performed to integrate these findings with existing literature and test whether differences in tidal volume explain conflicting results among randomized trials. Methods Studies were identified using MEDLINE, EMBASE, Cochrane Register of Controlled Trials, LILACS, and citation review. Included were randomized trials evaluating the effect on mortality of prone versus supine positioning during conventional ventilation for ARDS. The primary outcome was risk ratio of death at 60 days meta-analyzed using random effects models. Analysis stratified by high (>8 ml/kg predicted body weight) or low (≤8 ml/kg PBW) mean baseline tidal volume was planned a priori. Results Seven trials were identified including 2,119 patients, of whom 1,088 received prone positioning. Overall, prone positioning was not significantly associated with the risk ratio of death (RR 0.83; 95 % CI 0.68–1.02; p = 0.073; I2 = 64 %). When stratified by high or low tidal volume, prone positioning was associated with a significant decrease in RR of death only among studies with low baseline tidal volume (RR 0.66; 95 % CI 0.50–0.86; p = 0.002; I2 = 25 %). Stratification by tidal volume explained over half the between-study heterogeneity observed in the unstratified analysis. Conclusions Prone positioning is associated with significantly reduced mortality from ARDS in the low tidal volume era. Substantial heterogeneity across studies can be explained by differences in tidal volume. PMID:24435203

The effects of low tidal ventilation on lung strain correlate with respiratory system compliance.

PubMed

Xie, Jianfeng; Jin, Fang; Pan, Chun; Liu, Songqiao; Liu, Ling; Xu, Jingyuan; Yang, Yi; Qiu, Haibo

2017-02-03

The effect of alterations in tidal volume on mortality of acute respiratory distress syndrome (ARDS) is determined by respiratory system compliance. We aimed to investigate the effects of different tidal volumes on lung strain in ARDS patients who had various levels of respiratory system compliance. Nineteen patients were divided into high (C high group) and low (C low group) respiratory system compliance groups based on their respiratory system compliance values. We defined compliance ≥0.6 ml/(cmH 2 O/kg) as C high and compliance <0.6 ml/(cmH 2 O/kg) as C low . End-expiratory lung volumes (EELV) at various tidal volumes were measured by nitrogen wash-in/washout. Lung strain was calculated as the ratio between tidal volume and EELV. The primary outcome was that lung strain is a function of tidal volume in patients with various levels of respiratory system compliance. The mean baseline EELV, strain and respiratory system compliance values were 1873 ml, 0.31 and 0.65 ml/(cmH 2 O/kg), respectively; differences in all of these parameters were statistically significant between the two groups. For all participants, a positive correlation was found between the respiratory system compliance and EELV (R = 0.488, p = 0.034). Driving pressure and strain increased together as the tidal volume increased from 6 ml/kg predicted body weight (PBW) to 12 ml/kg PBW. Compared to the C high ARDS patients, the driving pressure was significantly higher in the C low patients at each tidal volume. Similar effects of lung strain were found for tidal volumes of 6 and 8 ml/kg PBW. The "lung injury" limits for driving pressure and lung strain were much easier to exceed with increases in the tidal volume in C low patients. Respiratory system compliance affected the relationships between tidal volume and driving pressure and lung strain in ARDS patients. These results showed that increasing tidal volume induced lung injury more easily in patients with low respiratory system compliance. Clinicaltrials.gov identifier NCT01864668 , Registered 21 May 2013.

Soluble Receptor for Advanced Glycation End-Products Predicts Impaired Alveolar Fluid Clearance in Acute Respiratory Distress Syndrome.

PubMed

Jabaudon, Matthieu; Blondonnet, Raiko; Roszyk, Laurence; Bouvier, Damien; Audard, Jules; Clairefond, Gael; Fournier, Mathilde; Marceau, Geoffroy; Déchelotte, Pierre; Pereira, Bruno; Sapin, Vincent; Constantin, Jean-Michel

2015-07-15

Levels of the soluble form of the receptor for advanced glycation end-products (sRAGE) are elevated during acute respiratory distress syndrome (ARDS) and correlate with severity and prognosis. Alveolar fluid clearance (AFC) is necessary for the resolution of lung edema but is impaired in most patients with ARDS. No reliable marker of this process has been investigated to date. To verify whether sRAGE could predict AFC during ARDS. Anesthetized CD-1 mice underwent orotracheal instillation of hydrochloric acid. At specified time points, lung injury was assessed by analysis of blood gases, alveolar permeability, lung histology, AFC, and plasma/bronchoalveolar fluid measurements of proinflammatory cytokines and sRAGE. Plasma sRAGE and AFC rates were also prospectively assessed in 30 patients with ARDS. The rate of AFC was inversely correlated with sRAGE levels in the plasma and the bronchoalveolar fluid of acid-injured mice (Spearman's ρ = -0.73 and -0.69, respectively; P < 10(-3)), and plasma sRAGE correlated with AFC in patients with ARDS (Spearman's ρ = -0.59; P < 10(-3)). Similarly, sRAGE levels were significantly associated with lung injury severity, and decreased over time in mice, whereas AFC was restored and lung injury resolved. Our results indicate that sRAGE levels could be a reliable predictor of impaired AFC during ARDS, and should stimulate further studies on the pathophysiologic implications of RAGE axis in the mechanisms leading to edema resolution. Clinical trial registered with www.clinicaltrials.gov (NCT 00811629).

[Late respiratory function complications following burns].

PubMed

Ernesto, S; Marduel, Y; Freymond, N; Pacheco, Y; Devouassoux, G

2008-03-01

Twenty five per cent of thermal injuries are associated with secondary respiratory events linked to several mechanisms. In the acute phase of the accident oedema of the airways, the fume inhalation syndrome and ARDS are the most common causes responsible for death in 60% of cases. Late respiratory complications are little known and neglected. They comprise obstructive ventilatory defects due to the inhalation syndrome and restrictive defects secondary to ARDS or to dermal injury. We report the case of a female patient, extensively burnt 2 years previously, admitted to hospital with severe acute respiratory failure complicating COPD. The presence of both restrictive and obstructive defects led to the suggestion of alternative underlying mechanisms such as the pulmonary consequences of ARDS and extensive dermal scars. The latter were responsible for an armour like thickening of the skin of the thorax compatible with the restrictive defect. These functional abnormalities and the potential severity of acute respiratory failure are indications for regular pulmonary follow-up of patients with severe circumferential scarring of the thorax who are at high risk for respiratory complications.

Alk5/Runx1 signaling mediated by extracellular vesicles promotes vascular repair in acute respiratory distress syndrome.

PubMed

Shah, Trushil; Qin, Shanshan; Vashi, Mona; Predescu, Dan N; Jeganathan, Niranjan; Bardita, Cristina; Ganesh, Balaji; diBartolo, Salvatore; Fogg, Louis F; Balk, Robert A; Predescu, Sanda A

2018-06-22

Pulmonary endothelial cells' (ECs) injury and apoptotic death are necessary and sufficient for the pathogenesis of the acute respiratory distress syndrome (ARDS), regardless of epithelial damage. Interaction of dysfunctional ECs with circulatory extracellular vesicles (EVs) holds therapeutic promise in ARDS. However, the presence in the blood of long-term ARDS survivors of EVs with a distinct phenotype compared to the EVs of non-surviving patients is not reported. With a multidisciplinary translational approach, we studied EVs from the blood of 33 patients with moderate-to-severe ARDS. The EVs were isolated from the blood of ARDS and control subjects. Immunoblotting and magnetic beads immunoisolation complemented by standardized flow cytometry and nanoparticles tracking analyses identified in the ARDS patients a subset of EVs with mesenchymal stem cell (MSC) origin (CD73 + CD105 + Cd34 - CD45 - ). These EVs have 4.7-fold greater counts compared to controls and comprise the transforming growth factor-beta receptor I (TβRI)/Alk5 and the Runx1 transcription factor. Time course analyses showed that the expression pattern of two Runx1 isoforms is critical for ARDS outcome: the p52 isoform shows a continuous expression, while the p66 is short-lived. A high ratio Runx1p66/p52 provided a survival advantage, regardless of age, sex, disease severity or length of stay in the intensive care unit. Moreover, the Runx1p66 isoform is transiently expressed by cultured human bone marrow-derived MSCs, it is released in the EVs recoverable from the conditioned media and stimulates the proliferation of lipopolysaccharide (LPS)-treated ECs. The findings are consistent with a causal effect of Runx1p66 expression on EC proliferation. Furthermore, morphological and functional assays showed that the EVs bearing the Runx1p66 enhanced junctional integrity of LPS-injured ECs and decreased lung histological severity in the LPS-treated mice. The expression pattern of Runx1 isoforms might be a reliable circulatory biomarker of ARDS activity and a novel determinant of the molecular mechanism for lung vascular/tissue repair and recovery after severe injury.

Cardiovascular disease in autoimmune rheumatic diseases.

PubMed

Hollan, Ivana; Meroni, Pier Luigi; Ahearn, Joseph M; Cohen Tervaert, J W; Curran, Sam; Goodyear, Carl S; Hestad, Knut A; Kahaleh, Bashar; Riggio, Marcello; Shields, Kelly; Wasko, Mary C

2013-08-01

Various autoimmune rheumatic diseases (ARDs), including rheumatoid arthritis, spondyloarthritis, vasculitis and systemic lupus erythematosus, are associated with premature atherosclerosis. However, premature atherosclerosis has not been uniformly observed in systemic sclerosis. Furthermore, although experimental models of atherosclerosis support the role of antiphospholipid antibodies in atherosclerosis, there is no clear evidence of premature atherosclerosis in antiphospholipid syndrome (APA). Ischemic events in APA are more likely to be caused by pro-thrombotic state than by enhanced atherosclerosis. Cardiovascular disease (CVD) in ARDs is caused by traditional and non-traditional risk factors. Besides other factors, inflammation and immunologic abnormalities, the quantity and quality of lipoproteins, hypertension, insulin resistance/hyperglycemia, obesity and underweight, presence of platelets bearing complement protein C4d, reduced number and function of endothelial progenitor cells, apoptosis of endothelial cells, epigenetic mechanisms, renal disease, periodontal disease, depression, hyperuricemia, hypothyroidism, sleep apnea and vitamin D deficiency may contribute to the premature CVD. Although most research has focused on systemic inflammation, vascular inflammation may play a crucial role in the premature CVD in ARDs. It may be involved in the development and destabilization of both atherosclerotic lesions and of aortic aneurysms (a known complication of ARDs). Inflammation in subintimal vascular and perivascular layers appears to frequently occur in CVD, with a higher frequency in ARD than in non-ARD patients. It is possible that this inflammation is caused by infections and/or autoimmunity, which might have consequences for treatment. Importantly, drugs targeting immunologic factors participating in the subintimal inflammation (e.g., T- and B-cells) might have a protective effect on CVD. Interestingly, vasa vasorum and cardiovascular adipose tissue may play an important role in atherogenesis. Inflammation and complement depositions in the vessel wall are likely to contribute to vascular stiffness. Based on biopsy findings, also inflammation in the myocardium and small vessels may contribute to premature CVD in ARDs (cardiac ischemia and heart failure). There is an enormous need for an improved CVD prevention in ARDs. Studies examining the effect of DMARDs/biologics on vascular inflammation and CV risk are warranted. Copyright © 2013 Elsevier B.V. All rights reserved.

Fifty Years of Research in ARDS. Is Acute Respiratory Distress Syndrome a Preventable Disease?

PubMed

Yadav, Hemang; Thompson, B Taylor; Gajic, Ognjen

2017-03-15

Despite significant advances in our understanding and management of patients with acute respiratory distress syndrome (ARDS), the morbidity and mortality from ARDS remains high. Given the limited number of effective treatments for established ARDS, the strategic focus of ARDS research has shifted toward identifying patients with or at high risk of ARDS early in the course of the underlying illness, when strategies to reduce the development and progression of ARDS and associated organ failures can be systematically evaluated. In this review, we summarize the rationale, current evidence, and future directions in ARDS prevention.

Altered molecular specificity of surfactant phosphatidycholine synthesis in patients with acute respiratory distress syndrome.

PubMed

Dushianthan, Ahilanandan; Goss, Victoria; Cusack, Rebecca; Grocott, Michael P W; Postle, Anthony D

2014-11-07

Acute respiratory distress syndrome (ARDS) is a life-threatening critical illness, characterised by qualitative and quantitative surfactant compositional changes associated with premature airway collapse, gas-exchange abnormalities and acute hypoxic respiratory failure. The underlying mechanisms for this dysregulation in surfactant metabolisms are not fully explored. Lack of therapeutic benefits from clinical trials, highlight the importance of detailed in-vivo analysis and characterisation of ARDS patients according to patterns of surfactant synthesis and metabolism. Ten patients with moderate to severe ARDS were recruited. Most (90%) suffered from pneumonia. They had an infusion of methyl-D9-choline chloride and small volume bronchoalveolar lavage fluid (BALF) was obtained at 0,6,12,24,48,72 and 96 hours. Controls were healthy volunteers, who had BALF at 24 and 48 hours after methyl-D9-choline infusion. Compositional analysis and enrichment patterns of stable isotope labelling of surfactant phosphatidylcholine (PC) was determined by electrospray ionisation mass spectrometry. BALF of patients with ARDS consisted of diminished total PC and fractional PC16:0/16:0 concentrations compared to healthy controls. Compositional analysis revealed, reductions in fractional compositions of saturated PC species with elevated levels of longer acyl chain unsaturated PC species. Molecular specificity of newly synthesised PC fraction showed time course variation, with lower PC16:0/16:0 composition at earlier time points, but achieved near equilibrium with endogenous composition at 48 hours after methyl-D9-choline infusion. The enrichment of methyl-D9-choline into surfactant total PC is nearly doubled in patients, with considerable variation between individuals. This study demonstrate significant alterations in composition and kinetics of surfactant PC extracted from ARDS patients. This novel approach may facilitate biochemical phenotyping of ARDS patients according to surfactant synthesis and metabolism, enabling individualised treatment approaches for the management of ARDS patients in the future.

46 CFR 154.1200 - Mechanical ventilation system: General.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 46 Shipping 5 2010-10-01 2010-10-01 false Mechanical ventilation system: General. 154.1200 Section... Equipment Cargo Area: Mechanical Ventilation System § 154.1200 Mechanical ventilation system: General. (a... cargo handling equipment must have a fixed, exhaust-type mechanical ventilation system. (b) The...

[Neurally adjusted ventilatory assist (NAVA). A new mode of assisted mechanical ventilation].

PubMed

Moerer, O; Barwing, J; Quintel, M

2008-10-01

The aim of mechanical ventilation is to assure gas exchange while efficiently unloading the respiratory muscles and mechanical ventilation is an integral part of the care of patients with acute respiratory failure. Modern lung protective strategies of mechanical ventilation include low-tidal-volume ventilation and the continuation of spontaneous breathing which has been shown to be beneficial in reducing atelectasis and improving oxygenation. Poor patient-ventilator interaction is a major issue during conventional assisted ventilation. Neurally adjusted ventilator assist (NAVA) is a new mode of mechanical ventilation that uses the electrical activity of the diaphragm (EAdi) to control the ventilator. First experimental studies showed an improved patient-ventilator synchrony and an efficient unloading of the respiratory muscles. Future clinical studies will have to show that NAVA is of clinical advantage when compared to conventional modes of assisted mechanical ventilation. This review characterizes NAVA according to current publications on this topic.

Cigarette Smoke Exposure and the Acute Respiratory Distress Syndrome

PubMed Central

Calfee, Carolyn S.; Matthay, Michael A.; Kangelaris, Kirsten N.; Siew, Edward D.; Janz, David R; Bernard, Gordon R.; May, Addison K; Jacob, Peyton; Havel, Christopher; Benowitz, Neal L.; Ware, Lorraine B.

2016-01-01

Objective The association between cigarette smoke exposure and the acute respiratory distress syndrome (ARDS) in patients with the most common ARDS risk factors of sepsis, pneumonia, and aspiration has not been well-studied. The goal of this study was to test the association between biomarker-confirmed cigarette smoking and ARDS in a diverse cohort. Design, Setting, Patients We obtained smoking histories and measured urine NNAL (a biomarker of cigarette smoke exposure) in 426 patients with ARDS risk factors (excluding trauma and transfusion) in a prospective cohort of critically ill patients at a single tertiary care center and tested the association between smoking and ARDS. Interventions None. Measurements and Main Results The association between cigarette smoke exposure and ARDS differed based on ARDS risk factor (p<0.02 for interaction). In patients with non-pulmonary sepsis as the primary ARDS risk factor (n=212), 39% of those with ARDS were current smokers by history, compared with 22% of those without ARDS (odds ratio 2.28 (95% CI 1.24–4.18); p=0.007). Likewise, cigarette smoke exposure as measured by urine NNAL was significantly associated with ARDS in this group. The increased risk of ARDS in non-pulmonary sepsis was restricted to patients with NNAL levels consistent with active smoking and was robust to adjustment for other ARDS predictors. Cigarette smoke exposure as measured by history or NNAL was not associated with ARDS in patients with other risk factors (e.g. pneumonia, aspiration). Conclusions Cigarette smoking measured both by history and by biomarker is associated with an increased risk of ARDS in patients with non-pulmonary sepsis. This finding has important implications for tobacco product regulation and for understanding the pathogenesis of ARDS. PMID:26010690

46 CFR 154.1205 - Mechanical ventilation system: Standards.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 46 Shipping 5 2010-10-01 2010-10-01 false Mechanical ventilation system: Standards. 154.1205... Equipment Cargo Area: Mechanical Ventilation System § 154.1205 Mechanical ventilation system: Standards. (a) Each exhaust type mechanical ventilation system required under § 154.1200 (a) must have ducts for...

Early detection of right ventricular dysfunction using transthoracic echocardiography in ARDS: a more objective approach.

PubMed

Wadia, Subeer Kanwar; Shah, Trushil G; Hedstrom, Grady; Kovach, Julie A; Tandon, Rajive

2016-12-01

Right ventricular (RV) dysfunction is an independent predictor of morbidity and mortality in acute respiratory distress syndrome (ARDS). Our goal was to describe morphologic changes in the RV using objective measures on transthoracic echocardiography (TTE) that occur following ARDS. We retrospectively measured changes in the following RV parameters from a pre-ARDS TTE to an ARDS TTE: tricuspid annular plane systolic excursion (TAPSE), myocardial performance index (MPI), fractional area change (FAC), systolic pulmonary artery pressure (SPAP), peak tricuspid regurgitant (TR) velocity, and septal shift. Over 24 months, 14 patients met inclusion/exclusion criteria. Mean TAPSE decreased from 22.4 mm pre-ARDS to 16.3 mm during ARDS, P<.001. Mean MPI increased from 0.19 to 0.38, P=.001. Mean FAC decreased from 60.8% to 41.2%, P=.003. Peak TR velocity increased from 2.67 m/s pre-ARDS to 3.31 m/s during ARDS, P=.02. SPAP and septal shift demonstrated trends but not statistically different between pre-ARDS and ARDS states. TAPSE correlated with ARDS severity (PaO 2 /FiO 2 ratios), P=.004, and was lower among 30-day nonsurvivors compared with survivors, P=.002. Mild RV dysfunction is common after ARDS onset. RV morphologic changes coupled with dysfunction can be detected noninvasively through TTE changes with TAPSE, MPI, and FAC. Mild RV dysfunction by TAPSE is associated with ARDS severity and mortality. © 2016, Wiley Periodicals, Inc.

RB-ARD: A proof of concept rule-based abort

NASA Technical Reports Server (NTRS)

Smith, Richard; Marinuzzi, John

1987-01-01

The Abort Region Determinator (ARD) is a console program in the space shuttle mission control center. During shuttle ascent, the Flight Dynamics Officer (FDO) uses the ARD to determine the possible abort modes and make abort calls for the crew. The goal of the Rule-based Abort region Determinator (RB/ARD) project was to test the concept of providing an onboard ARD for the shuttle or an automated ARD for the mission control center (MCC). A proof of concept rule-based system was developed on a LMI Lambda computer using PICON, a knowdedge-based system shell. Knowdedge derived from documented flight rules and ARD operation procedures was coded in PICON rules. These rules, in conjunction with modules of conventional code, enable the RB-ARD to carry out key parts of the ARD task. Current capabilities of the RB-ARD include: continuous updating of the available abort mode, recognition of a limited number of main engine faults and recommendation of safing actions. Safing actions recommended by the RB-ARD concern the Space Shuttle Main Engine (SSME) limit shutdown system and powerdown of the SSME Ac buses.

Homologous gene replacement in Physarum

DOE Office of Scientific and Technical Information (OSTI.GOV)

Burland, T.G.; Pallotta, D.

1995-01-01

The protist Physarum polycephalum is useful for analysis of several aspects of cellular and developmental biology. To expand the opportunities for experimental analysis of this organism, we have developed a method for gene replacement. We transformed Physarum amoebae with plasmid DNA carrying a mutant allele, ardD{Delta}1, of the ardD actin gene; ardD{Delta}1 mutates the critical carboxy-terminal region of the gene product. Because ardD is not expressed in the amoeba, replacement of ardD{sup +} with ardD{Delta}1 should not be lethal for this cell type. Transformants were obtained only when linear plasmid DNA was used. Most transformants carried one copy of ardD{Delta}1more » in addition to ardD{sup +}, but in two (5%), ardD{sup +} was replaced by a single copy of ardD{Delta}1. This is the first example of homologous gene replacement in Physarum. ardD{Delta}1 was stably maintained in the genome through growth, development and meiosis. We found no effect of ardD{Delta}l on viability, growth, or development of any of the various cell types of Physarum. Thus, the carboxy-terminal region of the ardD product appears not to perform a unique essential role in growth or development. Nevertheless, this method for homologous gene replacement can be applied to analyze the function of any cloned gene. 38 refs., 6 figs., 1 tab.« less

Interobserver Reliability of the Berlin ARDS Definition and Strategies to Improve the Reliability of ARDS Diagnosis.

PubMed

Sjoding, Michael W; Hofer, Timothy P; Co, Ivan; Courey, Anthony; Cooke, Colin R; Iwashyna, Theodore J

2018-02-01

Failure to reliably diagnose ARDS may be a major driver of negative clinical trials and underrecognition and treatment in clinical practice. We sought to examine the interobserver reliability of the Berlin ARDS definition and examine strategies for improving the reliability of ARDS diagnosis. Two hundred five patients with hypoxic respiratory failure from four ICUs were reviewed independently by three clinicians, who evaluated whether patients had ARDS, the diagnostic confidence of the reviewers, whether patients met individual ARDS criteria, and the time when criteria were met. Interobserver reliability of an ARDS diagnosis was "moderate" (kappa = 0.50; 95% CI, 0.40-0.59). Sixty-seven percent of diagnostic disagreements between clinicians reviewing the same patient was explained by differences in how chest imaging studies were interpreted, with other ARDS criteria contributing less (identification of ARDS risk factor, 15%; cardiac edema/volume overload exclusion, 7%). Combining the independent reviews of three clinicians can increase reliability to "substantial" (kappa = 0.75; 95% CI, 0.68-0.80). When a clinician diagnosed ARDS with "high confidence," all other clinicians agreed with the diagnosis in 72% of reviews. There was close agreement between clinicians about the time when a patient met all ARDS criteria if ARDS developed within the first 48 hours of hospitalization (median difference, 5 hours). The reliability of the Berlin ARDS definition is moderate, driven primarily by differences in chest imaging interpretation. Combining independent reviews by multiple clinicians or improving methods to identify bilateral infiltrates on chest imaging are important strategies for improving the reliability of ARDS diagnosis. Copyright © 2017 American College of Chest Physicians. All rights reserved.

Closed-loop mechanical ventilation for lung injury: a novel physiological-feedback mode following the principles of the open lung concept.

PubMed

Schwaiberger, David; Pickerodt, Philipp A; Pomprapa, Anake; Tjarks, Onno; Kork, Felix; Boemke, Willehad; Francis, Roland C E; Leonhardt, Steffen; Lachmann, Burkhard

2018-06-01

Adherence to low tidal volume (V T ) ventilation and selected positive end-expiratory pressures are low during mechanical ventilation for treatment of the acute respiratory distress syndrome. Using a pig model of severe lung injury, we tested the feasibility and physiological responses to a novel fully closed-loop mechanical ventilation algorithm based on the "open lung" concept. Lung injury was induced by surfactant washout in pigs (n = 8). Animals were ventilated following the principles of the "open lung approach" (OLA) using a fully closed-loop physiological feedback algorithm for mechanical ventilation. Standard gas exchange, respiratory- and hemodynamic parameters were measured. Electrical impedance tomography was used to quantify regional ventilation distribution during mechanical ventilation. Automatized mechanical ventilation provided strict adherence to low V T -ventilation for 6 h in severely lung injured pigs. Using the "open lung" approach, tidal volume delivery required low lung distending pressures, increased recruitment and ventilation of dorsal lung regions and improved arterial blood oxygenation. Physiological feedback closed-loop mechanical ventilation according to the principles of the open lung concept is feasible and provides low tidal volume ventilation without human intervention. Of importance, the "open lung approach"-ventilation improved gas exchange and reduced lung driving pressures by opening atelectasis and shifting of ventilation to dorsal lung regions.

Clinical challenges in mechanical ventilation.

PubMed

Goligher, Ewan C; Ferguson, Niall D; Brochard, Laurent J

2016-04-30

Mechanical ventilation supports gas exchange and alleviates the work of breathing when the respiratory muscles are overwhelmed by an acute pulmonary or systemic insult. Although mechanical ventilation is not generally considered a treatment for acute respiratory failure per se, ventilator management warrants close attention because inappropriate ventilation can result in injury to the lungs or respiratory muscles and worsen morbidity and mortality. Key clinical challenges include averting intubation in patients with respiratory failure with non-invasive techniques for respiratory support; delivering lung-protective ventilation to prevent ventilator-induced lung injury; maintaining adequate gas exchange in severely hypoxaemic patients; avoiding the development of ventilator-induced diaphragm dysfunction; and diagnosing and treating the many pathophysiological mechanisms that impair liberation from mechanical ventilation. Personalisation of mechanical ventilation based on individual physiological characteristics and responses to therapy can further improve outcomes. Copyright © 2016 Elsevier Ltd. All rights reserved.

Dual chemistry catalyzed by human acireductone dioxygenase

PubMed Central

Deshpande, Aditi R.; Pochapsky, Thomas C.; Petsko, Gregory A.

2017-01-01

Abstract Acireductone dioxygenase (ARD) from the methionine salvage pathway of Klebsiella oxytoca is the only known naturally occurring metalloenzyme that catalyzes different reactions in vivo based solely on the identity of the divalent transition metal ion (Fe2+ or Ni2+) bound in the active site. The iron-containing isozyme catalyzes the cleavage of substrate 1,2-dihydroxy-3-keto-5-(thiomethyl)pent-1-ene (acireductone) by O2 to formate and the ketoacid precursor of methionine, whereas the nickel-containing isozyme uses the same substrates to catalyze an off-pathway shunt to form methylthiopropionate, carbon monoxide and formate. This dual chemistry was recently demonstrated in vitro by ARD from Mus musculus (MmARD), providing the first example of a mammalian ARD exhibiting metal-dependent catalysis. We now show that human ARD (HsARD) is also capable of metal-dependent dual chemistry. Recombinant HsARD was expressed and purified to obtain a homogeneous enzyme with a single transition metal ion bound. As with MmARD, the Fe2+-bound HsARD shows the highest activity and catalyzes on-pathway chemistry, whereas Ni2+, Co2+ or Mn2+ forms catalyze off-pathway chemistry. The thermal stability of the HsARD isozymes is a function of the metal ion identity, with Ni2+-bound HsARD being the most stable followed by Co2+ and Fe2+, and Mn2+-bound HsARD being the least stable. As with the bacterial ARD, solution NMR data suggest that HsARD isozymes can have significant structural differences depending upon the metal ion bound. PMID:28062648

Early Intravascular Events are Associated with Development of ARDS.

PubMed

Abdulnour, Raja-Elie E; Gunderson, Tina; Barkas, Ioanna; Timmons, Jack Y; Barnig, Cindy; Gong, Michelle; Kor, Daryl J; Gajic, Ognjen; Talmor, Daniel; Carter, Rickey E; Levy, Bruce D

2018-05-21

The acute respiratory distress syndrome (ARDS) is a devastating illness with limited therapeutic options. A better understanding of early biochemical and immunological events in ARDS could inform the development of new preventive and treatment strategies. To determine select peripheral blood lipid mediator and leukocyte responses in patients at-risk for ARDS. Patients at risk for ARDS were randomized as part of a multicenter, double-blind clinical trial of aspirin versus placebo (LIPS-A; NCT01504867). Plasma thromboxane B2 (TxB2), 15-epi-LXA4 (aspirin-triggered lipoxin A4, ATL), and peripheral blood leukocyte number and activation were determined upon enrollment and after treatment with either aspirin or placebo. Thirty-three of 367 subjects (9.0%) developed ARDS after randomization. Baseline ATL levels, total monocyte counts, intermediate monocyte (IntMo) counts, and Mo-PA were associated with the development of ARDS. Peripheral blood neutrophil count and monocyte-platelet aggregates significantly decreased over time. Of note, 9 subjects developed ARDS after randomization yet prior to study drug initiation, including 7 subjects assigned to aspirin treatment. Subjects without ARDS at the time of first dose demonstrated a lower incidence of ARDS with aspirin treatment. Compared with placebo, aspirin significantly decreased TxB2 and increased the ATL/TxB2 ratio. Biomarkers of intravascular monocyte activation in at-risk patients were associated with development of ARDS. The potential clinical benefit of early aspirin for prevention of ARDS remains uncertain. Together, results of the biochemical and immunological analyses provide a window into the early pathogenesis of human ARDS, and represent potential vascular biomarkers of ARDS risk.

Acute Respiratory Distress Syndrome Measurement Error. Potential Effect on Clinical Study Results

PubMed Central

Cooke, Colin R.; Iwashyna, Theodore J.; Hofer, Timothy P.

2016-01-01

Rationale: Identifying patients with acute respiratory distress syndrome (ARDS) is a recognized challenge. Experts often have only moderate agreement when applying the clinical definition of ARDS to patients. However, no study has fully examined the implications of low reliability measurement of ARDS on clinical studies. Objectives: To investigate how the degree of variability in ARDS measurement commonly reported in clinical studies affects study power, the accuracy of treatment effect estimates, and the measured strength of risk factor associations. Methods: We examined the effect of ARDS measurement error in randomized clinical trials (RCTs) of ARDS-specific treatments and cohort studies using simulations. We varied the reliability of ARDS diagnosis, quantified as the interobserver reliability (κ-statistic) between two reviewers. In RCT simulations, patients identified as having ARDS were enrolled, and when measurement error was present, patients without ARDS could be enrolled. In cohort studies, risk factors as potential predictors were analyzed using reviewer-identified ARDS as the outcome variable. Measurements and Main Results: Lower reliability measurement of ARDS during patient enrollment in RCTs seriously degraded study power. Holding effect size constant, the sample size necessary to attain adequate statistical power increased by more than 50% as reliability declined, although the result was sensitive to ARDS prevalence. In a 1,400-patient clinical trial, the sample size necessary to maintain similar statistical power increased to over 1,900 when reliability declined from perfect to substantial (κ = 0.72). Lower reliability measurement diminished the apparent effectiveness of an ARDS-specific treatment from a 15.2% (95% confidence interval, 9.4–20.9%) absolute risk reduction in mortality to 10.9% (95% confidence interval, 4.7–16.2%) when reliability declined to moderate (κ = 0.51). In cohort studies, the effect on risk factor associations was similar. Conclusions: ARDS measurement error can seriously degrade statistical power and effect size estimates of clinical studies. The reliability of ARDS measurement warrants careful attention in future ARDS clinical studies. PMID:27159648

Immune-Neuroendocrine Interactions and Autoimmune Diseases

PubMed Central

Jara, Luis J.; Navarro, Carmen; Medina, Gabriela; Vera-Lastra, Olga; Blanco, Francisco

2006-01-01

The relationship between immune-neuroendocrine system is firmly established. The messengers of this connection are hormones, neuropeptides, neurotransmitters and cytokines. The immune-neuroendocrine system have the capacity to synthesize and release these molecules, which, in turn, can stimulate or suppress the activity of immune or neuroendocrine cells by binding to receptors. In fact, hormones, neuropeptides and neurotransmitters participate in innate and adaptive immune response.Autoimmune rheumatic diseases (ARD) are characterized by aberrant production of pro-inflammatory cytokines, which are a potent activator of the HPA axis. In consequence, high levels of pro-inflammatory hormones such as estrogens and prolactin, and low levels of glucocorticoids, an anti-inflammatory hormone, have been described in the active phase of ARD. In addition, high levels of pro-inflammatory hormones and cytokines have also been frequently detected in organ involvement of patients with ARD, suggesting an abnormal local neuroendocrine immune interaction. There is evidence that hormonal changes may appear before the symptomatic phase of the disease. Therefore, it is possible that a pro-inflammatory hormone favors the rupture of tolerance, which is a key feature of autoimmune diseases. The interactions between the immune-neuroendocrine system have a major impact on our understanding of the pathogenic mechanisms, diagnosis and therapy of ARD. PMID:17162354

Contribution of neutrophils to acute lung injury.

PubMed

Grommes, Jochen; Soehnlein, Oliver

2011-01-01

Treatment of acute lung injury (ALI) and its most severe form, acute respiratory distress syndrome (ARDS), remain unsolved problems of intensive care medicine. ALI/ARDS are characterized by lung edema due to increased permeability of the alveolar-capillary barrier and subsequent impairment of arterial oxygenation. Lung edema, endothelial and epithelial injury are accompanied by an influx of neutrophils into the interstitium and broncheoalveolar space. Hence, activation and recruitment of neutrophils are regarded to play a key role in progression of ALI/ARDS. Neutrophils are the first cells to be recruited to the site of inflammation and have a potent antimicrobial armour that includes oxidants, proteinases and cationic peptides. Under pathological circumstances, however, unregulated release of these microbicidal compounds into the extracellular space paradoxically can damage host tissues. This review focuses on the mechanisms of neutrophil recruitment into the lung and on the contribution of neutrophils to tissue damage in ALI.

Fifty Years of Research in ARDS. Genomic Contributions and Opportunities.

PubMed

Reilly, John P; Christie, Jason D; Meyer, Nuala J

2017-11-01

Clinical factors alone poorly explain acute respiratory distress syndrome (ARDS) risk and ARDS outcome. In the search for individual factors that may influence ARDS risk, the past 20 years have witnessed the identification of numerous genes and genetic variants that are associated with ARDS. The field of ARDS genomics has cycled from candidate gene association studies to bias-free approaches that identify new candidates, and increasing effort is made to understand the functional consequences that may underlie significant associations. More recently, methodologies of causal inference are being applied to maximize the information gained from genetic associations. Although challenges of sample size, both recognized and unrecognized phenotypic heterogeneity, and the paucity of early ARDS lung tissue limit some applications of the rapidly evolving field of genomic investigation, ongoing genetic research offers unique contributions to elucidating ARDS pathogenesis and the paradigm of precision ARDS medicine.

Antibiotic therapy in ventilator-associated tracheobronchitis: a literature review.

PubMed

Alves, Abel Eduardo; Pereira, José Manuel

2018-03-01

The concept of ventilator-associated tracheobronchitis is controversial; its definition is not unanimously accepted and often overlaps with ventilator-associated pneumonia. Ventilator-associated tracheobronchitis has an incidence similar to that of ventilator-associated pneumonia, with a high prevalence of isolated multiresistant agents, resulting in an increase in the time of mechanical ventilation and hospitalization but without an impact on mortality. The performance of quantitative cultures may allow better diagnostic definition of tracheobronchitis associated with mechanical ventilation, possibly avoiding the overdiagnosis of this condition. One of the major difficulties in differentiating between ventilator-associated tracheobronchitis and ventilator-associated pneumonia is the exclusion of a pulmonary infiltrate by chest radiography; thoracic computed tomography, thoracic ultrasonography, or invasive specimen collection may also be required. The institution of systemic antibiotic therapy does not improve the clinical impact of ventilator-associated tracheobronchitis, particularly in reducing time of mechanical ventilation, hospitalization or mortality, despite the possible reduced progression to ventilator-associated pneumonia. However, there are doubts regarding the methodology used. Thus, considering the high prevalence of tracheobronchitis associated with mechanical ventilation, routine treatment of this condition would result in high antibiotic usage without clear benefits. However, we suggest the institution of antibiotic therapy in patients with tracheobronchitis associated with mechanical ventilation and septic shock and/or worsening of oxygenation, and other auxiliary diagnostic tests should be simultaneously performed to exclude ventilator-associated pneumonia. This review provides a better understanding of the differentiation between tracheobronchitis associated with mechanical ventilation and pneumonia associated with mechanical ventilation, which can significantly decrease the use of antibiotics in critically ventilated patients.

Variable mechanical ventilation

PubMed Central

Fontela, Paula Caitano; Prestes, Renata Bernardy; Forgiarini Jr., Luiz Alberto; Friedman, Gilberto

2017-01-01

Objective To review the literature on the use of variable mechanical ventilation and the main outcomes of this technique. Methods Search, selection, and analysis of all original articles on variable ventilation, without restriction on the period of publication and language, available in the electronic databases LILACS, MEDLINE®, and PubMed, by searching the terms "variable ventilation" OR "noisy ventilation" OR "biologically variable ventilation". Results A total of 36 studies were selected. Of these, 24 were original studies, including 21 experimental studies and three clinical studies. Conclusion Several experimental studies reported the beneficial effects of distinct variable ventilation strategies on lung function using different models of lung injury and healthy lungs. Variable ventilation seems to be a viable strategy for improving gas exchange and respiratory mechanics and preventing lung injury associated with mechanical ventilation. However, further clinical studies are necessary to assess the potential of variable ventilation strategies for the clinical improvement of patients undergoing mechanical ventilation. PMID:28444076

Epigenetic Contribution of the Myosin Light Chain Kinase Gene to the Risk for Acute Respiratory Distress Syndrome

PubMed Central

Szilágyi, Keely L.; Liu, Cong; Zhang, Xu; Wang, Ting; Fortman, Jeffrey D.; Zhang, Wei; Garcia, Joe G.N.

2016-01-01

Acute respiratory distress syndrome (ARDS) is a devastating clinical syndrome with a considerable case fatality rate (~30-40%). Health disparities exist with African descent subjects (ADs) exhibiting greater mortality than European descent individuals (EDs). Myosin light chain kinase (MLCK) is encoded by MYLK whose genetic variants are implicated in ARDS pathogenesis and may influence ARDS mortality. As baseline population-specific epigenetic changes, i.e. cytosine modifications, have been observed between AD and ED individuals, epigenetic variations in MYLK may provide insights into ARDS disparities. We compared methylation levels of MYLK CpGs between ARDS patients and ICU controls overall and by ethnicity in a nested case control study of 39 ARDS cases and 75 non-ARDS intensive care unit controls. Two MYLK CpG sites (cg03892735, cg23344121) were differentially modified between ARDS subjects and controls (p<0.05; q<0.25) in a logistic regression model, where no effect modification from ethnicity or age was found. One CpG site was associated with ARDS in patients less than 58 years old, cg19611163 (intron 19,20). Two CpG sites were associated with ARDS in EDs only, gene body CpG (cg01894985, intron 2,3) and CpG (cg16212219, intron 31,32), with higher modification levels exhibited in ARDS subjects than controls. Cis-acting mQTL (modified cytosine quantitative trait loci) were identified using linear regression between local genetic variants and modification levels for two ARDS-associated CpGs (cg23344121, cg16212219). In summary, these ARDS-associated MYLK CpGs with effect modification by ethnicity and local mQTL, suggest that MYLK epigenetic variation and local genetic background may contribute to health disparities observed in ARDS. PMID:27543902

Lack of association of the caspase-12 long allele with community-acquired pneumonia in people of African descent.

PubMed

Chen, Jiwang; Wilson, Esther S; Dahmer, Mary K; Quasney, Michael W; Waterer, Grant W; Feldman, Charles; Wunderink, Richard G

2014-01-01

Community-acquired pneumonia (CAP) is a common cause of sepsis. Active full-length caspase-12 (CASP12L), confined to the people of African descent, has been associated with increased susceptibility to and mortality from severe sepsis. The objective of this study was to determine whether CASP12L was a marker for susceptibility and/or severity of CAP. We examined three CAP cohorts and two control populations: 241 adult Memphis African American CAP patients, 443 pediatric African American CAP patients, 90 adult South African CAP patients, 120 Memphis healthy adult African American controls and 405 adult Chicago African American controls. Clinical outcomes including mortality, acute respiratory distress syndrome (ARDS), septic shock or severe sepsis, need for mechanical ventilation, and S. pneumoniae bacteremia. Neither in the three individual CAP cohorts nor in the combined CAP cohorts, was mortality in CASP12L carriers significantly different from that in non-CASP12L carriers. No statistically significant association between genotype and any measures of CAP severity was found in any cohort. We conclude that the functional CASP12L allele is not a marker for susceptibility and/or severity of CAP.

Inhibition of forkhead boxO-specific transcription prevents mechanical ventilation-induced diaphragm dysfunction.

PubMed

Smuder, Ashley J; Sollanek, Kurt J; Min, Kisuk; Nelson, W Bradley; Powers, Scott K

2015-05-01

Mechanical ventilation is a lifesaving measure for patients with respiratory failure. However, prolonged mechanical ventilation results in diaphragm weakness, which contributes to problems in weaning from the ventilator. Therefore, identifying the signaling pathways responsible for mechanical ventilation-induced diaphragm weakness is essential to developing effective countermeasures to combat this important problem. In this regard, the forkhead boxO family of transcription factors is activated in the diaphragm during mechanical ventilation, and forkhead boxO-specific transcription can lead to enhanced proteolysis and muscle protein breakdown. Currently, the role that forkhead boxO activation plays in the development of mechanical ventilation-induced diaphragm weakness remains unknown. This study tested the hypothesis that mechanical ventilation-induced increases in forkhead boxO signaling contribute to ventilator-induced diaphragm weakness. University research laboratory. Young adult female Sprague-Dawley rats. Cause and effect was determined by inhibiting the activation of forkhead boxO in the rat diaphragm through the use of a dominant-negative forkhead boxO adeno-associated virus vector delivered directly to the diaphragm. Our results demonstrate that prolonged (12 hr) mechanical ventilation results in a significant decrease in both diaphragm muscle fiber size and diaphragm-specific force production. However, mechanically ventilated animals treated with dominant-negative forkhead boxO showed a significant attenuation of both diaphragm atrophy and contractile dysfunction. In addition, inhibiting forkhead boxO transcription attenuated the mechanical ventilation-induced activation of the ubiquitin-proteasome system, the autophagy/lysosomal system, and caspase-3. Forkhead boxO is necessary for the activation of key proteolytic systems essential for mechanical ventilation-induced diaphragm atrophy and contractile dysfunction. Collectively, these results suggest that targeting forkhead boxO transcription could be a key therapeutic target to combat ventilator-induced diaphragm dysfunction.

Intratracheal IL-6 protects against lung inflammation in direct, but not indirect, causes of acute lung injury in mice.

PubMed

Bhargava, Rhea; Janssen, William; Altmann, Christopher; Andrés-Hernando, Ana; Okamura, Kayo; Vandivier, R William; Ahuja, Nilesh; Faubel, Sarah

2013-01-01

Serum and bronchoalveolar fluid IL-6 are increased in patients with acute respiratory distress syndrome (ARDS) and predict prolonged mechanical ventilation and poor outcomes, although the role of intra-alveolar IL-6 in indirect lung injury is unknown. We investigated the role of endogenous and exogenous intra-alveolar IL-6 in AKI-mediated lung injury (indirect lung injury), intraperitoneal (IP) endotoxin administration (indirect lung injury) and, for comparison, intratracheal (IT) endotoxin administration (direct lung injury) with the hypothesis that IL-6 would exert a pro-inflammatory effect in these causes of acute lung inflammation. Bronchoalveolar cytokines (IL-6, CXCL1, TNF-α, IL-1β, and IL-10), BAL fluid neutrophils, lung inflammation (lung cytokines, MPO activity [a biochemical marker of neutrophil infiltration]), and serum cytokines were determined in adult male C57Bl/6 mice with no intervention or 4 hours after ischemic AKI (22 minutes of renal pedicle clamping), IP endotoxin (10 µg), or IT endotoxin (80 µg) with and without intratracheal (IT) IL-6 (25 ng or 200 ng) treatment. Lung inflammation was similar after AKI, IP endotoxin, and IT endotoxin. BAL fluid IL-6 was markedly increased after IT endotoxin, and not increased after AKI or IP endotoxin. Unexpectedly, IT IL-6 exerted an anti-inflammatory effect in healthy mice characterized by reduced BAL fluid cytokines. IT IL-6 also exerted an anti-inflammatory effect in IT endotoxin characterized by reduced BAL fluid cytokines and lung inflammation; IT IL-6 had no effect on lung inflammation in AKI or IP endotoxin. IL-6 exerts an anti-inflammatory effect in direct lung injury from IT endotoxin, yet has no role in the pathogenesis or treatment of indirect lung injury from AKI or IP endotoxin. Since intra-alveolar inflammation is important in the pathogenesis of direct, but not indirect, causes of lung inflammation, IT anti-inflammatory treatments may have a role in direct, but not indirect, causes of ARDS.

Vaspin protects against LPS-induced ARDS by inhibiting inflammation, apoptosis and reactive oxygen species generation in pulmonary endothelial cells via the Akt/GSK-3β pathway

PubMed Central

Qi, Di; Wang, Daoxin; Zhang, Chunrong; Tang, Xumao; He, Jing; Zhao, Yan; Deng, Wang; Deng, Xinyu

2017-01-01

Acute respiratory distress syndrome (ARDS) is characterized by uncontrolled extravasation of protein-rich fluids, which is caused by disruption and dysfunction of the barrier of pulmonary endothelial cells (ECs). Visceral adipose tissue-derived serine protease inhibitor (vaspin) is a novel adipokine with pleiotropic properties, which has been reported to exert beneficial effects against obesity-associated systemic vascular diseases; however, its effects on ARDS remain unknown. In the present study, mice were subjected to systemic administration of adenoviral vector expressing vaspin (Ad-vaspin) to examine its effects on lipopolysaccharide (LPS)-induced ARDS in vivo. Histological analysis was then conducted, and cytokine [tumor necrosis factor (TNF)-α, interleukin (IL)-6 and IL-10] levels, and intercellular cell adhesion molecule-1 (ICAM-1) and adherens junctions (AJs) expression were detected. In addition, human pulmonary microvascular ECs (HPMECs) were treated with recombinant human (rh)-vaspin to further investigate its molecular basis and underlying mechanism. The mRNA expression levels of inflammatory cytokines (TNF-α and IL-6) and endothelial-specific adhesion markers [vascular cell adhesion molecule-1 and E-selectin], activation of nuclear factor-κB, and cell viability and apoptosis were then examined. Furthermore, the expression of AJs and organization of the cytoskeleton, as well as expression and activity of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase and generation of reactive oxygen species (ROS) were determined. The results indicated that Ad-vaspin protected against LPS-induced ARDS by alleviating the pulmonary inflammatory response and pulmonary EC barrier dysfunction in mice, which was accompanied by activation of the protein kinase B (Akt)/glycogen synthase kinase (GSK)-3β pathway. In addition, pretreatment of HPMECs with rh-vaspin attenuated inflammation, apoptosis and ROS generation without alterations in AJs and cytoskeletal organization following LPS insult, which was accompanied by activation of the Akt/GSK3β pathway. In conclusion, the present study demonstrated that vaspin protects against LPS-induced ARDS by reversing EC barrier dysfunction via the suppression of inflammation, apoptosis and ROS production in pulmonary ECs, at least partially via activation of the Akt/GSK3β pathway. These findings provide evidence of a causal link between vaspin and EC dysfunction in ARDS, and suggest a potential therapeutic intervention for patients with ARDS. PMID:29039444

Vaspin protects against LPS‑induced ARDS by inhibiting inflammation, apoptosis and reactive oxygen species generation in pulmonary endothelial cells via the Akt/GSK‑3β pathway.

PubMed

Qi, Di; Wang, Daoxin; Zhang, Chunrong; Tang, Xumao; He, Jing; Zhao, Yan; Deng, Wang; Deng, Xinyu

2017-12-01

Acute respiratory distress syndrome (ARDS) is characterized by uncontrolled extravasation of protein‑rich fluids, which is caused by disruption and dysfunction of the barrier of pulmonary endothelial cells (ECs). Visceral adipose tissue‑derived serine protease inhibitor (vaspin) is a novel adipokine with pleiotropic properties, which has been reported to exert beneficial effects against obesity‑associated systemic vascular diseases; however, its effects on ARDS remain unknown. In the present study, mice were subjected to systemic administration of adenoviral vector expressing vaspin (Ad‑vaspin) to examine its effects on lipopolysaccharide (LPS)‑induced ARDS in vivo. Histological analysis was then conducted, and cytokine [tumor necrosis factor (TNF)‑α, interleukin (IL)‑6 and IL‑10] levels, and intercellular cell adhesion molecule‑1 (ICAM‑1) and adherens junctions (AJs) expression were detected. In addition, human pulmonary microvascular ECs (HPMECs) were treated with recombinant human (rh)‑vaspin to further investigate its molecular basis and underlying mechanism. The mRNA expression levels of inflammatory cytokines (TNF‑α and IL‑6) and endothelial‑specific adhesion markers [vascular cell adhesion molecule‑1 and E‑selectin], activation of nuclear factor‑κB, and cell viability and apoptosis were then examined. Furthermore, the expression of AJs and organization of the cytoskeleton, as well as expression and activity of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase and generation of reactive oxygen species (ROS) were determined. The results indicated that Ad‑vaspin protected against LPS‑induced ARDS by alleviating the pulmonary inflammatory response and pulmonary EC barrier dysfunction in mice, which was accompanied by activation of the protein kinase B (Akt)/glycogen synthase kinase (GSK)‑3β pathway. In addition, pretreatment of HPMECs with rh‑vaspin attenuated inflammation, apoptosis and ROS generation without alterations in AJs and cytoskeletal organization following LPS insult, which was accompanied by activation of the Akt/GSK3β pathway. In conclusion, the present study demonstrated that vaspin protects against LPS‑induced ARDS by reversing EC barrier dysfunction via the suppression of inflammation, apoptosis and ROS production in pulmonary ECs, at least partially via activation of the Akt/GSK3β pathway. These findings provide evidence of a causal link between vaspin and EC dysfunction in ARDS, and suggest a potential therapeutic intervention for patients with ARDS.

Numerical simulation of volume-controlled mechanical ventilated respiratory system with 2 different lungs.

PubMed

Shi, Yan; Zhang, Bolun; Cai, Maolin; Zhang, Xiaohua Douglas

2017-09-01

Mechanical ventilation is a key therapy for patients who cannot breathe adequately by themselves, and dynamics of mechanical ventilation system is of great significance for life support of patients. Recently, models of mechanical ventilated respiratory system with 1 lung are used to simulate the respiratory system of patients. However, humans have 2 lungs. When the respiratory characteristics of 2 lungs are different, a single-lung model cannot reflect real respiratory system. In this paper, to illustrate dynamic characteristics of mechanical ventilated respiratory system with 2 different lungs, we propose a mathematical model of mechanical ventilated respiratory system with 2 different lungs and conduct experiments to verify the model. Furthermore, we study the dynamics of mechanical ventilated respiratory system with 2 different lungs. This research study can be used for improving the efficiency and safety of volume-controlled mechanical ventilation system. Copyright © 2016 John Wiley & Sons, Ltd.

Distinct Molecular Phenotypes of Direct vs Indirect ARDS in Single-Center and Multicenter Studies

PubMed Central

Janz, David R.; Bernard, Gordon R.; May, Addison K.; Kangelaris, Kirsten N.; Matthay, Michael A.; Ware, Lorraine B.

2015-01-01

BACKGROUND: ARDS is a heterogeneous syndrome that encompasses lung injury from both direct and indirect sources. Direct ARDS (pneumonia, aspiration) has been hypothesized to cause more severe lung epithelial injury than indirect ARDS (eg, nonpulmonary sepsis); however, this hypothesis has not been well studied in humans. METHODS: We measured plasma biomarkers of lung epithelial and endothelial injury and inflammation in a single-center study of 100 patients with ARDS and severe sepsis and in a secondary analysis of 853 patients with ARDS drawn from a multicenter randomized controlled trial. Biomarker levels in patients with direct vs indirect ARDS were compared in both cohorts. RESULTS: In both studies, patients with direct ARDS had significantly higher levels of a biomarker of lung epithelial injury (surfactant protein D) and significantly lower levels of a biomarker of endothelial injury (angiopoietin-2) than those with indirect ARDS. These associations were robust to adjustment for severity of illness and ARDS severity. In the multicenter study, patients with direct ARDS also had lower levels of von Willebrand factor antigen and IL-6 and IL-8, markers of endothelial injury and inflammation, respectively. The prognostic value of the biomarkers was similar in direct and indirect ARDS. CONCLUSIONS: Direct lung injury in humans is characterized by a molecular phenotype consistent with more severe lung epithelial injury and less severe endothelial injury. The opposite pattern was identified in indirect lung injury. Clinical trials of novel therapies targeted specifically at the lung epithelium or endothelium may benefit from preferentially enrolling patients with direct and indirect ARDS, respectively. PMID:26033126

Distinct molecular phenotypes of direct vs indirect ARDS in single-center and multicenter studies.

PubMed

Calfee, Carolyn S; Janz, David R; Bernard, Gordon R; May, Addison K; Kangelaris, Kirsten N; Matthay, Michael A; Ware, Lorraine B

2015-06-01

ARDS is a heterogeneous syndrome that encompasses lung injury from both direct and indirect sources. Direct ARDS (pneumonia, aspiration) has been hypothesized to cause more severe lung epithelial injury than indirect ARDS (eg, nonpulmonary sepsis); however, this hypothesis has not been well studied in humans. We measured plasma biomarkers of lung epithelial and endothelial injury and inflammation in a single-center study of 100 patients with ARDS and severe sepsis and in a secondary analysis of 853 patients with ARDS drawn from a multicenter randomized controlled trial. Biomarker levels in patients with direct vs indirect ARDS were compared in both cohorts. In both studies, patients with direct ARDS had significantly higher levels of a biomarker of lung epithelial injury (surfactant protein D) and significantly lower levels of a biomarker of endothelial injury (angiopoietin-2) than those with indirect ARDS. These associations were robust to adjustment for severity of illness and ARDS severity. In the multicenter study, patients with direct ARDS also had lower levels of von Willebrand factor antigen and IL-6 and IL-8, markers of endothelial injury and inflammation, respectively. The prognostic value of the biomarkers was similar in direct and indirect ARDS. Direct lung injury in humans is characterized by a molecular phenotype consistent with more severe lung epithelial injury and less severe endothelial injury. The opposite pattern was identified in indirect lung injury. Clinical trials of novel therapies targeted specifically at the lung epithelium or endothelium may benefit from preferentially enrolling patients with direct and indirect ARDS, respectively.

Effects of Multiple Ventilation Courses and Duration of Mechanical Ventilation on Respiratory Outcomes in Extremely Low-Birth-Weight Infants.

PubMed

Jensen, Erik A; DeMauro, Sara B; Kornhauser, Michael; Aghai, Zubair H; Greenspan, Jay S; Dysart, Kevin C

2015-11-01

Extubation failure is common in extremely preterm infants. The current paucity of data on the adverse long-term respiratory outcomes associated with reinitiation of mechanical ventilation prevents assessment of the risks and benefits of a trial of extubation in this population. To evaluate whether exposure to multiple courses of mechanical ventilation increases the risk of adverse respiratory outcomes before and after adjustment for the cumulative duration of mechanical ventilation. We performed a retrospective cohort study of extremely low-birth-weight (ELBW; birth weight <1000 g) infants born from January 1, 2006, through December 31, 2012, who were receiving mechanical ventilation. Analysis was conducted between November 2014 and February 2015. Data were obtained from the Alere Neonatal Database. The primary study exposures were the cumulative duration of mechanical ventilation and the number of ventilation courses. The primary outcome was bronchopulmonary dysplasia (BPD) among survivors. Secondary outcomes were death, use of supplemental oxygen at discharge, and tracheostomy. We identified 3343 ELBW infants, of whom 2867 (85.8%) survived to discharge. Among the survivors, 1695 (59.1%) were diagnosed as having BPD, 856 (29.9%) received supplemental oxygen at discharge, and 31 (1.1%) underwent tracheostomy. Exposure to a greater number of mechanical ventilation courses was associated with a progressive increase in the risk of BPD and use of supplemental oxygen at discharge. Compared with a single ventilation course, the adjusted odds ratios for BPD ranged from 1.88 (95% CI, 1.54-2.31) among infants with 2 ventilation courses to 3.81 (95% CI, 2.88-5.04) among those with 4 or more courses. After adjustment for the cumulative duration of mechanical ventilation, the odds of BPD were only increased among infants exposed to 4 or more ventilation courses (adjusted odds ratio, 1.44; 95% CI, 1.04-2.01). The number of ventilation courses was not associated with increased risk of supplemental oxygen use at discharge after adjustment for the length of ventilation. A greater number of ventilation courses did not increase the risk of tracheostomy. Among ELBW infants, a longer cumulative duration of mechanical ventilation largely accounts for the increased risk of chronic respiratory morbidity associated with reinitiation of mechanical ventilation. These results support attempts of extubation in ELBW infants receiving mechanical ventilation on low ventilator settings, even when success is not guaranteed.

Continued under-recognition of acute respiratory distress syndrome after the Berlin definition: what is the solution?

PubMed

Laffey, John G; Pham, Tài; Bellani, Giacomo

2017-02-01

Timely recognition of acute respiratory distress syndrome (ARDS) may allow for more prompt management and less exacerbation of lung injury. However, the absence of a diagnostic test for ARDS means that the diagnosis of ARDS requires clinician recognition in what is usually a complicated and evolving illness. We review data concerning the extent of recognition of ARDS in the era of the Berlin definition of ARDS. ARDS continues to be under-recognized - even in the era of the more recent 'Berlin' definition, and significant delay in its recognition is common. Factors contributing to under-recognition may include the complexity of ARDS biology, low specificity of the consensus (diagnostic) criteria, and concerns about reliable interpretation of the chest radiograph. Understandably, 'external' factors are also at play: ICU occupancy and higher patient to clinician ratio impair recognition of ARDS. Timely recognition of ARDS appears important, as it is associated with the use of higher PEEP, prone positioning and neuromuscular blockade which can lower mortality. Computer-aided decision tools seem diagnostically useful, and together with the integration of reliable biomarkers, may further enhance and speed recognition of this syndrome. Significant numbers of patients with ARDS are still unrecognized by clinicians in the era of the Berlin definition of ARDS, with potentially important consequences for patient management and outcome.

History of Mechanical Ventilation. From Vesalius to Ventilator-induced Lung Injury.

PubMed

Slutsky, Arthur S

2015-05-15

Mechanical ventilation is a life-saving therapy that catalyzed the development of modern intensive care units. The origins of modern mechanical ventilation can be traced back about five centuries to the seminal work of Andreas Vesalius. This article is a short history of mechanical ventilation, tracing its origins over the centuries to the present day. One of the great advances in ventilatory support over the past few decades has been the development of lung-protective ventilatory strategies, based on our understanding of the iatrogenic consequences of mechanical ventilation such as ventilator-induced lung injury. These strategies have markedly improved clinical outcomes in patients with respiratory failure.

Epigenetic contribution of the myosin light chain kinase gene to the risk for acute respiratory distress syndrome.

PubMed

Szilágyi, Keely L; Liu, Cong; Zhang, Xu; Wang, Ting; Fortman, Jeffrey D; Zhang, Wei; Garcia, Joe G N

2017-02-01

Acute respiratory distress syndrome (ARDS) is a devastating clinical syndrome with a considerable case fatality rate (∼30%-40%). Health disparities exist with African descent (AD) subjects exhibiting greater mortality than European descent (ED) individuals. Myosin light chain kinase is encoded by MYLK, whose genetic variants are implicated in ARDS pathogenesis and may influence ARDS mortality. As baseline population-specific epigenetic changes, that is, cytosine modifications, have been observed between AD and ED individuals, epigenetic variations in MYLK may provide insights into ARDS disparities. We compared methylation levels of MYLK cytosine-guanine dinucleotides (CpGs) between ARDS patients and intensive care unit (ICU) controls overall and by ethnicity in a nested case-control study of 39 ARDS cases and 75 non-ARDS ICU controls. Two MYLK CpG sites (cg03892735 and cg23344121) were differentially modified between ARDS subjects and controls (P < 0.05; q < 0.25) in a logistic regression model, where no effect modification by ethnicity or age was found. One CpG site was associated with ARDS in patients aged <58 years, cg19611163 (intron 19, 20). Two CpG sites were associated with ARDS in EDs only, gene body CpG (cg01894985, intron 2, 3) and CpG (cg16212219, intron 31, 32), with higher modification levels exhibited in ARDS subjects than controls. Cis-acting modified cytosine quantitative trait loci (mQTL) were identified using linear regression between local genetic variants and modification levels for 2 ARDS-associated CpGs (cg23344121 and cg16212219). In summary, these ARDS-associated MYLK CpGs with effect modification by ethnicity and local mQTL suggest that MYLK epigenetic variation and local genetic background may contribute to health disparities observed in ARDS. Copyright © 2016 Elsevier Inc. All rights reserved.

Clinical Predictors of Hospital Mortality Differ Between Direct and Indirect ARDS.

PubMed

Luo, Liang; Shaver, Ciara M; Zhao, Zhiguo; Koyama, Tatsuki; Calfee, Carolyn S; Bastarache, Julie A; Ware, Lorraine B

2017-04-01

Direct (pulmonary) and indirect (extrapulmonary) ARDS are distinct syndromes with important pathophysiologic differences. The goal of this study was to determine whether clinical characteristics and predictors of mortality differ between direct or indirect ARDS. This retrospective observational cohort study included 417 patients with ARDS. Each patient was classified as having direct (pneumonia or aspiration, n = 250) or indirect (nonpulmonary sepsis or pancreatitis, n = 167) ARDS. Patients with direct ARDS had higher lung injury scores (3.0 vs 2.8; P < .001), lower Simplified Acute Physiology Score II scores (51 vs 62; P < .001), lower Acute Physiology and Chronic Health Evaluation II scores (27 vs 30; P < .001), and fewer nonpulmonary organ failures (1 vs 2; P < .001) compared with patients with indirect ARDS. Hospital mortality was similar (28% vs 31%). In patients with direct ARDS, age (OR, 1.29 per 10 years; P = .01; test for interaction, P = .03), lung injury scores (OR, 2.29 per point; P = .001; test for interaction, P = .058), and number of nonpulmonary organ failures (OR, 1.67; P = .01) were independent risk factors for increased hospital mortality. Preexisting diabetes mellitus was an independent risk factor for reduced hospital mortality (OR, 0.47; P = .04; test for interaction, P = .02). In indirect ARDS, only the number of organ failures was an independent predictor of mortality (OR, 2.08; P < .001). Despite lower severity of illness and fewer organ failures, patients with direct ARDS had mortality rates similar to patients with indirect ARDS. Factors previously associated with mortality during ARDS were only associated with mortality in direct ARDS. These findings suggest that direct and indirect ARDS have distinct features that may differentially affect risk prediction and clinical outcomes. Copyright © 2016 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.

Association of Heme Oxygenase 1 with Lung Protection in Malaria-Associated ALI/ARDS.

PubMed

Pereira, Marcelo L M; Ortolan, Luana S; Sercundes, Michelle K; Debone, Daniela; Murillo, Oscar; Lima, Flávia A; Marinho, Claudio R F; Epiphanio, Sabrina

2016-01-01

Malaria is a serious disease, caused by the parasite of the genus Plasmodium , which was responsible for 440,000 deaths in 2015. Acute lung injury/acute respiratory distress syndrome (ALI/ARDS) is one of the main clinical complications in severe malaria. The murine model DBA/2 reproduces the clinical signs of ALI/ARDS in humans, when infected with Plasmodium berghei ANKA. High levels of HO-1 were reported in cases of severe malaria. Our data indicated that the HO-1 mRNA and protein expression are increased in mice that develop malaria-associated ALI/ARDS (MA-ALI/ARDS). Additionally, the hemin, a HO-1 inducing drug, prevented mice from developing MA-ALI/ARDS when administered prior to the development of MA-ALI/ARDS in this model. Also, hemin treatment showed an amelioration of respiratory parameters in mice, high VEGF levels in the sera, and a decrease in vascular permeability in the lung, which are signs of ALI/ARDS. Therefore, the induction of HO-1 before the development of MA-ALI/ARDS could be protective. However, the increased expression of HO-1 on the onset of MA-ALI/ARDS development may represent an effort to revert the phenotype of this syndrome by the host. We therefore confirm that HO-1 inducing drugs could be used for prevention of MA-ALI/ARDS in humans.

Predictive Criteria to Study the Pathogenesis of Malaria-Associated ALI/ARDS in Mice

PubMed Central

Ortolan, Luana S.; Sercundes, Michelle K.; Debone, Daniela; Hagen, Stefano C. F.; D' Império Lima, Maria Regina; Alvarez, José M.; Marinho, Claudio R. F.; Epiphanio, Sabrina

2014-01-01

Malaria-associated acute lung injury/acute respiratory distress syndrome (ALI/ARDS) often results in morbidity and mortality. Murine models to study malaria-associated ALI/ARDS have been described; we still lack a method of distinguishing which mice will develop ALI/ARDS before death. This work aimed to characterize malaria-associated ALI/ARDS in a murine model and to demonstrate the first method to predict whether mice are suffering from ALI/ARDS before death. DBA/2 mice infected with Plasmodium berghei ANKA developing ALI/ARDS or hyperparasitemia (HP) were compared using histopathology, PaO2 measurement, pulmonary X-ray, breathing capacity, lung permeability, and serum vascular endothelial growth factor (VEGF) levels according to either the day of death or the suggested predictive criteria. We proposed a model to predict malaria-associated ALI/ARDS using breathing patterns (enhanced pause and frequency respiration) and parasitemia as predictive criteria from mice whose cause of death was known to retrospectively diagnose the sacrificed mice as likely to die of ALI/ARDS as early as 7 days after infection. Using this method, we showed increased VEGF levels and increased lung permeability in mice predicted to die of ALI/ARDS. This proposed method for accurately identifying mice suffering from ALI/ARDS before death will enable the use of this model to study the pathogenesis of this disease. PMID:25276057

Academic Emergency Medicine Physicians' Knowledge of Mechanical Ventilation.

PubMed

Wilcox, Susan R; Strout, Tania D; Schneider, Jeffrey I; Mitchell, Patricia M; Smith, Jessica; Lutfy-Clayton, Lucienne; Marcolini, Evie G; Aydin, Ani; Seigel, Todd A; Richards, Jeremy B

2016-05-01

Although emergency physicians frequently intubate patients, management of mechanical ventilation has not been emphasized in emergency medicine (EM) education or clinical practice. The objective of this study was to quantify EM attendings' education, experience, and knowledge regarding mechanical ventilation in the emergency department. We developed a survey of academic EM attendings' educational experiences with ventilators and a knowledge assessment tool with nine clinical questions. EM attendings at key teaching hospitals for seven EM residency training programs in the northeastern United States were invited to participate in this survey study. We performed correlation and regression analyses to evaluate the relationship between attendings' scores on the assessment instrument and their training, education, and comfort with ventilation. Of 394 EM attendings surveyed, 211 responded (53.6%). Of respondents, 74.5% reported receiving three or fewer hours of ventilation-related education from EM sources over the past year and 98 (46%) reported receiving between 0-1 hour of education. The overall correct response rate for the assessment tool was 73.4%, with a standard deviation of 19.9. The factors associated with a higher score were completion of an EM residency, prior emphasis on mechanical ventilation during one's own residency, working in a setting where an emergency physician bears primary responsibility for ventilator management, and level of comfort with managing ventilated patients. Physicians' comfort was associated with the frequency of ventilator changes and EM management of ventilation, as well as hours of education. EM attendings report caring for mechanically ventilated patients frequently, but most receive fewer than three educational hours a year on mechanical ventilation, and nearly half receive 0-1 hour. Physicians' performance on an assessment tool for mechanical ventilation is most strongly correlated with their self-reported comfort with mechanical ventilation.

Should we ever give steroids to ARDS patients?

PubMed Central

Hough, Catherine L.

2014-01-01

The development and severity of ARDS are closely related to dysregulated inflammation, and the duration of ARDS and eventual outcomes are related to persistent inflammation and abnormal fibroproliferation. Corticosteroids are potent modulators of inflammation and inhibitors of fibrosis that have been used since the description of the acute respiratory distress syndrome in attempts to improve outcomes. Randomized controlled trials of steroids for ARDS have answered some, but not all, questions regarding efficacy for prevention and treatment. First, there is no evidence that corticosteroids prevent the development of ARDS among patients at risk. Second, high dose and short course treatment with steroids does not improve the outcomes of patients with ARDS. And third, while there is compelling data that low dose and prolonged treatment with steroids improves pulmonary physiology in patients with ARDS, additional studies are needed to recommend treatment with steroids for ARDS. PMID:25453425

Effect of different seated positions on lung volume and oxygenation in acute respiratory distress syndrome.

PubMed

Dellamonica, J; Lerolle, N; Sargentini, C; Hubert, S; Beduneau, G; Di Marco, F; Mercat, A; Diehl, J L; Richard, J C M; Bernardin, G; Brochard, L

2013-06-01

Lung volume available for ventilation is markedly decreased during acute respiratory distress syndrome. Body positioning may contribute to increase lung volume and partial verticalization is simple to perform. This study evaluated whether verticalization had parallel effects on oxygenation and end expiratory lung volume (EELV). Prospective multicenter study in 40 mechanically ventilated patients with ALI/ARDS in five university hospital MICUs. We evaluated four 45-min successive trunk position epochs (supine slightly elevated at 15°; semi recumbent with trunk elevated at 45°; seated with trunk elevated at 60° and legs down at 45°; back to supine). Arterial blood gases, EELV measured using the nitrogen washin/washout, and static compliance were measured. Responders were defined by a PaO₂/FiO₂ increase >20 % between supine and seated position. Results are median [25th-75th percentiles]. With median PEEP = 10 cmH₂O, verticalization increased lung volume but only responders (13 patients, 32 %) had a significant increase in EELV/PBW (predicted body weight) compared to baseline. This increase persisted at least partially when patients were positioned back to supine. Responders had a lower EELV/PBW supine [14 mL/kg (13-15) vs. 18 mL/kg (15-27) (p = 0.005)] and a lower compliance [30 mL/cmH₂O (22-38) vs. 42 (30-46) (p = 0.01)] than non-responders. Strain decreased with verticalization for responders. EELV/PBW increase and PaO₂/FiO₂ increase were not correlated. Verticalization is easily achieved and improves oxygenation in approximately 32 % of the patients together with an increase in EELV. Nonetheless, effect of verticalization on EELV/PBW is not predictable by PaO₂/FiO₂ increase, its monitoring may be helpful for strain optimization.

Daily Goals Formulation and Enhanced Visualization of Mechanical Ventilation Variance Improves Mechanical Ventilation Score.

PubMed

Walsh, Brian K; Smallwood, Craig; Rettig, Jordan; Kacmarek, Robert M; Thompson, John; Arnold, John H

2017-03-01

The systematic implementation of evidence-based practice through the use of guidelines, checklists, and protocols mitigates the risks associated with mechanical ventilation, yet variation in practice remains prevalent. Recent advances in software and hardware have allowed for the development and deployment of an enhanced visualization tool that identifies mechanical ventilation goal variance. Our aim was to assess the utility of daily goal establishment and a computer-aided visualization of variance. This study was composed of 3 phases: a retrospective observational phase (baseline) followed by 2 prospective sequential interventions. Phase I intervention comprised daily goal establishment of mechanical ventilation. Phase II intervention was the setting and monitoring of daily goals of mechanical ventilation with a web-based data visualization system (T3). A single score of mechanical ventilation was developed to evaluate the outcome. The baseline phase evaluated 130 subjects, phase I enrolled 31 subjects, and phase II enrolled 36 subjects. There were no differences in demographic characteristics between cohorts. A total of 171 verbalizations of goals of mechanical ventilation were completed in phase I. The use of T3 increased by 87% from phase I. Mechanical ventilation score improved by 8.4% in phase I and 11.3% in phase II from baseline ( P = .032). The largest effect was in the low risk V T category, with a 40.3% improvement from baseline in phase I, which was maintained at 39% improvement from baseline in phase II ( P = .01). mechanical ventilation score was 9% higher on average in those who survived. Daily goal formation and computer-enhanced visualization of mechanical ventilation variance were associated with an improvement in goal attainment by evidence of an improved mechanical ventilation score. Further research is needed to determine whether improvements in mechanical ventilation score through a targeted, process-oriented intervention will lead to improved patient outcomes. (ClinicalTrials.gov registration NCT02184208.). Copyright © 2017 by Daedalus Enterprises.

A Pathophysiologic Approach to Biomarkers in Acute Respiratory Distress Syndrome

PubMed Central

Blondonnet, Raiko; Constantin, Jean-Michel; Sapin, Vincent; Jabaudon, Matthieu

2016-01-01

Acute respiratory distress syndrome (ARDS) is an acute-onset hypoxic condition with radiographic bilateral lung infiltration. It is characterized by an acute exudative phase combining diffuse alveolar damage and lung edema followed by a later fibroproliferative phase. Despite an improved understanding of ARDS pathobiology, our ability to predict the development of ARDS and risk-stratify patients with the disease remains limited. Biomarkers may help to identify patients at the highest risk of developing ARDS, assess response to therapy, predict outcome, and optimize enrollment in clinical trials. After a short description of ARDS pathobiology, here, we review the scientific evidence that supports the value of various ARDS biomarkers with regard to their major biological roles in ARDS-associated lung injury and/or repair. Ongoing research aims at identifying and characterizing novel biomarkers, in order to highlight relevant mechanistic explorations of lung injury and repair, and to ultimately develop innovative therapeutic approaches for ARDS patients. This review will focus on the pathophysiologic, diagnostic, and therapeutic implications of biomarkers in ARDS and on their utility to ultimately improve patient care. PMID:26980924

Endothelial biomarkers in human sepsis: pathogenesis and prognosis for ARDS

PubMed Central

Hendrickson, Carolyn M.; Matthay, Michael A.

2018-01-01

Experimental models of sepsis in small and large animals and a variety of in vitro preparations have established several basic mechanisms that drive endothelial injury. This review is focused on what can be learned from the results of clinical studies of plasma biomarkers of endothelial injury and inflammation in patients with sepsis. There is excellent evidence that elevated plasma levels of several biomarkers of endothelial injury, including von Willebrand factor antigen (VWF), angiopoietin-2 (Ang-2), and soluble fms-like tyrosine kinase 1 (sFLT-1), and biomarkers of inflammation, especially interleukin-8 (IL-8) and soluble tumor necrosis factor receptor (sTNFr), identify sepsis patients with a higher mortality. There are also some data that elevated levels of endothelial biomarkers can identify which patients with non-pulmonary sepsis will develop acute respiratory distress syndrome (ARDS). If ARDS patients are divided among those with indirect versus direct lung injury, then there is an association of elevated levels of endothelial biomarkers in indirect injury and markers of inflammation and alveolar epithelial injury in patients with direct lung injury. New research suggests that the combination of biologic and clinical markers may make it possible to segregate patients with ARDS into hypo- versus hyper-inflammatory phenotypes that may have implications for therapeutic responses to fluid therapy. Taken together, the studies reviewed here support a primary role of the microcirculation in the pathogenesis and prognosis of ARDS after sepsis. Biological differences identified by molecular patterns could explain heterogeneity of treatment effects that are not explained by clinical factors alone. PMID:29575977

Pleural liquid and kinetic friction coefficient of mesothelium after mechanical ventilation.

PubMed

Bodega, Francesca; Sironi, Chiara; Porta, Cristina; Zocchi, Luciano; Agostoni, Emilio

2015-01-15

Volume and protein concentration of pleural liquid in anesthetized rabbits after 1 or 3h of mechanical ventilation, with alveolar pressure equal to atmospheric at end expiration, were compared to those occurring after spontaneous breathing. Moreover, coefficient of kinetic friction between samples of visceral and parietal pleura, obtained after spontaneous or mechanical ventilation, sliding in vitro at physiological velocity under physiological load, was determined. Volume of pleural liquid after mechanical ventilation was similar to that previously found during spontaneous ventilation. This finding is contrary to expectation of Moriondo et al. (2005), based on measurement of lymphatic and interstitial pressure. Protein concentration of pleural liquid after mechanical ventilation was also similar to that occurring after spontaneous ventilation. Coefficient of kinetic friction after mechanical ventilation was 0.023±0.001, similar to that obtained after spontaneous breathing. Copyright © 2014 Elsevier B.V. All rights reserved.

Lung-protective mechanical ventilation does not protect against acute kidney injury in patients without lung injury at onset of mechanical ventilation.

PubMed

Cortjens, Bart; Royakkers, Annick A N M; Determann, Rogier M; van Suijlen, Jeroen D E; Kamphuis, Stephan S; Foppen, Jannetje; de Boer, Anita; Wieland, Cathrien W; Spronk, Peter E; Schultz, Marcus J; Bouman, Catherine S C

2012-06-01

Preclinical and clinical studies suggest that mechanical ventilation contributes to the development of acute kidney injury (AKI), particularly in the setting of lung-injurious ventilator strategies. To determine whether ventilator settings in critically ill patients without acute lung injury (ALI) at onset of mechanical ventilation affect the development of AKI. Secondary analysis of a randomized controlled trial (N = 150), comparing conventional tidal volume (V(T), 10 mL/kg) with low tidal volume (V(T), 6 mL/kg) mechanical ventilation in critically ill patients without ALI at randomization. During the first 5 days of mechanical ventilation, the RIFLE class was determined daily, whereas neutrophil gelatinase-associated lipocalin and cystatin C levels were measured in plasma collected on days 0, 2, and 4. Eighty-six patients had no AKI at inclusion, and 18 patients (21%) subsequently developed AKI, but without significant difference between ventilation strategies. (Cumulative hazard, 0.26 vs 0.23; P = .88.) The courses of neutrophil gelatinase-associated lipocalin and cystatin C plasma levels did not differ significantly between randomization groups. In the present study in critically patients without ALI at onset of mechanical ventilation, lower tidal volume ventilation did not reduce the development or worsening of AKI compared with conventional tidal volume ventilation. Copyright © 2012 Elsevier Inc. All rights reserved.

Autonomous Rendezvous and Docking Conference, volume 1

NASA Technical Reports Server (NTRS)

1990-01-01

This document consists of the presentation submitted at the Autonomous Rendezvous and Docking (ARD) Conference. It contains three volumes: ARD hardware technology; ARD software technology; and ARD operations. The purpose of this conference is to identify the technologies required for an on orbit demonstration of the ARD, assess the maturity of these technologies, and provide the necessary insight for a quality assessment of the programmatic management, technical, schedule, and cost risks.

Autonomous Rendezvous and Docking Conference, volume 3

NASA Technical Reports Server (NTRS)

1990-01-01

This document consists of the presentation submitted at the Autonomous Rendezvous and Docking (ARD) Conference. The document contains three volumes: ARD hardware technology; ARD software technology; and ARD operations. The purpose of this conference is to identify the technologies required for an on orbit demonstration of ARD, assess the maturity of these technologies, and provide the necessary insight for a quality assessment of programmatic management, technical, schedule, and cost risks.

Sequential production of leukaemia inhibitory factor by blood cell culture in patients with ARDS.

PubMed

Gruson, D; Hilbert, G; Juzan, M; Taupin, J L; Coulon, V; Moreau, J F; Gualde, N; Gbikpi-Benissan, G

1998-04-01

Leukaemia inhibitory factor (LIF) is a polyfunctional cytokine integrated in cytokine networks and its concentration has been shown to be elevated in bronchoalveolar lavage fluid of patients with the acute respiratory distress syndrome (ARDS). The aim of our study was to evaluate the production of LIF by culturing blood cells from patients with ARDS. 8 patients with ARDS, 8 patients with pneumonia and 5 healthy subjects. The blood samples were taken on day 1 after onset of ARDS. LIF was measured, in the cell-free supernatant, with an enzyme-linked immunosorbent assay after 24 h, 48 h and 72 h of blood cell culture. LIF was detectable in some patients in the ARDS group: at i) at 24 h and 48 h: in 2 patients ii) at 72 h in 4/5 patients (140 +/- 231 pg/ml). Only in the 4 patients in whom LIF was measured at 72 h was ARDS associated with the multiple organ dysfunction syndrome. Furthermore, among the 5 patients with ARDS who subsequently died, 4 had a detectable LIF. We have observed that LIF was produced only in ARDS, but not in all patients. The production of LIF seems to be a good indicator of the severity of ARDS. These preliminary results must be confirmed by a larger study.

Receptor for advanced glycation end-products and ARDS prediction: a multicentre observational study.

PubMed

Jabaudon, Matthieu; Berthelin, Pauline; Pranal, Thibaut; Roszyk, Laurence; Godet, Thomas; Faure, Jean-Sébastien; Chabanne, Russell; Eisenmann, Nathanael; Lautrette, Alexandre; Belville, Corinne; Blondonnet, Raiko; Cayot, Sophie; Gillart, Thierry; Pascal, Julien; Skrzypczak, Yvan; Souweine, Bertrand; Blanchon, Loic; Sapin, Vincent; Pereira, Bruno; Constantin, Jean-Michel

2018-02-08

Acute respiratory distress syndrome (ARDS) prediction remains challenging despite available clinical scores. To assess soluble receptor for advanced glycation end-products (sRAGE), a marker of lung epithelial injury, as a predictor of ARDS in a high-risk population, adult patients with at least one ARDS risk factor upon admission to participating intensive care units (ICUs) were enrolled in a multicentre, prospective study between June 2014 and January 2015. Plasma sRAGE and endogenous secretory RAGE (esRAGE) were measured at baseline (ICU admission) and 24 hours later (day one). Four AGER candidate single nucleotide polymorphisms (SNPs) were also assayed because of previous reports of functionality (rs1800625, rs1800624, rs3134940, and rs2070600). The primary outcome was ARDS development within seven days. Of 500 patients enrolled, 464 patients were analysed, and 59 developed ARDS by day seven. Higher baseline and day one plasma sRAGE, but not esRAGE, were independently associated with increased ARDS risk. AGER SNP rs2070600 (Ser/Ser) was associated with increased ARDS risk and higher plasma sRAGE in this cohort, although confirmatory studies are needed to assess the role of AGER SNPs in ARDS prediction. These findings suggest that among at-risk ICU patients, higher plasma sRAGE may identify those who are more likely to develop ARDS.

Neutrophil oxidative burst activation and the pattern of respiratory physiologic abnormalities in the fulminant post-traumatic adult respiratory distress syndrome.

PubMed

Rivkind, A I; Siegel, J H; Littleton, M; De Gaetano, A; Mamantov, T; Laghi, F; Stoklosa, J C

1991-01-01

The role of neutrophil oxidative burst activation (OBA) in the development of fulminant post-trauma adult respiratory distress syndrome (ARDS) was studied in 30 patients. Neutrophil (PMN) chemiluminescence (LE) was used as the index of OBA. Serially, for 8 days post-trauma, patient neutrophils (Pc) were studied in their own serum (Ps) normal serum (Ns), or Gey's solution (G). Ps was checked against normal neutrophils (Nc) for inhibition. LE was initiated by the addition of preopsonized zymosan to 1 x 10(6) PMN, the LE response monitored by luminometer, and the peak of the integral of LE recorded. Seven developed ARDS within the first 4 days; 12 patients developed sepsis (TS) but no ARDS, and 11 patients had uncomplicated trauma (TR). All ARDS showed increased LE (P less than 0.0001), at 48-96 hr. Patients without ARDS showed no significant increase in LE, although their mean injury severity (ISS) was the same. The ARDS LE response was mediated by activation of Pc [74%] with only a small but significant additional effect (6%) by ARDS serum (Ps): LE = 0.672 (Pc) + 0.24 [ARDS(Ps)] + 1343; N = 146, r2 0.733, P less than 0.0001. However, sera (Ps or Ns) was required, as incubation in G inhibited LE; [cells + s] greater than [cells + G], P less than 0.0001. LE is a biologic marker of ARDS, and the delay between injury and the LE indicated that initiation of ARDS may have therapeutic importance. Neutrophil activation in ARDS requires sera, but the ARDS effect appears mainly due to cells with only a small ARDS-specific serum-mediated role. The physiologic response to ARDS was evaluated by serial 8-hr studies of blood gases and pH; the respiratory index (RI) to pulmonary shunt (QS/QT) relationship, compliance (COMPL), and net fluid balance (DFLUID) PMN and platelet (PLAT) counts were also measured. Compared with TR and TS, the ARDS patients at 48-96 hr, showed increased RI, QS/QT, and DFluid requiring increased FiO2 and PEEP as COMPL and PLAT fell and LE rose. These changes were all simultaneously significant (P less than 0.05 to P less than 0.0001) by Bonferroni t-statistic applied to ANOVA. The clinical importance of these physiologic and biochemical responses was emphasized by the significantly (P less than 0.005) increased mortality in the ARDS patients. These data suggest that PMN LE and simple measures of respiratory function are early biologic markers of the development of fulminant post-traumatic ARDS and can be used to predict ARDS severity.

Lipopolysaccharide promotes pulmonary fibrosis in acute respiratory distress syndrome (ARDS) via lincRNA-p21 induced inhibition of Thy-1 expression.

PubMed

Zhou, Wen-Qin; Wang, Peng; Shao, Qiu-Ping; Wang, Jian

2016-08-01

Acute respiratory distress syndrome (ARDS) is a common clinical disorder characterized by pulmonary edema leading to acute lung damage and arterial hypoxemia. Pulmonary fibrosis is a progressive, fibrotic lung disorder, whose pathogenesis in ARDS remains speculative. LincRNA-p21 was a novel regulator of cell proliferation, apoptosis and DNA damage response. This study aims to investigate the effects and mechanism of lincRNA-p21 on pulmonary fibrosis in ARDS. Purified 10 mg/kg LPS was dropped into airways of C57BL/6 mice. Expression levels of lincRNA-p21 and Thy-1 were measured by real-time PCR or western blotting. Proliferation of lung fibroblasts was analyzed by BrdU incorporation assay. Lung and BAL collagen contents were estimated using colorimetric Sircol assay. LincRNA-p21 expression was time-dependently increased and Thy-1 expression was time-dependently reduced in a mouse model of ARDS and in LPS-treated lung fibroblasts. Meanwhile, lung fibroblast proliferation was also time-dependently elevated in LPS-treated lung fibroblasts. In addition, lung fibroblast proliferation could be promoted by lincRNA-p21 overexpression and LPS treatment, however, the elevated lung fibroblast proliferation was further abrogated by Thy-1 overexpression or lincRNA-p21 interference. And Thy-1 interference could elevate cell viability of lung fibroblasts and rescue the reduction of lung fibroblast proliferation induced by lincRNA-p21 interference. Moreover, lincRNA-p21 overexpression dramatically inhibited acetylation of H3 and H4 at the Thy-1 promoter and Thy-1 expression levels in HLF1 cells. Finally, lincRNA-p21 interference rescued LPS-induced increase of lung and BAL collagen contents. LincRNA-p21 could lead to pulmonary fibrosis in ARDS by inhibition of the expression of Thy-1.

Uncomplicated Plasmodium vivax malaria in pregnancy associated with mortality from acute respiratory distress syndrome.

PubMed

McGready, Rose; Wongsaen, Klanarong; Chu, Cindy S; Tun, Nay Win; Chotivanich, Kesinee; White, Nicholas J; Nosten, François

2014-05-27

The association between severe malaria and Plasmodium vivax species is contentious. On the Thai-Myanmar border, all pregnant women are followed systematically with active weekly malaria screening. Over a 27-year period of providing antenatal care, 48,983 have been prospectively followed until pregnancy outcome (miscarriage or delivery) and 4,298 women have had P. vivax detected at least once. Reported here is the first known P. vivax-associated death amongst these women. The initial patient presentation was of uncomplicated P. vivax (0.5% parasitaemia) in a term, multigravida woman who responded rapidly to oral artesunate and mefloquine treatment, clearing her blood stage parasites within 48 hours. The patient appeared well, was ambulatory and due to be discharged but became unwell with acute respiratory distress syndrome (ARDS) requiring ventilation three days (67 hours) into treatment. Despite induction and delivery of a stillborn foetus, ventilatory requirements increased and the patient died on day 7. The patient had a low body mass index. Sensitive detection with nested PCR confirmed only the presence of P. vivax species and concomitant infections such as tuberculosis and human immunodeficiency virus (HIV) were also ruled out. The contemporaneous treatment of acute uncomplicated P. vivax and the onset of ARDS on day 3 in this patient implies a possible but unconfirmed association with death in this patient. Assuming this death was caused by P. vivax, the risk of ARDS-related maternal mortality in this setting did not differ significantly between Plasmodium falciparum and P. vivax (0.24 per 1,000 (1/4,158) versus 0.23 per 1,000 (1/4,298), contrary to the increased risk of maternal mortality from P. falciparum compared to P. vivax, 2.89 per 1,000 (12/4,158) versus 0.23 per 1,000 (1/4,298), P = 0.003.

Polymorphisms in key pulmonary inflammatory pathways and the development of acute respiratory distress syndrome

PubMed Central

Brown, Samuel M.; Grissom, Colin K.; Rondina, Matthew T.; Hoidal, John R.; Scholand, Mary Beth; Wolff, Roger K.; Morris, Alan H.; Paine, Robert

2015-01-01

Purpose/Aim Acute Respiratory Distress Syndrome (ARDS) is an important clinical and public health problem. Why some at-risk individuals develop ARDS and others do not is unclear but may be related to differences in inflammatory and cell signaling systems. The Receptor for Advanced Glycation Endproducts (RAGE) and Granulocyte-Monocyte Stimulating Factor (GM-CSF) pathways have recently been implicated in pulmonary pathophysiology; whether genetic variation within these pathways contributes to ARDS risk or outcome is unknown. Materials and Methods We studied 842 patients from three centers in Utah and 14 non-Utah ARDS Network centers. We studied patients at risk for ARDS and patients with ARDS to determine whether Single Nucleotide Polymorphisms (SNPs) in the RAGE and GM-CSF pathways were associated with development of ARDS. We studied 29 SNPs in 5 genes within the two pathways and controlled for age, sepsis as ARDS risk factor, and severity of illness, while targeting a false discovery rate of ≤5%. In a secondary analysis we evaluated associations with mortality. Results Of 842 patients, 690 had ARDS, and 152 were at-risk. Sepsis was the risk factor for ARDS in 250 (30%) patients. When controlling for age, APACHE III score, sepsis as risk factor, and multiple comparisons, no SNPs were significantly associated with ARDS. In a secondary analysis, only rs743564 in CSF2 approached significance with regard to mortality (OR 2.17, unadjusted p = 0.005, adjusted p = 0.15). Conclusions Candidate SNPs within 5 genes in the RAGE and GM-CSF pathways were not significantly associated with development of ARDS in this multi-centric cohort. PMID:25513711

Evidence for chemokine synergy during neutrophil migration in ARDS.

PubMed

Williams, Andrew E; José, Ricardo J; Mercer, Paul F; Brealey, David; Parekh, Dhruv; Thickett, David R; O'Kane, Cecelia; McAuley, Danny F; Chambers, Rachel C

2017-01-01

Acute respiratory distress syndrome (ARDS) is a life-threatening condition characterised by pulmonary oedema, respiratory failure and severe inflammation. ARDS is further characterised by the recruitment of neutrophils into the lung interstitium and alveolar space. The factors that regulate neutrophil infiltration into the inflamed lung and our understanding of the pathomechanisms in ARDS remain incomplete. This study aimed at determining the role of the chemokine (C-C motif) ligand (CCL)2 and CCL7 in ARDS. CCL2 and CCL7 protein levels were measured in bronchoalveolar lavage (BAL) fluid obtained from lipopolysaccharide(LPS)-challenged human volunteers and two separate cohorts of patients with ARDS. Neutrophil chemotaxis to ARDS BAL fluid was evaluated and the contribution of each was assessed and compared with chemokine (C-X-C motif) ligand 8 (CXCL8). Chemokine receptor expression on neutrophils from blood or BAL fluid of patients with ARDS was analysed by flow cytometry. CCL2 and CCL7 were significantly elevated in BAL fluid recovered from LPS-challenged volunteers and patients with ARDS. BAL fluid from patients with ARDS was highly chemotactic for human neutrophils and neutralising either CCL2 or CCL7 attenuated the neutrophil chemotactic response. Moreover, CCL2 and CCL7 synergised with CXCL8 to promote neutrophil migration. Furthermore, neutrophils isolated from the blood or BAL fluid differentially regulated the cell surface expression of chemokine (C-X-C motif) receptor 1 and C-C chemokine receptor type 2 during ARDS. This study highlights important inflammatory chemokines involved in regulating neutrophil migration, which may have potential value as therapeutic targets for the treatment of ARDS. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Evidence for chemokine synergy during neutrophil migration in ARDS

PubMed Central

Williams, Andrew E; José, Ricardo J; Mercer, Paul F; Brealey, David; Parekh, Dhruv; Thickett, David R; O'Kane, Cecelia; McAuley, Danny F; Chambers, Rachel C

2017-01-01

Background Acute respiratory distress syndrome (ARDS) is a life-threatening condition characterised by pulmonary oedema, respiratory failure and severe inflammation. ARDS is further characterised by the recruitment of neutrophils into the lung interstitium and alveolar space. Objectives The factors that regulate neutrophil infiltration into the inflamed lung and our understanding of the pathomechanisms in ARDS remain incomplete. This study aimed at determining the role of the chemokine (C-C motif) ligand (CCL)2 and CCL7 in ARDS. Methods CCL2 and CCL7 protein levels were measured in bronchoalveolar lavage (BAL) fluid obtained from lipopolysaccharide(LPS)-challenged human volunteers and two separate cohorts of patients with ARDS. Neutrophil chemotaxis to ARDS BAL fluid was evaluated and the contribution of each was assessed and compared with chemokine (C-X-C motif) ligand 8 (CXCL8). Chemokine receptor expression on neutrophils from blood or BAL fluid of patients with ARDS was analysed by flow cytometry. Results CCL2 and CCL7 were significantly elevated in BAL fluid recovered from LPS-challenged volunteers and patients with ARDS. BAL fluid from patients with ARDS was highly chemotactic for human neutrophils and neutralising either CCL2 or CCL7 attenuated the neutrophil chemotactic response. Moreover, CCL2 and CCL7 synergised with CXCL8 to promote neutrophil migration. Furthermore, neutrophils isolated from the blood or BAL fluid differentially regulated the cell surface expression of chemokine (C-X-C motif) receptor 1 and C-C chemokine receptor type 2 during ARDS. Conclusion This study highlights important inflammatory chemokines involved in regulating neutrophil migration, which may have potential value as therapeutic targets for the treatment of ARDS. PMID:27496101

Reduction of duration and cost of mechanical ventilation in an intensive care unit by use of a ventilatory management team.

PubMed

Cohen, I L; Bari, N; Strosberg, M A; Weinberg, P F; Wacksman, R M; Millstein, B H; Fein, I A

1991-10-01

To test the hypothesis that a formal interdisciplinary team approach to managing ICU patients requiring mechanical ventilation enhances ICU efficiency. Retrospective review with cost-effectiveness analysis. A 20-bed medical-surgical ICU in a 450-bed community referral teaching hospital with a critical care fellowship training program. All patients requiring mechanical ventilation in the ICU were included, comparing patients admitted 1 yr before the inception of the ventilatory management team (group 1) with those patients admitted for 1 yr after the inception of the team (group 2). Group 1 included 198 patients with 206 episodes of mechanical ventilation and group 2 included 165 patients with 183 episodes of mechanical ventilation. A team consisting of an ICU attending physician, nurse, and respiratory therapist was formed to conduct rounds regularly and supervise the ventilatory management of ICU patients who were referred to the critical care service. The two study groups were demographically comparable. However, there were significant reductions in resource use in group 2. The number of days on mechanical ventilation decreased (3.9 days per episode of mechanical ventilation [95% confidence interval 0.3 to 7.5 days]), as did days in the ICU (3.3 days per episode of mechanical ventilation [90% confidence interval 0.3 to 6.3 days]), numbers of arterial blood gases (23.2 per episode of mechanical ventilation; p less than .001), and number of indwelling arterial catheters (1 per episode of mechanical ventilation; p less than .001). The estimated cost savings from these reductions was $1,303 per episode of mechanical ventilation. We conclude that a ventilatory management team, or some component thereof, can significantly and safely expedite the process of "weaning" patients from mechanical ventilatory support in the ICU.

Home Mechanical Ventilation: A 12-Year Population-Based Retrospective Cohort Study.

PubMed

Povitz, Marcus; Rose, Louise; Shariff, Salimah Z; Leonard, Sean; Welk, Blayne; Jenkyn, Krista Bray; Leasa, David J; Gershon, Andrea S

2018-04-01

Increasing numbers of individuals are being initiated on home mechanical ventilation, including noninvasive (bi-level) and invasive mechanical ventilation delivered via tracheostomy due to chronic respiratory failure to enable symptom management and promote quality of life. Given the high care needs of these individuals, a better understanding of the indications for home mechanical ventilation, and health-care utilization is needed. We performed a retrospective cohort study using provincial health administrative data from Ontario, Canada (population ∼13,000,000). Home mechanical ventilation users were characterized using health administrative data to determine the indications for home mechanical ventilation, the need for acute care at the time of ventilation approval, and their health service use and mortality rates following approval. The annual incidence of home mechanical ventilation approval rose from 1.8/100,000 in 2000 to 5.0/100,000 in 2012, or an annual increase of approximately 0.3/100,000 persons/y. The leading indications were neuromuscular disease, thoracic restriction, and COPD. The indication for the remainder could not be determined due to limitations of the administrative databases. Of the 4,670 individuals, 23.0% commenced home mechanical ventilation following an acute care hospitalization. Among individuals who survived at least 1 y, fewer required hospitalization in the year that followed home mechanical ventilation approval (29.9% vs 39.8%) as compared with the year prior. Utilization of home mechanical ventilation is increasing in Ontario, Canada, and further study is needed to clarify the factors contributing to this and to further optimize utilization of health-care resources. Copyright © 2018 by Daedalus Enterprises.

Early identification of patients at risk for acute respiratory distress syndrome among severe pneumonia: a retrospective cohort study

PubMed Central

Luo, Jian; Yu, He; Hu, Yue-Hong; Liu, Dan; Wang, Yi-Wei; Wang, Mao-Yun

2017-01-01

Background Severe pneumonia is the predominant cause for acute respiratory distress syndrome (ARDS). Identification of ARDS from patients with severe pneumonia remains a significant clinical problem due to the overlap of clinical presentations and symptoms. Early recognition of risks for ARDS from severe pneumonia is of great clinical value. Methods From April 2014 to December 2015, patients with severe pneumonia at admission were retrieved from the hospital database, of which ARDS developed within 7 days were further identified. We compared the demographic and clinical characteristics at admission between severe pneumonia patients with and without ARDS development, followed by analysis of potential predictors for ARDS development and mortality. Multivariate logistic regression and receiver operating characteristic (ROC) curves were performed to screen independent risk factors and identify their sensitivity in predicting ARDS development and prognosis. Results Compared with severe pneumonia without ARDS development, patients with ARDS development had shorter disease duration before admission, higher lung injury score (LIS), serum fibrinogen (FiB), and positive end-expiratory pressure (PEEP), lower Marshall score, sequential organ failure assessment score and proportion of cardiovascular and gastrointestinal diseases, but similar mortality. Serum FiB >5.15 g/L [adjusted odds ratio (OR) 1.893, 95% confidence interval (CI): 1.141–3.142, P=0.014] and PEEP >6.5 cmH2O (adjusted OR 1.651, 95% CI: 1.218–2.237, P=0.001) were independent predictors for ARDS development with a sensitivity of 58.3% and 87.5%, respectively, and pH <7.35 (adjusted OR 0.832, 95% CI: 0.702–0.985, P=0.033) was an independent risk factor for ARDS mortality with a sensitivity of 95.2%. Conclusions ARDS development risk could be early recognized by PEEP >6.5 cmH2O and serum FiB >5.15 g/L in severe pneumonia patients, and pH <7.35 is a reliable prognostic factor in predicting ARDS mortality risk. PMID:29268409

Thrombocytopenia Is Associated with Acute Respiratory Distress Syndrome Mortality: An International Study

PubMed Central

Duan, Meili; Li, Gang; Wang, Shupeng; Li, Wenxiong; Zhu, Zhaozhong; Wei, Yongyue; Christiani, David C.; Li, Ang; Zhu, Xi

2014-01-01

Background Early detection of the Acute Respiratory Distress Syndrome (ARDS) has the potential to improvethe prognosis of critically ill patients admitted to the intensive care unit (ICU). However, no reliable biomarkers are currently available for accurate early detection of ARDS in patients with predisposing conditions. Objectives This study examined risk factors and biomarkers for ARDS development and mortality in two prospective cohort studies. Methods We examined clinical risk factors for ARDS in a cohort of 178 patients in Beijing, China who were admitted to the ICU and were at high risk for ARDS. Identified biomarkers were then replicated in a second cohort of1,878 patients in Boston, USA. Results Of 178 patients recruited from participating hospitals in Beijing, 75 developed ARDS. After multivariate adjustment, sepsis (odds ratio [OR]:5.58, 95% CI: 1.70–18.3), pulmonary injury (OR: 3.22; 95% CI: 1.60–6.47), and thrombocytopenia, defined as platelet count <80×103/µL, (OR: 2.67; 95% CI: 1.27–5.62)were significantly associated with increased risk of developing ARDS. Thrombocytopenia was also associated with increased mortality in patients who developed ARDS (adjusted hazard ratio [AHR]: 1.38, 95% CI: 1.07–1.57) but not in those who did not develop ARDS(AHR: 1.25, 95% CI: 0.96–1.62). The presence of both thrombocytopenia and ARDS substantially increased 60-daymortality. Sensitivity analyses showed that a platelet count of <100×103/µLin combination with ARDS provide the highest prognostic value for mortality. These associations were replicated in the cohort of US patients. Conclusions This study of ICU patients in both China and US showed that thrombocytopenia is associated with an increased risk of ARDS and platelet count in combination with ARDS had a high predictive value for patient mortality. PMID:24732309

Derivation and validation of a two-biomarker panel for diagnosis of ARDS in patients with severe traumatic injuries

PubMed Central

Ware, Lorraine B; Zhao, Zhiguo; Koyama, Tatsuki; Brown, Ryan M; Semler, Matthew W; Janz, David R; May, Addison K; Fremont, Richard D; Matthay, Michael A; Cohen, Mitchell J; Calfee, Carolyn S

2017-01-01

Background Acute respiratory distress syndrome (ARDS) is common after severe traumatic injuries but is underdiagnosed and undertreated. We hypothesized that a panel of plasma biomarkers could be used to diagnose ARDS in severe trauma. To test this hypothesis, we derived and validated a biomarker panel in three independent cohorts and compared the diagnostic performance to clinician recognition of ARDS. Methods Eleven plasma biomarkers of inflammation, lung epithelial and endothelial injury were measured in a derivation cohort of 439 severe trauma patients. ARDS status was analyzed by two-investigator consensus, and cases were required to meet Berlin criteria on intensive care unit (ICU) day 1. Controls were subjects without ARDS during the first 4 days of study enrollment. A multivariable logistic regression model was used to generate probabilities for ARDS. A reduced model with the top two performing markers was then tested in two independent validation cohorts. To assess clinical diagnosis of ARDS, medical records in the derivation cohort were systematically searched for documentation of ARDS diagnosis made by a clinical provider. Results Among 11 biomarkers, the combination of the endothelial injury marker angiopoietin-2 (Ang-2) and the lung epithelial injury marker receptor for advanced glycation endproducts (RAGE) provided good discrimination for ARDS in the derivation cohort (area under the curve (AUC)=0.74 (95% CI 0.67 to 0.80). In the validation cohorts, the AUCs for this model were 0.70 (0.61 to 0.77) and 0.78 (0.71 to 0.84). In contrast, provider assessment demonstrated poor diagnostic accuracy for ARDS, with AUC of 0.55 (0.51 to 0.60). Discussion A two-biomarker panel consisting of Ang-2 and RAGE performed well across multiple patient cohorts and outperformed clinical providers for diagnosing ARDS in severe trauma. Clinical application of this model could improve both diagnosis and treatment of ARDS in patients with severe trauma. Level of evidence Diagnostic study, level II. PMID:29766112

Derivation and validation of a two-biomarker panel for diagnosis of ARDS in patients with severe traumatic injuries.

PubMed

Ware, Lorraine B; Zhao, Zhiguo; Koyama, Tatsuki; Brown, Ryan M; Semler, Matthew W; Janz, David R; May, Addison K; Fremont, Richard D; Matthay, Michael A; Cohen, Mitchell J; Calfee, Carolyn S

2017-01-01

Acute respiratory distress syndrome (ARDS) is common after severe traumatic injuries but is underdiagnosed and undertreated. We hypothesized that a panel of plasma biomarkers could be used to diagnose ARDS in severe trauma. To test this hypothesis, we derived and validated a biomarker panel in three independent cohorts and compared the diagnostic performance to clinician recognition of ARDS. Eleven plasma biomarkers of inflammation, lung epithelial and endothelial injury were measured in a derivation cohort of 439 severe trauma patients. ARDS status was analyzed by two-investigator consensus, and cases were required to meet Berlin criteria on intensive care unit (ICU) day 1. Controls were subjects without ARDS during the first 4 days of study enrollment. A multivariable logistic regression model was used to generate probabilities for ARDS. A reduced model with the top two performing markers was then tested in two independent validation cohorts. To assess clinical diagnosis of ARDS, medical records in the derivation cohort were systematically searched for documentation of ARDS diagnosis made by a clinical provider. Among 11 biomarkers, the combination of the endothelial injury marker angiopoietin-2 (Ang-2) and the lung epithelial injury marker receptor for advanced glycation endproducts (RAGE) provided good discrimination for ARDS in the derivation cohort (area under the curve (AUC)=0.74 (95% CI 0.67 to 0.80). In the validation cohorts, the AUCs for this model were 0.70 (0.61 to 0.77) and 0.78 (0.71 to 0.84). In contrast, provider assessment demonstrated poor diagnostic accuracy for ARDS, with AUC of 0.55 (0.51 to 0.60). A two-biomarker panel consisting of Ang-2 and RAGE performed well across multiple patient cohorts and outperformed clinical providers for diagnosing ARDS in severe trauma. Clinical application of this model could improve both diagnosis and treatment of ARDS in patients with severe trauma. Diagnostic study, level II.

Effect of a hepatitis B virus inhibitor, NZ-4, on capsid formation.

PubMed

Yang, Li; Wang, Ya-Juan; Chen, Hai-Jun; Shi, Li-Ping; Tong, Xian-Kun; Zhang, Yang-Ming; Wang, Gui-Feng; Wang, Wen-Long; Feng, Chun-Lan; He, Pei-Lan; Xu, Yi-Bin; Lu, Meng-Ji; Tang, Wei; Nan, Fa-Jun; Zuo, Jian-Ping

2016-01-01

During the hepatitis B virus (HBV) life cycle, nucleocapsid assembly is essential for HBV replication. Both RNA reverse transcription and DNA replication occur within the HBV nucleocapsid. HBV nucleocapsid is consisted of core protein (HBcAg), whose carboxy-terminal domain (CTD) contains an Arg-rich domain (ARD). The ARD of HBcAg does contribute to the encapsidation of pregenomic RNA (pgRNA). Previously, we reported a small-molecule, NZ-4, which dramatically reduced the HBV DNA level in an in vitro cell setting. Here, we explore the possible mechanisms by which NZ-4 inhibits HBV function. As an HBV inhibitor, NZ-4 leads to the formation of genome-free capsids, including a new population of capsid that runs faster on agarose gels. NZ-4's activity was dependent on the presence of the ARD I, containing at least one positively charged amino acid. NZ-4 might provide a new option for further development of HBV therapeutics for the treatment of chronic hepatitis B. Copyright © 2015. Published by Elsevier B.V.

ARDS User Manual

NASA Technical Reports Server (NTRS)

Fleming, David P.

2001-01-01

Personal computers (PCs) are now used extensively for engineering analysis. their capability exceeds that of mainframe computers of only a few years ago. Programs originally written for mainframes have been ported to PCs to make their use easier. One of these programs is ARDS (Analysis of Rotor Dynamic Systems) which was developed at Arizona State University (ASU) by Nelson et al. to quickly and accurately analyze rotor steady state and transient response using the method of component mode synthesis. The original ARDS program was ported to the PC in 1995. Several extensions were made at ASU to increase the capability of mainframe ARDS. These extensions have also been incorporated into the PC version of ARDS. Each mainframe extension had its own user manual generally covering only that extension. Thus to exploit the full capability of ARDS required a large set of user manuals. Moreover, necessary changes and enhancements for PC ARDS were undocumented. The present document is intended to remedy those problems by combining all pertinent information needed for the use of PC ARDS into one volume.

Clinical and Biological Heterogeneity in ARDS: Direct versus Indirect Lung Injury

PubMed Central

Shaver, Ciara M.; Bastarache, Julie A.

2014-01-01

Synopsis The acute respiratory distress syndrome (ARDS) is a heterogeneous group of illnesses affecting the pulmonary parenchyma with acute onset bilateral inflammatory pulmonary infiltrates with associated hypoxemia. ARDS occurs after two major types of pulmonary injury: direct lung injury affecting the lung epithelium or indirect lung injury disrupting the vascular endothelium. Greater understanding of the differences between direct and indirect lung injury may refine our classification of patients with ARDS and lead to development of new therapeutics targeted at specific subpopulations of patients with ARDS. In this review, we will summarize the differences between direct and indirect causes of ARDS in human patients and then will review current knowledge of the similarities and differences in ARDS pathogenesis based on experimental animal models of direct and indirect lung injury. While the separation between direct and indirect causes of ARDS may be oversimplified, it is a useful approach to advancing our current understanding of the pathogenesis of this complex and often fatal disease. PMID:25453415

[Cases and duration of mechanical ventilation in German hospitals : An analysis of DRG incentives and developments in respiratory medicine].

PubMed

Biermann, A; Geissler, A

2016-09-01

Diagnosis-related groups (DRGs) have been used to reimburse hospitals services in Germany since 2003/04. Like any other reimbursement system, DRGs offer specific incentives for hospitals that may lead to unintended consequences for patients. In the German context, specific procedures and their documentation are suspected to be primarily performed to increase hospital revenues. Mechanical ventilation of patients and particularly the duration of ventilation, which is an important variable for the DRG-classification, are often discussed to be among these procedures. The aim of this study was to examine incentives created by the German DRG-based payment system with regard to mechanical ventilation and to identify factors that explain the considerable increase of mechanically ventilated patients in recent years. Moreover, the assumption that hospitals perform mechanical ventilation in order to gain economic benefits was examined. In order to gain insights on the development of the number of mechanically ventilated patients, patient-level data provided by the German Federal Statistical Office and the German Institute for the Hospital Remuneration System were analyzed. The type of performed ventilation, the total number of ventilation hours, the age distribution, mortality and the DRG distribution for mechanical ventilation were calculated, using methods of descriptive and inferential statistics. Furthermore, changes in DRG-definitions and changes in respiratory medicine were compared for the years 2005-2012. Since the introduction of the DRG-based payment system in Germany, the hours of ventilation and the number of mechanically ventilated patients have substantially increased, while mortality has decreased. During the same period there has been a switch to less invasive ventilation methods. The age distribution has shifted to higher age-groups. A ventilation duration determined by DRG definitions could not be found. Due to advances in respiratory medicine, new ventilation methods have been introduced that are less prone to complications. This development has simultaneously improved survival rates. There was no evidence supporting the assumption that the duration of mechanical ventilation is influenced by the time intervals relevant for DRG grouping. However, presumably operational routines such as staff availability within early and late shifts of the hospital have a significant impact on the termination of mechanical ventilation.

Abort Region Determinator (ARD) module feasibility report. Mission planning, mission analysis and software formulation

NASA Technical Reports Server (NTRS)

Draeger, B. G.; Joyner, J. A.

1976-01-01

A detailed performance evaluation of the Abort Region Determinator (ARD) module design was provided in support of OFT-1 ascent and OFT-1 intact launch aborts. The evaluation method used compared ARD results against results obtained using the full-up Space Vehicle Dynamic Simulations program under the same conditions. Results were presented for each of the three major ARD math models: (1) the ascent numerical integrator; (2) the mass model, and (3) the second stage predictor as well as the total ARD module. These results demonstrate that the baselined ARD module meets all design objectives for mission control center orbital flight test launch/abort support.

A Ground Testbed to Advance US Capability in Autonomous Rendezvous and Docking Project

NASA Technical Reports Server (NTRS)

D'Souza, Chris

2014-01-01

This project will advance the Autonomous Rendezvous and Docking (AR&D) GNC system by testing it on hardware, particularly in a flight processor, with a goal of testing it in IPAS with the Waypoint L2 AR&D scenario. The entire Agency supports development of a Commodity for Autonomous Rendezvous and Docking (CARD) as outlined in the Agency-wide Community of Practice whitepaper entitled: "A Strategy for the U.S. to Develop and Maintain a Mainstream Capability for Automated/Autonomous Rendezvous and Docking in Low Earth Orbit and Beyond". The whitepaper establishes that 1) the US is in a continual state of AR&D point-designs and therefore there is no US "off-the-shelf" AR&D capability in existence today, 2) the US has fallen behind our foreign counterparts particularly in the autonomy of AR&D systems, 3) development of an AR&D commodity is a national need that would benefit NASA, our commercial partners, and DoD, and 4) an initial estimate indicates that the development of a standardized AR&D capability could save the US approximately $60M for each AR&D project and cut each project's AR&D flight system implementation time in half.

Pressure Dynamic Characteristics of Pressure Controlled Ventilation System of a Lung Simulator

PubMed Central

Shi, Yan; Ren, Shuai; Cai, Maolin; Xu, Weiqing; Deng, Qiyou

2014-01-01

Mechanical ventilation is an important life support treatment of critically ill patients, and air pressure dynamics of human lung affect ventilation treatment effects. In this paper, in order to obtain the influences of seven key parameters of mechanical ventilation system on the pressure dynamics of human lung, firstly, mechanical ventilation system was considered as a pure pneumatic system, and then its mathematical model was set up. Furthermore, to verify the mathematical model, a prototype mechanical ventilation system of a lung simulator was proposed for experimental study. Last, simulation and experimental studies on the air flow dynamic of the mechanical ventilation system were done, and then the pressure dynamic characteristics of the mechanical system were obtained. The study can be referred to in the pulmonary diagnostics, treatment, and design of various medical devices or diagnostic systems. PMID:25197318

Influences of Duration of Inspiratory Effort, Respiratory Mechanics, and Ventilator Type on Asynchrony With Pressure Support and Proportional Assist Ventilation.

PubMed

Vasconcelos, Renata S; Sales, Raquel P; Melo, Luíz H de P; Marinho, Liégina S; Bastos, Vasco Pd; Nogueira, Andréa da Nc; Ferreira, Juliana C; Holanda, Marcelo A

2017-05-01

Pressure support ventilation (PSV) is often associated with patient-ventilator asynchrony. Proportional assist ventilation (PAV) offers inspiratory assistance proportional to patient effort, minimizing patient-ventilator asynchrony. The objective of this study was to evaluate the influence of respiratory mechanics and patient effort on patient-ventilator asynchrony during PSV and PAV plus (PAV+). We used a mechanical lung simulator and studied 3 respiratory mechanics profiles (normal, obstructive, and restrictive), with variations in the duration of inspiratory effort: 0.5, 1.0, 1.5, and 2.0 s. The Auto-Trak system was studied in ventilators when available. Outcome measures included inspiratory trigger delay, expiratory trigger asynchrony, and tidal volume (V T ). Inspiratory trigger delay was greater in the obstructive respiratory mechanics profile and greatest with a effort of 2.0 s (160 ms); cycling asynchrony, particularly delayed cycling, was common in the obstructive profile, whereas the restrictive profile was associated with premature cycling. In comparison with PSV, PAV+ improved patient-ventilator synchrony, with a shorter triggering delay (28 ms vs 116 ms) and no cycling asynchrony in the restrictive profile. V T was lower with PAV+ than with PSV (630 mL vs 837 mL), as it was with the single-limb circuit ventilator (570 mL vs 837 mL). PAV+ mode was associated with longer cycling delays than were the other ventilation modes, especially for the obstructive profile and higher effort values. Auto-Trak eliminated automatic triggering. Mechanical ventilation asynchrony was influenced by effort, respiratory mechanics, ventilator type, and ventilation mode. In PSV mode, delayed cycling was associated with shorter effort in obstructive respiratory mechanics profiles, whereas premature cycling was more common with longer effort and a restrictive profile. PAV+ prevented premature cycling but not delayed cycling, especially in obstructive respiratory mechanics profiles, and it was associated with a lower V T . Copyright © 2017 by Daedalus Enterprises.

Comparison between a clinical diagnosis method and the surveillance technique of the Center for Disease Control and Prevention for identification of mechanical ventilator-associated pneumonia.

PubMed

Waltrick, Renata; Possamai, Dimitri Sauter; de Aguiar, Fernanda Perito; Dadam, Micheli; de Souza Filho, Valmir João; Ramos, Lucas Rocker; Laurett, Renata da Silva; Fujiwara, Kênia; Caldeira Filho, Milton; Koenig, Álvaro; Westphal, Glauco Adrieno

2015-01-01

>To evaluate the agreement between a new epidemiological surveillance method of the Center for Disease Control and Prevention and the clinical pulmonary infection score for mechanical ventilator-associated pneumonia detection. This was a prospective cohort study that evaluated patients in the intensive care units of two hospitals who were intubated for more than 48 hours between August 2013 and June 2014. Patients were evaluated daily by physical therapist using the clinical pulmonary infection score. A nurse independently applied the new surveillance method proposed by the Center for Disease Control and Prevention. The diagnostic agreement between the methods was evaluated. A clinical pulmonary infection score of ≥ 7 indicated a clinical diagnosis of mechanical ventilator-associated pneumonia, and the association of a clinical pulmonary infection score ≥ 7 with an isolated semiquantitative culture consisting of ≥ 104 colony-forming units indicated a definitive diagnosis. Of the 801 patients admitted to the intensive care units, 198 required mechanical ventilation. Of these, 168 were intubated for more than 48 hours. A total of 18 (10.7%) cases of mechanical ventilation-associated infectious conditions were identified, 14 (8.3%) of which exhibited possible or probable mechanical ventilator-associated pneumonia, which represented 35% (14/38) of mechanical ventilator-associated pneumonia cases. The Center for Disease Control and Prevention method identified cases of mechanical ventilator-associated pneumonia with a sensitivity of 0.37, specificity of 1.0, positive predictive value of 1.0, and negative predictive value of 0.84. The differences resulted in discrepancies in the mechanical ventilator-associated pneumonia incidence density (CDC, 5.2/1000 days of mechanical ventilation; clinical pulmonary infection score ≥ 7, 13.1/1000 days of mechanical ventilation). The Center for Disease Control and Prevention method failed to detect mechanical ventilator-associated pneumonia cases and may not be satisfactory as a surveillance method.

Mechanical ventilation during extracorporeal membrane oxygenation. An international survey.

PubMed

Marhong, Jonathan D; Telesnicki, Teagan; Munshi, Laveena; Del Sorbo, Lorenzo; Detsky, Michael; Fan, Eddy

2014-07-01

In patients with severe, acute respiratory failure undergoing venovenous extracorporeal membrane oxygenation (VV-ECMO), the optimal strategy for mechanical ventilation is unclear. Our objective was to describe ventilation practices used in centers registered with the Extracorporeal Life Support Organization (ELSO). We conducted an international cross-sectional survey of medical directors and ECMO program coordinators from all ELSO-registered centers. The survey was distributed using a commercial website that collected information on center characteristics, the presence of a mechanical ventilator protocol, ventilator settings, and weaning practices. E-mails were sent out to medical directors or coordinators at each ELSO center and their responses were pooled for analysis. We analyzed 141 (50%) individual responses from the 283 centers contacted across 28 countries. Only 27% of centers reported having an explicit mechanical ventilation protocol for ECMO patients. The majority of these centers (77%) reported "lung rest" to be the primary goal of mechanical ventilation, whereas 9% reported "lung recruitment" to be their ventilation strategy. A tidal volume of 6 ml/kg or less was targeted by 76% of respondents, and 58% targeted a positive end-expiratory pressure of 6-10 cm H2O while ventilating patients on VV-ECMO. Centers prioritized weaning VV-ECMO before mechanical ventilation. Although ventilation practices in patients supported by VV-ECMO vary across ELSO centers internationally, the majority of centers used a strategy that targeted lung-protective thresholds and prioritized weaning VV-ECMO over mechanical ventilation.

Autophagy in pulmonary macrophages mediates lung inflammatory injury via NLRP3 inflammasome activation during mechanical ventilation

PubMed Central

Zhang, Yang; Liu, Gongjian; Dull, Randal O.; Schwartz, David E.

2014-01-01

The inflammatory response is a primary mechanism in the pathogenesis of ventilator-induced lung injury. Autophagy is an essential, homeostatic process by which cells break down their own components. We explored the role of autophagy in the mechanisms of mechanical ventilation-induced lung inflammatory injury. Mice were subjected to low (7 ml/kg) or high (28 ml/kg) tidal volume ventilation for 2 h. Bone marrow-derived macrophages transfected with a scrambled or autophagy-related protein 5 small interfering RNA were administered to alveolar macrophage-depleted mice via a jugular venous cannula 30 min before the start of the ventilation protocol. In some experiments, mice were ventilated in the absence and presence of autophagy inhibitors 3-methyladenine (15 mg/kg ip) or trichostatin A (1 mg/kg ip). Mechanical ventilation with a high tidal volume caused rapid (within minutes) activation of autophagy in the lung. Conventional transmission electron microscopic examination of lung sections showed that mechanical ventilation-induced autophagy activation mainly occurred in lung macrophages. Autophagy activation in the lungs during mechanical ventilation was dramatically attenuated in alveolar macrophage-depleted mice. Selective silencing of autophagy-related protein 5 in lung macrophages abolished mechanical ventilation-induced nucleotide-binding oligomerization domain-like receptor containing pyrin domain 3 (NLRP3) inflammasome activation and lung inflammatory injury. Pharmacological inhibition of autophagy also significantly attenuated the inflammatory responses caused by lung hyperinflation. The activation of autophagy in macrophages mediates early lung inflammation during mechanical ventilation via NLRP3 inflammasome signaling. Inhibition of autophagy activation in lung macrophages may therefore provide a novel and promising strategy for the prevention and treatment of ventilator-induced lung injury. PMID:24838752

Duration of Mechanical Ventilation in the Emergency Department.

PubMed

Angotti, Lauren B; Richards, Jeremy B; Fisher, Daniel F; Sankoff, Jeffrey D; Seigel, Todd A; Al Ashry, Haitham S; Wilcox, Susan R

2017-08-01

Due to hospital crowding, mechanically ventilated patients are increasingly spending hours boarding in emergency departments (ED) before intensive care unit (ICU) admission. This study aims to evaluate the association between time ventilated in the ED and in-hospital mortality, duration of mechanical ventilation, ICU and hospital length of stay (LOS). This was a multi-center, prospective, observational study of patients ventilated in the ED, conducted at three academic Level I Trauma Centers from July 2011 to March 2013. All consecutive adult patients on invasive mechanical ventilation were eligible for enrollment. We performed a Cox regression to assess for a mortality effect for mechanically ventilated patients with each hour of increasing LOS in the ED and multivariable regression analyses to assess for independently significant contributors to in-hospital mortality. Our primary outcome was in-hospital mortality, with secondary outcomes of ventilator days, ICU LOS and hospital LOS. We further commented on use of lung protective ventilation and frequency of ventilator changes made in this cohort. We enrolled 535 patients, of whom 525 met all inclusion criteria. Altered mental status without respiratory pathology was the most common reason for intubation, followed by trauma and respiratory failure. Using iterated Cox regression, a mortality effect occurred at ED time of mechanical ventilation > 7 hours, and the longer ED stay was also associated with a longer total duration of intubation. However, adjusted multivariable regression analysis demonstrated only older age and admission to the neurosciences ICU as independently associated with increased mortality. Of interest, only 23.8% of patients ventilated in the ED for over seven hours had changes made to their ventilator. In a prospective observational study of patients mechanically ventilated in the ED, there was a significant mortality benefit to expedited transfer of patients into an appropriate ICU setting.

The incidence of ARDS and associated mortality in severe TBI using the Berlin definition.

PubMed

Aisiku, Imoigele P; Yamal, Jose-Miguel; Doshi, Pratik; Rubin, Maria Laura; Benoit, Julia S; Hannay, Julia; Tilley, Barbara C; Gopinath, Shankar; Robertson, Claudia S

2016-02-01

The incidence of adult respiratory distress syndrome (ARDS) in severe traumatic brain injury (TBI) is poorly reported. Recently, a new definition for ARDS was proposed, the Berlin definition. The percentage of patients represented by TBI in the Berlin criteria study is limited. This study describes the incidence and associated mortality of ARDS in TBI patients. The study was an analysis of the safety of erythropoietin administration and transfusion threshold on the incidence of ARDS in severe TBI patients. Three reviewers independently assessed all patients enrolled in the study for acute lung injury/ARDS using the Berlin and the American-European Consensus Conference (AECC) definitions. A Cox proportional hazards model was used to assess the relationship between ARDS and mortality and 6-month Glasgow Outcome Scale (GOS) score. Two hundred patients were enrolled in the study. Of the patients, 21% (41 of 200) and 26% (52 of 200) developed ARDS using the AECC and Berlin definitions, respectively, with a median time of 3 days (interquartile range, 3) after injury. ARDS by either definition was associated with increased mortality (p = 0.04) but not with differences in functional outcome as measured by the GOS score at 6 months. Adjusted analysis using the Berlin criteria showed an increased mortality associated with ADS (p = 0.01). Severe TBI is associated with an incidence of ARDS ranging from 20% to 25%. The incidence is comparable between the Berlin and AECC definitions. ARDS is associated with increased mortality in severe TBI patients, but further studies are needed to validate these findings. Epidemiologic study, level II.

Trends in mechanical ventilation: are we ventilating our patients in the best possible way?

PubMed

Dellaca', Raffaele L; Veneroni, Chiara; Farre', Ramon

2017-06-01

This review addresses how the combination of physiology, medicine and engineering principles contributed to the development and advancement of mechanical ventilation, emphasising the most urgent needs for improvement and the most promising directions of future development. Several aspects of mechanical ventilation are introduced, highlighting on one side the importance of interdisciplinary research for further development and, on the other, the importance of training physicians sufficiently on the technological aspects of modern devices to exploit properly the great complexity and potentials of this treatment. To learn how mechanical ventilation developed in recent decades and to provide a better understanding of the actual technology and practice.To learn how and why interdisciplinary research and competences are necessary for providing the best ventilation treatment to patients.To understand which are the most relevant technical limitations in modern mechanical ventilators that can affect their performance in delivery of the treatment.To better understand and classify ventilation modes.To learn the classification, benefits, drawbacks and future perspectives of automatic ventilation tailoring algorithms.

Protective mechanical ventilation does not exacerbate lung function impairment or lung inflammation following influenza A infection.

PubMed

Zosky, Graeme R; Cannizzaro, Vincenzo; Hantos, Zoltan; Sly, Peter D

2009-11-01

The degree to which mechanical ventilation induces ventilator-associated lung injury is dependent on the initial acute lung injury (ALI). Viral-induced ALI is poorly studied, and this study aimed to determine whether ALI induced by a clinically relevant infection is exacerbated by protective mechanical ventilation. Adult female BALB/c mice were inoculated with 10(4.5) plaque-forming units of influenza A/Mem/1/71 in 50 microl of medium or medium alone. This study used a protective ventilation strategy, whereby mice were anesthetized, tracheostomized, and mechanically ventilated for 2 h. Lung mechanics were measured periodically throughout the ventilation period using a modification of the forced oscillation technique to obtain measures of airway resistance and coefficients of tissue damping and tissue elastance. Thoracic gas volume was measured and used to obtain specific airway resistance, tissue damping, and tissue elastance. At the end of the ventilation period, a bronchoalveolar lavage sample was collected to measure inflammatory cells, macrophage inflammatory protein-2, IL-6, TNF-alpha, and protein leak. Influenza infection caused significant increases in inflammatory cells, protein leak, and deterioration in lung mechanics that were not exacerbated by mechanical ventilation, in contrast to previous studies using bacterial and mouse-specific viral infection. This study highlighted the importance of type and severity of lung injury in determining outcome following mechanical ventilation.

Controlled invasive mechanical ventilation strategies in obese patients undergoing surgery.

PubMed

Maia, Lígia de Albuquerque; Silva, Pedro Leme; Pelosi, Paolo; Rocco, Patricia Rieken Macedo

2017-06-01

The obesity prevalence is increasing in surgical population. As the number of obese surgical patients increases, so does the demand for mechanical ventilation. Nevertheless, ventilatory strategies in this population are challenging, since obesity results in pathophysiological changes in respiratory function. Areas covered: We reviewed the impact of obesity on respiratory system and the effects of controlled invasive mechanical ventilation strategies in obese patients undergoing surgery. To date, there is no consensus regarding the optimal invasive mechanical ventilation strategy for obese surgical patients, and no evidence that possible intraoperative beneficial effects on oxygenation and mechanics translate into better postoperative pulmonary function or improved outcomes. Expert commentary: Before determining the ideal intraoperative ventilation strategy, it is important to analyze the pathophysiology and comorbidities of each obese patient. Protective ventilation with low tidal volume, driving pressure, energy, and mechanical power should be employed during surgery; however, further studies are required to clarify the most effective ventilation strategies, such as the optimal positive end-expiratory pressure and whether recruitment maneuvers minimize lung injury. In this context, an ongoing trial of intraoperative ventilation in obese patients (PROBESE) should help determine the mechanical ventilation strategy that best improves clinical outcome in patients with body mass index≥35kg/m 2 .

Hydrotherapy for the long-term ventilated patient: A case study and implications for practice.

PubMed

Wegner, Sally; Thomas, Peter; James, Christine

2017-11-01

Hydrotherapy of mechanically ventilated patients has been shown to be safe and feasible in both the acute stages of critical illness and in those requiring long term mechanical ventilation. This case study describes the hydrotherapy sessions of a 36 year old female, who after suffering complications of pneumococcal meningitis, became an incomplete quadriplegic and required long term mechanical ventilation. When implementing hydrotherapy with patients on mechanical ventilation a number of factors should be considered. These include staff resources and training, airway and ventilation management, patient preparation and safety procedures. Hydrotherapy can be safely utilised with mechanically ventilated patients, and may facilitate a patient's ability to participate in active exercise and rehabilitation. Copyright © 2017 Australian College of Critical Care Nurses Ltd. All rights reserved.

Noise measurements during high-frequency oscillatory and conventional mechanical ventilation.

PubMed

Berens, R J; Weigle, C G

1995-10-01

To evaluate the noise levels with high-frequency oscillatory ventilation and conventional mechanical ventilation. An observational, prospective study. Pediatric intensive care unit. The caretakers and environment of the pediatric intensive care unit. High-frequency oscillatory and conventional mechanical ventilation. Caretakers evaluated noise using a visual analog scale. Noise was measured with a decibel meter and an octave band frequency filter. There was twice as much noise perceived by the caretakers and as measured on the decibel A scale. All measures showed significantly greater noise, especially at low frequencies, with high-frequency oscillatory ventilation. High-frequency oscillatory ventilation exposes the patient to twice as much noise as does the use of conventional mechanical ventilation.

Indoor Environmental Quality in Mechanically Ventilated, Energy-Efficient Buildings vs. Conventional Buildings.

PubMed

Wallner, Peter; Munoz, Ute; Tappler, Peter; Wanka, Anna; Kundi, Michael; Shelton, Janie F; Hutter, Hans-Peter

2015-11-06

Energy-efficient buildings need mechanical ventilation. However, there are concerns that inadequate mechanical ventilation may lead to impaired indoor air quality. Using a semi-experimental field study, we investigated if exposure of occupants of two types of buildings (mechanical vs. natural ventilation) differs with regard to indoor air pollutants and climate factors. We investigated living and bedrooms in 123 buildings (62 highly energy-efficient and 61 conventional buildings) built in the years 2010 to 2012 in Austria (mainly Vienna and Lower Austria). Measurements of indoor parameters (climate, chemical pollutants and biological contaminants) were conducted twice. In total, more than 3000 measurements were performed. Almost all indoor air quality and room climate parameters showed significantly better results in mechanically ventilated homes compared to those relying on ventilation from open windows and/or doors. This study does not support the hypothesis that occupants in mechanically ventilated low energy houses are exposed to lower indoor air quality.

Effects of types of ventilation system on indoor particle concentrations in residential buildings.

PubMed

Park, J S; Jee, N-Y; Jeong, J-W

2014-12-01

The objective of this study was to quantify the influence of ventilation systems on indoor particle concentrations in residential buildings. Fifteen occupied, single-family apartments were selected from three sites. The three sites have three different ventilation systems: unbalanced mechanical ventilation, balanced mechanical ventilation, and natural ventilation. Field measurements were conducted between April and June 2012, when outdoor air temperatures were comfortable. Number concentrations of particles, PM2.5 and CO2 , were continuously measured both outdoors and indoors. In the apartments with natural ventilation, I/O ratios of particle number concentrations ranged from 0.56 to 0.72 for submicron particles, and from 0.25 to 0.60 for particles larger than 1.0 μm. The daily average indoor particle concentration decreased to 50% below the outdoor level for submicron particles and 25% below the outdoor level for fine particles, when the apartments were mechanically ventilated. The two mechanical ventilation systems reduced the I/O ratios by 26% for submicron particles and 65% for fine particles compared with the natural ventilation. These results showed that mechanical ventilation can reduce exposure to outdoor particles in residential buildings. Results of this study confirm that mechanical ventilation with filtration can significantly reduce indoor particle levels compared with natural ventilation. The I/O ratios of particles substantially varied at the naturally ventilated apartments because of the influence of variable window opening conditions and unsteadiness of wind flow on the penetration of outdoor air particles. For better prediction of the exposure to outdoor particles in naturally ventilated residential buildings, it is important to understand the penetration of outdoor particles with variable window opening conditions. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Impact of Prolonged Mechanical Ventilation in Very Low Birth Weight Infants: Results From a National Cohort Study.

PubMed

Choi, Young-Bin; Lee, Juyoung; Park, Jisun; Jun, Yong Hoon

2018-03-01

To evaluate the in-hospital consequences of prolonged respiratory support with invasive mechanical ventilation in very low birth weight infants. A cohort study was performed using prospectively collected data from 69 neonatal intensive care units participating in the Korean national registry. In total, 3508 very low birth weight infants born between January 1, 2013 and December 31, 2014 were reviewed. The adjusted hazard ratio for death increased significantly for infants who received mechanical ventilation for more than 2 weeks compared with those were mechanically ventilated for 7 days or less. The individual mortality rate increased after 8 weeks, reaching 50% and 60% at 14 and 16 weeks of cumulative mechanical ventilation, respectively. After adjusting for potential confounders, the cumulative duration of mechanical ventilation was associated with a clinically significant increase in the odds of bronchopulmonary dysplasia and pulmonary hypertension. Mechanical ventilation exposure for longer than 2 weeks, compared with 7 days or less, was associated with retinopathy of prematurity requiring laser coagulation and periventricular leukomalacia. The odds of abnormal auditory screening test results were significantly increased in infants who needed mechanical ventilation for more than 4 weeks. A longer cumulative duration of mechanical ventilation was associated with increased lengths of hospitalization and parenteral nutrition and a higher probability of discharge with poor achievement of physical growth. Although mechanical ventilation is a life-saving intervention for premature infants, these results indicate that it is associated with negative consequences when applied for prolonged periods. Copyright © 2017 Elsevier Inc. All rights reserved.

Optimal right heart filling pressure in acute respiratory distress syndrome determined by strain echocardiography.

PubMed

Garcia-Montilla, Romel; Imam, Faryal; Miao, Mi; Stinson, Kathryn; Khan, Akram; Heitner, Stephen

2017-06-01

Right ventricular (RV) systolic dysfunction is common in acute respiratory distress syndrome (ARDS). While preload optimization is crucial in its management, dynamic fluid responsiveness indices lack reliability, and there is no consensus on target central venous pressure (CVP). We analyzed the utility of RV free wall longitudinal strain (RVFWS) in the estimation of optimal RV filling pressure in ARDS. A retrospective cross-sectional analysis of clinical data and echocardiograms of patients with ARDS was performed. Tricuspid annular plane systolic excursion (TAPSE), tricuspid peak systolic velocity (S'), RV fractional area change (RVFAC), RVFWS, CVP, systolic pulmonary artery pressure (SPAP), and left ventricular ejection fraction (LVEF) were measured. Fifty-one patients with moderate-severe ARDS were included. There were inverse correlations between CVP and TAPSE, S', RVFAC, RVFWS, and LVEF. The most significant was with RVFWS (r:.74, R 2 :.55, P:.00001). Direct correlations with creatinine and lactate were noted. Receiver operating characteristic analysis showed that RVFWS -21% (normal reference value) was associated with CVP: 13 mm Hg (AUC: 0.92, 95% CI: 0.83-1.00). Regression model analysis of CVP, and RVFWS interactions established an RVFWS range from -18% to -24%. RVFWS -24% corresponded to CVP: 11 mm Hg and RVFWS -18% to CVP: 15 mm Hg. Beyond a CVP of 15 mm Hg, biventricular systolic dysfunction rapidly ensues. Our data are the first to show that an RV filling pressure of 13±2 mm Hg-as by CVP-correlates with optimal RV mechanics as evaluated by strain echocardiography in patients with moderate-severe ARDS. © 2017, Wiley Periodicals, Inc.

Specialized Pro-resolving Mediators Regulate Alveolar Fluid Clearance during Acute Respiratory Distress Syndrome

PubMed Central

Wang, Qian; Yan, Song-Fan; Hao, Yu; Jin, Sheng-Wei

2018-01-01

Objective: Acute respiratory distress syndrome (ARDS) is an acute and lethal clinical syndrome that is characterized by the injury of alveolar epithelium, which impairs active fluid transport in the lung, and impedes the reabsorption of edema fluid from the alveolar space. This review aimed to discuss the role of pro-resolving mediators on the regulation of alveolar fluid clearance (AFC) in ARDS. Data Sources: Articles published up to September 2017 were selected from the PubMed, with the keywords of “alveolar fluid clearance” or “lung edema” or “acute lung injury” or “acute respiratory distress syndrome”, and “specialized pro-resolving mediators” or “lipoxin” or “resolvin” or “protectin” or “maresin” or “alveolar epithelial cells” or “aspirin-triggered lipid mediators” or “carbon monoxide and heme oxygenase” or “annexin A1”. Study Selection: We included all relevant articles published up to September 2017, with no limitation of study design. Results: Specialized pro-resolving mediators (SPMs), as the proinflammatory mediators, not only upregulated epithelial sodium channel, Na,K-ATPase, cystic fibrosis transmembrane conductance regulator (CFTR), and aquaporins levels, but also improved Na,K-ATPase activity to promote AFC in ARDS. In addition to the direct effects on ion channels and pumps of the alveolar epithelium, the SPMs also inhibited the inflammatory cytokine expression and improved the alveolar epithelial cell repair to enhance the AFC in ARDS. Conclusions: The present review discusses a novel mechanism for pulmonary edema fluid reabsorption. SPMs might provide new opportunities to design “reabsorption-targeted” therapies with high degrees of precision in controlling ALI/ARDS. PMID:29664060

Platelet CLEC-2 protects against lung injury via effects of its ligand podoplanin on inflammatory alveolar macrophages in the mouse

PubMed Central

Rayes, Julie; Wichaiyo, Surasak; Haining, Elizabeth J.; Lowe, Kate; Grygielska, Beata; Laloo, Ryan; Flodby, Per; Borok, Zea; Crandall, Edward D.; Thickett, David R.; Watson, Steve P.

2017-01-01

There is no therapeutic intervention proven to prevent acute respiratory distress syndrome (ARDS). Novel mechanistic insights into the pathophysiology of ARDS are therefore required. Platelets are implicated in regulating many of the pathogenic processes that occur during ARDS; however, the mechanisms remain elusive. The platelet receptor CLEC-2 has been shown to regulate vascular integrity at sites of acute inflammation. Therefore the purpose of this study was to establish the role of CLEC-2 and its ligand podoplanin in a mouse model of ARDS. Platelet-specific CLEC-2-deficient, as well as alveolar epithelial type I cell (AECI)-specific or hematopoietic-specific podoplanin deficient, mice were established using cre-loxP strategies. Combining these with intratracheal (IT) instillations of lipopolysaccharide (LPS), we demonstrate that arterial oxygen saturation decline in response to IT-LPS in platelet-specific CLEC-2-deficient mice is significantly augmented. An increase in bronchoalveolar lavage (BAL) neutrophils and protein was also observed 48 h post-IT-LPS, with significant increases in pro-inflammatory chemokines detected in BAL of platelet-specific CLEC-2-deficient animals. Deletion of podoplanin from hematopoietic cells but not AECIs also reduces lung function and increases pro-inflammatory chemokine expression following IT-LPS. Furthermore, we demonstrate that following IT-LPS, platelets are present in BAL in aggregates with neutrophils, which allows for CLEC-2 interaction with podoplanin expressed on BAL inflammatory alveolar macrophages. Taken together, these data suggest that the platelet CLEC-2-podoplanin signaling axis regulates the severity of lung inflammation in mice and is a possible novel target for therapeutic intervention in patients at risk of developing ARDS. PMID:28839100

Management and outcome of mechanically ventilated neurologic patients.

PubMed

Pelosi, Paolo; Ferguson, Niall D; Frutos-Vivar, Fernando; Anzueto, Antonio; Putensen, Christian; Raymondos, Konstantinos; Apezteguia, Carlos; Desmery, Pablo; Hurtado, Javier; Abroug, Fekri; Elizalde, José; Tomicic, Vinko; Cakar, Nahit; Gonzalez, Marco; Arabi, Yaseen; Moreno, Rui; Esteban, Andres

2011-06-01

To describe and compare characteristics, ventilatory practices, and associated outcomes among mechanically ventilated patients with different types of brain injury and between neurologic and nonneurologic patients. Secondary analysis of a prospective, observational, and multicenter study on mechanical ventilation. Three hundred forty-nine intensive care units from 23 countries. We included 552 mechanically ventilated neurologic patients (362 patients with stroke and 190 patients with brain trauma). For comparison we used a control group of 4,030 mixed patients who were ventilated for nonneurologic reasons. None. We collected demographics, ventilatory settings, organ failures, and complications arising during ventilation and outcomes. Multivariate logistic regression analysis was performed with intensive care unit mortality as the dependent variable. At admission, a Glasgow Coma Scale score ≤8 was observed in 68% of the stroke, 77% of the brain trauma, and 29% of the nonneurologic patients. Modes of ventilation and use of a lung-protective strategy within the first week of mechanical ventilation were similar between groups. In comparison with nonneurologic patients, patients with neurologic disease developed fewer complications over the course of mechanical ventilation with the exception of a higher rate of ventilator-associated pneumonia in the brain trauma cohort. Neurologic patients showed higher rates of tracheotomy and longer duration of mechanical ventilation. Mortality in the intensive care unit was significantly (p < .001) higher in patients with stroke (45%) than in brain trauma (29%) and nonneurologic disease (30%). Factors associated with mortality were: stroke (in comparison to brain trauma), Glasgow Coma Scale score on day 1, and severity at admission in the intensive care unit. In our study, one of every five mechanically ventilated patients received this therapy as a result of a neurologic disease. This cohort of patients showed a higher mortality rate than nonneurologic patients despite a lower incidence of extracerebral organ dysfunction.

Analysis of a Pediatric Home Mechanical Ventilator Population.

PubMed

Amirnovin, Rambod; Aghamohammadi, Sara; Riley, Carley; Woo, Marlyn S; Del Castillo, Sylvia

2018-05-01

The population of children requiring home mechanical ventilation has evolved over the years and has grown to include a variety of diagnoses and needs that have led to changes in the care of this unique population. The purpose of this study was to provide a descriptive analysis of pediatric patients requiring home mechanical ventilation after hospitalization and how the evolution of this technology has impacted their care. A retrospective, observational, longitudinal analysis of 164 children enrolled in a university-affiliated home mechanical ventilation program over 26 years was performed. Data included each child's primary diagnosis, date of tracheostomy placement, duration of mechanical ventilation during hospitalization that consisted of home mechanical ventilator initiation, total length of pediatric ICU stay, ventilator settings at time of discharge from pediatric ICU, and disposition (home, facility, or died). Univariate, bivariate, and regression analysis was used as appropriate. The most common diagnosis requiring the use of home mechanical ventilation was neuromuscular disease (53%), followed by chronic pulmonary disease (29%). The median length of stay in the pediatric ICU decreased significantly after the implementation of a ventilator ward (70 d [30-142] vs 36 d [18-67], P = .02). The distribution of subjects upon discharge was home (71%), skilled nursing facility (24%), and died (4%), with an increase in the proportion of subjects discharged on PEEP and those going to nursing facilities over time ( P = 0.02). The evolution of home mechanical ventilation has allowed earlier transition out of the pediatric ICU and with increasing disposition to skilled nursing facilities over time. There has also been a change in ventilator management, including increased use of PEEP upon discharge, possibly driven by changes in ventilators and in-patient practice patterns. Copyright © 2018 by Daedalus Enterprises.

Course of Weaning from Prolonged Mechanical Ventilation after Cardiac Surgery

PubMed Central

Herlihy, James P.; Koch, Stephen M.; Jackson, Robert; Nora, Hope

2006-01-01

In order to determine the temporal pattern of weaning from mechanical ventilation for patients undergoing prolonged mechanical ventilation after cardiac surgery, we performed a retrospective review of 21 patients' weaning courses at our long-term acute care hospital. Using multiple regression analysis of an estimate of individual patients' percentage of mechanical ventilator support per day (%MVSD), we determined that 14 of 21 patients (67%) showed a statistically significant quadratic or cubic relationship between time and %MVSD. These patients showed little or no improvement in their ventilator dependence until a point in time when, abruptly, they began to make rapid progress (a “wean turning point”), after which they progressed to discontinuation of mechanical ventilation in a relatively short period of time. The other 7 patients appeared to have a similar weaning pattern, although the data were not statistically significant. Most patients in the study group weaned from the ventilator through a specific temporal pattern that is newly described herein. Data analysis suggested that the mechanism for the development of a wean turning point was improvement of pulmonary mechanics rather than improvement in gas exchange or respiratory load. Although these observations need to be confirmed by a prospective trial, they may have implications for weaning cardiac surgery patients from prolonged mechanical ventilation, and possibly for weaning a broader group of patients who require prolonged mechanical ventilation. PMID:16878611

Neutrophil extracellular traps contribute to the pathogenesis of acid-aspiration-induced ALI/ARDS.

PubMed

Li, Haitao; Zhou, Xiaoting; Tan, Hongyi; Hu, Yongbin; Zhang, Lemeng; Liu, Shuai; Dai, Minhui; Li, Yi; Li, Qian; Mao, Zhi; Pan, Pinhua; Su, Xiaoli; Hu, Chengpin

2018-01-05

Acute lung injury/acute respiratory distress syndrome (ALI/ARDS) is a manifestation of systemic inflammation in the lungs, but the factors that trigger inflammation in ALI/ARDS are unclear. We hypothesized that neutrophil extracellular traps (NETs) contribute to the pathogenesis of acid aspiration-induced ALI/ARDS. Analysis of bronchial aspirates from ARDS patients showed that NETs were significantly correlated with the degree of ARDS (r = -0.5846, p = 0.0359). NETs in bronchoalveolar lavage fluid of acid-aspiration mice were significantly higher (141.6 ± 23.08) at 3 h after injury than those in the sham group (1234 ± 101.9; p = 0.003, n = 5 per group). Exogenous NETs aggravated lung injury, while alvelestat and DNase markedly attenuated the intensity of ARDS. We investigated whether NETs are involved in the severity of gastric aspiration-induced ARDS. Then, a hydrochloric acid aspiration-induced ALI murine model was used to assess whether NETs are pathogenic and whether targeting NETs is protective. Exogenous NETs were administered to mice. Alvelestat can inhibit neutrophil elastase (NE), which serves an important role in NET formation, so we investigated whether alvelestat could protect against ALI in cell and mouse models. NETs may contribute to ALI/ARDS by promoting tissue damage and systemic inflammation. Targeting NETs by alvelestat may be a potential therapeutic strategy.

Venovenous extracorporeal membrane oxygenation for ARDS: outcome analysis of a Croatian referral center for respiratory ECMO.

PubMed

Kutleša, Marko; Novokmet, Anđa; Josipović Mraović, Renata; Baršić, Bruno

2017-07-01

The use of venovenous extracorporeal membrane oxygenation (VV-ECMO) as a rescue therapy in severe acute respiratory distress syndrome (ARDS) has become well established; however, the affirmation of evidence on VV-ECMO application and the analysis of patient outcomes after VV-ECMO treatment for ARDS continues. The aim of the study is to identify variables that affected the outcome of patients treated with VV-ECMO for severe ARDS outside a major ECMO center. The study included adult patients with severe ARDS treated with ECMO at a tertiary care hospital in Zagreb, Croatia between October 2009 and July 2014. Patients were recruited from a prospective database. The study enrolled 40 patients, 20 of whom had H1N1-induced ARDS. The hospital mortality was 38%. The difference in mortality and long-term outcome in H1N1-induced ARDS as compared to non-H1N1-induced ARDS was not significant. Variables associated with mortality included immunosuppression, shock at time of admission, acute renal failure, occurrence of heparin-induced thrombocytopenia antibodies, nosocomial sepsis and duration of ECMO. The results of our study indicate that ECMO use in severe ARDS is feasible with low mortality and identify or assert the variables associated with adverse outcomes.

Extracorporeal Membrane Oxygenation for ARDS: National Trends in the United States 2008-2012.

PubMed

Natt, Bhupinder S; Desai, Hem; Singh, Nirmal; Poongkunran, Chithra; Parthasarathy, Sairam; Bime, Christian

2016-10-01

Recent advances in technology and protocols have made the use of extracorporeal membrane oxygenation (ECMO) a viable rescue therapy for patients with ARDS who present with refractory hypoxemia. Despite the lack of strong evidence supporting the use of ECMO in ARDS, its use seems to be increasing. We sought to determine recent trends in the use of ECMO for ARDS. We also assessed trends in mortality among patients with ARDS in whom ECMO was used. We performed a retrospective analysis using the largest all-payer in-patient healthcare database in the United States, the Healthcare Cost and Utilization project, the National In-patient Sample database from 2008 to 2012. Subjects with ARDS were identified using carefully chosen International Classification of Diseases, Ninth Revision codes. We found that in 2008, about 1 in 1,000 subjects with ARDS underwent ECMO. Over the subsequent 4-y time period, there was a 0.19% absolute increase and 70% relative increase in the use of ECMO for ARDS. The mortality rate among subjects with ARDS in whom ECMO was used declined from 78% in 2008 to 64% in 2012. We also found a trend toward a reduction in hospital stay among survivors. In the United States, between 2008 and 2012, there was an increasing trend toward the use of ECMO in patients with ARDS that coincided with a slight increase in survival among these patients. Copyright © 2016 by Daedalus Enterprises.

Mortality and pulmonary mechanics in relation to respiratory system and transpulmonary driving pressures in ARDS.

PubMed

Baedorf Kassis, Elias; Loring, Stephen H; Talmor, Daniel

2016-08-01

The driving pressure of the respiratory system has been shown to strongly correlate with mortality in a recent large retrospective ARDSnet study. Respiratory system driving pressure [plateau pressure-positive end-expiratory pressure (PEEP)] does not account for variable chest wall compliance. Esophageal manometry can be utilized to determine transpulmonary driving pressure. We have examined the relationships between respiratory system and transpulmonary driving pressure, pulmonary mechanics and 28-day mortality. Fifty-six patients from a previous study were analyzed to compare PEEP titration to maintain positive transpulmonary end-expiratory pressure to a control protocol. Respiratory system and transpulmonary driving pressures and pulmonary mechanics were examined at baseline, 5 min and 24 h. Analysis of variance and linear regression were used to compare 28 day survivors versus non-survivors and the intervention group versus the control group, respectively. At baseline and 5 min there was no difference in respiratory system or transpulmonary driving pressure. By 24 h, survivors had lower respiratory system and transpulmonary driving pressures. Similarly, by 24 h the intervention group had lower transpulmonary driving pressure. This decrease was explained by improved elastance and increased PEEP. The results suggest that utilizing PEEP titration to target positive transpulmonary pressure via esophageal manometry causes both improved elastance and driving pressures. Treatment strategies leading to decreased respiratory system and transpulmonary driving pressure at 24 h may be associated with improved 28 day mortality. Studies to clarify the role of respiratory system and transpulmonary driving pressures as a prognosticator and bedside ventilator target are warranted.

Initial mechanical ventilator settings and lung protective ventilation in the ED.

PubMed

Wilcox, Susan R; Richards, Jeremy B; Fisher, Daniel F; Sankoff, Jeffrey; Seigel, Todd A

2016-08-01

Mechanical ventilation with low tidal volumes has been shown to improve outcomes for patients both with and without acute respiratory distress syndrome. This study aims to characterize mechanically ventilated patients in the emergency department (ED), describe the initial ED ventilator settings, and assess for associations between lung protective ventilation strategies in the ED and outcomes. This was a multicenter, prospective, observational study of mechanical ventilation at 3 academic EDs. We defined lung protective ventilation as a tidal volume of less than or equal to 8 mL/kg of predicted body weight and compared outcomes for patients ventilated with lung protective vs non-lung protective ventilation, including inhospital mortality, ventilator days, intensive care unit length of stay, and hospital length of stay. Data from 433 patients were analyzed. Altered mental status without respiratory pathology was the most common reason for intubation, followed by trauma and respiratory failure. Two hundred sixty-one patients (60.3%) received lung protective ventilation, but most patients were ventilated with a low positive end-expiratory pressure, high fraction of inspired oxygen strategy. Patients were ventilated in the ED for a mean of 5 hours and 7 minutes but had few ventilator adjustments. Outcomes were not significantly different between patients receiving lung protective vs non-lung protective ventilation. Nearly 40% of ED patients were ventilated with non-lung protective ventilation as well as with low positive end-expiratory pressure and high fraction of inspired oxygen. Despite a mean ED ventilation time of more than 5 hours, few patients had adjustments made to their ventilators. Copyright © 2016 Elsevier Inc. All rights reserved.

Conservative fluid management prevents age-associated ventilator induced mortality.

PubMed

Herbert, Joseph A; Valentine, Michael S; Saravanan, Nivi; Schneck, Matthew B; Pidaparti, Ramana; Fowler, Alpha A; Reynolds, Angela M; Heise, Rebecca L

2016-08-01

Approximately 800 thousand patients require mechanical ventilation in the United States annually with an in-hospital mortality rate of over 30%. The majority of patients requiring mechanical ventilation are over the age of 65 and advanced age is known to increase the severity of ventilator-induced lung injury (VILI) and in-hospital mortality rates. However, the mechanisms which predispose aging ventilator patients to increased mortality rates are not fully understood. Ventilation with conservative fluid management decreases mortality rates in acute respiratory distress patients, but to date there has been no investigation of the effect of conservative fluid management on VILI and ventilator associated mortality rates. We hypothesized that age-associated increases in susceptibility and incidence of pulmonary edema strongly promote age-related increases in ventilator associated mortality. 2month old and 20month old male C57BL6 mice were mechanically ventilated with either high tidal volume (HVT) or low tidal volume (LVT) for up to 4h with either liberal or conservative fluid support. During ventilation, lung compliance, total lung capacity, and hysteresis curves were quantified. Following ventilation, bronchoalveolar lavage fluid was analyzed for total protein content and inflammatory cell infiltration. Wet to dry ratios were used to directly measure edema in excised lungs. Lung histology was performed to quantify alveolar barrier damage/destruction. Age matched non-ventilated mice were used as controls. At 4h, both advanced age and HVT ventilation significantly increased markers of inflammation and injury, degraded pulmonary mechanics, and decreased survival rates. Conservative fluid support significantly diminished pulmonary edema and improved pulmonary mechanics by 1h in advanced age HVT subjects. In 4h ventilations, conservative fluid support significantly diminished pulmonary edema, improved lung mechanics, and resulted in significantly lower mortality rates in older subjects. Our study demonstrates that conservative fluid alone can attenuate the age associated increase in ventilator associated mortality. Copyright © 2016 Elsevier Inc. All rights reserved.

Invasive Mechanical Ventilation and Mortality in Pediatric Hematopoietic Stem Cell Transplantation: A Multicenter Study.

PubMed

Rowan, Courtney M; Gertz, Shira J; McArthur, Jennifer; Fitzgerald, Julie C; Nitu, Mara E; Loomis, Ashley; Hsing, Deyin D; Duncan, Christine N; Mahadeo, Kris M; Smith, Lincoln S; Moffet, Jerelyn; Hall, Mark W; Pinos, Emily L; Cheifetz, Ira M; Tamburro, Robert F

2016-04-01

To establish the current respiratory practice patterns in pediatric hematopoietic stem cell transplant patients and investigate their associations with mortality across multiple centers. Retrospective cohort between 2009 and 2014. Twelve children's hospitals in the United States. Two hundred twenty-two pediatric allogeneic hematopoietic stem cell transplant recipients with acute respiratory failure using invasive mechanical ventilation. None. PICU mortality of our cohort was 60.4%. Mortality at 180 days post PICU discharge was 74%. Length of PICU stay prior to initiation of invasive mechanical ventilation was significantly lower in survivors, and the odds of mortality increased for longer length of PICU stay prior to intubation. A total of 91 patients (41%) received noninvasive ventilation at some point during their PICU stay prior to intubation. Noninvasive ventilation use preintubation was associated with increased mortality (odds ratio, 2.1; 95% CI, 1.2-3.6; p = 0.010). Patients ventilated longer than 15 days had higher odds of death (odds ratio, 2.4; 95% CI, 1.3-4.2; p = 0.004). Almost 40% of patients (n = 85) were placed on high-frequency oscillatory ventilation with a mortality of 76.5% (odds ratio, 3.3; 95% CI, 1.7-6.5; p = 0.0004). Of the 20 patients who survived high-frequency oscillatory ventilation, 18 were placed on high-frequency oscillatory ventilation no later than the third day of invasive mechanical ventilation. In this subset of 85 patients, transition to high-frequency oscillatory ventilation within 2 days of the start of invasive mechanical ventilation resulted in a 76% decrease in the odds of death compared with those who transitioned to high-frequency oscillatory ventilation later in the invasive mechanical ventilation course. This study suggests that perhaps earlier more aggressive critical care interventions in the pediatric hematopoietic stem cell transplant patient with respiratory failure requiring invasive mechanical ventilation may offer an opportunity to improve outcomes.

Conservative Fluid Management Prevents Age-Associated Ventilator Induced Mortality

PubMed Central

Herbert, Joseph A.; Valentine, Michael S.; Saravanan, Nivi; Schneck, Matthew B.; Pidaparti, Ramana; Fowler, Alpha A.; Reynolds, Angela M.; Heise, Rebecca L.

2017-01-01

Background Approximately 800 thousand patients require mechanical ventilation in the United States annually with an in-hospital mortality rate of over 30%. The majority of patients requiring mechanical ventilation are over the age of 65 and advanced age is known to increase the severity of ventilator-induced lung injury (VILI) and in-hosptial mortality rates. However, the mechanisms which predispose aging ventilator patients to increased mortality rates are not fully understood. Ventilation with conservative fluid management decreases mortality rates in acute respiratory distress patients, but to date there has been no investigation of the effect of conservative fluid management on VILI and ventilator associated mortality rates. We hypothesized that age-associated increases in susceptibility and incidence of pulmonary edema strongly promote age-related increases in ventilator associated mortality. Methods 2 month old and 20 month old male C57BL6 mice were mechanically ventilated with either high tidal volume (HVT) or low tidal volume (LVT) for up to 4 hours with either liberal or conservative fluid support. During ventilation, lung compliance, total lung capacity, and hysteresis curves were quantified. Following ventilation, bronchoalveolar lavage fluid was analyzed for total protein content and inflammatory cell infiltration. Wet to dry ratios were used to directly measure edema in excised lungs. Lung histology was performed to quantify alveolar barrier damage/destruction. Age matched non-ventilated mice were used as controls. Results At 4hrs, both advanced age and HVT ventilation significantly increased markers of inflammation and injury, degraded pulmonary mechanics, and decreased survival rates. Conservative fluid support significantly diminished pulmonary edema and improved pulmonary mechanics by 1hr in advanced age HVT subjects. In 4hr ventilations, conservative fluid support significantly diminished pulmonary edema, improved lung mechanics, and resulted in significantly lower mortality rates in older subjects. Conclusion Our study demonstrates that conservative fluid alone can attenuate the age associated increase in ventilator associated mortality. PMID:27188767

Ethical challenges in home mechanical ventilation: a secondary analysis.

PubMed

Dybwik, Knut; Nielsen, Erik Waage; Brinchmann, Berit Støre

2012-03-01

The aim of this study was to explore the ethical challenges in home mechanical ventilation based on a secondary analysis of qualitative empirical data. The data included perceptions of healthcare professionals in hospitals and community health services and family members of children and adults using home mechanical ventilation. The findings show that a number of ethical challenges, or dilemmas, arise at all levels in the course of treatment: deciding who should be offered home mechanical ventilation, respect for patient and family wishes, quality of life, dignity and equal access to home mechanical ventilation. Other challenges were the impacts home mechanical ventilation had on the patient, the family, the healthcare services and the allocation of resources. A better and broader understanding of these issues is crucial in order to improve the quality of care for both patient and family and assist healthcare professionals involved in home mechanical ventilation to make decisions for the good of the patient and his or her family.

Advanced Research Deposition System (ARDS) for processing CdTe solar cells

NASA Astrophysics Data System (ADS)

Barricklow, Keegan Corey

CdTe solar cells have been commercialized at the Gigawatt/year level. The development of volume manufacturing processes for next generation CdTe photovoltaics (PV) with higher efficiencies requires research systems with flexibility, scalability, repeatability and automation. The Advanced Research Deposition Systems (ARDS) developed by the Materials Engineering Laboratory (MEL) provides such a platform for the investigation of materials and manufacturing processes necessary to produce the next generation of CdTe PV. Limited by previous research systems, the ARDS was developed to provide process and hardware flexibility, accommodating advanced processing techniques, and capable of producing device quality films. The ARDS is a unique, in-line process tool with nine processing stations. The system was designed, built and assembled at the Materials Engineering Laboratory. Final assembly, startup, characterization and process development are the focus of this research. Many technical challenges encountered during the startup of the ARDS were addressed in this research. In this study, several hardware modifications needed for the reliable operation of the ARDS were designed, constructed and successfully incorporated into the ARDS. The effect of process condition on film properties for each process step was quantified. Process development to achieve 12% efficient baseline solar cell required investigation of discrete processing steps, troubleshooting process variation, and developing performance correlations. Subsequent to this research, many advances have been demonstrated with the ARDS. The ARDS consistently produces devices of 12% +/-.5% by the process of record (POR). The champion cell produced to date utilizing the ARDS has an efficiency of 16.2% on low cost commercial sodalime glass and utilizes advanced films. The ARDS has enabled investigation of advanced concepts for processing CdTe devices including, Plasma Cleaning, Plasma Enhanced Closed Space Sublimation (PECSS), Electron Reflector (ER) using Cd1-xMgxTe (CMT) structure and alternative device structures. The ARDS has been instrumental in the collaborative research with many institutions.

Mortality Predictors in Acute Respiratory Distress Syndrome Renal Transplant Recipients With ESKAPE/rESKAPE Pneumonia.

PubMed

Chu, L; Ye, Q F; Wan, Q Q; Zhou, J D

2015-10-01

A sustained immunosuppressive state in renal transplant recipients is a factor that can contribute to increased incidence of acute respiratory distress syndrome (ARDS) due to pneumonia. ARDS renal recipients with ESKAPE (E. faecium, S. aureus, K. pneumoniae, A. baumannii, P. aeruginosa, and Enterobacter spp.) pneumonia are probably related to high morbidity and mortality. We therefore sought to investigate the frequency of ESKAPE and resistant ESKAPE (rESKAPE) pathogens isolated from respiratory tract specimens of renal recipients with ARDS and determine the risk factors for mortality. A retrospective analysis of ARDS renal recipients with ESKAPE/rESKAPE pneumonia was reviewed. Multiple logistic regression analysis was conducted to identify the independent risk factors associated with infection-related mortality. During the study period, 88 ESKAPE pathogens obtained from respiratory tract specimens of 54 ARDS renal recipients were documented including 33 A. baumannii, 24 P. aeruginosa, 17 S. aureus, 6 K. pneumoniae, 8 Enterobacter species, and 0 E. Faecium. Among these ESKAPE organisms, 61.4% (54/88) were antimicrobial resistant. The risk factors for mortality independently associated with ARDS renal recipients with ESKAPE pneumonia were severe ARDS (odds ratio [OR] 4.3 (95% confidence interval [CI] 1.1-16.4), P = .032), serum creatinine level >1.5 mg/dL (OR 4.2 95% CI (1.0-17.9), P = .05) and body temperature less than 38°C (OR 5.0 (95% CI 1.3-19.6), P = .02) at ARDS onset. The independent determinants of mortality were associated with ARDS renal recipients with rESKAPE pneumonia were serum creatinine level >1.5 mg/dL (OR 13.7, 95% CI 1.3-142.1, P = .028) and body temperature less than 38°C (OR 5.5 (95% CI 1.1-26.6) at ARDS onset, P = .035). The majority of EPKAPE isolates were antimicrobial resistant. Mortality in ARDS renal recipients with ESKAPE/rESKAPE pneumonia was associated with the severity of ARDS, elevated serum creatinine level, or depressed febrile response at ARDS onset. Copyright © 2015 Elsevier Inc. All rights reserved.

Mechanical ventilator - infants

MedlinePlus

... this page: //medlineplus.gov/ency/article/007240.htm Mechanical ventilator - infants To use the sharing features on this page, please enable JavaScript. A mechanical ventilator is a machine that assists with breathing. ...

Mechanical ventilation with lower tidal volumes and positive end-expiratory pressure prevents pulmonary inflammation in patients without preexisting lung injury.

PubMed

Wolthuis, Esther K; Choi, Goda; Dessing, Mark C; Bresser, Paul; Lutter, Rene; Dzoljic, Misa; van der Poll, Tom; Vroom, Margreeth B; Hollmann, Markus; Schultz, Marcus J

2008-01-01

Mechanical ventilation with high tidal volumes aggravates lung injury in patients with acute lung injury or acute respiratory distress syndrome. The authors sought to determine the effects of short-term mechanical ventilation on local inflammatory responses in patients without preexisting lung injury. Patients scheduled to undergo an elective surgical procedure (lasting > or = 5 h) were randomly assigned to mechanical ventilation with either higher tidal volumes of 12 ml/kg ideal body weight and no positive end-expiratory pressure (PEEP) or lower tidal volumes of 6 ml/kg and 10 cm H2O PEEP. After induction of anesthesia and 5 h thereafter, bronchoalveolar lavage fluid and/or blood was investigated for polymorphonuclear cell influx, changes in levels of inflammatory markers, and nucleosomes. Mechanical ventilation with lower tidal volumes and PEEP (n = 21) attenuated the increase of pulmonary levels of interleukin (IL)-8, myeloperoxidase, and elastase as seen with higher tidal volumes and no PEEP (n = 19). Only for myeloperoxidase, a difference was found between the two ventilation strategies after 5 h of mechanical ventilation (P < 0.01). Levels of tumor necrosis factor alpha, IL-1alpha, IL-1beta, IL-6, macrophage inflammatory protein 1alpha, and macrophage inflammatory protein 1beta in the bronchoalveolar lavage fluid were not affected by mechanical ventilation. Plasma levels of IL-6 and IL-8 increased with mechanical ventilation, but there were no differences between the two ventilation groups. The use of lower tidal volumes and PEEP may limit pulmonary inflammation in mechanically ventilated patients without preexisting lung injury. The specific contribution of both lower tidal volumes and PEEP on the protective effects of the lung should be further investigated.

Epidemiology of Noninvasive Ventilation in Pediatric Cardiac ICUs.

PubMed

Romans, Ryan A; Schwartz, Steven M; Costello, John M; Chanani, Nikhil K; Prodhan, Parthak; Gazit, Avihu Z; Smith, Andrew H; Cooper, David S; Alten, Jeffrey; Mistry, Kshitij P; Zhang, Wenying; Donohue, Janet E; Gaies, Michael

2017-10-01

To describe the epidemiology of noninvasive ventilation therapy for patients admitted to pediatric cardiac ICUs and to assess practice variation across hospitals. Retrospective cohort study using prospectively collected clinical registry data. Pediatric Cardiac Critical Care Consortium clinical registry. Patients admitted to cardiac ICUs at PC4 hospitals. None. We analyzed all cardiac ICU encounters that included any respiratory support from October 2013 to December 2015. Noninvasive ventilation therapy included high flow nasal cannula and positive airway pressure support. We compared patient and, when relevant, perioperative characteristics of those receiving noninvasive ventilation to all others. Subgroup analysis was performed on neonates and infants undergoing major cardiovascular surgery. To examine duration of respiratory support, we created a casemix-adjustment model and calculated adjusted mean durations of total respiratory support (mechanical ventilation + noninvasive ventilation), mechanical ventilation, and noninvasive ventilation. We compared adjusted duration of support across hospitals. The cohort included 8,940 encounters from 15 hospitals: 3,950 (44%) received noninvasive ventilation and 72% were neonates and infants. Medical encounters were more likely to include noninvasive ventilation than surgical. In surgical neonates and infants, 2,032 (55%) received postoperative noninvasive ventilation. Neonates, extracardiac anomalies, single ventricle, procedure complexity, preoperative respiratory support, mechanical ventilation duration, and postoperative disease severity were associated with noninvasive ventilation therapy (p < 0.001 for all). Across hospitals, noninvasive ventilation use ranged from 32% to 65%, and adjusted mean noninvasive ventilation duration ranged from 1 to 4 days (3-d observed mean). Duration of total adjusted respiratory support was more strongly correlated with duration of mechanical ventilation compared with noninvasive ventilation (Pearson r = 0.93 vs 0.71, respectively). Noninvasive ventilation use is common in cardiac ICUs, especially in patients admitted for medical conditions, infants, and those undergoing high complexity surgery. We observed wide variation in noninvasive ventilation use across hospitals, though the primary driver of total respiratory support time seems to be duration of mechanical ventilation.

Recommendations for mechanical ventilation of critically ill children from the Paediatric Mechanical Ventilation Consensus Conference (PEMVECC).

PubMed

Kneyber, Martin C J; de Luca, Daniele; Calderini, Edoardo; Jarreau, Pierre-Henri; Javouhey, Etienne; Lopez-Herce, Jesus; Hammer, Jürg; Macrae, Duncan; Markhorst, Dick G; Medina, Alberto; Pons-Odena, Marti; Racca, Fabrizio; Wolf, Gerhard; Biban, Paolo; Brierley, Joe; Rimensberger, Peter C

2017-12-01

Much of the common practice in paediatric mechanical ventilation is based on personal experiences and what paediatric critical care practitioners have adopted from adult and neonatal experience. This presents a barrier to planning and interpretation of clinical trials on the use of specific and targeted interventions. We aim to establish a European consensus guideline on mechanical ventilation of critically children. The European Society for Paediatric and Neonatal Intensive Care initiated a consensus conference of international European experts in paediatric mechanical ventilation to provide recommendations using the Research and Development/University of California, Los Angeles, appropriateness method. An electronic literature search in PubMed and EMBASE was performed using a combination of medical subject heading terms and text words related to mechanical ventilation and disease-specific terms. The Paediatric Mechanical Ventilation Consensus Conference (PEMVECC) consisted of a panel of 15 experts who developed and voted on 152 recommendations related to the following topics: (1) general recommendations, (2) monitoring, (3) targets of oxygenation and ventilation, (4) supportive measures, (5) weaning and extubation readiness, (6) normal lungs, (7) obstructive diseases, (8) restrictive diseases, (9) mixed diseases, (10) chronically ventilated patients, (11) cardiac patients and (12) lung hypoplasia syndromes. There were 142 (93.4%) recommendations with "strong agreement". The final iteration of the recommendations had none with equipoise or disagreement. These recommendations should help to harmonise the approach to paediatric mechanical ventilation and can be proposed as a standard-of-care applicable in daily clinical practice and clinical research.

Metabolic Requirement of Septic Shock Patients Before and After Liberation From Mechanical Ventilation.

PubMed

Lee, Peggy Siu-Pik; Lee, Kar Lung; Betts, James A; Law, Kin Ip

2017-08-01

This study identified the difference in energy expenditure and substrate utilization of patients during and upon liberation from mechanical ventilation. Patients under intensive care who were diagnosed with septic shock and dependent on mechanical ventilation were recruited. Indirect calorimetry measurements were performed during and upon liberation from mechanical ventilation. Thirty-five patients were recruited (20 men and 15 women; mean age, 69 ± 10 years). Measured energy expenditures during ventilation and upon liberation were 2090 ± 489 kcal·d -1 and 1910 ± 579 kcal·d -1 , respectively ( P < .05). Energy intake was provided at 1148 ± 495 kcal·d -1 and differed significantly from all measured energy expenditures ( P < .05). Mean carbohydrate utilization was 0.19 ± 0.1 g·min -1 when patients were on mechanical ventilation compared with 0.15 ± 0.09 g·min -1 upon liberation ( P < .05). Mean lipid oxidation was 0.08 ± 0.05 g·min -1 during and 0.09 ± 0.07 g·min -1 upon liberation from mechanical ventilation ( P > .05). Measured energy expenditure was higher during than upon liberation from mechanical ventilation. This could be the increase in work of breathing from the continuous positive pressure support, repeated weaning cycles from mechanical ventilation, and/or the asynchronization between patients' respiration and ventilator support. Future studies should examine whether more appropriately matching energy expenditure with energy intake would promote positive health outcomes.

Tracheostomy and invasive mechanical ventilation in amyotrophic lateral sclerosis: decision-making factors and survival analysis.

PubMed

Kimura, Fumiharu

2016-04-28

Invasive and/or non-invasive mechanical ventilation are most important options of respiratory management in amyotrophic lateral sclerosis. We evaluated the frequency, clinical characteristics, decision-making factors about ventilation and survival analysis of 190 people with amyotrophic lateral sclerosis patients from 1990 until 2013. Thirty-one percentage of patients underwent tracheostomy invasive ventilation with the rate increasing more than the past 20 years. The ratio of tracheostomy invasive ventilation in patients >65 years old was significantly increased after 2000 (25%) as compared to before (10%). After 2010, the standard use of non-invasive ventilation showed a tendency to reduce the frequency of tracheostomy invasive ventilation. Mechanical ventilation prolonged median survival (75 months in tracheostomy invasive ventilation, 43 months in non-invasive ventilation vs natural course, 32 months). The life-extending effects by tracheostomy invasive ventilation were longer in younger patients ≤65 years old at the time of ventilation support than in older patients. Presence of partners and care at home were associated with better survival. Following factors related to the decision to perform tracheostomy invasive ventilation: patients ≤65 years old: greater use of non-invasive ventilation: presence of a spouse: faster tracheostomy: higher progression rate; and preserved motor functions. No patients who underwent tracheostomy invasive ventilation died from a decision to withdraw mechanical ventilation. The present study provides factors related to decision-making process and survival after tracheostomy and help clinicians and family members to expand the knowledge about ventilation.

Rationale and study design of PROVHILO - a worldwide multicenter randomized controlled trial on protective ventilation during general anesthesia for open abdominal surgery.

PubMed

Hemmes, Sabrine N T; Severgnini, Paolo; Jaber, Samir; Canet, Jaume; Wrigge, Hermann; Hiesmayr, Michael; Tschernko, Edda M; Hollmann, Markus W; Binnekade, Jan M; Hedenstierna, Göran; Putensen, Christian; de Abreu, Marcelo Gama; Pelosi, Paolo; Schultz, Marcus J

2011-05-06

Post-operative pulmonary complications add to the morbidity and mortality of surgical patients, in particular after general anesthesia >2 hours for abdominal surgery. Whether a protective mechanical ventilation strategy with higher levels of positive end-expiratory pressure (PEEP) and repeated recruitment maneuvers; the "open lung strategy", protects against post-operative pulmonary complications is uncertain. The present study aims at comparing a protective mechanical ventilation strategy with a conventional mechanical ventilation strategy during general anesthesia for abdominal non-laparoscopic surgery. The PROtective Ventilation using HIgh versus LOw positive end-expiratory pressure ("PROVHILO") trial is a worldwide investigator-initiated multicenter randomized controlled two-arm study. Nine hundred patients scheduled for non-laparoscopic abdominal surgery at high or intermediate risk for post-operative pulmonary complications are randomized to mechanical ventilation with the level of PEEP at 12 cmH(2)O with recruitment maneuvers (the lung-protective strategy) or mechanical ventilation with the level of PEEP at maximum 2 cmH(2)O without recruitment maneuvers (the conventional strategy). The primary endpoint is any post-operative pulmonary complication. The PROVHILO trial is the first randomized controlled trial powered to investigate whether an open lung mechanical ventilation strategy in short-term mechanical ventilation prevents against postoperative pulmonary complications. ISRCTN: ISRCTN70332574.

[Monitorization of respiratory mechanics in the ventilated patient].

PubMed

García-Prieto, E; Amado-Rodríguez, L; Albaiceta, G M

2014-01-01

Monitoring during mechanical ventilation allows the measurement of different parameters of respiratory mechanics. Accurate interpretation of these data can be useful for characterizing the situation of the different components of the respiratory system, and for guiding ventilator settings. In this review, we describe the basic concepts of respiratory mechanics, their interpretation, and their potential use in fine-tuning mechanical ventilation. Copyright © 2013 Elsevier España, S.L. y SEMICYUC. All rights reserved.

Trends in mechanical ventilation: are we ventilating our patients in the best possible way?

PubMed Central

Veneroni, Chiara; Farre’, Ramon

2017-01-01

This review addresses how the combination of physiology, medicine and engineering principles contributed to the development and advancement of mechanical ventilation, emphasising the most urgent needs for improvement and the most promising directions of future development. Several aspects of mechanical ventilation are introduced, highlighting on one side the importance of interdisciplinary research for further development and, on the other, the importance of training physicians sufficiently on the technological aspects of modern devices to exploit properly the great complexity and potentials of this treatment. Educational aims To learn how mechanical ventilation developed in recent decades and to provide a better understanding of the actual technology and practice. To learn how and why interdisciplinary research and competences are necessary for providing the best ventilation treatment to patients. To understand which are the most relevant technical limitations in modern mechanical ventilators that can affect their performance in delivery of the treatment. To better understand and classify ventilation modes. To learn the classification, benefits, drawbacks and future perspectives of automatic ventilation tailoring algorithms. PMID:28620428

Criteria for Postoperative Mechanical Ventilation After Thymectomy in Patients With Myasthenia Gravis: A Retrospective Analysis.

PubMed

Chigurupati, Keerthi; Gadhinglajkar, Shrinivas; Sreedhar, Rupa; Nair, Muraleedharan; Unnikrishnan, Madathipat; Pillai, Manjusha

2018-02-01

To determine the criteria for postoperative mechanical ventilation after thymectomy in patients with Myasthenia Gravis. Retrospective study. Teritiary care centre. 77 Myasthenia gravis patients operated for thymectomy were studied. After obtaining clearance from Institutional ethics committee, medical records of 77 patients with MG, who were operated for thymectomy between January 2005 and December 2015 were reviewed in a retrospective manner. Perioperative variables collected from the patient records were demographic data, duration of the disease, Osserman and Genkin classification, Anti-acetylcholine antibody (AChR) positivity, preoperative daily dose of drug, history of preoperative myasthenic crisis, preoperative vital capacity, technique of anesthesia, drugs used for anesthesia, perioperative complications, and duration of postoperative mechanical ventilation. The patients were divided into two groups, group I and group II consisting of those who required postoperative ventilation for < 300 minutes and > 300 minutes, respectively. The determinants of prolonged postoperative ventilation were studied. The requirement of mechanical ventilation was higher in patients with higher Osserman's grade of myasthenia gravis. Duration of the disease had no effect on the duration of mechanical ventilation in myasthenic patients post thymectomy (p = 0.89). The patients with a preoperative history of myasthenic crisis had a requirement for prolonged mechanical ventilation (p=0.03). Patients with preoperative vital capacity < 2.9 litres and preoperative CT scan showing thymoma had a requirement for prolonged mechanical ventilation with p values < 0.001 and 0.035, respectively. Patients who showed positivity for anti-acetylcholine antibodies had a prolonged mechanical ventilation (p=0.026). Preoperative dose of pyridostigmine and the choice of continuation or discontinuation of antcholinesterases on the day of surgery had no influence on the duration of mechanical ventilation (p value of 0.19 and 0.36 respectively). Epidural analgesia intra and postoperatively significantly reduced the requirement of mechanical ventilation (p=0.006). The predictors of postoperative ventilation in myasthenic patients undergoing thymectomy as per our study are: 1. Grade of myasthenia; 2. History of preoperative myasthenic crisis; 3. Anti-acetylcholine antibodies positivity; 4. Presence of thymoma; and 5. a vital capacity < 2.9 litres. Use of thoracic epidural as a part of combined anesthetic technique helps to reduce the need of mechanical ventilation in these patients. Copyright © 2018 Elsevier Inc. All rights reserved.

The leukocyte-stiffening property of plasma in early acute respiratory distress syndrome (ARDS) revealed by a microfluidic single-cell study: the role of cytokines and protection with antibodies.

PubMed

Preira, Pascal; Forel, Jean-Marie; Robert, Philippe; Nègre, Paulin; Biarnes-Pelicot, Martine; Xeridat, Francois; Bongrand, Pierre; Papazian, Laurent; Theodoly, Olivier

2016-01-12

Leukocyte-mediated pulmonary inflammation is a key pathophysiological mechanism involved in acute respiratory distress syndrome (ARDS). Massive sequestration of leukocytes in the pulmonary microvasculature is a major triggering event of the syndrome. We therefore investigated the potential role of leukocyte stiffness and adhesiveness in the sequestration of leukocytes in microvessels. This study was based on in vitro microfluidic assays using patient sera. Cell stiffness was assessed by measuring the entry time (ET) of a single cell into a microchannel with a 6 × 9-μm cross-section under a constant pressure drop (ΔP = 160 Pa). Primary neutrophils and monocytes, as well as the monocytic THP-1 cell line, were used. Cellular adhesiveness to human umbilical vein endothelial cells was examined using the laminar flow chamber method. We compared the properties of cells incubated with the sera of healthy volunteers (n = 5), patients presenting with acute cardiogenic pulmonary edema (ACPE; n = 6), and patients with ARDS (n = 22), of whom 13 were classified as having moderate to severe disease and the remaining 9 as having mild disease. Rapid and strong stiffening of primary neutrophils and monocytes was induced within 30 minutes (mean ET >50 seconds) by sera from the ARDS group compared with both the healthy subjects and the ACPE groups (mean ET <1 second) (p < 0.05). Systematic measurements with the THP-1 cell line allowed for the establishment of a strong correlation between stiffening and the severity of respiratory status (mean ET 0.82 ± 0.08 seconds for healthy subjects, 1.6 ± 1.0 seconds for ACPE groups, 10.5 ± 6.1 seconds for mild ARDS, and 20.0 ± 8.1 seconds for moderate to severe ARDS; p < 0.05). Stiffening correlated with the cytokines interleukin IL-1β, IL-8, tumor necrosis factor TNF-α, and IL-10 but not with interferon-γ, transforming growth factor-β, IL-6, or IL-17. Strong stiffening was induced by IL-1β, IL-8, and TNF-α but not by IL-10, and incubations with sera and blocking antibodies against IL-1β, IL-8, or TNF-α significantly diminished the stiffening effect of serum. In contrast, the measurements of integrin expression (CD11b, CD11a, CD18, CD49d) and leukocyte-endothelium adhesion showed a weak and slow response after incubation with the sera of patients with ARDS (several hours), suggesting a lesser role of leukocyte adhesiveness compared with leukocyte stiffness in early ARDS. The leukocyte stiffening induced by cytokines in the sera of patients might play a role in the sequestration of leukocytes in the lung capillary beds during early ARDS. The inhibition of leukocyte stiffening with blocking antibodies might inspire future therapeutic strategies.

Effects of positive end-expiratory pressure and recruitment maneuvers in a ventilator-induced injury mouse model

PubMed Central

Franzi, Lisa M.; Linderholm, Angela L.; Last, Jerold A.; Adams, Jason Y.; Harper, Richart W.

2017-01-01

Background Positive-pressure mechanical ventilation is an essential therapeutic intervention, yet it causes the clinical syndrome known as ventilator-induced lung injury. Various lung protective mechanical ventilation strategies have attempted to reduce or prevent ventilator-induced lung injury but few modalities have proven effective. A model that isolates the contribution of mechanical ventilation on the development of acute lung injury is needed to better understand biologic mechanisms that lead to ventilator-induced lung injury. Objectives To evaluate the effects of positive end-expiratory pressure and recruitment maneuvers in reducing lung injury in a ventilator-induced lung injury murine model in short- and longer-term ventilation. Methods 5–12 week-old female BALB/c mice (n = 85) were anesthetized, placed on mechanical ventilation for either 2 hrs or 4 hrs with either low tidal volume (8 ml/kg) or high tidal volume (15 ml/kg) with or without positive end-expiratory pressure and recruitment maneuvers. Results Alteration of the alveolar-capillary barrier was noted at 2 hrs of high tidal volume ventilation. Standardized histology scores, influx of bronchoalveolar lavage albumin, proinflammatory cytokines, and absolute neutrophils were significantly higher in the high-tidal volume ventilation group at 4 hours of ventilation. Application of positive end-expiratory pressure resulted in significantly decreased standardized histology scores and bronchoalveolar absolute neutrophil counts at low- and high-tidal volume ventilation, respectively. Recruitment maneuvers were essential to maintain pulmonary compliance at both 2 and 4 hrs of ventilation. Conclusions Signs of ventilator-induced lung injury are evident soon after high tidal volume ventilation (as early as 2 hours) and lung injury worsens with longer-term ventilation (4 hrs). Application of positive end-expiratory pressure and recruitment maneuvers are protective against worsening VILI across all time points. Dynamic compliance can be used guide the frequency of recruitment maneuvers to help ameloriate ventilator-induced lung injury. PMID:29112971

Artificial humidification for the mechanically ventilated patient.

PubMed

Selvaraj, N

Caring for patients who are mechanically ventilated poses many challenges for critical care nurses. It is important to humidify the patient's airways artificially to prevent complications such as ventilator-associated pneumonia. There is no gold standard to determine which type of humidification is best for patients who are artificially ventilated. This article provides an overview of commonly used artificial humidification for mechanically ventilated patients and discusses nurses' responsibilities in caring for patients receiving artificial humidification.

Non-invasive mechanical ventilation and mortality in elderly immunocompromised patients hospitalized with pneumonia: a retrospective cohort study.

PubMed

Johnson, Christopher S; Frei, Christopher R; Metersky, Mark L; Anzueto, Antonio R; Mortensen, Eric M

2014-01-27

Mortality after pneumonia in immunocompromised patients is higher than for immunocompetent patients. The use of non-invasive mechanical ventilation for patients with severe pneumonia may provide beneficial outcomes while circumventing potential complications associated with invasive mechanical ventilation. The aim of our study was to determine if the use of non-invasive mechanical ventilation in elderly immunocompromised patients with pneumonia is associated with higher all-cause mortality. In this retrospective cohort study, data were obtained from the Department of Veterans Affairs administrative databases. We included veterans age ≥65 years who were immunocompromised and hospitalized due to pneumonia. Multilevel logistic regression analysis was used to determine the relationship between the use of invasive versus non-invasive mechanical ventilation and 30-day and 90-day mortality. Of 1,946 patients in our cohort, 717 received non-invasive mechanical ventilation and 1,229 received invasive mechanical ventilation. There was no significant association between all-cause 30-day mortality and non-invasive versus invasive mechanical ventilation in our adjusted model (odds ratio (OR) 0.85, 95% confidence interval (CI) 0.66-1.10). However, those patients who received non-invasive mechanical ventilation had decreased 90-day mortality (OR 0.66, 95% CI 0.52-0.84). Additionally, receipt of guideline-concordant antibiotics in our immunocompromised cohort was significantly associated with decreased odds of 30-day mortality (OR 0.31, 95% CI 0.24-0.39) and 90-day mortality (OR 0.41, 95% CI 0.31-0.53). Our findings suggest that physicians should consider the use of non-invasive mechanical ventilation, when appropriate, for elderly immunocompromised patients hospitalized with pneumonia.