The role of complement system in septic shock.

PubMed

Charchaflieh, Jean; Wei, Jiandong; Labaze, Georges; Hou, Yunfang Joan; Babarsh, Benjamin; Stutz, Helen; Lee, Haekyung; Worah, Samrat; Zhang, Ming

2012-01-01

Septic shock is a critical clinical condition with a high mortality rate. A better understanding of the underlying mechanisms is important to develop effective therapies. Basic and clinical studies suggest that activation of complements in the common cascade, for example, complement component 3 (C3) and C5, is involved in the development of septic shock. The involvement of three upstream complement pathways in septic shock is more complicated. Both the classical and alternative pathways appear to be activated in septic shock, but the alternative pathway may be activated earlier than the classical pathway. Activation of these two pathways is essential to clear endotoxin. Recent investigations have shed light on the role of lectin complement pathway in septic shock. Published reports suggest a protective role of mannose-binding lectin (MBL) against sepsis. Our preliminary study of MBL-associated serine protease-2 (MASP-2) in septic shock patients indicated that acute decrease of MASP-2 in the early phase of septic shock might correlate with in-hospital mortality. It is unknown whether excessive activation of these three upstream complement pathways may contribute to the detrimental effects in septic shock. This paper also discusses additional complement-related pathogenic mechanisms and intervention strategies for septic shock.

Pathogens and outcomes in pediatric septic shock patients supported by extracorporeal membrane oxygenation.

PubMed

Chang, Tu-Hsuan; Wu, En-Ting; Lu, Chun-Yi; Huang, Shu-Chien; Yang, Tzu-I; Wang, Ching-Chia; Chen, Jong-Min; Lee, Ping-Ing; Huang, Li-Min; Chang, Luan-Yin

2017-08-04

Refractory septic shock is the leading cause of mortality in children. There is limited evidence to support extracorporeal membrane oxygenation (ECMO) use in pediatric septic shock. We described the etiology and outcomes of septic patients in our institution and attempted to find predictive factors. We retrospectively reviewed 55 pediatric patients with septic shock who required ECMO support in a tertiary medical center from 2008 to 2015. Septic shock was defined as culture proved or clinical suspected sepsis with hypotension or end-organ hypoperfusion. ECMO would be applied when pediatric advanced life support steps were performed thoroughly without clinical response. Patient's demographics, laboratory parameters before and after ECMO, and outcomes were analyzed. Among 55 children with ECMO support, 31% of them survived on discharge. For 25 immunocompromised patients, causal pathogens were found in 17 patients: 7 due to bacteremia, 9 with preexisting virus infections and one with invasive fungal infection. Among 30 previously healthy patients, causal pathogens were found in 18 patients: 10 due to bacteremia (the most common was pneumococcus), 7 with preexisting virus infections including influenza (n = 4), adenovirus (n = 2), RSV, and 1 patient had mixed virus and bacterial infections. Predictive factors associated with death were arterial blood gas pH, CO 2 and Glasgow Coma Scale (p < 0.05). SOFA score was a valuable predictive scoring system for outcome prediction (p < 0.05). Pediatric patients with refractory septic shock had high mortality rate and ECMO could be used as a rescue modality, and SOFA score could be applied to predict outcomes. Copyright © 2017. Published by Elsevier B.V.

Fulminant septic shock caused by Capnocytophaga canimorsus in Italy: Case report.

PubMed

Piccinelli, Giorgio; Caccuri, Francesca; De Peri, Elena; Tironi, Andrea; Odolini, Silvia; Notarangelo, Lucia Dora; Gargiulo, Franco; Castelli, Francesco; Latronico, Nicola; Facchetti, Fabio; Caruso, Arnaldo

2018-05-03

Capnocytophaga canimorsus infection was recently recognized as a zoonosis. We report the first case of fulminant septic shock in Italy caused by this pathogen. The patient, with a history of splenectomy, died at the main hospital in Brescia with a presumptive diagnosis of sepsis. PCR and sequencing on post mortem samples confirmed C. canimorsus as a causative organism. Our purpose is to alert medical professionals to the virulence of C. canimorsus in asplenic and immunocompromised patients. Copyright © 2018 The Author(s). Published by Elsevier Ltd.. All rights reserved.

Raoultella planticola bacteremia-induced fatal septic shock following burn injury.

PubMed

Yumoto, Tetsuya; Naito, Hiromichi; Ihoriya, Hiromi; Tsukahara, Kohei; Ota, Tomoyuki; Watanabe, Toshiyuki; Nakao, Atsunori

2018-05-04

Raoultella planticola, a Gram-negative, aerobic bacillus commonly isolated from soil and water, rarely causes invasive infections in humans. Septic shock from R. planticola after burn injury has not been previously reported. A 79-year-old male was admitted to the emergency intensive care unit after extensive flame burn injury. He accidently caught fire while burning trash and plunged into a nearby tank filled with contaminated rainwater to extinguish the fire. The patient developed septic shock on day 10. The blood culture detected R. planticola, which was identified using the VITEK-2 biochemical identification system. Although appropriate antibiotic treatment was continued, the patient died on day 12. Clinicians should be aware of fatal infections in patients with burn injury complicated by exposure to contaminated water.

Plasma levels of F-actin and F:G-actin ratio as potential new biomarkers in patients with septic shock.

PubMed

Belsky, Justin B; Morris, Daniel C; Bouchebl, Ralph; Filbin, Michael R; Bobbitt, Kevin R; Jaehne, Anja K; Rivers, Emanuel P

2016-01-01

To compare plasma levels of F-actin, G-actin and thymosin beta 4 (TB4) in humans with septic shock, noninfectious systemic inflammatory response syndrome (SIRS) and healthy controls. F-actin was significantly elevated in septic shock as compared with noninfectious SIRS and healthy controls. G-actin levels were greatest in the noninfectious SIRS group but significantly elevated in septic shock as compared with healthy controls. TB4 was not detectable in the septic shock or noninfectious SIRS group above the assay's lowest detection range (78 ng/ml). F-actin is significantly elevated in patients with septic shock as compared with noninfectious SIRS. F-actin and the F:G-actin ratio are potential biomarkers for the diagnosis of septic shock.

Effects of Carnosine (Beta-Alanyl-L-Histidine) in an Experimental Rat Model of Acute Kidney Injury Due to Septic Shock

PubMed Central

Sahin, Sabiha; Donmez, Dilek Burukoglu

2018-01-01

Background Acute kidney injury (AKI) secondary to sepsis is a major cause of morbidity and mortality in the human intensive care unit (ICU). Kidney function and the histological findings of AKI were investigated in an experimental rat model with sepsis induced by cecal ligation and puncture (CLP) and compared with and without treatment with carnosine (beta-alanyl-L-histidine). Material/Methods Twenty-four Sprague-Dawley rats were randomly divided into three groups consisting eight rats in each: Group 1 – control; Group 2 – septic shock; and Group 3 – septic shock treated with carnosine. Femoral vein and artery catheterization were applied in all rats. Rats in Group 1 underwent laparotomy and catheterization. The other two groups with septic shock underwent laparotomy, CLP, catheterization, and bladder cannulation. Rats in Group 3 received an intraperitoneal (IP) injection of 250 mg/kg carnosine, 60 min following CLP. Rats were monitored for blood pressure, pulse rate, and body temperature to assess responses to postoperative sepsis, and 10 mL/kg saline replacement was administered. Twenty-four hours following CLP, rats were sacrificed, and blood and renal tissue samples were collected. Results Statistically significant improvements were observed in kidney function, tissue and serum malondialdehyde levels, routine blood values, biochemical indices, and in histopathological findings in rats in Group 3 who were treated with carnosine, compared with Group 2 exposed to septic shock without carnosine treatment. Conclusions Carnosine (beta-alanyl-L-histidine) has been shown to have beneficial effects in reducing AKI due to septic shock in a rat model of septicemia. PMID:29334583

Early outcome of early-goal directed therapy for patients with sepsis or septic shock: a systematic review and meta-analysis of randomized controlled trials.

PubMed

Chen, Xiaofan; Zhu, Weifeng; Tan, Jing; Nie, Heyun; Liu, Liangming; Yan, Dongmei; Zhou, Xu; Sun, Xin

2017-04-18

Various trials and meta-analyses have reported conflicting results concerning the application of early goal-directed therapy (EGDT) for sepsis and septic shock. The aim of this study was to update the evidence by performing a systematic review and meta-analysis. Multiple databases were searched from initial through August, 2016 for randomized controlled trials (RCTs) which investigated the associations between the use of EGDT and mortality in patients with sepsis or septic shock. Meta-analysis was performed using random-effects model and heterogeneity was examined through subgroup analyses. The primary outcome of interest was patient all-cause mortality including hospital or ICU mortality. Seventeen RCTs including 6207 participants with 3234 in the EGDT group and 2973 in the control group were eligible for this study. Meta-analysis showed that EGDT did not significantly reduce hospital or intensive care unit (ICU) mortality (relative risk [RR] 0.89, 95% CI 0.78 to 1.02) compared with control group for patients with sepsis or septic shock. The findings of subgroup analyses stratified by study region, number of research center, year of enrollment, clinical setting, sample size, timing of EGDT almost remained constant with that of the primary analysis. Our findings provide evidence that EGDT offers neutral survival effects for patients with sepsis or septic shock. Further meta-analyses based on larger well-designed RCTs or individual patient data meta-analysis are required to explore the survival benefits of EDGT in patients with sepsis or septic shock.

The Septic Shock 3.0 Definition and Trials: A Vasopressin and Septic Shock Trial Experience.

PubMed

Russell, James A; Lee, Terry; Singer, Joel; Boyd, John H; Walley, Keith R

2017-06-01

The Septic Shock 3.0 definition could alter treatment comparisons in randomized controlled trials in septic shock. Our first hypothesis was that the vasopressin versus norepinephrine comparison and 28-day mortality of patients with Septic Shock 3.0 definition (lactate > 2 mmol/L) differ from vasopressin versus norepinephrine and mortality in Vasopressin and Septic Shock Trial. Our second hypothesis was that there are differences in plasma cytokine levels in Vasopressin and Septic Shock Trial for lactate less than or equal to 2 versus greater than 2 mmol/L. Retrospective analysis of randomized controlled trial. Multicenter ICUs. We compared vasopressin-to-norepinephrine group 28- and 90-day mortality in Vasopressin and Septic Shock Trial in lactate subgroups. We measured 39 cytokines to compare patients with lactate less than or equal to 2 versus greater than 2 mmol/L. Patients with septic shock with lactate greater than 2 mmol/L or less than or equal to 2 mmol/L, randomized to vasopressin or norepinephrine. Concealed vasopressin (0.03 U/min.) or norepinephrine infusions. The Septic Shock 3.0 definition would have decreased sample size by about half. The 28- and 90-day mortality rates were 10-12 % higher than the original Vasopressin and Septic Shock Trial mortality. There was a significantly (p = 0.028) lower mortality with vasopressin versus norepinephrine in lactate less than or equal to 2 mmol/L but no difference between treatment groups in lactate greater than 2 mmol/L. Nearly all cytokine levels were significantly higher in patients with lactate greater than 2 versus less than or equal to 2 mmol/L. The Septic Shock 3.0 definition decreased sample size by half and increased 28-day mortality rates by about 10%. Vasopressin lowered mortality versus norepinephrine if lactate was less than or equal to 2 mmol/L. Patients had higher plasma cytokines in lactate greater than 2 versus less than or equal to 2 mmol/L, a brisker cytokine response to infection. The Septic Shock 3.0 definition and our findings have important implications for trial design in septic shock.

Septic pulmonary embolism caused by a Klebsiella pneumoniae liver abscess: clinical characteristics, imaging findings, and clinical courses

PubMed Central

Chou, Deng-Wei; Wu, Shu-Ling; Chung, Kuo-Mou; Han, Shu-Chen

2015-01-01

OBJECTIVES: Septic pulmonary embolism caused by a Klebsiella (K.) pneumoniae liver abscess is rare but can cause considerable morbidity and mortality. However, clinical information regarding this condition is limited. This study was conducted to elucidate the full disease spectrum to improve its diagnosis and treatment. METHOD: We reviewed the clinical characteristics, imaging findings, and clinical courses of 14 patients diagnosed with septic pulmonary embolism caused by a K. pneumoniae liver abscess over a period of 9 years. RESULTS: The two most prevalent symptoms were fever and shortness of breath. Computed tomography findings included a feeding vessel sign (79%), nodules with or without cavities (79%), pleural effusions (71%), peripheral wedge-shaped opacities (64%), patchy ground-glass opacities (50%), air bronchograms within a nodule (36%), consolidations (21%), halo signs (14%), and lung abscesses (14%). Nine (64%) of the patients developed severe complications and required intensive care. According to follow-up chest radiography, the infiltrates and consolidations were resolved within two weeks, and the nodular opacities were resolved within one month. Two (14%) patients died of septic shock; one patient had metastatic meningitis, and the other had metastatic pericarditis. CONCLUSION: The clinical presentations ranged from insidious illness with fever and respiratory symptoms to respiratory failure and septic shock. A broad spectrum of imaging findings, ranging from nodules to multiple consolidations, was detected. Septic pulmonary embolism caused by a K. pneumoniae liver abscess combined with the metastatic infection of other vital organs confers a poor prognosis. PMID:26106957

Septic pulmonary embolism caused by a Klebsiella pneumoniae liver abscess: clinical characteristics, imaging findings, and clinical courses.

PubMed

Chou, Deng-Wei; Wu, Shu-Ling; Chung, Kuo-Mou; Han, Shu-Chen

2015-06-01

Septic pulmonary embolism caused by a Klebsiella (K.) pneumoniae liver abscess is rare but can cause considerable morbidity and mortality. However, clinical information regarding this condition is limited. This study was conducted to elucidate the full disease spectrum to improve its diagnosis and treatment. We reviewed the clinical characteristics, imaging findings, and clinical courses of 14 patients diagnosed with septic pulmonary embolism caused by a K. pneumoniae liver abscess over a period of 9 years. The two most prevalent symptoms were fever and shortness of breath. Computed tomography findings included a feeding vessel sign (79%), nodules with or without cavities (79%), pleural effusions (71%), peripheral wedge-shaped opacities (64%), patchy ground-glass opacities (50%), air bronchograms within a nodule (36%), consolidations (21%), halo signs (14%), and lung abscesses (14%). Nine (64%) of the patients developed severe complications and required intensive care. According to follow-up chest radiography, the infiltrates and consolidations were resolved within two weeks, and the nodular opacities were resolved within one month. Two (14%) patients died of septic shock; one patient had metastatic meningitis, and the other had metastatic pericarditis. The clinical presentations ranged from insidious illness with fever and respiratory symptoms to respiratory failure and septic shock. A broad spectrum of imaging findings, ranging from nodules to multiple consolidations, was detected. Septic pulmonary embolism caused by a K. pneumoniae liver abscess combined with the metastatic infection of other vital organs confers a poor prognosis.

Timing and causes of death in septic shock.

PubMed

Daviaud, Fabrice; Grimaldi, David; Dechartres, Agnès; Charpentier, Julien; Geri, Guillaume; Marin, Nathalie; Chiche, Jean-Daniel; Cariou, Alain; Mira, Jean-Paul; Pène, Frédéric

2015-12-01

Most studies about septic shock report a crude mortality rate that neither distinguishes between early and late deaths nor addresses the direct causes of death. We herein aimed to determine the modalities of death in septic shock. This was a 6-year (2008-2013) monocenter retrospective study. All consecutive patients diagnosed for septic shock within the first 48 h of intensive care unit (ICU) admission were included. Early and late deaths were defined as occurring within or after 3 days following ICU admission, respectively. The main cause of death in the ICU was determined from medical files. A multinomial logistic regression analysis using the status alive as the reference category was performed to identify the prognostic factors associated with early and late deaths. Five hundred forty-three patients were included, with a mean age of 66 ± 15 years and a high proportion (67 %) of comorbidities. The in-ICU and in-hospital mortality rates were 37.2 and 45 %, respectively. Deaths occurred early for 78 (32 %) and later on for 166 (68 %) patients in the ICU (n = 124) or in the hospital (n = 42). Early deaths were mainly attributable to intractable multiple organ failure related to the primary infection (82 %) and to mesenteric ischemia (6.4 %). In-ICU late deaths were directly related to end-of-life decisions in 29 % of patients and otherwise mostly related to ICU-acquired complications, including nosocomial infections (20.4 %) and mesenteric ischemia (16.6 %). Independent determinants of early death were age, malignancy, diabetes mellitus, no pathogen identification, and initial severity. Among 3-day survivors, independent risk factors for late death were age, cirrhosis, no pathogen identification, and previous corticosteroid treatment. Our study provides a comprehensive assessment of septic shock-related deaths. Identification of risk factors of early and late deaths may determine differential prognostic patterns.

Using terlipressin in a pediatric patient with septic shock resistant to catecholamines

PubMed Central

Erdogan, Seher; Bosnak, Mehmet

2017-01-01

Sepsis and septic shock are important causes of morbidity and mortality in critically ill children. The goal of treatment is to ensure adequate mean arterial pressure to maintain organ perfusion. The growing number of instances of peripheral vascular hyporeactivity to catecholamines has necessitated the search for alternative vasopressors. A 14-year-old boy had septic shock, with a high cardiac index and low systemic vascular resistance index (SVRI) measurements according to pulse contour analysis, despite treatment with dopamine, dobutamine, adrenaline, and noradrenaline infusions. A terlipressin (TP) 10 μg/kg intravenous bolus was administered, followed by a 1 μg/kg/minute continuous infusion. The response to TP treatment was assessed using pulse contour analysis. The mean arterial pressure and SVRI increased, and the cardiac index and heart rate decreased within 10 minutes after bolus administration of TP. Noradrenaline infusion could be reduced to 0.7 μg/kg/minute within 5 hours. The goal in presenting this case was to evaluate the vasoconstrictor effects of TP, a long-acting vasopressin analogue, in septic shock. PMID:29270582

Using terlipressin in a pediatric patient with septic shock resistant to catecholamines.

PubMed

Erdogan, Seher; Bosnak, Mehmet

2017-01-01

Sepsis and septic shock are important causes of morbidity and mortality in critically ill children. The goal of treatment is to ensure adequate mean arterial pressure to maintain organ perfusion. The growing number of instances of peripheral vascular hyporeactivity to catecholamines has necessitated the search for alternative vasopressors. A 14-year-old boy had septic shock, with a high cardiac index and low systemic vascular resistance index (SVRI) measurements according to pulse contour analysis, despite treatment with dopamine, dobutamine, adrenaline, and noradrenaline infusions. A terlipressin (TP) 10 μg/kg intravenous bolus was administered, followed by a 1 μg/kg/minute continuous infusion. The response to TP treatment was assessed using pulse contour analysis. The mean arterial pressure and SVRI increased, and the cardiac index and heart rate decreased within 10 minutes after bolus administration of TP. Noradrenaline infusion could be reduced to 0.7 μg/kg/minute within 5 hours. The goal in presenting this case was to evaluate the vasoconstrictor effects of TP, a long-acting vasopressin analogue, in septic shock.

Sepsis 2018: Definitions and Guideline Changes.

PubMed

Napolitano, Lena M

Sepsis is a global healthcare issue and continues to be the leading cause of death from infection. Early recognition and diagnosis of sepsis is required to prevent the transition into septic shock, which is associated with a mortality rate of 40% or more. New definitions for sepsis and septic shock (Third International Consensus Definitions for Sepsis and Septic Shock [Sepsis-3]) have been developed. A new screening tool for sepsis (quick Sequential Organ Failure Assessment [qSOFA]) has been proposed to predict the likelihood of poor outcome in out-of-intensive care unit (ICU) patients with clinical suspicion of sepsis. The Surviving Sepsis Campaign Guidelines were recently updated and include greater evidence-based recommendations for treatment of sepsis in attempts to reduce sepsis-associated mortality. This review discusses the new Sepsis-3 definitions and guidelines.

Relative Bradycardia in Patients with Septic Shock Requiring Vasopressor Therapy

PubMed Central

Beesley, Sarah J.; Wilson, Emily L.; Lanspa, Michael J.; Grissom, Colin K.; Shahul, Sajid; Talmor, Daniel; Brown, Samuel M.

2017-01-01

Importance Tachycardia is common in septic shock, but many patients with septic shock are relatively bradycardic. The incidence, determinants, and implications of relative bradycardia (heart rate <80 beats/min) in septic shock are unknown. Objective To determine mortality associated with patients who are relatively bradycardic while in septic shock. Design Retrospective study of patients admitted for septic shock to study ICUs during 2005-2013. Setting One large academic referral hospital and two community hospitals. Participants Adult patients with septic shock requiring vasopressors. Intervention None. Measurements Primary outcome was 28-day mortality. We used multivariate logistic regression to evaluate the association between relative bradycardia and mortality, controlling for confounding with inverse probability treatment weighting using a propensity score. Results We identified 1,554 patients with septic shock, of whom 686 (44%) met criteria for relative bradycardia at some time. Twenty-eight day mortality in this group was 21% compared to 34% in the never-bradycardic group (p<0.001). Relatively bradycardic patients were older (65 vs. 60 years, p<0.001) and had slightly lower illness severity (SOFA 10 vs 11, p = 0.004, and APACHE II 27 vs. 28, p=0.008). After inverse probability treatment weighting, covariates were balanced, and the association between relative bradycardia and survival persisted (p<0.001). Conclusions Relative bradycardia in patients with septic shock is associated with lower mortality, even after adjustment for confounding. Our data support expanded investigation into whether inducing relative bradycardia will benefit patients with septic shock. PMID:27618277

Relative Bradycardia in Patients With Septic Shock Requiring Vasopressor Therapy.

PubMed

Beesley, Sarah J; Wilson, Emily L; Lanspa, Michael J; Grissom, Colin K; Shahul, Sajid; Talmor, Daniel; Brown, Samuel M

2017-02-01

Tachycardia is common in septic shock, but many patients with septic shock are relatively bradycardic. The prevalence, determinants, and implications of relative bradycardia (heart rate, < 80 beats/min) in septic shock are unknown. To determine mortality associated with patients who are relatively bradycardic while in septic shock. Retrospective study of patients admitted for septic shock to study ICUs during 2005-2013. One large academic referral hospital and two community hospitals. Adult patients with septic shock requiring vasopressors. None. Primary outcome was 28-day mortality. We used multivariate logistic regression to evaluate the association between relative bradycardia and mortality, controlling for confounding with inverse probability treatment weighting using a propensity score. We identified 1,554 patients with septic shock, of whom 686 (44%) met criteria for relative bradycardia at some time. Twenty-eight-day mortality in this group was 21% compared to 34% in the never-bradycardic group (p < 0.001). Relatively bradycardic patients were older (65 vs 60 yr; p < 0.001) and had slightly lower illness severity (Sequential Organ Failure Assessment, 10 vs 11; p = 0.004; and Acute Physiology and Chronic Health Evaluation II, 27 vs 28; p = 0.008). After inverse probability treatment weighting, covariates were balanced, and the association between relative bradycardia and survival persisted (p < 0.001). Relative bradycardia in patients with septic shock is associated with lower mortality, even after adjustment for confounding. Our data support expanded investigation into whether inducing relative bradycardia will benefit patients with septic shock.

Protracted immune disorders at one year after ICU discharge in patients with septic shock.

PubMed

Riché, Florence; Chousterman, Benjamin G; Valleur, Patrice; Mebazaa, Alexandre; Launay, Jean-Marie; Gayat, Etienne

2018-02-21

Sepsis is a leading cause of mortality and critical illness worldwide and is associated with an increased mortality rate in the months following hospital discharge. The occurrence of persistent or new organ dysfunction(s) after septic shock raises questions about the mechanisms involved in the post-sepsis status. The present study aimed to explore the immune profiles of patients one year after being discharged from the intensive care unit (ICU) following treatment for abdominal septic shock. We conducted a prospective, single-center, observational study in the surgical ICU of a university hospital. Eighty-six consecutive patients admitted for septic shock of abdominal origin were included in this study. Fifteen different plasma biomarkers were measured at ICU admission, at ICU discharge and at one year after ICU discharge. Three different clusters of biomarkers were distinguished according to their functions, namely: (1) inflammatory response, (2) cell damage and apoptosis, (3) immunosuppression and resolution of inflammation. The primary objective was to characterize variations in the immune status of septic shock patients admitted to ICU up to one year after ICU discharge. The secondary objective was to evaluate the relationship between these biomarker variations and patient outcomes. At the onset of septic shock, we observed a cohesive pro-inflammatory profile and low levels of inflammation resolution markers. At ICU discharge, the immune status demonstrated decreased but persistent inflammation and increased immunosuppression, with elevated programmed cell death protein-1 (PD-1) levels, and a counterbalanced resolution process, with elevated levels of interleukin-10 (IL-10), resolvin D5 (RvD5), and IL-7. One year after hospital discharge, homeostasis was not completely restored with several markers of inflammation remaining elevated. Remarkably, IL-7 was persistently elevated, with levels comparable to those observed after ICU discharge, and PD-1, while lower, remained in the elevated abnormal range. In this study, protracted immune disturbances were observed one year after ICU discharge. The study results suggested the presence of long-lasting immune illness disorders following a long-term septic insult, indicating the need for long-term patient follow up after ICU discharge and questioning the use of immune intervention to restore immune homeostasis after abdominal septic shock.

Mortality Measures to Profile Hospital Performance for Patients With Septic Shock.

PubMed

Walkey, Allan J; Shieh, Meng-Shiou; Liu, Vincent X; Lindenauer, Peter K

2018-04-30

Sepsis care is becoming a more common target for hospital performance measurement, but few studies have evaluated the acceptability of sepsis or septic shock mortality as a potential performance measure. In the absence of a gold standard to identify septic shock in claims data, we assessed agreement and stability of hospital mortality performance under different case definitions. Retrospective cohort study. U.S. acute care hospitals. Hospitalized with septic shock at admission, identified by either implicit diagnosis criteria (charges for antibiotics, cultures, and vasopressors) or by explicit International Classification of Diseases, 9th revision, codes. None. We used hierarchical logistic regression models to determine hospital risk-standardized mortality rates and hospital performance outliers. We assessed agreement in hospital mortality rankings when septic shock cases were identified by either explicit International Classification of Diseases, 9th revision, codes or implicit diagnosis criteria. Kappa statistics and intraclass correlation coefficients were used to assess agreement in hospital risk-standardized mortality and hospital outlier status, respectively. Fifty-six thousand six-hundred seventy-three patients in 308 hospitals fulfilled at least one case definition for septic shock, whereas 19,136 (33.8%) met both the explicit International Classification of Diseases, 9th revision, and implicit septic shock definition. Hospitals varied widely in risk-standardized septic shock mortality (interquartile range of implicit diagnosis mortality: 25.4-33.5%; International Classification of Diseases, 9th revision, diagnosis: 30.2-38.0%). The median absolute difference in hospital ranking between septic shock cohorts defined by International Classification of Diseases, 9th revision, versus implicit criteria was 37 places (interquartile range, 16-70), with an intraclass correlation coefficient of 0.72, p value of less than 0.001; agreement between case definitions for identification of outlier hospitals was moderate (kappa, 0.44 [95% CI, 0.30-0.58]). Risk-standardized septic shock mortality rates varied considerably between hospitals, suggesting that septic shock is an important performance target. However, efforts to profile hospital performance were sensitive to septic shock case definitions, suggesting that septic shock mortality is not currently ready for widespread use as a hospital quality measure.

Diagnosis and management of sepsis

NASA Astrophysics Data System (ADS)

Arifin

2018-03-01

Sepsis is the life-threatening condition with organ dysfunction caused by dysregulated host response to the infection. Septic shock is part of sepsis where circulatory abnormalities and cellular metabolism occur. Sepsis and septic shock are still a problem in the world, where one in four people with sepsis will die. As well as any trauma case, acute myocardial infarction, or stroke, early identification and appropriate treatment of sepsis immediately after sepsis will improve the prognosis of the patient. Comprehensive management of septic patients is required, ranging from infection controls that include antibiotic administration and infection source control as well as hemodynamic stabilization that included fluid resuscitation and vasoactive drug delivery.

Mortality in a pediatric secondary-care hospital in post-conflict Liberia in 2009

PubMed Central

Couto, Thomaz Bittencourt; Farhat, Sylvia Costa Lima; Reid, Tony; Schvartsman, Cláudio

2013-01-01

ABSTRACT Objective: To describe and analyze the causes of death in a pediatric secondary-care hospital (run by Médecins sans Frontières), in Monrovia, Liberia, 6 years post-civil war, to determine the quality of care and mortality in a setting with limited resources. Methods: Data were retrospectively collected from March 2009 to October 2009. Patient charts and laboratory records were reviewed to verify cause of death. Additionally, charts of patients aged over 1 month with an infectious cause of death were analyzed for decompensated septic shock, or fluid-refractory septic shock. Results: Of 8,254 admitted pediatric patients, 531 died, with a mortality rate of 6.4%. Ninety percent of deaths occurred in children <5 years old. Most deaths occurred within 24 hours of admission. The main cause of death (76%) was infectious disease. Seventy-eight (23.6%) patients >1 month old with infectious disease met the criteria for septic shock, and 28 (8.6%) for decompensated or fluid-refractory septic shock. Conclusion: Since the end of Liberia's devastating civil war, Island Hospital has improved care and mortality outcomes, despite operating with limited resources. Based on the available data, mortality in Island Hospital appears to be lower than that of other Liberian and African institutions and similar to other hospitals run by Médecins sans Frontières across Africa. This can be explained by the financial and logistic support of Médecins sans Frontières. The highest mortality burden is related to infectious diseases and neonatal conditions. The mortality of sepsis varied among different infections. This suggests that further mortality reduction can be obtained by tackling sepsis management and improving neonatal care. PMID:24488377

Severe Sepsis and Septic Shock Cases Meeting Guidelines Among Patients in a University Hospital Setting.

PubMed

Charrier, J A; Steen, C L; Borrero, E

2017-01-01

A diagnosis of severe sepsis or septic shock has been shown to significantly increase mortality rate independent of other factors. Research has revealed all cause hospital case fatality rates have declined yet the percentage of severe sepsis cases continues to increase and age-adjusted mortality rates from severe sepsis and septic shock has significantly increased during the same time period. Patients with severe sepsis demonstrate ongoing mortality rate increases for up to 2 years following hospitalization when compared to aged matched controls of nonseptic patients. International guidelines with mortality benefit for the management of severe sepsis and septic shock have been illustrated in the latest surviving sepsis campaign. The objective of this study was to increase the percentage of patients admitted to the hospital with a diagnosis of severe sepsis or septic shock who met guidelines based on surviving sepsis campaign. A retrospective chart review was conducted for patients admitted to UHC from January 2016 to present to identify cases with a diagnosis of severe sepsis or septic shock, and whether they met guidelines set forth by surviving sepsis campaign both before and after an intervention program which included interviews with providers failing to meet protocol, educational sessions on guidelines to meet protocol, resident led quality improvement workshops to address barriers to meeting protocol, and development of an EMR power plan to assist providers on meeting protocol. 139 cases with a diagnosis, or meeting criteria for, severe sepsis or septic shock were identified during the period of 1/1/2016-9/30/2016 with an average of 43 percent of total cases which met guidelines. Trend analysis revealed increased compliance following resident lead intervention program with 31 percent and 49 percent before and after intervention, respectively. ICU data is currently being analyzed for meeting guidelines and have not been included in current data. The most common reason for failing guidelines was failure to obtain or repeat lactic acid on time (46 percent ); and failure to give timely antibiotics (22 percent );. The percentage of patients admitted to the hospital with a diagnosis of severe sepsis or septic shock at UHC meeting guidelines set forth by surviving sepsis campaign has improved following resident lead intervention program. Intervention strategies to further improve compliance with guidelines with a goal >60 percent are currently being analyzed.

Depressed left ventricular performance. Response to volume infusion in patients with sepsis and septic shock

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

Ognibene, F.P.; Parker, M.M.; Natanson, C.

Volume infusion, to increase preload and to enhance ventricular performance, is accepted as initial management of septic shock. Recent evidence has demonstrated depressed myocardial function in human septic shock. We analyzed left ventricular performance during volume infusion using serial data from simultaneously obtained pulmonary artery catheter hemodynamic measurements and radionuclide cineangiography. Critically ill control subjects (n = 14), patients with sepsis but without shock (n = 21), and patients with septic shock (n = 21) had prevolume infusion hemodynamic measurements determined and received statistically similar volumes of fluid resulting in similar increases in pulmonary capillary wedge pressure. There was amore » strong trend (p = 0.004) toward less of a change in left ventricular stroke work index (LVSWI) after volume infusion in patients with sepsis and septic shock compared with control subjects. The LVSWI response after volume infusion was significantly less in patients with septic shock when compared with critically ill control subjects (p less than 0.05). These data demonstrate significantly altered ventricular performance, as measured by LVSWI, in response to volume infusion in patients with septic shock.« less

Urgent care in gynaecology: resuscitation and management of sepsis and acute blood loss.

PubMed

Fischerova, Daniela

2009-10-01

Sepsis and/or acute blood loss can be encoutered as an emergency condition in gynaecology, especially in women with ectopic pregnancy/miscarriage, acute pelvic inflammatory disease (PID)/tuboovarian abscesses, post-puerperal sepsis/haemorrhage and even in postoperative scenarios. If underestimated or suboptimally treated, both can lead to an inadequate tissue perfusion (defined as shock) and the development of multi-organ failure. Morbidity and mortality after development of one of the shock syndromes (septic or haemorrhagic) correlates directly with the duration and severity of the malperfusion. The patient's prognosis depends on a prompt diagnosis of the presence of shock and immediate resuscitation to predefined physiological end-points, often before the cause of the shock has been identified. In septic shock, hypotension is primarily treated with fluid administration and eventually vasopressors, if required, in order to improve the circulation. Timely administration of antibiotics, control of infectious foci, appropriate use of corticoids and recombinant human activated protein C, tight glucose control, prophylaxis of deep vein thrombosis and stress ulcer prevention complete the therapy of septic shock. In haemorrhagic shock, the treatment primarily involves controlling haemorrhage, reversal of possible coagulopathy and administration of sufficient volumes of fluids and blood products to restore normal tissue perfusion.

Sepsis

MedlinePlus

Septicemia; Sepsis syndrome; Systemic inflammatory response syndrome; SIRS; Septic shock ... The symptoms of sepsis are not caused by the germs themselves. Instead, chemicals the body releases cause the response. A bacterial infection anywhere ...

Sepsis in general surgery: the 2005-2007 national surgical quality improvement program perspective.

PubMed

Moore, Laura J; Moore, Frederick A; Todd, S Rob; Jones, Stephen L; Turner, Krista L; Bass, Barbara L

2010-07-01

To document the incidence, mortality rate, and risk factors for sepsis and septic shock compared with pulmonary embolism and myocardial infarction in the general-surgery population. Retrospective review. American College of Surgeons National Surgical Quality Improvement Program institutions. General-surgery patients in the 2005-2007 National Surgical Quality Improvement Program data set. Incidence, mortality rate, and risk factors for sepsis and septic shock. Of 363 897 general-surgery patients, sepsis occurred in 8350 (2.3%), septic shock in 5977 (1.6%), pulmonary embolism in 1078 (0.3%), and myocardial infarction in 615 (0.2%). Thirty-day mortality rates for each of the groups were as follows: 5.4% for sepsis, 33.7% for septic shock, 9.1% for pulmonary embolism, and 32.0% for myocardial infarction. The septic-shock group had a greater percentage of patients older than 60 years (no sepsis, 40.2%; sepsis, 51.7%; and septic shock, 70.3%; P < .001). The need for emergency surgery resulted in more cases of sepsis (4.5%) and septic shock (4.9%) than did elective surgery (sepsis, 2.0%; septic shock, 1.2%) (P < .001). The presence of any comorbidity increased the risk of sepsis and septic shock 6-fold (odds ratio, 5.8; 95% confidence interval, 5.5-6.2) and increased the 30-day mortality rate 22-fold (odds ratio, 21.8; 95% confidence interval, 17.6-26.9). The incidences of sepsis and septic shock exceed those of pulmonary embolism and myocardial infarction. The risk factors for mortality include age older than 60 years, the need for emergency surgery, and the presence of any comorbidity. This study emphasizes the need for early recognition of patients at risk via aggressive screening and the rapid implementation of evidence-based guidelines.

Risk factors and pathogenic significance of severe sepsis and septic shock in 2286 patients with gram-negative bacteremia.

PubMed

Kang, Cheol-In; Song, Jae-Hoon; Chung, Doo Ryeon; Peck, Kyong Ran; Ko, Kwan Soo; Yeom, Joon-Sup; Ki, Hyun Kyun; Son, Jun Seong; Lee, Seung Soon; Kim, Yeon-Sook; Jung, Sook-In; Kim, Shin-Woo; Chang, Hyun-Ha; Ryu, Seong Yeol; Kwon, Ki Tae; Lee, Hyuck; Moon, Chisook

2011-01-01

The aim of this study was to identify risk factors for development of severe sepsis or septic shock and to evaluate the clinical impact of severe sepsis on outcome in patients with gram-negative bacteremia (GNB). From the database of a nationwide surveillance for bacteremia, patients with GNB were analyzed. Data of patients with severe sepsis or septic shock were compared with those of patient with sepsis. Of 2286 patients with GNB, 506 (22.1%) fulfilled the criteria of severe sepsis or septic shock. Factors associated with severe sepsis or septic shock in the multivariate analysis included renal disease, indwelling urinary catheter, hematologic malignancy, and neutropenia. The 30-day mortality of patients with severe sepsis or septic shock was significantly higher than that of patients with sepsis (39.5% [172/435] vs. 7.4% [86/1170]; P < 0.001). Multivariable analysis revealed that solid tumor, liver disease, pulmonary disease, pneumonia, and pathogens other than Escherichia coli, which were risk factors of development of severe sepsis or septic shock, were also found to be strong predictors of mortality. Severe sepsis or septic shock was a significant factor associated with mortality (OR, 3.34; 95% CI, 2.35-4.74), after adjustment for other variables predicting poor prognosis. Severe sepsis or septic shock was a common finding in patients with GNB, predicting a higher mortality rate. Renal disease and indwelling urinary catheter were the most important risk factors significantly associated with severe sepsis or septic shock among patients with GNB. Copyright © 2010 The British Infection Association. Published by Elsevier Ltd. All rights reserved.

Clinical impact of stress dose steroids in patients with septic shock: insights from the PROWESS-Shock trial.

PubMed

Póvoa, Pedro; Salluh, Jorge I F; Martinez, Maria L; Guillamat-Prats, Raquel; Gallup, Dianne; Al-Khalidi, Hussein R; Thompson, B Taylor; Ranieri, V Marco; Artigas, Antonio

2015-04-28

The aim of our study was to evaluate the clinical impact of the administration of intravenous steroids, alone or in conjunction with drotrecogin-alfa (activated) (DrotAA), on the outcomes in septic shock patients. We performed a sub-study of the PROWESS-Shock trial (septic shock patients who received fluids and vasopressors above a predefined threshold for at least 4 hours were randomized to receive either DrotAA or placebo for 96 hours). A propensity score for the administration of intravenous steroids for septic shock at baseline was constructed using multivariable logistic regression. Cox proportional hazards model using inverse probability of treatment weighting of the propensity score was used to estimate the effect of intravenous steroids, alone or in conjunction with DrotAA, on 28-day and 90-day all-cause mortality. A total of 1695 patients were enrolled of which 49.5% received intravenous steroids for treatment of septic shock at baseline (DrotAA + steroids N = 436; DrotAA + no steroids N = 414; placebo + steroids N = 403; placebo + no steroids N = 442). The propensity weighted risk of 28-day as well as 90-day mortality in those treated vs. those not treated with steroids did not differ among those randomized to DrotAA vs. placebo (interaction p-value = 0.38 and p = 0.27, respectively) nor was a difference detected within each randomized treatment. Similarly, the course of vasopressor use and cardiovascular SOFA did not appear to be influenced by steroid therapy. In patients with lung infection (N = 744), abdominal infection (N = 510), Gram-positive sepsis (N = 420) and Gram-negative sepsis (N = 461), the propensity weighted risk of 28-day as well as 90-day mortality in those treated vs. those not treated with steroids did not differ among those randomized to DrotAA vs. placebo nor was a difference detected within each randomized treatment. In the present study of septic shock patients, after adjustment for treatment selection bias, we were unable to find noticeable positive impact from intravenous steroids for treatment of septic shock at baseline either in patients randomized for DrotAA or placebo. Clinicaltrials.gov NCT00604214 . Registered 24 January 2008.

Hyperchloremia Is Associated With Complicated Course and Mortality in Pediatric Patients With Septic Shock.

PubMed

Stenson, Erin K; Cvijanovich, Natalie Z; Anas, Nick; Allen, Geoffrey L; Thomas, Neal J; Bigham, Michael T; Weiss, Scott L; Fitzgerald, Julie C; Checchia, Paul A; Meyer, Keith; Quasney, Michael; Hall, Mark; Gedeit, Rainer; Freishtat, Robert J; Nowak, Jeffrey; Raj, Shekhar S; Gertz, Shira; Grunwell, Jocelyn R; Wong, Hector R

2018-02-01

Hyperchloremia is associated with poor outcome among critically ill adults, but it is unknown if a similar association exists among critically ill children. We determined if hyperchloremia is associated with poor outcomes in children with septic shock. Retrospective analysis of a pediatric septic shock database. Twenty-nine PICUs in the United States. Eight hundred ninety children 10 years and younger with septic shock. None. We considered the minimum, maximum, and mean chloride values during the initial 7 days of septic shock for each study subject as separate hyperchloremia variables. Within each category, we considered hyperchloremia as a dichotomous variable defined as a serum concentration greater than or equal to 110 mmol/L. We used multivariable logistic regression to determine the association between the hyperchloremia variables and outcome, adjusted for illness severity. We considered all cause 28-day mortality and complicated course as the primary outcome variables. Complicated course was defined as mortality by 28 days or persistence of greater than or equal to two organ failures at day 7 of septic shock. Secondarily, we conducted a stratified analysis using a biomarker-based mortality risk stratification tool. There were 226 patients (25%) with a complicated course and 93 mortalities (10%). Seventy patients had a minimum chloride greater than or equal to 110 mmol/L, 179 had a mean chloride greater than or equal to 110 mmol/L, and 514 had a maximum chloride greater than or equal to 110 mmol/L. A minimum chloride greater than or equal to 110 mmol/L was associated with increased odds of complicated course (odds ratio, 1.9; 95% CI, 1.1-3.2; p = 0.023) and mortality (odds ratio, 3.7; 95% CI, 2.0-6.8; p < 0.001). A mean chloride greater than or equal to 110 mmol/L was also associated with increased odds of mortality (odds ratio, 2.1; 95% CI, 1.3-3.5; p = 0.002). The secondary analysis yielded similar results. Hyperchloremia is independently associated with poor outcomes among children with septic shock.

Vasopressin synthesis by the magnocellular neurons is different in the supraoptic nucleus and in the paraventricular nucleus in human and experimental septic shock.

PubMed

Sonneville, Romain; Guidoux, Céline; Barrett, Lucinda; Viltart, Odile; Mattot, Virginie; Polito, Andrea; Siami, Shidasp; de la Grandmaison, Geoffroy Lorin; Blanchard, Anne; Singer, Mervyn; Annane, Djillali; Gray, Françoise; Brouland, Jean-Philippe; Sharshar, Tarek

2010-05-01

Impaired arginine vasopressin (AVP) synthesis and release by the neurohypophyseal system, which includes the neurohypophysis and magnocellular neurons of the paraventricular and supraoptic nuclei, have been postulated in septic shock, but changes in this system have never been assessed in human septic shock, and only partially experimentally. We investigated AVP synthesis and release by the neurohypophyseal system in 9 patients who died from septic shock and 10 controls, and in 20 rats with fecal peritonitis-induced sepsis and 8 sham-operation controls. Ten rats died spontaneously from septic shock, and the others were sacrificed. In patients with septic shock, as in rats that died spontaneously following sepsis induction, AVP immunohistochemical expression was decreased in the neurohypophysis and supraoptic magnocellular neurons, whereas it was increased in the paraventricular magnocellular neurons. No significant change was observed in AVP messenger RiboNucleic Acid (mRNA) expression assessed by in situ hybridization in either paraventricular or supraoptic magnocellular cells. This study shows that both in human and experimental septic shock, AVP posttranscriptional synthesis and transport are differently modified in the magnocellular neurons of the supraoptic and paraventricular nuclei. This may account for the inappropriate AVP release in septic shock and suggests that distinct pathogenic mechanisms operate in these nuclei.

Vasopressin compared with norepinephrine augments the decline of plasma cytokine levels in septic shock.

PubMed

Russell, James A; Fjell, Chris; Hsu, Joseph L; Lee, Terry; Boyd, John; Thair, Simone; Singer, Joel; Patterson, Andrew J; Walley, Keith R

2013-08-01

Changes in plasma cytokine levels may predict mortality, and therapies (vasopressin versus norepinephrine) could change plasma cytokine levels in early septic shock. Our hypotheses were that changes in plasma cytokine levels over 24 hours differ between survivors and nonsurvivors, and that there are different effects of vasopressin and norepinephrine on plasma cytokine levels in septic shock. We studied 394 patients in a randomized, controlled trial of vasopressin versus norepinephrine in septic shock. We used hierarchical clustering and principal components analysis of the baseline cytokine concentrations to subgroup cytokines; we then compared survivors to nonsurvivors (28 d) and compared vasopressin- versus norepinephrine-induced changes in cytokine levels over 24 hours. A total of 39 plasma cytokines were measured at baseline and at 24 hours. Hierarchical clustering and principal components analysis grouped cytokines similarly. Survivors (versus nonsurvivors) had greater decreases of overall cytokine levels (P < 0.001). Vasopressin decreased overall 24-hour cytokine concentration compared with norepinephrine (P = 0.037). In less severe septic shock, the difference in plasma cytokine reduction over 24 hours between survivors and nonsurvivors was less pronounced than that seen in more severe septic shock. Furthermore, vasopressin decreased interferon-inducible protein 10 and granulocyte colony-stimulating factor more than did norepinephrine in less severe septic shock, whereas vasopressin decreased granulocyte-macrophage colony-stimulating factor in patients who had more severe shock. Survivors of septic shock had greater decreases of cytokines, chemokines and growth factors in early septic shock. Vasopressin decreased 24-hour plasma cytokine levels more than did norepinephrine. The vasopressin-associated decrease of cytokines differed according to severity of shock. Clinical trial registered with www.controlled-trials.com (ISRCTN94845869).

[Cardiac index, oxygen and serum lactate consumption in infants with hypovolemic and septic shock].

PubMed

Gaytán Becerril, A; Olvera Hidalgo, C; Vieto Rodríguez, E E; Chávez Angeles, D S; Elena Salas, M

1980-01-01

Determination was made of cardiac output (using the stain dilution technique), gases in blood and serum lactate levels in eight infants with hypovolemic shock and sixteen with septic shock. The data were carried to indexes (values per square meter of body surface). In children with hypovolemic shock the cardiac index was 1.88 +/- 0.031/min/m,2 while in septic patients it was 4.02 +/- 1.011/min/m2. The peripheral resistances were 3,079 din/min/cm.5 in hypovolemic cases and 907 din/min in the septic. In both groups serum lactante levels rised close to 4 mM 61. Oxigen consumption was found low in hypovolemic patients and slightly high in the septic. It is concluded that our data are similar to those reported in similar studies in adults and hypodynamic shock is shown in hypovolemic patients, while hyperdynamic shock appears in septic cases.

Bench-to-bedside review: Vasopressin in the management of septic shock

PubMed Central

2011-01-01

This review of vasopressin in septic shock differs from previous reviews by providing more information on the physiology and pathophysiology of vasopressin and vasopressin receptors, particularly because of recent interest in more specific AVPR1a agonists and new information from the Vasopressin and Septic Shock Trial (VASST), a randomized trial of vasopressin versus norepinephrine in septic shock. Relevant literature regarding vasopressin and other AVPR1a agonists was reviewed and synthesized. Vasopressin, a key stress hormone in response to hypotension, stimulates a family of receptors: AVPR1a, AVPR1b, AVPR2, oxytocin receptors and purinergic receptors. Rationales for use of vasopressin in septic shock are as follows: first, a deficiency of vasopressin in septic shock; second, low-dose vasopressin infusion improves blood pressure, decreases requirements for norepinephrine and improves renal function; and third, a recent randomized, controlled, concealed trial of vasopressin versus norepinephrine (VASST) suggests low-dose vasopressin may decrease mortality of less severe septic shock. Previous clinical studies of vasopressin in septic shock were small or not controlled. There was no difference in 28-day mortality between vasopressin-treated versus norepinephrine-treated patients (35% versus 39%, respectively) in VASST. There was potential benefit in the prospectively defined stratum of patients with less severe septic shock (5 to 14 μg/minute norepinephrine at randomization): vasopressin may have lowered mortality compared with norepinephrine (26% versus 36%, respectively, P = 0.04 within stratum). The result was robust: vasopressin also decreased mortality (compared with norepinephrine) if less severe septic shock was defined by the lowest quartile of arterial lactate or by use of one (versus more than one) vasopressor at baseline. Other investigators found greater hemodynamic effects of higher dose of vasopressin (0.06 units/minute) but also unique adverse effects (elevated liver enzymes and serum bilirubin). Use of higher dose vasopressin requires further evaluation of efficacy and safety. There are very few studies of interactions of therapies in critical care - or septic shock - and effects on mortality. Therefore, the interaction of vasopressin infusion, corticosteroid treatment and mortality of septic shock was evaluated in VASST. Low-dose vasopressin infusion plus corticosteroids significantly decreased 28-day mortality compared with corticosteroids plus norepinephrine (44% versus 35%, respectively, P = 0.03; P = 0.008 interaction statistic). Prospective randomized controlled trials would be necessary to confirm this interesting interaction. In conclusion, low-dose vasopressin may be effective in patients who have less severe septic shock already receiving norepinephrine (such as patients with modest norepinephrine infusion (5 to 15 μg/minute) or low serum lactate levels). The interaction of vasopressin infusion and corticosteroid treatment in septic shock requires further study. PMID:21892977

Initial resuscitation and management of pediatric septic shock

PubMed Central

Martin, Kelly; Weiss, Scott L.

2015-01-01

The pediatric sepsis syndrome remains a common cause of morbidity, mortality, and health care utilization costs worldwide. The initial resuscitation and management of pediatric sepsis is focused on 1) rapid recognition of abnormal tissue perfusion and restoration of adequate cardiovascular function, 2) eradication of the inciting invasive infection, including prompt administration of empiric broad-spectrum antimicrobial medications, and 3) supportive care of organ system dysfunction. Efforts to improve early and aggressive initial resuscitation and ongoing management strategies have improved outcomes in pediatric severe sepsis and septic shock, though many questions still remain as to the optimal therapeutic strategies for many patients. In this article, we will briefly review the definitions, epidemiology, clinical manifestations, and pathophysiology of sepsis and provide an extensive overview of both current and novel therapeutic strategies used to resuscitate and manage pediatric patients with severe sepsis and septic shock. PMID:25604591

Differential expression of the Nrf2-linked genes in pediatric septic shock.

PubMed

Grunwell, Jocelyn R; Weiss, Scott L; Cvijanovich, Natalie Z; Allen, Geoffrey L; Thomas, Neal J; Freishtat, Robert J; Anas, Nick; Meyer, Keith; Checchia, Paul A; Shanley, Thomas P; Bigham, Michael T; Fitzgerald, Julie; Howard, Kelli; Frank, Erin; Harmon, Kelli; Wong, Hector R

2015-09-17

Experimental data from animal models of sepsis support a role for a transcription factor, nuclear erythroid-related factor 2 p45-related factor 2 (Nrf2), as a master regulator of antioxidant and detoxifying genes and intermediary metabolism during stress. Prior analysis of a pediatric septic shock transcriptomic database showed that the Nrf2 response is a top 5 upregulated signaling pathway in early pediatric septic shock. We conducted a focused analysis of 267 Nrf2-linked genes using a multicenter, genome-wide expression database of 180 children with septic shock 10 years of age or younger and 53 healthy controls. The analysis involved RNA isolated from whole blood within 24 h of pediatric intensive care unit admission for septic shock and a false discovery rate of 5 %. We compared differentially expressed genes from (1) patients with septic shock and healthy controls and (2) across validated gene expression-based subclasses of pediatric septic shock (endotypes A and B) using several bioinformatic methods. We found upregulation of 123 Nrf2-linked genes in children with septic shock. The top gene network represented by these genes contained primarily enzymes with oxidoreductase activity involved in cellular lipid metabolism that were highly connected to the peroxisome proliferator activated receptor and the retinoic acid receptor families. Endotype A, which had higher organ failure burden and mortality, exhibited a greater downregulation of Nrf2-linked genes than endotype B, with 92 genes differentially regulated between endotypes. Our findings indicate that Nrf2-linked genes may contribute to alterations in oxidative signaling and intermediary metabolism in pediatric septic shock.

Time to antibiotics for septic shock: evaluating a proposed performance measure.

PubMed

Venkatesh, Arjun K; Avula, Umakanth; Bartimus, Holly; Reif, Justin; Schmidt, Michael J; Powell, Emilie S

2013-04-01

International guidelines recommend antibiotics within 1 hour of septic shock recognition; however, a recently proposed performance measure is focused on measuring antibiotic administration within 3 hours of emergency department (ED) arrival. Our objective was to describe the time course of septic shock and subsequent implications for performance measurement. Cross-sectional study of consecutive ED patients ultimately diagnosed with septic shock. All patients were evaluated at an urban, academic ED in 2006 to 2008. Primary outcomes included time to definition of septic shock and performance on 2 measures: antibiotics within 3 hours of ED arrival vs antibiotics within 1 hour of septic shock definition. Of 267 patients with septic shock, the median time to definition was 88 minutes (interquartile range, 37-156), and 217 patients (81.9%) met the definition within 3 hours of arrival. Of 221 (83.4%) of patients who received antibiotics within 3 hours of arrival, 38 (17.2%) did not receive antibiotics within 1 hour of definition. Of 207 patients who received antibiotics within 1 hour of definition, 11.6% (n = 24) did not receive antibiotics within 3 hours of arrival. The arrival measure did not accurately classify performance in 23.4% of patients. Nearly 1 of 5 patients cannot be captured for performance measurement within 3 hours of ED arrival due to the variable progression of septic shock. Use of this measure would misclassify performance in 23% of patients. Measuring antibiotic administration based on the clinical course of septic shock rather than from ED arrival would be more appropriate. Copyright © 2013 Elsevier Inc. All rights reserved.

An alternate pathophysiologic paradigm of sepsis and septic shock

PubMed Central

Kumar, Anand

2014-01-01

The advent of modern antimicrobial therapy following the discovery of penicillin during the 1940s yielded remarkable improvements in case fatality rate of serious infections including septic shock. Since then, pathogens have continuously evolved under selective antimicrobial pressure resulting in a lack of significant improvement in clinical effectiveness in the antimicrobial therapy of septic shock despite ever more broad-spectrum and potent drugs. In addition, although substantial effort and money has been expended on the development novel non-antimicrobial therapies of sepsis in the past 30 years, clinical progress in this regard has been limited. This review explores the possibility that the current pathophysiologic paradigm of septic shock fails to appropriately consider the primacy of the microbial burden of infection as the primary driver of septic organ dysfunction. An alternate paradigm is offered that suggests that has substantial implications for optimizing antimicrobial therapy in septic shock. This model of disease progression suggests the key to significant improvement in the outcome of septic shock may lie, in great part, with improvements in delivery of existing antimicrobials and other anti-infectious strategies. Recognition of the role of delays in administration of antimicrobial therapy in the poor outcomes of septic shock is central to this effort. However, therapeutic strategies that improve the degree of antimicrobial cidality likely also have a crucial role. PMID:24184742

Septic shock

MedlinePlus

... shock; Warm shock References Munford RS, Suffredini AF. Sepsis, severe sepsis, and septic shock. In: Bennett JE, Dolin R, ... D.A.M. Editorial team. Gangrene Read more Sepsis Read more Shock Read more A.D.A. ...

The Effects of Alternative Resuscitation Strategies on Acute Kidney Injury in Patients with Septic Shock.

PubMed

Kellum, John A; Chawla, Lakhmir S; Keener, Christopher; Singbartl, Kai; Palevsky, Paul M; Pike, Francis L; Yealy, Donald M; Huang, David T; Angus, Derek C

2016-02-01

Septic shock is a common cause of acute kidney injury (AKI), and fluid resuscitation is a major part of therapy. To determine if structured resuscitation designed to alter fluid, blood, and vasopressor use affects the development or severity of AKI or outcomes. Ancillary study to the ProCESS (Protocolized Care for Early Septic Shock) trial of alternative resuscitation strategies (two protocols vs. usual care) for septic shock. We studied 1,243 patients and classified AKI using serum creatinine and urine output. We determined recovery status at hospital discharge, examined rates of renal replacement therapy and fluid overload, and measured biomarkers of kidney damage. Among patients without evidence of AKI at enrollment, 37.6% of protocolized care and 38.1% of usual care patients developed kidney injury (P = 0.90). AKI duration (P = 0.59) and rates of renal replacement therapy did not differ between study arms (6.9% for protocolized care and 4.3% for usual care; P = 0.08). Fluid overload occurred in 8.3% of protocolized care and 6.3% of usual care patients (P = 0.26). Among patients with severe AKI, complete and partial recovery was 50.7 and 13.2% for protocolized patients and 49.1 and 13.4% for usual care patients (P = 0.93). Sixty-day hospital mortality was 6.2% for patients without AKI, 16.8% for those with stage 1, and 27.7% for stages 2 to 3. In patients with septic shock, AKI is common and associated with adverse outcomes, but it is not influenced by protocolized resuscitation compared with usual care.

In-Hospital Quality-of-Care Measures for Pediatric Sepsis Syndrome.

PubMed

Odetola, Folafoluwa O; Freed, Gary; Shevrin, Caroline; Madden, Brian; McCormick, Julie; Dombkowski, Kevin

2017-07-24

Sepsis syndrome, comprising sepsis, severe sepsis, and septic shock, is a leading cause of child mortality and morbidity, for which the delivery of time-sensitive care leads to improved survival. We aimed to describe the development and testing of quality measures for in-hospital care of pediatric sepsis syndrome. Seven measures of quality of care for children hospitalized with sepsis syndrome were developed by using an iterative process including literature review, development of concepts and candidate measures, and selection of measures for feasibility and importance by 2 panels of experts. The measures were tested for reliability and validity among children 0 to 18 years of age hospitalized with sepsis syndrome from January 1, 2012, to June 30, 2013. Of 27 hospitals, 59% had no protocol for the identification and treatment of pediatric sepsis syndrome. Blood culture was performed in only 70% of patients with pediatric sepsis syndrome. Antibiotics were administered within 1 hour of diagnosis in 70% of patients with pediatric severe sepsis or septic shock, and timely fluid resuscitation was performed in 50% of patients with severe sepsis or septic shock. Documentation of heart rate during fluid resuscitation of children with severe sepsis or septic shock was observed in 18% of cases. Two measures could not be rigorously tested for validity and reliability given the rarity of septic shock and were deemed infeasible. This multisite study to develop and validate measures of the quality of hospital care of children with sepsis syndrome highlights the existence of important gaps in delivery of care. Copyright © 2017 by the American Academy of Pediatrics.

Septic shock sera containing circulating histones induce dendritic cell-regulated necrosis in fatal septic shock patients.

PubMed

Raffray, Loic; Douchet, Isabelle; Augusto, Jean-Francois; Youssef, Jihad; Contin-Bordes, Cecile; Richez, Christophe; Duffau, Pierre; Truchetet, Marie-Elise; Moreau, Jean-Francois; Cazanave, Charles; Leroux, Lionel; Mourrissoux, Gaelle; Camou, Fabrice; Clouzeau, Benjamin; Jeannin, Pascale; Delneste, Yves; Gabinski, Claude; Guisset, Olivier; Lazaro, Estibaliz; Blanco, Patrick

2015-04-01

Innate immune system alterations, including dendritic cell loss, have been reproducibly observed in patients with septic shock and correlated to adverse outcomes or nosocomial infections. The goal of this study is to better understand the mechanisms behind this observation in order to better assess septic shock pathogenesis. Prospective, controlled experimental study. Research laboratory at an academic medical center. The study enrolled 71 patients, 49 with septic shock and 22 with cardiogenic shock. Seventeen healthy controls served as reference. In vitro monocyte-derived dendritic cells were generated from healthy volunteers. Sera were assessed for their ability to promote in vitro dendritic cell death through flow cytometry detection in each group of patients. The percentage of apoptotic or necrotic dendritic cells was evaluated by annexin-V and propidium iodide staining. We observed that only patients with septic shock and not patients with pure cardiogenic shock were characterized by a rapid and profound loss of circulating dendritic cells. In vitro analysis revealed that sera from patients with septic shock induced higher dendritic cell death compared to normal sera or cardiogenic shock (p<0.005). Sera from surviving patients induced dendritic cell death through a caspase-dependent apoptotic pathway, whereas sera from nonsurviving patients induced dendritic cell-regulated necrosis. Dendritic cell necrosis was not due to necroptosis but was dependent of the presence of circulating histone. The toxicity of histones toward dendritic cell could be prevented by recombinant human activated protein C. Finally, we observed a direct correlation between the levels of circulating histones in patients and the ability of the sera to promote dendritic cell-regulated necrosis. The study demonstrates a differential mechanism of dendritic cell death in patients with septic shock that is dependent on the severity of the disease.

Plasma interferon-gamma and interleukin-10 concentrations in systemic meningococcal disease compared with severe systemic Gram-positive septic shock.

PubMed

Bjerre, Anna; Brusletto, Berit; Høiby, Ernst Arne; Kierulf, Peter; Brandtzaeg, Petter

2004-02-01

To analyze plasma interferon-gamma and interleukin-10 concentrations in patients with systemic meningococcal disease and patients with severe Gram-positive septic shock caused by Streptococcus pneumoniae or Staphylococcus aureus. To study the in vitro cytokine (interferon-gamma and interleukin-10) responses in a whole blood model boosted with heat-killed Neisseria meningitidis, S. pneumoniae, and S. aureus before and after treatment with recombinant interleukin-10 or recombinant interferon-gamma. Experimental study. Laboratory. Plasma samples were collected from patients with systemic meningococcal disease (n = 66) and patients with severe Gram-positive septic shock caused by S. pneumoniae (n = 4) or S. aureus (n = 3). Whole blood was boosted with heat-killed N. meningitidis, S. pneumoniae, and S. aureus (1 x 106 colony forming units/mL), and plasmas were analyzed for interleukin-10 or interferon-gamma at 0, 5, 12, and 24 hrs. Furthermore, recombinant interleukin-10 or recombinant interferon-gamma was added before bacteria, and the effect on the secretion of interferon-gamma and interleukin-10, respectively, was analyzed after 24 hrs. The median concentration of interferon-gamma was 15 pg/mL and of interleukin-10 was 10,269 pg/mL in patients with meningococcal septic shock (n = 24) compared with median interferon-gamma concentration of 3400 pg/mL and interleukin-10 concentration of 465 pg/mL in patients with severe Gram-positive shock (p =.001). Increased interferon-gamma concentrations were associated with case fatality (p =.011). In a whole blood model we demonstrated that 1 x 106 colony forming units/mL of N. meningitidis induced more interleukin-10 but less interferon-gamma than S. pneumoniae. S. aureus induced minimal secretion of both cytokines. Recombinant interleukin-10 efficiently down-regulated the secretion of interferon-gamma, and vice versa, as shown in a whole blood model. We speculate whether high concentrations of interleukin-10 contribute to the low concentrations of interferon-gamma in fulminant meningococcal septicemia. In addition, it appears as if interferon-gamma plays a minor role in the pathophysiology of meningococcal septic shock.

Epidemiology and Clinical Relevance of Toxic Shock Syndrome in US Children.

PubMed

Gaensbauer, James T; Birkholz, Meghan; Smit, Michael A; Garcia, Roger; Todd, James K

2018-03-27

It is important for clinicians to recognize the contribution of toxic shock syndrome (TSS) to the overall burden of pediatric septic shock because the clinical features, optimal therapy and prognosis differ from non-TSS septic shock. We analyzed cases of pediatric septic shock reported to the Pediatric Health Information Systems (PHIS) database between 2009 and 2013 to define the clinical and demographic characteristics of pediatric TSS in the US. Using a validated ICD-9 coding strategy we identified patients with infectious shock among inpatients age 1 to 18 years, and classified cases of staphylococcal and streptococcal TSS for comparison with non-TSS cases. Of 8,226 cases of pediatric septic shock, 909 (11.1%) were classified as TSS and 562 (6.8%) were possible TSS cases. Staphylococcal TSS represented the majority (83%) of TSS cases, and occurred more commonly in females and at an older age. Compared with non-TSS septic shock, TSS had significantly lower fatality rates, disease severity, and length of hospital stay, and was present more often at the time of admission (p<0.001 for each). Streptococcal TSS was associated with poorer outcomes than staphylococcal TSS. Treatment for TSS differed from non-TSS septic shock in use of more clindamycin, vancomycin and IVIG, and less need for vasopressors. Results demonstrate a significant contribution of TSS to the burden of pediatric septic shock in the US. The findings emphasize the importance of inclusion of TSS diagnostic and therapeutic considerations in sepsis treatment protocols for children.

Frequency and clinical outcomes of ESKAPE bacteremia in solid organ transplantation and the risk factors for mortality.

PubMed

Ye, Q F; Zhao, J; Wan, Q Q; Qiao, B B; Zhou, J D

2014-10-01

Although bacteremias caused by the 6 ESKAPE pathogens (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter species) have recently been highlighted as a serious complication in solid organ transplant (SOT), more information is urgently needed. We sought to investigate the frequency and clinical outcomes of ESKAPE bacteremia in SOT and determine the risk factors for mortality. A retrospective analysis of bacteremia after SOT was reviewed. Risk factors for mortality caused by ESKAPE bacteremia were identified. Eighty-four episodes of bacteremia were caused by ESKAPE strains. Of these strains, 41 were caused by resistant ESKAPE (rESKAPE) organisms. The only factor for bacteremia-related mortality independently associated with ESKAPE was septic shock (odds ratio [OR] = 21.017, 95% confidence interval [CI] = 5.038-87.682, P < 0.001). The factors for bacteremia-related mortality independently associated with rESKAPE bacteremia were septic shock (OR = 16.558, 95% CI = 6.620-104.668, P = 0.003) and age ≥40 years (OR = 7.521, 95% CI = 1.196-47.292, P = 0.031). To improve the outcomes of transplantation, more effective therapeutic treatments are of paramount importance when older SOT recipients with bacteremia due to ESKAPE/rESKAPE organisms present with septic shock. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Evaluating the Impact of Classroom Education on the Management of Septic Shock Using Human Patient Simulation.

PubMed

Lighthall, Geoffrey K; Bahmani, Dona; Gaba, David

2016-02-01

Classroom lectures are the mainstay of imparting knowledge in a structured manner and have the additional goals of stimulating critical thinking, lifelong learning, and improvements in patient care. The impact of lectures on patient care is difficult to examine in critical care because of the heterogeneity in patient conditions and personnel as well as confounders such as time pressure, interruptions, fatigue, and nonstandardized observation methods. The critical care environment was recreated in a simulation laboratory using a high-fidelity mannequin simulator, where a mannequin simulator with a standardized script for septic shock was presented to trainees. The reproducibility of this patient and associated conditions allowed the evaluation of "clinical performance" in the management of septic shock. In a previous study, we developed and validated tools for the quantitative analysis of house staff managing septic shock simulations. In the present analysis, we examined whether measures of clinical performance were improved in those cases where a lecture on the management of shock preceded a simulated exercise on the management of septic shock. The administration of the septic shock simulations allowed for performance measurements to be calculated for both medical interns and for subsequent management by a larger resident-led team. The analysis revealed that receiving a lecture on shock before managing a simulated patient with septic shock did not produce scores higher than for those who did not receive the previous lecture. This result was similar for both interns managing the patient and for subsequent management by a resident-led team. We failed to find an immediate impact on clinical performance in simulations of septic shock after a lecture on the management of this syndrome. Lectures are likely not a reliable sole method for improving clinical performance in the management of complex disease processes.

Genome-Level Longitudinal Expression of Signaling Pathways and Gene Networks in Pediatric Septic Shock

PubMed Central

Shanley, Thomas P; Cvijanovich, Natalie; Lin, Richard; Allen, Geoffrey L; Thomas, Neal J; Doctor, Allan; Kalyanaraman, Meena; Tofil, Nancy M; Penfil, Scott; Monaco, Marie; Odoms, Kelli; Barnes, Michael; Sakthivel, Bhuvaneswari; Aronow, Bruce J; Wong, Hector R

2007-01-01

We have conducted longitudinal studies focused on the expression profiles of signaling pathways and gene networks in children with septic shock. Genome-level expression profiles were generated from whole blood-derived RNA of children with septic shock (n = 30) corresponding to day one and day three of septic shock, respectively. Based on sequential statistical and expression filters, day one and day three of septic shock were characterized by differential regulation of 2,142 and 2,504 gene probes, respectively, relative to controls (n = 15). Venn analysis demonstrated 239 unique genes in the day one dataset, 598 unique genes in the day three dataset, and 1,906 genes common to both datasets. Functional analyses demonstrated time-dependent, differential regulation of genes involved in multiple signaling pathways and gene networks primarily related to immunity and inflammation. Notably, multiple and distinct gene networks involving T cell- and MHC antigen-related biology were persistently downregulated on both day one and day three. Further analyses demonstrated large scale, persistent downregulation of genes corresponding to functional annotations related to zinc homeostasis. These data represent the largest reported cohort of patients with septic shock subjected to longitudinal genome-level expression profiling. The data further advance our genome-level understanding of pediatric septic shock and support novel hypotheses. PMID:17932561

Diagnostic value of Pentraxin-3 in patients with sepsis and septic shock in accordance with latest sepsis-3 definitions.

PubMed

Hamed, Sonja; Behnes, Michael; Pauly, Dominic; Lepiorz, Dominic; Barre, Max; Becher, Tobias; Lang, Siegfried; Akin, Ibrahim; Borggrefe, Martin; Bertsch, Thomas; Hoffmann, Ursula

2017-08-09

Pentraxin-3 (PTX-3) is an acute-phase protein involved in inflammatory and infectious processes. This study assesses its diagnostic and prognostic value in patients with sepsis or septic shock in a medical intensive care unit (ICU). The study includes 213 ICU patients with clinical criteria of sepsis and septic shock. 77 donors served as controls. Plasma levels of PTX-3, procalcitonin (PCT) and interleukin-6 were measured on day 1, 3 and 8. PTX-3 correlated with higher lactate levels as well as with APACHE II and SOFA scores (p = 0.0001). PTX-3 levels of patients with sepsis or septic shock were consistently significantly higher than in the control group (p ≤ 0.001). Plasma levels were able to discriminate sepsis and septic shock significantly on day 1, 3 and 8 (range of AUC 0.73-0.92, p = 0.0001). Uniform cut-off levels were defined at ≥5 ng/ml for at least sepsis, ≥9 ng/ml for septic shock (p = 0.0001). PTX-3 reveals diagnostic value for sepsis and septic shock during the first week of intensive care treatment, comparable to interleukin-6 according to latest Sepsis-3 definitions. NCT01535534 . Registered 14.02.2012.

Effectiveness of anisodamine for the treatment of critically ill patients with septic shock (ACIdoSIS study): study protocol for randomized controlled trial

PubMed Central

Zhou, Jiancang; Shang, You; Wang, Xin’an; Yin, Rui; Zhu, Zhenhua; Chen, Wensen; Tian, Xin; Yu, Yuetian; Zuo, Xiangrong; Chen, Kun; Ji, Xuqing; Ni, Hongying

2015-01-01

Background Septic shock is an important contributor of mortality in the intensive care unit (ICU). Although strenuous effort has been made to improve its outcome, the mortality rate is only marginally decreased. The present study aimed to investigate the effectiveness of anisodamine in the treatment of septic shock, in the hope that the drug will provide alternatives to the treatment of septic shock. Methods The study is a multi-center randomized controlled clinical trial. Study population will include critically ill patients with septic shock requiring vasopressor use. Blocked randomization was performed where anisodamine and control treatments were allocated at random in a ratio of 1:1 in blocks of sizes 2, 4, 6, 8, and 10 to 354 subjects. Interim analysis will be performed. The primary study end point is the hospital mortality, and other secondary study endpoints include ICU mortality, length of stay in ICU and hospital, organ failure free days. Adverse events including new onset psychosis, urinary retention, significant hypotension and tachycardia will be reported. Discussion The study will provide new insight into the treatment of septic shock and can help to reduce mortality rate of septic shock. Trial registration NCT02442440 (https://register.clinicaltrials.gov/). PMID:26605292

[Use of quantitative electroencephalogram in patients with septic shock].

PubMed

Ma, Yujie; Ouyang, Bin; Guan, Xiangdong

2016-01-19

To observe the quantitative electroencephalogram (qEEG) characteristics of the patients with septic shock in intensive care unit (ICU), and to find the early presence and severity of septic-associated encephalopathy (SAE) in these patients. During November 2014 to August 2015, 26 cases with septic shock were included from the ICU of the First Affiliated Hospital, Sun Yat-sen University.During the same period, 14 healthy volunteers were included as control. The brain function instrument was used to monitor the patients by the bed, placing leads as the internationally used 10-20 system, bipolar longitudinal F3-P3, F4-P4 four channels, and then consecutive clips of 5 minutes was chosen, using the average value of the clips, the amplitude integrated electroencephalogram (aEEG), relative frequency band energy, spectrum entropy, relative alpha ariability to carry out statistical analysis.And the qEEG features of septic shock patients with different Glasgow coma scale (GCS) levels were also analyzed. (1) 96% of the patients with septic shock had EEG abnormalities.Alpha frequency band energy, alpha ariability, aEEG amplitude, spectrum entropy decreased significantly (P<0.05=, while the delta frequency band energy significantly increased (P<0.05=. (2) aEEG amplitude decline appeared in 34% of patients with septic shock, and within the septic shock groups, amplitude decreased significantly (P<0.05= in patients with GCS under five. Patients with septic shock tends to have diffuse inhibition in EEG, and the inhibition degree can reflect cerebral lesion degree; changes of EEG frequency as early warning indicators of brain damage are sensitive, and the decline of amplitude often indicates critical injury.

Speckle tracking echocardiography in patients with septic shock: a case control study (SPECKSS).

PubMed

Ng, Pauline Yeung; Sin, Wai Ching; Ng, Andrew Kei-Yan; Chan, Wai Ming

2016-05-14

Sepsis-induced myocardial dysfunction is a well-recognized condition and confers worse outcomes in septic patients. Echocardiographic assessment by conventional parameters such as left ventricular ejection fraction (LVEF) is often affected by ongoing changes in preload and afterload conditions. Novel echocardiographic technologies such as speckle tracking echocardiography (STE) have evolved for direct assessment of the myocardial function. We investigate the measurement of myocardial strain by speckle tracking echocardiography for the diagnosis of sepsis-induced myocardial dysfunction. This is a case-control study at a university-affiliated medical intensive care unit. Consecutive adult medical patients admitted with a diagnosis of septic shock were included. Patients with other causes of myocardial dysfunction were excluded. They were compared to age-matched, gender-matched, and cardiovascular risk-factor-matched controls, who were admitted to hospital for sepsis but did not develop septic shock. Transthoracic echocardiography was performed on all patients within 24 hours of diagnosis, and a reassessment echocardiogram was performed in the study group of patients upon recovery. Patients with septic shock (n = 33) (study group) and 29 matched patients with sepsis but no septic shock (control group) were recruited. The mean sequential organ failure assessment (SOFA) score for the study and control groups were 10.2 and 1.6, respectively (P < 0.001). In patients with septic shock, the mean arterial pressure was lower (76 mmHg vs 82 mmHg, P = 0.032), and the heart rate was higher (99 bpm vs 86 bpm, P = 0.008). The cardiac output (5.9 L/min vs 5.5 L/min, P = 0.401) and systemic vascular resistance (1090 dynes•sec/cm(5) vs 1194 dynes•sec/cm(5), P = 0.303) were similar. The study group had a greater degree of myocardial dysfunction measured by global longitudinal strain (GLS) (-14.5 % vs -18.3 %, P <0.001), and the myocardial strain differed upon diagnosis and recovery (-14.5 % vs -16.0 %, P = 0.010). Conventional echocardiographic measurements such as LVEF (59 % in the study group vs 61 % in the control group, P = 0.169) did not differ between the two groups. Speckle tracking echocardiography can detect significant left ventricular impairment in patients with septic shock, which was not otherwise detectable by conventional echocardiography. The reversible nature of myocardial dysfunction in sepsis was also demonstrable. This echocardiographic technique is useful in the diagnosis and monitoring of sepsis-induced myocardial dysfunction.

Peripherally administered orexin improves survival of mice with endotoxin shock

PubMed Central

Ogawa, Yasuhiro; Irukayama-Tomobe, Yoko; Murakoshi, Nobuyuki; Kiyama, Maiko; Ishikawa, Yui; Hosokawa, Naoto; Tominaga, Hiromu; Uchida, Shuntaro; Kimura, Saki; Kanuka, Mika; Morita, Miho; Hamada, Michito; Takahashi, Satoru; Hayashi, Yu; Yanagisawa, Masashi

2016-01-01

Sepsis is a systemic inflammatory response to infection, accounting for the most common cause of death in intensive care units. Here, we report that peripheral administration of the hypothalamic neuropeptide orexin improves the survival of mice with lipopolysaccharide (LPS) induced endotoxin shock, a well-studied septic shock model. The effect is accompanied by a suppression of excessive cytokine production and an increase of catecholamines and corticosterone. We found that peripherally administered orexin penetrates the blood-brain barrier under endotoxin shock, and that central administration of orexin also suppresses the cytokine production and improves the survival, indicating orexin’s direct action in the central nervous system (CNS). Orexin helps restore body temperature and potentiates cardiovascular function in LPS-injected mice. Pleiotropic modulation of inflammatory response by orexin through the CNS may constitute a novel therapeutic approach for septic shock. DOI: http://dx.doi.org/10.7554/eLife.21055.001 PMID:28035899

IL-1B rs16944 polymorphism is related to septic shock and death.

PubMed

Jiménez-Sousa, María Ángeles; Medrano, Luz M; Liu, Pilar; Almansa, Raquel; Fernández-Rodríguez, Amanda; Gómez-Sánchez, Esther; Rico, Lucía; Heredia-Rodríguez, María; Gómez-Pesquera, Estefanía; Tamayo, Eduardo; Resino, Salvador

2017-01-01

IL-1β is a primary mediator of systemic inflammatory response syndrome (SIRS) and it may lead to shock septic. Our aim was to analyse whether IL-1B rs16944 polymorphism is associated with the onset of septic shock and death after major surgery. We performed a case-control study on 467 patients who underwent major cardiac or abdominal surgery. Of them, 205 patients developed septic shock (cases, SS group) and 262 patients developed SIRS (controls, SIRS group). The primary outcome variables were the development of septic shock and death within 90 days after diagnosis of septic shock. The IL-1B rs16944 polymorphism was genotyped by Sequenom's MassARRAY platform. The association analysis was performed under a recessive genetic model (AA vs. GG/GC). The frequency of septic shock was higher in patients with IL-1B rs16944 AA genotype than in patients with IL-1B rs16944 GG/AG genotype when all patients were taken into account (63·6% vs. 41·8%; P = 0·006), cardiac surgery (52·2% vs. 33·3%; P = 0·072) and abdominal surgery (76·2% vs. 50·2%; P = 0·023). However, the IL-1B rs16944 AA genotype was only associated with higher likelihood of septic shock in the analysis of all population [adjusted odds ratio (aOR) = 2·26 (95%CI = 1·03; 4·97; P = 0·042], but not when it was stratified by cardiac surgery (P = 0·175) or abdominal surgery (P = 0·467). Similarly, IL-1B rs16944 AA genotype was also associated with higher likelihood of septic shock-related death in all population [aOR = 2·67 (95%CI = 1·07; 4·97); P = 0·035]. IL-1B rs16944 AA genotype seems to be related to the onset of septic shock and death in patients who underwent major surgery. © 2016 Stichting European Society for Clinical Investigation Journal Foundation.

Urinary obstruction is an important complicating factor in patients with septic shock due to urinary infection.

PubMed

Reyner, Karina; Heffner, Alan C; Karvetski, Colleen H

2016-04-01

Urinary tract infection (UTI) is a common cause of severe sepsis, and anatomic urologic obstruction is a recognized factor for complicated disease. We aimed to identify the incidence of urinary obstruction complicating acute septic shock and determine the characteristics and outcomes of this group. Patients prospectively enrolled in a sepsis treatment pathway registry between October 2013 and July 2014 were reviewed for the diagnosis of UTI. Standardized medical record review was performed to confirm sepsis due to UTI and determine clinical variables including the presence of anatomic urinary obstruction. Patients with septic shock due to UTI with obstruction were compared with those without obstruction. The primary outcomes were incidence of urinary obstruction and hospital mortality. Among 1084 registry enrollees, 209 (19.2%) met inclusion criteria for the study. Acute anatomic obstruction was identified in 22 (10.5%) patients. Hospital mortality in patients with obstruction was 27.3% compared with 11.2% in patients without obstruction (absolute difference of 16.1%; P = .03; 95% confidence interval [CI], 1.2%-30.9%). Hospital length of stay among survivors was 12.8 days compared with 8.3 days (absolute difference of 4.5 days; P = .04; 95% CI, 0.2-8.8 days). History of urinary stone disease was independently associated with obstruction (odds ratio, 5.6; 95% CI, 2.2-14.3). Approximately 1 in 10 patients presenting with septic shock due to a urinary source is complicated by anatomic urinary obstruction. These patients have significantly higher mortality compared with patients without obstruction. Early imaging of patients with septic shock due to suspected urinary source should be considered to identify obstruction requiring emergency intervention. Copyright © 2015 Elsevier Inc. All rights reserved.

Procalcitonin as a diagnostic biomarker for septic shock and bloodstream infection in burn patients from the Formosa Fun Coast dust explosion.

PubMed

Wu, Rui-Xin; Chiu, Chih-Chien; Lin, Tzu-Chao; Yang, Ya-Sung; Lee, Yi; Lin, Jung-Chung; Chang, Feng-Yee

2017-12-01

Infection is the most common cause of death following burn injury. The study was conducted to compare the diagnostic value of serum procalcitonin (PCT) with the other current benchmarks as early predictors of septic shock and bloodstream infection in burn patients. We included 24 patients admitted to the Burn Unit of a medical center from June 2015 to December 2015 from the Formosa Fun Coast dust explosion. We categorized all patients at initial admission into either sepsis or septic shock groups. Laboratory tests including the worst PCT and C-reactive protein (CRP) levels, platelet (PLT), and white blood cell (WBC) count were performed at <48 h after admission. Patients were also classified in two groups with subsequent bacteremia and non-bacteremia groups during hospitalization. Significantly higher PCT levels were observed among participants with septic shock compared to those with sepsis (47.19 vs. 1.18 ng/mL, respectively; p < 0.001). Patients with bacteremia had significantly elevated PCT levels compared to patients without bacteremia (29.54 versus 1.81 ng/mL, respectively, p < 0.05). No significant differences were found in CRP levels, PLT, and WBC count between the two groups. PCT levels showed reasonable discriminative power (cut-off: 5.12 ng/mL; p = 0.01) in predicting of bloodstream infection in burn patients and the area under receiver operating curves was 0.92. PCT levels can be helpful in determining the septic shock and bloodstream infection in burn patients but CRP levels, PLT, and WBC count were of little diagnostic value. Copyright © 2017. Published by Elsevier B.V.

Pivotal role of glutathione depletion in plasma-induced endothelial oxidative stress during sepsis.

PubMed

Huet, Olivier; Cherreau, Christaine; Nicco, Carole; Dupic, Laurent; Conti, Marc; Borderie, Didier; Pene, Frédéric; Vicaut, Eric; Benhamou, Dan; Mira, Jean-Paul; Duranteau, Jacques; Batteux, Frédéric

2008-08-01

Plasma from septic shock patients can induce production of reactive oxygen species (ROS) by human umbilical vein endothelial cells (HUVEC) in vitro. How endothelial cells defend themselves against ROS under increased oxidative stress has not yet been examined. This study investigates the antioxidant defenses of HUVEC exposed to plasma obtained from either septic shock patients or healthy volunteers. Prospective, observational study. Medical intensive care unit in a university hospital. Twenty-five patients with septic shock and 10 healthy volunteers. Blood samples were collected within the first 24 hrs of septic shock. In vitro HUVEC production of ROS was studied by spectrofluorimetry using 2',7'-dichlorodihydrofluorescein diacetate fluorescent dye. Reactive nitrogen species were also assessed. Intracellular reduced glutathione (GSH) levels were measured using monochlorobimane fluorescent dye. Activity of catalase and superoxide dismutase in HUVEC were also measured. Cell death was assessed using YOPRO fluorescent dye and the MTT assay. On admission, the septic shock population's mean age was 55 yrs old, the mean Sequential Organ Failure Assessment score was 12, mean simplified acute physiology score was 50, and intensive care unit mortality rate was 45%. Evaluation of HUVEC antioxidant defenses showed a significantly decreased GSH level, increased catalase activity, and unchanged superoxide dismutase activity. ROS levels and cell death were significantly reduced when cells were pretreated with N-acetylcysteine or GSH, but no changes in reactive nitrogen species were observed. This study demonstrates that plasma-induced ROS production by HUVEC is associated with an intracellular decrease in reduced GSH. Both ROS levels and cell death decreased when N-acetylcysteine or GSH were added before exposing the cells to plasma. These data suggest a pivotal role of alterations in GSH in damage caused by sepsis-generated ROS in endothelial cell.

Mitigation of septic shock in mice and rhesus monkeys by human chorionic gonadotrophin-related oligopeptides

PubMed Central

Khan, N A; Vierboom, M P M; van Holten – Neelen, C; Breedveld, E; Zuiderwijk-Sick, E; Khan, A; Kondova, I; Braskamp, G; Savelkoul, H F J; Dik, W A; ‘t Hart, B A; Benner, R

2010-01-01

The marked improvement of several immune-mediated inflammatory diseases during pregnancy has drawn attention to pregnancy hormones as potential therapeutics for such disorders. Low molecular weight fractions derived from the pregnancy hormone human chorionic gonadotrophin (hCG) have remarkable potent immunosuppressive effects in mouse models of diabetes and septic shock. Based on these data we have designed a set of oligopeptides related to the primary structure of hCG and tested these in models of septic shock in mice and rhesus monkeys. We demonstrate that mice exposed to lipopolysaccharide (LPS) and treated subsequently with selected tri-, tetra-, penta- and hepta-meric oligopeptides (i.e. MTR, VVC, MTRV, LQGV, AQGV, VLPALP, VLPALPQ) are protected against fatal LPS-induced septic shock. Moreover, administration of a cocktail of three selected oligopeptides (LQGV, AQGV and VLPALP) improved the pathological features markedly and nearly improved haemodynamic parameters associated with intravenous Escherichia coli-induced septic shock in rhesus monkeys. These data indicate that the designed hCG-related oligopeptides may present a potential treatment for the initial hyperdynamic phase of septic shock in humans. PMID:20345979

Staphylococcus aureus Regulatory RNAs as Potential Biomarkers for Bloodstream Infections

PubMed Central

Bordeau, Valérie; Cady, Anne; Revest, Matthieu; Rostan, Octavie; Sassi, Mohamed; Tattevin, Pierre; Donnio, Pierre-Yves

2016-01-01

Staphylococcus aureus is a commensal bacterium and pathogen. Identifying biomarkers for the transition from colonization to disease caused by this organism would be useful. Several S. aureus small RNAs (sRNAs) regulate virulence. We investigated presence and expression of 8 sRNAs in 83 S. aureus strains from 42 patients with sepsis or septic shock and 41 asymptomatic colonized carriers. Small pathogenicity island sRNAs sprB and sprC were clade specific. Six sRNAs had variable expression not correlated with clinical status. Expression of RNAIII was lower in strains from septic shock patients than in strains from colonized patients. When RNAIII was associated with expression of sprD, colonizing strains could be discriminated from strains in patients with bloodstream infections, including patients with sepsis and septic shock. Isolates associated with colonization might have sRNAs with target expression different from those of disease isolates. Monitoring expression of RNAIII and sprD could help determine severity of bloodstream infections. PMID:27224202

Staphylococcus aureus Regulatory RNAs as Potential Biomarkers for Bloodstream Infections.

PubMed

Bordeau, Valérie; Cady, Anne; Revest, Matthieu; Rostan, Octavie; Sassi, Mohamed; Tattevin, Pierre; Donnio, Pierre-Yves; Felden, Brice

2016-09-01

Staphylococcus aureus is a commensal bacterium and pathogen. Identifying biomarkers for the transition from colonization to disease caused by this organism would be useful. Several S. aureus small RNAs (sRNAs) regulate virulence. We investigated presence and expression of 8 sRNAs in 83 S. aureus strains from 42 patients with sepsis or septic shock and 41 asymptomatic colonized carriers. Small pathogenicity island sRNAs sprB and sprC were clade specific. Six sRNAs had variable expression not correlated with clinical status. Expression of RNAIII was lower in strains from septic shock patients than in strains from colonized patients. When RNAIII was associated with expression of sprD, colonizing strains could be discriminated from strains in patients with bloodstream infections, including patients with sepsis and septic shock. Isolates associated with colonization might have sRNAs with target expression different from those of disease isolates. Monitoring expression of RNAIII and sprD could help determine severity of bloodstream infections.

CRH Affects the Phenotypic Expression of Sepsis-Associated Virulence Factors by Streptococcus pneumoniae Serotype 1 In vitro

PubMed Central

Ngo Ndjom, Colette G.; Kantor, Lindsay V.; Jones, Harlan P.

2017-01-01

Sepsis is a life-threatening health condition caused by infectious pathogens of the respiratory tract, and accounts for 28–50% of annual deaths in the US alone. Current treatment regimen advocates the use of corticosteroids as adjunct treatment with antibiotics, for their broad inhibitory effect on the activity and production of pro-inflammatory mediators. However, despite their use, corticosteroids have not proven to be able to reverse the death incidence among septic patients. We have previously demonstrated the potential for neuroendocrine factors to directly influence Streptococcus pneumoniae virulence, which may in turn mediate disease outcome leading to sepsis and septic shock. The current study investigated the role of Corticotropin-releasing hormone (CRH) in mediating key markers of pneumococcal virulence as important phenotypic determinants of sepsis and septic shock risks. In vitro cultures of serotype 1 pneumococcal strain with CRH promoted growth rate, increased capsule thickness and penicillin resistance, as well as induced pneumolysin gene expression. These results thus provide significant insights of CRH–pathogen interactions useful in understanding the underlying mechanisms of neuroendocrine factor's role in the onset of community acquired pneumonias (CAP), sepsis and septic shock. PMID:28690980

Hitch-hiker taken for a ride: an unusual cause of myocarditis, septic shock and adult respiratory distress syndrome

PubMed Central

Kushawaha, Anurag; Brown, Mark; Martin, Ismael; Evenhuis, Walther

2013-01-01

Rocky Mountain spotted fever (RMSF) is a serious tick-borne illness caused by Rickettsia rickettsii that is endemic in southeastern USA. Although RMSF has been described as causing the classic clinical triad of fever, headache and a characteristic rash, serious and potentially life-threatening manifestations can occur. Cardiopulmonary involvement, although infrequent, may occur with severe cases of RMSF. Rickettsial myocarditis is an uncommon occurrence. We present a case of a previously healthy 26-year-old man, who was hitch-hiking across the southeastern USA, with serologically proven RMSF causing adult respiratory distress syndrome, septic shock and myocarditis manifested by elevated cardiac enzymes and decrease in myocardial function. After treatment with antibiotics, the myocarditis resolved. Therefore, although unusual, clinicians should be aware of possible myocardial involvement in patients with appropriate tick-exposure histories or other clinical signs of RMSF. PMID:23314875

Enrollment into a time sensitive clinical study in the critical care setting: results from computerized septic shock sniffer implementation.

PubMed

Herasevich, Vitaly; Pieper, Matthew S; Pulido, Juan; Gajic, Ognjen

2011-01-01

Recruitment of patients into time sensitive clinical trials in intensive care units (ICU) poses a significant challenge. Enrollment is limited by delayed recognition and late notification of research personnel. The objective of the present study was to evaluate the effectiveness of the implementation of electronic screening (septic shock sniffer) regarding enrollment into a time sensitive (24 h after onset) clinical study of echocardiography in severe sepsis and septic shock. We developed and tested a near-real time computerized alert system, the septic shock sniffer, based on established severe sepsis/septic shock diagnostic criteria. A sniffer scanned patients' data in the electronic medical records and notified the research coordinator on call through an institutional paging system of potentially eligible patients. The performance of the septic shock sniffer was assessed. The septic shock sniffer performed well with a positive predictive value of 34%. Electronic screening doubled enrollment, with 68 of 4460 ICU admissions enrolled during the 9 months after implementation versus 37 of 4149 ICU admissions before sniffer implementation (p<0.05). Efficiency was limited by study coordinator availability (not available at nights or weekends). Automated electronic medical records screening improves the efficiency of enrollment and should be a routine tool for the recruitment of patients into time sensitive clinical trials in the ICU setting.

Enrollment into a time sensitive clinical study in the critical care setting: results from computerized septic shock sniffer implementation

PubMed Central

Pieper, Matthew S; Pulido, Juan; Gajic, Ognjen

2011-01-01

Objective Recruitment of patients into time sensitive clinical trials in intensive care units (ICU) poses a significant challenge. Enrollment is limited by delayed recognition and late notification of research personnel. The objective of the present study was to evaluate the effectiveness of the implementation of electronic screening (septic shock sniffer) regarding enrollment into a time sensitive (24 h after onset) clinical study of echocardiography in severe sepsis and septic shock. Design We developed and tested a near-real time computerized alert system, the septic shock sniffer, based on established severe sepsis/septic shock diagnostic criteria. A sniffer scanned patients' data in the electronic medical records and notified the research coordinator on call through an institutional paging system of potentially eligible patients. Measurement The performance of the septic shock sniffer was assessed. Results The septic shock sniffer performed well with a positive predictive value of 34%. Electronic screening doubled enrollment, with 68 of 4460 ICU admissions enrolled during the 9 months after implementation versus 37 of 4149 ICU admissions before sniffer implementation (p<0.05). Efficiency was limited by study coordinator availability (not available at nights or weekends). Conclusions Automated electronic medical records screening improves the efficiency of enrollment and should be a routine tool for the recruitment of patients into time sensitive clinical trials in the ICU setting. PMID:21508415

Time- and fluid-sensitive resuscitation for hemodynamic support of children in septic shock: barriers to the implementation of the American College of Critical Care Medicine/Pediatric Advanced Life Support Guidelines in a pediatric intensive care unit in a developing world.

PubMed

Oliveira, Cláudio F; Nogueira de Sá, Flávio R; Oliveira, Débora S F; Gottschald, Adriana F C; Moura, Juliana D G; Shibata, Audrey R O; Troster, Eduardo J; Vaz, Flávio A C; Carcillo, Joseph A

2008-12-01

To analyze mortality rates of children with severe sepsis and septic shock in relation to time-sensitive fluid resuscitation and treatments received and to define barriers to the implementation of the American College of Critical Care Medicine/Pediatric Advanced Life Support guidelines in a pediatric intensive care unit in a developing country. Retrospective chart review and prospective analysis of septic shock treatment in a pediatric intensive care unit of a tertiary care teaching hospital. Ninety patients with severe sepsis or septic shock admitted between July 2002 and June 2003 were included in this study. Of the 90 patients, 83% had septic shock and 17% had severe sepsis; 80 patients had preexisting severe chronic diseases. Patients with septic shock who received less than a 20-mL/kg dose of resuscitation fluid in the first hour of treatment had a mortality rate of 73%, whereas patients who received more than a 40-mL/kg dose in the first hour of treatment had a mortality rate of 33% (P < 0.05). Patients treated less than 30 minutes after diagnosis of severe sepsis and septic shock had a significantly lower mortality rate (40%) than patients treated more than 60 minutes after diagnosis (P < 0.05). Controlling for the risk of mortality, early fluid resuscitation was associated with a 3-fold reduction in the odds of death (odds ratio, 0.33; 95% confidence interval, 0.13-0.85). The most important barriers to achieve adequate severe sepsis and septic shock treatment were lack of adequate vascular access, lack of recognition of early shock, shortage of health care providers, and nonuse of goals and treatment protocols. The mortality rate was higher for children older than 2 years, for those who received less than 40 mL/kg in the first hour, and for those whose treatment was not initiated in the first 30 minutes after the diagnosis of septic shock. The acknowledgment of existing barriers to a timely fluid administration and the establishment of objectives to overcome these barriers may lead to a more successful implementation of the American College of Critical Care Medicine guidelines and reduced mortality rates for children with septic shock in the developing world.

Assessment of Neutrophil Function in Patients with Septic Shock: Comparison of Methods

PubMed Central

Wenisch, C.; Fladerer, P.; Patruta, S.; Krause, R.; Hörl, W.

2001-01-01

Patients with septic shock are shown to have decreased neutrophil phagocytic function by multiple assays, and their assessment by whole-blood assays (fluorescence-activated cell sorter analysis) correlates with assays requiring isolated neutrophils (microscopic and spectrophotometric assays). For patients with similar underlying conditions but without septic shock, this correlation does not occur. PMID:11139215

Terlipressin: vasopressin analog and novel drug for septic shock.

PubMed

Pesaturo, Adam B; Jennings, Heath R; Voils, Stacy A

2006-12-01

To review and assess available literature on chemistry, pharmacology, pharmacodynamics, pharmacokinetics, clinical studies, adverse events, drug interactions, and dosing and administration of terlipressin in septic shock. A literature search of MEDLINE (1966-September 2006), International Pharmaceutical Abstracts (1970-September 2006), and Cochrane database (third quarter 2006) was conducted, using key terms of terlipressin, lypressin, triglycyl-lysine vasopressin, hemodynamic support, septic shock, vasopressor, and V1 receptor agonist. Bibliographies of relevant articles were reviewed for additional references. Available English-language literature, including abstracts, animal studies, preclinical studies, clinical trials, and review articles, were examined. Because of potentially favorable pharmacokinetics versus vasopressin and limited availability of vasopressin in some countries, the effects of terlipressin, a vasopressin analog, have been studied recently for the treatment of septic shock. When administered as a 1-2 mg intravenous dose in patients with septic shock, terlipressin increases mean arterial pressure, urine output, systemic vascular resistance index, pulmonary vascular resistance index, and left and right ventricular stroke work index while decreasing heart rate, cardiac output, lactate, and oxygen delivery and consumption index. It is unclear whether lower doses of terlipressin would produce a similar vasopressor response with fewer cardiopulmonary effects and whether the effects of the drug on oxygen transport indices are detrimental. Terlipressin is a promising investigational medication for treatment of septic shock. Small trials have shown terlipressin to have favorable effects on hemodynamics in patients with septic shock refractory to conventional vasopressor treatment. It should be used with extreme caution in patients with underlying cardiac or pulmonary dysfunction. Further studies are needed to verify safety, efficacy, and dosing of terlipressin in patients with septic shock, and its use cannot be recommended in lieu of vasopressin at this time.

Early decreased neutrophil responsiveness is related to late onset sepsis in multitrauma patients: An international cohort study.

PubMed

Groeneveld, Kathelijne M; Koenderman, Leo; Warren, Brian L; Jol, Saskia; Leenen, Luke P H; Hietbrink, Falco

2017-01-01

Severe trauma can lead to the development of infectious complications after several days, such as sepsis. Early identification of patients at risk will aid anticipating these complications. The aim of this study was to test the relation between the acute (<24 hours) inflammatory response after injury measured by neutrophil responsiveness and the late (>5 days) development of septic complications and validate this in different trauma populations. Two prospective, observational, cohort series in the Netherlands and South Africa, consisting of severely injured trauma patients. Neutrophil responsiveness by fMLF-induced active FcγRII was measured in whole blood flowcytometry, as read out for the systemic immune response within hours after trauma. Sepsis was scored daily. Ten of the 36 included Dutch patients developed septic shock. In patients with septic shock, neutrophils showed a lower expression of fMLF-induced active FcγRII immediately after trauma when compared to patients without septic shock (P = 0.001). In South Africa 11 of 73 included patients developed septic shock. Again neutrophils showed lower expression of fMLF induced active FcγRII (P = 0.001). In the combined cohort, all patients who developed septic shock demonstrated a decreased neutrophil responsiveness. Low responsiveness of neutrophils for the innate stimulus fMLF immediately after trauma preceded the development of septic shock during admission by almost a week and did not depend on a geographical/racial background, hospital protocols and health care facilities. Decreased neutrophil responsiveness appears to be a prerequisite for septic shock after trauma. This might enable anticipation of this severe complication in trauma patients.

Clinical outcome comparison of patients with septic shock defined by the new sepsis-3 criteria and by previous criteria

PubMed Central

Ryoo, Seung Mok; Kang, Gu Hyun; Shin, Tae Gun; Hwang, Sung Yeon; Kim, Kyuseok; Jo, You Hwan; Park, Yoo Seok; Choi, Sung-Hyuk; Yoon, Young Hoon; Kwon, Woon Yong; Suh, Gil Joon; Lim, Tae Ho; Han, Kap Su; Choi, Han Sung; Chung, Sung Phil

2018-01-01

Background We compared the clinical characteristics and outcomes between the new definition of sepsis-3 septic shock and the definition previously used from 1991 until recently. Methods We conducted an observational study using a prospective, multi-center registry of septic shock from October 2015 to February 2017. Registry data were collected by 10 emergency departments (EDs) in tertiary hospitals that are members of the Korean Shock Society. Data on septic shock patients who met the previous septic shock definition were collected. The patients were divided into a sepsis-3 defined septic shock group, made up of those who met the new criteria for refractory hypotension with hyperlactatemia, and a group of those who met only the 1991 definition for septic shock. The primary outcome was 90-day mortality, and secondary outcomes were 28-day mortality and in-hospital mortality. Results Of all 1,028 included patients, 574 (55.8%) met the septic shock criteria for sepsis-3, leaving 454 patients who met only the previous definition. Those who met the sepsis-3 criteria demonstrated higher comorbidity than those who met the previous definition (83.1% vs. 75.3%, P<0.01), but there was no difference in infection focus. The sequential organ failure assessment (SOFA) (initial/maximal), the acute physiology, and the chronic health evaluation II scores were significantly higher in for those who met the sepsis-3 criteria [6.5±3.1 vs. 5.0±2.9, 9.3±3.8 vs. 6.6±3.4, and 20.0 (15.0–26.0) vs. 15.0 (10.0–20.3), respectively; P<0.01]. The 90-day mortality was significantly higher in the sepsis-3 group (32.1% vs. 23.3%; P<0.01). In-hospital and 28-day mortality were also higher in the sepsis-3 group (26.8% vs. 17.1% and 25.1% vs. 16.5%, respectively; P<0.01). Conclusions The new definition of septic shock successfully selected patients with greater severities and worse outcomes. PMID:29607156

Time Course of Septic Shock in Immunocompromised and Nonimmunocompromised Patients.

PubMed

Jamme, Matthieu; Daviaud, Fabrice; Charpentier, Julien; Marin, Nathalie; Thy, Michaël; Hourmant, Yannick; Mira, Jean-Paul; Pène, Frédéric

2017-12-01

To address the impact of underlying immune conditions on the course of septic shock with respect to both mortality and the development of acute infectious and noninfectious complications. An 8-year (2008-2015) monocenter retrospective study. A medical ICU in a tertiary care center. Patients diagnosed for septic shock within the first 48 hours of ICU admission were included. Patients were classified in four subgroups with respect to their immune status: nonimmunocompromised and immunocompromised distributed into hematologic or solid malignancies and nonmalignant immunosuppression. Outcomes were in-hospital death and the development of ischemic and hemorrhagic complications and ICU-acquired infections. The determinants of death and complications were addressed by multivariate competing risk analysis. None. Eight hundred one patients were included. Among them, 305 (38%) were immunocompromised, distributed into solid tumors (122), hematologic malignancies (106), and nonmalignant immunosuppression (77). The overall 3-day, in-ICU, and in-hospital mortality rates were 14.1%, 37.3%, and 41.3%, respectively. Patients with solid tumors displayed increased in-hospital mortality (cause-specific hazard, 2.20 [95% CI, 1.64-2.96]; p < 0.001). ICU-acquired infections occurred in 211 of the 3-day survivors (33%). In addition, 95 (11.8%) and 70 (8.7%) patients exhibited severe ischemic or hemorrhagic complications during the ICU stay. There was no association between the immune status and the occurrence of ICU-acquired infections. Nonmalignant immunosuppression and hematologic malignancies were independently associated with increased risks of severe ischemic events (cause-specific hazard, 2.12 [1.14-3.96]; p = 0.02) and hemorrhage (cause-specific hazard, 3.17 [1.41-7.13]; p = 0.005), respectively. The underlying immune status impacts on the course of septic shock and on the susceptibility to ICU-acquired complications. This emphasizes the complexity of sepsis syndromes in relation with comorbid conditions and raises the question of the relevant endpoints in clinical studies.

Developing a New Definition and Assessing New Clinical Criteria for Septic Shock: For the Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3).

PubMed

Shankar-Hari, Manu; Phillips, Gary S; Levy, Mitchell L; Seymour, Christopher W; Liu, Vincent X; Deutschman, Clifford S; Angus, Derek C; Rubenfeld, Gordon D; Singer, Mervyn

2016-02-23

Septic shock currently refers to a state of acute circulatory failure associated with infection. Emerging biological insights and reported variation in epidemiology challenge the validity of this definition. To develop a new definition and clinical criteria for identifying septic shock in adults. The Society of Critical Care Medicine and the European Society of Intensive Care Medicine convened a task force (19 participants) to revise current sepsis/septic shock definitions. Three sets of studies were conducted: (1) a systematic review and meta-analysis of observational studies in adults published between January 1, 1992, and December 25, 2015, to determine clinical criteria currently reported to identify septic shock and inform the Delphi process; (2) a Delphi study among the task force comprising 3 surveys and discussions of results from the systematic review, surveys, and cohort studies to achieve consensus on a new septic shock definition and clinical criteria; and (3) cohort studies to test variables identified by the Delphi process using Surviving Sepsis Campaign (SSC) (2005-2010; n = 28,150), University of Pittsburgh Medical Center (UPMC) (2010-2012; n = 1,309,025), and Kaiser Permanente Northern California (KPNC) (2009-2013; n = 1,847,165) electronic health record (EHR) data sets. Evidence for and agreement on septic shock definitions and criteria. The systematic review identified 44 studies reporting septic shock outcomes (total of 166,479 patients) from a total of 92 sepsis epidemiology studies reporting different cutoffs and combinations for blood pressure (BP), fluid resuscitation, vasopressors, serum lactate level, and base deficit to identify septic shock. The septic shock-associated crude mortality was 46.5% (95% CI, 42.7%-50.3%), with significant between-study statistical heterogeneity (I2 = 99.5%; τ2 = 182.5; P < .001). The Delphi process identified hypotension, serum lactate level, and vasopressor therapy as variables to test using cohort studies. Based on these 3 variables alone or in combination, 6 patient groups were generated. Examination of the SSC database demonstrated that the patient group requiring vasopressors to maintain mean BP 65 mm Hg or greater and having a serum lactate level greater than 2 mmol/L (18 mg/dL) after fluid resuscitation had a significantly higher mortality (42.3% [95% CI, 41.2%-43.3%]) in risk-adjusted comparisons with the other 5 groups derived using either serum lactate level greater than 2 mmol/L alone or combinations of hypotension, vasopressors, and serum lactate level 2 mmol/L or lower. These findings were validated in the UPMC and KPNC data sets. Based on a consensus process using results from a systematic review, surveys, and cohort studies, septic shock is defined as a subset of sepsis in which underlying circulatory, cellular, and metabolic abnormalities are associated with a greater risk of mortality than sepsis alone. Adult patients with septic shock can be identified using the clinical criteria of hypotension requiring vasopressor therapy to maintain mean BP 65 mm Hg or greater and having a serum lactate level greater than 2 mmol/L after adequate fluid resuscitation.

Plasma granulocyte colony-stimulating factor and granulocyte-macrophage colony-stimulating factor levels in critical illness including sepsis and septic shock: relation to disease severity, multiple organ dysfunction, and mortality.

PubMed

Presneill, J J; Waring, P M; Layton, J E; Maher, D W; Cebon, J; Harley, N S; Wilson, J W; Cade, J F

2000-07-01

To define the circulating levels of granulocyte colony-stimulating factor (G-CSF) and granulocyte-macrophage colony-stimulating factor (GM-CSF) during critical illness and to determine their relationship to the severity of illness as measured by the Acute Physiology and Chronic Health Evaluation (APACHE) II score, the development of multiple organ dysfunction, or mortality. Prospective cohort study. University hospital intensive care unit. A total of 82 critically ill adult patients in four clinically defined groups, namely septic shock (n = 29), sepsis without shock (n = 17), shock without sepsis (n = 22), and nonseptic, nonshock controls (n = 14). None. During day 1 of septic shock, peak plasma levels of G-CSF, interleukin (IL)-6, and leukemia inhibitory factor (LIF), but not GM-CSF, were greater than in sepsis or shock alone (p < .001), and were correlated among themselves (rs = 0.44-0.77; p < .02) and with the APACHE II score (rs = 0.25-0.40; p = .03 to .18). G-CSF, IL-6, and UF, and sepsis, shock, septic shock, and APACHE II scores were strongly associated with organ dysfunction or 5-day mortality by univariate analysis. However, multiple logistic regression analysis showed that only septic shock remained significantly associated with organ dysfunction and only APACHE II scores and shock with 5-day mortality. Similarly, peak G-CSF, IL-6, and LIF were poorly predictive of 30-day mortality. Plasma levels of G-CSF, IL-6, and LIF are greatly elevated in critical illness, including septic shock, and are correlated with one another and with the severity of illness. However, they are not independently predictive of mortality, or the development of multiple organ dysfunction. GM-CSF was rarely elevated, suggesting different roles for G-CSF and GM-CSF in human septic shock.

Mortality related to invasive infections, sepsis, and septic shock in critically ill children in Australia and New Zealand, 2002-13: a multicentre retrospective cohort study.

PubMed

Schlapbach, Luregn J; Straney, Lahn; Alexander, Janet; MacLaren, Graeme; Festa, Marino; Schibler, Andreas; Slater, Anthony

2015-01-01

Severe infections kill more than 4·5 million children every year. Population-based data for severe infections in children requiring admission to intensive care units (ICUs) are scarce. We assessed changes in incidence and mortality of severe infections in critically ill children in Australia and New Zealand. We did a retrospective multicentre cohort study of children requiring intensive care in Australia and New Zealand between 2002 and 2013, with data from the Australian and New Zealand Paediatric Intensive Care Registry. We included children younger than 16 years with invasive infection, sepsis, or septic shock. We assessed incidence and mortality in the ICU for 2002-07 versus 2008-13. During the study period, 97 127 children were admitted to ICUs, 11 574 (11·9%) had severe infections, including 6688 (6·9%) with invasive infections, 2847 (2·9%) with sepsis, and 2039 (2·1%) with septic shock. Age-standardised incidence increased each year by an average of 0·56 cases per 100 000 children (95% CI 0·41-0·71) for invasive infections, 0·09 cases per 100 000 children (0·00-0·17) for sepsis, and 0·08 cases per 100 000 children (0·04-0·12) for septic shock. 260 (3·9%) of 6688 patients with invasive infection died, 159 (5·6%) of 2847 with sepsis died, and 346 (17·0%) of 2039 with septic shock died, compared with 2893 (3·0%) of all paediatric ICU admissions. Children admitted with invasive infections, sepsis, and septic shock accounted for 765 (26·4%) of 2893 paediatric deaths in ICUs. Comparing 2008-13 with 2002-07, risk-adjusted mortality decreased significantly for invasive infections (odds ratio 0·72, 95% CI 0·56-0·94; p=0·016), and for sepsis (0·66, 0·47-0·93; p=0·016), but not significantly for septic shock (0·79, 0·61-1·01; p=0·065). Severe infections remain a major cause of mortality in paediatric ICUs, representing a major public health problem. Future studies should focus on patients with the highest risk of poor outcome, and assess the effectiveness of present sepsis interventions in children. National Medical Health and Research Council, Australian Resuscitation Outcomes Consortium, Centre of Research Excellence (1029983). Copyright © 2015 Elsevier Ltd. All rights reserved.

Acute Neonatal Parotitis with Late-Onset Septic Shock due to Streptococcus agalactiae

PubMed Central

Boulyana, M.

2014-01-01

Acute neonatal parotitis (ANP) is a very rare disease. Most cases are managed conservatively; early antibiotics and adequate hydration may reduce the need for surgery. The most common cause of ANP is Staphylococcus aureus. We report a rare case of acute neonatal parotitis with late-onset septic shock due to Streptococcus agalactiae. The diagnosis was confirmed with ultrasound and isolation of Streptococcus agalactiae from blood culture. The patient was treated successfully with 10 days of intravenous antibiotics and supportive measures. Despite being rare, streptococcal ANP should be considered in the etiological diagnosis of neonatal sepsis. Early diagnosis and appropriate antibiotic might prevent serious complications. PMID:24653847

Volume Overload: Prevalence, Risk Factors, and Functional Outcome in Survivors of Septic Shock

PubMed Central

Carlbom, David; Caldwell, Ellen; Himmelfarb, Jonathan; Hough, Catherine L.

2015-01-01

Rationale: Survivors of septic shock have impaired functional status. Volume overload is associated with poor outcomes in patients with septic shock, but the impact of volume overload on functional outcome and discharge destination of survivors is unknown. Objectives: This study describes patterns of fluid management both during and after septic shock. We examined factors associated with volume overload upon intensive care unit (ICU) discharge. We then examined associations between volume overload upon ICU discharge, mobility limitation, and discharge to a healthcare facility in septic shock survivors, with the hypothesis that volume overload is associated with increased odds of these outcomes. Methods: We retrospectively reviewed the medical records of 247 patients admitted with septic shock to an academic county hospital between June 2009 and April 2012 who survived to ICU discharge. We defined volume overload as a fluid balance expected to increase the subject’s admission weight by 10%. Statistical methods included unadjusted analyses and multivariable logistic regression. Measurements and Main Results: Eighty-six percent of patients had a positive fluid balance, and 35% had volume overload upon ICU discharge. Factors associated with volume overload in unadjusted analyses included more severe illness, cirrhosis, blood transfusion during shock, and higher volumes of fluid administration both during and after shock. Blood transfusion during shock was independently associated with increased odds of volume overload (odds ratio [OR], 2.65; 95% confidence interval [CI], 1.33–5.27; P = 0.01) after adjusting for preexisting conditions and severity of illness. Only 42% of patients received at least one dose of a diuretic during their hospitalization. Volume overload upon ICU discharge was independently associated with inability to ambulate upon hospital discharge (OR, 2.29; 95% CI, 1.24–4.25; P = 0.01) and, in patients admitted from home, upon discharge to a healthcare facility (OR, 2.34; 95% CI, 1.1–4.98; P = 0.03). Conclusions: Volume overload is independently associated with impaired mobility and discharge to a healthcare facility in survivors of septic shock. Prevention and treatment of volume overload in patients with septic shock warrants further investigation. PMID:26394090

Extracorporeal membrane oxygenation for refractory septic shock in adults.

PubMed

Park, Taek Kyu; Yang, Jeong Hoon; Jeon, Kyeongman; Choi, Seung-Hyuk; Choi, Jin-Ho; Gwon, Hyeon-Cheol; Chung, Chi Ryang; Park, Chi Min; Cho, Yang Hyun; Sung, Kiick; Suh, Gee Young

2015-02-01

The role of extracorporeal membrane oxygenation (ECMO) remains controversial in adult patients with refractory septic shock. We sought to describe the clinical outcomes of adult patients supported by ECMO during septic shock refractory to conventional treatment. We analysed consecutive adult patients with refractory septic shock, assisted by an ECMO system between January 2005 and December 2013 in a single-centre registry. The primary outcome was survival to hospital discharge. A total of 32 patients (21 males) received ECMO support for refractory septic shock. Of these, 14 patients (43.8%) had undergone cardiopulmonary resuscitation (CPR) and 7 patients (21.9%) did not achieve the return of spontaneous circulation until initiation of ECMO flow. ECMO was weaned off successfully in 13 patients (40.6%) and 7 patients (21.9%) survived to hospital discharge. The survivors had lower peak lactate (4.5 vs 15.1 mmol/l, P = 0.03), lower Sepsis-related Organ Failure Assessment day 3 score (15 vs 18, P = 0.01) and higher peak troponin I (32.8 vs 3.7 ng/ml, P = 0.02) than the non-survivors. None of the patients (31.3%) in whom ECMO was initiated more than 30.5 h after onset of septic shock, survived. In multivariable-adjusted models, CPR [adjusted hazard ratio (HR), 4.61; 95% confidence interval (CI), 1.55-13.69; P = 0.006] was an independent predictor of in-hospital mortality after ECMO in patients with refractory septic shock. Higher peak troponin I > 15 ng/ml (adjusted HR, 0.34; 95% CI, 0.12-0.97; P = 0.04) was associated with a lower risk of in-hospital mortality. Survival to hospital discharge remained low in adult patients with refractory septic shock despite ECMO support. Our findings suggest that implantation of ECMO during refractory septic shock could be considered in patients with severe myocardial injury but should be avoided in patients who have received CPR. © The Author 2014. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.

[Septic shock Fusobacterium necrophorum from origin gynecological at complicated an acute respiratory distress syndrome: a variant of Lemierre's syndrome].

PubMed

Huynh-Moynot, Sophie; Commandeur, Diane; Danguy des Déserts, Marc; Drouillard, Isabelle; Leguen, Patrick; Ould-Ahmed, Mehdi

2011-01-01

We report a case of a female patient of 47 years old who presents in a state of septic shock with acute insufficient respiratory complicated with syndrome of acute respiratory distress, together with a list of abdominal pain and polyarthralgia too. In her case of medical history, it is retained that she has had a intra-uterine device since 6 years without medical follow up. The initial thoraco-abdomino-pelvic scan shows a left ovarian vein thrombosis, as well as the opaqueness alveolus diffused interstitiel bilaterally and an aspect of ileitis. The IUD is taken off because of sudden occuring of purulent leucorrhoea. This results in a clinical and paraclinical improvement, whereas aminopenicillin was administered to the patient since 1 week. The microbiological blood test allows to put in evidence Fusobacterium necrophorum found in a blood culture and is sensitive to the amoxicilline-acide clavulanique and metronidazole. Isolation of this bacteria, classically found in Lemierre's syndrome, allowed to explain the multilfocalization of the symtoms and the list of pain. The whole concerns about a variant of Lemierre's syndrom: a state of septic shock secondary then caused by the anaerobic Gram negative bacilli, which is a commensal bacteria of the female genital tractus, complicated of septic emboli typical.

Risk Factors for Development of Septic Shock in Patients with Urinary Tract Infection

PubMed Central

Hsiao, Chih-Yen; Yang, Huang-Yu; Chang, Chih-Hsiang; Lin, Hsing-Lin; Wu, Chao-Yi; Hsiao, Meng-Chang; Hung, Peir-Haur; Liu, Su-Hsun; Weng, Cheng-Hao; Lee, Cheng-Chia; Chen, Yung-Chang; Wu, Tzu-Chin

2015-01-01

Introduction. Severe sepsis and septic shock are associated with substantial mortality. However, few studies have assessed the risk of septic shock among patients who suffered from urinary tract infection (UTI). Materials and Methods. This retrospective study recruited UTI cases from an acute care hospital between January 2006 and October 2012 with prospective data collection. Results. Of the 710 participants admitted for UTI, 80 patients (11.3%) had septic shock. The rate of bacteremia is 27.9%; acute kidney injury is 12.7%, and the mortality rate is 0.28%. Multivariable logistic regression analyses indicated that coronary artery disease (CAD) (OR: 2.521, 95% CI: 1.129–5.628, P = 0.024), congestive heart failure (CHF) (OR: 4.638, 95% CI: 1.908–11.273, P = 0.001), and acute kidney injury (AKI) (OR: 2.992, 95% CI: 1.610–5.561, P = 0.001) were independently associated with septic shock in patients admitted with UTI. In addition, congestive heart failure (female, OR: 4.076, 95% CI: 1.355–12.262, P = 0.012; male, OR: 5.676, 95% CI: 1.103–29.220, P = 0.038, resp.) and AKI (female, OR: 2.995, 95% CI: 1.355–6.621, P = 0.007; male, OR: 3.359, 95% CI: 1.158–9.747, P = 0.026, resp.) were significantly associated with risk of septic shock in both gender groups. Conclusion. This study showed that patients with a medical history of CAD or CHF have a higher risk of shock when admitted for UTI treatment. AKI, a complication of UTI, was also associated with septic shock. Therefore, prompt and aggressive management is recommended for those with higher risks to prevent subsequent treatment failure in UTI patients. PMID:26380292

Pancreatic injury in patients with septic shock: A literature review

PubMed Central

Chaari, Anis; Abdel Hakim, Karim; Bousselmi, Kamel; Etman, Mahmoud; El Bahr, Mohamed; El Saka, Ahmed; Hamza, Eman; Ismail, Mohamed; Khalil, Elsayed Mahmoud; Kauts, Vipin; Casey, William Francis

2016-01-01

Sepsis and septic shock are life threatening condition associated with high mortality rate in critically-ill patients. This high mortality is mainly related to the inadequacy between oxygen delivery and cellular demand leading to the onset of multiorgan dysfunction. Whether this multiorgan failure affect the pancreas is not fully investigated. In fact, pancreatic injury may occur because of ischemia, overwhelming inflammatory response, oxidative stress, cellular apoptosis and/or metabolic derangement. Increased serum amylase and/or lipase levels are common in patients with septic shock. However, imaging test rarely reveal significant pancreatic damage. Whether pancreatic dysfunction does affect the prognosis of patients with septic shock or not is still a matter of debate. In fact, only few studies with limited sample size assessed the clinical relevance of the pancreatic injury in this group of patients. In this review, we aimed to describe the epidemiology and the physiopathology of pancreatic injury in septic shock patients, to clarify whether it requires specific management and to assess its prognostic value. Our main finding is that pancreatic injury does not significantly affect the outcome in septic shock patients. Hence, increased serum pancreatic enzymes without clinical features of acute pancreatitis do not require further imaging investigations and specific therapeutic intervention. PMID:27559431

The role of contact system in septic shock: the next target? An overview of the current evidence.

PubMed

Nicola, Henrique

2017-01-01

Septic shock remains challenging to intensive care units worldwide, despite recent documented improvement in mortality over the years. Multiple new therapies have been attempted without success in large clinical trials. Evidence concerning the role of the contact system and bradykinin on septic shock physiological manifestations is shown by this article. The objective of the study is to review the current evidence linking contact system activation and septic shock, as well as efficacy of available therapies targeting this pathophysiological pathway and to evaluate the potential of further researching the matter. Multiple animal studies are already available and suggestive of a meaningful role of contact system activation on septic shock. However, human trials are still scarce, and the ones available are not enough to establish such a strong connection. Furthermore, attempted therapies have been successful across multiple species, but not as much in humans. Therefore, contact system and septic shock relationship remains plentiful in questions to be answered in the coming years or decades. Whether the contact system is not as relevant in humans as it is in animals or there is only lack of evidence remains to be explained. The subject is an attractive open field for further research aiming to aid in tackling such a burdensome condition.

The effects of physical therapy with neuromuscular electrical stimulation in patients with septic shock

PubMed Central

Lago, Alessandra Fabiane; de Oliveira, Anamaria Siriani; de Souza, Hugo Celso Dutra; da Silva, João Santana; Basile-Filho, Anibal; Gastaldi, Ada Clarice

2018-01-01

Abstract Introduction: Septic shock is a potentially fatal organ dysfunction caused by an imbalance of the host response to infection. The changes in microcirculation during sepsis can be explained by the alterations in the endothelial barrier function. Endothelial progenitor cells (EPCs) are a potential recovery index of endothelial function and it an increase in response to neuromuscular electrical stimulation (NMES) was demonstrated. Therefore, the objective of this study is to investigate the effects of NMES in patients with septic shock. Methods and analysis: It is a study protocol for a randomized cross-over design in an intensive care unit of a tertiary University hospital. Thirty-one patients aged 18 to 65 years. The study will be divided in 2 phases: the phase one will be held in the first 72 hours of septic shock and the phase two after 3 days of first assessment. Patients will be randomly selected to the intervention protocol (decubitus position with the limbs raised and NMES) and control protocol (decubitus position with the limbs raised without NMES). After this procedure, the patients will be allocated in group 1 (intervention and control protocol) or group 2 (control and intervention protocol) with a wash-out period of 4 to 6 hours between them. The main outcome is mobilization of EPCs. The secondary outcome is metabolic and hemodynamic data. A linear mixed model will be used for analysis of dependent variables and estimated values of the mean of the differences of each effect. PMID:29419665

Implementation of an Inpatient Pediatric Sepsis Identification Pathway.

PubMed

Bradshaw, Chanda; Goodman, Ilyssa; Rosenberg, Rebecca; Bandera, Christopher; Fierman, Arthur; Rudy, Bret

2016-03-01

Early identification and treatment of severe sepsis and septic shock improves outcomes. We sought to identify and evaluate children with possible sepsis on a pediatric medical/surgical unit through successful implementation of a sepsis identification pathway. The sepsis identification pathway, a vital sign screen and subsequent physician evaluation, was implemented in October 2013. Quality improvement interventions were used to improve physician and nursing adherence with the pathway. We reviewed charts of patients with positive screens on a monthly basis to assess for nursing recognition/physician notification, physician evaluation for sepsis, and subsequent physician diagnosis of sepsis and severe sepsis/septic shock. Adherence data were analyzed on a run chart and statistical process control p-chart. Nursing and physician pathway adherence of >80% was achieved over a 6-month period and sustained for the following 6 months. The direction of improvements met standard criteria for special causes. Over a 1-year period, there were 963 admissions to the unit. Positive screens occurred in 161 (16.7%) of these admissions and 38 (23.5%) of these had a physician diagnosis of sepsis, severe sepsis, or septic shock. One patient with neutropenia and septic shock had a negative sepsis screen due to lack of initial fever. Using quality improvement methodology, we successfully implemented a sepsis identification pathway on our pediatric unit. The pathway provided a standardized process to identify and evaluate children with possible sepsis requiring timely evaluation and treatment. Copyright © 2016 by the American Academy of Pediatrics.

Disseminated viridians streptococcus (Streptococcus mitis) infection presenting with toxic shock-like syndrome.

PubMed

Intalapaporn, Poj; Wongcharoen, Sunee; Chinapha, Anongnart; Jariyasethpong, Tavatchai

2013-03-01

The authors report a case of a 35-year-old man with no known underlying disease who presented with fever, cellulitis with hemorrhagic blebs on the left leg, monoarthricular left knee arthritis, multiple organ failure and septic shock. His clinical syndrome was compatible with toxic shock syndrome and his blood grew alpha hemolytic (viridians) Streptococcus mitis. To our knowledge, there are few reported cases of toxic shock syndrome cause by Streptococcus mitis in immune-competent adults.

Control groups in recent septic shock trials: a systematic review.

PubMed

Pettilä, Ville; Hjortrup, Peter Buhl; Jakob, Stephan M; Wilkman, Erika; Perner, Anders; Takala, Jukka

2016-12-01

The interpretation of septic shock trial data is profoundly affected by patients, control intervention, co-interventions and selected outcome measures. We evaluated the reporting of control groups in recent septic shock trials. We searched for original articles presenting randomized clinical trials (RCTs) in adult septic shock patients from 2006 to 2016. We included RCTs focusing on septic shock patients with at least two parallel groups and at least 50 patients in the control group. We selected and evaluated data items regarding patients, control group characteristics, and mortality outcomes, and calculated a data completeness score to provide an overall view of quality of reporting. A total of 24 RCTs were included (mean n = 287 patients and 71 % of eligible patients were randomized). Of the 24 studies, 14 (58 %) presented baseline data on vasopressors and 58 % the proportion of patients with elevated lactate values. Five studies (21 %) provided data to estimate the proportion of septic shock patients fulfilling the Sepsis-3 definition. The mean data completeness score was 19 out of 36 (range 8-32). Of 18 predefined control group characteristics, a mean of 8 (range 2-17) were reported. Only 2 (8 %) trials provided adequate data to confirm that their control group treatment represented usual care. Recent trials in septic shock provide inadequate data on the control group treatment and hemodynamic values. We propose a standardized trial dataset to be created and validated, comprising characteristics of patient population, interventions administered, hemodynamic values achieved, surrogate organ dysfunction, and mortality outcomes, to allow better analysis and interpretation of future trial results.

Erythrocyte selenium concentration predicts intensive care unit and hospital mortality in patients with septic shock: a prospective observational study

PubMed Central

2014-01-01

Introduction Selenoenzymes can modulate the extent of oxidative stress, which is recognized as a key feature of septic shock. The pathophysiologic role of erythrocyte selenium concentration in patients with septic shock remains unknown. Therefore, the objective of this study was to evaluate the association of erythrocyte selenium concentration with glutathione peroxidase (GPx1) activity, GPx1 polymorphisms and with ICU and hospital mortality in septic shock patients. Methods This prospective study included all patients older than 18 years with septic shock on admission or during their ICU stay, admitted to one of the three ICUs of our institution, from January to August 2012. At the time of the patients’ enrollment, demographic information was recorded. Blood samples were taken within the first 72 hours of the patients’ admission or within 72 hours of the septic shock diagnosis for determination of selenium status, protein carbonyl concentration, GPx1 activity and GPx1 Pro198Leu polymorphism (rs 1050450) genotyping. Results A total of 110 consecutive patients were evaluated. The mean age was 57.6 ± 15.9 years, 63.6% were male. Regarding selenium status, only erythrocyte selenium concentration was lower in patients who died in the ICU. The frequencies for GPx1 Pro198Leu polymorphism were 55%, 38% and 7% for Pro/Pro, Pro/Leu and Leu/Leu, respectively. In the logistic regression models, erythrocyte selenium concentration was associated with ICU and hospital mortality in patients with septic shock even after adjustment for protein carbonyl concentration and acute physiology and chronic health evaluation II score (APACHE II) or sequential organ failure assessment (SOFA). Conclusions Erythrocyte selenium concentration was a predictor of ICU and hospital mortality in patients with septic shock. However, this effect was not due to GPx1 activity or Pro198Leu polymorphism. PMID:24887198

Diagnostic accuracy of a screening electronic alert tool for severe sepsis and septic shock in the emergency department.

PubMed

Alsolamy, Sami; Al Salamah, Majid; Al Thagafi, Majed; Al-Dorzi, Hasan M; Marini, Abdellatif M; Aljerian, Nawfal; Al-Enezi, Farhan; Al-Hunaidi, Fatimah; Mahmoud, Ahmed M; Alamry, Ahmed; Arabi, Yaseen M

2014-12-05

Early recognition of severe sepsis and septic shock is challenging. The aim of this study was to determine the diagnostic accuracy of an electronic alert system in detecting severe sepsis or septic shock among emergency department (ED) patients. An electronic sepsis alert system was developed as a part of a quality-improvement project for severe sepsis and septic shock. The system screened all adult ED patients for a combination of systemic inflammatory response syndrome and organ dysfunction criteria (hypotension, hypoxemia or lactic acidosis). This study included all patients older than 14 years who presented to the ED of a tertiary care academic medical center from Oct. 1, 2012 to Jan. 31, 2013. As a comparator, emergency medicine physicians or the critical care physician identified the patients with severe sepsis or septic shock. In the ED, vital signs were manually entered into the hospital electronic heath record every hour in the critical care area and every two hours in other areas. We also calculated the time from the alert to the intensive care unit (ICU) referral. Of the 49,838 patients who presented to the ED, 222 (0.4%) were identified to have severe sepsis or septic shock. The electronic sepsis alert had a sensitivity of 93.18% (95% CI, 88.78% - 96.00%), specificity of 98.44 (95% CI, 98.33% - 98.55%), positive predictive value of 20.98% (95% CI, 18.50% - 23.70%) and negative predictive value of 99.97% (95% CI, 99.95% - 99.98%) for severe sepsis and septic shock. The alert preceded ICU referral by a median of 4.02 hours (Q1 - Q3: 1.25-8.55). Our study shows that electronic sepsis alert tool has high sensitivity and specificity in recognizing severe sepsis and septic shock, which may improve early recognition and management.

Differential expression of the nuclear-encoded mitochondrial transcriptome in pediatric septic shock.

PubMed

Weiss, Scott L; Cvijanovich, Natalie Z; Allen, Geoffrey L; Thomas, Neal J; Freishtat, Robert J; Anas, Nick; Meyer, Keith; Checchia, Paul A; Shanley, Thomas P; Bigham, Michael T; Fitzgerald, Julie; Banschbach, Sharon; Beckman, Eileen; Howard, Kelli; Frank, Erin; Harmon, Kelli; Wong, Hector R

2014-11-19

Increasing evidence supports a role for mitochondrial dysfunction in organ injury and immune dysregulation in sepsis. Although differential expression of mitochondrial genes in blood cells has been reported for several diseases in which bioenergetic failure is a postulated mechanism, there are no data about the blood cell mitochondrial transcriptome in pediatric sepsis. We conducted a focused analysis using a multicenter genome-wide expression database of 180 children ≤ 10 years of age with septic shock and 53 healthy controls. Using total RNA isolated from whole blood within 24 hours of PICU admission for septic shock, we evaluated 296 nuclear-encoded mitochondrial genes using a false discovery rate of 1%. A series of bioinformatic approaches were applied to compare differentially expressed genes across previously validated gene expression-based subclasses (groups A, B, and C) of pediatric septic shock. In total, 118 genes were differentially regulated in subjects with septic shock compared to healthy controls, including 48 genes that were upregulated and 70 that were downregulated. The top scoring canonical pathway was oxidative phosphorylation, with general downregulation of the 51 genes corresponding to the electron transport system (ETS). The top two gene networks were composed primarily of mitochondrial ribosomal proteins highly connected to ETS complex I, and genes encoding for ETS complexes I, II, and IV that were highly connected to the peroxisome proliferator activated receptor (PPAR) family. There were 162 mitochondrial genes differentially regulated between groups A, B, and C. Group A, which had the highest maximum number of organ failures and mortality, exhibited a greater downregulation of mitochondrial genes compared to groups B and C. Based on a focused analysis of a pediatric septic shock transcriptomic database, nuclear-encoded mitochondrial genes were differentially regulated early in pediatric septic shock compared to healthy controls, as well as across genotypic and phenotypic distinct pediatric septic shock subclasses. The nuclear genome may be an important mechanism contributing to alterations in mitochondrial bioenergetic function and outcomes in pediatric sepsis.

ACTIVATION OF COMMON ANTIVIRAL PATHWAYS CAN POTENTIATE INFLAMMATORY RESPONSES TO SEPTIC SHOCK

PubMed Central

Doughty, Lesley A.; Carlton, Stacey; Galen, Benjamin; Cooma-Ramberan, Indranie; Chung, Chung-Shiang; Ayala, Alfred

2006-01-01

Induction of the antiviral cytokine interferon α/β (IFN-α/β) is common in many viral infections. The impact of ongoing antiviral responses on subsequent bacterial infection is not well understood. In human disease, bacterial superinfection complicating a viral infection can result in significant morbidity and mortality. We injected mice with polyinosinic-polycytidylic (PIC) acid, a TLR3 ligand and known IFN-α/β inducer as well as nuclear factor κB (NF-κB) activator to simulate very early antiviral pathways. We then challenged mice with an in vivo septic shock model characterized by slowly evolving bacterial infection to simulate bacterial superinfection early during a viral infection. Our data demonstrated robust induction of IFN-α in serum within 24 h of PIC injection with IFN-α/β–dependent major histocompatibility antigen class II up-regulation on peritoneal macrophages. PIC pretreatment before septic shock resulted in augmented tumor necrosis factor alpha and interleukins 6 and 10 and heightened lethality compared with septic shock alone. Intact IFN-α/β signaling was necessary for augmentation of the inflammatory response to in vivo septic shock and to both TLR2 and TLR4 agonists in vitro. To assess the NF-κB contribution to PIC-modulated inflammatory responses to septic shock, we treated with parthenolide an NF-κB inhibitor before PIC and septic shock. Parthenolide did not inhibit IFN-α induction by PIC. Inhibition of NF-κB by parthenolide did reduce IFN-α–mediated potentiation of the cytokine response and lethality from septic shock. Our data demonstrate that pathways activated early during many viral infections can have a detrimental impact on the outcome of subsequent bacterial infection. These pathways may be critical to understanding the heightened morbidity and mortality from bacterial superinfection after viral infection in human disease. PMID:16878028

Temporal changes in management and outcome of septic shock in patients with malignancies in the intensive care unit.

PubMed

Pène, Frédéric; Percheron, Stéphanie; Lemiale, Virginie; Viallon, Vivian; Claessens, Yann-Erick; Marqué, Sophie; Charpentier, Julien; Angus, Derek C; Cariou, Alain; Chiche, Jean-Daniel; Mira, Jean-Paul

2008-03-01

Septic shock is a severe, often terminal, complication of malignancy. For patients without malignancy, outcome from septic shock has improved with new advances in care. We wished to explore whether outcome from septic shock has similarly improved for cancer patients, with regard to implementation of recent adjuvant therapies. An 8-yr retrospective observational study. A 24-bed medical intensive care unit in a university hospital. Patients were 238 consecutive cancer patients (solid tumors or hematologic malignancies) with septic shock admitted to the intensive care unit within two consecutive 4-yr periods: 1998-2001 and 2002-2005. None. Septic shock occurred in 90 patients in 1998-2001 and 148 in 2002-2005. Management of septic shock between the two periods mostly differed by emergence of adjuvant therapies of sepsis (mainly low-dose glucocorticoids) and intensive insulin therapy and a more frequent use of renal replacement therapy in the recent period. Short-term survival rates were significantly higher during 2002-2005 compared with the previous 4-yr period: 28-day, intensive care unit, and hospital survival rates were 47.3% vs. 27.8% (p = .003), 41.2% vs. 26.7% (p = .02), and 36.5% vs. 21.1% (p = .01), respectively. After adjustment, intensive care unit admission between 2002 and 2005 was an independent favorable prognostic factor for short-term outcome. Improved survival was mainly observed in patients who did not require renal replacement therapy during their stay in the intensive care unit (hospital survival 65% in 2002-2005 vs. 21.4% in 1998-2001, p < .001). Improved outcome in critically ill cancer patients extended to the subgroup of patients with septic shock. This might be ascribed both to a better selection of patients and to improvements in the care and management, including new therapeutic strategies for sepsis.

[Complications and cause of death in mexican children with rocky mountain spotted fever].

PubMed

Martínez-Medina, Miguel Ángel; Rascón-Alcantar, Adela

Rocky Mountain spotted fever is a life threatening disease caused by Rickettsia rickettsia, characterized by multisystem involvement. We studied 19 dead children with Rocky Mountain spotted fever. All children who were suspected of having rickettsial infections were defined as having Rocky Mountain spotted fever by serology test and clinical features. Through the analysis of each case, we identified the clinical profile and complications associated to the death of a patient. In nine (69.2%) of 13 cases that died in the first three days of admission, the associated condition was septic shock. Others complications included respiratory distress causes by non-cardiogenic pulmonary edema, renal impairment, and multiple organ damage. The main cause of death in this study was septic shock. The fatality rate from Rocky Mountain spotted fever can be related to the severity of the infection, delay in diagnosis, and delay in initiation of antibiotic therapy. Pulmonary edema and cerebral edema can be usually precipitated by administration of excess intravenous fluids.

Impact of case volume on survival of septic shock in patients with malignancies.

PubMed

Zuber, Benjamin; Tran, Thi-Chien; Aegerter, Philippe; Grimaldi, David; Charpentier, Julien; Guidet, Bertrand; Mira, Jean-Paul; Pène, Frédéric

2012-01-01

Septic shock is a frequent and severe complication in the course of malignancies. In a large multicenter cohort of septic shock patients with hematologic malignancies and solid tumors, we assessed the temporal trend in survival and the prognostic factors, with particular emphasis on case volume. A 12-yr multicenter retrospective cohort study of prospectively collected data. Cancer patients with septic shock were selected over a 12-yr period (1997-2008) from a French regional database (CUB-Réa). The following variables were extracted: demographic characteristics, type of malignancy, characteristics of infection, severity-of-illness score (Simplified Acute Physiology Score II), organ failure supports, and vital status. For each unit, a running mean annual volume of admissions was calculated for the purpose of categorization into volume tertiles. Prognostic factors were analyzed by a conditional multivariate logistic model after matching on a propensity score of being admitted to a high-volume unit and on the year of admission. None. A total of 3,437 patients were included in the study. The intensive care unit mortality rate dramatically dropped over time (from 70.4% in 1997 to 52.5% in 2008, relative decrease 25.4%, p < .001). Participating units were distributed into low-volume (< five patients per year), medium-volume (five to 12 patients per year), and high-volume (≥ 13 patients per year) tertiles. A medical cause for intensive care unit admission, Simplified Acute Physiology Score II, invasive mechanical ventilation, renal replacement therapy, fungal infections, and unknown microorganism were identified as poor prognostic factors. Case volume demonstrated a strong influence on survival, admission in a high-volume unit being associated with a marked decrease in mortality as compared to low-volume units (adjusted odds ratio 0.63; 95% confidence interval [0.46-0.87], p = .002). Survival of septic shock patients with malignancies markedly increased over the recent years. Furthermore, we identified case volume as a major prognostic factor in this setting.

Beneficial effects of the heme oxygenase-1/carbon monoxide system in patients with severe sepsis/septic shock.

PubMed

Takaki, Shoji; Takeyama, Naoshi; Kajita, Yuka; Yabuki, Teru; Noguchi, Hiroki; Miki, Yasuo; Inoue, Yasusuke; Nakagawa, Takashi; Noguchi, Hiroshi

2010-01-01

We evaluated the relations among the arterial carbon monoxide (CO) concentration, heme oxygenase (HO)-1 expression by monocytes, oxidative stress, plasma levels of cytokines and bilirubin, and the outcome of patients with severe sepsis or septic shock. Thirty-six patients who fulfilled the criteria for severe sepsis or septic shock and 21 other patients without sepsis during their stay in the intensive care unit were studied. HO-1 protein expression by monocytes, arterial CO, oxidative stress, bilirubin, and cytokines were measured. Arterial blood CO, cytokine, and bilirubin levels, and monocyte HO-1 protein expression were higher in patients with severe sepsis/septic shock than in non-septic patients. Increased HO-1 expression was related to the arterial CO concentration and oxidative stress. There was a positive correlation between survival and increased HO-1 protein expression or a higher CO level. Arterial CO and monocyte HO-1 protein expression were increased in critically ill patients, particularly those with severe sepsis or septic shock, suggesting that oxidative stress is closely related to HO-1 expression. The HO-1/CO system may play an important role in sepsis.

Mortality Prediction Model of Septic Shock Patients Based on Routinely Recorded Data

PubMed Central

Carrara, Marta; Baselli, Giuseppe; Ferrario, Manuela

2015-01-01

We studied the problem of mortality prediction in two datasets, the first composed of 23 septic shock patients and the second composed of 73 septic subjects selected from the public database MIMIC-II. For each patient we derived hemodynamic variables, laboratory results, and clinical information of the first 48 hours after shock onset and we performed univariate and multivariate analyses to predict mortality in the following 7 days. The results show interesting features that individually identify significant differences between survivors and nonsurvivors and features which gain importance only when considered together with the others in a multivariate regression model. This preliminary study on two small septic shock populations represents a novel contribution towards new personalized models for an integration of multiparameter patient information to improve critical care management of shock patients. PMID:26557154

Septic Shock due to Vibrio alginolyticus in a Cirrhotic Patient: The First Case in Korea

PubMed Central

Lee, Dong-Young; Moon, Soo-Youn; Lee, Sang-Oh; Yang, Hee-Young; Lee, Hee-Joo

2008-01-01

We describe a case of septic shock due to Vibrio alginolyticus presenting with fever and bilateral leg pain. Despite intensive management with antibiotics and inotropic agents, the patient died from septic shock 1 day after hospitalization. V. alginolyticus was isolated from both leg wounds and a blood culture. To the best of our knowledge, this is the first reported case of V. alginolyticus bacteremia in Korea. PMID:18452273

Application of the new Sepsis-3 definition in a cohort of patients with severe sepsis and septic shock admitted to Intensive Care Unit from the Emergency Department.

PubMed

García-Gigorro, Renata; Molina-Collado, Zaira; Sáez-de la Fuente, Ignacio; Sanchez-Izquierdo, José Ángel; Montejo González, Juan Carlos

2018-04-18

After the publication of the new definition for sepsis and septic shock, our objective is to analyse the evolution of patients admitted to ICU with an infection process using the previous and new recommendations. This is a sub-analysis of a previous observational prospective study. We included 98 patients admitted to ICU from the emergency department due to infection during an 18-month period. We studied the clinical evolution during ICU admission and hospital mortality. According to Sepsis-2 definition, 78% percent had septic shock and using Sepsis-3 criteria, 52%; hospital mortality was 29 and 41%, respectively. The RR of hospital mortality of septic shock was 10.3 (95% CI: 2.8-37.5) compared to patients without shock. The 30-day probability survival of patients with sepsis and septic shock were 78% and 68%, respectively (long rank < 0.001). In our experience, the incorporation of the SOFA score and lactate levels to the new definition could help improve the evaluation of risk of hospital death. Copyright © 2018 Elsevier España, S.L.U. All rights reserved.

Developing a New Definition and Assessing New Clinical Criteria for Septic Shock

PubMed Central

Shankar-Hari, Manu; Phillips, Gary S.; Levy, Mitchell L.; Seymour, Christopher W.; Liu, Vincent X.; Deutschman, Clifford S.; Angus, Derek C.; Rubenfeld, Gordon D.; Singer, Mervyn

2016-01-01

IMPORTANCE Septic shock currently refers to a state of acute circulatory failure associated with infection. Emerging biological insights and reported variation in epidemiology challenge the validity of this definition. OBJECTIVE To develop a new definition and clinical criteria for identifying septic shock in adults. DESIGN, SETTING, AND PARTICIPANTS The Society of Critical Care Medicine and the European Society of Intensive Care Medicine convened a task force (19 participants) to revise current sepsis/septic shock definitions. Three sets of studies were conducted: (1) a systematic review and meta-analysis of observational studies in adults published between January 1, 1992, and December 25, 2015, to determine clinical criteria currently reported to identify septic shock and inform the Delphi process; (2) a Delphi study among the task force comprising 3 surveys and discussions of results from the systematic review, surveys, and cohort studies to achieve consensus on a new septic shock definition and clinical criteria; and (3) cohort studies to test variables identified by the Delphi process using Surviving Sepsis Campaign (SSC) (2005–2010; n = 28 150), University of Pittsburgh Medical Center (UPMC) (2010–2012; n = 1 309 025), and Kaiser Permanente Northern California (KPNC) (2009–2013; n = 1 847 165) electronic health record (EHR) data sets. MAIN OUTCOMES AND MEASURES Evidence for and agreement on septic shock definitions and criteria. RESULTS The systematic review identified 44 studies reporting septic shock outcomes (total of 166 479 patients) from a total of 92 sepsis epidemiology studies reporting different cutoffs and combinations for blood pressure (BP), fluid resuscitation, vasopressors, serum lactate level, and base deficit to identify septic shock. The septic shock–associated crude mortality was 46.5% (95%CI, 42.7%–50.3%), with significant between-study statistical heterogeneity (I2 = 99.5%; τ2 = 182.5; P < .001). The Delphi process identified hypotension, serum lactate level, and vasopressor therapy as variables to test using cohort studies. Based on these 3 variables alone or in combination, 6 patient groups were generated. Examination of the SSC database demonstrated that the patient group requiring vasopressors to maintain mean BP 65 mmHg or greater and having a serum lactate level greater than 2 mmol/L (18 mg/dL) after fluid resuscitation had a significantly higher mortality (42.3%[95%CI, 41.2%–43.3%]) in risk-adjusted comparisons with the other 5 groups derived using either serum lactate level greater than 2 mmol/L alone or combinations of hypotension, vasopressors, and serum lactate level 2 mmol/L or lower. These findings were validated in the UPMC and KPNC data sets. CONCLUSIONS AND RELEVANCE Based on a consensus process using results from a systematic review, surveys, and cohort studies, septic shock is defined as a subset of sepsis in which underlying circulatory, cellular, and metabolic abnormalities are associated with a greater risk of mortality than sepsis alone. Adult patients with septic shock can be identified using the clinical criteria of hypotension requiring vasopressor therapy to maintain mean BP 65 mmHg or greater and having a serum lactate level greater than 2 mmol/L after adequate fluid resuscitation. PMID:26903336

Effects of etomidate on complications related to intubation and on mortality in septic shock patients treated with hydrocortisone: a propensity score analysis

PubMed Central

2012-01-01

Introduction Endotracheal intubation in the ICU is associated with a high incidence of complications. Etomidate use is debated in septic shock because it increases the risk of critical illness-related corticosteroid insufficiency, which may impact outcome. We hypothesized that hydrocortisone, administered in all septic shock cases in our ICU, may counteract some negative effects of etomidate. The aim of our study was to compare septic shock patients who received etomidate versus another induction drug both for short-term safety and for long-term outcomes. Methods A single-center observational study was carried out in septic shock patients, treated with hydrocortisone and intubated within the first 48 hours of septic shock. Co-primary end points were life-threatening complications incidence occurring within the first hour after intubation and mortality during the ICU stay. Statistical analyses included unmatched and matched cohorts using a propensity score analysis. P < 0.05 was considered significant. Results Sixty patients in the etomidate cohort and 42 patients in the non-etomidate cohort were included. Critical illness-related corticosteroid insufficiency was 79% in the etomidate cohort and 52% in the non-etomidate cohort (P = 0.01). After intubation, life-threatening complications occurred in 36% of the patients whatever the cohort. After adjustment with propensity score analysis, etomidate was a protective factor for death in the ICU both in unmatched (hazard ratio, 0.33 (0.15 to 0.75); P < 0.01)) and matched cohorts (hazard ratio, 0.33 (0.112 to 0.988); P = 0.04). Conclusion In septic shock patients treated with hydrocortisone, etomidate did not decrease life-threatening complications following intubation, but when associated with hydrocortisone it also did not impair outcome. PMID:23171852

Is Thrombocytopenia an Early Prognostic Marker in Septic Shock?

PubMed

Thiery-Antier, Nadiejda; Binquet, Christine; Vinault, Sandrine; Meziani, Ferhat; Boisramé-Helms, Julie; Quenot, Jean-Pierre

2016-04-01

To assess whether early thrombocytopenia during septic shock is associated with an increased risk of death at day 28 and to identify risk factors associated with a low platelet count. Prospective, multicenter, observational cohort study. Fourteen ICUs from 10 French university teaching and nonacademic hospitals. Consecutive adult patients with septic shock admitted between November 2009 and September 2011 were eligible. None. Of the 1,495 eligible patients, 1,486 (99.4%) were included. Simplified Acute Physiology Score II score of greater than or equal to 56, immunosuppression, age of more than 65 years, cirrhosis, bacteremia (p ≤ 0.001 for each), and urinary sepsis (p = 0.005) were globally associated with an increased risk of thrombocytopenia within the first 24 hours following the onset of septic shock. Survival at day 28 estimated by the Kaplan-Meier method was lower in patients with thrombocytopenia and decreased with thrombocytopenia severity. By multivariate Cox regression, a platelet count of less than or equal to 100,000/mm3 was independently associated with a significantly increased risk of death within the 28 days following septic shock onset. The risk of death increased with the severity of thrombocytopenia (hazard ratio, 1.65; 95% CI, 1.31-2.08 for a platelet count below 50,000/mm3 vs > 150,000/mm3; p < 0.0001). This is the first study to investigate thrombocytopenia within the first 24 hours of septic shock onset as a prognostic marker of survival at day 28 in a large cohort of ICU patients. Measuring platelet count is inexpensive and easily feasible for the physician in routine practice, and thus, it could represent an easy "alert system" among patients in septic shock.

Microparticle-associated tissue factor activity correlates with plasma levels of bacterial lipopolysaccharides in meningococcal septic shock.

PubMed

Hellum, Marit; Øvstebø, Reidun; Brusletto, Berit S; Berg, Jens P; Brandtzaeg, Petter; Henriksson, Carola E

2014-03-01

The plasma level of bacterial lipopolysaccharides (LPS) is associated with activation of the coagulation system, inhibition of fibrinolysis and the nature of the clinical presentation and outcome in patients with meningococcal disease. Tissue factor (TF)-bearing microparticles (MPs) appear to contribute to the pathogenesis of disseminated intravascular coagulation (DIC). The aim of this study was to investigate the relationship between MP-associated TF activity and the level of bacterial LPS in plasma from patients with meningococcal septic shock and meningitis. MPs isolated from citrated plasmas were assessed for TF-dependent activity with both a plasma-based thrombin generation assay (CAT) and whole blood-based thromboelastometry (ROTEM). The LPS level was measured using a chromogenic Limulus amebocyte lysate assay. MPs obtained from patients with meningococcal septic shock initiated significantly more efficient and TF-dependent thrombin generation in the CAT assay compared to MPs from patients with meningococcal meningitis. Differences in MP-associated TF activity between the septic shock patients and the meningitis patients were also evident when MPs were added to whole blood using ROTEM. The level of plasma LPS in patients with septic shock (range 2-2,100 EU/mL) was correlated with thrombogram parameters in the CAT assay; lagtime (r(s)=-0.84), time to peak (rs=-0.83), peak (r(s)=0.85) and ETP (r(s)=0.83). MPs obtained from patients with meningococcal septic shock displayed more efficient TF-dependent thrombin generation and clot formation compared to MPs from meningitis patients. MP-associated TF activity was closely associated with plasma LPS levels in the septic shock group. Copyright © 2013 Elsevier Ltd. All rights reserved.

Prognostic impact of isolated right ventricular dysfunction in sepsis and septic shock: an 8-year historical cohort study.

PubMed

Vallabhajosyula, Saraschandra; Kumar, Mukesh; Pandompatam, Govind; Sakhuja, Ankit; Kashyap, Rahul; Kashani, Kianoush; Gajic, Ognjen; Geske, Jeffrey B; Jentzer, Jacob C

2017-09-07

Echocardiographic myocardial dysfunction is reported commonly in sepsis and septic shock, but there are limited data on sepsis-related right ventricular dysfunction. This study sought to evaluate the association of right ventricular dysfunction with clinical outcomes in patients with severe sepsis and septic shock. Historical cohort study of adult patients admitted to all intensive care units at the Mayo Clinic from January 1, 2007 through December 31, 2014 for severe sepsis and septic shock, who had an echocardiogram performed within 72 h of admission. Patients with prior heart failure, cor-pulmonale, pulmonary hypertension and valvular disease were excluded. Right ventricular dysfunction was defined by the American Society of Echocardiography criteria. Outcomes included 1-year survival, in-hospital mortality and length of stay. Right ventricular dysfunction was present in 214 (55%) of 388 patients who met the inclusion criteria-isolated right ventricular dysfunction was seen in 100 (47%) and combined right and left ventricular dysfunction in 114 (53%). The baseline characteristics were similar between cohorts except for the higher mechanical ventilation use in patients with isolated right ventricular dysfunction. Echocardiographic findings demonstrated lower right ventricular and tricuspid valve velocities in patients with right ventricular dysfunction and lower left ventricular ejection fraction and increased mitral E/e' ratios in patients with combined right and left ventricular dysfunction. After adjustment for age, comorbidity, illness severity, septic shock and use of mechanical ventilation, isolated right ventricular dysfunction was independently associated with worse 1-year survival-hazard ratio 1.6 [95% confidence interval 1.2-2.1; p = 0.002) in patients with sepsis and septic shock. Isolated right ventricular dysfunction is seen commonly in sepsis and septic shock and is associated with worse long-term survival.

The Impact of the Sepsis-3 Septic Shock Definition on Previously Defined Septic Shock Patients.

PubMed

Sterling, Sarah A; Puskarich, Michael A; Glass, Andrew F; Guirgis, Faheem; Jones, Alan E

2017-09-01

The Third International Consensus Definitions Task Force (Sepsis-3) recently recommended changes to the definitions of sepsis. The impact of these changes remains unclear. Our objective was to determine the outcomes of patients meeting Sepsis-3 septic shock criteria versus patients meeting the "old" (1991) criteria of septic shock only. Secondary analysis of two clinical trials of early septic shock resuscitation. Large academic emergency departments in the United States. Patients with suspected infection, more than or equal to two systemic inflammatory response syndrome criteria, and systolic blood pressure less than 90 mm Hg after fluid resuscitation. Patients were further categorized as Sepsis-3 septic shock if they demonstrated hypotension, received vasopressors, and exhibited a lactate greater than 2 mmol/L. We compared in-hospital mortality in patients who met the old definition only with those who met the Sepsis-3 criteria. Four hundred seventy patients were included in the present analysis. Two hundred (42.5%) met Sepsis-3 criteria, whereas 270 (57.4%) met only the old definition. Patients meeting Sepsis-3 criteria demonstrated higher severity of illness by Sequential Organ Failure Assessment score (9 vs 5; p < 0.001) and mortality (29% vs 14%; p < 0.001). Subgroup analysis of 127 patients meeting only the old definition demonstrated significant mortality benefit following implementation of a quantitative resuscitation protocol (35% vs 10%; p = 0.006). In this analysis, 57% of patients meeting old definition for septic shock did not meet Sepsis-3 criteria. Although Sepsis-3 criteria identified a group of patients with increased organ failure and higher mortality, those patients who met the old criteria and not Sepsis-3 criteria still demonstrated significant organ failure and 14% mortality rate.

Use of a novel hemoadsorption device for cytokine removal as adjuvant therapy in a patient with septic shock with multi-organ dysfunction: A case study.

PubMed

Basu, Reshma; Pathak, Sunjay; Goyal, Jyoti; Chaudhry, Rajeev; Goel, Rati B; Barwal, Anil

2014-12-01

CytoSorb(®) (CytoSorbents Corporation, USA) is a novel sorbent hemoadsorption device for cytokine removal. The aim of this study was to examine the clinical use of CytoSorb(®) in the management of patient with septic shock. We used this device as an adjuvant to stabilize a young patient with multi-organ failure and severe sepsis with septic shock. A 36-year-old female patient was hospitalized with the complaints of malaise, general body ache, and breathing difficulty and had a medical history of diabetes mellitus type II, hypertension, obstructive sleep apnea, hypothyroidism and morbid obesity. She was diagnosed to have septic shock with multi-organ dysfunction (MODS) and a low perfusion state. CytoSorb(®) hemoadsorption column was used as an attempt at blood purification. Acute physiology and chronic health evaluation score, MODS score, and sequential organ failure assessment score were measured before and after the device application. CytoSorb application as an adjuvant therapy could be considered in septic shock.

Use of a novel hemoadsorption device for cytokine removal as adjuvant therapy in a patient with septic shock with multi-organ dysfunction: A case study

PubMed Central

Basu, Reshma; Pathak, Sunjay; Goyal, Jyoti; Chaudhry, Rajeev; Goel, Rati B.; Barwal, Anil

2014-01-01

CytoSorb® (CytoSorbents Corporation, USA) is a novel sorbent hemoadsorption device for cytokine removal. The aim of this study was to examine the clinical use of CytoSorb® in the management of patient with septic shock. We used this device as an adjuvant to stabilize a young patient with multi-organ failure and severe sepsis with septic shock. A 36-year-old female patient was hospitalized with the complaints of malaise, general body ache, and breathing difficulty and had a medical history of diabetes mellitus type II, hypertension, obstructive sleep apnea, hypothyroidism and morbid obesity. She was diagnosed to have septic shock with multi-organ dysfunction (MODS) and a low perfusion state. CytoSorb® hemoadsorption column was used as an attempt at blood purification. Acute physiology and chronic health evaluation score, MODS score, and sequential organ failure assessment score were measured before and after the device application. CytoSorb application as an adjuvant therapy could be considered in septic shock. PMID:25538418

Changes in muscle tissue oxygenation during stagnant ischemia in septic patients.

PubMed

Pareznik, Roman; Knezevic, Rajko; Voga, Gorazd; Podbregar, Matej

2006-01-01

To determine changes in the rate of thenar muscles tissue deoxygenation during stagnant ischemia in patients with severe sepsis and septic shock. Prospective observational study in the medical ICU of a general hospital. Consecutive patients admitted to ICU with septic shock (n=6), severe sepsis (n=6), localized infection (n=3), and healthy volunteers (n=15). Upper limb ischemia was induced by rapid automatic pneumatic cuff inflation around upper arm. Thenar muscle tissue oxygen saturation (StO2) was measured continuously by near-infrared spectroscopy before and during upper limb ischemia. StO(2) before intervention was comparable in patients with septic shock, severe sepsis, or localized infection and healthy volunteers (89 [65, 92]% vs. 82 [72, 91]% vs. 87 [85, 92]% vs. 83 [79, 93]%, respectively; p>0.1). The rate of StO(2) decrease during stagnant ischemia after initial hemodynamic stabilization was slower in septic shock patients than in those with severe sepsis or localized infection and in controls (-7.0 [-3.6, -11.0] %/min vs. -10.4 [-7.8, -13.3] %/min vs. -19.5 [-12.3, -23.3] vs. -37.4 [-27.3, -56.2] %/min, respectively; p=0.041). At ICU discharge the rate of StO2 decrease did not differ between the septic shock, severe sepsis, and localized infection groups (-17.0 [-9.3, -28.9] %/min vs. -19.9 [-13.3, -23.6] %/min vs. -23.1 [-20.7, -26.2] %/min, respectively), but remained slower than in controls (p<0.01). The rate of StO2 decrease was correlated with Sequential Organ Failure Assessment (SOFA) score (r=0.739, p<0.001). After hemodynamic stabilization thenar muscle tissue oxygen saturation during stagnant ischemia decreases slower in septic shock patients than in patients with severe sepsis or localized infection and in healthy volunteers. During ICU stay and improvement of sepsis the muscle tissue deoxygenation rate increases in survivors of both septic shock and severe sepsis and was correlated with SOFA score.

Right in Front of Our Eyes: Evolution of Streptococcal Toxic Shock Syndrome with Ischemic Optic Neuropathy.

PubMed

Elhamamsy, Salaheldin M; Al-Qadi, Mazen O; Minami, Taro; Neill, Marguerite

2016-12-01

Toxic shock syndrome occurs from dysregulation of host inflammatory responses. Toxin- producing strains of Group A streptococcus cause TSS. Ischemic optic neuropathy rarely complicates septic shock. We present a rare case of streptococcal pharyngitis complicated by septic arthritis and TSS with reversible blindness due to non-arteritic ischemic optic neuropathy. A 28-year-old man drove to our ED with exudative pharyngitis. A rapid streptococcal test was positive. While awaiting oral penicillin he became hypotensive refractory to IV fluids and developed knee effusion. The patient noted progressive dimming of his vision. Arthrocentesis yielded GAS. ICU course was complicated by ARDS but after 2 weeks the patient was weaned off vasopressors and the ventilator. He regained his vision and had no neurological sequelae. The patient's GAS isolate was M protein gene (emm) type 1 and T type 1. He was followed in the IM clinic for 9 months post discharge with complete resolution of symptoms. The rapidity of the development of shock is attributed to streptococcal exotoxins acting as superantigens. GAS type M1 is commonly associated with severe shock in TSS. The severe shock was the likely cause of his ischemic optic neuropathy. Early recognition and aggressive management of TSS are crucial to clinical outcome. [Full article available at http://rimed.org/rimedicaljournal-2016-12.asp].

Renal Blood Flow, Glomerular Filtration Rate, and Renal Oxygenation in Early Clinical Septic Shock.

PubMed

Skytte Larsson, Jenny; Krumbholz, Vitus; Enskog, Anders; Bragadottir, Gudrun; Redfors, Bengt; Ricksten, Sven-Erik

2018-06-01

Data on renal hemodynamics, function, and oxygenation in early clinical septic shock are lacking. We therefore measured renal blood flow, glomerular filtration rate, renal oxygen consumption, and oxygenation in patients with early septic shock. Prospective comparative study. General and cardiothoracic ICUs. Patients with norepinephrine-dependent early septic shock (n = 8) were studied within 24 hours after arrival in the ICU and compared with postcardiac surgery patients without acute kidney injury (comparator group, n = 58). None. Data on systemic hemodynamics and renal variables were obtained during two 30-minute periods. Renal blood flow was measured by the infusion clearance of para-aminohippuric acid, corrected for renal extraction of para-aminohippuric acid. Renal filtration fraction was measured by renal extraction of chromium-51 labeled EDTA. Renal oxygenation was estimated from renal oxygen extraction. Renal oxygen delivery (-24%; p = 0.037) and the renal blood flow-to-cardiac index ratio (-21%; p = 0.018) were lower, renal vascular resistance was higher (26%; p = 0.027), whereas renal blood flow tended to be lower (-19%; p = 0.068) in the septic group. Glomerular filtration rate (-32%; p = 0.006) and renal sodium reabsorption (-29%; p = 0.014) were both lower in the septic group. Neither renal filtration fraction nor renal oxygen consumption differed significantly between groups. Renal oxygen extraction was significantly higher in the septic group (28%; p = 0.022). In the septic group, markers of tubular injury were elevated. In early clinical septic shock, renal function was lower, which was accompanied by renal vasoconstriction, a lower renal oxygen delivery, impaired renal oxygenation, and tubular sodium reabsorption at a high oxygen cost compared with controls.

[The importance of endotoxin producing bacterias for practical purposes

PubMed

Schimmel, Dietrich

1994-01-01

Lipopolysaccharides (endotoxin) cause according to resorption out of the intestinal tract or aerogenic inhalation or by a septic infection clinical signs. The clinical reactions are praeshock symptoms, acute forms of shock and death. The experimental intratracheally administration of lipopolysaccharides into calves caused pneumonic lesions without bacterial experimental infection.

Survival of Primates in Lethal Septic Shock Following Delayed Treatment with Steroid.

DTIC Science & Technology

1981-02-26

TECHNICAL REPORT NO. 142 SURVIVAL OF PRIMATES IN LETHAL SEPTIC SHOCK FOLLOWING DELAYED TREAMENT WIn STEROID L. B. Hinshaw, L. T. Archer, B. K. Belier ...2. Schumer W: Steroids in the treatment of clinical septic shock. Ann Surg 184:333-341, 1976. 3. Hinshaw LB, Belier PK, Archer LT, Flournoy DJ, White...not preventable by antibiotic alone. Infect Immun ZS:538-5)7, 1979. 6. Hinshaw LB, Archer LT, Belier -Todd BK, Coalson .JJ, Flournoy DL, Passey R

Designing and testing computer based screening engine for severe sepsis/septic shock.

PubMed

Herasevich, V; Afessa, B; Chute, C G; Gajic, O

2008-11-06

This study addresses the role of a sepsis "sniffer", an automatic screening tool for the timely identification of patients with severe sepsis/septic shock, based electronic medical records. During the two months prospective implementation in a medical intensive care unit, 37 of 320 consecutive patients developed severe sepsis/septic shock. The sniffer demonstrated a sensitivity of 48% and specificity of 86%, and positive predictive value 32%. Further improvements are needed prior to the implementation of sepsis sniffer in clinical practice and research.

The effects of physical therapy with neuromuscular electrical stimulation in patients with septic shock: Study protocol for a randomized cross-over design.

PubMed

Lago, Alessandra Fabiane; de Oliveira, Anamaria Siriani; de Souza, Hugo Celso Dutra; da Silva, João Santana; Basile-Filho, Anibal; Gastaldi, Ada Clarice

2018-02-01

Septic shock is a potentially fatal organ dysfunction caused by an imbalance of the host response to infection. The changes in microcirculation during sepsis can be explained by the alterations in the endothelial barrier function. Endothelial progenitor cells (EPCs) are a potential recovery index of endothelial function and it an increase in response to neuromuscular electrical stimulation (NMES) was demonstrated. Therefore, the objective of this study is to investigate the effects of NMES in patients with septic shock. It is a study protocol for a randomized cross-over design in an intensive care unit of a tertiary University hospital. Thirty-one patients aged 18 to 65 years. The study will be divided in 2 phases: the phase one will be held in the first 72 hours of septic shock and the phase two after 3 days of first assessment. Patients will be randomly selected to the intervention protocol (decubitus position with the limbs raised and NMES) and control protocol (decubitus position with the limbs raised without NMES). After this procedure, the patients will be allocated in group 1 (intervention and control protocol) or group 2 (control and intervention protocol) with a wash-out period of 4 to 6 hours between them. The main outcome is mobilization of EPCs. The secondary outcome is metabolic and hemodynamic data. A linear mixed model will be used for analysis of dependent variables and estimated values of the mean of the differences of each effect.

Estimating Ten-Year Trends in Septic Shock Incidence and Mortality in United States Academic Medical Centers Using Clinical Data.

PubMed

Kadri, Sameer S; Rhee, Chanu; Strich, Jeffrey R; Morales, Megan K; Hohmann, Samuel; Menchaca, Jonathan; Suffredini, Anthony F; Danner, Robert L; Klompas, Michael

2017-02-01

Reports that septic shock incidence is rising and mortality rates declining may be confounded by improving recognition of sepsis and changing coding practices. We compared trends in septic shock incidence and mortality in academic hospitals using clinical vs claims data. We identified all patients with concurrent blood cultures, antibiotics, and vasopressors for ≥ two consecutive days, and all patients with International Classification of Diseases, 9th edition (ICD-9) codes for septic shock, at 27 academic hospitals from 2005 to 2014. We compared annual incidence and mortality trends. We reviewed 967 records from three hospitals to estimate the accuracy of each method. Of 6.5 million adult hospitalizations, 99,312 (1.5%) were flagged by clinical criteria, 82,350 (1.3%) by ICD-9 codes, and 44,651 (0.7%) by both. Sensitivity for clinical criteria was higher than claims (74.8% vs 48.3%; P < .01), whereas positive predictive value was comparable (83% vs 89%; P = .23). Septic shock incidence, based on clinical criteria, rose from 12.8 to 18.6 cases per 1,000 hospitalizations (average, 4.9% increase/y; 95% CI, 4.0%-5.9%), while mortality declined from 54.9% to 50.7% (average, 0.6% decline/y; 95% CI, 0.4%-0.8%). In contrast, septic shock incidence, based on ICD-9 codes, increased from 6.7 to 19.3 per 1,000 hospitalizations (19.8% increase/y; 95% CI, 16.6%-20.9%), while mortality decreased from 48.3% to 39.3% (1.2% decline/y; 95% CI, 0.9%-1.6%). A clinical surveillance definition based on concurrent vasopressors, blood cultures, and antibiotics accurately identifies septic shock hospitalizations and suggests that the incidence of patients receiving treatment for septic shock has risen and mortality rates have fallen, but less dramatically than estimated on the basis of ICD-9 codes. Copyright © 2016 American College of Chest Physicians. All rights reserved.

Inhaled nitric oxide in acute respiratory distress syndrome with and without septic shock requiring norepinephrine administration: a dose–response study

PubMed Central

Mourgeon, Eric; Puybasset, Louis; Law-Koune, Jean-Dominique; Lu, Qin; Abdennour, Lamine; Gallart, Lluis; Malassine, Patrick; Rao, GS Umamaheswara; Cluzel, Philippe; Bennani, Abdelhai; Coriat, Pierre; Rouby, Jean-Jacques

1997-01-01

Background: The aim of this prospective study was to assess whether the presence of septic shock could influence the dose response to inhaled nitric oxide (NO) in NO-responding patients with adult respiratory distress syndrome (ARDS). Results: Eight patients with ARDS and without septic shock (PaO2 = 95 ± 16 mmHg, PEEP = 0, FiO2 = 1.0), and eight patients with ARDS and septic shock (PaO2 = 88 ± 11 mmHg, PEEP = 0, FiO2 = 1.0) receiving exclusively norepinephrine were studied. All responded to 15 ppm inhaled NO with an increase in PaO2 of at least 40 mmHg, at FiO2 1.0 and PEEP 10 cmH2O. Inspiratory intratracheal NO concentrations were recorded continuously using a fast response time chemiluminescence apparatus. Seven inspiratory NO concentrations were randomly administered: 0.15, 0.45, 1.5, 4.5, 15, 45 and 150 ppm. In both groups, NO induced a dose-dependent decrease in mean pulmonary artery pressure (MPAP), pulmonary vascular resistance index (PVRI), and venous admixture (QVA/QT), and a dose-dependent increase in PaO2/FiO2 (P ≤ 0.012). Dose-response of MPAP and PVRI were similar in both groups with a plateau effect at 4.5 ppm. Dose-response of PaO2/FiO2 was influenced by the presence of septic shock. No plateau effect was observed in patients with septic shock and PaO2/FiO2 increased by 173 ± 37% at 150 ppm. In patients without septic shock, an 82 ± 26% increase in PaO2/FiO2 was observed with a plateau effect obtained at 15 ppm. In both groups, dose-response curves demonstrated a marked interindividual variability and in five patients pulmonary vascular effect and improvement in arterial oxygenation were dissociated. Conclusion: For similar NOinduced decreases in MPAP and PVRI in both groups, the increase in arterial oxygenation was more marked in patients with septic shock. PMID:11056694

Cellular Mechanisms of Myocardial Depression in Porcine Septic Shock.

PubMed

Jarkovska, Dagmar; Markova, Michaela; Horak, Jan; Nalos, Lukas; Benes, Jan; Al-Obeidallah, Mahmoud; Tuma, Zdenek; Sviglerova, Jitka; Kuncova, Jitka; Matejovic, Martin; Stengl, Milan

2018-01-01

The complex pathogenesis of sepsis and septic shock involves myocardial depression, the pathophysiology of which, however, remains unclear. In this study, cellular mechanisms of myocardial depression were addressed in a clinically relevant, large animal (porcine) model of sepsis and septic shock. Sepsis was induced by fecal peritonitis in eight anesthetized, mechanically ventilated, and instrumented pigs of both sexes and continued for 24 h. In eight control pigs, an identical experiment but without sepsis induction was performed. In vitro analysis of cardiac function included measurements of action potentials and contractions in the right ventricle trabeculae, measurements of sarcomeric contractions, calcium transients and calcium current in isolated cardiac myocytes, and analysis of mitochondrial respiration by ultrasensitive oxygraphy. Increased values of modified sequential organ failure assessment score and serum lactate levels documented the development of sepsis/septic shock, accompanied by hyperdynamic circulation with high heart rate, increased cardiac output, peripheral vasodilation, and decreased stroke volume. In septic trabeculae, action potential duration was shortened and contraction force reduced. In septic cardiac myocytes, sarcomeric contractions, calcium transients, and L-type calcium current were all suppressed. Similar relaxation trajectory of the intracellular calcium-cell length phase-plane diagram indicated unchanged calcium responsiveness of myofilaments. Mitochondrial respiration was diminished through inhibition of Complex II and Complex IV. Defective calcium handling with reduced calcium current and transients, together with inhibition of mitochondrial respiration, appears to represent the dominant cellular mechanisms of myocardial depression in porcine septic shock.

Effect of Hydrocortisone on Development of Shock Among Patients With Severe Sepsis: The HYPRESS Randomized Clinical Trial.

PubMed

Keh, Didier; Trips, Evelyn; Marx, Gernot; Wirtz, Stefan P; Abduljawwad, Emad; Bercker, Sven; Bogatsch, Holger; Briegel, Josef; Engel, Christoph; Gerlach, Herwig; Goldmann, Anton; Kuhn, Sven-Olaf; Hüter, Lars; Meier-Hellmann, Andreas; Nierhaus, Axel; Kluge, Stefan; Lehmke, Josefa; Loeffler, Markus; Oppert, Michael; Resener, Kerstin; Schädler, Dirk; Schuerholz, Tobias; Simon, Philipp; Weiler, Norbert; Weyland, Andreas; Reinhart, Konrad; Brunkhorst, Frank M

2016-11-01

Adjunctive hydrocortisone therapy is suggested by the Surviving Sepsis Campaign in refractory septic shock only. The efficacy of hydrocortisone in patients with severe sepsis without shock remains controversial. To determine whether hydrocortisone therapy in patients with severe sepsis prevents the development of septic shock. Double-blind, randomized clinical trial conducted from January 13, 2009, to August 27, 2013, with a follow-up of 180 days until February 23, 2014. The trial was performed in 34 intermediate or intensive care units of university and community hospitals in Germany, and it included 380 adult patients with severe sepsis who were not in septic shock. Patients were randomly allocated 1:1 either to receive a continuous infusion of 200 mg of hydrocortisone for 5 days followed by dose tapering until day 11 (n = 190) or to receive placebo (n = 190). The primary outcome was development of septic shock within 14 days. Secondary outcomes were time until septic shock, mortality in the intensive care unit or hospital, survival up to 180 days, and assessment of secondary infections, weaning failure, muscle weakness, and hyperglycemia (blood glucose level >150 mg/dL [to convert to millimoles per liter, multiply by 0.0555]). The intention-to-treat population consisted of 353 patients (64.9% male; mean [SD] age, 65.0 [14.4] years). Septic shock occurred in 36 of 170 patients (21.2%) in the hydrocortisone group and 39 of 170 patients (22.9%) in the placebo group (difference, -1.8%; 95% CI, -10.7% to 7.2%; P = .70). No significant differences were observed between the hydrocortisone and placebo groups for time until septic shock; mortality in the intensive care unit or in the hospital; or mortality at 28 days (15 of 171 patients [8.8%] vs 14 of 170 patients [8.2%], respectively; difference, 0.5%; 95% CI, -5.6% to 6.7%; P = .86), 90 days (34 of 171 patients [19.9%] vs 28 of 168 patients [16.7%]; difference, 3.2%; 95% CI, -5.1% to 11.4%; P = .44), and 180 days (45 of 168 patients [26.8%] vs 37 of 167 patients [22.2%], respectively; difference, 4.6%; 95% CI, -4.6% to 13.7%; P = .32). In the hydrocortisone vs placebo groups, 21.5% vs 16.9% had secondary infections, 8.6% vs 8.5% had weaning failure, 30.7% vs 23.8% had muscle weakness, and 90.9% vs 81.5% had hyperglycemia. Among adults with severe sepsis not in septic shock, use of hydrocortisone compared with placebo did not reduce the risk of septic shock within 14 days. These findings do not support the use of hydrocortisone in these patients. clinicaltrials.gov Identifier: NCT00670254.

Anthrapyrazolone analogues intercept inflammatory JNK signals to moderate endotoxin induced septic shock

NASA Astrophysics Data System (ADS)

Prasad, Karothu Durga; Trinath, Jamma; Biswas, Ansuman; Sekar, Kanagaraj; Balaji, Kithiganahalli N.; Guru Row, Tayur N.

2014-11-01

Severe sepsis or septic shock is one of the rising causes for mortality worldwide representing nearly 10% of intensive care unit admissions. Susceptibility to sepsis is identified to be mediated by innate pattern recognition receptors and responsive signaling pathways of the host. The c-Jun N-terminal Kinase (JNK)-mediated signaling events play critical role in bacterial infection triggered multi-organ failure, cardiac dysfunction and mortality. In the context of kinase specificities, an extensive library of anthrapyrazolone analogues has been investigated for the selective inhibition of c-JNK and thereby to gain control over the inflammation associated risks. In our comprehensive biochemical characterization, it is observed that alkyl and halogen substitution on the periphery of anthrapyrazolone increases the binding potency of the inhibitors specifically towards JNK. Further, it is demonstrated that hydrophobic and hydrophilic interactions generated by these small molecules effectively block endotoxin-induced inflammatory genes expression in in vitro and septic shock in vivo, in a mouse model, with remarkable efficacies. Altogether, the obtained results rationalize the significance of the diversity oriented synthesis of small molecules for selective inhibition of JNK and their potential in the treatment of severe sepsis.

The innate immune response in HIV/AIDS septic shock patients: a comparative study.

PubMed

Amancio, Rodrigo T; Japiassu, Andre M; Gomes, Rachel N; Mesquita, Emersom C; Assis, Edson F; Medeiros, Denise M; Grinsztejn, Beatriz; Bozza, Patrícia T; Castro-Faria Neto, Hugo C; Bozza, Fernando A

2013-01-01

In recent years, the incidence of sepsis has increased in critically ill HIV/AIDS patients, and the presence of severe sepsis emerged as a major determinant of outcomes in this population. The inflammatory response and deregulated cytokine production play key roles in the pathophysiology of sepsis; however, these mechanisms have not been fully characterized in HIV/AIDS septic patients. We conducted a prospective cohort study that included HIV/AIDS and non-HIV patients with septic shock. We measured clinical parameters and biomarkers (C-reactive protein and cytokine levels) on the first day of septic shock and compared these parameters between HIV/AIDS and non-HIV patients. We included 30 HIV/AIDS septic shock patients and 30 non-HIV septic shock patients. The HIV/AIDS patients presented low CD4 cell counts (72 [7-268] cells/mm(3)), and 17 (57%) patients were on HAART before hospital admission. Both groups were similar according to the acute severity scores and hospital mortality. The IL-6, IL-10 and G-CSF levels were associated with hospital mortality in the HIV/AIDS septic group; however, the CRP levels and the surrogates of innate immune activation (cytokines) were similar among HIV/AIDS and non-HIV septic patients. Age (odds ratio 1.05, CI 95% 1.02-1.09, p=0.002) and the IL-6 levels (odds ratio 1.00, CI 95% 1.00-1.01, p=0.05) were independent risk factors for hospital mortality. IL-6, IL-10 and G-CSF are biomarkers that can be used to predict prognosis and outcomes in HIV/AIDS septic patients. Although HIV/AIDS patients are immunocompromised, an innate immune response can be activated in these patients, which is similar to that in the non-HIV septic population. In addition, age and the IL-6 levels are independent risk factors for hospital mortality irrespective of HIV/AIDS disease.

Blood Poisoning: When to See a Doctor

MedlinePlus

... However, bacteremia and infection can potentially progress to sepsis and septic shock, serious illnesses that require prompt ... valves or other tissues, or progress to severe sepsis and septic shock, which may be life-threatening. ...

Hemoadsorption by CytoSorb in septic patients: a case series.

PubMed

Kogelmann, Klaus; Jarczak, Dominik; Scheller, Morten; Drüner, Matthias

2017-03-27

Septic shock, defined as life-threatening organ dysfunction caused by a dysregulated host response to infection, is a highly lethal condition that causes substantial morbidity and mortality among critically ill patients. One of the hallmarks of sepsis is the excessive release of cytokines and other inflammatory mediators causing refractory hypotension, tissue damage, metabolic acidosis and ultimately multiple organ failure. In this context, cytokine reduction by hemoadsorption represents a new concept for blood purification, developed to attenuate the overwhelming systemic levels of pro-inflammatory and anti-inflammatory mediators released in the early phase of sepsis. In the present case series, we evaluated the impact of a new hemoadsorption device (CytoSorb) used as adjunctive therapy, on hemodynamics and clinically relevant outcome parameters in 26 critically ill patients with septic shock and in need of renal replacement therapy. We found that treatment of these patients with septic shock was associated with hemodynamic stabilization and a reduction in blood lactate levels. Actual mortality in the overall patient population was lower than mortality predicted by acute physiology and chronic health evaluation II (APACHE II). These effects seem to be more pronounced in patients in whom therapy started within 24 h of sepsis diagnosis, whereas a delay in the start of therapy was associated with a poor response to therapy in terms of reduction of catecholamine demand and survival. Moreover, from our patient population, medical patients seemed to benefit more than post-surgical patients in terms of survival. Treatment using the CytoSorb device was safe and well-tolerated with no device-related adverse events during or after the treatment sessions. Hemoadsorption using CytoSorb resulted in rapid hemodynamic stabilization and increased survival, particularly in patients in whom therapy was started early. Given the positive clinical experience of this case series, randomized controlled trials are urgently needed to define the potential benefits of this new treatment option.

Fluid therapy for septic shock resuscitation: which fluid should be used?

PubMed

Corrêa, Thiago Domingos; Rocha, Leonardo Lima; Pessoa, Camila Menezes Souza; Silva, Eliézer; de Assuncao, Murillo Santucci Cesar

2015-01-01

Early resuscitation of septic shock patients reduces the sepsis-related morbidity and mortality. The main goals of septic shock resuscitation include volemic expansion, maintenance of adequate tissue perfusion and oxygen delivery, guided by central venous pressure, mean arterial pressure, mixed or central venous oxygen saturation and arterial lactate levels. An aggressive fluid resuscitation, possibly in association with vasopressors, inotropes and red blood cell concentrate transfusion may be necessary to achieve those hemodynamic goals. Nonetheless, even though fluid administration is one of the most common interventions offered to critically ill patients, the most appropriate type of fluid to be used remains controversial. According to recently published clinical trials, crystalloid solutions seem to be the most appropriate type of fluids for initial resuscitation of septic shock patients. Balanced crystalloids have theoretical advantages over the classic solutions, but there is not enough evidence to indicate it as first-line treatment. Additionally, when large amounts of fluids are necessary to restore the hemodynamic stability, albumin solutions may be a safe and effective alternative. Hydroxyethyl starches solutions must be avoided in septic patients due to the increased risk of acute renal failure, increased need for renal replacement therapy and increased mortality. Our objective was to present a narrative review of the literature regarding the major types of fluids and their main drawbacks in the initial resuscitation of the septic shock patients.

Septic Shock Alters Mitochondrial Respiration of Lymphoid Cell-Lines and Human Peripheral Blood Mononuclear Cells: The Role of Plasma.

PubMed

Clere-Jehl, Raphael; Helms, Julie; Kassem, Mohamad; Le Borgne, Pierrick; Delabranche, Xavier; Charles, Anne-Laure; Geny, Bernard; Meziani, Ferhat; Bilbault, Pascal

2018-02-14

In septic shock patients, post-septic immunosuppression state following the systemic inflammatory response syndrome is responsible for nosocomial infections, with subsequent increased mortality. The aim of the present study was to assess the underlying cellular mechanisms of the post-septic immunosuppression state, by investigating mitochondrial functions of peripheral blood mononuclear cells (PBMCs) from septic shock patients over 7 days. Eighteen patients admitted to a French intensive care unit for septic shock were included. At days 1 and 7, PBMCs were isolated by Ficoll density gradient centrifugation. Mitochondrial respiration of intact septic PBMCs was assessed versus control group PBMCs, by measuring O2 consumption in plasma, using high-resolution respirometry. Mitochondrial respiration was then compared between septic plasmas and control plasmas for control PBMCs, septic PBMCs and lymphoid cell-line (CEM). To investigate the role of plasma, we measured several plasma cytokines, among them HMGB1, by ELISA. Basal O2 consumption of septic shock PBMCs was of 8.27 ± 3.39 and 10.48 ± 3.99 pmol/s/10 cells at days 1 and 7 respectively, significantly higher than in control PBMCs (5.37 ± 1.46 pmol/s/10 cells, p < 0.05). Septic patient PBMCs showed a lower response to oligomycin, suggesting a reduced ATP-synthase activity, as well as an increased response to FCCP suggesting an increased mitochondrial respiratory capacity. At 6 hours, septic plasmas showed a decreased O2 consumption of CEM (4.73 ± 1.46 vs. 6.58 ± 1.53, p < 0.05) as well as in control group PBMCs (1.76 ± 0.36 vs. 2.70 ± 0.42, p < 0.05), and triggered a decreased ATP-synthase activity but an increased response to FCCP. These differences are not explained by different cell survival. High HMGB1 levels were significantly associated with reduced PBMCs mitochondrial respiration. Septic plasma impairs mitochondrial respiration in immune cells, with a possible role of the proinflammatory protein HMGB1, leading to a subsequent compensation, probably by enzymatic activation. This compensation result is an improvement of global mitochondrial respiratory capacity, but without restoring ATP-synthase activity.

Comparison of the effects of albumin and crystalloid on mortality in adult patients with severe sepsis and septic shock: a meta-analysis of randomized clinical trials.

PubMed

Xu, Jing-Yuan; Chen, Qi-Hong; Xie, Jian-Feng; Pan, Chun; Liu, Song-Qiao; Huang, Li-Wei; Yang, Cong-Shan; Liu, Ling; Huang, Ying-Zi; Guo, Feng-Mei; Yang, Yi; Qiu, Hai-Bo

2014-12-15

The aim of this study was to examine whether albumin reduced mortality when employed for the resuscitation of adult patients with severe sepsis and septic shock compared with crystalloid by meta-analysis. We searched for and gathered data from MEDLINE, Elsevier, Cochrane Central Register of Controlled Trials and Web of Science databases. Studies were eligible if they compared the effects of albumin versus crystalloid therapy on mortality in adult patients with severe sepsis and septic shock. Two reviewers extracted data independently. Disagreements were resolved by discussion with other two reviewers until a consensus was achieved. Data including mortality, sample size of the patients with severe sepsis, sample size of the patients with septic shock and resuscitation endpoints were extracted. Data were analyzed by the methods recommended by the Cochrane Collaboration Review Manager 4.2 software. A total of 5,534 records were identified through the initial search. Five studies compared albumin with crystalloid. In total, 3,658 severe sepsis and 2,180 septic shock patients were included in the meta-analysis. The heterogeneity was determined to be non-significant (P = 0.86, I(2) = 0%). Compared with crystalloid, a trend toward reduced 90-day mortality was observed in severe sepsis patients resuscitated with albumin (odds ratio (OR) 0.88; 95% CI, 0.76 to 1.01; P = 0.08). However, the use of albumin for resuscitation significantly decreased 90-day mortality in septic shock patients (OR 0.81; 95% CI, 0.67 to 0.97; P = 0.03). Compared with saline, the use of albumin for resuscitation slightly improved outcome in severe sepsis patients (OR 0.81; 95% CI, 0.64 to 1.08; P = 0.09). In this meta-analysis, a trend toward reduced 90-day mortality was observed in severe sepsis patients resuscitated with albumin compared with crystalloid and saline. Moreover, the 90-day mortality of patients with septic shock decreased significantly.

Comparison of procalcitonin and high-sensitivity C-reactive protein for the diagnosis of sepsis and septic shock in the oldest old patients.

PubMed

Zhang, Hongmin; Wang, Xiaoting; Zhang, Qing; Xia, Ying; Liu, Dawei

2017-08-01

Although the role of serum procalcitonin (PCT) and high-sensitivity C-reactive protein (hs-CRP) in the diagnosis of sepsis and septic shock is well studied, it has not been investigated among oldest old patients. The aim of our study is to determine the role of PCT and hs-CRP in the assessment of sepsis and septic shock in this specific group of patients in the ICU. This is a prospective observational study. Patients >85 years of age admitted to the ICU from May 1st, 2016 to February 1st, 2017 were evaluated. Patients were divided into a sepsis and septic shock group(sepsis/SS) and a non-sepsis group. Serum levels of PCT, hs-CRP and the WBC were measured within 12 h of admission. A total of 70 patients aged 85 years and older were enrolled in this study. Fifty patients were labelled as sepsis/SS and the other 20 were labelled non-sepsis. A ROC analysis showed that the area under the curves (AUC) of hs-CRP and PCT for the discrimination of sepsis/SS patients were 0.825 (95% confidence interval[CI]: 0.73-0.92; P < 0.001) and 0.819 (95%CI:0.72-0.92; p < 0.001), respectively. In a subgroup analysis of the sepsis/SS group, 27 patients had sepsis, while the other 23 patients had septic shock. The ROC analysis showed that the AUCs of hs-CRP and PCT for the discrimination of septic shock patients from sepsis patients were 0.751 (95% CI: 0.62-0.88; P = 0.002) and 0.719 (95% CI:0.57-0.86; p = 0.007), respectively. For the oldest old patients, hs-CRP is not inferior to PCT in the diagnosis of sepsis and septic shock.

Low-dose hydrocortisone therapy attenuates septic shock in adult patients but does not reduce 28-day mortality: a meta-analysis of randomized controlled trials.

PubMed

Wang, Changsong; Sun, Jiaxiao; Zheng, Juanjuan; Guo, Lei; Ma, Hongyan; Zhang, Yang; Zhang, Fengmin; Li, Enyou

2014-02-01

The role of low-dose hydrocortisone in attenuating septic shock and reducing short-term mortality in adult patients with septic shock is unclear. We conducted a meta-analysis of previous studies to determine whether hydrocortisone could ameliorate the effects of septic shock at 7 and 28 days and reduce 28-day morality. Randomized controlled trials (RCTs) of corticosteroids versus placebo (or supportive treatment alone) were retrieved from electronic searches (Medline, Embase, and Cochrane Library databases; LILACS; and Web of Knowledge) and manual searches (up to May 2012). From a pool of 1949 potentially relevant articles, duplicate independent review identified 10 relevant, RCTs of low-dose hydrocortisone therapy in septic shock. Four pairs of reviewers agreed on the criteria for trial eligibility. One reviewer entered the data into the computer, and 3 reviewers checked the data. Missing data were obtained from the authors of the relevant trials. The primary outcome analyzed was an estimate of 28-day mortality. Eight publications were included in the meta-analysis. Low-dose hydrocortisone therapy did not reduce 28-day mortality (N = 1063; odds ratio (OR) = 0.891, 95% confidence interval (CI), 0.69-1.15). Low-dose hydrocortisone therapy ameliorated shock at 7 days (6 RCTs, N = 964, OR = 2.078, 95% CI, 1.58-2.73, P < 0.0001, and I = 26.9%) and 28 days (6 RCTs, N = 947, OR = 1.495, 95% CI, 1.12-1.99, P = 0.006, and I = 0.0%). Although low-dose hydrocortisone therapy ameliorates septic shock at 7 and 28 days, it does not reduce 28-day mortality.

Effect of unfractionated heparin on endothelial glycocalyx in a septic shock model.

PubMed

Yini, S; Heng, Z; Xin, A; Xiaochun, M

2015-02-01

The constituents of vascular endothelial glycocalyx, such as syndecan-1 and heparan sulphate (HS), can be detected in the plasma of patients and animals with septic shock. However, the dynamics of glycocalyx degradation and its association with inflammation remains largely unknown. In this study, we investigated the association between the biomarkers of acute endothelial glycocalyx degradation and inflammatory factors. We also evaluated the effect of unfractionated heparin (UFH) on glycocalyx shedding in a canine septic shock model. Twenty adult beagle dogs were randomly allocated to one of the following four groups (n = 5): (1) a sham group; (2) a shock group [3.5 × 10(8) colony-forming unit (cfu) Escherichia coli (E. coli)/kg]; (3) a basic therapy group (sensitive antibiotics and 0.9% saline, 10 ml/kg/h); and (4) a heparin group (40 units/kg/h UFH plus basic therapy). After the onset of septic shock, systemic haemodynamic indices were measured. Endothelial glycocalyx degradation markers (i.e., syndecan-1, HS) and inflammatory factors [i.e., interleukin 6 (IL-6), tumour necrosis factor (TNF)-α], platelet count and activated partial thromboplastin time were measured at various time points. A lethal dose of E. coli induced a progressive septic shock model. We observed increased syndecan-1 and HS levels, which correlated with IL-6 and TNF-α in the septic shock model. The glycocalyx shedding was reduced by UFH, which might be regulated by the inhibition of inflammatory factors. A therapeutic dose of UFH can protect glycocalyx from shedding by inhibiting inflammation. Additional studies with larger sample sizes are needed to confirm our conclusions. © 2014 The Acta Anaesthesiologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

Septic encephalopathy and septic encephalitis‬‬.

PubMed

Tauber, Simone C; Eiffert, Helmut; Brück, Wolfgang; Nau, Roland

2017-02-01

During the last two decades, septic encephalopathy (SE) was recognized as a clinically relevant problem with a high prevalence in patients at admission and during their hospital stay. SE is a condition associated with increased mortality and morbidity such as long-term cognitive impairment. Areas covered: This review illustrates the pathophysiology of sepsis-associated encephalopathy and encephalitis involving blood-brain-barrier dysfunction and neuroinflammation caused by endothelial and microglial activation by endogenous or pathogen-derived compounds, hypoxia by impaired microvascular regulation and septic shock as well as imbalance of neurotransmitters. The continuum between septic-embolic and septic-metastatic encephalitis and SE is underlined by histological findings. The options of technical examinations and biomarkers to diagnose SE are discussed together with established therapeutic options as well as current experimental approaches. Expert commentary: An outlook for clinicians is provided including promising diagnostic approaches by means of new imaging techniques. Clinical trials with drugs already established for other indications such as statins, erythropoietin and minocycline are warranted in the future.

Combined milrinone and enteral metoprolol therapy in patients with septic myocardial depression

PubMed Central

Schmittinger, Christian A; Dünser, Martin W; Haller, Maria; Ulmer, Hanno; Luckner, Günter; Torgersen, Christian; Jochberger, Stefan; Hasibeder, Walter R

2008-01-01

Introduction The multifactorial etiology of septic cardiomyopathy is not fully elucidated. Recently, high catecholamine levels have been suggested to contribute to impaired myocardial function. Methods This retrospective analysis summarizes our preliminary clinical experience with the combined use of milrinone and enteral metoprolol therapy in 40 patients with septic shock and cardiac depression. Patients with other causes of shock or cardiac failure, patients with beta-blocker therapy initiated more than 48 hours after shock onset, and patients with pre-existent decompensated congestive heart failure were excluded. In all study patients, beta blockers were initiated only after stabilization of cardiovascular function (17.7 ± 15.5 hours after shock onset or intensive care unit admission) in order to decrease the heart rate to less than 95 beats per minute (bpm). Hemodynamic data and laboratory parameters were extracted from medical charts and documented before and 6, 12, 24, 48, 72, and 96 hours after the first metoprolol dosage. Adverse cardiovascular events were documented. Descriptive statistical methods and a linear mixed-effects model were used for statistical analysis. Results Heart rate control (65 to 95 bpm) was achieved in 97.5% of patients (n = 39) within 12.2 ± 12.4 hours. Heart rate, central venous pressure, and norepinephrine, arginine vasopressin, and milrinone dosages decreased (all P < 0.001). Cardiac index and cardiac power index remained unchanged whereas stroke volume index increased (P = 0.002). In two patients (5%), metoprolol was discontinued because of asymptomatic bradycardia. Norepinephrine and milrinone dosages were increased in nine (22.5%) and six (15%) patients, respectively. pH increased (P < 0.001) whereas arterial lactate (P < 0.001), serum C-reactive protein (P = 0.001), and creatinine (P = 0.02) levels decreased during the observation period. Twenty-eight-day mortality was 33%. Conclusion Low doses of enteral metoprolol in combination with phosphodiesterase inhibitors are feasible in patients with septic shock and cardiac depression but no overt heart failure. Future prospective controlled trials on the use of beta blockers for septic cardiomyopathy and their influence on proinflammatory cytokines are warranted. PMID:18680591

Troponin elevation in severe sepsis and septic shock: the role of left ventricular diastolic dysfunction and right ventricular dilatation*.

PubMed

Landesberg, Giora; Jaffe, Allan S; Gilon, Dan; Levin, Phillip D; Goodman, Sergey; Abu-Baih, Abed; Beeri, Ronen; Weissman, Charles; Sprung, Charles L; Landesberg, Amir

2014-04-01

Serum troponin concentrations predict mortality in almost every clinical setting they have been examined, including sepsis. However, the causes for troponin elevations in sepsis are poorly understood. We hypothesized that detailed investigation of myocardial dysfunction by echocardiography can provide insight into the possible causes of troponin elevation and its association with mortality in sepsis. Prospective, analytic cohort study. Tertiary academic institute. A cohort of ICU patients with severe sepsis or septic shock. Advanced echocardiography using global strain, strain-rate imaging and 3D left and right ventricular volume analyses in addition to the standard echocardiography, and concomitant high-sensitivity troponin-T measurement in patients with severe sepsis or septic shock. Two hundred twenty-five echocardiograms and concomitant high-sensitivity troponin-T measurements were performed in a cohort of 106 patients within the first days of severe sepsis or septic shock (2.1 ± 1.4 measurements/patient). Combining echocardiographic and clinical variables, left ventricular diastolic dysfunction defined as increased mitral E-to-strain-rate e'-wave ratio, right ventricular dilatation (increased right ventricular end-systolic volume index), high Acute Physiology and Chronic Health Evaluation-II score, and low glomerular filtration rate best correlated with elevated log-transformed concomitant high-sensitivity troponin-T concentrations (mixed linear model: t = 3.8, 3.3, 2.8, and -2.1 and p = 0.001, 0.0002, 0.006, and 0.007, respectively). Left ventricular systolic dysfunction determined by reduced strain-rate s'-wave or low ejection fraction did not significantly correlate with log(concomitant high-sensitivity troponin-T). Forty-one patients (39%) died in-hospital. Right ventricular end-systolic volume index and left ventricular strain-rate e'-wave predicted in-hospital mortality, independent of Acute Physiology and Chronic Health Evaluation-II score (logistic regression: Wald = 8.4, 6.6, and 9.8 and p = 0.004, 0.010, and 0.001, respectively). Concomitant high-sensitivity troponin-T predicted mortality in univariate analysis (Wald = 8.4; p = 0.004), but not when combined with right ventricular end-systolic volume index and strain-rate e'-wave in the multivariate analysis (Wald = 2.3, 4.6, and 6.2 and p = 0.13, 0.032, and 0.012, respectively). Left ventricular diastolic dysfunction and right ventricular dilatation are the echocardiographic variables correlating best with concomitant high-sensitivity troponin-T concentrations. Left ventricular diastolic and right ventricular systolic dysfunction seem to explain the association of troponin with mortality in severe sepsis and septic shock.

Epidemiology and Outcome of Severe Sepsis and Septic Shock in Intensive Care Units in Mainland China

PubMed Central

Zhou, Jianfang; Qian, Chuanyun; Zhao, Mingyan; Yu, Xiangyou; Kang, Yan; Ma, Xiaochun; Ai, Yuhang; Xu, Yuan; Liu, Dexin; An, Youzhong; Wu, Dawei; Sun, Renhua; Li, Shusheng; Hu, Zhenjie; Cao, Xiangyuan; Zhou, Fachun; Jiang, Li; Lin, Jiandong; Mao, Enqiang; Qin, Tiehe; He, Zhenyang; Zhou, Lihua; Du, Bin

2014-01-01

Introduction Information about sepsis in mainland China remains scarce and incomplete. The purpose of this study was to describe the epidemiology and outcome of severe sepsis and septic shock in mixed ICU in mainland China, as well as the independent predictors of mortality. Methods We performed a 2-month prospective, observational cohort study in 22 closed multi-disciplinary intensive care units (ICUs). All admissions into those ICUs during the study period were screened and patients with severe sepsis or septic shock were included. Results A total of 484 patients, 37.3 per 100 ICU admissions were diagnosed with severe sepsis (n = 365) or septic shock (n = 119) according to clinical criteria and included into this study. The most frequent sites of infection were the lung and abdomen. The overall ICU and hospital mortality rates were 28.7% (n = 139) and 33.5% (n = 162), respectively. In multivariate analyses, APACHE II score (odds ratio[OR], 1.068; 95% confidential interval[CI], 1.027–1.109), presence of ARDS (OR, 2.676; 95%CI, 1.691–4.235), bloodstream infection (OR, 2.520; 95%CI, 1.142–5.564) and comorbidity of cancer (OR, 2.246; 95%CI, 1.141–4.420) were significantly associated with mortality. Conclusions Our results indicated that severe sepsis and septic shock were common complications in ICU patients and with high mortality in China, and can be of help to know more about severe sepsis and septic shock in China and to improve characterization and risk stratification in these patients. PMID:25226033

Effect of mode of hydrocortisone administration on glycemic control in patients with septic shock: a prospective randomized trial.

PubMed

Loisa, Pekka; Parviainen, Ilkka; Tenhunen, Jyrki; Hovilehto, Seppo; Ruokonen, Esko

2007-01-01

Low-dose hydrocortisone treatment is widely accepted therapy for the treatment of vasopressor-dependent septic shock. The question of whether corticosteroids should be given to septic shock patients by continuous or by bolus infusion is still unanswered. Hydrocortisone induces hyperglycemia and it is possible that continuous hydrocortisone infusion would reduce the fluctuations in blood glucose levels and that tight blood glucose control could be better achieved with this approach. In this prospective randomized study, we compared the blood glucose profiles, insulin requirements, amount of nursing workload needed, and shock reversal in 48 septic shock patients who received hydrocortisone treatment either by bolus or by continuous infusion with equivalent dose (200 mg/day). Duration of hydrocortisone treatment was five days. The mean blood glucose levels were similar in the two groups, but the number of hyperglycemic episodes was significantly higher in those patients who received bolus therapy (15.7 +/- 8.5 versus 10.5 +/- 8.6 episodes per patient, p = 0.039). Also, more changes in insulin infusion rate were needed to maintain strict normoglycemia in the bolus group (4.7 +/- 2.2 versus 3.4 +/- 1.9 adjustments per patient per day, p = 0.038). Hypoglycemic episodes were rare in both groups. No difference was seen in shock reversal. Strict normoglycemia is more easily achieved if the hydrocortisone therapy is given to septic shock patients by continuous infusion. This approach also reduces nursing workload needed to maintain tight blood glucose control.

Infectious Etiologies and Patient Outcomes in Pediatric Septic Shock.

PubMed

Ames, Stefanie G; Workman, Jennifer K; Olson, Jared A; Korgenski, E Kent; Masotti, Susan; Knackstedt, Elizabeth D; Bratton, Susan L; Larsen, Gitte Y

2017-03-01

Septic shock remains an important cause of death and disability in children. Optimal care requires early recognition and treatment. We evaluated a retrospective cohort of children (age <19) treated in our emergency department (ED) for septic shock during 2008-2012 to investigate the association between timing of antibiotic therapy and outcomes. The exposures were (1) receipt of empiric antibiotics in ≤1 hour and (2) receipt of appropriate antibiotics in ≤1 hour. The primary outcome was development of new or progressive multiple system organ dysfunction syndrome (NP-MODS). The secondary outcome was mortality. Among 321 patients admitted to intensive care, 48% (n = 153) received empiric antibiotics in ≤1 hour. These patients were more ill at presentation with significantly greater median pediatric index of mortality 2 (PIM2) scores and were more likely to receive recommended resuscitation in the ED (61% vs 14%); however, rates of NP-MODS (9% vs 12%) and hospital mortality (7% vs 4%) were similar to those treated later. Early, appropriate antibiotics were administered to 33% (n = 67) of patients with identified or suspected bacterial infection. These patients had significantly greater PIM2 scores but similar rates of NP-MODS (15% vs 15%) and hospital mortality (10% vs 6%) to those treated later. Critically ill children with septic shock treated in a children's hospital ED who received antibiotics in ≤1 hour were significantly more severely ill than those treated later, but they did not have increased risk of NP-MODS or death. © The Author 2016. Published by Oxford University Press on behalf of The Journal of the Pediatric Infectious Diseases Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Liberal Versus Restrictive Intravenous Fluid Therapy for Early Septic Shock: Rationale for a Randomized Trial.

PubMed

Self, Wesley H; Semler, Matthew W; Bellomo, Rinaldo; Brown, Samuel M; deBoisblanc, Bennett P; Exline, Matthew C; Ginde, Adit A; Grissom, Colin K; Janz, David R; Jones, Alan E; Liu, Kathleen D; Macdonald, Stephen P J; Miller, Chadwick D; Park, Pauline K; Reineck, Lora A; Rice, Todd W; Steingrub, Jay S; Talmor, Daniel; Yealy, Donald M; Douglas, Ivor S; Shapiro, Nathan I

2018-05-09

Prompt intravenous fluid therapy is a fundamental treatment for patients with septic shock. However, the optimal approach for administering intravenous fluid in septic shock resuscitation is unknown. Two competing strategies are emerging: a liberal fluids approach, consisting of a larger volume of initial fluid (50 to 75 mL/kg [4 to 6 L in an 80-kg adult] during the first 6 hours) and later use of vasopressors, versus a restrictive fluids approach, consisting of a smaller volume of initial fluid (≤30 mL/kg [≤2 to 3 L]), with earlier reliance on vasopressor infusions to maintain blood pressure and perfusion. Early fluid therapy may enhance or maintain tissue perfusion by increasing venous return and cardiac output. However, fluid administration may also have deleterious effects by causing edema within vital organs, leading to organ dysfunction and impairment of oxygen delivery. Conversely, a restrictive fluids approach primarily relies on vasopressors to reverse hypotension and maintain perfusion while limiting the administration of fluid. Both strategies have some evidence to support their use but lack robust data to confirm the benefit of one strategy over the other, creating clinical and scientific equipoise. As part of the National Heart, Lung, and Blood Institute Prevention and Early Treatment of Acute Lung Injury Network, we designed a randomized clinical trial to compare the liberal and restrictive fluids strategies, the Crystalloid Liberal or Vasopressor Early Resuscitation in Sepsis trial. The purpose of this article is to review the current literature on approaches to early fluid resuscitation in adults with septic shock and outline the rationale for the upcoming trial. Copyright © 2018 American College of Emergency Physicians. Published by Elsevier Inc. All rights reserved.

The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3)

PubMed Central

Singer, Mervyn; Deutschman, Clifford S.; Seymour, Christopher Warren; Shankar-Hari, Manu; Annane, Djillali; Bauer, Michael; Bellomo, Rinaldo; Bernard, Gordon R.; Chiche, Jean-Daniel; Coopersmith, Craig M.; Hotchkiss, Richard S.; Levy, Mitchell M.; Marshall, John C.; Martin, Greg S.; Opal, Steven M.; Rubenfeld, Gordon D.; van der Poll, Tom; Vincent, Jean-Louis; Angus, Derek C.

2016-01-01

IMPORTANCE Definitions of sepsis and septic shock were last revised in 2001. Considerable advances have since been made into the pathobiology (changes in organ function, morphology, cell biology, biochemistry, immunology, and circulation), management, and epidemiology of sepsis, suggesting the need for reexamination. OBJECTIVE To evaluate and, as needed, update definitions for sepsis and septic shock. PROCESS A task force (n = 19) with expertise in sepsis pathobiology, clinical trials, and epidemiology was convened by the Society of Critical Care Medicine and the European Society of Intensive Care Medicine. Definitions and clinical criteria were generated through meetings, Delphi processes, analysis of electronic health record databases, and voting, followed by circulation to international professional societies, requesting peer review and endorsement (by 31 societies listed in the Acknowledgment). KEY FINDINGS FROMEVIDENCE SYNTHESIS Limitations of previous definitions included an excessive focus on inflammation, the misleading model that sepsis follows a continuum through severe sepsis to shock, and inadequate specificity and sensitivity of the systemic inflammatory response syndrome (SIRS) criteria. Multiple definitions and terminologies are currently in use for sepsis, septic shock, and organ dysfunction, leading to discrepancies in reported incidence and observed mortality. The task force concluded the term severe sepsis was redundant. RECOMMENDATIONS Sepsis should be defined as life-threatening organ dysfunction caused by a dysregulated host response to infection. For clinical operationalization, organ dysfunction can be represented by an increase in the Sequential [Sepsis-related] Organ Failure Assessment (SOFA) score of 2 points or more, which is associated with an in-hospital mortality greater than 10%. Septic shock should be defined as a subset of sepsis in which particularly profound circulatory, cellular, and metabolic abnormalities are associated with a greater risk of mortality than with sepsis alone. Patients with septic shock can be clinically identified by a vasopressor requirement to maintain a mean arterial pressure of 65 mm Hg or greater and serum lactate level greater than 2 mmol/L (>18 mg/dL) in the absence of hypovolemia. This combination is associated with hospital mortality rates greater than 40%. In out-of-hospital, emergency department, or general hospital ward settings, adult patients with suspected infection can be rapidly identified as being more likely to have poor outcomes typical of sepsis if they have at least 2 of the following clinical criteria that together constitute a new bedside clinical score termed quickSOFA (qSOFA): respiratory rate of 22/min or greater, altered mentation, or systolic blood pressure of 100 mm Hg or less. CONCLUSIONS AND RELEVANCE These updated definitions and clinical criteria should replace previous definitions, offer greater consistency for epidemiologic studies and clinical trials, and facilitate earlier recognition and more timely management of patients with sepsis or at risk of developing sepsis. PMID:26903338

The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3).

PubMed

Singer, Mervyn; Deutschman, Clifford S; Seymour, Christopher Warren; Shankar-Hari, Manu; Annane, Djillali; Bauer, Michael; Bellomo, Rinaldo; Bernard, Gordon R; Chiche, Jean-Daniel; Coopersmith, Craig M; Hotchkiss, Richard S; Levy, Mitchell M; Marshall, John C; Martin, Greg S; Opal, Steven M; Rubenfeld, Gordon D; van der Poll, Tom; Vincent, Jean-Louis; Angus, Derek C

2016-02-23

Definitions of sepsis and septic shock were last revised in 2001. Considerable advances have since been made into the pathobiology (changes in organ function, morphology, cell biology, biochemistry, immunology, and circulation), management, and epidemiology of sepsis, suggesting the need for reexamination. To evaluate and, as needed, update definitions for sepsis and septic shock. A task force (n = 19) with expertise in sepsis pathobiology, clinical trials, and epidemiology was convened by the Society of Critical Care Medicine and the European Society of Intensive Care Medicine. Definitions and clinical criteria were generated through meetings, Delphi processes, analysis of electronic health record databases, and voting, followed by circulation to international professional societies, requesting peer review and endorsement (by 31 societies listed in the Acknowledgment). Limitations of previous definitions included an excessive focus on inflammation, the misleading model that sepsis follows a continuum through severe sepsis to shock, and inadequate specificity and sensitivity of the systemic inflammatory response syndrome (SIRS) criteria. Multiple definitions and terminologies are currently in use for sepsis, septic shock, and organ dysfunction, leading to discrepancies in reported incidence and observed mortality. The task force concluded the term severe sepsis was redundant. Sepsis should be defined as life-threatening organ dysfunction caused by a dysregulated host response to infection. For clinical operationalization, organ dysfunction can be represented by an increase in the Sequential [Sepsis-related] Organ Failure Assessment (SOFA) score of 2 points or more, which is associated with an in-hospital mortality greater than 10%. Septic shock should be defined as a subset of sepsis in which particularly profound circulatory, cellular, and metabolic abnormalities are associated with a greater risk of mortality than with sepsis alone. Patients with septic shock can be clinically identified by a vasopressor requirement to maintain a mean arterial pressure of 65 mm Hg or greater and serum lactate level greater than 2 mmol/L (>18 mg/dL) in the absence of hypovolemia. This combination is associated with hospital mortality rates greater than 40%. In out-of-hospital, emergency department, or general hospital ward settings, adult patients with suspected infection can be rapidly identified as being more likely to have poor outcomes typical of sepsis if they have at least 2 of the following clinical criteria that together constitute a new bedside clinical score termed quickSOFA (qSOFA): respiratory rate of 22/min or greater, altered mentation, or systolic blood pressure of 100 mm Hg or less. These updated definitions and clinical criteria should replace previous definitions, offer greater consistency for epidemiologic studies and clinical trials, and facilitate earlier recognition and more timely management of patients with sepsis or at risk of developing sepsis.

Sepsis and Septic Shock Strategies.

PubMed

Armstrong, Bracken A; Betzold, Richard D; May, Addison K

2017-12-01

Three therapeutic principles most substantially improve organ dysfunction and survival in sepsis: early, appropriate antimicrobial therapy; restoration of adequate cellular perfusion; timely source control. The new definitions of sepsis and septic shock reflect the inadequate sensitivity, specify, and lack of prognostication of systemic inflammatory response syndrome criteria. Sequential (sepsis-related) organ failure assessment more effectively prognosticates in sepsis and critical illness. Inadequate cellular perfusion accelerates injury and reestablishing perfusion limits injury. Multiple organ systems are affected by sepsis and septic shock and an evidence-based multipronged approach to systems-based therapy in critical illness results in improve outcomes. Copyright © 2017 Elsevier Inc. All rights reserved.

Management of Acute Respiratory Failure in the Patient with Sepsis or Septic Shock.

PubMed

Moore, Sarah; Weiss, Brian; Pascual, Jose L; Kaplan, Lewis J

Sepsis and septic shock are each commonly accompanied by acute respiratory failure and the need for invasive as well as non-invasive ventilation throughout a patient's intensive care unit course. We explore the underpinnings of acute respiratory failure of pulmonary as well as non-pulmonary origin in the context of invasive and non-invasive management approaches. Both pharmacologic and non-pharmacologic adjuncts to ventilatory and oxygenation support are highlighted as well. Finally, rescue modalities are positioned within the intensivist's armamentarium for global care of support of the critically ill or injured patient with sepsis or septic shock.

Early administration of hydrocortisone replacement after the advent of septic shock: impact on survival and immune response*.

PubMed

Katsenos, Chrysostomos S; Antonopoulou, Anastasia N; Apostolidou, Efterpi N; Ioakeimidou, Aikaterini; Kalpakou, Georgia Th; Papanikolaou, Metaxia N; Pistiki, Aikaterini C; Mpalla, Margarita C; Paraschos, Michael D; Patrani, Maria A; Pratikaki, Maria E; Retsas, Theodoros A; Savva, Athina A; Vassiliagkou, Spyridoula D; Lekkou, Alexandra A; Dimopoulou, Ioanna; Routsi, Christina; Mandragos, Konstantinos E

2014-07-01

To investigate the impact of early initiation of hydrocortisone therapy on the clinical course of septic shock and on cytokine release. Prospective study in patients with septic shock treated with low doses of hydrocortisone. ICUs and general wards. Over a 2-year period, 170 patients with septic shock treated with low doses of hydrocortisone were enrolled. Blood was sampled from 34 patients for isolation of peripheral blood mononuclear cells and cytokine stimulation before and 24 hours after the start of hydrocortisone. None. After quartile analysis, patients were divided into those with early initiation of hydrocortisone (< 9 hr after vasopressors, n = 46) and those with late initiation of hydrocortisone (> 9 hr after vasopressors, n = 124). After adjusting for disease severity and type of infection, a protective effect of early hydrocortisone administration against unfavorable outcome was found (hazard ratio, 0.20; p = 0.012). Time of discontinuation of vasopressors was earlier among patients with initiation of hydrocortisone within 9 hours. Production of tumor necrosis factor-α was lower among patients who had had hydrocortisone early. In patients receiving hydrocortisone for septic shock, early initiation of treatment was associated with improved survival. This treatment was also associated with attenuated stimulation of tumor necrosis factor-α.

Serum thiamine concentration and oxidative stress as predictors of mortality in patients with septic shock.

PubMed

Costa, Nara Aline; Gut, Ana Lúcia; de Souza Dorna, Mariana; Pimentel, José Alexandre Coelho; Cozzolino, Silvia Maria Franciscato; Azevedo, Paula Schmidt; Fernandes, Ana Angélica Henrique; Zornoff, Leonardo Antonio Mamede; de Paiva, Sergio Alberto Rupp; Minicucci, Marcos Ferreira

2014-04-01

The purpose of the study is to determine the influence of serum thiamine, glutathione peroxidase (GPx) activity, and serum protein carbonyl concentrations in hospital mortality in patients with septic shock. This prospective study included all patients with septic shock on admission or during intensive care unit (ICU) stay, older than 18 years, admitted to 1 of the 3 ICUs of the Botucatu Medical School, from January to August 2012. Demographic information, clinical evaluation, and blood sample were taken within the first 72 hours of the patient's admission or within 72 hours after septic shock diagnosis for serum thiamine, GPx activity, and protein carbonyl determination. One hundred eight consecutive patients were evaluated. The mean age was 57.5 ± 16.0 years, 63% were male, 54.6% died in the ICU, and 71.3% had thiamine deficiency. Thiamine was not associated with oxidative stress. Neither vitamin B1 levels nor the GPx activity was associated with outcomes in these patients. However, protein carbonyl concentration was associated with increased mortality. In patients with septic shock, oxidative stress was associated with mortality. On the other hand, thiamine was not associated with oxidative stress or mortality in these patients. Copyright © 2014 Elsevier Inc. All rights reserved.

The Impact of Timing of Antibiotics on Outcomes in Severe Sepsis and Septic Shock: A Systematic Review and Meta-analysis

PubMed Central

Sterling, Sarah A.; Miller, W. Ryan; Pryor, Jason; Puskarich, Michael A.; Jones, Alan E.

2015-01-01

Objectives We sought to systematically review and meta-analyze the available data on the association between timing of antibiotic administration and mortality in severe sepsis and septic shock. Data Sources and Study Selection A comprehensive search was performed using a pre-defined protocol. Inclusion criteria: adult patients with severe sepsis or septic shock, reported time to antibiotic administration in relation to ED triage and/or shock recognition, and mortality. Exclusion criteria: immunosuppressed populations, review article, editorial, or non-human studies. Data Extraction Two reviewers screened abstracts with a third reviewer arbitrating. The effect of time to antibiotic administration on mortality was based on current guideline recommendations: 1) administration within 3 hours of ED triage; 2) administration within 1 hour of severe sepsis/septic shock recognition. Odds Ratios (OR) were calculated using a random effect model. The primary outcome was mortality. Data Synthesis 1123 publications were identified and 11 were included in the analysis. Among the 11 included studies, 16,178 patients were evaluable for antibiotic administration from ED triage. Patients who received antibiotics more than 3 hours after ED triage (< 3 hours reference), had a pooled OR for mortality of 1.16 (0.92 to 1.46, p = 0.21). A total of 11,017 patients were evaluable for antibiotic administration from severe sepsis/septic shock recognition. Patients who received antibiotics more than 1 hour after severe sepsis/shock recognition (< 1 hour reference) had a pooled OR for mortality of 1.46 (0.89 to 2.40, p = 0.13). There was no increased mortality in the pooled ORs for each hourly delay from <1 to >5 hours in antibiotic administration from severe sepsis/shock recognition. Conclusion Using the available pooled data we found no significant mortality benefit of administering antibiotics within 3 hours of ED triage or within 1 hour of shock recognition in severe sepsis and septic shock. These results suggest that currently recommended timing metrics as measures of quality of care are not supported by the available evidence. PMID:26121073

Central venous pressure and shock index predict lack of hemodynamic response to volume expansion in septic shock: a prospective, observational study.

PubMed

Lanspa, Michael J; Brown, Samuel M; Hirshberg, Eliotte L; Jones, Jason P; Grissom, Colin K

2012-12-01

Volume expansion is a common therapeutic intervention in septic shock, although patient response to the intervention is difficult to predict. Central venous pressure (CVP) and shock index have been used independently to guide volume expansion, although their use is questionable. We hypothesize that a combination of these measurements will be useful. In a prospective, observational study, patients with early septic shock received 10-mL/kg volume expansion at their treating physician's discretion after brief initial resuscitation in the emergency department. Central venous pressure and shock index were measured before volume expansion interventions. Cardiac index was measured immediately before and after the volume expansion using transthoracic echocardiography. Hemodynamic response was defined as an increase in a cardiac index of 15% or greater. Thirty-four volume expansions were observed in 25 patients. A CVP of 8 mm Hg or greater and a shock index of 1 beat min(-1) mm Hg(-1) or less individually had a good negative predictive value (83% and 88%, respectively). Of 34 volume expansions, the combination of both a high CVP and a low shock index was extremely unlikely to elicit hemodynamic response (negative predictive value, 93%; P = .02). Volume expansion in patients with early septic shock with a CVP of 8 mm Hg or greater and a shock index of 1 beat min(-1) mm Hg(-1) or less is unlikely to lead to an increase in cardiac index. Copyright © 2012 Elsevier Inc. All rights reserved.

Hemoadsorption in a Case of Severe Septic Shock and Necrotizing Fasciitis Caused by Nontraumatic Renal Rupture due to Pyelonephritis with Obstructive Uropathy.

PubMed

Kousoulas, Lampros; Wittel, Uwe; Fichtner-Feigl, Stefan; Utzolino, Stefan

2018-01-01

Nontraumatic renal rupture due to pyelonephritis with obstructive uropathy is an uncommon but life-threatening situation. A 25-year-old female presented to the emergency department with acute worsening of abdominal pain that began four weeks earlier. She was found to have peritonitis, leukocytosis, severe lactic acidosis, and a pronounced anemia and imaging was consistent with nontraumatic renal rupture with retroperitoneal abscess, perforation of the colon, and severe necrotizing fasciitis of the right lower limb. She underwent a right nephrectomy, a right hemicolectomy, surgical debridement of the retroperitoneum, and an upper thigh amputation. Due to severe septic shock and rhabdomyolysis with acute renal failure we performed a combined treatment of hemoadsorption using a Cytosorb hemoadsorber and continuous venovenous hemodialysis (CVVHD). Subsequently the patient recovered and was discharged home with no signs of infections and with normal renal function. We present a case of pyelonephritis with nontraumatic renal rupture leading to necrotizing fasciitis with osteomyelitis of the lower limb. The early treatment of the patient with a Cytosorb hemoadsorber led to a rapid hemodynamic and metabolic stabilization and preservation of the renal function, suggesting that hemoadsorption might be a rescue therapy in patients with severe septic shock and traumatic rhabdomyolysis.

Hemoadsorption in a Case of Severe Septic Shock and Necrotizing Fasciitis Caused by Nontraumatic Renal Rupture due to Pyelonephritis with Obstructive Uropathy

PubMed Central

Wittel, Uwe; Fichtner-Feigl, Stefan; Utzolino, Stefan

2018-01-01

Background Nontraumatic renal rupture due to pyelonephritis with obstructive uropathy is an uncommon but life-threatening situation. Case Presentation A 25-year-old female presented to the emergency department with acute worsening of abdominal pain that began four weeks earlier. She was found to have peritonitis, leukocytosis, severe lactic acidosis, and a pronounced anemia and imaging was consistent with nontraumatic renal rupture with retroperitoneal abscess, perforation of the colon, and severe necrotizing fasciitis of the right lower limb. She underwent a right nephrectomy, a right hemicolectomy, surgical debridement of the retroperitoneum, and an upper thigh amputation. Due to severe septic shock and rhabdomyolysis with acute renal failure we performed a combined treatment of hemoadsorption using a Cytosorb hemoadsorber and continuous venovenous hemodialysis (CVVHD). Subsequently the patient recovered and was discharged home with no signs of infections and with normal renal function. Conclusion We present a case of pyelonephritis with nontraumatic renal rupture leading to necrotizing fasciitis with osteomyelitis of the lower limb. The early treatment of the patient with a Cytosorb hemoadsorber led to a rapid hemodynamic and metabolic stabilization and preservation of the renal function, suggesting that hemoadsorption might be a rescue therapy in patients with severe septic shock and traumatic rhabdomyolysis. PMID:29854478

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.

Comparative safety and efficacy of vasopressors for mortality in septic shock: A network meta-analysis.

PubMed

Nagendran, Myura; Maruthappu, Mahiben; Gordon, Anthony C; Gurusamy, Kurinchi S

2016-05-01

Septic shock is a life-threatening condition requiring vasopressor agents to support the circulatory system. Several agents exist with choice typically guided by the specific clinical scenario. We used a network meta-analysis approach to rate the comparative efficacy and safety of vasopressors for mortality and arrhythmia incidence in septic shock patients. We performed a comprehensive electronic database search including Medline, Embase, Science Citation Index Expanded and the Cochrane database. Randomised trials investigating vasopressor agents in septic shock patients and specifically assessing 28-day mortality or arrhythmia incidence were included. A Bayesian network meta-analysis was performed using Markov chain Monte Carlo methods. Thirteen trials of low to moderate risk of bias in which 3146 patients were randomised were included. There was no pairwise evidence to suggest one agent was superior over another for mortality. In the network meta-analysis, vasopressin was significantly superior to dopamine (OR 0.68 (95% CI 0.5 to 0.94)) for mortality. For arrhythmia incidence, standard pairwise meta-analyses confirmed that dopamine led to a higher incidence of arrhythmias than norepinephrine (OR 2.69 (95% CI 2.08 to 3.47)). In the network meta-analysis, there was no evidence of superiority of one agent over another. In this network meta-analysis, vasopressin was superior to dopamine for 28-day mortality in septic shock. Existing pairwise information supports the use of norepinephrine over dopamine. Our findings suggest that dopamine should be avoided in patients with septic shock and that other vasopressor agents should continue to be based on existing guidelines and clinical judgement of the specific presentation of the patient.

American College of Critical Care Medicine Clinical Practice Parameters for Hemodynamic Support of Pediatric and Neonatal Septic Shock.

PubMed

Davis, Alan L; Carcillo, Joseph A; Aneja, Rajesh K; Deymann, Andreas J; Lin, John C; Nguyen, Trung C; Okhuysen-Cawley, Regina S; Relvas, Monica S; Rozenfeld, Ranna A; Skippen, Peter W; Stojadinovic, Bonnie J; Williams, Eric A; Yeh, Tim S; Balamuth, Fran; Brierley, Joe; de Caen, Allan R; Cheifetz, Ira M; Choong, Karen; Conway, Edward; Cornell, Timothy; Doctor, Allan; Dugas, Marc-Andre; Feldman, Jonathan D; Fitzgerald, Julie C; Flori, Heidi R; Fortenberry, James D; Graciano, Ana Lia; Greenwald, Bruce M; Hall, Mark W; Han, Yong Yun; Hernan, Lynn J; Irazuzta, Jose E; Iselin, Elizabeth; van der Jagt, Elise W; Jeffries, Howard E; Kache, Saraswati; Katyal, Chhavi; Kissoon, Niranjan Tex; Kon, Alexander A; Kutko, Martha C; MacLaren, Graeme; Maul, Timothy; Mehta, Renuka; Odetola, Fola; Parbuoni, Kristine; Paul, Raina; Peters, Mark J; Ranjit, Suchitra; Reuter-Rice, Karin E; Schnitzler, Eduardo J; Scott, Halden F; Torres, Adalberto; Weingarten-Abrams, Jacki; Weiss, Scott L; Zimmerman, Jerry J; Zuckerberg, Aaron L

2017-06-01

The American College of Critical Care Medicine provided 2002 and 2007 guidelines for hemodynamic support of newborn and pediatric septic shock. Provide the 2014 update of the 2007 American College of Critical Care Medicine "Clinical Guidelines for Hemodynamic Support of Neonates and Children with Septic Shock." Society of Critical Care Medicine members were identified from general solicitation at Society of Critical Care Medicine Educational and Scientific Symposia (2006-2014). The PubMed/Medline/Embase literature (2006-14) was searched by the Society of Critical Care Medicine librarian using the keywords: sepsis, septicemia, septic shock, endotoxemia, persistent pulmonary hypertension, nitric oxide, extracorporeal membrane oxygenation, and American College of Critical Care Medicine guidelines in the newborn and pediatric age groups. The 2002 and 2007 guidelines were widely disseminated, translated into Spanish and Portuguese, and incorporated into Society of Critical Care Medicine and American Heart Association/Pediatric Advanced Life Support sanctioned recommendations. The review of new literature highlights two tertiary pediatric centers that implemented quality improvement initiatives to improve early septic shock recognition and first-hour compliance to these guidelines. Improved compliance reduced hospital mortality from 4% to 2%. Analysis of Global Sepsis Initiative data in resource rich developed and developing nations further showed improved hospital mortality with compliance to first-hour and stabilization guideline recommendations. The major new recommendation in the 2014 update is consideration of institution-specific use of 1) a "recognition bundle" containing a trigger tool for rapid identification of patients with septic shock, 2) a "resuscitation and stabilization bundle" to help adherence to best practice principles, and 3) a "performance bundle" to identify and overcome perceived barriers to the pursuit of best practice principles.

Increased survival of cirrhotic patients with septic shock.

PubMed

Sauneuf, Bertrand; Champigneulle, Benoit; Soummer, Alexis; Mongardon, Nicolas; Charpentier, Julien; Cariou, Alain; Chiche, Jean-Daniel; Mallet, Vincent; Mira, Jean-Paul; Pène, Frédéric

2013-04-19

The overall outcome of septic shock has been recently improved. We sought to determine whether this survival gain extends to the high-risk subgroup of patients with cirrhosis. Cirrhotic patients with septic shock admitted to a medical intensive care unit (ICU) during two consecutive periods (1997-2004 and 2005-2010) were retrospectively studied. Forty-seven and 42 cirrhotic patients presented with septic shock in 1997-2004 and 2005-2010, respectively. The recent period differed from the previous one by implementation of adjuvant treatments of septic shock including albumin infusion as fluid volume therapy, low-dose glucocorticoids, and intensive insulin therapy. ICU and hospital survival markedly improved over time (40% in 2005-2010 vs. 17% in 1997-2004, P = 0.02 and 29% in 2005-2010 vs. 6% in 1997-2004, P = 0.009, respectively). Furthermore, this survival gain in the latter period was sustained for 6 months (survival rate 24% in 2005-2010 vs. 6% in 1997-2004, P = 0.06). After adjustment with age, the liver disease stage (Child-Pugh score), and the critical illness severity score (SOFA score), ICU admission between 2005 and 2010 remained an independent favorable prognostic factor (odds ratio (OR) 0.09, 95% confidence interval (CI) 0.02-0.4, P = 0.004). The stage of the underlying liver disease was also independently associated with hospital mortality (Child-Pugh score: OR 1.42 per point, 95% CI 1.06-1.9, P = 0.018). In the light of advances in management of both cirrhosis and septic shock, survival of such patients substantially increased over recent years. The stage of the underlying liver disease and the related therapeutic options should be included in the decision-making process for ICU admission.

Changes in peroxisome proliferator-activated receptor-gamma activity in children with septic shock.

PubMed

Kaplan, Jennifer M; Denenberg, Alvin; Monaco, Marie; Nowell, Marchele; Wong, Hector; Zingarelli, Basilia

2010-01-01

To assess changes in peroxisome proliferator-activated receptor-gamma (PPARgamma) in peripheral blood mononuclear cells (PBMC) from critically ill children with sepsis. Additionally, to investigate the effects of sepsis on the endogenous activator of PPARgamma, 15-deoxy-(12,14)-PGJ(2) (15d-PGJ(2)), and the downstream targets of PPARgamma activity, adiponectin and resistin. Single-center, prospective case-control study in critically ill children with systemic inflammatory response syndrome, sepsis or septic shock. PPARgamma nuclear protein expression was decreased but PPARgamma activity was increased in PBMC from children with septic shock compared with controls. PPARgamma activity on day 1 was significantly higher in patients with higher pediatric risk of mortality (PRISM) score compared with controls [mean 0.22 optical density (OD) +/- standard error of the mean (SEM) 0.03 versus 0.12 OD +/- 0.02; p < 0.001]. Patients with resolved sepsis had increased levels of the endogenous PPARgamma ligand, 15d-PGJ(2), compared with patients with systemic inflammatory response syndrome (SIRS) and septic shock (77.7 +/- 21.7 versus 58 +/- 16.5 pg/ml; p = 0.03). Plasma high-molecular-weight adiponectin (HMWA) and resistin levels were increased in patients with septic shock on day 1 and were significantly higher in patients with higher PRISM scores. Nonsurvivors from sepsis had higher resistin levels on the first day of hospitalization compared with survivors from septic shock [660 ng/ml, interquartile range (IQR) 585-833 ng/ml versus 143 ng/ml, IQR 66-342 ng/ml; p < 0.05]. Sepsis is associated with altered PPARgamma expression and activity in PBMC. Plasma adipokines correlate with risk of mortality scores in sepsis and may be useful biomarkers. Further studies are needed to understand the mechanisms underlying changes in PPARgamma in sepsis.

4-Phenylbutyric Acid Reveals Good Beneficial Effects on Vital Organ Function via Anti-Endoplasmic Reticulum Stress in Septic Rats.

PubMed

Liu, Liangming; Wu, Huiling; Zang, JiaTao; Yang, Guangming; Zhu, Yu; Wu, Yue; Chen, Xiangyun; Lan, Dan; Li, Tao

2016-08-01

Sepsis and septic shock are the common complications in ICUs. Vital organ function disorder contributes a critical role in high mortality after severe sepsis or septic shock, in which endoplasmic reticulum stress plays an important role. Whether anti-endoplasmic reticulum stress with 4-phenylbutyric acid is beneficial to sepsis and the underlying mechanisms are not known. Laboratory investigation. State Key Laboratory of Trauma, Burns and Combined Injury. Sprague-Dawley rats. Using cecal ligation and puncture-induced septic shock rats, lipopolysaccharide-treated vascular smooth muscle cells, and cardiomyocytes, effects of 4-phenylbutyric acid on vital organ function and the relationship with endoplasmic reticulum stress and endoplasmic reticulum stress-mediated inflammation, apoptosis, and oxidative stress were observed. Conventional treatment, including fluid resuscitation, vasopressin, and antibiotic, only slightly improved the hemodynamic variable, such as mean arterial blood pressure and cardiac output, and slightly improved the vital organ function and the animal survival of septic shock rats. Supplementation of 4-phenylbutyric acid (5 mg/kg; anti-endoplasmic reticulum stress), especially administered at early stage, significantly improved the hemodynamic variables, vital organ function, such as liver, renal, and intestinal barrier function, and animal survival in septic shock rats. 4-Phenylbutyric acid application inhibited the endoplasmic reticulum stress and endoplasmic reticulum stress-related proteins, such as CCAAT/enhancer-binding protein homologous protein in vital organs, such as heart and superior mesenteric artery after severe sepsis. Further studies showed that 4-phenylbutyric acid inhibited endoplasmic reticulum stress-mediated cytokine release, apoptosis, and oxidative stress via inhibition of nuclear factor-κB, caspase-3 and caspase-9, and increasing glutathione peroxidase and superoxide dismutase expression, respectively. Anti-endoplasmic reticulum stress with 4-phenylbutyric acid is beneficial to septic shock. This beneficial effect of 4-phenylbutyric acid is closely related to the inhibition of endoplasmic reticulum stress-mediated oxidative stress, apoptosis, and cytokine release. This finding provides a potential therapeutic measure for clinical critical conditions, such as severe sepsis.

Sepsis Definitions: The Search for Gold and What CMS Got Wrong.

PubMed

Kalantari, Annahieta; Mallemat, Haney; Weingart, Scott D

2017-08-01

On October 1, 2015, the United States Centers for Medicare and Medicaid Services (CMS) issued a core measure addressing the care of septic patients. These core measures are controversial among healthcare providers. This article will address that there is no gold standard definition for sepsis, severe sepsis or septic shock and the CMS-assigned definitions for severe sepsis and septic shock are premature and inconsistent with evidence-based definitions.

Early prediction of norepinephrine dependency and refractory septic shock with a multimodal approach of vascular failure.

PubMed

Conrad, Marie; Perez, Pierre; Thivilier, Carine; Levy, Bruno

2015-08-01

The purpose of the study is to improve our ability to detect catecholamine dependency and refractory septic shock. Fifty-one patients with septic shock were studied within the first 4 hours of norepinephrine administration. Patients were divided into 2 groups according to their evolution in the intensive care unit, namely, group A, shock reversal, and group B, no shock reversal. Reversal of shock was defined as the maintenance of a systolic blood pressure greater than or equal to 90 mm Hg without vasopressor support for 24 hours or more. Vascular reactivity was tested using incremental doses of phenylephrine. Muscle tissue oxygen saturation and its changes during a vascular occlusion test were measured. Group B patients had a higher Sequential Organ Failure Assessment (SOFA) score and lactate level and more frequently received norepinephrine and renal replacement. Overall mortality was 100% in group B (16/16) and 20% (7/35) in group A. Phenylephrine increased mean arterial pressure in a dose-dependent manner more significantly in group A patients than in group B (P = .0004). Basal tissue oxygen saturation and the recovery slope after vascular occlusion test were lower in group B. In multivariate analysis, 4 parameters remained independently associated with mortality: the increase in mean arterial pressure at phenylephrine 6 μg/kg per minute, the recovery slope, SOFA score, and norepinephrine doses at H0. The intensity of septic shock-induced vascular hyporesponsiveness to vasopressor is tightly linked to septic shock severity and evolution and may potentially be identified early with simple to obtain parameters such as near-infrared spectroscopy value, SOFA score, or norepinephrine dose. Copyright © 2015 Elsevier Inc. All rights reserved.

High pentraxin 3 level predicts septic shock and bacteremia at the onset of febrile neutropenia after intensive chemotherapy of hematologic patients

PubMed Central

Vänskä, Matti; Koivula, Irma; Hämäläinen, Sari; Pulkki, Kari; Nousiainen, Tapio; Jantunen, Esa; Juutilainen, Auni

2011-01-01

We evaluated pentraxin 3 as a marker for complications of neutropenic fever in 100 hematologic patients receiving intensive chemotherapy. Pentraxin 3 and C-reactive protein were measured at fever onset and then daily to day 3. Bacteremia was observed in 19 patients and septic shock in 5 patients (three deaths). In comparison to C-reactive protein, pentraxin 3 achieved its maximum more rapidly. Pentraxin 3 correlated not only with the same day C-reactive protein but also with the next day C-reactive protein. High pentraxin 3 on day 0 was associated with the development of septic shock (P=0.009) and bacteremia (P=0.046). The non-survivors had constantly high pentraxin 3 levels. To conclude, pentraxin 3 is an early predictor of complications in hematologic patients with neutropenic fever. High level of pentraxin 3 predicts septic shock and bacteremia already at the onset of febrile neutropenia. (ClinicalTrials.gov Identifier: NCT00781040.) PMID:21880642

Leukemia inhibitory factor protects against experimental lethal Escherichia coli septic shock in mice.

PubMed Central

Waring, P M; Waring, L J; Billington, T; Metcalf, D

1995-01-01

Leukemia inhibitory factor (LIF) has recently been associated with septic shock in humans. In this study we sought to determine, in mice, the role of LIF in septic shock. During sublethal endotoxemia, serum LIF levels, as determined by radio-receptor competition assay, peaked at 2 h and were low (3 ng/ml), whereas in lethal Escherichia coli septic shock serum LIF levels rose progressively (> 30 ng/ml) in the premorbid phase coincident with the development of tissue injury. Single i.v. injections of high doses (up to 50 micrograms per mouse) of recombinant murine LIF had no obvious acute detrimental effects, whereas continued i.p. administration (30 micrograms per mouse per day) for 3-4 days induced a fatal catabolic state without evidence of preceding hemodynamic collapse or shock. Simultaneous or subsequent administration of high doses of LIF had no effect on mortality from sublethal and lethal E. coli septic shock, whereas prior administration conferred significant protection against lethality (P << 0.001 by log-rank test), an effect that was dose and interval dependent. This protective effect resembled endotoxin tolerance and was characterized by suppression of E. coli-induced serum tumor necrosis factor concentration (P < 0.05), reduction in the number of viable bacteria (P < 0.05), and prevention of sepsis-induced tissue injury. These observations suggest that systemic LIF production is part of the host response to both endotoxin and sepsis-induced tissue injury. Images Fig. 2 Fig. 5 PMID:7877978

Reversible increase in maximal cortisol secretion rate in septic shock.

PubMed

Dorin, Richard I; Qualls, Clifford R; Torpy, David J; Schrader, Ronald M; Urban, Frank K

2015-03-01

Cortisol clearance is reduced in sepsis and may contribute to the development of impaired adrenocortical function that is thought to contribute to the pathophysiology of critical illness-related corticosteroid insufficiency. We sought to assess adrenocortical function using computer-assisted numerical modeling methodology to characterize and compare maximal cortisol secretion rate and free cortisol half-life in septic shock, sepsis, and healthy control subjects. Post hoc analysis of previously published total cortisol, free cortisol, corticosteroid-binding globulin, and albumin concentration data. Single academic medical center. Subjects included septic shock (n = 45), sepsis (n = 25), and healthy controls (n = 10). I.v. cosyntropin (250 μg). Solutions for maximal cortisol secretion rate and free cortisol half-life were obtained by least squares solution of simultaneous, nonlinear differential equations that account for free cortisol appearance and elimination as well as reversible binding to corticosteroid-binding globulin and albumin. Maximal cortisol secretion rate was significantly greater in septic shock (0.83 nM/s [0.44, 1.58 nM/s] reported as median [lower quartile, upper quartile]) compared with sepsis (0.51 nM/s [0.36, 0.62 nM/s]; p = 0.007) and controls (0.49 nM/s [0.42, 0.62 nM/s]; p = 0.04). The variance of maximal cortisol secretion rate in septic shock was also greater than that of sepsis or control groups (F test, p < 0.001). Free cortisol half-life was significantly increased in septic shock (4.6 min [2.2, 6.3 min]) and sepsis (3.0 min [2.3, 4.8 min] when compared with controls (2.0 min [1.2, 2.6 min]) (both p < 0.004). Results obtained by numerical modeling are consistent with comparable measures obtained by the gold standard stable isotope dilution method. Septic shock is associated with generally not only higher levels but also greater variance of maximal cortisol secretion rate when compared with control and sepsis groups. Additional studies would be needed to determine whether assessment of cortisol kinetic parameters such as maximal cortisol secretion rate and free cortisol half-life is useful in the diagnosis or management of critical illness-related corticosteroid insufficiency.

The apelinergic system as an alternative to catecholamines in low-output septic shock.

PubMed

Coquerel, David; Sainsily, Xavier; Dumont, Lauralyne; Sarret, Philippe; Marsault, Éric; Auger-Messier, Mannix; Lesur, Olivier

2018-01-19

Catecholamines, in concert with fluid resuscitation, have long been recommended in the management of septic shock. However, not all patients respond positively and controversy surrounding the efficacy-to-safety profile of catecholamines has emerged, trending toward decatecholaminization. Contextually, it is time to re-examine the "maintaining blood pressure" paradigm by identifying safer and life-saving alternatives. We put in perspective the emerging and growing knowledge on a promising alternative avenue: the apelinergic system. This target exhibits invaluable pleiotropic properties, including inodilator activity, cardio-renal protection, and control of fluid homeostasis. Taken together, its effects are expected to be greatly beneficial for patients in septic shock.

Diabetes insipidus after discontinuation of vasopressin infusion for septic shock.

PubMed

Rana, H; Ferguson, N; Dicpinigaitis, P V

2018-04-01

Despite widespread use of vasopressin for the treatment of septic shock, few cases of diabetes insipidus (DI) following its discontinuation have been reported. A 54-year-old man presented with pneumonia progressing to septic shock, requiring norepinephrine and vasopressin for refractory hypotension. After clinical improvement, the patient on 3 separate occasions developed polyuria and severe hypernatremia upon discontinuation of vasopressin, with prompt recovery upon its resumption. Occurrence of DI upon discontinuation of vasopressin infusion appears to be rare, but incidence may be underestimated due to a paucity of published reports. Actual incidence and underlying mechanism of this phenomenon remain to be elucidated. © 2017 John Wiley & Sons Ltd.

Effects of arm elevation on radial artery pressure: a new method to distinguish hypovolemic shock and septic shock from hypotension.

PubMed

Xie, Zhiyi; Zhang, Zhenyu; Xu, Yuan; Zhou, Hua; Wu, Sheng; Wang, Zhong

2018-06-01

In this prospective observational study, we investigated the variability in radial artery invasive blood pressure associated with arm elevation in patients with different hemodynamic types. We carried out a prospective observational study using data from 73 general anesthesia hepatobiliary postoperative adult patients admitted to an ICU over a 1-year period. A standard procedure was used for the arm elevation test. The value of invasive radial arterial pressure was recorded at baseline, and 30 and 60 s after the arm had been raised from 0° to 90°. We compared the blood pressure before versus after arm elevation, and between hemodynamically stable, hypovolemic shock, and septic shock patient groups. In all 73 patients, systolic arterial pressure (SAP) decreased, diastolic arterial pressure (DAP) increased, and pulse pressure (PP) decreased at 30 and 60 s after arm elevation (P<0.01), but the mean arterial pressure (MAP) was unchanged (P>0.05). On comparing 30 and 60 s, there was no significant difference in SAP, DAP, PP, or MAP (P>0.05). In 40 hemodynamically stable patients, SAP and PP decreased, and DAP and MAP increased significantly at 30 and 60 s after arm elevation compared with baseline (P<0.01). In 16 hypovolemic patients, SAP, DAP, and MAP increased significantly compared with baseline at 30 and 60 s (P<0.01), but PP was unchanged (P>0.05). In 17 patients with septic shock, SAP, PP, and MAP decreased significantly versus baseline at 30 and 60 s (P<0.01), but DAP was unchanged (P>0.05). Comparison of the absolute value of pressure change of septic shock patients at 30 s after raising the arm showed that SAP, DAP, and MAP changes were significantly lower compared with those in hypovolemic shock and hemodynamically stable patients (P<0.01). The areas under the receiver operator characteristic curve for predicting septic shock was 0.930 [95% confidence interval (CI): 0.867-0.992, P< 0.001] for change value at 30 s after arm elevation of SAP. The best cut-off point for the SAP change value was -5 mmHg or less, with a sensitivity of 94.12%, a specificity of 80.36%, a positive likelihood ratio of 4.79 (95% CI: 2.8-8.2), and a negative likelihood ratio of 0.073 (95% CI: 0.01-0.5). Our study shows that hypovolemic shock and septic shock patients have significantly different radial artery invasive blood pressure changes in an arm elevation test, which could be applied as a new method to distinguish hypovolemic shock and septic shock from hypotension.

Variation in the use of renal replacement therapy in patients with septic shock: a substudy of the prospective multicenter observational FINNAKI study

PubMed Central

2014-01-01

Introduction Indications for renal replacement therapy (RRT) have not been generally standardized and vary among intensive care units (ICUs). We aimed to assess the proportion, indications, and modality of RRT, as well as the association between the proportion of RRT use and 90-day mortality in patients with septic shock in Finnish adult ICUs. Methods We identified patients with septic shock from the prospective observational multicenter FINNAKI study conducted between 1 September 2011 and 1 February 2012. We divided the ICUs into high-RRT and low-RRT ICUs according to the median of the proportion of RRT-treated patients with septic shock. Differences in indications, and modality of RRT between ICU groups were assessed. Finally, we performed an adjusted logistic regression analysis to evaluate the possible association of the ICU group (high vs. low-RRT) with 90-day mortality. Results Of the 726 patients with septic shock, 131 (18.0%, 95% CI 15.2 to 20.9%) were treated with RRT. The proportion of RRT-treated patients varied from 3% up to 36% (median 19%) among ICUs. High-RRT ICUs included nine ICUs (354 patients) and low-RRT ICUs eight ICUs (372 patients). In the high-RRT ICUs patients with septic shock were older (P = 0.04), had more cardiovascular (P <0.001) and renal failures (P = 0.003) on the first day in the ICU, were more often mechanically ventilated, and received higher maximum doses of norepinephrine (0.25 μg/kg/min vs. 0.18 μg/kg/min, P <0.001) than in the low-RRT ICUs. No significant differences in indications for or modality of RRT existed between the ICU groups. The crude 90-day mortality rate for patients with septic shock was 36.2% (95% CI 31.1 to 41.3%) in the high-RRT ICUs compared to 33.9% (95% CI 29.0 to 38.8%) in the low-RRT ICUs, P = 0.5. In an adjusted logistic regression analysis the ICU group (high-RRT or low-RRT ICUs) was not associated with 90-day mortality. Conclusions Patients with septic shock in ICUs with a high proportion of RRT had more severe organ dysfunctions and received more organ-supportive treatments. Importantly, the ICU group (high-RRT or low-RRT group) was not associated with 90-day mortality. PMID:24499547

Increased DNA damage and increased apoptosis and necrosis in patients with severe sepsis and septic shock.

PubMed

Bahar, Ilhan; Elay, Gülseren; Başkol, Gulden; Sungur, Murat; Donmez-Altuntas, Hamiyet

2018-02-01

Reactive oxygen species (ROS) has a key role in the pathogenesis of sepsis. We wanted to evaluate ROS-associated lymphocyte necrosis and apoptosis. A total of 51 patients were included in the study, 29 in the patient group and 22 in the control group. Blood samples were taken from patients in the patient group during severe sepsis or septic shock, then again once they had recovered. Oxidative DNA damage was evaluated by 8-hydroxy-2'-deoxyguanosine (8-OHdG) levels. Peripheral blood lymphocytes from patients were evaluated with a microscope immediately. The rate of apoptosis and necrosis of lymphocytes were evaluated according to the number of cells in the peripheral. The level of 8-OHdG increased with severe sepsis or septic shock. There were significant differences between the pre- and post-treatment values for apoptotic cell frequency (4.21±3.15 vs. 3.82±3.07, P<0.05) and necrotic cell frequency (4.75±3.61 vs. 4.09±3.37, P<0.05). Apoptosis and necrosis was increased during severe sepsis and septic shock, and apoptosis increase also continued after recovery, but necrosis decreased following disease recovery. CONCLUSıONS: In patients with severe sepsis or septic shock, apoptosis and necrosis were increased along with increased 8-OHdG level. Copyright © 2017 Elsevier Inc. All rights reserved.

Early detection strategy and mortality reduction in severe sepsis.

PubMed

Westphal, Glauco Adrieno; Feijó, Janaína; Andrade, Patrícia Silva de; Trindade, Louise; Suchard, Cezar; Monteiro, Márcio Andrei Gil; Martins, Sheila Fonseca; Nunes, Fernanda; Caldeira Filho, Milton

2009-06-01

To evaluate the impact of implementing an institutional policy for detection of severe sepsis and septic shock. Study before (stage I), after (stage II) with prospective data collection in a 195 bed public hospital.. Stage I: Patients with severe sepsis or septic shock were included consecutively over 15 months and treated according to the Surviving Sepsis Campaign guidelines. Stage II: In the 10 subsequent months, patients with severe sepsis or septic shock were enrolled based on an active search for signs suggesting infection (SSI) in hospitalized patients. The two stages were compared for demographic variables, time needed for recognition of at least two signs suggesting infection (SSI-Δt), compliance to the bundles of 6 and 24 hours and mortality. We identified 124 patients with severe sepsis or septic shock, 68 in stage I and 56 in stage II. The demographic variables were similar in both stages. The Δt-SSI was 34 ± 54 hours in stage I and 7 ± 8.4 hours in stage II (p <0.001). There was no difference in compliance to the bundles. In parallel there was significant reduction of mortality rates at 28 days (54.4% versus 30%, p <0.02) and hospital (67.6% versus 41%, p <0.003). The strategy used helped to identify early risk of sepsis and resulted in decreased mortality associated with severe sepsis and septic shock.

Mean arterial pressure target in patients with septic shock.

PubMed

Beloncle, Francois; Radermacher, Peter; Guerin, Claude; Asfar, Pierre

2016-07-01

In patients with septic shock, a mean arterial pressure higher than 65 mmHg is recommended by the Surviving Sepsis Campaign Guidelines. However, a precise mean arterial pressure target has not been delineated. The aim of this paper was to review the physiological rationale and clinical evidence for increasing mean arterial pressure in septic shock. A mean arterial pressure level lower than renal autoregulatory threshold may lead to renal dysfunction. However, adjusting macrocirculation objectives in particular after the early phase of septic shock may not correct established microcirculation impairments. Moreover, sympathetic over-stimulation due to high doses of vasopressor (needed to achieve high mean arterial pressure targets) may be associated with numerous harmful effects. Observational and small short term interventional studies did not provide a definitive answer to this question but suggested that a high mean arterial pressure (around 75-85 mmHg) may prevent acute kidney injury in some patients. The SEPSISPAM Trial, a large prospective, randomized, controlled study, compared the targets of High (i.e. 80 to 85 mm Hg) versus Low (i.e. 65 to 70 mm Hg) mean arterial pressure in patients with septic shock. The mortality was not different in the two groups. However in patients with chronic hypertension, there were significantly less renal failure in the high mean arterial pressure group than the low mean arterial pressure group.

Basic and advanced echocardiographic evaluation of myocardial dysfunction in sepsis and septic shock.

PubMed

Vallabhajosyula, S; Pruthi, S; Shah, S; Wiley, B M; Mankad, S V; Jentzer, J C

2018-01-01

Sepsis continues to be a leading cause of mortality and morbidity in the intensive care unit. Cardiovascular dysfunction in sepsis is associated with worse short- and long-term outcomes. Sepsis-related myocardial dysfunction is noted in 20%-65% of these patients and manifests as isolated or combined left or right ventricular systolic or diastolic dysfunction. Echocardiography is the most commonly used modality for the diagnosis of sepsis-related myocardial dysfunction. With the increasing use of ultrasonography in the intensive care unit, there is a renewed interest in sepsis-related myocardial dysfunction. This review summarises the current scope of literature focused on sepsis-related myocardial dysfunction and highlights the use of basic and advanced echocardiographic techniques for the diagnosis of sepsis-related myocardial dysfunction and the management of sepsis and septic shock.

Early Immune Function and Duration of Organ Dysfunction in Critically Ill Septic Children.

PubMed

Muszynski, Jennifer A; Nofziger, Ryan; Moore-Clingenpeel, Melissa; Greathouse, Kristin; Anglim, Larissa; Steele, Lisa; Hensley, Josey; Hanson-Huber, Lisa; Nateri, Jyotsna; Ramilo, Octavio; Hall, Mark W

2018-02-22

Late immune suppression is associated with nosocomial infection and mortality in septic adults and children. Relationships between early immune suppression and outcomes in septic children remain unclear. Prospective observational study to test the hypothesis that early innate and adaptive immune suppression are associated with longer duration of organ dysfunction in children with severe sepsis/septic shock. Methods, Measurements and Main Results: Children aged < 18 years meeting consensus criteria for severe sepsis or septic shock were sampled within 48 hours of sepsis onset. Healthy controls were sampled once. Innate immune function was quantified by whole blood ex vivo lipopolysaccharide-induced TNFα production capacity. Adaptive immune function was quantified by ex vivo phytohemagglutinin-induced IFNγ production capacity. 102 septic children and 35 healthy children were enrolled. Compared to healthy children, septic children demonstrated lower LPS-induced TNFα production (p < 0.0001) and lower PHA-induced IFNγ production (p<0.0001). Among septic children, early innate and adaptive immune suppression were associated with greater number of days with multiple organ dysfunction (MODS) and greater number of days with any organ dysfunction. On multivariable analyses, early innate immune suppression remained independently associated with increased MODS days [aRR 1.2 (1.03, 1.5)] and organ dysfunction days [aRR 1.2 (1.1, 1.3)]. Critically ill children with severe sepsis or septic shock demonstrate early innate and adaptive immune suppression. Early suppression of both innate and adaptive immunity are associated with longer duration of organ dysfunction and may be useful markers to guide investigations of immunomodulatory therapies in septic children.

Genetic variation in heat shock protein 70 is associated with septic shock: narrowing the association to a specific haplotype.

PubMed

Kee, C; Cheong, K Y; Pham, K; Waterer, G W; Temple, S E L

2008-12-01

Heat shock protein 70 (HSP70) plays a major role in immune responses. Polymorphisms within the gene have been associated with development of septic shock. This study refines the region of the HSP70 gene associated with development of septic shock and confirms its functionality. Subjects (n = 31) were grouped into one of three haplotypes based on their HSPA1B-179C>T and HSPA1B1267A>G genotypes. Mononuclear cells from these subjects were stimulated with heat-killed bacteria (10(7 )colony-forming units/mL Escherichia coli or Streptococcus pneumoniae) for 8 and 21 h. HSP70 and tumour necrosis factor (TNF) mRNA and protein levels were measured by reverse transcriptase-polymerase chain reaction and ELISA, respectively. The HSPA1B-179*C:1267*A haplotype was associated with significantly lower levels of HSPA1B mRNA and protein and higher production of TNF mRNA and protein compared to the other haplotypes. Induction of HSP70 was TNF independent. These results suggest that the HSPA1B-179C>T:1267A>G haplotype is functional and may explain the association of the HSP70 gene with development of septic shock.

Reduced oxygen utilization in septic shock: disorder or adaptation?

PubMed

Steiner, Alexandre A

2015-01-01

A fall in oxygen utilization during septic or endotoxic shock is thought to reflect circulatory hypoxia or mitochondrial dysfunction, but these pathology-oriented hypotheses do not explain all clinical observations. Here we discuss an alternative hypothesis of how oxygen utilization could fall as the result of a physiological thermometabolic adaptation.

Tension pneumocephalus mimicking septic shock: a case report.

PubMed

Miranda, Caroline; Mahta, Ali; Wheeler, Lee Adam; Tsiouris, A John; Kamel, Hooman

2018-02-01

Tension pneumocephalus can lead to rapid neurologic deterioration. We report for the first time its association with aseptic systemic inflammatory response syndrome mimicking septic shock and the efficacy of prompt neurosurgical intervention and critical care support in treating this condition. A 64-year-old man underwent 2-stage olfactory groove meningioma resection. The patient developed altered mental status and gait instability on postoperative day 6. Imaging showed significant pneumocephalus. The patient subsequently developed worsening mental status, respiratory failure, and profound shock requiring multiple vasopressors. Bedside needle decompression, identification and repair of the cranial fossa defect, and critical care support led to improved mental status and reversal of shock and multiorgan dysfunction. Thorough evaluation revealed no evidence of an underlying infection. In this case, tension pneumocephalus incited an aseptic systemic inflammatory response syndrome mimicking septic shock. Prompt neurosurgical correction of pneumocephalus and critical care support not only improved neurologic status, but also reversed shock. Such a complication indicates the importance of close monitoring of patients with progressive pneumocephalus.

Correlation of Blood Gas Parameters with Central Venous Pressure in Patients with Septic Shock; a Pilot Study

PubMed Central

Baratloo, Alireza; Rahmati, Farhad; Rouhipour, Alaleh; Motamedi, Maryam; Gheytanchi, Elmira; Amini, Fariba; Safari, Saeed

2014-01-01

Objective: To determine the correlation between blood gas parameters and central venous pressure (CVP) in patients suffering from septic shock. Methods: Forty adult patients with diagnosis of septic shock who were admitted to the emergency department (ED) of Shohadaye Tajrish Hospital affiliated with Shahid Beheshti University of Medical Sciences, and met inclusion and exclusion criteria were enrolled. For all patients, sampling was done for venous blood gas analysis, serum sodium and chlorine levels. At the time of sampling; blood pressure, pulse rate and CVP were recorded. Correlation between blood gas parameters and hemodynamic indices were. Results: A significant direct correlation between CVP with anion gap (AG) and inversely with base deficit (BD) and bicarbonate. CVP also showed a relative correlation with pH, whereas it was not correlated with BD/ AG ratio and serum chlorine level. There was no significant association between CVP and clinical parameters including shock index (SI) and mean arterial pressure (MAP). Conclusion: It seems that some of non invasive blood gas parameters could be served as alternative to invasive measures such as CVP in treatment planning of patients referred to an ED with septic shock. PMID:27162870

Diagnostic and prognostic value of presepsin in the management of sepsis in the emergency department: a multicenter prospective study.

PubMed

Ulla, Marco; Pizzolato, Elisa; Lucchiari, Manuela; Loiacono, Maria; Soardo, Flavia; Forno, Daniela; Morello, Fulvio; Lupia, Enrico; Moiraghi, Corrado; Mengozzi, Giulio; Battista, Stefania

2013-07-30

Sepsis, severe sepsis and septic shock are common conditions with high mortality. Their early diagnosis in the Emergency Department (ED) is one of the keys to improving survival. Procalcitonin (PCT) has been used as a biomarker in septic patients but has limited specificity and can be elevated in other scenarios of systemic inflammatory response syndrome (SIRS). Soluble CD14 (sCD14) or presepsin is the free fragment of a glycoprotein expressed on monocytes and macrophages. Preliminary reports suggest that levels of presepsin are significantly higher in septic patients than in healthy individuals. The aim of this study is to investigate the diagnostic and prognostic value of presepsin compared to PCT in people presenting at the ED with SIRS and suspected sepsis or septic shock. This study was conducted in two major hospitals in Turin, Italy. One hundred six patients presenting to the EDs with suspected sepsis or septic shock were included, and another eighty-three patients affected by SIRS, but with no clinical evidence of infection, were recruited as controls. Blood samples were collected at first medical evaluation and for some patients after 24 and 72 h. The samples were analyzed using the PATHFAST Presepsin assay for sCD14, and commercial kits were used for other determinations (for example, PCT). Definitive diagnosis and survival rates were obtained afterward by analysis of digital medical records. Elevated concentrations of presepsin at presentation were observed in septic patients compared to control patients. The same trend was observed for mean values of PCT. Higher values of presepsin were observed in septic patients at presentation (time 0). The diagnostic accuracy of PCT was generally higher, and areas under the curve (AUCs) were 0.875 for PCT and 0.701 for presepsin. Mean presepsin values were significantly higher in nonsurvivor septic patients (60-day mortality) than in survivors. No significant correlation was noted between PCT and survival. In our experience, presepsin was useful in the early diagnosis of infection in a complex population of patients with SIRS, sepsis, severe sepsis and septic shock who presented to the ED. Presepsin showed a significant prognostic value, and initial values were significantly correlated with in-hospital mortality of patients affected by sepsis, severe sepsis or septic shock.

Diagnostic and prognostic value of presepsin in the management of sepsis in the emergency department: a multicenter prospective study

PubMed Central

2013-01-01

Introduction Sepsis, severe sepsis and septic shock are common conditions with high mortality. Their early diagnosis in the Emergency Department (ED) is one of the keys to improving survival. Procalcitonin (PCT) has been used as a biomarker in septic patients but has limited specificity and can be elevated in other scenarios of systemic inflammatory response syndrome (SIRS). Soluble CD14 (sCD14) or presepsin is the free fragment of a glycoprotein expressed on monocytes and macrophages. Preliminary reports suggest that levels of presepsin are significantly higher in septic patients than in healthy individuals. The aim of this study is to investigate the diagnostic and prognostic value of presepsin compared to PCT in people presenting at the ED with SIRS and suspected sepsis or septic shock. Methods This study was conducted in two major hospitals in Turin, Italy. One hundred six patients presenting to the EDs with suspected sepsis or septic shock were included, and another eighty-three patients affected by SIRS, but with no clinical evidence of infection, were recruited as controls. Blood samples were collected at first medical evaluation and for some patients after 24 and 72 h. The samples were analyzed using the PATHFAST Presepsin assay for sCD14, and commercial kits were used for other determinations (for example, PCT). Definitive diagnosis and survival rates were obtained afterward by analysis of digital medical records. Results Elevated concentrations of presepsin at presentation were observed in septic patients compared to control patients. The same trend was observed for mean values of PCT. Higher values of presepsin were observed in septic patients at presentation (time 0). The diagnostic accuracy of PCT was generally higher, and areas under the curve (AUCs) were 0.875 for PCT and 0.701 for presepsin. Mean presepsin values were significantly higher in nonsurvivor septic patients (60-day mortality) than in survivors. No significant correlation was noted between PCT and survival. Conclusions In our experience, presepsin was useful in the early diagnosis of infection in a complex population of patients with SIRS, sepsis, severe sepsis and septic shock who presented to the ED. Presepsin showed a significant prognostic value, and initial values were significantly correlated with in-hospital mortality of patients affected by sepsis, severe sepsis or septic shock. PMID:23899120

Cost effectiveness analysis of an initial ICU admission as compared to a delayed ICU admission in patients with severe sepsis or in septic shock.

PubMed

Champunot, Ratapum; Thawitsri, Thammasak; Kamsawang, Nataya; Sirichote, Visanu; Nopmaneejumruslers, Cherdchai

2014-01-01

To assess the cost effectiveness of an initial ICU admissionforpatients with severe sepsis or those in septic shock following the initial resuscitation in the emergency department. Mortality data was generated through retrospective data obtained from 1,048 adult patients with severe sepsis or in septic shock from one tertiary care and eight community hospitals in Phitsanulok during the period of October 2010 to September 2011. These patients were categorized into two groups; as either admitted from the emergency department directly to the ICU (stated as an immediate ICU admission) or admitted from the emergency department to the general hospital ward due to an unavailability of lCU beds (stated as a delayed ICU admission). The overall direct costs and characteristics were simulated from a second group of 994 adult patients, admitted a year later from selected data by the ICD-10 codes [International Classification of Diseases, 10th edition] with the same conditions of severe sepsis and septic shock (September 2011 through September 2012), as there was no collection of costs and characteristics during the first period (October 2010 through September 2011). A decision tree model and an incremental cost-effectiveness ratio (ICER) were used for the analyses of the cost-effectiveness. There were no significant differences in either the mean ages or lengths of stay between both groups. All-cause mortality rates have shown an incidence of 22.2% for the immediate ICU admission group and an incidence of 46.3% in the delayed ICUadmission group (odds ratio for the immediate ICU admission group was 0. 479 with a 95% confidence interval, 0.376-0.611). Total costs (mean, 95% CI) of the immediate ICUadmission group [37,194 baht (32,389-44,926)] were higher than had been seen in the delayed ICU admission group [26,275 (24,300-27,936)]. Incremental cost was 10,919 baht. ICER for the immediate ICU admission group was 45,307 baht per life saved. Immediate ICU admission for patients with severe sepsis or in septic shock following the initial resuscitation in the emergency department has shown a satisfactory cost-effectiveness profile in low-to-middle income countries.

Comparison of Hydroxocobalamin Versus Norepinephrine Versus Saline in a Swine Model of Servere Septic Shock

DTIC Science & Technology

2016-05-20

approval.) Cobalamin as a treatment for battle associated severe sepsis -induced shock in swine (Sus Scrofa) 6. TITLE OF MATERIAL TO BE PUBLISHED OR...Comparison of hydroxocbalamin versus norepinephrine versus saline in a swine model of severe septic shock. Background: Sepsis is associated with a mortality...HSP 70) have been suggested to be biomarkers of severe sepsis and may be useful indicators of treatment success. Hydroxocobalamin {HOC), which

Cystatin C as an early marker of acute kidney injury in septic shock.

PubMed

Ortuño-Andériz, F; Cabello-Clotet, N; Vidart-Simón, N; Postigo-Hernández, C; Domingo-Marín, S; Sánchez-García, M

2015-03-01

To describe the utility of determining plasma cystatinC concentrations in the diagnosis of acute incident kidney injury in septic shock. Prospective series of 50 patients with septic shock and plasma creatinine levels <2mg/dL hospitalized in an intensive care unit. Clinical and laboratory follow-ups were conducted, with measurements of cystatinC, urea and plasma creatinine levels from the diagnosis of septic shock to 5days later. The severity of the septic shock was assessed with the RIFLE scale. Twenty patients (40%) developed acute kidney injury: 8 (16%) were categorized as RIFLE-R, 5 (10%) as RIFLE-I and 7 (14%) as RIFLE-F. All patients categorized as RIFLE-F required extracorporeal renal clearance. Eighteen (36%) patients died, 8 (20%) of whom had developed acute kidney injury in their evolution. There was poor correlation between plasma creatinine and cystatin C levels (r=.501; P=.001), which disappeared upon reaching any degree of renal impairment on the RIFLE scale. CystatinC levels increased earlier and were better able to identify patients who would develop serious renal function impairment (RIFLE-F) than creatinine and urea levels. The initial cystatinC levels were related to mortality at 30days (OR=1.16; 95%CI: 03-.85). For patients who developed acute septic kidney injury, the plasma cystatinC levels increased before the classical markers of renal function. CystatinC also constitutes a severity biomarker that correlates with progression to RIFLE-F, the need for extrarenal clearance and, ultimately, mortality. This precocity could be useful for starting measures that prevent the progression of renal dysfunction. Copyright © 2014 Elsevier España, S.L.U. All rights reserved.

Cardiac Troponin Is a Predictor of Septic Shock Mortality in Cancer Patients in an Emergency Department: A Retrospective Cohort Study.

PubMed

Yang, Zhi; Qdaisat, Aiham; Hu, Zhihuang; Wagar, Elizabeth A; Reyes-Gibby, Cielito; Meng, Qing H; Yeung, Sai-Ching J

2016-01-01

Septic shock may be associated with myocardial damage; however, the prognostic value of cardiac enzymes in cancer patients with septic shock is unknown. In this study, we evaluated the prognostic significance of cardiac enzymes in combination with established prognostic factors in predicting the 7-day mortality rate of patients with septic shock, and we constructed a new scoring system, Septic Oncologic Patients in Emergency Department (SOPED), which includes cardiac enzymes, to predict 7-day mortality rates. We performed a retrospective cohort study of 375 adult cancer patients with septic shock who visited the emergency department of a comprehensive cancer center between 01/01/2004 and 12/31/2013. The 7-day and 28-day mortality rates were 19.7% and 37.6%, respectively. The creatine kinase myocardial band fraction and troponin-I were significantly higher in patients who died in ≤7 days and ≤28 days than in those who did not. In Cox regression models, troponin-I >0.05 ng/mL plus Predisposition, Infection, Response, and Organ Failure (PIRO2011) or Mortality in Emergency Department Sepsis (MEDS) score was a significant predictor of survival for ≤7 days. With our new SOPED scoring system, the receiver operating characteristic area under the curve was 0.836, higher than those for PIRO2011 and MEDS. Troponin-I >0.05 ng/mL was an important predictor of short-term mortality (≤7 days). The SOPED scoring system, which incorporated troponin-I, was more prognostically accurate than were other scores for 7-day mortality. Large multicenter studies are needed to verify our results and prospectively validate the prognostic performance of the SOPED score.

Effect of hypothermia on splenic leukocyte modulation and survival duration in severely septic rats.

PubMed

Willis, Rhett N; Charles, Eric J; Guidry, Christopher A; Chordia, Mahendra D; Davies, Stephen W; Yang, Zequan; Sawyer, Robert G

2017-07-01

Therapeutic hypothermia (HT) in severe septic shock is associated with prolonged survival. We hypothesized that moderate HT would prolong survival and modulate the inflammatory response in rats with septic shock by exerting its therapeutic effect on splenic leukocytes. Severe septic shock was created in rats by cecal ligation and incision (CLI). One hour after CLI or laparotomy, rats were randomized to sham, normothermia (NT), or 4 h of HT followed by 2 h of rewarming. HT (31 ± 1°C) was induced using a cooling blanket and monitored via a rectal temperature probe. Survival duration was 2.78 ± 1.0 h in NT rats and 8.33 ± 0.32 h in HT rats (n = 8/group, P < 0.0001). In separate groups, 3 h after CLI, the spleen weight was significantly smaller in NT rats (769 ± 100 mg) than in HT rats (947 ± 157 mg, P = 0.04). Fluorescent immunostaining of formyl peptide receptors on leukocytes in spleen tissue showed considerably higher formyl peptide receptor expression in HT rats than in NT rats. Significantly elevated proinflammatory cytokines and myeloperoxidase enzyme in plasma were found in NT rats compared with HT rats. Anti-inflammatory cytokine, interleukin-10, was significantly higher in HT rats. Both proinflammatory cytokines and plasma myeloperoxidase were significantly reduced in splenectomized NT rats. Moderate hypothermic therapy significantly prolongs the survival duration of rats with severe septic shock. HT dampens the inflammatory response during septic shock by modulating the spleen to an anti-inflammatory mode and preventing the spleen from releasing activated splenic leukocytes into the blood. Copyright © 2017 Elsevier Inc. All rights reserved.

Angiotensin II in Refractory Septic Shock.

PubMed

Antonucci, Elio; Gleeson, Patrick J; Annoni, Filippo; Agosta, Sara; Orlando, Sergio; Taccone, Fabio Silvio; Velissaris, Dimitrios; Scolletta, Sabino

2017-05-01

Refractory septic shock is defined as persistently low mean arterial blood pressure despite volume resuscitation and titrated vasopressors/inotropes in patients with a proven or suspected infection and concomitant organ dysfunction. Its management typically requires high doses of catecholamines, which can induce significant adverse effects such as ischemia and arrhythmias. Angiotensin II (Ang II), a key product of the renin-angiotensin-aldosterone system, is a vasopressor agent that could be used in conjunction with other vasopressors to stabilize critically ill patients during refractory septic shock, and reduce catecholamine requirements. However, very few clinical data are available to support Ang II administration in this setting. Here, we review the current literature on this topic to better understand the role of Ang II administration during refractory septic shock, differentiating experimental from clinical studies. We also consider the potential role of exogenous Ang II administration in specific organ dysfunction and possible pitfalls with Ang II in sepsis. Various issues remain unresolved and future studies should investigate important topics such as: the optimal dose and timing of Ang II administration, a comparison between Ang II and the other vasopressors (epinephrine; vasopressin), and Ang II effects on microcirculation.

Genome-wide expression profiling in pediatric septic shock

PubMed Central

Wong, Hector R.

2013-01-01

For nearly a decade, our research group has had the privilege of developing and mining a multi-center, microarray-based, genome-wide expression database of critically ill children (≤ 10 years of age) with septic shock. Using bioinformatic and systems biology approaches, the expression data generated through this discovery-oriented, exploratory approach have been leveraged for a variety of objectives, which will be reviewed. Fundamental observations include wide spread repression of gene programs corresponding to the adaptive immune system, and biologically significant differential patterns of gene expression across developmental age groups. The data have also identified gene expression-based subclasses of pediatric septic shock having clinically relevant phenotypic differences. The data have also been leveraged for the discovery of novel therapeutic targets, and for the discovery and development of novel stratification and diagnostic biomarkers. Almost a decade of genome-wide expression profiling in pediatric septic shock is now demonstrating tangible results. The studies have progressed from an initial discovery-oriented and exploratory phase, to a new phase where the data are being translated and applied to address several areas of clinical need. PMID:23329198

Role of circulating soluble chemokines in septic shock.

PubMed

de Pablo, R; Monserrat, J; Prieto, A; Alvarez-Mon, M

2013-11-01

Chemokines are a large superfamily of small proteins that function not only in leukocyte trafficking, but are also necessary for linkage between innate and adaptive immunity. Little is known about their role in septic shock. We hypothesized that serum levels of the most important chemokines are related to organ failure, disease severity and outcome. A prospective observational study was carried out. Surgical-clinical Intensive Care Unit. Ninety-two patients diagnosed with septic shock using international criteria. Forty patients were excluded due to acquired immunity disturbances. Samples from 36 healthy controls were also analyzed. None. In 46% of the patients who suffered acute respiratory distress syndrome (ARDS), IL-8 levels were higher than in patients without ARDS (499.9±194.1 vs. 190.8±91.7 pg/ml; P=.039). This molecule was also higher in 36% of the patients with sepsis-induced acute renal failure (ARF) (453.3±181.6 vs. 201.3±95.9 pg/ml; P=.049). Coagulopathy was found in 19% of the septic shock patients with elevated serum IL-8 levels (635.8±292.3 vs. 218.7±87.0 pg/ml; P=.010), elevated MIP-1α (91.4±27.3 vs. 58.8±11.1 pg/ml; P=.044), and low circulating RANTES levels (8162.2±6321.0 vs. 18781.8±11.1 pg/ml; P=.027). No significant differences were found between survivors and non-survivors at any time of follow-up. Upon admission to the ICU, IL-8 is a reliable biomarker of sepsis-induced AFR, ARDS and coagulopathy. Altered circulating MIP-1α and RANTES levels are also found in patients with septic shock and coagulopathy. However, chemokines do not appear to be good biomarkers of mortality in septic shock. Copyright © 2012 Elsevier España, S.L. and SEMICYUC. All rights reserved.

Prognostic value of brachioradialis muscle oxygen saturation index and vascular occlusion test in septic shock patients.

PubMed

Marín-Corral, J; Claverias, L; Bodí, M; Pascual, S; Dubin, A; Gea, J; Rodriguez, A

2016-05-01

To compare rSO2 (muscle oxygen saturation index) static and dynamic variables obtained by NIRS (Near Infrared Spectroscopy) in brachioradialis muscle of septic shock patients and its prognostic implications. Prospective and observational study. Intensive care unit. Septic shock patients and healthy volunteers. The probe of a NIRS device (INVOS 5100) was placed on the brachioradialis muscle during a vascular occlusion test (VOT). Baseline, minimum and maximum rSO2 values, deoxygenation rate (DeOx), reoxygenation slope (ReOx) and delta value. Septic shock patients (n=35) had lower baseline rSO2 (63.8±12.2 vs. 69.3±3.3%, p<0.05), slower DeOx (-0.54±0.31 vs. -0.91±0.35%/s, p=0.001), slower ReOx (2.67±2.17 vs. 9.46±3.5%/s, p<0.001) and lower delta (3.25±5.71 vs. 15.1±3.9%, p<0.001) when compared to healthy subjects (n=20). Among septic shock patients, non-survivors showed lower baseline rSO2 (57.0±9.6 vs. 69.8±11.3%, p=0.001), lower minimum rSO2 (36.0±12.8 vs. 51.3±14.8%, p<0.01) and lower maximum rSO2 values (60.6±10.6 vs. 73.3±11.2%, p<0.01). Baseline rSO2 was a good mortality predictor (AUC 0.79; 95%CI: 0.63-0.94, p<0.01). Dynamic parameters obtained with VOT did not improve the results. Septic shock patients present an important alteration of microcirculation that can be evaluated by NIRS with prognostic implications. Monitoring microvascular reactivity in the brachioradialis muscle using VOT with our device does not seem to improve the prognostic value of baseline rSO2. Copyright © 2015 Elsevier España, S.L.U. and SEMICYUC. All rights reserved.

n-Butanol extract from Folium isatidis inhibits lipopolysaccharide-induced inflammatory cytokine production in macrophages and protects mice against lipopolysaccharide-induced endotoxic shock

PubMed Central

Jiang, Lili; Lu, Yili; Jin, Jiahui; Dong, Lili; Xu, Fengli; Chen, Shuangshuang; Wang, Zhanyue; Liang, Guang; Shan, Xiaoou

2015-01-01

Sepsis, which is caused by severe infection, is an important cause of mortality, but effective clinical treatment against sepsis is extremely limited. As the main component of the outer membrane of Gram-negative bacteria, lipopolysaccharide (LPS) plays a major role in inflammatory responses. Studies have shown beneficial pharmacological effects for Folium isatidis. The present study further illuminated the effects of n-butanol extract from Folium isatidis in LPS-induced septic shock and identified the main active chemical components. Our study showed that pretreatment with n-butanol extract from Folium isatidis not only significantly inhibited LPS-induced tumor necrosis factor-α and interleukin-6 production but also markedly and dose dependently enhanced the recruitment of MyD88, the phosphorylation of extracellular signal-regulated kinase, and the degradation of IκB-α. Additionally, the extract exhibited dramatic protective effects against lung injury and death in mice with septic shock. Eight main active compounds were identified, including organic acids, glycoside, indolinones, and flavonoids. These findings provide a perspective on the respiratory protection offered by n-butanol extract from Folium isatidis in LPS-induced sepsis and outline a novel therapeutic strategy for the treatment of sepsis. PMID:26491261

Anti-inflammatory effect of a Nuphar lutea partially purified leaf extract in murine models of septic shock.

PubMed

Ozer, J; Levi, T; Golan-Goldhirsh, A; Gopas, J

2015-02-23

Various plant organs of Nuphar lutea (L.) SM. (Nymphaeaceae) are used in traditional medicine for the treatment of arthritis, fever, aches, pains and inflammation. The main purpose of this study was to determine the anti-inflammatory effect of Nuphar lutea leaf extract (NUP) in two septic shock models: (1) Survival of mice challenged with a lethal dose of LPS, determination of pro-inflammatory and anti-inflammatory cytokines in serum, as well as in peritoneal macrophages in cell culture. (2) The effect of NUP in a murine model of fecal-induced peritonitis. NUP pre-treatment partially protected mice in two models of acute septic shock. We concluded that NUP is anti-inflammatory by inhibiting the NF-κB pathway, modulating cytokine production and ERK phosphorylation. A significant average survival rate (60%) of LPS lethally-challenged mice was achieved by pre-treatment with NUP. In addition, NUP pre-treatment reduced nuclear NF-κB translocation in peritoneal macrophages. The production of pro-inflammatory cytokines, TNF-α, IL-6 and IL-12, in the sera of LPS-treated mice or in the supernatants of peritoneal macrophages stimulated with LPS for 2-6 h was also decreased by NUP. Pre-treatment with NUP caused a significant increase in the anti-inflammatory cytokine IL-10. The NUP pre-treatment reduced and delayed mortality in mice with fecal-induced peritonitis. Our studies also revealed that NUP pre-treatment induced a dose-dependent phosphorylation of ERK in peritoneal macrophages. Since most of the reports about the anti-inflammatory effect of Nuphar lutea refer to rhizome and root powder and extracts, it is important to clarify the effectiveness of leaf extract as a source for such activity. NUP pre-treatment partially protected mice in two models of acute septic shock. We concluded that NUP is anti-inflammatory by inhibiting the NF-κB pathway, modulating cytokine production and ERK phosphorylation. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Efficacy of polymyxin B-immobilized fiber hemoperfusion for patients with septic shock caused by Gram-negative bacillus infection.

PubMed

Saito, Nobuyuki; Sugiyama, Kazuhiro; Ohnuma, Testu; Kanemura, Takashi; Nasu, Michitaka; Yoshidomi, Yuya; Tsujimoto, Yuta; Adachi, Hiroshi; Koami, Hiroyuki; Tochiki, Aito; Hori, Kota; Wagatsuma, Yukiko; Matsumoto, Hisashi

2017-01-01

Septic shock-associated mortality in intensive care units (ICUs) remains high, with reported rates ranging 30-50%. In particular, Gram-negative bacilli (GNB), which induce significant inflammation and consequent multiple organ failure, are the etiological bacterial agent in 40% of severe sepsis cases. Hemoperfusion using polymyxin B-immobilized fiber (PMX), which adsorbs endotoxin, is expected to reduce the inflammatory sepsis cascade due to GNB. However, the clinical efficacy of this treatment has not yet been demonstrated. Here, we aimed to verify the efficacy of endotoxin adsorption therapy using PMX through a retrospective analysis of 413 patients who received broad spectrum antimicrobial treatment for GNB-related septic shock between January 2009 and December 2012 in 11 ICUs of Japanese tertiary hospitals. After aligning the patients' treatment time phases, we classified patients in two groups depending on whether PMX hemoperfusion (PMXHP) therapy was administered or not within 24 hours after ICU admission (PMXHP group: n = 134, conventional group: n = 279). The primary study endpoint was the mortality rate at 28 days after ICU admission. The mean age was 72.4 (standard deviation: 12.6) years, and the mean Sequential Organ Failure Assessment score at ICU admission was 9.9 (3.4). The infection sites included intra-abdominal (38.0%), pulmonary (18.9%), and urinary tract (32.2%), and two thirds of all patients had GNB-related bacteremia. Notably, the mortality at 28 days after ICU admission did not differ between the groups (PMXHP: 29.1% vs. conventional: 29.0%, P = 0.98), and PMXHP therapy was not found to improve this outcome in a Cox regression analysis (hazard ratio = 1.16; 95% confidence interval, 0.81-1.64, P = 0.407). We conclude that PMX-based endotoxin adsorption within 24 hours from ICU admission was not associated with mortality among patients with septic shock due to GNB. University Hospital Medical Information Network Clinical Trial Registry (UMIN-CTR ID: UMIN000012748).

Cardiovascular response to dobutamine stress predicts outcome in severe sepsis and septic shock.

PubMed

Kumar, Anand; Schupp, Elizabeth; Bunnell, Eugene; Ali, Amjad; Milcarek, Barry; Parrillo, Joseph E

2008-01-01

During septic shock, resistance to the haemodynamic effects of catecholamine vasopressors and inotropes is a well-recognised marker of mortality risk. However, the specific cardiovascular or metabolic response elements that are most closely associated with outcome have not been well defined. The objective of this study was to assess cardiovascular and metabolic responses to dobutamine as correlates of outcome in patients with severe sepsis or septic shock. A prospective, non-randomised, non-blinded interventional study of graded dobutamine challenge (0, 5, 10, and 15 mug/kg/min) in adult patients who had undergone pulmonary artery catheterisation within 48 hours of onset of severe sepsis or septic shock (8 survivors/15 non-survivors) was performed. Radionuclide cineangiography during graded infusion was used to determine biventricular ejection fractions at each increment of dobutamine. In univariate analysis, a variety of cardiovascular or haemodynamic and oxygen transport or metabolic variables (at the point of maximum cardiac index response for a given subject) were associated with survival including: increased stroke volume index (p = 0.0003); right ventricular end-diastolic volume index (p = 0.0047); left ventricular stroke work index (p = 0.0054); oxygen delivery index (p = 0.0084); cardiac index (p = 0.0093); systolic blood pressure/left ventricular end-systolic volume index ratio (p = 0.0188); left ventricular ejection fraction (p = 0.0160); venous oxygen content (p = 0.0208); mixed venous oxygen saturation (p = 0.0234); pulse pressure (p = 0.0403); decreased pulmonary artery diastolic pressure (p = 0.0133); systemic vascular resistance index (p = 0.0154); extraction ratio (p = 0.0160); and pulmonary vascular resistance index (p = 0.0390). Increases of stroke volume index of greater than or less than 8.5 mL/m2 were concordant with survival or death in 21 of 23 cases. Multivariate profile construction showed stroke volume index as the dominant discriminating variable for survival with the systolic blood pressure/left ventricular end-systolic volume index ratio alone among all other variables significantly improving the model. Survivors maintain cardiac responsiveness to catecholamine stimulation during septic shock. Survival from severe sepsis or septic shock is associated with increased cardiac performance and contractility indices during dobutamine infusion. Further studies are required to determine whether these parameters are predictive of outcome in a larger severe sepsis/septic shock population.

Antimicrobial resistance patterns, clinical features, and risk factors for septic shock and death of nosocomial E coli bacteremia in adult patients with hematological disease: A monocenter retrospective study in China.

PubMed

Ma, Jie; Li, Ning; Liu, Yajie; Wang, Chong; Liu, Xiaoyan; Chen, Shengmei; Xie, Xinsheng; Gan, Silin; Wang, Meng; Cao, Weijie; Wang, Fang; Liu, Yanfan; Wan, Dingming; Sun, Ling; Sun, Hui

2017-05-01

The aim of this retrospective analysis was to evaluate the antimicrobial resistance, clinical features, and risk factors for septic shock and death of nosocomial E coli bacteremia in adult patients in a single hematological center in China. A retrospective case-control study of 157 adult hematological patients with 168 episodes of E coli bacteremia was initiated from April 2012 to July 2015. Antimicrobial susceptibility as well as antimicrobial co-resistance rates were analyzed. Clinical features and outcomes were also studied. In addition, risk factors for septic shock and death were investigated. Among the 553 positive blood isolates during the study period, the prevalence of E coli was 33.3% and ESBL production strains represented 61.9% of those examined. In all the E coli strains isolated, 85.6% were multidrug-resistance (MDR), 2.4% were extensive drug resistance (XDR), and 6.0% were resistant to carbapenems. More MDR phenotype was noted in ESBL-EC strains (98.6% vs 62.8%, P<.001) and isolates from neutropenic patients (98.6% vs 62.8%, P < .001). In the antimicrobial susceptibility test, carbapenems and amikacin exhibited not only higher in vitro activity against E coli (94.0% and 92.0%, respectively), but lower co-resistance rates to other antibiotics. Carbapenem resistant strains retained full sensitivity to tigecycline and 60% to amikacin. Piperacillin/tazobatam was the third sensitive drug to both ESBL-EC (77.1%) and non-ESBL-EC (86.0%). In our series, 81.6% episodes received appropriate initial antibiotic treatment and no significant decrease in it was found in bacteremia due to ESBL E coli and patients with neutropenia, septic shock. Septic shock was noted in 15.5% patients and the overall 30-day mortality rate was 21.7%. Multivariate analysis revealed that induction chemotherapy (OR 2.126; 95% CI 1.624-11.332; P = .003) and polymicrobial infection (OR 3.628; 95% CI 1.065-21.219; P = .041) were risk factors for septic shock, whereas male (OR 2.223; 95% CI 1.132-12.022; P < .01) and septic shock (OR 52.359; 95% CI 19.951-292.690; P = .030) were risk factors for death.In the hematology department, ESBL-producing and MDR are widely prevalent in E coli bacteremia which is still a major life-threatening problem, especially for patients with septic shock. For empirical antimicrobial therapy, combination based on aminoglycoside, especially amikacin, will be helpful to increase the antimicrobial coverage against ESBL-EC while combining tigecycline with aminoglycoside should be considered for seriously carbapenem-resistant infectious patients.

Sepsis in Obstetrics: Clinical Features and Early Warning Tools.

PubMed

Parfitt, Sheryl E; Bogat, Mary L; Hering, Sandra L; Ottley, Charlotte; Roth, Cheryl

Morbidity and mortality associated with sepsis has gained widespread attention on a local, state, and national level, yet, it remains a complicated disorder that can be difficult to identify in a timely manner. Sepsis in obstetric patients further complicates the diagnosis as alterations in physiology related to pregnancy can mask sepsis indicators normally seen in the general population. If early signs of sepsis go unrecognized, septic shock can develop, leading to organ dysfunction and potential death. Maternal early warning tools have been designed to assist clinicians in recognizing early indications of illness. Through use of clinical pathway-specific tools, disease processes may be detected early, subsequently benefitting patients with aggressive treatment management and intervention.This article is the second in a series of three that discuss the importance of sepsis and septic shock in pregnancy. Risk factors, causes of sepsis, signs and symptoms, and maternal early warning tools are discussed.

Septicemia from Lactobacillus rhamnosus GG, from a Probiotic Enriched Yogurt, in a Patient with Autologous Stem Cell Transplantation.

PubMed

Koyama, Satoshi; Fujita, Hiroyuki; Shimosato, Takeshi; Kamijo, Aki; Ishiyama, Yasufumi; Yamamoto, Eri; Ishii, Yoshimi; Hattori, Yukako; Hagihara, Maki; Yamazaki, Etsuko; Tomita, Naoto; Nakajima, Hideaki

2018-02-17

Probiotic-rich foods are consumed without much restriction. We report here, a case of septic shock caused by yogurt derived Lactobacillus species in a 54-year-old male patient with acute promyelocytic leukemia, in second complete remission, and who was an autologous stem cell transplantation recipient. He received high dose chemotherapy and autologous peripheral blood stem cell transplantation. He ingested commercially available probiotic-enriched yogurt because of severe diarrhea. One week later, he developed septic shock, and the pathogen was determined by strain-specific PCR analysis as Lactobacillus rhamnosus GG (ATCC 53103), which was found to be identical with the strain in the yogurt he consumed. Thus, because even low virulent Lactobacilli in the probiotic products can be pathogenic in the compromised hosts, ingestion of such products should be considered with caution in neutropenic patients with severe diarrhea, such as stem cell transplantation recipients.

From amino acids polymers, antimicrobial peptides, and histones, to their possible role in the pathogenesis of septic shock: a historical perspective

PubMed Central

Ginsburg, Isaac; van Heerden, Peter Vernon; Koren, Erez

2017-01-01

This paper describes the evolution of our understanding of the biological role played by synthetic and natural antimicrobial cationic peptides and by the highly basic nuclear histones as modulators of infection, postinfectious sequelae, trauma, and coagulation phenomena. The authors discuss the effects of the synthetic polymers of basic poly α amino acids, poly l-lysine, and poly l-arginine on blood coagulation, fibrinolysis, bacterial killing, and blood vessels; the properties of natural and synthetic antimicrobial cationic peptides as potential replacements or adjuncts to antibiotics; polycations as opsonizing agents promoting endocytosis/phagocytosis; polycations and muramidases as activators of autolytic wall enzymes in bacteria, causing bacteriolysis and tissue damage; and polycations and nuclear histones as potential virulence factors and as markers of sepsis, septic shock, disseminated intravasclar coagulopathy, acute lung injury, pancreatitis, trauma, and other additional clinical disorders PMID:28203100

Docosahexaenoic acid, but not eicosapentaenoic acid, improves septic shock-induced arterial dysfunction in rats

PubMed Central

Clere-Jehl, Raphaël; Le Borgne, Pierrick; Merdji, Hamid; Auger, Cyril; Schini-Kerth, Valérie; Meziani, Ferhat

2017-01-01

Introduction Long chain n-3 fatty acid supplementation may modulate septic shock-induced host response to pathogen-induced sepsis. The composition of lipid emulsions for parenteral nutrition however remains a real challenge in intensive care, depending on their fatty acid content. Because they have not been assessed yet, we aimed at determining the respective effects of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) during septic shock-induced vascular dysfunction. Methods In a peritonitis-induced septic shock model, rats were infused with EPA, DHA, an EPA/DHA mixture or 5% dextrose (D5) during 22 hours. From H18, rats were resuscitated and monitored during 4 hours. At H22, plasma, aorta and mesenteric resistance arteries were collected to perform ex vivo experiments. Results We have shown that septic rats needed an active resuscitation with fluid challenge and norepinephrine treatment, while SHAM rats did not. In septic rats, norepinephrine requirements were significantly decreased in DHA and EPA/DHA groups (10.6±12.0 and 3.7±8.0 μg/kg/min respectively versus 17.4±19.3 μg/kg/min in D5 group, p<0.05) and DHA infusion significantly improved contractile response to phenylephrine through nitric oxide pathway inhibition. DHA moreover significantly reduced vascular oxidative stress and nitric oxide production, phosphorylated IκB expression and vasodilative prostaglandin production. DHA also significantly decreased polyunsaturated fatty acid pro-inflammatory mediators and significantly increased several anti-inflammatory metabolites. Conclusions DHA infusion in septic rats improved hemodynamic dysfunction through decreased vascular oxidative stress and inflammation, while EPA infusion did not have beneficial effects. PMID:29261735

Rapid changes in the serum total protein and globulin levels in complications caused by facultatively pathogenic Gram-negative bacteria.

PubMed

Petrás, G; Kiss, S; Juraszek, J; Merétey, K

1978-01-01

The changes in the levels of total protein and four globulin fractions were followed up throughout the entire course of complications caused by Gram-negative facultative pathogens in 37 acute cases of respiratory insufficiency accompanying different underlying illnesses and in 9 chronic, bedridden patients given artificial ventilation. At the onset of the infectious complications, in the first place in septic shock, the levels of various globulin fractions showed a decrease corresponding to a half-life of 2 to 4 days. Neither the increased catabolism, nor the protein losses by the urine and tracheal secretions offer a sufficient explanation for the escape of globulins of this extent from the plasma. It seems that this is a consequence of the increase in capillary permeability due to the effect of antigen-antibody reactions and that of endotoxin. As a result, in the critical phase of the infectious complications, at the point of culmination, e.g. in septic shock, diminished amount of different globulins is transported to the site of utilization, that is, to the inflammatory area.

An Innovative Approach for The Integration of Proteomics and Metabolomics Data In Severe Septic Shock Patients Stratified for Mortality.

PubMed

Cambiaghi, Alice; Díaz, Ramón; Martinez, Julia Bauzá; Odena, Antonia; Brunelli, Laura; Caironi, Pietro; Masson, Serge; Baselli, Giuseppe; Ristagno, Giuseppe; Gattinoni, Luciano; de Oliveira, Eliandre; Pastorelli, Roberta; Ferrario, Manuela

2018-04-27

In this work, we examined plasma metabolome, proteome and clinical features in patients with severe septic shock enrolled in the multicenter ALBIOS study. The objective was to identify changes in the levels of metabolites involved in septic shock progression and to integrate this information with the variation occurring in proteins and clinical data. Mass spectrometry-based targeted metabolomics and untargeted proteomics allowed us to quantify absolute metabolites concentration and relative proteins abundance. We computed the ratio D7/D1 to take into account their variation from day 1 (D1) to day 7 (D7) after shock diagnosis. Patients were divided into two groups according to 28-day mortality. Three different elastic net logistic regression models were built: one on metabolites only, one on metabolites and proteins and one to integrate metabolomics and proteomics data with clinical parameters. Linear discriminant analysis and Partial least squares Discriminant Analysis were also implemented. All the obtained models correctly classified the observations in the testing set. By looking at the variable importance (VIP) and the selected features, the integration of metabolomics with proteomics data showed the importance of circulating lipids and coagulation cascade in septic shock progression, thus capturing a further layer of biological information complementary to metabolomics information.

Effects of Increasing Hydrocortisone to 300 mg Per Day in the Treatment of Septic Shock: a Pilot Study.

PubMed

Hyvernat, Hervé; Barel, Rémy; Gentilhomme, Anne; Césari-Giordani, Jean François; Freche, Annie; Kaidomar, Michel; Goubaux, Bernard; Pradier, Christian; Dellamonica, Jean; Bernardin, Gilles

2016-11-01

The Surviving Sepsis Campaign guidelines recommend hydrocortisone in septic shock only when fluid resuscitation and vasopressors fail to restore hemodynamic stability. Hydrocortisone administration modalities are supported only by low-grade recommendations. Our main objective here was to determine differences in 28-day mortality between two low-dose hydrocortisone regimens for the treatment of septic shock. We performed a multicenter, prospective, randomized, double-blind, pilot study in four adult medical intensive care units. Patients presenting septic shock were rapidly administered one of two regimens of hydrocortisone, either a 50-mg intravenous bolus every 6 h during 7 days (200-mg group; n = 59) or a 100-mg initial bolus followed by a continuous infusion of 300 mg daily for 5 days (300-mg group; n = 63). Hydrocortisone was stopped abruptly at the end of treatment. There were no significant differences between the 200-mg and 300-mg groups as concerns 28-day mortality (respectively 52.5% vs. 44.4% [RR 0.84, 95% CI, 0.58-1.22, P = 0.47]), refractory shock incidence or delay from shock to vasopressor cessation. There were also no differences in adverse events between the groups. Shock relapse after hydrocortisone cessation was independent of hydrocortisone regimens, but it was associated with the persistence of infection and the use of etomidate. The resumption of hydrocortisone due to shock relapse was significantly more frequent in the 300-mg group. We found no differences in mortality or adverse events between the two hydrocortisone administration regimens. Shock relapse was significantly associated with the persistence of infection and the use of etomidate.

The effects of aspirin, flurbiprofen, and NO-donating acetylsalicylic acid (NCX 4016) on mice models of endotoxic and septic shock.

PubMed

Ulu, Nadir; Iskit, Alper Bektaş; Sökmensüer, Cenk; Güç, Mustafa Oğuz

2015-01-01

Nitric oxide-donating nonsteroidal antiinflammatory drugs (NO-NSAIDs) are a promising new class of antiinflammatory agents, which are obtained by adding NO-donating moieties to the existing conventional NSAID molecules. The aim of this study was to investigate the effects of aspirin, flurbiprofen, and NO-donating acetylsalicylic acid (NCX 4016) on cecal ligation and puncture (CLP) and endotoxin-induced septic shock (LPS) models in mice. Overall survival and spleen and liver weights were monitored in LPS and CLP models. Histopathological examinations of liver and spleen were performed at the end of the experimental protocols. NCX 4016 was able to reverse the increased spleen weight in CLP-operated animals, whereas aspirin or flurbiprofen did not. Similar to the results of the CLP model, none of the drugs modified the survival rates in the LPS model. Flurbiprofen in particular produced significant histopathological damage in spleens and livers, which was less significant with aspirin. NCX 4016 did not cause any liver damage. NCX 4016 has the potential to be used in septic states, while special attention has to be paid to the effects of aspirin and flurbiprofen on the liver and spleen.

The Noninvasive Carbon Dioxide Gradient (NICO2G) during Hemorrhagic Shock

DTIC Science & Technology

2014-07-01

as well as a tPCO2- PaCO2 gap more than 16 mmHg were reported to be associated with poor outcomes in patients with septic shock (18). Previously, our...shortcomings, which include the need for frequent calibration with a tank of standardized cali- bration gas (24), relative bulk, need for a heated sensor, and...hemorrhagic, septic , and cardiogenic shock (27). Van der Linden et al. (28) demonstrated a venous-arterial gradient for PCO2 in hemorrhaged dogs. There was

A Case Report and Literature Review of Scrub Typhus With Acute Abdomen and Septic Shock in a Child-The Role of Leukocytoclastic Vasculitis and Granulysin.

PubMed

Chang, Po-Hsiung; Cheng, Yu-Pin; Chang, Po-Sheng; Lo, Chiao-Wei; Lin, Lung-Huang; Lu, Chin-Fang; Chung, Wen-Hung

2018-04-24

Scrub typhus is becoming a clinically important cause of acute undifferentiated febrile illness in Taiwan. The incubation period is between 6 and 21 days after exposure. It is transmitted by chiggers (larva of trombiculid mite) in long grasses and in dirt-floor homes, with infection characterized by a flu-like illness of fever, headache, and myalgia lasting approximately 1 week. It has various systemic manifestations, including GI symptoms. In some, the illness progresses to multiorgan dysfunction syndrome and death. We report on a 13-year-old boy who lived in Taipei City and who had initially tentative diagnosis of acute pyrexia of unknown origin with high fever up to 40.3°C for 1 week, but later had thrombocytopenia and diffuse abdominal pain with peritoneal sign suspected acute appendicitis. During the clinical course, septic shock and disseminated intravascular coagulopathy (DIC) were noted. There were skin rash in his trunk and extremities and an eschar with black crust surrounded by a scaling erythematous rim on his right buttock. In addition, we got the information of his travel history in Green Island and Orchid Island for 10 days.With the correct antibiotics, vancomycin, meropenem, and doxycycline, the patient was getting better and corresponding with high level of granulysin and tumor necrosis factor-alpha. The diagnosis of scrub typhus was confirmed by the biopsy of eschar and high quantitative real-time polymerase chain reaction values of Orientia tsutsugamushi (16sRNA and 56 kDa) tested by Centers for Disease Control and Prevention, Taiwan. Histopathological findings of the eschar revealed the leukocytoclastic vasculitis, crust and thrombus formation with many gram-negative microorganisms, O. tsutsugamushi demonstrated by 47 kDa monoclonal antibody immunohistochemical stain and electromicroscopy. After the careful selection of appropriate antibiotics including meropenem, vancomycin, and doxycycline, he recovered and was subsequently discharged 7 days after admission. This case highlights that scrub typhus infection can mimic acute abdomen and septic shock with DIC. This rare presentation of acute abdomen and septic shock with thrombocytopenia and DIC caused by scrub typhus should remind physicians to be alert to the possibility of acute abdomen and febrile illness resulting from scrub typhus.

Triiodothyronine Administration in a Model of Septic Shock: A Randomized Blinded Placebo-Controlled Trial.

PubMed

Maiden, Matthew J; Chapman, Marianne J; Torpy, David J; Kuchel, Timothy R; Clarke, Iain J; Nash, Coralie H; Fraser, Jonathan D; Ludbrook, Guy L

2016-06-01

Triiodothyronine concentration in plasma decreases during septic shock and may contribute to multiple organ dysfunction. We sought to determine the safety and efficacy of administering triiodothyronine, with and without hydrocortisone, in a model of septic shock. Randomized blinded placebo-controlled trial. Preclinical research laboratory. Thirty-two sheep rendered septic with IV Escherichia coli and receiving protocol-guided sedation, ventilation, IV fluids, and norepinephrine infusion. Two hours following induction of sepsis, 32 sheep received a 24-hour IV infusion of 1) placebo + placebo, 2) triiodothyronine + placebo, 3) hydrocortisone + placebo, or 4) triiodothyronine + hydrocortisone. Primary outcome was the total amount of norepinephrine required to maintain a target mean arterial pressure; secondary outcomes included hemodynamic and metabolic indices. Plasma triiodothyronine levels increased to supraphysiological concentrations with hormonal therapy. Following 24 hours of study drug infusion, the amount of norepinephrine required was no different between the study groups (mean ± SD μg/kg; placebo + placebo group 208 ± 392; triiodothyronine + placebo group 501 ± 370; hydrocortisone + placebo group 167 ± 286; triiodothyronine + hydrocortisone group 466 ± 495; p = 0.20). There was no significant treatment effect on any hemodynamic variable, metabolic parameter, or measure of organ function. A 24-hour infusion of triiodothyronine, with or without hydrocortisone, in an ovine model of septic shock did not markedly alter norepinephrine requirement or any other physiological parameter.

Systolic blood pressure variability in patients with early severe sepsis or septic shock: a prospective cohort study.

PubMed

Tang, Yi; Sorenson, Jeff; Lanspa, Michael; Grissom, Colin K; Mathews, V J; Brown, Samuel M

2017-06-17

Severe sepsis and septic shock are often lethal syndromes, in which the autonomic nervous system may fail to maintain adequate blood pressure. Heart rate variability has been associated with outcomes in sepsis. Whether systolic blood pressure (SBP) variability is associated with clinical outcomes in septic patients is unknown. The propose of this study is to determine whether variability in SBP correlates with vasopressor independence and mortality among septic patients. We prospectively studied patients with severe sepsis or septic shock, admitted to an intensive care unit (ICU) with an arterial catheter. We analyzed SBP variability on the first 5-min window immediately following ICU admission. We performed principal component analysis of multidimensional complexity, and used the first principal component (PC 1 ) as input for Firth logistic regression, controlling for mean systolic pressure (SBP) in the primary analyses, and Acute Physiology and Chronic Health Evaluation (APACHE) II score or NEE dose in the ancillary analyses. Prespecified outcomes were vasopressor independence at 24 h (primary), and 28-day mortality (secondary). We studied 51 patients, 51% of whom achieved vasopressor independence at 24 h. Ten percent died at 28 days. PC 1 represented 26% of the variance in complexity measures. PC 1 was not associated with vasopressor independence on Firth logistic regression (OR 1.04; 95% CI: 0.93-1.16; p = 0.54), but was associated with 28-day mortality (OR 1.16, 95% CI: 1.01-1.35, p = 0.040). Early SBP variability appears to be associated with 28-day mortality in patients with severe sepsis and septic shock.

Triggering Receptor Expressed on Myeloid Cells-1 Signaling: Protective and Pathogenic Roles on Streptococcal Toxic-Shock-Like Syndrome Caused by Streptococcus suis.

PubMed

Han, Li; Fu, Lei; Peng, Yongbo; Zhang, Anding

2018-01-01

Streptococcus suis infections can cause septic shock, which is referred to as streptococcal toxic-shock-like syndrome (STSLS). The disease is characterized by a severe inflammatory response, multiple organ failure, and high mortality. However, no superantigen that is responsible for toxic shock syndrome was detected in S. suis , indicating that the mechanism underlying STSLS is different and remains to be elucidated. Triggering receptor expressed on myeloid cells-1 (TREM-1), belonging to the Ig superfamily, is an activating receptor expressed on myeloid cells, and has been recognized as a critical immunomodulator in several inflammatory diseases of both infectious and non-infectious etiologies. In this review, we discuss the current understanding of the immunoregulatory functions of TREM-1 on acute infectious diseases and then highlight the crucial roles of TREM-1 on the development of STSLS.

Vascular ATP-sensitive potassium channels are over-expressed and partially regulated by nitric oxide in experimental septic shock.

PubMed

Collin, Solène; Sennoun, Nacira; Dron, Anne-Gaëlle; de la Bourdonnaye, Mathilde; Montemont, Chantal; Asfar, Pierre; Lacolley, Patrick; Meziani, Ferhat; Levy, Bruno

2011-05-01

To study the activation and expression of vascular (aorta and small mesenteric arteries) potassium channels during septic shock with or without modulation of the NO pathway. Septic shock was induced in rats by peritonitis. Selective inhibitors of vascular K(ATP) (PNU-37883A) or BK(Ca) [iberiotoxin (IbTX)] channels were used to demonstrate their involvement in vascular hyporeactivity. Vascular response to phenylephrine was measured on aorta and small mesenteric arteries mounted on a wire myograph. Vascular expression of potassium channels was studied by PCR and Western blot, in the presence or absence of 1400W, an inducible NO synthase (iNOS) inhibitor. Aortic activation of the transcriptional factor nuclear factor-kappaB (NF-κB) was assessed by electrophoretic mobility shift assay. Arterial pressure as well as in vivo and ex vivo vascular reactivity were reduced by sepsis and improved by PNU-37883A but not by IbTX. Sepsis was associated with an up-regulation of mRNA and protein expression of vascular K(ATP) channels, while expression of vascular BK(Ca) channels remained unchanged. Selective iNOS inhibition blunted the sepsis-induced increase in aortic NO, decreased NF-κB activation, and down-regulated vascular K(ATP) channel expression. Vascular K(ATP) but not BK(Ca) channels are activated, over-expressed, and partially regulated by NO via NF-κB activation during septic shock. Their selective inhibition restores arterial pressure and vascular reactivity and decreases lactate concentration. The present data suggest that selective vascular K(ATP) channel inhibitors offer potential therapeutic perspectives for septic shock.

A multiplex cytokine score for the prediction of disease severity in pediatric hematology/oncology patients with septic shock.

PubMed

Xu, Xiao-Jun; Tang, Yong-Min; Song, Hua; Yang, Shi-Long; Xu, Wei-Qun; Shi, Shu-Wen; Zhao, Ning; Liao, Chan

2013-11-01

Although many inflammatory cytokines are prognostic in sepsis, the utility of cytokines in evaluating disease severity in pediatric hematology/oncology patients with septic shock was rarely studied. On the other hand, a single particular cytokine is far from ideal in guiding therapeutic intervention, but combination of multiple biomarkers improves the accuracy. In this prospective observational study, 111 episodes of septic shock in pediatric hematology/oncology patients were enrolled from 2006 through 2012. Blood samples were taken for inflammatory cytokine measurement by cytometric bead array (CBA) technology at the initial onset of septic shock. Interleukin (IL)-6 and IL-10 were significantly elevated in majority of patients, while tumor necrosis factor (TNF)-α and interferon (IFN)-γ were markedly increased in patients with high pediatric index of mortality 2 (PIM2) score and non-survivors. All the four cytokines paralleled the PIM2 score and differentially correlated with hemodynamic disorder and fatal outcomes. The pediatric multiplex cytokine score (PMCS), which integrated the four cytokines into one score system, was related to hemodynamic disorder and mortality as well, but showed more powerful prediction ability than each of the four cytokines. PMCS was an independent predictive factor for fatal outcome, presenting similar discriminative power with PIM2, with accuracy of 0.83 (95% CI, 0.71-0.94). In conclusion, this study develops a cytokine scoring system based on CBA technique, which performs well in disease severity and fatality prediction in pediatric hematology/oncology patients with septic shock. Copyright © 2013 Elsevier Ltd. All rights reserved.

Response to the high-dose corticotrophin stimulation test depends on plasma adrenocotropin hormone levels in septic shock.

PubMed

Llompart-Pou, Juan Antonio; Raurich, Joan Maria; Ayestarán, Ignacio; Fernández-de-Castillo, Ana G; Pérez-Bárcena, Jon; Ibáñez, Jordi

2012-06-01

The use of the high-dose corticotrophin stimulation test (HDCST) as a guide to use low-dose steroid therapy in septic shock is controversial. The adrenocotropin hormone (ACTH) constitutes the immediate stimuli to produce cortisol. We evaluated the correlation of the response to the HDCST with plasma ACTH levels in patients with septic shock. This is a retrospective review of 102 patients with septic shock in which adrenal function was evaluated using the HDCST and plasma ACTH levels were measured. Patients with a δ cortisol of 9 μg/dL or less were considered as nonresponders or with subnormal response. The association between plasma ACTH levels and the response to the HDCST was investigated. Sixty-four patients (62.7%) had a subnormal response. Plasma ACTH levels were higher in patients with subnormal response (19.8 [11.7-31.4] vs 10.0 [7.0-21.2] pg/mL; P = .002). Patients in the highest quartile of plasma ACTH had lower δ cortisol (P = .014) and higher percentage of subnormal response (P = .005). The optimal cutoff point of plasma ACTH level with fewest false classifications was 10 pg/mL (sensitivity, 0.83 [95% confidence interval, 074-0.90] and specificity, 0.50 [95% confidence interval, 0.74-0.90]). Patients with septic shock with higher plasma ACTH values presented a subnormal response to the HDCST. The number of patients who failed to the HDCST was higher as plasma ACTH increased. Copyright © 2012 Elsevier Inc. All rights reserved.

Intravenous administration of hypertonic sodium chloride solution with dextran or isotonic sodium chloride solution for treatment of septic shock secondary to pyometra in dogs.

PubMed

Fantoni, D T; Auler Junior, J O; Futema, F; Cortopassi, S R; Migliati, E R; Faustino, M; de Oliveira, C M

1999-11-01

To determine effects of i.v. administration of hypertonic saline (7.5% NaCl) solution with 6% dextran 70 (HSSD) or isotonic saline (0.9% NaCl) solution (ISS) to dogs with septic shock secondary to pyometra. Prospective, randomized, clinical study. 14 client-owned dogs with septic shock secondary to pyometra. Prior to emergency ovariohysterectomy, catheters were placed in pulmonary and femoral arteries of each dog to evaluate hemodynamic and oxygenation status. Immediately prior to surgery, 7 dogs received HSSD (4 ml/kg [1.82 ml/lb] of body weight, i.v.) and 7 dogs received ISS (32 ml/kg [14.54 ml/lb], i.v.) during a 5-minute period. Measurements of hemodynamic and oxygenation variables were obtained before and 5 and 20 minutes after administration of fluids. Mean arterial pressure (MAP) increased significantly 5 and 20 minutes after administration of HSSD, whereas ISS did not affect MAP. However, cardiac output, cardiac index, and oxygen delivery increased and hematocrit decreased after both treatments. Oxygen consumption and extraction rate and degree of acidosis did not improve after either treatment. Intravenous administration of small volumes of HSSD to dogs with septic shock secondary to pyometra resulted in improvement of hemodynamic and oxygenation status. Although cardiac output, cardiac index, and oxygen delivery improved after administration of a volume of ISS equal to 8 times that of HSSD, MAP increased to > 80 mm Hg only after treatment with HSSD. Administration of HSSD may be an effective treatment for septic shock in dogs.

Continuation of Statin Therapy and Vasopressor Use in Septic Shock.

PubMed

Zechmeister, Carrie; Hurren, Jeff; McNorton, Kelly

2015-07-01

Studies have evaluated the use of statins in sepsis; however, no human studies have explored their effect on vasopressor requirements in septic shock. The primary objective was to determine the effect of prehospital statin continuation on duration of vasopressor therapy in patients with septic shock. Secondary objectives included maximum and average vasopressor dose and in-hospital mortality. This was a retrospective, institutional board-approved, observational cohort study in a community teaching hospital; 119 adult intensive care unit (ICU) patients with an ICD-9 code for septic shock and prehospital statin therapy were evaluated. Multivariate analyses were performed to address confounders. Of the 1229 patients screened, 119 (10%) met inclusion criteria; 73 patients (61%) had a statin continued within 24 hours of ICU admission. Crude analysis demonstrated no difference in vasopressor duration in the statin versus no statin group (3.3 vs 4.8 days; P = 0.21). There was no difference in either maximum (17.9 ± 16.1 vs 23.8 ± 21.7 µg/min norepinephrine equivalents [NEQs]; P = 0.1) or average vasopressor dose (9.5 ± 8.4 vs 12.1 ± 11.5 µg/min NEQ; P = 0.17). There was a decrease in mortality in the statin patients (43% vs 67 %; P = 0.05). On adjustment for potential confounders, there was no difference in any outcome, with a persistent trend toward lower mortality in the statin group. Continuation of prehospital statin therapy decreased neither duration nor dose of vasopressors in patients with septic shock but yielded a trend toward decreased mortality. © The Author(s) 2015.

The Absence of Fever Is Associated With Higher Mortality and Decreased Antibiotic and IV Fluid Administration in Emergency Department Patients With Suspected Septic Shock.

PubMed

Henning, Daniel J; Carey, Jeremy R; Oedorf, Kimie; Day, Danielle E; Redfield, Colby S; Huguenel, Colin J; Roberts, Jonathan C; Sanchez, Leon D; Wolfe, Richard E; Shapiro, Nathan I

2017-06-01

This study evaluates whether emergency department septic shock patients without a fever (reported or measured) receive less IV fluids, have decreased antibiotic administration, and suffer increased in-hospital mortality. This was a secondary analysis of a prospective, observational study of patients with shock. The study was conducted in an urban, academic emergency department. The original study enrolled consecutive adult (aged 18 yr or older) emergency department patients from November 11, 2012, to September 23, 2013, who met one of the following shock criteria: 1) systolic blood pressure less than 90 mm Hg after at least 1L IV fluids, 2) new vasopressor requirement, or 3) systolic blood pressure less than 90 mm Hg and IV fluids held for concern of fluid overload. The current study is limited to patients with septic shock. Patients were grouped as febrile if they had a subjective fever or a measured temperature >100.4°F documented in the emergency department; afebrile patients lacked both. Among 378 patients with septic shock, 207 of 378 (55%; 50-60%) were febrile by history or measurement. Afebrile patients had lower rates of antibiotic administration in the emergency department (81% vs 94%; p < 0.01), lower mean volumes of IV fluids (2,607 vs 3,013 mL; p < 0.01), and higher in-hospital mortality rates (33% vs 11%; p < 0.01). After adjusting for bicarbonate less than 20 mEq/L, lactate concentration, respiratory rate greater than or equal to 24 breaths/min, emergency department antibiotics, and emergency department IV fluids volume, being afebrile remained a significant predictor of in-hospital mortality (odds ratio, 4.3; 95% CI, 2.2-8.2; area under the curve = 0.83). In emergency department patients with septic shock, afebrile patients received lower rates of emergency department antibiotic administration, lower mean IV fluids volume, and suffered higher in-hospital mortality.

DGAEE, a newly synthesized derivative of glycyrrhetinic acid, potently attenuates mouse septic shock via its main metabolite DGA in an IL-10-dependent manner.

PubMed

Luo, Jinque; Liu, Mei; Wu, Xin; Dou, Yannong; Xia, Yufeng; Dai, Yue; Wei, Zhifeng

2015-12-01

Endotoxin can stimulate inflammatory cytokine release from monocytes/macrophages and result in septic shock. Glycyrrhetinic acid (GA), the main bioactive component of licorice, possesses substantial anti-inflammatory activity. Here, we explored effect of 11-deoxy-18α-glycyrrhetinic acid-30-ethyl ester (DGAEE), a newly synthesized derivative of GA, on septic shock. DGAEE and its main metabolite 11-deoxy-18α-glycyrrhetinic acid (DGA) significantly alleviated septic shock as evidenced by improvements of survival rates, lung histopathological changes and wet/dry ratio in lipopolysaccharide (LPS)/D-galactosamine-stimulated mice, and decreased blood pressure in LPS/D-galactosamine-stimulated rats. The two compounds decreased serum levels of NO, TNF-α, IL-6, IL-1β, and increased the level of IL-10 more potently in mice. In LPS-stimulated RAW 264.7 cells, DGA but not DGAEE showed marked regulation of NO, TNF-α, IL-6 and IL-10 levels, suggesting that DGAEE display anti-shock effect by DGA rather than itself. Moreover, the neutralizing antibody against IL-10 markedly prohibited the inhibitory effect of DGA on the production of cytokines from RAW 264.7 cells, and AS101 (an inhibitor of IL-10 biosynthesis) almost completely reversed the anti-shock effect of DGA in mice. In addition, DGA did not affect activation of NF-κB-p65 and p38 MAPK as well as IκBα degradation, but moderately reduced activation of ERK and JNK, and markedly increased phosphorylation of GSK3β in LPS-stimulated RAW 264.7 cells. LY294002 (an inhibitor of GSK3β phosphorylation) and LiCl (an inhibitor of GSK3β activity) diminished and potentiated increase of IL-10 levels by DGA, respectively. In conclusion, DGAEE alleviates septic shock through DGA in an IL-10-dependent manner, and the mechanism is related to inactivation of GSK3β. Copyright © 2015 Elsevier B.V. All rights reserved.

Treatment of Pediatric Septic Shock With the Surviving Sepsis Campaign Guidelines and PICU Patient Outcomes.

PubMed

Workman, Jennifer K; Ames, Stefanie G; Reeder, Ron W; Korgenski, E Kent; Masotti, Susan M; Bratton, Susan L; Larsen, Gitte Y

2016-10-01

The Surviving Sepsis Campaign recommends rapid recognition and treatment of severe sepsis and septic shock. Few reports have evaluated the impact of these recommendations in pediatrics. We sought to determine if outcomes in patients who received initial care compliant with the Surviving Sepsis Campaign time goals differed from those treated more slowly. Single center retrospective cohort study. Emergency department and PICU at an academic children's hospital. Three hundred twenty-one patients treated for septic shock in the emergency department and admitted directly to the PICU. None. The exposure was receipt of emergency department care compliant with the Surviving Sepsis Campaign recommendations (delivery of IV fluids, IV antibiotics, and vasoactive infusions within 1 hr of shock recognition). The primary outcome was development of new or progressive multiple organ dysfunction syndrome. Secondary outcomes included mortality, need for mechanical ventilation or vasoactive medications, and hospital and PICU length of stay. Of the 321 children studied, 117 received Surviving Sepsis Campaign compliant care in the emergency department and 204 did not. New or progressive multiple organ dysfunction syndrome developed in nine of the patients (7.7%) who received Surviving Sepsis Campaign compliant care and 25 (12.3%) who did not (p = 0.26). There were 17 deaths; overall mortality rate was 5%. There were no significant differences between groups in any of the secondary outcomes. Although only 36% of patients met the Surviving Sepsis Campaign guideline recommendation of bundled care within 1 hour of shock recognition, 75% of patients received the recommended interventions in less than 3 hours. Treatment for pediatric septic shock in compliance with the Surviving Sepsis Campaign recommendations was not associated with better outcomes compared with children whose initial therapies in the emergency department were administered more slowly. However, all patients were treated rapidly and we report low morbidity and mortality. This underscores the importance of rapid recognition and treatment of septic shock.

The prognostic performance of the complement system in septic patients in emergency department: a cohort study.

PubMed

Zhao, Xin; Chen, Yun-Xia; Li, Chun-Sheng

2015-01-01

To investigate the prognostic performance of complement components in septic patients, complement 3, membrane attack complex (MAC) and mannose-binding lectin were measured and compared among adult patients with sepsis, severe sepsis and septic shock, as well as between in-hospital nonsurvivors and survivors. The prognostic value of complement components was compared with mortality in emergency department sepsis (MEDS) score. Median complement 3, MAC and mannose-binding lectin increased directly with the sepsis, severe sepsis and septic shock groups, and were significantly higher in nonsurvivors than in survivors. MEDS and MAC independently predicted in-hospital mortality. The prognostic performance of MAC was superior to MEDS as analyzed by receiver operating characteristic curve and area under the curve.

Misdirected Sympathy: The Role of Sympatholysis in Sepsis and Septic Shock.

PubMed

Ferreira, Jason A; Bissell, Brittany D

2018-02-01

The spectrum of sepsis and septic shock remains a highly prevalent disease state, carrying a high risk of morbidity and mortality. The sympathetic nervous system (SNS) plays an important role in this initial cascade, enabling the host to respond to invading pathogens; however, prolonged activation can become pathological. The potential for unregulated sympathetic tone to become of detriment in patients with sepsis has fueled interest in the role and impact of sympatholysis, the selective inhibition of sympathetic tone. The cornerstone of septic shock therapy for decades has been the supplementation of catecholamines and thus potential further perpetuation of this sympathetic dysregulation. Although the theory of sympatholysis circulates around cardiovascular effects and stroke volume optimization, the impact of augmenting the SNS may extend well beyond this, including the impacts on the immune system, inflammatory cascade, and even gene transcription. Presently, the most robust clinical evidence involves the use of the cardioselective β-blocker esmolol in patients with septic shock with persistent tachycardia secondary to catecholamine use. Evidence is isolated only to animal models with α-agonists. Future evidence stands to elucidate the balance of sympathetic and autonomic tone as well as the potential role of redirecting and maximizing sympathetic activity.

Ischemic necrosis of the tongue in surgical patients with septic shock: a case report.

PubMed

Cho, Jinbeom; Sung, Kiyoung; Lee, Dosang

2016-07-19

As the tongue is a well-vascularized organ, ischemic necrosis of the tongue is a rare disease entity. Critically ill patients with profound shock may experience end-organ hypoperfusion, which might result in tongue necrosis. However, to our best knowledge, there are no reports regarding ischemic necrosis of the tongue in surgical patients with septic shock. Two patients recently developed ischemic necrosis of the tongue in our surgical intensive care unit. Both patients had undergone emergent surgery for ischemic enteritis and developed postoperative septic shock. The first patient responded to critical treatment with a short period of circulatory shock, and the delivered dose of the vasopressor seemed to be acceptable. In contrast, the second patient developed postoperative refractory shock, and high-dose vasopressor treatment was required to maintain adequate tissue perfusion. Both patients developed ischemic necrosis of the tongue and died shortly after its emergence, despite vigorous resuscitation. We suggest that ischemic necrosis of the tongue is an under-reported manifestation of any type of circulatory shock, which may have a complex pathogenic mechanism. Clinicians should be aware of the possibility of ischemic necrosis of the tongue in patients with circulatory shock, even if the patient exhibits clinical improvement, as this awareness may facilitate estimation of their prognosis and preparation for clinical deterioration.

Polymyxin-B hemoperfusion in septic patients: analysis of a multicenter registry.

PubMed

Cutuli, Salvatore Lucio; Artigas, Antonio; Fumagalli, Roberto; Monti, Gianpaola; Ranieri, Vito Marco; Ronco, Claudio; Antonelli, Massimo

2016-12-01

In 2010, the EUPHAS 2 collaborative group created a registry with the purpose of recording data from critically ill patients suffering from severe sepsis and septic shock treated with polymyxin-B hemoperfusion (PMX-HP) for endotoxin removal. The aim of the registry was to verify the application of PMX-HP in the daily clinical practice. The EUPHAS 2 registry involved 57 centers between January 2010 and December 2014, collecting retrospective data of 357 patients (297 in Europe and 60 in Asia) suffering from severe sepsis and septic shock caused by proved or suspected infection related to Gram negative bacteria. All patients received atleast one cycle of extracorporeal endotoxin removal by PMX-HP. Septic shock was diagnosed in 305 (85.4 %) patients. The most common source of infection was abdominal (44.0 %) followed by pulmonary (17.6 %). Gram negative bacteria represented 60.6 % of the pathogens responsible of infection. After 72 h from the first cycle of PMX-HP, some of the SOFA score components significantly improved with respect to baseline: cardiovascular (2.16 ± 1.77 from 3.32 ± 1.29, p < 0.0001), respiratory (1.95 ± 0.95 from 2.40 ± 1.06, p < 0.001) and renal (1.84 ± 1.77 from 2.23 ± 1.62, p = 0.013). Overall 28-day survival rate was 54.5 % (60.4 % in abdominal and 47.5 % in pulmonary infection). Patients with abdominal infection treated with PMX-HP within 24 h from the diagnosis of septic shock had a 28-day survival rate of 64.5 %. Patients showing a significantly cardiovascular improvement after PMX-HP had a 28-survival rate of 75 % in comparison to the 39 % of patients who did not (p < 0.001). Cox regression analysis found the variation of cardiovascular, respiratory and coagulation SOFA to be independent covariates for 28-day survival. In European patients were observed a higher 28-day (58.8 vs. 34.5 %, p = 0.003), ICU (59 vs. 36.7 %, p = 0.006) and hospital survival rate (53.2 vs. 35 %, p = 0.02) than in Asian patients. However, the two populations were highly heterogeneous in terms of source of infection and severity scores at admission. The EUPHAS 2 is the largest registry conducted outside Japan on the clinical use of PMX-HP in septic patients. Data analysis confirmed the feasibility of PMX-HP to treat septic patients in daily clinical practice, showing clinical benefits associated with endotoxin removal without significant adverse events related to the extracorporeal technique.

Biomarkers for pediatric sepsis and septic shock

PubMed Central

Standage, Stephen W; Wong, Hector R

2011-01-01

Sepsis is a clinical syndrome defined by physiologic changes indicative of systemic inflammation, which are likely attributable to documented or suspected infection. Septic shock is the progression of those physiologic changes to the extent that delivery of oxygen and metabolic substrate to tissues is compromised. Biomarkers have the potential to diagnose, monitor, stratify and predict outcome in these syndromes. C-reactive protein is elevated in inflammatory and infectious conditions and has long been used as a biomarker indicating infection. Procalcitonin has more recently been shown to better distinguish infection from inflammation. Newer candidate biomarkers for infection include IL-18 and CD64. Lactate facilitates the diagnosis of septic shock and the monitoring of its progression. Multiple stratification biomarkers based on genome-wide expression profiling are under active investigation and present exciting future possibilities. PMID:21171879

The choice of catecholamines in septic shock: more and more good arguments to strengthen the known position, but don't lose the faith!

PubMed

Meier-Hellmann, Andreas

2006-01-01

The choice of catecholamines for hemodynamic stabilisation in septic shock patients has been an ongoing debate for several years. Several studies have investigated the regional effects in septic patients. Because of an often very small sample size, because of inconsistent results and because of methodical problems in the monitoring techniques used in these studies, however, it is not possible to provide clear recommendations concerning the use of catecholamines in sepsis. Prospective and adequate-sized studies are necessary because outcome data are completely lacking.

Combination of Acute Physiology and Chronic Health Evaluation II score, early lactate area, and N-terminal prohormone of brain natriuretic peptide levels as a predictor of mortality in geriatric patients with septic shock.

PubMed

Wang, Hao; Li, Zhong; Yin, Mei; Chen, Xiao-Mei; Ding, Shi-Fang; Li, Chen; Zhai, Qian; Li, Yuan; Liu, Han; Wu, Da-Wei

2015-04-01

Given the high mortality rates in elderly patients with septic shock, the early recognition of patients at greatest risk of death is crucial for the implementation of early intervention strategies. Serum lactate and N-terminal prohormone of brain natriuretic peptide (NT-proBNP) levels are often elevated in elderly patients with septic shock and are therefore important biomarkers of metabolic and cardiac dysfunction. We hypothesized that a risk stratification system that incorporates the Acute Physiology and Chronic Health Evaluation (APACHE) II score and lactate and NT-proBNP biomarkers would better predict mortality in geriatric patients with septic shock than the APACHE II score alone. A single-center prospective study was conducted from January 2012 to December 2013 in a 30-bed intensive care unit of a triservice hospital. The lactate area score was defined as the sum of the area under the curve of serial lactate levels measured during the 24 hours following admission divided by 24. The NT-proBNP score was assigned based on NT-proBNP levels measured at admission. The combined score was calculated by adding the lactate area and NT-proBNP scores to the APACHE II score. Multivariate logistic regression analyses and receiver operating characteristic curves were used to evaluate which variables and scoring systems served as the best predictors of mortality in elderly septic patients. A total of 115 patients with septic shock were included in the study. The overall 28-day mortality rate was 67.0%. When compared to survivors, nonsurvivors had significantly higher lactate area scores, NT-proBNP scores, APACHE II scores, and combined scores. In the multivariate regression model, the combined score, lactate area score, and mechanical ventilation were independent risk factors associated with death. Receiver operating characteristic curves indicated that the combined score had significantly greater predictive power when compared to the APACHE II score or the NT-proBNP score (P < .05). A combined score that incorporates the APACHE II score with early lactate area and NT-proBNP levels is a useful method for risk stratification in geriatric patients with septic shock. Copyright © 2014 Elsevier Inc. All rights reserved.

An Emergency Department Validation of the SEP-3 Sepsis and Septic Shock Definitions and Comparison With 1992 Consensus Definitions.

PubMed

Henning, Daniel J; Puskarich, Michael A; Self, Wesley H; Howell, Michael D; Donnino, Michael W; Yealy, Donald M; Jones, Alan E; Shapiro, Nathan I

2017-10-01

The Third International Consensus Definitions Task Force (SEP-3) proposed revised criteria defining sepsis and septic shock. We seek to evaluate the performance of the SEP-3 definitions for prediction of inhospital mortality in an emergency department (ED) population and compare the performance of the SEP-3 definitions to that of the previous definitions. This was a secondary analysis of 3 prospectively collected, observational cohorts of infected ED subjects aged 18 years or older. The primary outcome was all-cause inhospital mortality. In accordance with the SEP-3 definitions, we calculated test characteristics of sepsis (quick Sequential Organ Failure Assessment [qSOFA] score ≥2) and septic shock (vasopressor dependence plus lactate level >2.0 mmol/L) for mortality and compared them to the original 1992 consensus definitions. We identified 7,754 ED patients with suspected infection overall; 117 had no documented mental status evaluation, leaving 7,637 patients included in the analysis. The mortality rate for the overall population was 4.4% (95% confidence interval [CI] 3.9% to 4.9%). The mortality rate for patients with qSOFA score greater than or equal to 2 was 14.2% (95% CI 12.2% to 16.2%), with a sensitivity of 52% (95% CI 46% to 57%) and specificity of 86% (95% CI 85% to 87%) to predict mortality. The original systemic inflammatory response syndrome-based 1992 consensus sepsis definition had a 6.8% (95% CI 6.0% to 7.7%) mortality rate, sensitivity of 83% (95% CI 79% to 87%), and specificity of 50% (95% CI 49% to 51%). The SEP-3 septic shock mortality was 23% (95% CI 16% to 30%), with a sensitivity of 12% (95% CI 11% to 13%) and specificity of 98.4% (95% CI 98.1% to 98.7%). The original 1992 septic shock definition had a 22% (95% CI 17% to 27%) mortality rate, sensitivity of 23% (95% CI 18% to 28%), and specificity of 96.6% (95% CI 96.2% to 97.0%). Both the new SEP-3 and original sepsis definitions stratify ED patients at risk for mortality, albeit with differing performances. In terms of mortality prediction, the SEP-3 definitions had improved specificity, but at the cost of sensitivity. Use of either approach requires a clearly intended target: more sensitivity versus specificity. Copyright © 2017 American College of Emergency Physicians. Published by Elsevier Inc. All rights reserved.

Serratia marcescens harboring SME-4 in Brazil: A silent threat.

PubMed

Cayô, Rodrigo; Leme, Rodrigo Cuiabano Paes; Streling, Ana Paula; Matos, Adriana Pereira; Nodari, Carolina Silva; Chaves, Jessica Reis Esteves; Brandão, Jorge Luiz Ferreira; de Almeida, Maíra Fernandes; Carrareto, Valério; de Castro Pereira, Marco Aurélio; de Almeida, Jean Pierre Aquino; Ferreira, Demian Candido; Gales, Ana Cristina

2017-04-01

The intrinsic polymyxin resistance displayed by Serratia marcescens makes the acquisition of carbapenemase encoding genes a worrisome event. This study report a SME-4-producing S. marcescens isolate causing septic shock in Brazil. The insertion of novel resistance determinants and their consequent spread in our territory is noteworthy. Copyright © 2017 Elsevier Inc. All rights reserved.

Hydrocortisone fails to abolish NF-κB1 protein nuclear translocation in deletion allele carriers of the NFKB1 promoter polymorphism (-94ins/delATTG) and is associated with increased 30-day mortality in septic shock.

PubMed

Schäfer, Simon T; Gessner, Sophia; Scherag, André; Rump, Katharina; Frey, Ulrich H; Siffert, Winfried; Westendorf, Astrid M; Steinmann, Jörg; Peters, Jürgen; Adamzik, Michael

2014-01-01

Previous investigations and meta-analyses on the effect of glucocorticoids on mortality in septic shock revealed mixed results. This heterogeneity might be evoked by genetic variations. Such candidate is a promoter polymorphism (-94ins/delATTG) of the gene encoding the ubiquitous transcription-factor nuclear-factor-κB (NF-κB) which binds to recognition elements in the promoter of several genes encoding for the innate immune-system. In turn, hydrocortisone inhibits NF-κB nuclear translocation and thus transcription of key immune-response regulators. Accordingly, we tested the hypotheses that hydrocortisone has a NFKB1 genotype dependent effect on 1) NF-κB1 nuclear translocation evoked by lipopolysaccharide (LPS) in monocytes in vitro, and 2) mortality in septic shock. Monocytes of volunteers with the homozygous insertion (II; n = 5) or deletion (DD; n = 6) NFKB1 genotype were incubated with 10 µgml-1 LPS ± hydrocortisone (10-5M), and NF-κB1 nuclear translocation was assessed (immunofluorescence). Furthermore, we analyzed 30-day-mortality in 160 patients with septic shock stratified for both genotype and hydrocortisone therapy. Hydrocortisone inhibited LPS induced nuclear translocation of NF-κB1 in II (25%±11;p = 0.0001) but not in DD genotypes (51%±15;p = n.s.). Onehundredandfour of 160 patients with septic shock received hydrocortisone, at the discretion of the intensivist. NFKB1 deletion allele carriers (ID/DD) receiving hydrocortisone had a much greater 30-day-mortality (57.6%) than II genotypes (24.4%; HR:3.18, 95%-CI:1.61-6.28;p = 0.001). In contrast, 30-day mortality was 22.2% in ID/DD and 25.0% in II genotypes without hydrocortisone therapy. Results were similar when using propensity score matching to account for possible bias in the intensivists' decision to administer hydrocortisone. Hydrocortisone fails to inhibit LPS induced nuclear NF-κB1 translocation in deletion allele carriers of the NFKB1 promoter polymorphism (-94ins/delATTG). In septic shock, hydrocortisone treatment is associated with markedly increased 30-day-mortality only in such carriers. Accordingly, previous heterogeneous results regarding the benefit of hydrocortisone in septic shock may be reconciled by genetic variation of the NFKB1 promoter polymorphism.

Hydrocortisone Fails to Abolish NF-κB1 Protein Nuclear Translocation in Deletion Allele Carriers of the NFKB1 Promoter Polymorphism (-94ins/delATTG) and Is Associated with Increased 30-Day Mortality in Septic Shock

PubMed Central

Schäfer, Simon T.; Gessner, Sophia; Scherag, André; Rump, Katharina; Frey, Ulrich H.; Siffert, Winfried; Westendorf, Astrid M.; Steinmann, Jörg; Peters, Jürgen; Adamzik, Michael

2014-01-01

Background Previous investigations and meta-analyses on the effect of glucocorticoids on mortality in septic shock revealed mixed results. This heterogeneity might be evoked by genetic variations. Such candidate is a promoter polymorphism (-94ins/delATTG) of the gene encoding the ubiquitous transcription-factor nuclear-factor-κB (NF-κB) which binds to recognition elements in the promoter of several genes encoding for the innate immune-system. In turn, hydrocortisone inhibits NF-κB nuclear translocation and thus transcription of key immune-response regulators. Accordingly, we tested the hypotheses that hydrocortisone has a NFKB1 genotype dependent effect on 1) NF-κB1 nuclear translocation evoked by lipopolysaccharide (LPS) in monocytes in vitro, and 2) mortality in septic shock. Methods Monocytes of volunteers with the homozygous insertion (II; n = 5) or deletion (DD; n = 6) NFKB1 genotype were incubated with 10 µgml-1 LPS ± hydrocortisone (10-5M), and NF-κB1 nuclear translocation was assessed (immunofluorescence). Furthermore, we analyzed 30-day-mortality in 160 patients with septic shock stratified for both genotype and hydrocortisone therapy. Results Hydrocortisone inhibited LPS induced nuclear translocation of NF-κB1 in II (25%±11;p = 0.0001) but not in DD genotypes (51%±15;p = n.s.). Onehundredandfour of 160 patients with septic shock received hydrocortisone, at the discretion of the intensivist. NFKB1 deletion allele carriers (ID/DD) receiving hydrocortisone had a much greater 30-day-mortality (57.6%) than II genotypes (24.4%; HR:3.18, 95%-CI:1.61-6.28;p = 0.001). In contrast, 30-day mortality was 22.2% in ID/DD and 25.0% in II genotypes without hydrocortisone therapy. Results were similar when using propensity score matching to account for possible bias in the intensivists' decision to administer hydrocortisone. Conclusion Hydrocortisone fails to inhibit LPS induced nuclear NF-κB1 translocation in deletion allele carriers of the NFKB1 promoter polymorphism (-94ins/delATTG). In septic shock, hydrocortisone treatment is associated with markedly increased 30-day-mortality only in such carriers. Accordingly, previous heterogeneous results regarding the benefit of hydrocortisone in septic shock may be reconciled by genetic variation of the NFKB1 promoter polymorphism. PMID:25133403

Clinical characteristics, sepsis interventions and outcomes in the obese patients with septic shock: an international multicenter cohort study

PubMed Central

2013-01-01

Introduction Data are sparse as to whether obesity influences the risk of death in critically ill patients with septic shock. We sought to examine the possible impact of obesity, as assessed by body mass index (BMI), on hospital mortality in septic shock patients. Methods We performed a nested cohort study within a retrospective database of patients with septic shock conducted in 28 medical centers in Canada, United States and Saudi Arabia between 1996 and 2008. Patients were classified according to the World Health Organization criteria for BMI. Multivariate logistic regression analysis was performed to evaluate the association between obesity and hospital mortality. Results Of the 8,670 patients with septic shock, 2,882 (33.2%) had height and weight data recorded at ICU admission and constituted the study group. Obese patients were more likely to have skin and soft tissue infections and less likely to have pneumonia with predominantly Gram-positive microorganisms. Crystalloid and colloid resuscitation fluids in the first six hours were given at significantly lower volumes per kg in the obese and very obese patients compared to underweight and normal weight patients (for crystalloids: 55.0 ± 40.1 ml/kg for underweight, 43.2 ± 33.4 for normal BMI, 37.1 ± 30.8 for obese and 27.7 ± 22.0 for very obese). Antimicrobial doses per kg were also different among BMI groups. Crude analysis showed that obese and very obese patients had lower hospital mortality compared to normal weight patients (odds ratio (OR) 0.80, 95% confidence interval (CI) 0.66 to 0.97 for obese and OR 0.61, 95% CI 0.44 to 0.85 for very obese patients). After adjusting for baseline characteristics and sepsis interventions, the association became non-significant (OR 0.80, 95% CI 0.62 to 1.02 for obese and OR 0.69, 95% CI 0.45 to 1.04 for very obese). Conclusions The obesity paradox (lower mortality in the obese) documented in other populations is also observed in septic shock. This may be related in part to differences in patient characteristics. However, the true paradox may lie in the variations in the sepsis interventions, such as the administration of resuscitation fluids and antimicrobial therapy. Considering the obesity epidemic and its impact on critical care, further studies are warranted to examine whether a weight-based approach to common therapeutic interventions in septic shock influences outcome. PMID:23594407

Prescribing patterns of hydrocortisone in septic shock: a single-center experience of how surviving sepsis guidelines are interpreted and translated into bedside practice.

PubMed

Contrael, Katlynd M; Killian, Alley J; Gregg, Sara R; Buchman, Timothy G; Coopersmith, Craig M

2013-10-01

The Surviving Sepsis Campaign suggests giving hydrocortisone to septic patients only if their "blood pressure is poorly responsive to fluid resuscitation and vasopressor therapy." Because the definition of "poorly responsive" is not provided, the purpose of this study was to identify prescribing triggers for hydrocortisone in septic shock. Retrospective chart review of patients with septic shock over 17 months, who received hydrocortisone, followed by a survey of all intensivists who attended in the study ICUs to determine whether provider attitudes matched clinical practice. Eight ICUs in an academic hospital and a hybrid academic/community hospital. A total of 155 patients with septic shock in whom vasopressors were initiated and hydrocortisone was prescribed. Ninety-nine patients (64%) were already receiving two vasopressors before hydrocortisone was prescribed. An additional 22 patients were on a single high-dose vasopressor prior to corticosteroid initiation. Of patients who survived to have their hydrocortisone dose changed, 57% had their corticosteroids tapered, whereas 43% were abruptly discontinued. Seventy-six percent of patients were no longer on vasopressors when the first dosing change was made. Twenty-seven out of 36 intensivists (75%) completed the survey. The majority (72%) defined "poorly responsive to vasopressors" as the presence of two vasopressors, and 70% stated that they required patients to be off vasopressors prior to altering the corticosteroid dose. Significant variability exists when corticosteroids are prescribed for septic shock, with the most common interpretation in our institution of "poorly responsive to fluid resuscitation and vasopressor therapy" being the presence of two vasopressors. The method and timing of corticosteroid discontinuation also differed among providers. Self-described prescribing patterns from intensivists closely matched their actual behavior, suggesting variability is due to differing interpretations of the guidelines themselves, rather than a deficit in knowledge translation.

Evolution of Acute Kidney Injury and Its Association With Systemic Hemodynamics in Children With Fluid-Refractory Septic Shock.

PubMed

Deep, Akash; Sagar, Hiremath; Goonasekera, Chulananda; Karthikeyan, Palaniswamy; Brierley, Joe; Douiri, Abdel

2018-07-01

There are no studies in pediatrics evaluating the progression of acute kidney injury in septic shock. We investigated the evolution of sepsis-associated acute kidney injury and its association with systemic hemodynamics in children with fluid-refractory septic shock. Prospective cohort study. PICU of a tertiary care hospital. All patients with fluid-refractory septic shock (n = 61) between September 2010 and February 2014. Hemodynamic variables using noninvasive ultrasound cardiac output monitor were measured at admission and 6 hourly thereafter till 48 hours. We used the Kidney Disease: Improving Global Outcomes criteria to define and stage acute kidney injury. Associations between various hemodynamic variables and development of acute kidney injury were evaluated. Severe acute kidney injury was defined as stage 2 or 3 acute kidney injury and was compared with no acute kidney injury or stage 1 acute kidney injury. Severe acute kidney injury developed in 29.5% (n = 18) of the 61 children with fluid-refractory septic shock, whereas 43 patients (70.49%) had either no or stage 1 acute kidney injury. Most patients who developed acute kidney injury did so within the first 48 hours of PICU admission. Severe acute kidney injury conferred a three-fold increased risk of death by day 28 (hazard ratio, 3.23; 95% CI, 1.52-6.67; p = 0.002), longer ICU stay, and increased duration of mechanical ventilation. Central venous pressure at presentation was higher in severe acute kidney injury by 5 cm H2O. Highest lactate in the first 24 hours of PICU admission, low diastolic blood pressure, low systemic vascular resistance index at admission were associated with severe acute kidney injury. This model reliably predicted stage 2/3 acute kidney injury by day 3 with area under the curve equals to 94%; 95% CI, 88.3-99.99. None of the other hemodynamic variables showed any association with severe acute kidney injury. Manifestations of sepsis-associated acute kidney injury often occur early after PICU admission and is associated with increased morbidity and mortality. There is a need to develop a predictive model in septic shock which could facilitate early detection of acute kidney injury.

N-terminal pro-brain natriuretic peptide and cardiac troponin I for the prognostic utility in elderly patients with severe sepsis or septic shock in intensive care unit: A retrospective study.

PubMed

Cheng, Hui; Fan, Wei-Ze; Wang, Sheng-Chi; Liu, Zhao-Hui; Zang, Hui-Ling; Wang, Li-Zhong; Liu, Hong-Juan; Shen, Xiao-Hui; Liang, Shao-Qing

2015-06-01

Using biomarkers to predict mortality in patient with severe sepsis or septic shock is of importance, as these patients frequently have high mortality and unsatisfied outcome. N-terminal pro-brain natriuretic peptide (NT-proBNP) and cardiac troponin I (cTnI) play extremely important roles in prognostic value in the mortality of severe sepsis and septic shock. The present study was retrospectively designed to evaluate the predicting mortality of NT-proBNP and cTnI in elderly patients with severe sepsis or septic shock administered in the intensive care unit (ICU) and also to evaluate whether the predicting ability of Acute Physiology and Chronic Health Evaluation II (APACHE-II) score or C-reactive protein (CRP) was increased in combination with the biomarkers. A cohort of 430 patients (aged ≥65 years) with severe sepsis or septic shock admitted to our ICU between October 2011 and December 2013 was included in the study. Patient data including clinical, laboratory, and survival and mortality were collected. All patients were examined with NT-proBNP, cTnI, CRP, and APACHE-II score and were categorized as the survived and deceased groups according to the outcome 30 days after ICU treatment. The levels of NT-proBNP and cTnI (P < .01) or CRP (P < .05) were significantly higher in the deceased group than those in the survived group. The predicting mortality of APACHE-II score alone was low but largely improved, when it was combined with both NT-proBNP and cTnI (P < .05). The alteration of NT-proBNP and cTnI levels strongly predicated the ICU prognosis in elderly patients with severe sepsis or septic shock. N-terminal pro-brain natriuretic peptide and cTnI were superior to CRP in predicting mortality. The predicting ability of APACHE-II score was improved only when combined with NT-proBNP and cTnI. Copyright © 2014 Elsevier Inc. All rights reserved.

Continuous cytokine haemoadsorption incorporated into a venoarterial ECMO circuit for the management of postcardiotomy cardiogenic and septic shock - a case report.

PubMed

Nemeth, Endre; Szigeti, Szabolcs; Varga, Tamas; Daroczi, Laszlo; Barati, Zoltan; Merkely, Bela; Gal, Janos

2018-05-01

The acute surgical treatment of infective endocarditis (IE) carries a high risk of postoperative mortality. Most complications are linked to uncontrolled sepsis and inflammatory processes. Cytokine haemoadsorption is an extracorporeal technique which has benefits reported in haemodynamic stability and inflammatory response. A 46-year-old male patient underwent emergency cardiac surgery due to progressive IE. Postcardiotomy cardiogenic shock associated with cardiac surgery required the implantation of venoarterial (VA)-ECMO. Three days later, the patient developed secondary septic shock. The novel application of continuous CytoSorb TM treatment installed in the VA-ECMO circuit is demonstrated in this case during the management of simultaneous shocks. Advanced intensive care led to an improvement in the patient's condition, which facilitated successful weaning from mechanical ventilation. However, the patient died from a new onset fulminant septic shock two months after his initial cardiac surgery. VA-ECMO is suitable for installation of the CytoSorb TM cartridge. This modality could be an option for high-volume, continuous cytokine haemoadsorption when VA-ECMO is employed without renal replacement therapy. This specific application of CytoSorb TM was safe, feasible and contributed to the optimal management of simultaneous shocks.

The cell wall components peptidoglycan and lipoteichoic acid from Staphylococcus aureus act in synergy to cause shock and multiple organ failure.

PubMed Central

De Kimpe, S J; Kengatharan, M; Thiemermann, C; Vane, J R

1995-01-01

Although the incidence of Gram-positive sepsis has risen strongly, it is unclear how Gram-positive organisms (without endotoxin) initiate septic shock. We investigated whether two cell wall components from Staphylococcus aureus, peptidoglycan (PepG) and lipoteichoic acid (LTA), can induce the inflammatory response and multiple organ dysfunction syndrome (MODS) associated with septic shock caused by Gram-positive organisms. In cultured macrophages, LTA (10 micrograms/ml), but not PepG (100 micrograms/ml), induces the release of nitric oxide measured as nitrite. PepG, however, caused a 4-fold increase in the production of nitrite elicited by LTA. Furthermore, PepG antibodies inhibited the release of nitrite elicited by killed S. aureus. Administration of both PepG (10 mg/kg; i.v.) and LTA (3 mg/kg; i.v.) in anesthetized rats resulted in the release of tumor necrosis factor alpha and interferon gamma and MODS, as indicated by a decrease in arterial oxygen pressure (lung) and an increase in plasma concentrations of bilirubin and alanine aminotransferase (liver), creatinine and urea (kidney), lipase (pancreas), and creatine kinase (heart or skeletal muscle). There was also the expression of inducible nitric oxide synthase in these organs, circulatory failure, and 50% mortality. These effects were not observed after administration of PepG or LTA alone. Even a high dose of LTA (10 mg/kg) causes only circulatory failure but no MODS. Thus, our results demonstrate that the two bacterial wall components, PepG and LTA, work together to cause systemic inflammation and multiple systems failure associated with Gram-positive organisms. Images Fig. 2 PMID:7479784

The duration of hypotension before the initiation of antibiotic treatment is a critical determinant of survival in a murine model of Escherichia coli septic shock: association with serum lactate and inflammatory cytokine levels.

PubMed

Kumar, Anand; Haery, Cameron; Paladugu, Bhanu; Kumar, Aseem; Symeoneides, Simon; Taiberg, Leo; Osman, Jailan; Trenholme, Gordon; Opal, Steven M; Goldfarb, Roy; Parrillo, Joseph E

2006-01-15

This study was designed to examine the relationship between the timing of antibiotic treatment and both survival rates and hemodynamic/inflammatory correlates of survival in a murine model of Escherichia coli septic shock. Surgical implantation of an E. coli (O18:K1:H7)-laced, gelatin capsule-encased fibrinogen clot was used to generate a bacteremic model of murine septic shock. Survival duration, hemodynamic responses, and circulating serum tumor necrosis factor (TNF)-alpha , interleukin (IL)-6, and lactate levels were assessed in relation to increasing delays in or absence of antibiotic treatment. A critical inflection point with respect to survival occurred between 12 and 15 h after implantation. When initiated at or before 12 h, antibiotic treatment resulted in < or = 20% mortality, but, when initiated at or after 15 h, it resulted in >85% mortality. Physiologically relevant hypotension developed in untreated septic mice by 12 h after implantation. Values for heart rate differed between untreated septic mice and sham-infected control mice by 6 h after implantation, whereas values for cardiac output and stroke volume did not differ until at least 18-24 h after implantation. Antibiotic treatment initiated > or = 12 h after implantation was associated with persistence of increased circulating serum lactate, TNF- alpha , and IL-6 levels. The timing of antibiotic treatment relative to hypotension is closely associated with survival in this murine model of septic shock. Delay in antibiotic treatment results in the persistence of inflammatory/stress markers even after antibiotic treatment is initiated.

Evaluation of lactate, white blood cell count, neutrophil count, procalcitonin and immature granulocyte count as biomarkers for sepsis in emergency department patients.

PubMed

Karon, Brad S; Tolan, Nicole V; Wockenfus, Amy M; Block, Darci R; Baumann, Nikola A; Bryant, Sandra C; Clements, Casey M

2017-11-01

Lactate, white blood cell (WBC) and neutrophil count, procalcitonin and immature granulocyte (IG) count were compared for the prediction of sepsis, and severe sepsis or septic shock, in patients presenting to the emergency department (ED). We prospectively enrolled 501 ED patients with a sepsis panel ordered for suspicion of sepsis. WBC, neutrophil, and IG counts were measured on a Sysmex XT-2000i analyzer. Lactate was measured by i-STAT, and procalcitonin by Brahms Kryptor. We classified patients as having sepsis using a simplification of the 1992 consensus conference sepsis definitions. Patients with sepsis were further classified as having severe sepsis or septic shock using established criteria. Univariate receiver operating characteristic (ROC) analysis was performed to determine odds ratio (OR), area under the ROC curve (AUC), and sensitivity/specificity at optimal cut-off for prediction of sepsis (vs. no sepsis), and prediction of severe sepsis or septic shock (vs. no sepsis). There were 267 patients without sepsis; and 234 with sepsis, including 35 patients with severe sepsis or septic shock. Lactate had the highest OR (1.44, 95th% CI 1.20-1.73) for the prediction of sepsis; while WBC, neutrophil count and percent (neutrophil/WBC) had OR>1.00 (p<0.05). All biomarkers had AUC<0.70 and sensitivity and specificity <70% at the optimal cut-off. Initial lactate was the best biomarker for predicting severe sepsis or septic shock, with an odds ratio (95th% CI) of 2.70 (2.02-3.61) and AUC 0.89 (0.82-0.96). Traditional biomarkers (lactate, WBC, neutrophil count, procalcitonin, IG) have limited utility in the prediction of sepsis. Copyright © 2017 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

Refractory septic shock in children: a European Society of Paediatric and Neonatal Intensive Care definition.

PubMed

Morin, Luc; Ray, Samiran; Wilson, Clare; Remy, Solenn; Benissa, Mohamed Rida; Jansen, Nicolaas J G; Javouhey, Etienne; Peters, Mark J; Kneyber, Martin; De Luca, Daniele; Nadel, Simon; Schlapbach, Luregn Jan; Maclaren, Graeme; Tissieres, Pierre

2016-12-01

Although overall paediatric septic shock mortality is decreasing, refractory septic shock (RSS) is still associated with high mortality. A definition for RSS is urgently needed to facilitate earlier identification and treatment. We aim to establish a European society of paediatric and neonatal intensive care (ESPNIC) experts' definition of paediatric RSS. We conducted a two-round Delphi study followed by an observational multicentre retrospective study. One hundred and fourteen paediatric intensivists answered a clinical case-based, two-round Delphi survey, identifying clinical items consistent with RSS. Multivariate analysis of these items in a development single-centre cohort (70 patients, 30 % mortality) facilitated development of RSS definitions based on either a bedside or computed severity score. Both scores were subsequently tested in a validation cohort (six centres, 424 patients, 11.6 % mortality). From the Delphi process, the draft definition included evidence of myocardial dysfunction and high blood lactate levels despite high vasopressor treatment. When assessed in the development population, each item was independently associated with the need for extracorporeal life support (ECLS) or death. Resultant bedside and computed septic shock scores had high discriminative power against the need for ECLS or death, with areas under the receiver operating characteristics curve of 0.920 (95 % CI 0.89-0.94), and 0.956 (95 % CI 0.93-0.97), respectively. RSS defined by a bedside score equal to or higher than 2 and a computed score equal to or higher than 3.5 was associated with a significant increase in mortality. This ESPNIC definition of RSS accurately identifies children with the most severe form of septic shock.

Lactate clearance in septic shock is not a surrogate for improved microcirculatory flow

PubMed Central

Puskarich, Michael A.; Shapiro, Nathan I.; Massey, Michael J.; Kline, Jeffrey A.; Jones, Alan E.

2016-01-01

Introduction Failure to normalize lactate is associated with poor outcomes in septic shock. It has been suggested that persistently elevated lactate may result from regional ischemia due to disturbed and/or heterogenous microcirculatory blood flow. Objectives The goal of this study was to determine if lactate clearance may serve as a surrogate marker for changes in microcirculatory blood flow in patients with septic shock. Methods This was a prospective observational study performed within a previously published clinical trial of L-carnitine for the treatment of vasopressor-dependent septic shock. Intravital video microscopy was performed at enrollment and 12 hours later, and microcirculatory flow index (MFI) was assessed. Associations between enrollment MFI, lactate, and SOFA score were determined, in addition to associations between ΔMFI, lactate clearance, and ΔSOFA. A preplanned subgroup analysis of only patients with an elevated initial lactate was performed. Results We enrolled a total of 31 patients, 23 with survival to and sufficient quality videos both at enrollment and 12 hours. ΔMFI, lactate clearance, and ΔSOFA were 0.1 (IQR 0, 0.3), 18% (IQR −10%, 46%), and −2 (IQR −4, 0). Both ΔMFI and lactate clearance were associated with ΔSOFA (β = −5.3, p = 0.01 and β = −3.5, 0.047), but not with each other, even in the subgroup of patients with an initially elevated lactate. Conclusion We observed no association between degree of lactate clearance and change in microcirculatory blood flow in patients with septic shock. These data suggest against the hypothesis that lactate clearance may be used as a surrogate marker of microcirculatory blood flow. PMID:26825368

Impact of Dobutamine in Patients With Septic Shock: A Meta-Regression Analysis.

PubMed

Nadeem, Rashid; Sockanathan, Shivani; Singh, Mukesh; Hussain, Tamseela; Kent, Patrick; AbuAlreesh, Sarah

2017-05-01

Septic shock frequently requires vasopressor agents. Conflicting evidence exists for use of inotropes in patients with septic shock. Data from English studies on human adult septic shock patients were collected. A total of 83 studies were reviewed, while 11 studies with 21 data sets including 239 patients were pooled for meta-regression analysis. For VO2, pooled difference in means (PDM) was 0.274. For cardiac index (CI), PDM was 0.783. For delivery of oxygen, PDM was -0.890. For heart rate, PDM was -0.714. For left ventricle stroke work index, PDM was 0.375. For mean arterial pressure, PDM was -0.204. For mean pulmonary artery pressure, PDM was 0.085. For O2 extraction, PDM was 0.647. For PaCO2, PDM was -0.053. For PaO2, PDM was 0.282. For pulmonary artery occlusive pressure, PDM was 0.270. For pulmonary capillary wedge pressure, PDM was 0.300. For PVO2, PDM was -0.492. For right atrial pressure, PDM was 0.246. For SaO2, PDM was 0.604. For stroke volume index, PDM was 0.446. For SvO2, PDM was -0.816. For systemic vascular resistance, PDM was -0.600. For systemic vascular resistance index, PDM was 0.319. Meta-regression analysis was performed for VO2, DO2, CI, and O2 extraction. Age was found to be significant confounding factor for CI, DO2, and O2 extraction. APACHE score was not found to be a significant confounding factor for any of the parameters. Dobutamine seems to have a positive effect on cardiovascular parameters in patients with septic shock. Prospective studies with larger samples are required to further validate this observation.

Radial to femoral arterial blood pressure differences in septic shock patients receiving high-dose norepinephrine therapy.

PubMed

Kim, Won Young; Jun, Jong Hun; Huh, Jin Won; Hong, Sang Bum; Lim, Chae-Man; Koh, Younsuck

2013-12-01

The accuracy of arterial blood pressure (ABP) monitoring is crucial in treating septic shock patients. Clinically significant differences in central to peripheral ABP could develop into sepsis during vasopressor therapy. The aim of this study was to investigate the difference between radial (peripheral) and femoral (central) ABP in septic shock patients receiving high-dose norepinephrine (NE) therapy. This prospective observational study comparing simultaneous intra-arterial measurements of radial and femoral ABP was performed at a university-affiliated, tertiary referral center between October 2008 and March 2009. Patients with septic shock who needed continuous blood pressure monitoring and high-dose NE therapy 0.1 µg/kg per minute or greater to maintain mean arterial pressure (MAP) of 65 mmHg or greater were included. Statistical analysis was conducted using the Bland-Altman method for comparison of repeated measures. In total, 250 sets of systolic, mean, and diastolic femoral and radial ABP were recorded at baseline and after NE titration. Arterial blood pressure readings from the radial artery were underestimated compared with those from the femoral artery. Overall bias (mean difference between simultaneous measurements) between radial and femoral MAP was +4.9 mmHg; however, during high-dose NE therapy, the bias increased to +6.2 mmHg (95% limits of agreement: -6.0 to +18.3 mmHg). Clinically significant radial-femoral MAP differences (MAP ≥5 mmHg) occurred in up to 62.2% of patients with high-dose NE therapy. Radial artery pressure frequently underestimates central pressure in septic shock patients receiving high-dose NE therapy. Femoral arterial pressure monitoring may be more appropriate when high-dose NE therapy is administered.

The impact of duration of organ dysfunction on the outcome of patients with severe sepsis and septic shock.

PubMed

Freitas, Flávio G R; Salomão, Reinaldo; Tereran, Nathalia; Mazza, Bruno Franco; Assunção, Murillo; Jackiu, Mirian; Fernandes, Haggeas; Machado, Flávia Ribeiro

2008-08-01

This study aimed to assess the impact of the duration of organ dysfunction on the outcome of patients with severe sepsis or septic shock. Clinical data were collected from hospital charts of patients with severe sepsis and septic shock admitted to a mixed intensive care unit from November 2003 to February 2004. The duration of organ dysfunction prior to diagnosis was correlated with mortality. Results were considered significant if p<0.05. Fifty-six patients were enrolled. Mean age was 55.6+/-20.7 years, mean APACHE II score was 20.6+/-6.9, and mean SOFA score was 7.9+/-3.7. Thirty-six patients (64.3%) had septic shock. The mean duration of organ dysfunction was 1.9+/-1.9 days. Within the univariate analysis, the variables correlated with hospital mortality were: age (p=0.015), APACHE II (p=0.008), onset outside the intensive care unit (p=0.05), blood glucose control (p=0.05) and duration of organ dysfunction (p=0.0004). In the multivariate analysis, only a duration of organ dysfunction persisting longer than 48 hours correlated with mortality (p=0.004, OR: 8.73 (2.37-32.14)), whereas the APACHE II score remained only a slightly significant factor (p=0.049, OR: 1.11 (1.00-1.23)). Patients who received therapeutic interventions within the first 48 hours after the onset of organ dysfunction exhibited lower mortality (32.1% vs. 82.1%, p=0.0001). These findings suggest that the diagnosis of organ dysfunction is not being made in a timely manner. The time elapsed between the onset of organ dysfunction and initiation of therapeutic intervention can be quite long, and this represents an important determinant of survival in cases of severe sepsis and septic shock.

Serum Neutrophil Gelatinase-associated Lipocalin (NGAL) as a Marker of Acute Kidney Injury in Critically Ill Children with Septic Shock

PubMed Central

Wheeler, Derek S.; Devarajan, Prasad; Ma, Qing; Harmon, Kelli; Monaco, Marie; Cvijanovich, Natalie; Wong, Hector R.

2009-01-01

Objective To validate serum neutrophil gelatinase-associated lipocalin (NGAL) as an early biomarker for acute kidney injury (AKI) in critically ill children with septic shock. Design Observational cohort study. Setting 15 North American pediatric intensive care units (PICU). Patients A total of 143 critically ill children with SIRS or septic shock and 25 healthy controls. Interventions None. Measurements and Main Results Serum NGAL was measured during the first 24 hours of admission to the PICU. AKI was defined as a blood urea nitrogen (BUN) concentration > 100 mg/dL, serum creatinine > 2 mg/dL in the absence of pre-existing renal disease, or the need for dialysis. There was a significant difference in serum NGAL between healthy children (median 80 ng/mL, IQR 55.5-85.5 ng/mL), critically ill children with SIRS (median 107.5 ng/mL, IQR 89-178.5 ng/mL), and critically ill children with septic shock (median 302 ng/mL, IQR 151-570 ng/mL; p<0.001). AKI developed in 22 out of 143 (15.4%) critically ill children. Serum NGAL was significantly increased in critically ill children with AKI (median 355 ng/mL, IQR 166-1322 ng/mL) compared to those without AKI (median 186 ng/mL, IQR 98-365 ng/mL; p=0.009). Conclusions Serum NGAL is a highly sensitive, but nonspecific predictor of AKI in critically ill children with septic shock. Further validation of serum NGAL as a biomarker of AKI in this population is warranted. PMID:18379258

Serum neutrophil gelatinase-associated lipocalin (NGAL) as a marker of acute kidney injury in critically ill children with septic shock.

PubMed

Wheeler, Derek S; Devarajan, Prasad; Ma, Qing; Harmon, Kelli; Monaco, Marie; Cvijanovich, Natalie; Wong, Hector R

2008-04-01

To validate serum neutrophil gelatinase-associated lipocalin (NGAL) as an early biomarker for acute kidney injury in critically ill children with septic shock. Observational cohort study. Fifteen North American pediatric intensive care units (PICUs). A total of 143 critically ill children with systemic inflammatory response syndrome (SIRS) or septic shock and 25 healthy controls. None. Serum NGAL was measured during the first 24 hrs of admission to the PICU. Acute kidney injury was defined as a blood urea nitrogen concentration >100 mg/dL, serum creatinine >2 mg/dL in the absence of preexisting renal disease, or the need for dialysis. There was a significant difference in serum NGAL between healthy children (median 80 ng/mL, interquartile ratio [IQR] 55.5-85.5 ng/mL), critically ill children with SIRS (median 107.5 ng/mL, IQR 89-178.5 ng/mL), and critically ill children with septic shock (median 302 ng/mL, IQR 151-570 ng/mL; p < .001). Acute kidney injury developed in 22 of 143 (15.4%) critically ill children. Serum NGAL was significantly increased in critically ill children with acute kidney injury (median 355 ng/mL, IQR 166-1322 ng/mL) compared with those without acute kidney injury (median 186 ng/mL, IQR 98-365 ng/mL; p = .009). Serum NGAL is a highly sensitive but nonspecific predictor of acute kidney injury in critically ill children with septic shock. Further validation of serum NGAL as a biomarker of acute kidney injury in this population is warranted.

Accuracy of microscopic urine analysis and chest radiography in patients with severe sepsis and septic shock.

PubMed

Capp, Roberta; Chang, Yuchiao; Brown, David F M

2012-01-01

Diagnosis of source of infection in patients with septic shock and severe sepsis needs to be done rapidly and accurately to guide appropriate antibiotic therapy. The purpose of this study is to evaluate the accuracy of two diagnostic studies used in the emergency department (ED) to guide diagnosis of source of infection in this patient population. This was a retrospective review of ED patients admitted to an intensive care unit with the diagnosis of severe sepsis or septic shock over a 12-month period. We evaluated accuracy of initial microscopic urine analysis testing and chest radiography in the diagnosis of urinary tract infections and pneumonia, respectively. Of the 1400 patients admitted to intensive care units, 170 patients met criteria for severe sepsis and septic shock. There were a total of 47 patients diagnosed with urinary tract infection, and their initial microscopic urine analysis with counts>10 white blood cells were 80% sensitive (95% confidence interval [CI] .66-.90) and 66% specific (95% CI .52-.77) for the positive final urine culture result. There were 85 patients with final diagnosis of pneumonia. The sensitivity and specificity of initial chest radiography were, respectively, 58% (95% CI .46-.68) and 91% (95% CI .81-.95) for the diagnosis of pneumonia. In patients with severe sepsis and septic shock, the chest radiograph has low sensitivity of 58%, whereas urine analysis has a low specificity of 66%. Given the importance of appropriate antibiotic selection and optimal but not perfect test characteristics, this population may benefit from broad-spectrum antibiotics, rather than antibiotics tailored toward a particular source of infection. Published by Elsevier Inc.

Comparison of PIRO, SOFA, and MEDS scores for predicting mortality in emergency department patients with severe sepsis and septic shock.

PubMed

Macdonald, Stephen P J; Arendts, Glenn; Fatovich, Daniel M; Brown, Simon G A

2014-11-01

The Predisposition Insult Response and Organ failure (PIRO) scoring system has been developed for use in the emergency department (ED) to risk stratify sepsis cases, but has not been well studied among high-risk patients with severe sepsis and septic shock. The PIRO score was compared with the Sequential Organ Failure Assessment (SOFA) and Mortality in ED Sepsis (MEDS) scores to predict mortality in ED patients with features suggesting severe sepsis or septic shock in the ED. This was an analysis of sepsis patients enrolled in a prospective observational ED study of patients presenting with evidence of shock, hypoxemia, or other organ failure. PIRO, MEDS, and SOFA scores were calculated from ED data. Analysis compared areas under the receiver operator characteristic (ROC) curves for 30-day mortality. Of 240 enrolled patients, final diagnoses were septic shock in 128 (53%), severe sepsis without shock in 70 (29%), and infection with no organ dysfunction in 42 (18%). Forty-eight (20%) patients died within 30 days of presentation. Area under the ROC curve (AUC) for mortality was 0.86 (95% confidence interval [CI] = 0.80 to 0.92) for PIRO, 0.81 (95% CI = 0.74 to 0.88) for MEDS, and 0.78 (95% CI = 0.71 to 0.87) for SOFA scores. Pairwise comparisons of the AUC were as follows: PIRO versus SOFA, p = 0.01; PIRO versus MEDS, p = 0.064; and MEDS versus SOFA; p = 0.37. Mortality increased with increasing PIRO scores: PIRO < 5, 0%; PIRO 5 to 9, 5%; PIRO 10 to 14, 5%; PIRO 15 to 19, 37%; and PIRO ≥ 20, 80% (p < 0.001). The MEDS score also showed increasing mortality with higher scores: MEDS < 5, 0%; MEDS 5 to 7, 12%; MEDS 8 to 11, 15%; MEDS 12 to 14, 48%; and MEDS > 15, 65% (p < 0.001). The PIRO model, taking into account comorbidities and septic source as well as physiologic status, performed better than the SOFA score and similarly to the MEDS score for predicting mortality in ED patients with severe sepsis and septic shock. These findings have implications for identifying and managing high-risk patients and for the design of clinical trials in sepsis. © 2014 by the Society for Academic Emergency Medicine.

Prognosis of patients excluded by the definition of septic shock based on their lactate levels after initial fluid resuscitation: a prospective multi-center observational study.

PubMed

Ko, Byuk Sung; Kim, Kyuseok; Choi, Sung-Hyuk; Kang, Gu Hyun; Shin, Tae Gun; Jo, You Hwan; Ryoo, Seung Mok; Beom, Jin Ho; Kwon, Woon Yong; Han, Kap Su; Choi, Han Sung; Chung, Sung Phil; Suh, Gil Joon; Lim, Tae Ho; Kim, Won Young

2018-02-24

Septic shock can be defined both by the presence of hyperlactatemia and need of vasopressors. Lactate levels should be measured after volume resuscitation (as per the Sepsis-3 definition). However, currently, no studies have evaluated patients who have been excluded by the new criteria for septic shock. The aim of this study was to determine the clinical characteristics and prognosis of these patients, based on their lactate levels after initial fluid resuscitation. This observational study was performed using a prospective, multi-center registry of septic shock, with the participation of 10 hospitals in the Korean Shock Society, between October 2015 and February 2017. We compared the 28-day mortality between patients who were excluded from the new definition (defined as lactate level <2 mmol/L after volume resuscitation) and those who were not (≥2 mmol/L after volume resuscitation), from among a cohort of patients with refractory hypotension, and requiring the use of vasopressors. Other outcome variables such as in-hospital mortality, intensive care unit (ICU) stay (days), Sequential Organ Failure Assessment (SOFA) scores and Acute Physiology and Chronic Health Evaluation (APACHE) II scores were also analyzed. Of 567 patients with refractory hypotension, requiring the use of vasopressors, 435 had elevated lactate levels, while 83 did not have elevated lactate levels (either initially or after volume resuscitation), and 49 (8.2%) had elevated lactate levels initially, which normalized after fluid resuscitation. Thus, these 49 patients were excluded by the new definition of septic shock. These patients, in whom perfusion was restored, demonstrated significantly lower age, platelet count, and initial and subsequent lactate levels (all p < 0.01). Similarly, significantly lower 28-day mortality was observed in these patients than in those who had not been excluded (8.2% vs 25.5%, p = 0.02). In-hospital mortality and the maximum SOFA score were also significantly lower in the excluded patients group (p = 0.03, both). It seems reasonable for septic shock to be defined by the lactate levels after volume resuscitation. However, owing to the small number of patients in whom lactate levels were improved, further study is warranted.

Early reversible acute kidney injury is associated with improved survival in septic shock.

PubMed

Sood, Manish M; Shafer, Leigh Anne; Ho, Julie; Reslerova, Martina; Martinka, Greg; Keenan, Sean; Dial, Sandra; Wood, Gordon; Rigatto, Claudio; Kumar, Anand

2014-10-01

The fact that acute kidney injury (AKI) is associated with worse clinical outcomes forms the basis of most AKI prognostic scoring systems. However, early reversibility of renal dysfunction in acute illness is not considered in such systems. We sought to determine whether early (≤24 hours after shock documentation) reversibility of AKI was independently associated with in-hospital mortality in septic shock. Patient information was derived from an international database of septic shock cases from 28 different institutions in Canada, the United States and Saudi Arabia. Data from a final cohort of 5443 patients admitted with septic shock between Jan 1996 and Dec 2009 was analyzed. The following 4 definitions were used in regards to AKI status: (1) reversible AKI = AKI of any RIFLE severity prevalent at shock diagnosis or incident at 6 hours post-diagnosis that reverses by 24 hours, (2) persistent AKI = AKI prevalent at shock diagnosis and persisting during the entire 24 hours post-shock diagnosis, (3) new AKI = AKI incident between 6 and 24 hours post-shock diagnosis, and (4) improved AKI = AKI prevalent at shock diagnosis or incident at 6 hours post followed by improvement of AKI severity across at least one RIFLE category over the first 24 hours. Cox proportional hazards were used to determine the association between AKI status and in-hospital mortality. During the first 24 hours, reversible AKI occurred in 13.0%, persistent AKI in 54.9%, new AKI in 11.7%, and no AKI in 22.4%. In adjusted analyses, reversible AKI was associated with improved survival (HR, 0.64; 95% CI, 0.53-0.77) compared to no AKI (referent), persistent AKI (HR, 0.99; 95% CI, 0.88-1.11), and new AKI (HR, 1.41; 95% CI, 1.22-1.62). Improved AKI occurred in 19.1% with improvement across any RIFLE category associated with a significant decrease in mortality (HR, 0.53; 95% CI, 0.45-0.63). More rapid antimicrobial administration, lower Acute Physiology and Chronic Health Evaluation II score, lower age, and a smaller number of failed organs (excluding renal) on the day of shock as well as community-acquired infection were independently associated with reversible AKI. In septic shock, reversible AKI within the first 24 hours of admission confers a survival benefit compared to no, new, or persistent AKI. Prognostic AKI classification schemes should consider integration of early AKI reversibility into the scoring system. Copyright © 2014 Elsevier Inc. All rights reserved.

Risk factors for mortality in liver transplant recipients with ESKAPE infection.

PubMed

Song, S H; Li, X X; Wan, Q Q; Ye, Q F

2014-12-01

Although infections caused by the pathogens Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter spp (ESKAPE) have recently been identified as serious emerging problems in solid organ transplant, no information in liver transplant (LT) recipients is available. We sought to investigate the risk factors for associated mortality in LT recipients with ESKAPE infections. A retrospective analysis of infection after LT was reviewed. Risk factors for mortality caused by ESKAPE infection were identified. Fifty-three episodes of infections caused by ESKAPE were documented in 51 LT recipients. The main sites of infection were the bloodstream (49.0%), the lungs (33.3%), and the intra-abdominal/biliary tract (17.6%). The risk factors for mortality independently associated with ESKAPE infection were female sex (odds ratio [OR] = 6.6, 95% confidence interval [CI] = 1.1-40.8, P = .042), septic shock (OR = 30.1, 95% CI = 3.7-244.8, P = .001), and lymphocyte counts <300/mm(3) (OR = 20.2, 95% CI = 2.9-142.2, P = .003). To improve the results of LT, more effective therapeutic treatments are of paramount importance when female LT recipients with ESKAPE infection present with septic shock and decreased lymphocyte counts. Copyright © 2014 Elsevier Inc. All rights reserved.

Drotrecogin alfa (activated) in adults with septic shock.

PubMed

Ranieri, V Marco; Thompson, B Taylor; Barie, Philip S; Dhainaut, Jean-François; Douglas, Ivor S; Finfer, Simon; Gårdlund, Bengt; Marshall, John C; Rhodes, Andrew; Artigas, Antonio; Payen, Didier; Tenhunen, Jyrki; Al-Khalidi, Hussein R; Thompson, Vivian; Janes, Jonathan; Macias, William L; Vangerow, Burkhard; Williams, Mark D

2012-05-31

There have been conflicting reports on the efficacy of recombinant human activated protein C, or drotrecogin alfa (activated) (DrotAA), for the treatment of patients with septic shock. In this randomized, double-blind, placebo-controlled, multicenter trial, we assigned 1697 patients with infection, systemic inflammation, and shock who were receiving fluids and vasopressors above a threshold dose for 4 hours to receive either DrotAA (at a dose of 24 μg per kilogram of body weight per hour) or placebo for 96 hours. The primary outcome was death from any cause 28 days after randomization. At 28 days, 223 of 846 patients (26.4%) in the DrotAA group and 202 of 834 (24.2%) in the placebo group had died (relative risk in the DrotAA group, 1.09; 95% confidence interval [CI], 0.92 to 1.28; P=0.31). At 90 days, 287 of 842 patients (34.1%) in the DrotAA group and 269 of 822 (32.7%) in the placebo group had died (relative risk, 1.04; 95% CI, 0.90 to 1.19; P=0.56). Among patients with severe protein C deficiency at baseline, 98 of 342 (28.7%) in the DrotAA group had died at 28 days, as compared with 102 of 331 (30.8%) in the placebo group (risk ratio, 0.93; 95% CI, 0.74 to 1.17; P=0.54). Similarly, rates of death at 28 and 90 days were not significantly different in other predefined subgroups, including patients at increased risk for death. Serious bleeding during the treatment period occurred in 10 patients in the DrotAA group and 8 in the placebo group (P=0.81). DrotAA did not significantly reduce mortality at 28 or 90 days, as compared with placebo, in patients with septic shock. (Funded by Eli Lilly; PROWESS-SHOCK ClinicalTrials.gov number, NCT00604214.).

Lactate clearance cut off for early mortality prediction in adult sepsis and septic shock patients

NASA Astrophysics Data System (ADS)

Sinto, R.; Widodo, D.; Pohan, H. T.

2018-03-01

Previous lactate clearance cut off for early mortality prediction in sepsis and septic shock patient was determined by consensus from small sample size-study. We investigated the best lactate clearance cut off and its ability to predict early mortality in sepsis and septic shock patients. This cohort study was conducted in Intensive Care Unit of CiptoMangunkusumo Hospital in 2013. Patients’ lactate clearance and eight other resuscitationendpoints were recorded, and theoutcome was observed during the first 120 hours. The clearance cut off was determined using receiver operating characteristic (ROC) analysis, and its ability was investigated with Cox’s proportional hazard regression analysis using other resuscitation endpoints as confounders. Total of 268 subjects was included, of whom 70 (26.11%) subjects died within the first 120 hours. The area under ROC of lactate clearance to predict early mortality was 0.78 (95% % confidence interval [CI] 0.71-0.84) with best cut off was <7.5% (sensitivity and specificity 88.99% and 81.4% respectively). Compared with group achieving lactate clearance target, group not achieving lactate clearance target had to increase early mortality risk (adjusted hazard ratio 13.42; 95%CI 7.19-25.07). In conclusion, the best lactate clearance cut off as anearly mortality predictor in sepsis and septic shock patients is 7.5%.

Glucocorticoid Receptor Polymorphisms and Outcomes in Pediatric Septic Shock.

PubMed

Cvijanovich, Natalie Z; Anas, Nick; Allen, Geoffrey L; Thomas, Neal J; Bigham, Michael T; Weiss, Scott L; Fitzgerald, Julie; Checchia, Paul A; Meyer, Keith; Quasney, Michael; Gedeit, Rainer; Freishtat, Robert J; Nowak, Jeffrey; Raj, Shekhar S; Gertz, Shira; Grunwell, Jocelyn R; Opoka, Amy; Wong, Hector R

2017-04-01

Polymorphisms of the glucocorticoid receptor gene are associated with outcome and corticosteroid responsiveness among patients with inflammatory disorders. We conducted a candidate gene association study to test the hypothesis that these polymorphisms are associated with outcome and corticosteroid responsiveness among children with septic shock. We genotyped 482 children with septic shock for the presence of two glucocorticoid receptor polymorphisms (rs56149945 and rs41423247) associated with increased sensitivity and one glucocorticoid receptor polymorphism (rs6198) associated with decreased sensitivity to corticosteroids. The primary outcome variable was complicated course, defined as 28-day mortality or the persistence of two or more organ failures 7 days after a septic shock diagnosis. We used logistic regression to test for an association between corticosteroid exposure and outcome, within genotype group, and adjusted for illness severity. Multiple PICUs in the United States. Standard care. There were no differences in outcome when comparing the various genotype groups. Among patients homozygous for the wild-type glucocorticoid receptor allele, corticosteroids were independently associated with increased odds of complicated course (odds ratio, 2.30; 95% CI, 1.01-5.21; p = 0.047). Based on these glucocorticoid receptor polymorphisms, we could not detect a beneficial effect of corticosteroids among any genotype group. Among children homozygous for the wild-type allele, corticosteroids were independently associated with increased odds of poor outcome.

The impact of endocrine supplementation on adverse events in septic shock.

PubMed

Bissell, Brittany D; Erdman, Michael J; Smotherman, Carmen; Kraemer, Dale F; Ferreira, Jason A

2015-12-01

The objective of this study was to compare the incidence of severe adverse events of vasopressin vs hydrocortisone for endocrine support therapy in patients with septic shock. This was a retrospective, propensity-matched cohort of patients admitted to the medical intensive care unit with septic shock between February 2012 and February 2015. Patients were included if vasopressin or hydrocortisone was administered for hemodynamic support secondary to norepinephrine. In the unmatched cohort of 124 patients, vasopressin was associated with a significant decrease in the number of severe adverse events (P=.03). In the matched cohort, severe adverse events occurred 3 times as often in patients receiving hydrocortisone; however, this difference was not statistically significant. (odds ratio, 3.33; 95% confidence interval, 0.92-12.11; P=.06). In the matched cohort, vasopressin was associated with a faster time to hemodynamic stability (P<.05) and discontinuation of hemodynamic support (P<.01) with an increased requirement for third-line therapy (P<.01). No statistical differences were seen in length of stay (intensive care unit and hospital), length of mechanical ventilation, and in-hospital mortality. Given the lower incidence of adverse events and faster time to hemodynamic stability, vasopressin appears to be the most advantageous endocrine agent for hemodynamic support in septic shock. Copyright © 2015 Elsevier Inc. All rights reserved.

Thiamine in septic shock patients with alcohol use disorders: An observational pilot study.

PubMed

Holmberg, Mathias Johan; Moskowitz, Ari; Patel, Parth Vijay; Grossestreuer, Anne Victoria; Uber, Amy; Stankovic, Nikola; Andersen, Lars Wiuff; Donnino, Michael William

2018-02-01

Alcohol-use disorders (AUDs) have been associated with increased sepsis-related mortality. As patients with AUDs are often thiamine deficient, we investigated practice patterns relating to thiamine administration in patients with AUDs presenting with septic shock and explored the association between receipt of thiamine and mortality. We performed a retrospective cohort study of patients presenting with septic shock between 2008 and 2014 at a single tertiary care center. We identified patients with an AUD diagnosis, orders for microbial cultures and use of antibiotics, vasopressor dependency, and lactate levels≥4mmol/L. We excluded those who received thiamine later than 48h of sepsis onset. We included 53 patients. Thirty-four (64%) patients received thiamine. Five patients (15%) received their first thiamine dose in the emergency department. The median time to thiamine administration was 9 (quartiles: 4, 18) hours. The first thiamine dose was most often given parenterally (68%) and for 100mg (88%). In those receiving thiamine, 15/34 (44%) died, compared to 15/19 (79%) of those not receiving thiamine, p=0.02. A considerable proportion of patients with AUDs admitted for septic shock do not receive thiamine. Thiamine administration in this patient population was associated with decreased mortality. Copyright © 2017 Elsevier Inc. All rights reserved.

Decreased levels of alpha-1-acid glycoprotein are related to the mortality of septic patients in the emergency department.

PubMed

Barroso-Sousa, Romualdo; Lobo, Romulo R; Mendonça, Patricia R; Memória, Renan R; Spiller, Fernando; Cunha, Fernando Q; Pazin-Filho, Antonio

2013-01-01

To determine the validity of alpha-1-acid glycoprotein as a novel biomarker for mortality in patients with severe sepsis. We prospectively included patients with severe sepsis or septic shock at the emergency department at a single tertiary referral teaching hospital. All of the patients were enrolled within the first 24 hours of emergency department admission, and clinical data and blood samples were obtained. As the primary outcome, we investigated the association of serum levels of alpha-1-acid glycoprotein and 96-hour mortality with logistic regression analysis and generalized estimating equations adjusted for age, sex, shock status and Acute Physiology and Chronic Health Evaluation II score. Patients with septic shock had lower alpha-1-acid glycoprotein levels at the time of emergency department admission compared to patients without shock (respectively, 149.1 ±42.7 vs. 189.8 ±68.6; p = 0.005). Similarly, non-survivors in the first 96 hours were also characterized by lower levels of alpha-1-acid glycoprotein at the time of emergency department admission compared to survivors (respectively, 132.18 ±50.2 vs. 179.8 ±61.4; p = 0.01). In an adjusted analysis, alpha-1-acid glycoprotein levels ≤120 mg/dL were significantly associated with 96-hour mortality (odds ratio = 14.37; 95% confidence interval = 1.58 to 130.21). Septic shock patients exhibited lower circulating alpha-1-acid glycoprotein levels than patients without shock. Alpha-1-acid glycoprotein levels were independently associated with 96-hour mortality in individuals with severe sepsis.

Fluid overload and kidney failure in children with severe sepsis and septic shock: A cohort study.

PubMed

Naveda Romero, Omar E; Naveda Meléndez, Andrea F

2017-04-01

In children with sepsis, fluid overload as a result of an aggressive fluid replacement or excessive fluid administration may result in kidney impairment and increased mortality. Objective. To determine the association between fluid overload and the rate of kidney failure in a group of children with severe sepsis and septic shock. This was a prospective cohort study conducted in the intensive care unit of Hospital Universitario de Pediatría “Dr. Agustín Zubillaga” (Barquisimeto, Lara State, Venezuela), between March 2013 and May 2016, in children with severe sepsis or septic shock. One hundred and forty-nine patients were included in the analysis. Sepsis predominated in 59.7% of cases; patients' average age was 6.4 ± 3.3 years old, their average weight was 17.8 ± 3.6 kg, 30.2% had fluid overload, and overall mortality was 25.5%. Kidney failure occurred in 16.1% of cases. A binary logistic regression model was used to identify fluid overload (odds ratio [OR]: 1.5; 95% confidence interval [CI]: 1.2-4.9, p = 0.028) and shock for more than 2 days (OR: 1.7; 95% CI: 1.3-6.3, p = 0.039) as independent predictors of kidney failure. In addition, a significant increase in the risk of mortality among children with kidney failure and fluid overload was observed as per the Kaplan-Meier method (p= 0.019). Fluid overload and shock for more than 2 days increase the risk for kidney failure in critically ill children with severe sepsis and septic shock.

[Appendiceal abscess in the third gestational trimester of pregnancy, complications pre and postoperatively].

PubMed

Cyrkowicz, A; Cibor, Z; Słowińska-Zabówka, M; Kisiel, W; Oleksy, P; Orczyk, K; Bajorek, M; Kwiek, G

1996-01-01

Delayed surgical intervention connected with misdiagnosis of preterm labour and urinary tract infection caused in gravida 3 in 34th gestational week appendiceal abscess, septic shock, stillbirth by cesarean section, necessity of hysterectomy, recidivism of multi peritoneal and pleural abscesses. Although the patient was rescued the retrospective pro memoria considerations of our procedure are regarded.

Capnocytophaga canimorsus Sepsis Following a Minor Dog Bite to the Finger: Case Report.

PubMed

Dedy, Nicolas J; Coghill, Sarah; Chandrashekar, Nanda Kumar S; Bindra, Randy R

2016-01-01

Capnocytophaga canimorsus is a gram-negative bacillus present in the oral cavities of 22% to 74% of healthy dogs. Capnocytophaga canimorsus has unique virulence factors that enable it to evade the human immune system and cause life-threatening sepsis following a dog bite. We report a previously well 68-year-old woman who presented with septic shock and multiorgan failure following a seemingly minor dog bite to the finger. The patient required intensive care treatment, intravenous antibiotic therapy, and multiple surgical procedures including amputation of the affected finger. The septicemia and coagulopathy that ensued resulted in gangrene and amputation of additional fingers and toes. The purpose of this report is to raise awareness of this organism among hand surgeons when faced with a patient presenting in septic shock and minimal signs at the site of a dog bite. Copyright © 2016 American Society for Surgery of the Hand. Published by Elsevier Inc. All rights reserved.

Successfully treated necrotizing fasciitis using extracorporeal life support combined with hemoadsorption device and continuous renal replacement therapy.

PubMed

Eid, Maroua; Fouquet, Olivier; Darreau, Cédric; Pierrot, Marc; Kouatchet, Achille; Mercat, Alain; Baufreton, Christophe

2018-03-01

Necrotizing fasciitis represents a life-threatening infectious condition that causes spreading necrotisis of superficial fascia and subcutaneous cellular tissues. We describe the case of a patient diagnosed with septic and toxic shocks leading to multiple organ failure successfully treated with a combination of extracorporeal life support, continuous renal replacement therapy, and a hemoadsorption device. A 41-year-old patient presented with necrotizing fasciitis and multi-organ failure. Initial extracorporeal life support therapy was implanted, compensating for systolic failure. Due to acute renal failure that persisted in time, continuous renal replacement therapy was added. Despite these treatments and as a last attempt to control the septic condition, a CytoSorb ® hemoadsorption device was installed in parallel to the extracorporeal life support circuit and two sessions were run. During the days following CytoSorb ® treatment, hemodynamic stabilization was observed, as well as normalization of lactic acidosis and blood parameters. This case describes the successful use of CytoSorb ® with continuous renal replacement therapy and extracorporeal life support in a combined way to overcome a critical phase of septic shock in a young adult patient. This combination of treatments turned out to be efficient for this patient in the context of necrotizing fasciitis.

Plasmapheresis in severe septic shock with disseminated intravascular coagulation.

PubMed

Zilow, E P; Selle, B; Zilow, G

1994-01-01

An 18-year-old female with CNS relapse of acute lymphoblastic leukemia after previous complete remission of the disease underwent chemotherapy. Due to the therapy she suffered from profound suppression of bone marrow with consecutive thrombocytopenia and leukopenia. Despite prophylactic treatment, severe septicemia occurred with septic shock, hemolysis and disseminated intravascular coagulation (DIC). As the clinical course became uncontrollable by means of conventional therapy, including broad-spectrum antibiotics, substitution of fresh frozen plasma, antithrombin III and heparin therapy, plasma exchange was used as a rescue therapy. This method succeeded in effective replacement of clotting factors and normalization of coagulation, in removal of fibrinogen degradation products and probably of toxins and shock mediators. The patient recovered from shock.

Pre-operative labs: Wasted dollars or predictors of post-operative cardiac and septic events in orthopaedic trauma patients?

PubMed

Lakomkin, Nikita; Sathiyakumar, Vasanth; Dodd, Ashley C; Jahangir, A Alex; Whiting, Paul S; Obremskey, William T; Sethi, Manish K

2016-06-01

As US healthcare expenditures continue to rise, there is significant pressure to reduce the cost of inpatient medical services. Studies have estimated that over 70% of routine labs may not yield clinical benefits while adding over $300 in costs per day for every inpatient. Although orthopaedic trauma patients tend to have longer inpatient stays and hip fractures have been associated with significant morbidity, there is a dearth of data examining pre-operative labs in predicting post-operative adverse events in these populations. The purpose of this study was to assess whether pre-operative labs significantly predict post-operative cardiac and septic complications in orthopaedic trauma and hip fracture patients. Between 2006 and 2013, 56,336 (15.6%) orthopaedic trauma patients were identified and 27,441 patients (7.6%) were diagnosed with hip fractures. Pre-operative labs included sodium, BUN, creatinine, albumin, bilirubin, SGOT, alkaline phosphatase, white count, hematocrit, platelet count, prothrombin time, INR, and partial thromboplastin time. For each of these labs, patients were deemed to have normal or abnormal values. Patients were noted to have developed cardiac or septic complications if they sustained (1) myocardial infarction (MI), (2) cardiac arrest, or (3) septic shock within 30 days after surgery. Separate regressions incorporating over 40 patient characteristics including age, gender, pre-operative comorbidities, and labs were performed for orthopaedic trauma patients in order to determine whether pre-operative labs predicted adverse cardiac or septic outcomes. 749 (1.3%) orthopaedic trauma patients developed cardiac complications and 311 (0.6%) developed septic shock. Multivariate regression demonstrated that abnormal pre-operative platelet values were significantly predictive of post-operative cardiac arrest (OR: 11.107, p=0.036), and abnormal bilirubin levels were predictive (OR: 8.487, p=0.008) of the development of septic shock in trauma patients. In the hip fracture cohort, abnormal partial thromboplastin time was significantly associated with post-operative myocardial infarction (OR: 15.083, p=0.046), and abnormal bilirubin (OR: 58.674, p=0.002) significantly predicted the onset of septic shock. This is the first study to demonstrate the utility of pre-operative labs in predicting perioperative cardiac and septic adverse events in orthopaedic trauma and hip fracture patients. Particular attention should be paid to haematologic/coagulation labs (platelets, PTT) and bilirubin values. Prognostic Level II. Copyright © 2016 Elsevier Ltd. All rights reserved.

Traumatic hemorrhage of occult phaeochromocytoma in a patient with septic shock

PubMed Central

Moazzam, Mohammad Shahnawaz; Ahmed, Syed Moied; Bano, Shahjahan

2010-01-01

Phaeochromocytoma can have a variety of presentations; however, traumatic hemorrhage into a phaeochromocytoma is a very rare presentation. Diagnosing and managing a critically ill, septic patient with a Phaeochromocytoma can be very challenging. We report a case of 53 years old man with a previously undiagnosed Phaeochromocytoma, who presented initially with bowel perforation following an assault. Following a laparotomy for bowel resection and anastomosis, whilst on the intensive care unit, he developed paroxysmal severe hypertension overlying septic shock. Phaeochromocytoma was confirmed using a computed tomography scan and urinary assay of metanephrine and catecholamines. We managed the haemodynamic instability using labetalol and noradrenaline infusions. As his septic state improved he was convention therapy and following control of his symptoms over the next few weeks, he underwent an uncomplicated right sided adrenalectomy. He made a full recovery. PMID:20930983

The New Sepsis Definitions: Implications for the Basic and Translational Research Communities.

PubMed

Coopersmith, Craig M; Deutschman, Clifford S

2017-03-01

New definitions of sepsis and septic shock were published in early 2016, updating old definitions that have not been revisited since 2001. These new definitions should profoundly affect sepsis research. In addition, these papers present clinical criteria for identifying infected patients who are highly likely to have or to develop sepsis or septic shock. In contrast to previous approaches, these new clinical criteria are evidence based. In this review, two of the authors of the new definitions detail the content of the papers and explore the implications for shock and sepsis researchers.

CE: Assessing Patients During Septic Shock Resuscitation.

PubMed

Bridges, Elizabeth

2017-10-01

: In 2015, the Surviving Sepsis Campaign six-hour bundle was updated. The revised version now recommends documenting the reassessment of volume status and tissue perfusion after initial fluid resuscitation through a repeated focused examination. This article addresses the practice and interpretation of two components of this examination in adults: capillary refill time and skin mottling score. It further discusses how to best integrate these noninvasive parameters into the care of patients undergoing resuscitation for septic shock.

[Septic shock due to infective endocarditis of stimulation system of implantable cardioverter-defibrillator].

PubMed

Porubčinová, I; Porubčin, S; Stančák, B; Beňa, M; Sabol, F

2012-01-01

We present a case of a 60-year old patient hospitalized at the Department of Infectious Diseases and Travel Medicine, Medical faculty of UPJS and L. Pasteurs University Hospital in Kosice with suspected gastroenteritis. The patient was admitted to an intensive care unit because of the signs of septic shock. Within one hour from admission, the patient was administered early goal directed therapy for septic shock. Subsequently, infectious endocarditis of stimulation electrodes and tricuspid valve was identified as the origin of the infection. The stimulation system was then explanted from a stabilized and afebrile patient at the Department of cardiac Surgery of Eastern Slovak Institute of Cardiac and Vascular Diseases in Kosice. This case should emphasise frequently atypical course of this serious disease and the need for early identification of severe sepsis to enable timely management to affect mortality.

Pylephlebitis and Crohn's disease: A rare case of septic shock.

PubMed

Scaringi, Stefano; Giudici, Francesco; Gabbani, Giacomo; Zambonin, Daniela; Morelli, Marco; Carrà, Rossella; Bechi, Paolo

2017-01-01

Troncular pylephlebitis, defined as septic thrombophlebitis of the portal vein, is usually secondary to suppurative infection from the regions drained by the portal system. Therefore, pylephlebitis can occur from the portal vein main tributaries. The occurrence of mesenteric pylephlebitis in Crohn's disease is extremely rare. We describe a case of septic shock due to mesenteric pylephlebitis in a 47 years old male affected with Crohn's disease. The patient was admitted to the emergency department after he had been complained from 3h of a peri-umbilical abdominal pain associated to fever and shivering quickly followed by a severe hypotension. His medical history included histologically confirmed ileal Crohn's disease diagnosed 4 years before and treated with mesalamine only. Computed tomography scan confirmed the mesenteric pylephlebitis diagnosis. After medical therapy with antibiotics and systemic nutrition, the patient was successfully operated to treat his ileal Crohn's disease. In our case, the quick onset of a septic shock was not due to a peritonitis complicating a Crohn's disease, but to a rare condition not needing an urgent surgical resolution. This report shows that, even in Crohn's disease, once diagnosis is performed, antibiotic therapy associated to enteral and parenteral nutrition can lead to a complete clinical remission of mesenteric pylephlebitis, mandatory to perform an elective surgery. This case highlights the importance of promptly considerate and treat mesenteric pylephlebitis in presence of a septic shock in a Crohn's disease patient who is not showing clinical signs of peritonitis. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

Inactivation of catecholamines by superoxide gives new insights on the pathogenesis of septic shock

PubMed Central

Macarthur, Heather; Westfall, Thomas C.; Riley, Dennis P.; Misko, Thomas P.; Salvemini, Daniela

2000-01-01

A major feature of septic shock is the development of a vascular crisis characterized by nonresponsiveness to sympathetic vasoconstrictor agents and the subsequent irreversible fall in blood pressure. In addition, sepsis, like other inflammatory conditions, results in a large increase in the production of free radicals, including superoxide anions (O2⨪) within the body. Here we show that O2⨪ reacts with catecholamines deactivating them in vitro. Moreover, this deactivation would appear to account for the hyporeactivity to exogenous catecholamines observed in sepsis, because administration of a superoxide dismutase (SOD) mimetic to a rat model of septic shock to remove excess O2⨪ restored the vasopressor responses to norepinephrine. This treatment with the SOD mimetic also reversed the hypotension in these animals; suggesting that deactivation of endogenous norepinephrine by O2⨪ contributes significantly to this aspect of the vascular crisis. Indeed, the plasma concentrations of both norepinephrine and epinephrine in septic rats treated with the SOD mimetic were significantly higher than in untreated rats. Interestingly, the plasma concentrations for norepinephrine and epinephrine were inversely related to the plasma concentrations of adrenochromes, the product of the autoxidation of catecholamines initiated by O2⨪. We propose, therefore, that the use of a SOD mimetic represents a new paradigm for the treatment of septic shock. By removing O2⨪, exogenous and endogenous catecholamines are protected from autoxidation. As a result, both hyporeactivity and hypotension are reversed, generation of potentially toxic adrenochromes is reduced, and survival rate is improved. PMID:10944234

Management and outcomes of severe dengue patients presenting with sepsis in a tropical country.

PubMed

Teparrukkul, Prapit; Hantrakun, Viriya; Day, Nicholas P J; West, T Eoin; Limmathurotsakul, Direk

2017-01-01

Dengue is a common cause of infection in adults in tropical countries. Sepsis is a syndrome of systemic manifestations induced by infection of any organisms; including bacterial, fungal and viral agents. Here, we investigated the diagnosis, management and outcomes of dengue patients presenting with sepsis in a prospective study of community-acquired sepsis in Thailand. From June to December 2015, 874 adult patients (age≥18 years) with suspected or documented community-acquired infection, with ≥3 diagnostic criteria for sepsis according to the Surviving Sepsis Campaign 2012, and within 24 hours of admission were evaluated. Serum was stored and later tested for dengue PCR assays. A total of 126 patients had dengue PCR assays positive (2 DENV-1, 12 DENV-2, 24 DENV-3 and 88 DENV-4), and 5 of them (4%) died. We found that attending physicians suspected dengue infection on admission in 84 patients (67%), and recorded dengue infection as the final diagnosis in 96 patients (76%). Four of five fatal cases were diagnosed and treated as septic shock not due to dengue. In multivariable analysis, there was a trend showing that age≥60 years, hypoxemia and misdiagnosis of dengue by attending physicians were associated with 28-day mortality. A number of adult patients who died of dengue are misdiagnosed as severe sepsis and septic shock. Diagnosis of dengue based on clinical features alone is difficult. Rapid diagnostic tests for dengue may need to be routinely used in adult patients presenting with sepsis and septic shock in tropical countries. This approach could improve diagnosis and management of those patients.

Factors influencing antimicrobial resistance and outcome of Gram-negative bloodstream infections in children.

PubMed

Ivády, Balázs; Kenesei, Éva; Tóth-Heyn, Péter; Kertész, Gabriella; Tárkányi, Klára; Kassa, Csaba; Ujhelyi, Enikő; Mikos, Borbála; Sápi, Erzsébet; Varga-Heier, Krisztina; Guóth, Gábor; Szabó, Dóra

2016-06-01

The aim of this study was to collect data about pediatric Gram-negative bloodstream infections (BSI) to determine the factors that influence multidrug resistance (MDR), clinical course and outcome of children affected by Gram-negative sepsis. In this observational, prospective, multicenter study we collected cases of pediatric Gram-negative BSI during a 2-year period. We analyzed epidemiological, microbiological and clinical factors that associated with acquisition of MDR infections and outcome. One-hundred and thirty-five BSI episodes were analyzed. Median age of children was 0.5 years (IQR 0.1-6.17, range 0-17 years). Predominant bacteria were Enterobacteriaceae (68.3 %), and Pseudomonas spp. (17.9 %). Multidrug resistance was detected in 45/134 cases (33.6 %), with the highest rates in Escherichia coli, Enterobacter and Pseudomonas spp. Acquisition of MDR pathogens was significantly associated with prior cephalosporin treatment, older age, admission to hemato-oncology unit, polymicrobial infections, higher rate of development of septic shock, and multiple organ failures. All-cause mortality was 17.9 %. Presence of septic shock at presentation and parenteral nutrition were associated with higher mortality. Pseudomonas spp., and Enterobacter spp. BSIs had the highest rate of mortality. Inappropriate empiric antibiotic therapy was more frequent in MDR patients, although not significantly associated with poor outcome. Rates of multidrug resistance and mortality in children with Gram-negative bloodstream infections remain high in our settings. Empiric broad-spectrum antibiotics and combination therapy could be recommended, especially in children with malignant diseases, patients admitted to the PICU, and for cases with septic shock, who have higher mortality risk.

Toxic shock syndrome due to community-acquired methicillin-resistant Staphylococcus aureus infection: Two case reports and a literature review in Japan.

PubMed

Sada, Ryuichi; Fukuda, Saori; Ishimaru, Hiroyasu

2017-01-01

Community-acquired methicillin-resistant Staphylococcus aureus has been spreading worldwide, including in Japan. However, few cases of toxic shock syndrome caused by Community-acquired methicillin-resistant Staphylococcus aureus have been reported in Japan. We report 2 cases, in middle-aged women, of toxic shock syndrome due to Community-acquired methicillin-resistant Staphylococcus aureus via a vaginal portal of entry. The first patient had used a tampon and the second patient had vaginitis due to a cleft narrowing associated with vulvar lichen sclerosus. Both patients were admitted to our hospital with septic shock and severe acute kidney injury and subsequently recovered with appropriate antibiotic treatment. In our review of the literature, 8 cases of toxic shock syndrome caused by Community-acquired methicillin-resistant Staphylococcus aureus were reported in Japan. In these 8 cases, the main portals of entry were the skin and respiratory tract; however, the portal of entry of Community-acquired methicillin-resistant Staphylococcus aureus from a vaginal lesion has not been reported in Japan previously.

Decreased levels of alpha-1-acid glycoprotein are related to the mortality of septic patients in the emergency department

PubMed Central

Barroso-Sousa, Romualdo; Lobo, Romulo R.; Mendonça, Patricia R.; Memória, Renan R.; Spiller, Fernando; Cunha, Fernando Q.; Pazin-Filho, Antonio

2013-01-01

OBJECTIVE: To determine the validity of alpha-1-acid glycoprotein as a novel biomarker for mortality in patients with severe sepsis. METHODS: We prospectively included patients with severe sepsis or septic shock at the emergency department at a single tertiary referral teaching hospital. All of the patients were enrolled within the first 24 hours of emergency department admission, and clinical data and blood samples were obtained. As the primary outcome, we investigated the association of serum levels of alpha-1-acid glycoprotein and 96-hour mortality with logistic regression analysis and generalized estimating equations adjusted for age, sex, shock status and Acute Physiology and Chronic Health Evaluation II score. RESULTS: Patients with septic shock had lower alpha-1-acid glycoprotein levels at the time of emergency department admission compared to patients without shock (respectively, 149.1±42.7 vs. 189.8±68.6; p = 0.005). Similarly, non-survivors in the first 96 hours were also characterized by lower levels of alpha-1-acid glycoprotein at the time of emergency department admission compared to survivors (respectively, 132.18±50.2 vs. 179.8±61.4; p = 0.01). In an adjusted analysis, alpha-1-acid glycoprotein levels ≤120 mg/dL were significantly associated with 96-hour mortality (odds ratio = 14.37; 95% confidence interval = 1.58 to 130.21). CONCLUSION: Septic shock patients exhibited lower circulating alpha-1-acid glycoprotein levels than patients without shock. Alpha-1-acid glycoprotein levels were independently associated with 96-hour mortality in individuals with severe sepsis. PMID:24037010

Dispatch and prehospital transport for acute septic patients: an observational study.

PubMed

Pedersen, Peter Bank; Henriksen, Daniel Pilsgaard; Mikkelsen, Søren; Lassen, Annmarie Touborg

2017-05-12

In order to dispatch ambulances with the correct level of urgency, the dispatch center has to balance the perceived urgency and traffic safety considerations with the available resources. As urgency is not clear in all clinical situations, some high urgency patients may end up with a suboptimal mode of transport. Patients with severe sepsis or septic shock suffer from highly time dependent conditions but they present with a wide range of symptoms, which might be difficult to identify in the dispatch system. The aim of the study is to investigate the modes of prehospital transport among acute admitted patients with sepsis, severe sepsis and septic shock. We included all adult patients (≥15 years) presenting to an acute medical unit at Odense University Hospital with a first-time admission of community-acquired sepsis between September 2010-August 2011. Cases and prehospital ambulance transport were identified by structured manual chart review. In all cases it was registered, whether the ordinary ambulance was assisted by the mobile emergency care unit (MECU), manned by anesthesiologists. We included 1,713 patients median age 72 years (IQR 57-81), 793 (46.3%) male, 621 (36.3%) had sepsis, 1,071 (62.5%) severe sepsis, and 21 (1.2%) septic shock. In the group of sepsis patients, 390 (62.8%) arrived without public prehospital transport, 197 (31.7%) were transported by ambulance, and 34 (5.5%) were assisted by MECU. In the group of severe sepsis patients, the same percentage 62.8% arrived without public pre-hospital transport, a lower percentage 28.2% were transported by ambulance, and a larger percentage 9.0% were transported by MECU. Among 21 patients with septic shock, 10 arrived without public pre-hospital transport (47.7%), 7 (33.3%) were transported by ambulance, and 4 (19.0%) by MECU. The 30-day mortality hazard ratio was associated with mode of transport, with the adjusted highest hazard ratio found in the group of MECU transported patients 1.76 (95%Cl 1.16-2.66). A substantial proportion of patients with severe sepsis and septic shock arrive to hospital without public prehospital transport or by unspecialized ambulances.

Hepatic blood flow measurement III. Total hepatic blood flow measured by ICG clearance and electromagnetic flowmeters in a canine septic shock model.

PubMed Central

Nxumalo, J L; Teranaka, M; Schenk, W G

1978-01-01

The validity of the ICG clearance method for the measurement of THBF in abnormal circulatory states remains questionable. In this study THBF measured by this method is compared with the electromagnetic flow technique in a canine spetic model. Good correlation is demonstrated between the two in normal control animals. However, in the septic animals the ICG underestimated the electromagnetic flow result by 20%. This is true in both the high and the low cardiac output septic shock pictures that emerge. In the septic animals, the total hepatic blood flow as measured by the ICG was almost equal to the portal vein flow alone measured by the electromagnetic flowmeters suggesting that this was the quantity it was measuring in this abnormal state. Pathophysiologic mechanisms that may explain the discrepancy are given. PMID:637587

Comparative analysis of survival between elderly and non-elderly severe sepsis and septic shock resuscitated patients

PubMed Central

Palomba, Henrique; Corrêa, Thiago Domingos; Silva, Eliézer; Pardini, Andreia; de Assuncao, Murillo Santucci Cesar

2015-01-01

Objective To compare outcomes between elderly (≥65 years old) and non-elderly (<65 years old) resuscitated severe sepsis and septic shock patients and determine predictors of death among elderly patients. Methods Retrospective cohort study including 848 severe sepsis and septic shock patients admitted to the intensive care unit between January 2006 and March 2012. Results Elderly patients accounted for 62.6% (531/848) and non-elderly patients for 37.4% (317/848). Elderly patients had a higher APACHE II score [22 (18-28) versus 19 (15-24); p<0.001], compared to non-elderly patients, although the number of organ dysfunctions did not differ between the groups. No significant differences were found in 28-day and in-hospital mortality rates between elderly and non-elderly patients. The length of hospital stay was higher in elderly compared to non-elderly patients admitted with severe sepsis and septic shock [18 (10-41) versus 14 (8-29) days, respectively; p=0.0001]. Predictors of death among elderly patients included age, site of diagnosis, APACHE II score, need for mechanical ventilation and vasopressors. Conclusion In this study population early resuscitation of elderly patients was not associated with increased in-hospital mortality. Prospective studies addressing the long-term impact on functional status and quality of life are necessary. PMID:26313436

Rethinking the concept of sepsis and septic shock.

PubMed

A Cabrita, Joana; Pinheiro, Isabel; Menezes Falcão, L

2018-06-16

Sepsis is a major global health problem and represents a challenge for physicians all over the world. The knowledge of sepsis and septic shock is a topic of interest among the scientific community and society in general. New guidelines for management of sepsis and septic shock were developed in 2016, providing an update on this area. In Sepsis-3 new definitions for sepsis and septic shock were published. The purpose of this narrative review is to discuss and compare the new criteria of 2016 with the old criteria, purposing at the same time an alternative approach for this topic. SOFA criteria (Sequential Organ Failure Assessment Score) are more complete, but too extensive and usually difficult to apply outside the intensive care units, therefore inducing potentially delay in the proper treatment. We purpose combined criteria for the selection of sepsis patients. Initially, we could apply qSOFA (quick Sepsis Related Organ Failure Assessment) criteria, due to its easy application, associated with the SIRS (systemic inflammatory response syndrome) criteria, allowing to select the patients who are infected and need faster treatment. In that way we would use the best of old and newest criteria, allowing the early selection of patients who are infected and require faster treatment, while the search for a better and faster tool continues. Copyright © 2018 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.

Management of septic shock and severe infections in migrants and returning travelers requiring critical care.

PubMed

Alp, E; Erdem, H; Rello, J

2016-04-01

During the past decade, global human movement created a virtually "borderless world". Consequently, the developed world is facing "forgotten" and now imported infectious diseases. Many infections are observed upon travel and migration, and the clinical spectrum is diverse, ranging from asymptomatic infection to severe septic shock. The severity of infection depends on the etiology and timeliness of diagnosis. While assessing the etiology of severe infection in travelers and migrants, it is important to acquire a detailed clinical history; geography, dates of travel, places visited, type of transportation, lay-overs and intermediate stops, potential exposure to exotic diseases, and activities that were undertaken during travelling and prophylaxis and vaccines either taken or not before travel are all important parameters. Tuberculosis, malaria, pneumonia, visceral leishmaniasis, enteric fever and hemorrhagic fever are the most common etiologies in severely infected travelers and migrants. The management of severe sepsis and septic shock in migrants and returning travelers requires a systematic approach in the evaluation of these patients based on travel history. Early and broad-spectrum therapy is recommended for the management of septic shock comprising broad spectrum antibiotics, source control, fluid therapy and hemodynamic support, corticosteroids, tight glycemic control, and organ support and monitoring. We here review the diagnostic and therapeutic routing of severely ill travelers and migrants, stratified by the nature of the infectious agents most often encountered among them.

First successful combination of ECMO with cytokine removal therapy in cardiogenic septic shock: a case report.

PubMed

Bruenger, Frank; Kizner, Lukasz; Weile, Jan; Morshuis, Michael; Gummert, Jan F

2015-02-01

A new hemoadsorption device intended as adjunctive treatment for patients with elevated cytokine levels in the setting of SIRS and sepsis has shown promising results. We report on the beneficial application of the device in a patient with cardiogenic septic shock receiving combined extracorporeal life support with rECMO, LVAD, and CVVH despite his highly septic condition. A 39-year-old patient presented with fulminant ARDS and cardiogenic septic shock. A veno-arterial ECMO was implanted for circulatory support. During the course of illness, the patient developed acute renal failure in addition to his chronic renal insufficiency, making initiation of CVVH necessary. Due to a complete cardiac arrest in both ventricles, a left ventricular assist device (LVAD) in combination with right ECMO (rECMO) was implanted despite manifest septic conditions. In the post-operative course IL-6 levels and vasopressor dosages increased drastically. A CytoSorb hemoadsorption device was therefore installed in the CVVH circuit and 3 sessions were run during the following 4 days. During CytoSorb treatment, inflammatory markers IL-6, procalcitonin, and C-reactive protein decreased concomitant with significantly reduced vasopressor support. No adverse device-related side effects were documented during or after the treatment sessions. This is the first clinical case report of a highly septic patient treated with the combined use of LVAD, rECMO, CVVH, and CytoSorb. The combination was practical, technically feasible, and beneficial for the patient. This combination represents a reasonable approach to improve survival in patients with multiple organ dysfunction necessitating several organ supportive techniques.

Randomized, Double-Blind, Placebo-Controlled Trial of Thiamine as a Metabolic Resuscitator in Septic Shock: A Pilot Study.

PubMed

Donnino, Michael W; Andersen, Lars W; Chase, Maureen; Berg, Katherine M; Tidswell, Mark; Giberson, Tyler; Wolfe, Richard; Moskowitz, Ari; Smithline, Howard; Ngo, Long; Cocchi, Michael N

2016-02-01

To determine if intravenous thiamine would reduce lactate in patients with septic shock. Randomized, double-blind, placebo-controlled trial. Two US hospitals. Adult patients with septic shock and elevated (> 3 mmol/L) lactate between 2010 and 2014. Thiamine 200 mg or matching placebo twice daily for 7 days or until hospital discharge. The primary outcome was lactate levels 24 hours after the first study dose. Of 715 patients meeting the inclusion criteria, 88 patients were enrolled and received study drug. There was no difference in the primary outcome of lactate levels at 24 hours after study start between the thiamine and placebo groups (median: 2.5 mmol/L [1.5, 3.4] vs. 2.6 mmol/L [1.6, 5.1], p = 0.40). There was no difference in secondary outcomes including time to shock reversal, severity of illness and mortality. 35% of the patients were thiamine deficient at baseline. In this predefined subgroup, those in the thiamine treatment group had statistically significantly lower lactate levels at 24 hours (median 2.1 mmol/L [1.4, 2.5] vs. 3.1 [1.9, 8.3], p = 0.03). There was a statistically significant decrease in mortality over time in those receiving thiamine in this subgroup (p = 0.047). Administration of thiamine did not improve lactate levels or other outcomes in the overall group of patients with septic shock and elevated lactate. In those with baseline thiamine deficiency, patients in the thiamine group had significantly lower lactate levels at 24 hours and a possible decrease in mortality over time.

Mechanisms of Thrombocytopenia During Septic Shock: A Multiplex Cluster Analysis of Endogenous Sepsis Mediators.

PubMed

Bedet, Alexandre; Razazi, Keyvan; Boissier, Florence; Surenaud, Mathieu; Hue, Sophie; Giraudier, Stéphane; Brun-Buisson, Christian; Mekontso Dessap, Armand

2018-06-01

Thrombocytopenia is a common feature of sepsis and may involve various mechanisms often related to the inflammatory response. This study aimed at evaluating factors associated with thrombocytopenia during human septic shock. In particular, we used a multiplex analysis to assess the role of endogenous sepsis mediators. Prospective, observational study. Thrombocytopenia was defined as an absolute platelet count <100 G/L or a 50% relative decrease in platelet count during the first week of septic shock. Plasma concentrations of 27 endogenous mediators involved in sepsis and platelet pathophysiology were assessed at day-1 using a multi-analyte Milliplex human cytokine kit. Patients with underlying diseases at risk of thrombocytopenia (hematological malignancies, chemotherapy, cirrhosis, and chronic heart failure) were excluded. Thrombocytopenia occurred in 33 (55%) of 60 patients assessed. Patients with thrombocytopenia were more prone to present with extrapulmonary infections and bacteremia. Disseminated intravascular coagulation was frequent (81%) in these patients. Unbiased hierarchical clustering identified five different clusters of sepsis mediators, including one with markers of platelet activation (e.g., thrombospondin-1) positively associated with platelet count, one with markers of inflammation (e.g., tumor necrosis factor alpha and heat shock protein 70), and endothelial dysfunction (e.g., intercellular adhesion molecule-1 and vascular cell adhesion molecule-1) negatively associated with platelet count, and another involving growth factors of thrombopoiesis (e.g., thrombopoietin), also negatively associated with platelet count. Surrogates of hemodilution (e.g., hypoprotidemia and higher fluid balance) were also associated with thrombocytopenia. Multiple mechanisms seemed involved in thrombocytopenia during septic shock, including endothelial dysfunction/coagulopathy, hemodilution, and altered thrombopoiesis.

Lactate clearance as the predictor of outcome in pediatric septic shock.

PubMed

Choudhary, Richa; Sitaraman, Sadasivan; Choudhary, Anita

2017-01-01

Septic shock can rapidly evolve into multiple system organ failure and death. In the recent years, hyperlactatemia has been found to be a risk factor for mortality in critically ill adults. To evaluate the predictive value of lactate clearance and to determine the optimal cut-off value for predicting outcome in children with septic shock. A prospective observational study was performed on children with septic shock admitted to pediatric Intensive Care Unit (PICU). Serial lactate levels were measured at PICU admission, 24 and 48 h later. Lactate clearance, percent decrease in lactate level in 24 h, was calculated. The primary outcome measure was survival or nonsurvival at the end of hospital stay. We performed receiver operating characteristic analyses to calculate optimal cut-off values. The mean lactate levels at admission were significantly higher in the nonsurvivors than survivors, 5.12 ± 3.51 versus 3.13 ± 1.71 mmol/L ( P = 0.0001). The cut-off for lactate level at admission for the best prediction of mortality was determined as ≥4 mmol/L (odds ratio 5.4; 95% confidence interval [CI] =2.45-12.09). Mean lactate clearance was significantly higher in survivors than nonsurvivors (17.9 ± 39.9 vs. -23.2 ± 62.7; P < 0.0001). A lactate clearance rate of <10% at 24 h had a sensitivity and specificity of 78.7% and 72.2%, respectively and a positive predictive value of 83.1% for death. Failure to achieve a lactate clearance of more than 10% was associated with greater risk of mortality (likelihood ratio + 2.83; 95% CI = 1.82-4.41). Serial lactate levels can be used to predict outcome in pediatric septic shock. A 24 h lactate clearance cut-off of <10% is a predictor of in-hospital mortality in such patients.

Coronary flow reserve is associated with tissue ischemia and is an additive predictor of intensive care unit mortality to traditional risk scores in septic shock.

PubMed

Ikonomidis, Ignatios; Makavos, George; Nikitas, Nikitas; Paraskevaidis, Ioannis; Diamantakis, Argyris; Kopterides, Petros; Theodorakopoulou, Maria; Parissis, John; Lekakis, John; Armaganidis, Apostolos; Dimopoulou, Ioanna

2014-03-01

Reduced coronary velocity flow reserve (CFR) is associated with poor outcome in patients with cardiovascular disease. We investigated whether CFR is associated with tissue ischemia and acidosis, impaired myocardial deformation and adverse outcome in patients with septic shock. In 70 mechanically-ventilated patients with septic shock, we examined: a) S' and E' mitral annular velocities using tissue Doppler imaging (TDI), b) CFR of the left anterior descending artery after adenosine infusion using transesophageal Doppler echocardiography and c) lactate, pyruvate and glycerol in tissue by means of a microdialysis (MD) catheter inserted into the subcutaneous adipose tissue as markers of tissue ischemia and acidosis. SOFA and APACHE II prognostic scores and mortality in the intensive care unit (ICU) were recorded. Reduced CFR, S' and E' as well as increased E/E' correlated with increased SOFA, APACHE II and MD lactate to pyruvate ratio (p<0.05 for all correlations). Impaired TDI markers also correlated with increased MD glycerol (p<0.05). Reduced CFR correlated with decreased E' (p<0.05). CFR was 1.8 ± 0.42 in non-survivors (n=34) versus 2.08 ± 0.44 in survivors (p=0.007). A CFR<1.90 predicted mortality with sensitivity of 70% and specificity of 69% (area under the curve 77%; p=0.003). CFR had an additive value to APACHE (chi-square change: 4.358, p=0.03) and SOFA (chi-square change: 3.692, p=0.04) for the prediction of mortality. Tissue ischemia and acidosis is a common pathophysiological link between decreased CFR and impaired LV myocardial deformation in septic shock. CFR is an additive predictor of ICU mortality to traditional risk scores in septic shock. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Prediction of pediatric sepsis mortality within 1 h of intensive care admission.

PubMed

Schlapbach, Luregn J; MacLaren, Graeme; Festa, Marino; Alexander, Janet; Erickson, Simon; Beca, John; Slater, Anthony; Schibler, Andreas; Pilcher, David; Millar, Johnny; Straney, Lahn

2017-08-01

The definitions of sepsis and septic shock have recently been revised in adults, but contemporary data are needed to inform similar approaches in children. Multicenter cohort study including children <16 years admitted with sepsis or septic shock to ICUs in Australia and New Zealand in the period 2012-2015. We assessed septic shock criteria at ICU admission to define sepsis severity, using 30-day mortality as outcome. Through multivariable logistic regression, a pediatric sepsis score was derived using variables available within 60 min of ICU admission. Of 42,523 pediatric admissions, 4403 children were admitted with invasive infection, including 1697 diagnosed as having sepsis/septic shock on admission. Mortality was 8.5% (144/1697) and 50.7% of deaths occurred within 48 h of admission. The presence of septic shock as defined by the 2005 consensus was sensitive but not specific in predicting mortality (AUC = 0.69; 95% CI 0.65-0.72). Combinations of hypotension, vasopressor therapy, and lactate >2 mmol/l discriminated poorly (AUC <0.60). Multivariate models showed that oxygenation markers, ventilatory support, hypotension, cardiac arrest, serum lactate, pupil responsiveness, and immunosuppression were the best-performing predictors (0.843; 0.811-0.875). We derived a pediatric sepsis score (0.817; 0.779-0.855), and every one-point increase was associated with a 28.5% (23.8-33.2%) increase in the odds of death. Children with a score ≥6 had 19.8% mortality and accounted for 74.3% of deaths. The sepsis score performed comparably when applied to all children admitted with invasive infection (0.810; 0.781-0.840). We observed mortality patterns specific to pediatric sepsis that support the need for specialized definitions of sepsis severity in children. We demonstrated the importance of lactate, cardiovascular, and respiratory derangements at ICU admission for the identification of children with substantially higher risk of sepsis mortality.

Group A streptococcal toxic shock syndrome secondary to necrotizing pelvic inflammatory disease in a postmenopausal woman.

PubMed

Paulson, Qiwei; Douglass, Elizabeth; Moreno, Alejandro; Aydelotte, Jayson

2016-01-01

Group A β-hemolytic streptococcus (GAS) is well known to cause upper respiratory tract or cutaneous infections, but some more virulent species of GAS can lead to a rapidly progressive life threatening soft tissue necrotizing infection and streptococcal toxic shock syndrome (STSS). In the modern era, GAS infections within the female reproductive tract leading to STSS are unusual and are often the result of retained products of conception or intrauterine devices. This report describes a case of GAS necrotizing pelvic infection in a previously healthy menopausal woman with no obvious portal of entry. Her clinical course rapidly progressed to septic shock and multiorgan failure. She required multiple surgeries in addition to targeted antimicrobials and aggressive management of shock and organ failures. After a prolonged hospital stay, she had a full recovery.

Sequential N-Terminal Pro-B-Type Natriuretic Peptide and High-Sensitivity Cardiac Troponin Measurements During Albumin Replacement in Patients With Severe Sepsis or Septic Shock.

PubMed

Masson, Serge; Caironi, Pietro; Fanizza, Caterina; Carrer, Sara; Caricato, Anselmo; Fassini, Paola; Vago, Tarcisio; Romero, Marilena; Tognoni, Gianni; Gattinoni, Luciano; Latini, Roberto

2016-04-01

Myocardial dysfunction is a frequent complication in patients with severe sepsis and can worsen the prognosis. We investigated whether circulating biomarkers related to myocardial function and injury predicted outcome and were associated with albumin replacement. A multicenter, randomized clinical trial about albumin replacement in severe sepsis or septic shock (the Albumin Italian Outcome Sepsis trial). Forty ICUs in Italy. Nine hundred and ninety-five patients with severe sepsis or septic shock. Randomization to albumin and crystalloid solutions or crystalloid solutions alone. Plasma concentrations of N- terminal pro-B-type natriuretic peptide and high-sensitivity cardiac troponin T were measured 1, 2, and 7 days after enrollment. We tested the relationship of single marker measurements or changes over time with clinical events, organ dysfunctions, albumin replacement, and ICU or 90-day mortality in the overall population and after stratification by shock. N-terminal pro-B-type natriuretic peptide levels were abnormal in 97.4% of the patients and high-sensitivity cardiac troponin T in 84.5%, with higher concentrations in those with shock. After extensive adjustments, N-terminal pro-B-type natriuretic peptide concentrations predicted ICU or 90-day mortality, better than high-sensitivity cardiac troponin T. Early changes in N-terminal pro-B-type natriuretic peptide or high-sensitivity cardiac troponin T concentrations were independently associated with subsequent mortality in patients with shock. Patients given albumin had significantly higher N-terminal pro-B-type natriuretic peptide levels; in addition, early rise in N-terminal pro-B-type natriuretic peptide was associated with a better outcome in this subgroup. Circulating N-terminal pro-B-type natriuretic peptide and high-sensitivity cardiac troponin T are frequently elevated in severe sepsis or septic shock and have relevant prognostic value, which may be important in monitoring the clinical efficacy of supporting therapy.

Case of streptococcal toxic shock syndrome caused by rapidly progressive group A hemolytic streptococcal infection during postoperative chemotherapy for cervical cancer.

PubMed

Nogami, Yuya; Tsuji, Kousuke; Banno, Kouji; Umene, Kiyoko; Katakura, Satomi; Kisu, Iori; Tominaga, Eiichiro; Aoki, Daisuke

2014-01-01

Streptococcal toxic shock syndrome (STSS) is a severe infectious disease caused by group A hemolytic streptococcus (Streptococcus pyogenes). This condition is a serious disease that involves rapidly progressive septic shock. We experienced a case of STSS caused by primary peritonitis during treatment with paclitaxel and cisplatin (TP therapy) as postoperative chemotherapy for cervical cancer. STSS mostly develops after extremity pain, but initial influenza-like symptoms of fever, chill, myalgia and gastrointestinal symptoms may also occur. TP therapy is used to treat many cancers, including gynecological cancer, but may cause adverse reactions of neuropathy and nephrotoxicity and sometimes fever, arthralgia, myalgia, abdominal pain and general malaise. The case reported here indicates that development of STSS can be delayed after chemotherapy and that primary STSS symptoms may be overlooked because they may be viewed as adverse reactions to chemotherapy. To our knowledge, this is the first report of a case of STSS during chemotherapy. © 2013 The Authors. Journal of Obstetrics and Gynaecology Research © 2013 Japan Society of Obstetrics and Gynecology.

Effects of a novel cytokine haemoadsorbtion system on inflammatory response in septic shock after cephalic pancreatectomy – a case report

PubMed Central

Tomescu, Dana; Dima, Simona O.; Tănăsescu, Sabina; Tănase, Cristiana Pistol; Năstase, Anca; Popescu, Mihai

2014-01-01

Severe sepsis and septic shock are associated with an inflammatory cascade that is primarily responsible for multiple organ dysfunction. To date, there are no specific treatments designed to modulate and rebalance inflammatory cytokines levels. We present a case of a 50 years old man with postoperative septic shock after undergoing cephalic pancreatectomy for a pancreatic cystic tumor. The use of a haemoadsorbtion device (CytoSorb®) in combination with continuous veno-venous haemofiltration was associated with a decrease in TNFα, IL-1β and IFNγ and an increase in IL-10 levels measured before and after two consecutive procedures. The effect of CytoSorb® on inflammatory cytokines translated into a more stable haemodynamic profile with a stable cardiac output and normalization of systemic vascular resistance index and decreased vasopressor requirements. Further prospective large clinical trials are required in order to determine the indications for CytoSorb® and to evaluate the overall outcome. PMID:28913446

Effects of a novel cytokine haemoadsorbtion system on inflammatory response in septic shock after cephalic pancreatectomy - a case report.

PubMed

Tomescu, Dana; Dima, Simona O; Tănăsescu, Sabina; Tănase, Cristiana Pistol; Năstase, Anca; Popescu, Mihai

2014-10-01

Severe sepsis and septic shock are associated with an inflammatory cascade that is primarily responsible for multiple organ dysfunction. To date, there are no specific treatments designed to modulate and rebalance inflammatory cytokines levels. We present a case of a 50 years old man with postoperative septic shock after undergoing cephalic pancreatectomy for a pancreatic cystic tumor. The use of a haemoadsorbtion device (CytoSorb ® ) in combination with continuous veno-venous haemofiltration was associated with a decrease in TNFα, IL-1β and IFNγ and an increase in IL-10 levels measured before and after two consecutive procedures. The effect of CytoSorb ® on inflammatory cytokines translated into a more stable haemodynamic profile with a stable cardiac output and normalization of systemic vascular resistance index and decreased vasopressor requirements. Further prospective large clinical trials are required in order to determine the indications for CytoSorb ® and to evaluate the overall outcome.

Trial of early, goal-directed resuscitation for septic shock.

PubMed

Mouncey, Paul R; Osborn, Tiffany M; Power, G Sarah; Harrison, David A; Sadique, M Zia; Grieve, Richard D; Jahan, Rahi; Harvey, Sheila E; Bell, Derek; Bion, Julian F; Coats, Timothy J; Singer, Mervyn; Young, J Duncan; Rowan, Kathryn M

2015-04-02

Early, goal-directed therapy (EGDT) is recommended in international guidelines for the resuscitation of patients presenting with early septic shock. However, adoption has been limited, and uncertainty about its effectiveness remains. We conducted a pragmatic randomized trial with an integrated cost-effectiveness analysis in 56 hospitals in England. Patients were randomly assigned to receive either EGDT (a 6-hour resuscitation protocol) or usual care. The primary clinical outcome was all-cause mortality at 90 days. We enrolled 1260 patients, with 630 assigned to EGDT and 630 to usual care. By 90 days, 184 of 623 patients (29.5%) in the EGDT group and 181 of 620 patients (29.2%) in the usual-care group had died (relative risk in the EGDT group, 1.01; 95% confidence interval [CI], 0.85 to 1.20; P=0.90), for an absolute risk reduction in the EGDT group of -0.3 percentage points (95% CI, -5.4 to 4.7). Increased treatment intensity in the EGDT group was indicated by increased use of intravenous fluids, vasoactive drugs, and red-cell transfusions and reflected by significantly worse organ-failure scores, more days receiving advanced cardiovascular support, and longer stays in the intensive care unit. There were no significant differences in any other secondary outcomes, including health-related quality of life, or in rates of serious adverse events. On average, EGDT increased costs, and the probability that it was cost-effective was below 20%. In patients with septic shock who were identified early and received intravenous antibiotics and adequate fluid resuscitation, hemodynamic management according to a strict EGDT protocol did not lead to an improvement in outcome. (Funded by the United Kingdom National Institute for Health Research Health Technology Assessment Programme; ProMISe Current Controlled Trials number, ISRCTN36307479.).

Melatonin and human mitochondrial diseases

PubMed Central

Sharafati-Chaleshtori, Reza; Shirzad, Hedayatollah; Rafieian-Kopaei, Mahmoud; Soltani, Amin

2017-01-01

Mitochondrial dysfunction is one of the main causative factors in a wide variety of complications such as neurodegenerative disorders, ischemia/reperfusion, aging process, and septic shock. Decrease in respiratory complex activity, increase in free radical production, increase in mitochondrial synthase activity, increase in nitric oxide production, and impair in electron transport system and/or mitochondrial permeability are considered as the main factors responsible for mitochondrial dysfunction. Melatonin, the pineal gland hormone, is selectively taken up by mitochondria and acts as a powerful antioxidant, regulating the mitochondrial bioenergetic function. Melatonin increases the permeability of membranes and is the stimulator of antioxidant enzymes including superoxide dismutase, glutathione peroxidase, glutathione reductase, and catalase. It also acts as an inhibitor of lipoxygenase. Melatonin can cause resistance to oxidation damage by fixing the microsomal membranes. Melatonin has been shown to retard aging and inhibit neurodegenerative disorders, ischemia/reperfusion, septic shock, diabetes, cancer, and other complications related to oxidative stress. The purpose of the current study, other than introducing melatonin, was to present the recent findings on clinical effects in diseases related to mitochondrial dysfunction including diabetes, cancer, gastrointestinal diseases, and diseases related to brain function. PMID:28400824

Antibiotic therapy prior to hospital admission is associated with reduced septic shock and need for mechanical ventilation in patients with community-acquired pneumonia.

PubMed

Amaro, Rosanel; Sellarés, Jacobo; Polverino, Eva; Cillóniz, Catia; Ferrer, Miquel; Fernández-Barat, Laia; Mensa, Josep; Niederman, Michael S; Torres, Antoni

2017-05-01

A subgroup of patients admitted to the hospital with a diagnosis of community-acquired pneumonia (CAP) have received antibiotic therapy prior to admission for the current episode of pneumonia. The objective of this study was to assess the clinical course of patients receiving antibiotics prior to admission, compared to patients not previously treated. An observational cohort of 3364 CAP patients consecutively admitted to our hospital, and prospectively included, were studied. We collected clinical, microbiological and biochemical parameters, focusing on recent antibiotics received prior to admission. 610 (18%) patients received antibiotics prior to hospital admission for the current CAP episode. Patients with previous antibiotic use developed septic shock less frequently (4% vs. 7%, p = 0.007) and required invasive ventilation less often (3% vs. 6%, p = 0.002). After adjustment by different covariate factors and propensity score, antibiotic therapy was still independently associated with a lower incidence of septic shock at admission (OR 0.54 [95% CI 0.31-0.95], p = 0.03) and less need for invasive ventilation (OR 0.38 [95% CI 0.16-0.91], p = 0.03). In this cohort, recent use of antibiotics before hospital admission in CAP seems to be associated with a lower incidence of septic shock on admission and a lower need for invasive ventilation. Copyright © 2017 The British Infection Association. Published by Elsevier Ltd. All rights reserved.

Endotype Transitions During the Acute Phase of Pediatric Septic Shock Reflect Changing Risk and Treatment Response.

PubMed

Wong, Hector R; Cvijanovich, Natalie Z; Anas, Nick; Allen, Geoffrey L; Thomas, Neal J; Bigham, Michael T; Weiss, Scott L; Fitzgerald, Julie C; Checchia, Paul A; Meyer, Keith; Quasney, Michael; Hall, Mark; Gedeit, Rainer; Freishtat, Robert J; Nowak, Jeffrey; Lutfi, Riad; Gertz, Shira; Grunwell, Jocelyn R; Lindsell, Christopher J

2018-03-01

We previously identified septic shock endotypes A and B based on 100 genes reflecting adaptive immunity and glucocorticoid receptor signaling. The endotypes differ with respect to outcome and corticosteroid responsiveness. We determined whether endotypes change during the initial 3 days of illness, and whether changes are associated with outcomes. Observational cohort study including existing and newly enrolled participants. Multiple PICUs. Children with septic shock. None. We measured the 100 endotyping genes at day 1 and day 3 of illness in 375 patients. We determined if endotype assignment changes over time, and whether changing endotype is associated with corticosteroid response and outcomes. We used multivariable logistic regression to adjust for illness severity, age, and comorbidity burden. Among the 132 subjects assigned to endotype A on day 1, 56 (42%) transitioned to endotype B by day 3. Among 243 subjects assigned to endotype B on day 1, 77 (32%) transitioned to endotype A by day 3. Assignment to endotype A on day 1 was associated with increased odds of mortality. This risk was modified by the subsequent day 3 endotype assignment. Corticosteroids were associated with increased risk of mortality among subjects who persisted as endotype A. A substantial proportion of children with septic shock transition endotypes during the acute phase of illness. The risk of poor outcome and the response to corticosteroids change with changes in endotype assignment. Patients persisting as endotype A are at highest risk of poor outcomes.

Combining central venous-to-arterial partial pressure of carbon dioxide difference and central venous oxygen saturation to guide resuscitation in septic shock.

PubMed

Du, Wei; Liu, Da-Wei; Wang, Xiao-Ting; Long, Yun; Chai, Wen-Zhao; Zhou, Xiang; Rui, Xi

2013-12-01

Central venous oxygen saturation (Scvo2) is a useful therapeutic target when treating septic shock. We hypothesized that combining Scvo2 and central venous-to-arterial partial pressure of carbon dioxide difference (△Pco2) may provide additional information about survival. We performed a retrospective analysis of 172 patients treated for septic shock. All patients were treated using goal-directed therapy to achieve Scvo2 ≥ 70%. After 6 hours of treatment, we divided patients into 4 groups based on Scvo2 (<70% or ≥ 70%) and △Pco2 (<6 mm Hg or ≥ 6 mm Hg). Overall, 28-day mortality was 35.5%. For patients in whom the Scvo2 target was not achieved at 6 hours, mortality was 50.0%, compared with 29.5% in those in whom Scvo2 exceeded 70% (P = .009). In patients with Scvo2 ≥ 70%, mortality was lower if △Pco2 was <6 mm Hg than if △Pco2 was ≥ 6 mm Hg (56.1% vs 16.1%, respectively; P < .001) and 6-hour lactate clearance was superior (0.01 ± 0.61 vs 0.21 ± 0.31, respectively; P = .016). The combination of Scvo2 and △Pco2 appears to predict outcome in critically ill patients resuscitated from septic shock better than Scvo2 alone. Patients who meet both targets appear to clear lactate more efficiently. © 2013.

Relative adrenal insufficiency in severe congestive heart failure with preserved systolic function: a case report.

PubMed

Lovelock, Joshua D; Coslet, Sandra; Johnson, Marie; Rich, Stuart; Gomberg-Maitland, Mardi

2007-09-01

Relative adrenal insufficiency in critically ill patients is an important syndrome in septic shock. The insufficient stress response of the hypothalamic-pituitary-adrenal axis in acute illness contributes to hemodynamic instability. Treatment of this state in septic shock improves patient outcomes. In this report, we describe the case of a patient with severe diastolic dysfunction who presented in cardiogenic shock associated with relative adrenal insufficiency and had a complete recovery with corticosteroid replacement. Alteration of the hypothalamic-pituitary-adrenal axis may be more prevalent than suspected in end-stage heart failure, and the diagnosis and treatment of this syndrome may ultimately improve outcomes in a subgroup of heart failure patients.

Children’s Hospital Integrated Patient Electronic Record System (CHIPERS) Continuation

DTIC Science & Technology

2012-10-01

decision support, electronic health record, pediatric critical care, neonatal intensive care 17 HFlori@mail.cho.org     3       Table of Contents...and/or shock with the ACCM and  CHRCO Clinical Guidelines for Hemodynamic Support of  Neonates  and Children with  Severe Sepsis and Septic Shock...Hospital & Research Center Oakland Clinical Guidelines for Hemodynamic Support of  Neonates  and Children with Severe Sepsis and Septic Shock. We will

Evaluation of the preventative effects exerted by Lactobacillus fermentum in an experimental model of septic shock induced in mice.

PubMed

Arribas, Belén; Rodríguez-Cabezas, Maria Elena; Comalada, Mònica; Bailón, Elvira; Camuesco, Desireé; Olivares, Mónica; Xaus, Jordi; Zarzuelo, Antonio; Gálvez, Julio

2009-01-01

The preventative effects of the probiotic Lactobacillus fermentum CECT5716 were evaluated in the lipopolysaccharide (LPS) model of septic shock in mice. The probiotic was administered suspended in drinking water at the final concentration of 108 colony-forming units/ml for 2 weeks before the induction of an endotoxic shock by an intraperitoneal injection of LPS (400 microg/200 microl per mouse). Blood and different organs were collected after 24 h to evaluate the severity of the endotoxic shock and the preventative effects of the probiotic. L. fermentum reduced TNF-alpha levels in blood, which promotes the major alterations observed during septic shock, as well as the infiltration of activated neutrophils into the lungs. Furthermore, free radical overproduction and oxidative stress were associated with a significant decrease in hepatic glutathione levels in septic mice, and with an excessive NO production attributed to the induction of the inducible isoform of NO synthase (iNOS). In fact, hepatic glutathione levels were significantly increased in the group of mice receiving the probiotic, and the increased iNOS expression both in the colon and lungs was down-regulated in those mice treated with L. fermentum. Finally, pre-treatment with L. fermentum may also exert its protective action modulating the expression of different cytokines in splenocyte-derived T cells such us IL-2, IL-5, IL-6 or IL-10. In conclusion, pre-treatment with L. fermentum may exert its protective action against LPS-induced organ damage in mice by a combination of several actions including its antioxidant properties and by reduction of the synthesis of the pro-inflammatory TNF-alpha and IL-6.

Hydrocortisone Therapy in Catecholamine-Resistant Pediatric Septic Shock: A Pragmatic Analysis of Clinician Practice and Association With Outcomes.

PubMed

Nichols, Blake; Kubis, Sherri; Hewlett, Jennifer; Yehya, Nadir; Srinivasan, Vijay

2017-09-01

The 2012 Surviving Sepsis Campaign pediatric guidelines recommend stress dose hydrocortisone in children experiencing catecholamine-dependent septic shock with suspected or proven absolute adrenal insufficiency. We evaluated whether stress dose hydrocortisone therapy in children with catecholamine dependent septic shock correlated with random serum total cortisol levels and was associated with improved outcomes. Retrospective cohort study. Non-cardiac PICU. Critically ill children (1 mo to 18 yr) admitted between January 1, 2013, and December 31, 2013, with catecholamine dependent septic shock who had random serum total cortisol levels measured prior to potential stress dose hydrocortisone therapy. None. The cohort was dichotomized to random serum total cortisol less than 18 mcg/dL and greater than or equal to 18 mcg/dL. Associations of stress dose hydrocortisone with outcomes: PICU mortality, PICU and hospital length of stay, ventilator-free days, and vasopressor-free days were examined. Seventy children with catecholamine-dependent septic shock and measured random serum total cortisol levels were eligible (16% PICU mortality). Although 43% (30/70) had random serum total cortisol less than 18 μg/dL, 60% (42/70) received stress dose hydrocortisone. Children with random serum total cortisol less than 18 μg/dL had lower severity of illness and lower Vasopressor Inotrope Scores than those with random serum total cortisol greater than or equal to 18 μg/dL (all p < 0.05). Children with stress dose hydrocortisone had higher severity of illness and PICU mortality than those without stress dose hydrocortisone (all p < 0.05). Mean random serum total cortisol levels were similar in children with and without stress dose hydrocortisone (21.1 vs 18.7 μg/dL; p = 0.69). In children with random serum total cortisol less than 18 μg/dL, stress dose hydrocortisone was associated with greater PICU and hospital length of stay and fewer ventilator-free days (all p < 0.05). In children with random serum total cortisol greater than 18 μg/dL, stress dose hydrocortisone was associated with greater PICU mortality and fewer ventilator-free days and vasopressor-free days (all p < 0.05). Stress dose hydrocortisone therapy in children with catecholamine-dependent septic shock correlated more with severity of illness than random serum total cortisol levels and was associated with worse outcomes, irrespective of random serum total cortisol levels.

Timing of vasopressor initiation and mortality in septic shock: a cohort study

PubMed Central

2014-01-01

Introduction Despite recent advances in the management of septic shock, mortality remains unacceptably high. Earlier initiation of key therapies including appropriate antimicrobials and fluid resuscitation appears to reduce the mortality in this condition. This study examined whether early initiation of vasopressor therapy is associated with improved survival in fluid therapy-refractory septic shock. Methods Utilizing a well-established database, relevant information including duration of time to vasopressor administration following the initial documentation of recurrent/persistent hypotension associated with septic shock was assessed in 8,670 adult patients from 28 ICUs in Canada, the United States of America, and Saudi Arabia. The primary endpoint was survival to hospital discharge. Secondary endpoints were length of ICU and hospital stay as well as duration of ventilator support and vasopressor dependence. Analysis involved multivariate linear and logistic regression analysis. Results In total, 8,640 patients met the definition of septic shock with time of vasopressor/inotropic initiation documented. Of these, 6,514 were suitable for analysis. The overall unadjusted hospital mortality rate was 53%. Independent mortality correlates included liver failure (odds ratio (OR) 3.46, 95% confidence interval (CI), 2.67 to 4.48), metastatic cancer (OR 1.63, CI, 1.32 to 2.01), AIDS (OR 1.91, CI, 1.29 to 2.49), hematologic malignancy (OR 1.88, CI, 1.46 to 2.41), neutropenia (OR 1.78, CI, 1.27 to 2.49) and chronic hypertension (OR 0.62 CI, 0.52 to 0.73). Delay of initiation of appropriate antimicrobial therapy (OR 1.07/hr, CI, 1.06 to 1.08), age (OR 1.03/yr, CI, 1.02 to 1.03), and Acute Physiology and Chronic Health Evaluation (APACHE) II Score (OR 1.11/point, CI, 1.10 to 1.12) were also found to be significant independent correlates of mortality. After adjustment, only a weak correlation between vasopressor delay and hospital mortality was found (adjusted OR 1.02/hr, 95% CI 1.01 to 1.03, P <0.001). This weak effect was entirely driven by the group of patients with the longest delays (>14.1 hours). There was no significant relationship of vasopressor initiation delay to duration of vasopressor therapy (P = 0.313) and only a trend to longer duration of ventilator support (P = 0.055) among survivors. Conclusion Marked delays in initiation of vasopressor/inotropic therapy are associated with a small increase in mortality risk in patients with septic shock. PMID:24887489

4G/5G polymorphism of PAI-1 gene is associated with multiple organ dysfunction and septic shock in pneumonia induced severe sepsis: prospective, observational, genetic study.

PubMed

Madách, Krisztina; Aladzsity, István; Szilágyi, Agnes; Fust, George; Gál, János; Pénzes, István; Prohászka, Zoltán

2010-01-01

Activation of inflammation and coagulation are closely related and mutually interdependent in sepsis. The acute-phase protein, plasminogen activator inhibitor-1 (PAI-1) is a key element in the inhibition of fibrinolysis. Elevated levels of PAI-1 have been related to worse outcome in pneumonia. We aimed to evaluate the effect of functionally relevant 4G/5G polymorphism of PAI-1 gene in pneumonia induced sepsis. We enrolled 208 Caucasian patients with severe sepsis due to pneumonia admitted to an intensive care unit (ICU). Patients were followed up until ICU discharge or death. Clinical data were collected prospectively and the PAI-1 4G/5G polymorphism was genotyped by polymerase chain reaction-restriction fragment length polymorphism technique. Patients were stratified according to the occurrence of multiple organ dysfunction syndrome, septic shock or death. We found that carriers of the PAI-1 4G/4G and 4G/5G genotypes have a 2.74-fold higher risk for multiple organ dysfunction syndrome (odds ratio [OR] 95% confidence interval [CI] = 1.335 - 5.604; p = 0.006) and a 2.57-fold higher risk for septic shock (OR 95%CI = 1.180 - 5.615; p = 0.018) than 5G/5G carriers. The multivariate logistic regression analysis adjusted for independent predictors, such as age, nosocomial pneumonia and positive microbiological culture also supported that carriers of the 4G allele have a higher prevalence of multiple organ dysfunction syndrome (adjusted odds ratio [aOR] = 2.957; 95%CI = 1.306 -6.698; p = 0.009) and septic shock (aOR = 2.603; 95%CI = 1.137 - 5.959; p = 0.024). However, genotype and allele analyses have not shown any significant difference regarding mortality in models non-adjusted or adjusted for acute physiology and chronic health evaluation (APACHE) II. Patients bearing the 4G allele had higher disseminated intravascular coagulation (DIC) score at admission (p = 0.007) than 5G/5G carriers. Moreover, in 4G allele carriers the length of ICU stay of non-survivors was longer (p = 0.091), fewer ventilation-free days (p = 0.008) and days without septic shock (p = 0.095) were observed during the first 28 days. In Caucasian patients with severe sepsis due to pneumonia carriers of the 4G allele of PAI-1 polymorphism have higher risk for multiple organ dysfunction syndrome and septic shock and in agreement they showed more fulminant disease progression based on continuous clinical variables.

[Procalcitonin as a diagnostic marker in systemic inflammatory response syndrome (SIRS) and sepsis].

PubMed

Hryckiewicz, Katarzyna; Juszczyk, Jacek; Samet, Alfred; Arłukowicz, Elzbieta; Sledzińska, Anna; Bolewska, Beata

2006-01-01

Evaluation the value of procalcitonin as a diagnostic and prognostic marker in septic patients and patients with systemic inflammatory response syndrome (SIRS). 126 patients were included into the study. The patients were divided into four groups: 1--septic patients with positive blood cultures, 2--septic patients with negative blood cultures, 3--patients with SIRS, 4--patients without sepsis and SIRS. PCT level was measured by imunoluminometric assay (LUMItest) and immunochromatographic assay (PCT-Q). PCT level is higher in patients with sepsis than in patients with SIRS. PCT level is only slightly elevated in patients without sepsis and SIRS. The highest PCT level is found in patients with septic shock. In patients with the clinical improvement the frequency of PCT level increase is approximately twice lower than in patients who died. Measurement of PCT level on the first, second and third day of hospitalization has no prognostic value. There is no significant difference in PCT level in sepsis caused by Gram positive and Gram negative bacteria. PCT is a useful marker in diagnosis of sepsis but its role in monitoring the severity of sepsis requires more clinical studies.

[Whole-blood transfusion for hemorrhagic shock resuscitation: two cases in Djibouti].

PubMed

Cordier, P Y; Eve, O; Dehan, C; Topin, F; Menguy, P; Bertani, A; Massoure, P L; Kaiser, E

2012-01-01

Hemorrhagic shock requires early aggressive treatment, including transfusion of packed red blood cells and hemostatic resuscitation. In austere environments, when component therapy is not available, warm fresh whole-blood transfusion is a convenient treatment. It provides red blood cells, clotting factors, and functional platelets. Therefore it is commonly used in military practice to treat hemorrhagic shock in combat casualties. At Bouffard Hospital Center in Djibouti, the supply of packed red blood cells is limited, and apheresis platelets are unavailable. We used whole blood transfusion in two civilian patients with life-threatening non-traumatic hemorrhages. One had massive bleeding caused by disseminated intravascular coagulation due to septic shock; the second was a 39 year-old pregnant woman with uterine rupture. In both cases, whole blood transfusion (twelve and ten 500 mL bags respectively), combined with etiological treatment, enabled coagulopathy correction, hemorrhage control, and satisfactory recovery.

Skeletal Muscle and Lymphocyte Mitochondrial Dysfunctions in Septic Shock Trigger ICU-Acquired Weakness and Sepsis-Induced Immunoparalysis.

PubMed

Maestraggi, Quentin; Lebas, Benjamin; Clere-Jehl, Raphaël; Ludes, Pierre-Olivier; Chamaraux-Tran, Thiên-Nga; Schneider, Francis; Diemunsch, Pierre; Geny, Bernard; Pottecher, Julien

2017-01-01

Fundamental events driving the pathological processes of septic shock-induced multiorgan failure (MOF) at the cellular and subcellular levels remain debated. Emerging data implicate mitochondrial dysfunction as a critical factor in the pathogenesis of sepsis-associated MOF. If macrocirculatory and microcirculatory dysfunctions undoubtedly participate in organ dysfunction at the early stage of septic shock, an intrinsic bioenergetic failure, sometimes called "cytopathic hypoxia," perpetuates cellular dysfunction. Short-term failure of vital organs immediately threatens patient survival but long-term recovery is also severely hindered by persistent dysfunction of organs traditionally described as nonvital, such as skeletal muscle and peripheral blood mononuclear cells (PBMCs). In this review, we will stress how and why a persistent mitochondrial dysfunction in skeletal muscles and PBMC could impair survival in patients who overcome the first acute phase of their septic episode. First, muscle wasting protracts weaning from mechanical ventilation, increases the risk of mechanical ventilator-associated pneumonia, and creates a state of ICU-acquired muscle weakness, compelling the patient to bed. Second, failure of the immune system ("immunoparalysis") translates into its inability to clear infectious foci and predisposes the patient to recurrent nosocomial infections. We will finally emphasize how mitochondrial-targeted therapies could represent a realistic strategy to promote long-term recovery after sepsis.

Assessment of Diagnostic and Prognostic Role of Copeptin in the Clinical Setting of Sepsis.

PubMed

Battista, Stefania; Audisio, Umberto; Galluzzo, Claudia; Maggiorotto, Matteo; Masoero, Monica; Forno, Daniela; Pizzolato, Elisa; Ulla, Marco; Lucchiari, Manuela; Vitale, Annarita; Moiraghi, Corrado; Lupia, Enrico; Settanni, Fabio; Mengozzi, Giulio

2016-01-01

The diagnostic and prognostic usefulness of copeptin were evaluated in septic patients, as compared to procalcitonin assessment. In this single centre and observational study 105 patients were enrolled: 24 with sepsis, 25 with severe sepsis, 15 with septic shock, and 41 controls, divided in two subgroups (15 patients with gastrointestinal bleeding and 26 with suspected SIRS secondary to trauma, acute coronary syndrome, and pulmonary embolism). Biomarkers were determined at the first medical evaluation and thereafter 24, 48, and 72 hours after admission. Definitive diagnosis and in-hospital survival rates at 30 days were obtained through analysis of medical records. At entry, copeptin proved to be able to distinguish cases from controls and also sepsis group from septic shock group, while procalcitonin could distinguish also severe sepsis from septic shock group. Areas under the ROC curve for copeptin and procalcitonin were 0.845 and 0.861, respectively. Noteworthy, patients with copeptin concentrations higher than the threshold value (23.2 pmol/L), calculated from the ROC curve, at admission presented higher 30-day mortality. No significant differences were found in copeptin temporal profile among different subgroups. Copeptin showed promising diagnostic and prognostic role in the management of sepsis, together with its possible role in monitoring the response to treatment.

Assessment of Diagnostic and Prognostic Role of Copeptin in the Clinical Setting of Sepsis

PubMed Central

Battista, Stefania; Audisio, Umberto; Galluzzo, Claudia; Maggiorotto, Matteo; Masoero, Monica; Forno, Daniela; Pizzolato, Elisa; Ulla, Marco; Lucchiari, Manuela; Vitale, Annarita; Moiraghi, Corrado; Lupia, Enrico; Settanni, Fabio; Mengozzi, Giulio

2016-01-01

The diagnostic and prognostic usefulness of copeptin were evaluated in septic patients, as compared to procalcitonin assessment. In this single centre and observational study 105 patients were enrolled: 24 with sepsis, 25 with severe sepsis, 15 with septic shock, and 41 controls, divided in two subgroups (15 patients with gastrointestinal bleeding and 26 with suspected SIRS secondary to trauma, acute coronary syndrome, and pulmonary embolism). Biomarkers were determined at the first medical evaluation and thereafter 24, 48, and 72 hours after admission. Definitive diagnosis and in-hospital survival rates at 30 days were obtained through analysis of medical records. At entry, copeptin proved to be able to distinguish cases from controls and also sepsis group from septic shock group, while procalcitonin could distinguish also severe sepsis from septic shock group. Areas under the ROC curve for copeptin and procalcitonin were 0.845 and 0.861, respectively. Noteworthy, patients with copeptin concentrations higher than the threshold value (23.2 pmol/L), calculated from the ROC curve, at admission presented higher 30-day mortality. No significant differences were found in copeptin temporal profile among different subgroups. Copeptin showed promising diagnostic and prognostic role in the management of sepsis, together with its possible role in monitoring the response to treatment. PMID:27366743

How to choose the therapeutic goals to improve tissue perfusion in septic shock

PubMed Central

de Assuncao, Murillo Santucci Cesar; Corrêa, Thiago Domingos; Bravim, Bruno de Arruda; Silva, Eliézer

2015-01-01

The early recognition and treatment of severe sepsis and septic shock is the key to a successful outcome. The longer the delay in starting treatment, the worse the prognosis due to persistent tissue hypoperfusion and consequent development and worsening of organ dysfunction. One of the main mechanisms responsible for the development of cellular dysfunction is tissue hypoxia. The adjustments necessary for adequate tissue blood flow and therefore of oxygen supply to metabolic demand according to the assessment of the cardiac index and oxygen extraction rate should be performed during resuscitation period, especially in high complexity patients. New technologies, easily handled at the bedside, and new studies that directly assess the impact of macro-hemodynamic parameter optimization on microcirculation and in the clinical outcome of septic patients, are needed. PMID:26313438

Hydrocortisone plus Fludrocortisone for Adults with Septic Shock.

PubMed

Annane, Djillali; Renault, Alain; Brun-Buisson, Christian; Megarbane, Bruno; Quenot, Jean-Pierre; Siami, Shidasp; Cariou, Alain; Forceville, Xavier; Schwebel, Carole; Martin, Claude; Timsit, Jean-François; Misset, Benoît; Ali Benali, Mohamed; Colin, Gwenhael; Souweine, Bertrand; Asehnoune, Karim; Mercier, Emmanuelle; Chimot, Loïc; Charpentier, Claire; François, Bruno; Boulain, Thierry; Petitpas, Franck; Constantin, Jean-Michel; Dhonneur, Gilles; Baudin, François; Combes, Alain; Bohé, Julien; Loriferne, Jean-François; Amathieu, Roland; Cook, Fabrice; Slama, Michel; Leroy, Olivier; Capellier, Gilles; Dargent, Auguste; Hissem, Tarik; Maxime, Virginie; Bellissant, Eric

2018-03-01

Septic shock is characterized by dysregulation of the host response to infection, with circulatory, cellular, and metabolic abnormalities. We hypothesized that therapy with hydrocortisone plus fludrocortisone or with drotrecogin alfa (activated), which can modulate the host response, would improve the clinical outcomes of patients with septic shock. In this multicenter, double-blind, randomized trial with a 2-by-2 factorial design, we evaluated the effect of hydrocortisone-plus-fludrocortisone therapy, drotrecogin alfa (activated), the combination of the three drugs, or their respective placebos. The primary outcome was 90-day all-cause mortality. Secondary outcomes included mortality at intensive care unit (ICU) discharge and hospital discharge and at day 28 and day 180 and the number of days alive and free of vasopressors, mechanical ventilation, or organ failure. After drotrecogin alfa (activated) was withdrawn from the market, the trial continued with a two-group parallel design. The analysis compared patients who received hydrocortisone plus fludrocortisone with those who did not (placebo group). Among the 1241 patients included in the trial, the 90-day mortality was 43.0% (264 of 614 patients) in the hydrocortisone-plus-fludrocortisone group and 49.1% (308 of 627 patients) in the placebo group (P=0.03). The relative risk of death in the hydrocortisone-plus-fludrocortisone group was 0.88 (95% confidence interval, 0.78 to 0.99). Mortality was significantly lower in the hydrocortisone-plus-fludrocortisone group than in the placebo group at ICU discharge (35.4% vs. 41.0%, P=0.04), hospital discharge (39.0% vs. 45.3%, P=0.02), and day 180 (46.6% vs. 52.5%, P=0.04) but not at day 28 (33.7% and 38.9%, respectively; P=0.06). The number of vasopressor-free days to day 28 was significantly higher in the hydrocortisone-plus-fludrocortisone group than in the placebo group (17 vs. 15 days, P<0.001), as was the number of organ-failure-free days (14 vs. 12 days, P=0.003). The number of ventilator-free days was similar in the two groups (11 days in the hydrocortisone-plus-fludrocortisone group and 10 in the placebo group, P=0.07). The rate of serious adverse events did not differ significantly between the two groups, but hyperglycemia was more common in hydrocortisone-plus-fludrocortisone group. In this trial involving patients with septic shock, 90-day all-cause mortality was lower among those who received hydrocortisone plus fludrocortisone than among those who received placebo. (Funded by Programme Hospitalier de Recherche Clinique 2007 of the French Ministry of Social Affairs and Health; APROCCHSS ClinicalTrials.gov number, NCT00625209 .).

In neonates S100A8/S100A9 alarmins prevent the expansion of a specific inflammatory monocyte population promoting septic shock.

PubMed

Heinemann, Anna S; Pirr, Sabine; Fehlhaber, Beate; Mellinger, Lara; Burgmann, Johanna; Busse, Mandy; Ginzel, Marco; Friesenhagen, Judith; von Köckritz-Blickwede, Maren; Ulas, Thomas; von Kaisenberg, Constantin S; Roth, Johannes; Vogl, Thomas; Viemann, Dorothee

2017-03-01

The high susceptibility of newborn infants to sepsis is ascribed to an immaturity of the neonatal immune system, but the molecular mechanisms remain unclear. Newborn monocytes massively release the alarmins S100A8/S100A9. In adults, these are major regulators of immunosuppressive myeloid-derived suppressor cells (MDSCs). We investigated whether S100A8/S100A9 cause an expansion of monocytic MDSCs (Mo-MDSCs) in neonates, thereby contributing to an immunocompromised state. Mo-MDSCs have been assigned to CD14 + /human leukocyte antigen (HLA)-DR - /low /CD33 + monocytes in humans and to CD11b + /Gr-1 int /Ly6G - /Ly6C hi cells in mice. We found monocytes with these phenotypes significantly expanded in their respective newborns. Functionally, however, they did not prove immunosuppressive but rather responded inflammatorily to microbial stimulation. Their expansion did not correlate with high S100A8/S100A9 levels in cord blood. Murine studies revealed an excessive expansion of CD11b + /Gr-1 int /Ly6G - /Ly6C hi monocytes in S100A9 -/- neonates compared to wild-type neonates. This strong baseline expansion was associated with hyperinflammatory responses during endotoxemia and fatal septic courses. Treating S100A9 -/- neonates directly after birth with S100A8/S100A9 alarmins prevented excessive expansion of this inflammatory monocyte population and death from septic shock. Our data suggest that a specific population of inflammatory monocytes promotes fatal courses of sepsis in neonates if its expansion is not regulated by S100A8/S100A9 alarmins.-Heinemann, A. S., Pirr, S., Fehlhaber, B., Mellinger, L., Burgmann, J., Busse, M., Ginzel, M., Friesenhagen, J., von Köckritz-Blickwede, M., Ulas, T., von Kaisenberg, C. S., Roth, J., Vogl, T., Viemann, D. In neonates S100A8/S100A9 alarmins prevent the expansion of a specific inflammatory monocyte population promoting septic shock. © FASEB.

Comparable increase of B-type natriuretic peptide and amino-terminal pro-B-type natriuretic peptide levels in patients with severe sepsis, septic shock, and acute heart failure.

PubMed

Rudiger, Alain; Gasser, Stefan; Fischler, Manuel; Hornemann, Thorsten; von Eckardstein, Arnold; Maggiorini, Marco

2006-08-01

B-type natriuretic peptide (BNP) and N-terminal pro-BNP measurements are used for the diagnosis of congestive heart failure (HF). However, the diagnostic value of these tests is unknown under septic conditions. We compared patients with severe sepsis or septic shock and patients with acute HF to unravel the influence of the underlying diagnosis on BNP and N-terminal pro-BNP levels. Prospective, clinical study. Academic medical intensive care unit (ICU). A total of 249 consecutive patients were screened for the diagnosis of sepsis or HF. Sepsis was defined according to published guidelines. HF was diagnosed in the presence of an underlying heart disease and congestive HF, pulmonary edema, or cardiogenic shock. BNP and N-terminal pro-BNP were measured from blood samples that were drawn daily for routine analysis. We identified 24 patients with severe sepsis or septic shock and 51 patients with acute HF. At admission, the median (range) BNP and N-terminal pro-BNP levels were 572 (13-1,300) and 6,526 (198-70,000) ng/L in patients with sepsis and 581 (6-1,300) and 4,300 (126-70,000) ng/L in patients with HF. The natriuretic peptide levels increased during the ICU stay, but the differences between the groups were not significant. Nine patients with sepsis and eight patients with HF were monitored with a pulmonary artery catheter. Mean (sd) pulmonary artery occlusion pressure were 16 (4.2) and 22 (5.3) mm Hg (p = .02), and cardiac indexes were 4.6 (2.8) and 2.2 (0.6) L/min/m (p = .03) in patients with sepsis and HF, respectively. Despite these clear hemodynamic differences BNP and N-terminal pro-BNP levels were not statistically different between the two groups. In patients with severe sepsis or septic shock, BNP and N-terminal pro-BNP values are highly elevated and, despite significant hemodynamic differences, comparable with those found in acute HF patients. It remains to be determined how elevations of natriuretic peptide levels are linked to inflammation and sepsis-associated myocardial dysfunction.

Multi-complexity measures of heart rate variability and the effect of vasopressor titration: a prospective cohort study of patients with septic shock.

PubMed

Brown, Samuel M; Sorensen, Jeffrey; Lanspa, Michael J; Rondina, Matthew T; Grissom, Colin K; Shahul, Sajid; Mathews, V J

2016-10-10

Septic shock is a common and often devastating syndrome marked by severe cardiovascular dysfunction commonly managed with vasopressors. Whether markers of heart rate complexity before vasopressor up-titration could be used to predict success of the up-titration is not known. We studied patients with septic shock requiring vasopressor, newly admitted to the intensive care unit. We measured the complexity of heart rate variability (using the ratio of fractal exponents from detrended fluctuation analysis) in the 5 min before all vasopressor up-titrations in the first 24 h of an intensive care unit (ICU) admission. A successful up-titration was defined as one that did not require further up-titration (or decrease in mean arterial pressure) for 60 min. We studied 95 patients with septic shock, with a median APACHE II of 27 (IQR: 20-37). The median number of up-titrations, normalized to 24 h, was 12.2 (IQR: 8-17) with a maximum of 49. Of the up-titrations, the median proportion of successful interventions was 0.28 (IQR: 0.12-0.42). The median of mean arterial pressure (MAP) at the time of a vasopressor up-titration was 66 mmHg; the average infusion rate of norepinephrine at the time of an up-titration was 0.11 mcg/kg/min. The ratio of fractal exponents was not associated with successful up-titration on univariate or multivariate regression. On exploratory secondary analyses, however, the long-term fractal exponent was associated (p = 0.003) with success of up-titration. Independent of heart rate variability, MAP was associated (p < 0.001) with success of vasopressor up-titration, while neither Sequential Organ Failure Assessment (SOFA) nor Acute Physiology and Chronic Health Evaluation II (APACHE II) score was associated with vasopressor titration. Only a third of vasopressor up-titrations were successful among patients with septic shock. MAP and the long-term fractal exponent were associated with success of up-titration. These two, complementary variables may be important to the development of rational vasopressor titration protocols.

Comparison of Two Sepsis Recognition Methods in a Pediatric Emergency Department

PubMed Central

Balamuth, Fran; Alpern, Elizabeth R.; Grundmeier, Robert W.; Chilutti, Marianne; Weiss, Scott L.; Fitzgerald, Julie C.; Hayes, Katie; Bilker, Warren; Lautenbach, Ebbing

2015-01-01

Objectives To compare the effectiveness of physician judgment and an electronic algorithmic alert to identify pediatric patients with severe sepsis/septic shock in a pediatric emergency department (ED). Methods This was an observational cohort study of patients older than 56 days with fever or hypothermia. All patients were evaluated for potential sepsis in real time by the ED clinical team. An electronic algorithmic alert was retrospectively applied to identify patients with potential sepsis independent of physician judgment. The primary outcome was the proportion of patients correctly identified with severe sepsis/septic shock defined by consensus criteria. Test characteristics were determined and receiver operating characteristic (ROC) curves were compared. Results Of 19,524 eligible patient visits, 88 patients developed consensus-confirmed severe sepsis or septic shock. Physician judgment identified 159, and the algorithmic alert identified 3,301 patients with potential sepsis. Physician judgment had sensitivity of 72.7% (95% CI = 72.1% to 73.4%) and specificity 99.5% (95% CI = 99.4% to 99.6%); the algorithmic alert had sensitivity 92.1% (95% CI = 91.7% to 92.4%), and specificity 83.4% (95% CI = 82.9% to 83.9%) for severe sepsis/septic shock. There was no significant difference in the area under the ROC curve for physician judgment (0.86, 95% CI = 0.81 to 0.91) or the algorithm (0.88, 95% CI = 0.85 to 0.91; p = 0.54). A combination method using either positive physician judgment or an algorithmic alert improved sensitivity to 96.6% and specificity to 83.3%. A sequential approach, in which positive identification by the algorithmic alert was then confirmed by physician judgment, achieved 68.2% sensitivity and 99.6% specificity. Positive and negative predictive values for physician judgment vs. algorithmic alert were 40.3% vs. 2.5% and 99.88 % vs. 99.96%, respectively. Conclusions The electronic algorithmic alert was more sensitive but less specific than physician judgment for recognition of pediatric severe sepsis and septic shock. These findings can help to guide institutions in selecting pediatric sepsis recognition methods based on institutional needs and priorities. PMID:26474032

Comparison of Two Sepsis Recognition Methods in a Pediatric Emergency Department.

PubMed

Balamuth, Fran; Alpern, Elizabeth R; Grundmeier, Robert W; Chilutti, Marianne; Weiss, Scott L; Fitzgerald, Julie C; Hayes, Katie; Bilker, Warren; Lautenbach, Ebbing

2015-11-01

The objective was to compare the effectiveness of physician judgment and an electronic algorithmic alert to identify pediatric patients with severe sepsis/septic shock in a pediatric emergency department (ED). This was an observational cohort study of patients older than 56 days with fever or hypothermia. All patients were evaluated for potential sepsis in real time by the ED clinical team. An electronic algorithmic alert was retrospectively applied to identify patients with potential sepsis independent of physician judgment. The primary outcome was the proportion of patients correctly identified with severe sepsis/septic shock defined by consensus criteria. Test characteristics were determined and receiver operating characteristic (ROC) curves were compared. Of 19,524 eligible patient visits, 88 patients developed consensus-confirmed severe sepsis or septic shock. Physician judgment identified 159 and the algorithmic alert identified 3,301 patients with potential sepsis. Physician judgment had sensitivity of 72.7% (95% confidence interval [CI] = 72.1% to 73.4%) and specificity of 99.5% (95% CI = 99.4% to 99.6%); the algorithmic alert had sensitivity of 92.1% (95% CI = 91.7% to 92.4%) and specificity of 83.4% (95% CI = 82.9% to 83.9%) for severe sepsis/septic shock. There was no significant difference in the area under the ROC curve for physician judgment (0.86, 95% CI = 0.81 to 0.91) or the algorithm (0.88, 95% CI = 0.85 to 0.91; p = 0.54). A combination method using either positive physician judgment or an algorithmic alert improved sensitivity to 96.6% and specificity to 83.3%. A sequential approach, in which positive identification by the algorithmic alert was then confirmed by physician judgment, achieved 68.2% sensitivity and 99.6% specificity. Positive and negative predictive values for physician judgment versus algorithmic alert were 40.3% versus 2.5% and 99.88% versus 99.96%, respectively. The electronic algorithmic alert was more sensitive but less specific than physician judgment for recognition of pediatric severe sepsis and septic shock. These findings can help to guide institutions in selecting pediatric sepsis recognition methods based on institutional needs and priorities. © 2015 by the Society for Academic Emergency Medicine.

Risk factors and outcomes of bacteremia caused by drug-resistant ESKAPE pathogens in solid-organ transplant recipients.

PubMed

Bodro, Marta; Sabé, Núria; Tubau, Fe; Lladó, Laura; Baliellas, Carme; Roca, Josep; Cruzado, Josep Maria; Carratalà, Jordi

2013-11-15

Although infections due to the six ESKAPE pathogens have recently been identified as a serious emerging problem, information regarding bacteremia caused by these organisms in solid-organ transplant (SOT) recipients is lacking. We sought to determine the frequency, risk factors, and outcomes of bacteremia due to drug-resistant ESKAPE (rESKAPE) organisms in liver, kidney, and heart adult transplant recipients. All episodes of bacteremia prospectively documented in hospitalized SOT recipients from 2007 to 2012 were analyzed. Of 276 episodes of bacteremia, 54 (19.6%) were due to rESKAPE strains (vancomycin-resistant Enterococcus faecium [0], methicillin-resistant Staphylococcus aureus [5], extended-spectrum β-lactamase-producing Klebsiella pneumoniae [10], carbapenem-resistant Acinetobacter baumannii [8], carbapenem- and quinolone-resistant Pseudomonas aeruginosa [26], and derepressed chromosomal β-lactam and extended-spectrum β-lactamase-producing Enterobacter species [5]). Factors independently associated with rESKAPE bacteremia were prior transplantation, septic shock, and prior antibiotic therapy. Patients with rESKAPE bacteremia more often received inappropriate empirical antibiotic therapy than the others (41% vs. 21.6%; P=0.01). Overall case-fatality rate (30 days) was higher in patients with rESKAPE bacteremia (35.2% vs. 14.4%; P=0.001). Bacteremia due to rESKAPE pathogens is frequent in SOT recipients and causes significant morbidity and mortality. rESKAPE organisms should be considered when selecting empirical antibiotic therapy for hospitalized SOT recipients presenting with septic shock, particularly those with prior transplantation and antibiotic use.

Abortion at Gondar College Hospital, Ethiopia.

PubMed

Yusuf, L; Zein, Z A

2001-05-01

To review the pattern and magnitude of abortion in order to establish baseline facts and data for future studies. A descriptive cross-sectional study. Gondar College of Medical Sciences Hospital, Gondar, Ethiopia. Most of the subjects originated from the Gondar city and were married housewives, parous and relatively young. The abortion rate and ratio per 100 pregnancies and deliveries were 11.5 and 16.4, respectively. Only 13.4% of the patients admitted history of interference with the pregnancy. Previous history of abortion was obtained in 10.6% of the patients. The mean gestational ages for septic and non-septic cases were 14.6 and 15.2 weeks, respectively even though pregnancies less than 12 weeks from the last normal menstrual period accounted for 50.5%. The commonly diagnosed clinical type was incomplete, followed by inevitable and threatened abortion. The vast majority of the clinical conditions were non-septic (85.1 %) and spontaneous(85.6 %). The most common complications registered were anaemia, genital tract infection, shock of various causes and soft tissue injury. Four mothers died of abortion-related complications. The mean hospital stays for non-septic and septic abortion were three and five days, respectively. The study has attempted to address the issue of abortion in its general clinical pattern in relation to the various parameters. Being comprehensive, it also provides awareness and sensitivity on the magnitude of abortion and is assumed quite helpful for policy and decision makers.

Applying dynamic parameters to predict hemodynamic response to volume expansion in spontaneously breathing patients with septic shock

PubMed Central

Lanspa, Michael J.; Grissom, Colin K.; Hirshberg, Eliotte L.; Jones, Jason P.; Brown, Samuel M.

2013-01-01

Background Volume expansion is a mainstay of therapy in septic shock, although its effect is difficult to predict using conventional measurements. Dynamic parameters, which vary with respiratory changes, appear to predict hemodynamic response to fluid challenge in mechanically ventilated, paralyzed patients. Whether they predict response in patients who are free from mechanical ventilation is unknown. We hypothesized that dynamic parameters would be predictive in patients not receiving mechanical ventilation. Methods This is a prospective, observational, pilot study. Patients with early septic shock and who were not receiving mechanical ventilation received 10 ml/kg volume expansion (VE) at their treating physician's discretion after initial resuscitation in the emergency department. We used transthoracic echocardiography to measure vena cava collapsibility index (VCCI) and aortic velocity variation (AoVV) prior to VE. We used a pulse contour analysis device to measure stroke volume variation (SVV). Cardiac index was measured immediately before and after VE using transthoracic echocardiography. Hemodynamic response was defined as an increase in cardiac index ≥ 15%. Results 14 patients received VE, 5 of which demonstrated a hemodynamic response. VCCI and SVV were predictive (Area under curve = 0.83, 0.92, respectively). Optimal thresholds were calculated: VCCI ≥ 15% (Positive predictive value, PPV 62%, negative predictive value, NPV 100%, p = 0.03); SVV ≥ 17% (PPV 100%, NPV 82%, p = 0.03). AoVV was not predictive. Conclusions VCCI and SVV predict hemodynamic response to fluid challenge patients with septic shock who are not mechanically ventilated. Optimal thresholds differ from those described in mechanically ventilated patients. PMID:23324885

Mitochondrial Changes in Platelets Are Not Related to Those in Skeletal Muscle during Human Septic Shock

PubMed Central

Protti, Alessandro; Fortunato, Francesco; Caspani, Maria L.; Pluderi, Mauro; Lucchini, Valeria; Grimoldi, Nadia; Solimeno, Luigi P.; Fagiolari, Gigliola; Ciscato, Patrizia; Zella, Samis M. A.; Moggio, Maurizio; Comi, Giacomo P.; Gattinoni, Luciano

2014-01-01

Platelets can serve as general markers of mitochondrial (dys)function during several human diseases. Whether this holds true even during sepsis is unknown. Using spectrophotometry, we measured mitochondrial respiratory chain biochemistry in platelets and triceps brachii muscle of thirty patients with septic shock (within 24 hours from admission to Intensive Care) and ten surgical controls (during surgery). Results were expressed relative to citrate synthase (CS) activity, a marker of mitochondrial density. Patients with septic shock had lower nicotinamide adenine dinucleotide dehydrogenase (NADH)/CS (p = 0.015), complex I/CS (p = 0.018), complex I and III/CS (p<0.001) and complex IV/CS (p = 0.012) activities in platelets but higher complex I/CS activity (p = 0.021) in triceps brachii muscle than controls. Overall, NADH/CS (r2 = 0.00; p = 0.683) complex I/CS (r2 = 0.05; p = 0.173), complex I and III/CS (r2 = 0.01; p = 0.485), succinate dehydrogenase (SDH)/CS (r2 = 0.00; p = 0.884), complex II and III/CS (r2 = 0.00; p = 0.927) and complex IV/CS (r2 = 0.00; p = 0.906) activities in platelets were not associated with those in triceps brachii muscle. In conclusion, several respiratory chain enzymes were variably inhibited in platelets, but not in triceps brachii muscle, of patients with septic shock. Sepsis-induced mitochondrial changes in platelets do not reflect those in other organs. PMID:24787741

Patient and Organizational Factors Associated With Delays in Antimicrobial Therapy for Septic Shock.

PubMed

Amaral, Andre C K B; Fowler, Robert A; Pinto, Ruxandra; Rubenfeld, Gordon D; Ellis, Paul; Bookatz, Brian; Marshall, John C; Martinka, Greg; Keenan, Sean; Laporta, Denny; Roberts, Daniel; Kumar, Anand

2016-12-01

To identify clinical and organizational factors associated with delays in antimicrobial therapy for septic shock. In a retrospective cohort of critically ill patients with septic shock. Twenty-four ICUs. A total of 6,720 patients with septic shock. None. Higher Acute Physiology Score (+24 min per 5 Acute Physiology Score points; p < 0.0001); older age (+16 min per 10 yr; p < 0.0001); presence of comorbidities (+35 min; p < 0.0001); hospital length of stay before hypotension: less than 3 days (+50 min; p < 0.0001), between 3 and 7 days (+121 min; p < 0.0001), and longer than 7 days (+130 min; p < 0.0001); and a diagnosis of pneumonia (+45 min; p < 0.01) were associated with longer times to antimicrobial therapy. Two variables were associated with shorter times to antimicrobial therapy: community-acquired infections (-53 min; p < 0.001) and higher temperature (-15 min per 1°C; p < 0.0001). After adjusting for confounders, admissions to academic hospitals (+52 min; p< 0.05), and transfers from medical wards (medical vs surgical ward admission; +39 min; p < 0.05) had longer times to antimicrobial therapy. Admissions from the emergency department (emergency department vs surgical ward admission, -47 min; p< 0.001) had shorter times to antimicrobial therapy. We identified clinical and organizational factors that can serve as evidence-based targets for future quality-improvement initiatives on antimicrobial timing. The observation that academic hospitals are more likely to delay antimicrobials should be further explored in future trials.

Very high volume hemofiltration with the Cascade system in septic shock patients.

PubMed

Quenot, Jean-Pierre; Binquet, Christine; Vinsonneau, Christophe; Barbar, Saber-David; Vinault, Sandrine; Deckert, Valerie; Lemaire, Stéphanie; Hassain, Ali Ait; Bruyère, Rémi; Souweine, Bertrand; Lagrost, Laurent; Adrie, Christophe

2015-12-01

We compared hemodynamic and biological effects of the Cascade system, which uses very high volume hemofiltration (HVHF) (120 mL kg(-1) h(-1)), with those of usual care in patients with septic shock. Multicenter, prospective, randomized, open-label trial in three intensive care units (ICU). Adults with septic shock with administration of epinephrine/norepinephrine were eligible. Patients were randomized to usual care plus HVHF (Cascade group), or usual care alone (control group). Primary end point was the number of catecholamine-free days up to 28 days after randomization. Secondary end points were number of days free of mechanical ventilation, renal replacement therapy (RRT) or ICU up to 90 days, and 7-, 28-, and 90-day mortality. We included 60 patients (29 Cascade, 31 usual care). Baseline characteristics were comparable. Median number of catecholamine-free days was 22 [IQR 11-23] vs 20 [0-25] for Cascade vs control; there was no significant difference even after adjustment. There was no significant difference in number of mechanical ventilation-free days or ICU requirement. Median number of RRT-free days was 85 [46-90] vs 74 [0-90] for Cascade vs control groups, p = 0.42. By multivariate analysis, the number of RRT-free days was significantly higher in the Cascade group (up to 25 days higher after adjustment). There was no difference in mortality at 7, 28, or 90 days. Very HVHF using the Cascade system can safely be used in patients presenting with septic shock, but it was not associated with a reduction in the need for catecholamines during the first 28 days.

Hypoalbuminemia, Low Base Excess Values, and Tachypnea Predict 28-Day Mortality in Severe Sepsis and Septic Shock Patients in the Emergency Department.

PubMed

Seo, Min Ho; Choa, Minhong; You, Je Sung; Lee, Hye Sun; Hong, Jung Hwa; Park, Yoo Seok; Chung, Sung Phil; Park, Incheol

2016-11-01

The objective of this study was to develop a new nomogram that can predict 28-day mortality in severe sepsis and/or septic shock patients using a combination of several biomarkers that are inexpensive and readily available in most emergency departments, with and without scoring systems. We enrolled 561 patients who were admitted to an emergency department (ED) and received early goal-directed therapy for severe sepsis or septic shock. We collected demographic data, initial vital signs, and laboratory data sampled at the time of ED admission. Patients were randomly assigned to a training set or validation set. For the training set, we generated models using independent variables associated with 28-day mortality by multivariate analysis, and developed a new nomogram for the prediction of 28-day mortality. Thereafter, the diagnostic accuracy of the nomogram was tested using the validation set. The prediction model that included albumin, base excess, and respiratory rate demonstrated the largest area under the receiver operating characteristic curve (AUC) value of 0.8173 [95% confidence interval (CI), 0.7605-0.8741]. The logistic analysis revealed that a conventional scoring system was not associated with 28-day mortality. In the validation set, the discrimination of a newly developed nomogram was also good, with an AUC value of 0.7537 (95% CI, 0.6563-0.8512). Our new nomogram is valuable in predicting the 28-day mortality of patients with severe sepsis and/or septic shock in the emergency department. Moreover, our readily available nomogram is superior to conventional scoring systems in predicting mortality.

Severe sepsis and septic shock in pre-hospital emergency medicine: survey results of medical directors of emergency medical services concerning antibiotics, blood cultures and algorithms.

PubMed

Casu, Sebastian; Häske, David

2016-06-01

Delayed antibiotic treatment for patients in severe sepsis and septic shock decreases the probability of survival. In this survey, medical directors of different emergency medical services (EMS) in Germany were asked if they are prepared for pre-hospital sepsis therapy with antibiotics or special algorithms to evaluate the individual preparations of the different rescue areas for the treatment of patients with this infectious disease. The objective of the survey was to obtain a general picture of the current status of the EMS with respect to rapid antibiotic treatment for sepsis. A total of 166 medical directors were invited to complete a short survey on behalf of the different rescue service districts in Germany via an electronic cover letter. Of the rescue districts, 25.6 % (n = 20) stated that they keep antibiotics on EMS vehicles. In addition, 2.6 % carry blood cultures on the vehicles. The most common antibiotic is ceftriaxone (third generation cephalosporin). In total, 8 (10.3 %) rescue districts use an algorithm for patients with sepsis, severe sepsis or septic shock. Although the German EMS is an emergency physician-based rescue system, special opportunities in the form of antibiotics on emergency physician vehicles are missing. Simultaneously, only 10.3 % of the rescue districts use a special algorithm for sepsis therapy. Sepsis, severe sepsis and septic shock do not appear to be prioritized as highly as these deadly diseases should be in the pre-hospital setting.

Norepinephrine kinetics and dynamics in septic shock and trauma patients.

PubMed

Beloeil, H; Mazoit, J-X; Benhamou, D; Duranteau, J

2005-12-01

There is considerable variability in the inter-patient response to norepinephrine. Pharmacokinetic studies of dopamine infusion in volunteers and in patients have also shown large variability. The purpose of this study was to define the pharmacokinetics of norepinephrine in septic shock and trauma patients. After Ethical Committee approval and written informed family consent, 12 patients with septic shock and 11 trauma patients requiring norepinephrine infusion were studied. Norepinephrine dose was increased in three successive steps of 0.1 mg kg(-1) min(-1) at 15-min intervals (20% maximum allowed increase in arterial pressure). Arterial blood was sampled before and at 0.5, 13, and 15 min after each infusion rate change and 30 s, 1, 2, 5, 10, and 15 min after return to baseline dosing. Norepinephrine was assayed by HPLC. The pharmacokinetics were modelled using NONMEM (one-compartment model). The effects of group, body weight (BW), gender and SAPS II (Simplified Acute Physiology Score II) [Le Gall JR, Lemeshow S, Saulnier F. A new Simplified Acute Physiology Score (SAPS II) based on a European/North American multicenter study. J Am Med Assoc 1993; 270: 2957-63] patients score on clearance (CL) and volume of distribution (V) were tested. Group, gender, and BW did not influence CL or V. CL was negatively related to SAPS II. CL and T(1/2) varied from 3 litre min(-1) and 2 min, respectively, when SAPS II=20 to 0.9 litre min(-1) and 6.8 min when SAPS II=60. In trauma patients and in septic shock patients, norepinephrine clearance is negatively related to SAPS II.

Accuracy of a real-time continuous glucose monitoring system in children with septic shock: A pilot study.

PubMed

Prabhudesai, Sumant; Kanjani, Amruta; Bhagat, Isha; Ravikumar, Karnam G; Ramachandran, Bala

2015-11-01

The aim of this prospective, observational study was to determine the accuracy of a real-time continuous glucose monitoring system (CGMS) in children with septic shock. Children aged 30 days to 18 years admitted to the Pediatric Intensive Care Unit with septic shock were included. A real-time CGMS sensor was used to obtain interstitial glucose readings. CGMS readings were compared statistically with simultaneous laboratory blood glucose (BG). Nineteen children were included, and 235 pairs of BG-CGMS readings were obtained. BG and CGMS had a correlation coefficient of 0.61 (P < 0.001) and a median relative absolute difference of 17.29%. On Clarke's error grid analysis, 222 (94.5%) readings were in the clinically acceptable zones (A and B). When BG was < 70, 70-180, and > 180 mg/dL, 44%, 100%, and 76.9% readings were in zones A and B, respectively (P < 0.001). The accuracy of CGMS was not affected by the presence of edema, acidosis, vasopressors, steroids, or renal replacement therapy. On receiver operating characteristics curve analysis, a CGMS reading <97 mg/dL predicted hypoglycemia (sensitivity 85.2%, specificity 75%, area under the curve [AUC] =0.85). A reading > 141 mg/dL predicted hyperglycemia (sensitivity 84.6%, specificity 89.6%, AUC = 0.87). CGMS provides a fairly, accurate estimate of BG in children with septic shock. It is unaffected by a variety of clinical variables. The accuracy over extremes of blood sugar may be a concern. We recommend larger studies to evaluate its use for the early detection of hypoglycemia and hyperglycemia.

Blood pressure targets for vasopressor therapy: a systematic review.

PubMed

D'Aragon, Frederick; Belley-Cote, Emilie P; Meade, Maureen O; Lauzier, François; Adhikari, Neill K J; Briel, Matthias; Lalu, Manoj; Kanji, Salmaan; Asfar, Pierre; Turgeon, Alexis F; Fox-Robichaud, Alison; Marshall, John C; Lamontagne, François

2015-06-01

Physicians often prescribe vasopressors to correct pathological vasodilation and improve tissue perfusion in patients with septic shock, but the evidence to inform practice on vasopressor dosing is weak. We undertook a systematic review of clinical studies evaluating different blood pressure targets for the dosing of vasopressors in septic shock. We searched MEDLINE, EMBASE, CENTRAL (to November 2013), reference lists from included articles, and trial registries for randomized controlled trials (RCTs) and observational and crossover intervention studies comparing different blood pressure targets for vasopressor therapy in septic shock. Two reviewers independently selected eligible studies and extracted data on standardized forms. We identified 2 RCTs and 10 crossover trials but no observational studies meeting our criteria. Only one RCT measured clinical outcomes after comparing mean arterial pressure targets of 80 to 85 mmHg versus 65 to 70 mmHg. There was no effect on 28-day mortality, but confidence intervals were wide (hazard ratio, 95% confidence interval [95% CI] 0.84 - 1.38). In contrast, this intervention was associated with a greater risk of atrial fibrillation (relative risk, 2.36; 95% CI, 1.18 - 4.72) and a lower risk of renal replacement therapy in hypertensive patients (relative risk, 0.75; 95% CI, 0.57 - 1.0). Crossover trials suggest that achieving higher blood pressure targets by increasing vasopressor doses increases heart rate and cardiac index with no effect on serum lactate. Our findings underscore the paucity of clinical evidence to guide the administration of vasopressors in critically ill patients with septic shock. Further rigorous research is needed to establish an evidence base for vasopressor administration in this population.

Lung protein leakage in feline septic shock.

PubMed

Schützer, K M; Larsson, A; Risberg, B; Falk, A

1993-06-01

The aim of the present study was to explore lung microvascular leakage of protein and water in a feline model of septic shock, using a double isotope technique with external gamma camera detection and gravimetric lung water measurements. The experiments were performed on artificially ventilated cats. One group of cats (n = 8) was given an infusion of live Escherichia coli bacteria, and another group (n = 5) served as a control group receiving saline. Plasma transferrin was radiolabeled in vivo with indium-113m-chloride, and erythrocytes were labeled with technetium-99m. The distribution of these isotopes in the lungs was continuously measured with a gamma camera. A normalized slope index (NSI) was calculated, indicative of the transferrin accumulation corrected for changes in local blood volume that reflect protein leakage. In the septic group there was a protein leakage after bacterial infusion, with a NSI of 39 x 10(-4) +/- 5 x 10(-4) min-1 (mean +/- SEM), and the PaO2 diminished from 21 +/- 1 to 9.5 +/- 1 kPa. In control cats a slight protein leakage with a NSI of 9 +/- 10(-4) +/- 2 x 10(-4) min-1 was detected, probably caused by the operative procedure, but PaO2 did not change. Wet-to-dry-weight ratios of postmortem lungs were not significantly different between the groups. It was concluded that an intravenous infusion of live E. coli bacteria induces a lung capillary protein leakage without increased lung water and a concomitantly disturbed gas exchange.(ABSTRACT TRUNCATED AT 250 WORDS)

Epidemiology of sepsis in intensive care units in Turkey: a multicenter, point-prevalence study.

PubMed

Baykara, Nur; Akalın, Halis; Arslantaş, Mustafa Kemal; Hancı, Volkan; Çağlayan, Çiğdem; Kahveci, Ferda; Demirağ, Kubilay; Baydemir, Canan; Ünal, Necmettin

2018-04-16

The prevalence and mortality of sepsis are largely unknown in Turkey, a country with high antibiotic resistance. A national, multicenter, point-prevalence study was conducted to determine the prevalence, causative microorganisms, and outcome of sepsis in intensive care units (ICUs) in Turkey. A total of 132 ICUs from 94 hospitals participated. All patients (aged > 18 years) present at the participating ICUs or admitted for any duration within a 24-h period (08:00 on January 27, 2016 to 08:00 on January 28, 2016) were included. The presence of systemic inflammatory response syndrome (SIRS), severe sepsis, and septic shock were assessed and documented based on the consensus criteria of the American College of Chest Physicians and Society of Critical Care Medicine (SEPSIS-I) in infected patients. Patients with septic shock were also assessed using the SEPSIS-III definitions. Data regarding demographics, illness severity, comorbidities, microbiology, therapies, length of stay, and outcomes (dead/alive during 30 days) were recorded. Of the 1499 patients included in the analysis, 237 (15.8%) had infection without SIRS, 163 (10.8%) had infection with SIRS, 260 (17.3%) had severe sepsis without shock, and 203 (13.5%) had septic shock. The mortality rates were higher in patients with severe sepsis (55.7%) and septic shock (70.4%) than those with infection alone (24.8%) and infection + SIRS (31.2%) (p < 0.001). According to SEPSIS-III, 104 (6.9%) patients had septic shock (mortality rate, 75.9%). The respiratory system (71.6%) was the most common site of infection, and Acinetobacter spp. (33.7%) were the most common isolated pathogen. Approximately, 74.9%, 39.1%, and 26.5% of Acinetobacter, Klebsiella, and Pseudomonas spp. isolates, respectively, were carbapenem-resistant, which was not associated with a higher mortality risk. Age, acute physiology and chronic health evaluation II score at ICU admission, sequential organ failure assessment score on study day, solid organ malignancy, presence of severe sepsis or shock, Candida spp. infection, renal replacement treatment, and a nurse-to-patient ratio of 1:4 (compared with a nurse-to-patient ratio of 1:2) were independent predictors of mortality in infected patients. A high prevalence of sepsis and an unacceptably high mortality rate were observed in Turkish ICUs. Although the prevalence of carbapenem resistance was high in Turkish ICUs, it was not associated with a higher risk for mortality. ClinicalTrials.gov ID NCT03249246 . Date: August 15, 2017. Retrospectively registered.

[New recommendations on the use of human albumin solutions in patients with severe sepsis and septic shock. A critical evaluation of the literature].

PubMed

Latour-Pérez, J

2013-01-01

The third edition of the Surviving Sepsis Campaign guidelines opens the door to the use of albumin for fluid resuscitation in patients with severe sepsis and septic shock. This recommendation is based on a recent meta-analysis that included studies with evidence of insufficient plasma expansion in the control group and studies performed in children with malaria with clear statistical heterogeneity (P for interaction=.02). After excluding pediatric studies, the confidence interval of the effect estimate was consistent with a mortality excess in the group treated with albumin (OR=.87 [95%CI: .71 to 1.07]). Two new randomized studies reported after publication of the meta-analysis found no benefit in patients treated with albumin. Given the uncertainty about the true effect of albumin (due to the existence of indirectness and imprecision) and its cost considerations, it is suggested not to use albumin in the initial resuscitation of patients with severe sepsis and septic shock (GRADE2C). Copyright © 2013 Elsevier España, S.L. and SEMICYUC. All rights reserved.

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.

Brain lesions in septic shock: a magnetic resonance imaging study.

PubMed

Sharshar, Tarek; Carlier, Robert; Bernard, Francis; Guidoux, Céline; Brouland, Jean-Philippe; Nardi, Olivier; de la Grandmaison, Geoffroy Lorin; Aboab, Jérôme; Gray, Françoise; Menon, David; Annane, Djillali

2007-05-01

Understanding of sepsis-induced brain dysfunction remains poor, and relies mainly on data from animals or post-mortem studies in patients. The current study provided findings from magnetic resonance imaging of the brain in septic shock. Nine patients with septic shock and brain dysfunction [7 women, median age 63 years (interquartile range 61-79 years), SAPS II: 48 (44-56), SOFA: 8 (6-10)] underwent brain magnetic resonance imaging including gradient echo T1-weighted, fluid-attenuated inversion recovery (FLAIR), T2-weighted and diffusion isotropic images, and mapping of apparent diffusion coefficient. Brain imaging was normal in two patients, showed multiple ischaemic strokes in two patients, and in the remaining patients showed white matter lesions at the level of the centrum semiovale, predominating around Virchow-Robin spaces, ranging from small multiple areas to diffuse lesions, and characterised by hyperintensity on FLAIR images. The main lesions were also characterised by reduced signal on diffusion isotropic images and increased apparent diffusion coefficient. The lesions of the white matter worsened with increasing duration of shock and were correlated with Glasgow Outcome Score. This preliminary study showed that sepsis-induced brain lesions can be documented by magnetic resonance imaging. These lesions predominated in the white matter, suggesting increased blood-brain barrier permeability, and were associated with poor outcome.

Group A streptococcal infections in obstetrics and gynecology.

PubMed

Rimawi, Bassam H; Soper, David E; Eschenbach, David A

2012-12-01

Group A streptococcal (GAS) infections continue to be an infrequent, but potentially lethal infections in women despite the victory over childbed fever in the 1800s. Invasive group A streptococcal infection still causes 40% of septic deaths among patients with postpartum endometritis, necrotizing fasciitis, and toxic shock syndrome. Many times symptoms and signs of this infection are nonspecific, but laboratory evaluation can suggest serious infection. The prudent combination of antibiotic and surgical therapy can be lifesaving.

Outcome and prognostic factors in critically ill patients with systemic lupus erythematosus: a retrospective study.

PubMed

Hsu, Chia-Lin; Chen, Kuan-Yu; Yeh, Pu-Sheng; Hsu, Yeong-Long; Chang, Hou-Tai; Shau, Wen-Yi; Yu, Chia-Li; Yang, Pan-Chyr

2005-06-01

Systemic lupus erythematosus (SLE) is an archetypal autoimmune disease, involving multiple organ systems with varying course and prognosis. However, there is a paucity of clinical data regarding prognostic factors in SLE patients admitted to the intensive care unit (ICU). From January 1992 to December 2000, all patients admitted to the ICU with a diagnosis of SLE were included. Patients were excluded if the diagnosis of SLE was established at or after ICU admission. A multivariate logistic regression model was applied using Acute Physiology and Chronic Health Evaluation II scores and variables that were at least moderately associated (P < 0.2) with survival in the univariate analysis. A total of 51 patients meeting the criteria were included. The mortality rate was 47%. The most common cause of admission was pneumonia with acute respiratory distress syndrome. Multivariate logistic regression analysis showed that intracranial haemorrhage occurring while the patient was in the ICU (relative risk = 18.68), complicating gastrointestinal bleeding (relative risk = 6.97) and concurrent septic shock (relative risk = 77.06) were associated with greater risk of dying, whereas causes of ICU admission and Acute Physiology and Chronic Health Evaluation II score were not significantly associated with death. The mortality rate in critically ill SLE patients was high. Gastrointestinal bleeding, intracranial haemorrhage and septic shock were significant prognostic factors in SLE patients admitted to the ICU.

Preliminary clinical evaluation of automated analysis of the sublingual microcirculation in the assessment of patients with septic shock: Comparison of automated versus semi-automated software.

PubMed

Sharawy, Nivin; Mukhtar, Ahmed; Islam, Sufia; Mahrous, Reham; Mohamed, Hassan; Ali, Mohamed; Hakeem, Amr A; Hossny, Osama; Refaa, Amera; Saka, Ahmed; Cerny, Vladimir; Whynot, Sara; George, Ronald B; Lehmann, Christian

2017-01-01

The outcome of patients in septic shock has been shown to be related to changes within the microcirculation. Modern imaging technologies are available to generate high resolution video recordings of the microcirculation in humans. However, evaluation of the microcirculation is not yet implemented in the routine clinical monitoring of critically ill patients. This is mainly due to large amount of time and user interaction required by the current video analysis software. The aim of this study was to validate a newly developed automated method (CCTools®) for microcirculatory analysis of sublingual capillary perfusion in septic patients in comparison to standard semi-automated software (AVA3®). 204 videos from 47 patients were recorded using incident dark field (IDF) imaging. Total vessel density (TVD), proportion of perfused vessels (PPV), perfused vessel density (PVD), microvascular flow index (MFI) and heterogeneity index (HI) were measured using AVA3® and CCTools®. Significant differences between the numeric results obtained by the two different software packages were observed. The values for TVD, PVD and MFI were statistically related though. The automated software technique successes to show septic shock induced microcirculation alterations in near real time. However, we found wide degrees of agreement between AVA3® and CCTools® values due to several technical factors that should be considered in the future studies.

Severe leptospirosis with multiple organ failure successfully treated by plasma exchange and high-volume hemofiltration.

PubMed

Bourquin, Vincent; Ponte, Belén; Hirschel, Bernard; Pugin, Jérôme; Martin, Pierre-Yves; Saudan, Patrick

2011-01-01

Background. Leptospirosis is a spirochetal zoonosis with complex clinical features including renal and liver failure. Case report. We report the case of a Swiss fisherman presenting with leptospirosis. After initial improvement, refractory septic shock and severe liver and kidney failure developed. The expected mortality was estimated at 90% with clinical scores. The patient underwent plasma exchanges and high-volume hemofiltration (HVHF) with complete recovery of hepatic and kidney functions. Discussion. Plasma exchanges and HVHF may confer survival benefit on patients with severe leptospirosis, refractory septic shock, and multiple-organ failure.

Eustachian Valve Endocarditis: Echocardiographic Diagnosis in a Critical Care Patient.

PubMed

Alves, Mariana; Faria, Rita; Messias, António; Meneses-Oliveira, Carlos

2018-01-01

Eustachian valve endocarditis is rare. A literature review revealed that only 29 cases have been reported and, among them, there is only one mention of an intensive care unit (ICU) admission. We present an 82-year-old man without previous medical records who presented with septic shock with multiple organ dysfunction. The patient was admitted to the ICU and deteriorated with combined shock (septic + cardiogenic). A second ultrasound screen detected a prominent Eustachian valve with mobile multilobulated vegetation attached. Transesophageal echocardiography confirmed a 12 mm oscillating mass attached to a visible Eustachian valve.

4G/5G polymorphism of PAI-1 gene is associated with multiple organ dysfunction and septic shock in pneumonia induced severe sepsis: prospective, observational, genetic study

PubMed Central

2010-01-01

Introduction Activation of inflammation and coagulation are closely related and mutually interdependent in sepsis. The acute-phase protein, plasminogen activator inhibitor-1 (PAI-1) is a key element in the inhibition of fibrinolysis. Elevated levels of PAI-1 have been related to worse outcome in pneumonia. We aimed to evaluate the effect of functionally relevant 4G/5G polymorphism of PAI-1 gene in pneumonia induced sepsis. Methods We enrolled 208 Caucasian patients with severe sepsis due to pneumonia admitted to an intensive care unit (ICU). Patients were followed up until ICU discharge or death. Clinical data were collected prospectively and the PAI-1 4G/5G polymorphism was genotyped by polymerase chain reaction-restriction fragment length polymorphism technique. Patients were stratified according to the occurrence of multiple organ dysfunction syndrome, septic shock or death. Results We found that carriers of the PAI-1 4G/4G and 4G/5G genotypes have a 2.74-fold higher risk for multiple organ dysfunction syndrome (odds ratio [OR] 95% confidence interval [CI] = 1.335 - 5.604; p = 0.006) and a 2.57-fold higher risk for septic shock (OR 95%CI = 1.180 - 5.615; p = 0.018) than 5G/5G carriers. The multivariate logistic regression analysis adjusted for independent predictors, such as age, nosocomial pneumonia and positive microbiological culture also supported that carriers of the 4G allele have a higher prevalence of multiple organ dysfunction syndrome (adjusted odds ratio [aOR] = 2.957; 95%CI = 1.306 -6.698; p = 0.009) and septic shock (aOR = 2.603; 95%CI = 1.137 - 5.959; p = 0.024). However, genotype and allele analyses have not shown any significant difference regarding mortality in models non-adjusted or adjusted for acute physiology and chronic health evaluation (APACHE) II. Patients bearing the 4G allele had higher disseminated intravascular coagulation (DIC) score at admission (p = 0.007) than 5G/5G carriers. Moreover, in 4G allele carriers the length of ICU stay of non-survivors was longer (p = 0.091), fewer ventilation-free days (p = 0.008) and days without septic shock (p = 0.095) were observed during the first 28 days. Conclusions In Caucasian patients with severe sepsis due to pneumonia carriers of the 4G allele of PAI-1 polymorphism have higher risk for multiple organ dysfunction syndrome and septic shock and in agreement they showed more fulminant disease progression based on continuous clinical variables. PMID:20429897

Association of Fluid Resuscitation Initiation Within 30 Minutes of Severe Sepsis and Septic Shock Recognition With Reduced Mortality and Length of Stay.

PubMed

Leisman, Daniel; Wie, Benjamin; Doerfler, Martin; Bianculli, Andrea; Ward, Mary Frances; Akerman, Meredith; D'Angelo, John K; Zemmel D'Amore, Jason A

2016-09-01

We evaluate the association of intravenous fluid resuscitation initiation within 30 minutes of severe sepsis or septic shock identification in the emergency department (ED) with inhospital mortality and hospital length of stay. We also compare intravenous fluid resuscitation initiated at various times from severe sepsis or septic shock identification's association with the same outcomes. This was a review of a prospective, observational cohort of all ED severe sepsis or septic shock patients during 13 months, captured in a performance improvement database at a single, urban, tertiary care facility (90,000 ED visits/year). The primary exposure was initiation of a crystalloid bolus at 30 mL/kg within 30 minutes of severe sepsis or septic shock identification. Secondary analysis compared intravenous fluid initiated within 30, 31 to 60, or 61 to 180 minutes, or when intravenous fluid resuscitation was initiated at greater than 180 minutes or not provided. Of 1,866 subjects, 53.6% were men, 72.5% were white, mean age was 72 years (SD 16.6 years), and mean initial lactate level was 2.8 mmol/L. Eighty-six percent of subjects were administered intravenous antibiotics within 180 minutes; 1,193 (64%) had intravenous fluid initiated within 30 minutes. Mortality was lower in the within 30 minutes group (159 [13.3%] versus 123 [18.3%]; 95% confidence interval [CI] 1.4% to 8.5%), as was median hospital length of stay (6 days [95% CI 6 to 7] versus 7 days [95% CI 7 to 8]). In multivariate regression that included adjustment for age, lactate, hypotension, acute organ dysfunction, and Emergency Severity Index score, intravenous fluid within 30 minutes was associated with lower mortality (odds ratio 0.63; 95% CI 0.46 to 0.86) and 12% shorter length of stay (hazard ratio=1.14; 95% CI 1.02 to 1.27). In secondary analysis, mortality increased with later intravenous fluid resuscitation initiation: 13.3% (≤30 minutes) versus 16.0% (31 to 60 minutes) versus 16.9% (61 to 180 minutes) versus 19.7% (>180 minutes). Median hospital length of stay also increased with later intravenous fluid initiation: 6 days (95% CI 6 to 7 days) versus 7 days (95% CI 6 to 7 days) versus 7 days (95% CI 6 to 8 days) versus 8 days (95% CI 7 to 9 days). The time of intravenous fluid resuscitation initiation was associated with improved mortality and could be used as an easier obtained alternative to intravenous fluid completion time as a performance indicator in severe sepsis and septic shock management. Copyright © 2016 American College of Emergency Physicians. Published by Elsevier Inc. All rights reserved.

[Surgical intensive care medicine. Current therapy concepts for septic diseases].

PubMed

Niederbichler, A D; Ipaktchi, K; Jokuszies, A; Hirsch, T; Altintas, M A; Handschin, A E; Busch, K H; Gellert, M; Steinau, H-U; Vogt, P M; Steinsträsser, L

2009-10-01

The clinical appearance of septic disorders is characterized by an enormous dynamic. The sepsis-induced dysbalance of the immune system necessitates immediate and aggressive therapeutic interventions to prevent further damage progression of the disease to septic shock and multiple organ failure. This includes supportive therapy to normalize and maintain organ and tissue perfusion as well as the identification of the infection focus. In cases where an infectious focus is identified, surgical source control frequently is a key element of the treatment strategy besides pharmacologic and supportive measures. The integrative approach of the management of septic patients requires rapid communication between the involved medical disciplines and the nursing personnel. Therefore, this article outlines current therapeutic concepts of septic diseases as well as central nursing aspects.

[The impacts of low-dose corticosteroids infusion given in different manners on refractory septic shock patients].

PubMed

Chen, Zhi; Yang, Chunli; He, Huiwei; He, Zhaohui

2015-06-01

To discuss the influence of different ways of low-dose corticosteroids infusion on hemodynamics, changes in blood glucose level and prognosis in patients with refractory septic shock. A prospective single-blind randomized controlled trial was conducted. Refractory septic shock patients admitted to the Department of Critical Care Medicine of Jiangxi Provincial People's Hospital from April 1st, 2013 to October 31st, 2014 were enrolled for the study. The patients were divided into control group and research group by random number table. Besides conventional treatment for septic shock, patients in control group were given 200 mg/d hydrocortisone intravenous infusion lasting for 2 hours, while those of research group were given 8.33 mg/h hydrocortisone per hour with an intravenous pump. Treatment lasted for 5 continuous days for both groups. The changes in heart rate (HR), mean arterial pressure (MAP), central venous pressure (CVP) and arterial blood lactic acid in both groups were observed at the time of enroldment and 6 hours, 24 hours, 48 hours, and 5 days after the treatment. With a dynamic blood glucose monitor, mean blood glucose (MBG) level, largest amplitude of glycemic excursions (LAGE), glucose variability (GV), and the ratio of hyperglycaemia time were recorded. The duration of shock, length of intensive care unit (ICU) stay, total length of hospital stay, and 28-day mortality of both groups were recorded. Seventy-nine septic shock patients were assigned to the treatment, with 41 in control group, and 38 in research group. Compared with control group, 6-hour MAP in research group was obviously lowered [mmHg (1 mmHg=0.133 kPa): 66.31±4.38 vs. 68.58±4.86, t=1.062, P=0.033], but there were no significant differences in HR, MAP, CVP, lactic acid clearance and norepinephrine (NE) utilization rates at other time points between two groups. No significant difference in MBG was found between research group and control group (mmol/L: 8.69±2.14 vs. 9.95±3.87, t=1.771, P=0.080), but LAGE, GV, the ratio of hyperglycemia time in research group were significantly lower than those of the control group [LAGE (mmol/L): 17.18±8.97 vs. 22.71±11.80, t=2.331, P=0.022; GV (mmol/L): 2.57±1.05 vs. 3.16±1.37, t=2.136, P=0.036; the ratio of hyperglycemia time: (43.1±11.7)% vs. (49.4±15.3)%, t=2.044, P=0.044]. There was no statistical difference in the following features between research group and control group, such as the duration of shock (days: 3.47±0.98 vs. 3.61±1.07, t=0.605, P=0.547), length of ICU stay (days: 8.74±3.12 vs. 9.97±3.37, t=1.543, P=0.120), total length of hospital stay (days: 18.34±9.27 vs. 19.58±9.83, t=0.576, P=0.566) and 28-day mortality rate (23.68% vs. 26.83%, χ2=0.103, P=0.748). Compared with slow intravenous infusion, a continuous intravenous supplementation of small amount of hydrocortisone to patients with refractory septic shock could stabilize blood glucose levels and maintain metabolic balance efficiently. However, in both groups there was no significant difference in the efficiency in stabilizing hemodynamics, shortening shock duration, reducing ICU or hospital days and decreasing 28-day mortality.

Effects of sodium nitroprusside on splanchnic microcirculation in a resuscitated porcine model of septic shock.

PubMed

Assadi, A; Desebbe, O; Kaminski, C; Rimmelé, T; Bénatir, F; Goudable, J; Chassard, D; Allaouchiche, B

2008-01-01

We tested the hypothesis that sodium nitroprusside (SNP) might improve the impairment of hepatosplanchnic microcirculatory blood flow (MBF) in septic shock. Fourteen pigs were anaesthetized and their lungs mechanically ventilated. Sepsis was induced with i.v. infusion of live Pseudomonas aeruginosa [1x10(8) colony forming units (CFU) ml(-1) kg(-1)] for 1 h. Sixty minutes later, the animals received in a random succession either SNP or normal saline for 30 min. Mean arterial pressure (MAP), cardiac index (CI), mean pulmonary artery pressure (MPAP), carbon dioxide tension of the ileal mucosa (PCO2; by gas tonometry), ileal mucosal and hepatic MBF by laser Doppler flowmetry, blood gases, and lactates were assessed before, during administration, and 30 min after discontinuing the test drug. Bacterial infusion promoted hypodynamic shock (MAP -18%, CI -33%, ileal MBF -19%, and hepatic MBF -27%), which was converted to normodynamic shock by resuscitation. During SNP infusion, ileal mucosal MBF significantly increased (+19%) compared with control (P = 0.033). Although hepatic MBF increased (+42% from baseline), this did not differ from control. In order to maintain a constant central venous pressure and MAP, fluid loading and norepinephrine (P < 0.01) were increased. Acid-base status was not altered by SNP. In a resuscitated porcine model of the early phase of septic shock, SNP improved ileal mucosal MBF but required a concomitant increase in fluid and norepinephrine supplements to maintain constant systemic haemodynamic parameters.

[Pharmaconutrition with parenteral selenium in sepsis].

PubMed

Langlois, P L; de Oliveira Figliolino, L F; Hardy, G; Manzanares, W

2014-04-01

Critical illness is characterized by oxidative stress which leads to multiple organ failure, and sepsis-related organ dysfunction remains the most common cause of death in the intensive care unit. Over the last 2 decades, different antioxidant therapies have been developed to improve outcomes in septic patients. According to recent evidence, selenium therapy should be considered the cornerstone of the antioxidant strategies. Selenium given as selenious acid or sodium selenite should be considered as a drug or pharmaconutrient with prooxidant and cytotoxic effects when a loading dose in intravenous bolus form is administered, particularly in the early stage of severe sepsis/septic shock. To date, several phase ii trials have demonstrated that selenium therapy may be able to decrease mortality, improve organ dysfunction and reduce infections in critically ill septic patients. The effect of selenium therapy in sepsis syndrome must be confirmed by large, well designed phase iii clinical trials. The purpose of this review is to discuss current evidence on selenium pharmaconutrition in sepsis syndrome. Copyright © 2013 Elsevier España, S.L. and SEMICYUC. All rights reserved.

[Assistenza cardiocircolatoria. (Cardio-circulatory care)].

PubMed

Cogo, P E

2010-06-01

Mortality in pediatric cardiovascular failure is markedly improved with the advent of neonatal and pediatric intensive care and with the implementation of treatment guidelines. In 2002 the American College of Critical Care Medicine Clinical Practice Parameters for Hemodynamic Support of Pediatric and Neonatal Shock reported mortality rates of 0%-5% in previously healthy and 10% in chronically ill children with septic shock associated with implementation of "best clinical practices". Early recognition of shock is the key to successful resuscitation in critically ill children. Often, shock results in or co-exists with myo-cardial dysfunction or acute lung injury. Recognition and appropriate management of these insults is crucial for successful outcomes. Resuscitation should be directed to restoration of tissue perfusion and normalization of cardiac and respiratory function. The underlying cause of shock should also be addressed urgently. The physiological response of individual children to shock resuscitation varies and is often unpredictable. Therefore, repeated assessments of vital parameters are needed for taking appropriate decisions. Global indices of tissue oxygen delivery help in targeting therapies more accurately. Isotonic fluids form the cornerstone of treatment and the amount required for resuscitation is based on etiologies and therapeutic response. After resuscitation has been initiated, targeted history and clinical evaluation must be performed to ascertain the cause of shock and management of co-morbidities should be implemented simultaneously. While the management of shock can be protocol based, the treatment needs to be individualized depending on the suspected etiology and therapeutic response particularly for children who suffer from congenital heart disease.

A comparison of the effect of convection against diffusion in hemodynamics and cytokines clearance in an experimental model of septic shock.

PubMed

Herrera-Gutiérrez, Manuel E; Seller-Pérez, Gemma; Arias-Verdú, Dolores; Granados, Maria M; Dominguez, Juan M; Navarrete, Rocío; Morgaz, Juán; Gómez-Villamandos, Rafael

2012-10-01

Replacement therapies based on the use of convection have value for the removal of inflammatory mediators. Such therapies have been proposed for the management of septic shock, but diffusion has not proved useful in this scenario, unless high-flow membranes are used. The exact role of diffusion in these cases remains to be clarified because continuous replacement therapies are usually delivered with low-flow membranes and mixed convection-diffusion modalities. However, studies specifically addressing this problem have not been performed. Our aim was to define the efficacy of hemofiltration (convection) and hemodialysis (diffusion) in cytokine clearance and hemodynamic improvement in an experimental model of septic shock. Shock was induced in 15 beagle dogs (weight 10-15 kg) by infusion of 1 mg/kg of ultrapure Escherichia coli lipopolysaccharide diluted in 20 mL saline for 10 minutes. Five animals were followed without interventions (controls), five animals were treated with convection (100 mL kg h) for 6 hours, and five animals were treated with diffusion (100 mL kg h) for 6 hours. All subjects in the control group died during the study, whereas all treated subjects survived. Mean arterial pressure, cardiac output, systolic variability volume, systemic vascular resistances, dPMax, and pulmonary compliance improved in treated subjects. However, the differences in mean arterial pressure and cardiac output were significant only in the convection group and not in the diffusion-treated group.Tumor necrosis factor α rose equally in all groups and decreased only in treated subjects. Interleukin 6 rose in the three groups but decreased only in the convection group and remained unchanged in the control and diffusion groups. Convection and diffusion improved survival and hemodynamic parameters in a septic shock model. Improvement was more pronounced with convection, a difference that may be explained by convective clearance of cytokines.

A multicenter multinational study of abdominal candidiasis: epidemiology, outcomes and predictors of mortality.

PubMed

Bassetti, Matteo; Righi, Elda; Ansaldi, Filippo; Merelli, Maria; Scarparo, Claudio; Antonelli, Massimo; Garnacho-Montero, Jose; Diaz-Martin, Ana; Palacios-Garcia, Inmaculada; Luzzati, Roberto; Rosin, Chiara; Lagunes, Leonel; Rello, Jordi; Almirante, Benito; Scotton, Pier Giorgio; Baldin, Gianmaria; Dimopoulos, George; Nucci, Marcio; Munoz, Patricia; Vena, Antonio; Bouza, Emilio; de Egea, Viviana; Colombo, Arnaldo Lopes; Tascini, Carlo; Menichetti, Francesco; Tagliaferri, Enrico; Brugnaro, Pierluigi; Sanguinetti, Maurizio; Mesini, Alessio; Sganga, Gabriele; Viscoli, Claudio; Tumbarello, Mario

2015-09-01

Clinical data on patients with intra-abdominal candidiasis (IAC) is still scarce. We collected data from 13 hospitals in Italy, Spain, Brazil, and Greece over a 3-year period (2011-2013) including patients from ICU, medical, and surgical wards. A total of 481 patients were included in the study. Of these, 27% were hospitalized in ICU. Mean age was 63 years and 57% of patients were male. IAC mainly consisted of secondary peritonitis (41%) and abdominal abscesses (30%); 68 (14%) cases were also candidemic and 331 (69%) had concomitant bacterial infections. The most commonly isolated Candida species were C. albicans (n = 308 isolates, 64%) and C. glabrata (n = 76, 16%). Antifungal treatment included echinocandins (64%), azoles (32%), and amphotericin B (4%). Septic shock was documented in 40.5% of patients. Overall 30-day hospital mortality was 27% with 38.9% mortality in ICU. Multivariate logistic regression showed that age (OR 1.05, 95% CI 1.03-1.07, P < 0.001), increments in 1-point APACHE II scores (OR 1.05, 95% CI 1.01-1.08, P = 0.028), secondary peritonitis (OR 1.72, 95% CI 1.02-2.89, P = 0.019), septic shock (OR 3.29, 95% CI 1.88-5.86, P < 0.001), and absence of adequate abdominal source control (OR 3.35, 95% CI 2.01-5.63, P < 0.001) were associated with mortality. In patients with septic shock, absence of source control correlated with mortality rates above 60% irrespective of administration of an adequate antifungal therapy. Low percentages of concomitant candidemia and high mortality rates are documented in IAC. In patients presenting with septic shock, source control is fundamental.

Shenfu injection for improving cellular immunity and clinical outcome in patients with sepsis or septic shock.

PubMed

Zhang, Ning; Liu, Jianhua; Qiu, Zeliang; Ye, Yiping; Zhang, Jian; Lou, Tianzheng

2017-01-01

To assess the efficacy of Shenfu injection (SFI) for enhancing cellular immunity and improving the clinical outcomes of patients with septic shock. Patients with sepsis were randomly assigned to receive either SFI at a dose of 100mL every 24hours for 7 consecutive days or a placebo in addition to conventional therapy. The immunologic parameters were collected on days 1, 3, and 7 after the above treatments, and the clinical outcomes were updated for 28days. Of these160 patients, 3 were excluded from the analysis due to protocol violation and withdrawal of consent; thus, 157 completed the study (78 in the SFI group and 79 in the placebo group). We found that SFI increased both CD4 + and CD8 + T cells in peripheral blood and up-regulated HLA-DR expression in monocytes (P<.05). Furthermore, SFI was also found to restore ex vivo monocytic tumor necrosis factor α and interleukin 6 proinflammatory cytokine release in response to the endotoxin (P<.05). Importantly, the SFI group showed better clinical outcomes than did the placebo group in terms of the duration of vasopressor use (P=.008), Acute Physiology and Chronic Health Evaluation II score (P=.034), Marshall score (P=.01), and length of intensive care unit stay (10.5±3.2 vs 12.2±2.8days; P=.012). However, the 28-day mortality rate was not significantly different between the SFI (20.5%; 16/78) and placebo groups (27.8%; -22/79; P=.28). These findings suggest that SFI can enhance the cellular immunity of patients with septic shock and could be a promising adjunctive treatment for patients with septic shock. Copyright © 2016 Elsevier Inc. All rights reserved.

A non-synonymous SNP in the NOS2 associated with septic shock in patients with sepsis in Chinese populations.

PubMed

Wang, Zhifu; Feng, Kai; Yue, Maoxing; Lu, Xiaoguang; Zheng, Qihan; Zhang, Hongxing; Zhai, Yun; Li, Peiyao; Yu, Lixia; Cai, Mi; Zhang, Xiumei; Kang, Xin; Shi, Weihai; Xia, Xia; Chen, Xi; Cao, Pengbo; Li, Yuanfeng; Chen, Huipeng; Ling, Yan; Li, Yuxia; He, Fuchu; Zhou, Gangqiao

2013-03-01

Sepsis represents a systemic inflammatory response to infection and its sequelae include severe sepsis, septic shock, multiple organ dysfunction syndrome (MODS) and death. Studies in mice and humans indicate that the inducible nitric oxide synthase (iNOS, NOS2) plays an important role in the development of sepsis and its sequelae. It was reported that several single nucleotide polymorphisms (SNPs) within NOS2 could influence the production or activity of NOS2. In this study, we assessed whether SNPs within NOS2 gene were associated with severity of sepsis in Chinese populations. A case-control study was conducted, which included 299 and 280 unrelated patients with sepsis recruited from Liaoning and Jiangsu provinces in China, respectively. Six SNPs within NOS2 were genotyped using Sequenom MassARRAY system. The associations between the SNPs and risk of sepsis complications were estimated by a binary logistic regression model adjusted for confounding factors. Functional assay was performed to assess the biological significance. The GA + AA genotype of a non-synonymous SNP in the exon 16 of NOS2 (rs2297518: G>A) was significantly associated with increased susceptibility to septic shock compared with GG genotype in Liaoning population (OR = 3.29, 95% CI = 1.40-7.72, P = 0.0047). This association was confirmed in the Jiangsu population (OR = 3.49, 95% CI = 1.57-7.79, P = 0.0019). Furthermore, the functional assay performed in the immortalized lymphocyte cell lines indicated that the at-risk GA genotype had a tendency of higher NOS2 activity than the GG genotype (P = 0.32). Our findings suggest that the NOS2 rs2297518 may play a role in mediating the susceptibility to septic shock in patients with sepsis in Chinese populations.

Surviving Sepsis Campaign: International Guidelines for Management of Sepsis and Septic Shock: 2016.

PubMed

Rhodes, Andrew; Evans, Laura E; Alhazzani, Waleed; Levy, Mitchell M; Antonelli, Massimo; Ferrer, Ricard; Kumar, Anand; Sevransky, Jonathan E; Sprung, Charles L; Nunnally, Mark E; Rochwerg, Bram; Rubenfeld, Gordon D; Angus, Derek C; Annane, Djillali; Beale, Richard J; Bellinghan, Geoffrey J; Bernard, Gordon R; Chiche, Jean-Daniel; Coopersmith, Craig; De Backer, Daniel P; French, Craig J; Fujishima, Seitaro; Gerlach, Herwig; Hidalgo, Jorge Luis; Hollenberg, Steven M; Jones, Alan E; Karnad, Dilip R; Kleinpell, Ruth M; Koh, Younsuk; Lisboa, Thiago Costa; Machado, Flavia R; Marini, John J; Marshall, John C; Mazuski, John E; McIntyre, Lauralyn A; McLean, Anthony S; Mehta, Sangeeta; Moreno, Rui P; Myburgh, John; Navalesi, Paolo; Nishida, Osamu; Osborn, Tiffany M; Perner, Anders; Plunkett, Colleen M; Ranieri, Marco; Schorr, Christa A; Seckel, Maureen A; Seymour, Christopher W; Shieh, Lisa; Shukri, Khalid A; Simpson, Steven Q; Singer, Mervyn; Thompson, B Taylor; Townsend, Sean R; Van der Poll, Thomas; Vincent, Jean-Louis; Wiersinga, W Joost; Zimmerman, Janice L; Dellinger, R Phillip

2017-03-01

To provide an update to "Surviving Sepsis Campaign Guidelines for Management of Sepsis and Septic Shock: 2012". A consensus committee of 55 international experts representing 25 international organizations was convened. Nominal groups were assembled at key international meetings (for those committee members attending the conference). A formal conflict-of-interest (COI) policy was developed at the onset of the process and enforced throughout. A stand-alone meeting was held for all panel members in December 2015. Teleconferences and electronic-based discussion among subgroups and among the entire committee served as an integral part of the development. The panel consisted of five sections: hemodynamics, infection, adjunctive therapies, metabolic, and ventilation. Population, intervention, comparison, and outcomes (PICO) questions were reviewed and updated as needed, and evidence profiles were generated. Each subgroup generated a list of questions, searched for best available evidence, and then followed the principles of the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system to assess the quality of evidence from high to very low, and to formulate recommendations as strong or weak, or best practice statement when applicable. The Surviving Sepsis Guideline panel provided 93 statements on early management and resuscitation of patients with sepsis or septic shock. Overall, 32 were strong recommendations, 39 were weak recommendations, and 18 were best-practice statements. No recommendation was provided for four questions. Substantial agreement exists among a large cohort of international experts regarding many strong recommendations for the best care of patients with sepsis. Although a significant number of aspects of care have relatively weak support, evidence-based recommendations regarding the acute management of sepsis and septic shock are the foundation of improved outcomes for these critically ill patients with high mortality.

Surviving Sepsis Campaign: International Guidelines for Management of Sepsis and Septic Shock: 2016.

PubMed

Rhodes, Andrew; Evans, Laura E; Alhazzani, Waleed; Levy, Mitchell M; Antonelli, Massimo; Ferrer, Ricard; Kumar, Anand; Sevransky, Jonathan E; Sprung, Charles L; Nunnally, Mark E; Rochwerg, Bram; Rubenfeld, Gordon D; Angus, Derek C; Annane, Djillali; Beale, Richard J; Bellinghan, Geoffrey J; Bernard, Gordon R; Chiche, Jean-Daniel; Coopersmith, Craig; De Backer, Daniel P; French, Craig J; Fujishima, Seitaro; Gerlach, Herwig; Hidalgo, Jorge Luis; Hollenberg, Steven M; Jones, Alan E; Karnad, Dilip R; Kleinpell, Ruth M; Koh, Younsuck; Lisboa, Thiago Costa; Machado, Flavia R; Marini, John J; Marshall, John C; Mazuski, John E; McIntyre, Lauralyn A; McLean, Anthony S; Mehta, Sangeeta; Moreno, Rui P; Myburgh, John; Navalesi, Paolo; Nishida, Osamu; Osborn, Tiffany M; Perner, Anders; Plunkett, Colleen M; Ranieri, Marco; Schorr, Christa A; Seckel, Maureen A; Seymour, Christopher W; Shieh, Lisa; Shukri, Khalid A; Simpson, Steven Q; Singer, Mervyn; Thompson, B Taylor; Townsend, Sean R; Van der Poll, Thomas; Vincent, Jean-Louis; Wiersinga, W Joost; Zimmerman, Janice L; Dellinger, R Phillip

2017-03-01

To provide an update to "Surviving Sepsis Campaign Guidelines for Management of Sepsis and Septic Shock: 2012." A consensus committee of 55 international experts representing 25 international organizations was convened. Nominal groups were assembled at key international meetings (for those committee members attending the conference). A formal conflict-of-interest (COI) policy was developed at the onset of the process and enforced throughout. A stand-alone meeting was held for all panel members in December 2015. Teleconferences and electronic-based discussion among subgroups and among the entire committee served as an integral part of the development. The panel consisted of five sections: hemodynamics, infection, adjunctive therapies, metabolic, and ventilation. Population, intervention, comparison, and outcomes (PICO) questions were reviewed and updated as needed, and evidence profiles were generated. Each subgroup generated a list of questions, searched for best available evidence, and then followed the principles of the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system to assess the quality of evidence from high to very low, and to formulate recommendations as strong or weak, or best practice statement when applicable. The Surviving Sepsis Guideline panel provided 93 statements on early management and resuscitation of patients with sepsis or septic shock. Overall, 32 were strong recommendations, 39 were weak recommendations, and 18 were best-practice statements. No recommendation was provided for four questions. Substantial agreement exists among a large cohort of international experts regarding many strong recommendations for the best care of patients with sepsis. Although a significant number of aspects of care have relatively weak support, evidence-based recommendations regarding the acute management of sepsis and septic shock are the foundation of improved outcomes for these critically ill patients with high mortality.

Outcomes in critically ill cancer patients with septic shock of pulmonary origin.

PubMed

de Montmollin, Etienne; Tandjaoui-Lambiotte, Yacine; Legrand, Mattieu; Lambert, Jérôme; Mokart, Djamel; Kouatchet, Achille; Lemiale, Virginie; Pène, Frédéric; Bruneel, Fabrice; Vincent, François; Mayaux, Julien; Chevret, Sylvie; Azoulay, Elie

2013-03-01

Increased therapeutic intensity has translated into better survival at a price of infectious and toxic life-threatening complications, chiefly affecting the lungs. Yet, no study specifically evaluated outcomes in cancer patients admitted to the intensive care unit (ICU) for septic shock of pulmonary origin. This is a multicenter cohort study of cancer patients admitted to the ICU for septic shock and pneumonia between 1998 and 2008. Independent determinants of hospital mortality were assessed using a multivariate logistic regression model. Prognostic impact of persistence or acquisition of organ failures was evaluated by survival conditional probabilities. During the 10-year study period, 218 patients were included. Hematologic malignancy (mostly non-Hodgkin lymphoma and acute leukemia) affected 84%, and solid tumors (mostly lung cancer) affected 16% of patients. Chemotherapy was recently administered in 89% of patients, and 24.5% of patients were recipients of hematopoietic stem cell transplantation (35 autologous, 18 allogeneic). At the time of ICU admission, 60% of patients were in partial or complete remission. All patients received vasopressors; invasive mechanical ventilation (MV) was needed in 78.4% and dialysis in 30% of patients. Intensive care unit and hospital mortality rates were 56.4% and 62.4%, respectively. Independent risk factors for hospital mortality were age older than 60 years, time between first symptoms and ICU admission, use of invasive MV, need for invasive MV after use of noninvasive ventilation, and coma. Analysis of survival probability showed that there was no temporal threshold after which persistence or gain of organ dysfunction indicated no hope for survival. Survival in cancer patients with septic shock from pulmonary origin is substantial, even when organ dysfunctions are not rapidly reversible. Delayed ICU management is an independent predictor of death. Studies assessing survival benefits from early ICU management are warranted.

Impact of Source Control in Patients With Severe Sepsis and Septic Shock.

PubMed

Martínez, María Luisa; Ferrer, Ricard; Torrents, Eva; Guillamat-Prats, Raquel; Gomà, Gemma; Suárez, David; Álvarez-Rocha, Luis; Pozo Laderas, Juan Carlos; Martín-Loeches, Ignacio; Levy, Mitchell M; Artigas, Antonio

2017-01-01

Time to clearance of pathogens is probably critical to outcome in septic shock. Current guidelines recommend intervention for source control within 12 hours after diagnosis. We aimed to determine the epidemiology of source control in the management of sepsis and to analyze the impact of timing to source control on mortality. Prospective observational analysis of the Antibiotic Intervention in Severe Sepsis study, a Spanish national multicenter educational intervention to improve antibiotherapy in sepsis. Ninety-nine medical-surgical ICUs in Spain. We enrolled 3,663 patients with severe sepsis or septic shock during three 4-month periods between 2011 and 2013. Source control and hospital mortality. A total of 1,173 patients (32%) underwent source control, predominantly for abdominal, urinary, and soft-tissue infections. Compared with patients who did not require source control, patients who underwent source control were older, with a greater prevalence of shock, major organ dysfunction, bacteremia, inflammatory markers, and lactic acidemia. In addition, compliance with the resuscitation bundle was worse in those undergoing source control. In patients who underwent source control, crude ICU mortality was lower (21.2% vs 25.1%; p = 0.010); after adjustment for confounding factors, hospital mortality was also lower (odds ratio, 0.809 [95% CI, 0.658-0.994]; p = 0.044). In this observational database analysis, source control after 12 hours was not associated with higher mortality (27.6% vs 26.8%; p = 0.789). Despite greater severity and worse compliance with resuscitation bundles, mortality was lower in septic patients who underwent source control than in those who did not. The time to source control could not be linked to survival in this observational database.

Cardiac ischemia in patients with septic shock randomized to vasopressin or norepinephrine

PubMed Central

2013-01-01

Introduction Cardiac troponins are sensitive and specific biomarkers of myocardial necrosis. We evaluated troponin, CK, and ECG abnormalities in patients with septic shock and compared the effect of vasopressin (VP) versus norepinephrine (NE) on troponin, CK, and ECGs. Methods This was a prospective substudy of a randomized trial. Adults with septic shock randomly received, blinded, a low-dose infusion of VP (0.01 to 0.03 U/min) or NE (5 to 15 μg/min) in addition to open-label vasopressors, titrated to maintain a mean blood pressure of 65 to 75 mm Hg. Troponin I/T, CK, and CK-MB were measured, and 12-lead ECGs were recorded before study drug, and 6 hours, 2 days, and 4 days after study-drug initiation. Two physician readers, blinded to patient data and drug, independently interpreted ECGs. Results We enrolled 121 patients (median age, 63.9 years (interquartile range (IQR), 51.1 to 75.3), mean APACHE II 28.6 (SD 7.7)): 65 in the VP group and 56 in the NE group. At the four time points, 26%, 36%, 32%, and 21% of patients had troponin elevations, respectively. Baseline characteristics and outcomes were similar between patients with positive versus negative troponin levels. Troponin and CK levels and rates of ischemic ECG changes were similar in the VP and the NE groups. In multivariable analysis, only APACHE II was associated with 28-day mortality (OR, 1.07; 95% CI, 1.01 to 1.14; P = 0.033). Conclusions Troponin elevation is common in adults with septic shock. We observed no significant differences in troponin, CK, and ECGs in patients treated with vasopressin and norepinephrine. Troponin elevation was not an independent predictor of mortality. Trial registration Controlled-trials.com ISRCTN94845869 PMID:23786655

Diagnostic potential of endotoxin scattering photometry for sepsis and septic shock.

PubMed

Shimizu, Tomoharu; Obata, Toru; Sonoda, Hiromichi; Akabori, Hiroya; Miyake, Tohru; Yamamoto, Hiroshi; Tabata, Takahisa; Eguchi, Yutaka; Tani, Tohru

2013-12-01

Endotoxin scattering photometry (ESP) is a novel Limulus amebocyte lysate (LAL) assay that uses a laser light-scattering particle-counting method. In the present study, we compared ESP, standard turbidimetric LAL assay, and procalcitonin assay for the evaluation of sepsis after emergency gastrointestinal surgery. A total of 174 samples were collected from 40 adult patients undergoing emergency gastrointestinal surgery and 10 patients with colorectal cancer undergoing elective surgery as nonseptic controls. Plasma endotoxin levels were measured with ESP and turbidimetric LAL assay, and plasma procalcitonin levels were assessed with a standard procalcitonin assay. Plasma endotoxin and procalcitonin levels increased corresponding to the degree of sepsis. Endotoxin scattering photometry significantly discriminated between patients with or without septic shock: sensitivity, 81.1%; specificity, 76.6%; positive predictive value, 48.4%; negative predictive value, 93.8%; and accuracy, 77.6%. The area under the receiver operating characteristic curve for septic shock with the ESP assay (endotoxin cutoff value, 23.8 pg/mL) was 0.8532 ± 0.0301 (95% confidence interval, 0.7841-0.9030; P < 0.0001). The predictive power of ESP was superior to that of turbidimetric assay (difference, 0.1965 ± 0.0588; 95% confidence interval, 0.0812-0.3117; P = 0.0008). There was no significant difference in predictive power between ESP and procalcitonin assay. Endotoxin scattering photometry also discriminated between patients with and without sepsis. Area under the receiver operating characteristic curve analysis showed that ESP had the best predictive power for diagnosing sepsis. In conclusion, compared with turbidimetric LAL assay, ESP more sensitively detected plasma endotoxin and significantly discriminated between sepsis and septic shock in patients undergoing gastrointestinal emergency surgery.

Septic shock secondary to β-hemolytic streptococcus-induced necrotizing fasciitis treated with a novel cytokine adsorption therapy.

PubMed

Hetz, Hubert; Berger, Reinhard; Recknagel, Peter; Steltzer, Heinz

2014-05-01

Numerous animal studies and preliminary data from a clinical trial in septic patients demonstrated that a decrease in blood cytokine levels using an extracorporeal cytokine filter (CytoSorb) can effectively attenuate the inflammatory response during sepsis and possibly improve outcomes. A 60-year-old female was admitted to hospital due to a forearm fracture. After surgical wound care by osteosynthesis the patient developed surgical wound infection which progressed to necrotizing fasciitis. All diagnostic criteria for SIRS were evident with additional proven infection from β-hemolytic streptococcus. On admission to the ICU, the patient presented a full picture of multiple organ dysfunction syndrome due to septic shock including kidney failure, lung failure as well as thrombocytopenia, metabolic acidosis, and arterial hypotension. After one day on mechanical ventilation and an IL-6 level of 70,000 pg/ml the patient was treated with CytoSorb therapy over a period of four days, resulting in a significant reduction of IL-6 to 66 pg/ml and an overall improvement of the patient's condition. Despite the necessity of enucleation, the patient was successfully stabilized until control of the surgical infectious source was achieved. Importantly, treatment was safe and well-tolerated, without any adverse events. This is the first report of the clinical application of CytoSorb hemoadsorption in combination with a CRRT in a patient with septic shock. CytoSorb as described was able to significantly reduce IL-6 plasma levels and decrease vasopressor need while no adverse and device-related events occurred. CytoSorb seems to be an interesting and safe extracorporeal therapy to stabilize and bridge septic patients to surgery or recovery.

Modeling Blood Filtration in the Treatment of Septic Shock

NASA Astrophysics Data System (ADS)

Foster, Glenn; Hubler, Alfred

2007-03-01

Sepsis, the overreaction of the inflammation and coagulation responses to infection, is the leading cause of death in non-coronary intensive care unit patients in the US. Anti-mediator drugs have been generally ineffective, but by considering the network of cytokine interactions, we illustrate how filtering the cytokines in the blood leads to a reduced response. We further illustrate by applying an appropriate filter to existing immune response models as well as discuss both practical and optimal filter parameters.

Comparative Analysis of Hepatic CD14 Expression between Two Different Endotoxin Shock Model Mice: Relation between Hepatic Injury and CD14 Expression

PubMed Central

Hozumi, Hiroyasu; Tada, Rui; Murakami, Taisuke; Adachi, Yoshiyuki; Ohno, Naohito

2013-01-01

CD14 is a glycoprotein that recognizes gram-negative bacterial lipopolysaccharide (LPS) and exists in both membrane-bound and soluble forms. Infectious and/or inflammatory diseases induce CD14 expression, which may be involved in the pathology of endotoxin shock. We previously found that the expression of CD14 protein differs among the endotoxin shock models used, although the reasons for these differences are unclear. We hypothesized that the differences in CD14 expression might be due to liver injury, because the hepatic tissue produces CD14 protein. We investigated CD14 expression in the plasma and liver in the carrageenan (CAR)-primed and D-galN-primed mouse models of endotoxin shock. Our results showed that severe liver injury was not induced in CAR-primed endotoxin shock model mice. In this CAR-primed model, the higher mRNA and protein expression of CD14 was observed in the liver, especially in the interlobular bile duct in contrast to D-galN-primed-endotoxin shock model mice. Our findings indicated that the molecular mechanism(s) underlying septic shock in CAR-primed and D-galN-primed endotoxin shock models are quite different. Because CD14 expression is correlated with clinical observations, the CAR-primed endotoxin shock model might be useful for studying the functions of CD14 during septic shock in vivo. PMID:23308276

Hypothermia in the sepsis syndrome and clinical outcome. The Methylprednisolone Severe Sepsis Study Group.

PubMed

Clemmer, T P; Fisher, C J; Bone, R C; Slotman, G J; Metz, C A; Thomas, F O

1992-10-01

To evaluate the consequences of clinical hypothermia associated with sepsis syndrome and septic shock. Analysis of data from a multi-institutional, randomized, placebo-controlled, prospective study with predetermined end-point analysis of development of shock, recovery from shock, hospital length of stay, and death. Multi-institutional medical and surgical ICUs. Patients meeting predetermined criteria for severe sepsis syndrome. Appropriate sepsis and shock care with 50% of patients receiving methylprednisolone and 50% receiving placebo. The occurrence rate of hypothermia (< 35.5 degrees C) is 9% in this population. When compared with febrile patients, hypothermic patients had a higher frequency of central nervous system dysfunction (88% vs. 60%), increased serum bilirubin concentration (35% vs. 15%), prolonged prothrombin times (50% vs. 23%), shock (94% vs. 61%), failure to recover from shock (66% vs. 26%), and death (62% vs. 26%). The hypothermic patients were also more likely to be classified as having a rapidly or ultimately fatal disease upon study admission. This prospective study confirms that hypothermia associated with sepsis syndrome has a significant relationship to outcome manifest by increased frequency of shock and death from shock. This finding is in sharp contrast to the protective effects of induced hypothermia in septic animals and perhaps man.

Clinical practice parameters for hemodynamic support of pediatric and neonatal septic shock: 2007 update from the American College of Critical Care Medicine

PubMed Central

Brierley, Joe; Carcillo, Joseph A.; Choong, Karen; Cornell, Tim; DeCaen, Allan; Deymann, Andreas; Doctor, Allan; Davis, Alan; Duff, John; Dugas, Marc-Andre; Duncan, Alan; Evans, Barry; Feldman, Jonathan; Felmet, Kathryn; Fisher, Gene; Frankel, Lorry; Jeffries, Howard; Greenwald, Bruce; Gutierrez, Juan; Hall, Mark; Han, Yong Y.; Hanson, James; Hazelzet, Jan; Hernan, Lynn; Kiff, Jane; Kissoon, Niranjan; Kon, Alexander; Irazusta, Jose; Lin, John; Lorts, Angie; Mariscalco, Michelle; Mehta, Renuka; Nadel, Simon; Nguyen, Trung; Nicholson, Carol; Peters, Mark; Okhuysen-Cawley, Regina; Poulton, Tom; Relves, Monica; Rodriguez, Agustin; Rozenfeld, Ranna; Schnitzler, Eduardo; Shanley, Tom; Skache, Sara; Skippen, Peter; Torres, Adalberto; von Dessauer, Bettina; Weingarten, Jacki; Yeh, Timothy; Zaritsky, Arno; Stojadinovic, Bonnie; Zimmerman, Jerry; Zuckerberg, Aaron

2013-01-01

Background The Institute of Medicine calls for the use of clinical guidelines and practice parameters to promote “best practices” and to improve patient outcomes. Objective 2007 update of the 2002 American College of Critical Care Medicine Clinical Guidelines for Hemodynamic Support of Neonates and Children with Septic Shock. Participants Society of Critical Care Medicine members with special interest in neonatal and pediatric septic shock were identified from general solicitation at the Society of Critical Care Medicine Educational and Scientific Symposia (2001–2006). Methods The Pubmed/MEDLINE literature database (1966–2006) was searched using the keywords and phrases: sepsis, septicemia, septic shock, endotoxemia, persistent pulmonary hypertension, nitric oxide, extracorporeal membrane oxygenation (ECMO), and American College of Critical Care Medicine guidelines. Best practice centers that reported best outcomes were identified and their practices examined as models of care. Using a modified Delphi method, 30 experts graded new literature. Over 30 additional experts then reviewed the updated recommendations. The document was subsequently modified until there was greater than 90% expert consensus. Results The 2002 guidelines were widely disseminated, translated into Spanish and Portuguese, and incorporated into Society of Critical Care Medicine and AHA sanctioned recommendations. Centers that implemented the 2002 guidelines reported best practice outcomes (hospital mortality 1%–3% in previously healthy, and 7%– 10% in chronically ill children). Early use of 2002 guidelines was associated with improved outcome in the community hospital emergency department (number needed to treat = 3.3) and tertiary pediatric intensive care setting (number needed to treat = 3.6); every hour that went by without guideline adherence was associated with a 1.4-fold increased mortality risk. The updated 2007 guidelines continue to recognize an increased likelihood that children with septic shock, compared with adults, require 1) proportionally larger quantities of fluid, 2) inotrope and vasodilator therapies, 3) hydrocortisone for absolute adrenal insufficiency, and 4) ECMO for refractory shock. The major new recommendation in the 2007 update is earlier use of inotrope support through peripheral access until central access is attained. Conclusion The 2007 update continues to emphasize early use of age-specific therapies to attain time-sensitive goals, specifically recommending 1) first hour fluid resuscitation and inotrope therapy directed to goals of threshold heart rates, normal blood pressure, and capillary refill ≤2 secs, and 2) subsequent intensive care unit hemodynamic support directed to goals of central venous oxygen saturation >70% and cardiac index 3.3–6.0 L/min/m2. PMID:19325359

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.

Initial fluid resuscitation following adjusted body weight dosing is associated with improved mortality in obese patients with suspected septic shock.

PubMed

Taylor, Stephanie Parks; Karvetski, Colleen H; Templin, Megan A; Heffner, Alan C; Taylor, Brice T

2018-02-01

The optimal initial fluid resuscitation strategy for obese patients with septic shock is unknown. We evaluated fluid resuscitation strategies across BMI groups. Retrospective analysis of 4157 patients in a multicenter activation pathway for treatment of septic shock between 2014 and 2016. 1293 (31.3%) patients were obese (BMI≥30). Overall, higher BMI was associated with lower mortality, however this survival advantage was eliminated in adjusted analyses. Patients with higher BMI received significantly less fluid per kilogram at 3h than did patients with lower BMI (p≤0.001). In obese patients, fluid given at 3h mimicked a dosing strategy based on actual body weight (ABW) in 780 (72.2%), adjusted body weight (AdjBW) in 95 (8.8%), and ideal body weight (IBW) in 205 (19.0%). After adjusting for condition- and treatment-related variables, dosing based on AdjBW was associated with improved mortality compared to ABW (OR 0.45; 95% CI [0.19, 1.07]) and IBW (OR 0.29; 95% CI [0.11,0.74]). Using AdjBW to calculate initial fluid resuscitation volume for obese patients with suspected shock may improve outcomes compared to other weight-based dosing strategies. The optimal fluid dosing strategy for obese patients should be a focus of future prospective research. Copyright © 2017 Elsevier Inc. All rights reserved.

Multifocal necrotising fasciitis and septic shock complicating varicella infection in an adult

PubMed Central

Mifsud, Simon; Schembri, Emma Louise; Mallia Azzopardi, Charles; Zammit, Maria Alessandra

2013-01-01

A 35-year-old woman with a 3-day history of chickenpox, presented to the hospital in septic shock and with multifocal, non-adjacent lesions of necrotising fasciitis. Necrotising fasciitis is a rare yet life-threatening complication of chickenpox. Blood cultures and wound swabs confirmed the presence of Streptococcus pyogenes. The initial emergency management included oxygen, aggressive fluid resuscitation and antimicrobial therapy. Once the patient was stabilised, surgical management ensued. This included debridement and eventual grafting of the necrotic skin lesions. Intensive management and follow-up for 8 weeks were required before the patient was deemed fit for discharge. PMID:24130210

[Septic shock following platelet transfusion contaminated with Citrobacter koseri in a child with postchemotherapy febrile neutropenia].

PubMed

Tichit, R; Saumet, L; Marchandin, H; Haouy, S; Latry, P; Sirvent, N

2016-01-01

The bacterial transfusion risk is currently the greatest infectious risk of blood transfusion. We report the case of a child with postchemotherapy febrile neutropenia who presented septic shock following platelet transfusion contaminated with Citrobacter koseri. The life-threatening development could have been avoided by strict compliance with good clinical practice. The stability of mortality rates due to adverse effects of bacterial proliferation during platelet transfusions in France since 1994 calls for optimization of all preventive measures throughout the transfusion chain and perfect knowledge of transfusion rules by medical staff and care givers. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

Receptors, mediators, and mechanisms involved in bacterial sepsis and septic shock.

PubMed

Van Amersfoort, Edwin S; Van Berkel, Theo J C; Kuiper, Johan

2003-07-01

Bacterial sepsis and septic shock result from the overproduction of inflammatory mediators as a consequence of the interaction of the immune system with bacteria and bacterial wall constituents in the body. Bacterial cell wall constituents such as lipopolysaccharide, peptidoglycans, and lipoteichoic acid are particularly responsible for the deleterious effects of bacteria. These constituents interact in the body with a large number of proteins and receptors, and this interaction determines the eventual inflammatory effect of the compounds. Within the circulation bacterial constituents interact with proteins such as plasma lipoproteins and lipopolysaccharide binding protein. The interaction of the bacterial constituents with receptors on the surface of mononuclear cells is mainly responsible for the induction of proinflammatory mediators by the bacterial constituents. The role of individual receptors such as the toll-like receptors and CD14 in the induction of proinflammatory cytokines and adhesion molecules is discussed in detail. In addition, the roles of a number of other receptors that bind bacterial compounds such as scavenger receptors and their modulating role in inflammation are described. Finally, the therapies for the treatment of bacterial sepsis and septic shock are discussed in relation to the action of the aforementioned receptors and proteins.

Near-infrared spectroscopy during stagnant ischemia estimates central venous oxygen saturation and mixed venous oxygen saturation discrepancy in patients with severe left heart failure and additional sepsis/septic shock.

PubMed

Mozina, Hugo; Podbregar, Matej

2010-01-01

Discrepancies of 5-24% between superior vena cava oxygen saturation (ScvO2) and mixed venous oxygen saturation (SvO2) have been reported in patients with severe heart failure. Thenar muscle tissue oxygenation (StO2) measured with near-infrared spectroscopy (NIRS) during arterial occlusion testing decreases slower in sepsis/septic shock patients (lower StO2 deoxygenation rate). The StO2 deoxygenation rate is influenced by dobutamine. The aim of this study was to determine the relationship between the StO2 deoxygenation rate and the ScvO2-SvO2 discrepancy in patients with severe left heart failure and additional sepsis/septic shock treated with or without dobutamine. Fifty-two patients with severe left heart failure due to primary heart disease with additional severe sepsis/septic shock were included. SvO2 and ScvO2 were compared to the thenar muscle StO2 before and during arterial occlusion. SvO2 correlated significantly with ScvO2 (Pearson correlation 0.659, P = 0.001), however, Bland Altman analysis showed a clinically important difference between both variables (ScvO2-SvO2 mean 72 +/- 8%, ScvO2-SvO2 difference 9.4 +/- 7.5%). The ScvO2-SvO2 difference correlated with plasma lactate (Pearson correlation 0.400, P = 0.003) and the StO2 deoxygenation rate (Pearson correlation 0.651, P = 0.001). In the group of patients treated with dobutamine, the ScvO2-SvO2 difference correlated with plasma lactate (Pearson correlation 0.389, P = 0.011) and the StO2 deoxygenation rate (Pearson correlation 0.777, P = 0.0001). In patients with severe heart failure with additional severe sepsis/septic shock the ScvO2-SvO2 discrepancy presents a clinical problem. In these patients the skeletal muscle StO2 deoxygenation rate is inversely proportional to the difference between ScvO2 and SvO2; dobutamine does not influence this relationship. When using ScvO2 as a treatment goal, the NIRS measurement may prove to be a useful non-invasive diagnostic test to uncover patients with a normal ScvO2 but potentially an abnormally low SvO2. NCT00384644 ClinicalTrials.Gov.

Agreement in electrocardiogram interpretation in patients with septic shock.

PubMed

Mehta, Sangeeta; Granton, John; Lapinsky, Stephen E; Newton, Gary; Bandayrel, Kristofer; Little, Anjuli; Siau, Chuin; Cook, Deborah J; Ayers, Dieter; Singer, Joel; Lee, Terry C; Walley, Keith R; Storms, Michelle; Cooper, Jamie; Holmes, Cheryl L; Hebert, Paul; Gordon, Anthony C; Presneill, Jeff; Russell, James A

2011-09-01

The reliability of electrocardiogram interpretation to diagnose myocardial ischemia in critically ill patients is unclear. In adults with septic shock, we assessed intra- and inter-rater agreement of electrocardiogram interpretation, and the effect of knowledge of troponin values on these interpretations. Prospective substudy of a randomized trial of vasopressin vs. norepinephrine in septic shock. Nine Canadian intensive care units. Adults with septic shock requiring at least 5 μg/min of norepinephrine for 6 hrs. Twelve-lead electrocardiograms were recorded before study drug, and 6 hrs, 2 days, and 4 days after study drug initiation. Two physician readers, blinded to patient data and group, independently interpreted electrocardiograms on three occasions (first two readings were blinded to patient data; third reading was unblinded to troponin). To calibrate and refine definitions, both readers initially reviewed 25 trial electrocardiograms representing normal to abnormal. Cohen's Kappa and the φ statistic were used to analyze intra- and inter-rater agreement. One hundred twenty-one patients (62.2 ± 16.5 yrs, Acute Physiology and Chronic Health Evaluation II 28.6 ± 7.7) had 373 electrocardiograms. Blinded to troponin, readers 1 and 2 interpreted 46.4% and 30.0% of electrocardiograms as normal, and 15.3% and 12.3% as ischemic, respectively. Intrarater agreement was moderate for overall ischemia (κ 0.54 and 0.58), moderate/good for "normal" (κ 0.69 and 0.55), fair to good for specific signs of ischemia (ST elevation, T inversion, and Q waves, reader 1 κ 0.40 to 0.69; reader 2 κ 0.56 to 0.70); and good/very good for atrial arrhythmias (κ 0.84 and 0.79) and bundle branch block (κ 0.88 and 0.79). Inter-rater agreement was fair for ischemia (κ 0.29), moderate for ST elevation (κ 0.48), T inversion (κ 0.52), and Q waves (κ 0.44), good for bundle branch block (κ 0.78), and very good for atrial arrhythmias (κ 0.83). Inter-rater agreement for ischemia improved from fair to moderate (κ 0.52, p = .028) when unblinded to troponin. In patients with septic shock, inter-rater agreement of electrocardiogram interpretation for myocardial ischemia was fair, and improved with troponin knowledge.

Timing of antibiotics, volume, and vasoactive infusions in children with sepsis admitted to intensive care.

PubMed

van Paridon, Bregje M; Sheppard, Cathy; G, Garcia Guerra; Joffe, Ari R

2015-08-17

Early administration of antibiotics for sepsis, and of fluid boluses and vasoactive agents for septic shock, is recommended. Evidence for this in children is limited. The Alberta Sepsis Network prospectively enrolled eligible children admitted to the Pediatric Intensive Care Unit (PICU) with sepsis from 04/2012-10/2014. Demographics, severity of illness, and outcomes variables were prospectively entered into the ASN database after deferred consent. Timing of interventions were determined by retrospective chart review using a study manual and case-report-form. We aimed to determine the association of intervention timing and outcome in children with sepsis. Univariate (t-test and Fisher's Exact) and multiple linear regression statistics evaluated predictors of outcomes of PICU length of stay (LOS) and ventilation days. Seventy-nine children, age median 60 (IQR 22-133) months, 40 (51%) female, 39 (49%) with severe underlying co-morbidity, 44 (56%) with septic shock, and median PRISM-III 10.5 [IQR 6.0-17.0] were enrolled. Most patients presented in an ED: 36 (46%) at an outlying hospital ED, and 21 (27%) at the Children's Hospital ED. Most infections were pneumonia with/without empyema (42, 53%), meningitis (11, 14%), or bacteremia (10, 13%). The time from presentation to acceptable antibiotic administration was a median of 115.0 [IQR 59.0-323.0] minutes; 20 (25%) of patients received their antibiotics in the first hour from presentation. Independent predictors of PICU LOS were PRISM-III, and severe underlying co-morbidity, but not time to antibiotics. In the septic shock subgroup, the volume of fluid boluses given in the first 2 hours was independently associated with longer PICU LOS (effect size 0.22 days; 95% CI 0.5, 0.38; per ml/kg). Independent predictors of ventilator days were PRISM-III score and severe underlying co-morbidity. In the septic shock subgroup, volume of fluid boluses in the first 2 hours was independently associated with more ventilator days (effect size 0.09 days; 95% CI 0.02, 0.15; per ml/kg). Higher volume of early fluid boluses in children with sepsis and septic shock was independently associated with longer PICU LOS and ventilator days. More study on the benefits and harms of fluid bolus therapy in children are needed.

Total Intravenous Anesthesia for Major Burn Surgery

DTIC Science & Technology

2013-04-30

been used in burn centers, particularly for frequent debride- ments, dressing changes, and tanking (hydro- therapy) procedures outside of the...2.0 mg/kg for patients with, e.g., burn shock or septic shock. Several conditions are typically considered con- traindications to ketamine use, but

Prognostic value of extravascular lung water and its potential role in guiding fluid therapy in septic shock after initial resuscitation.

PubMed

Wang, Hao; Cui, Na; Su, Longxiang; Long, Yun; Wang, Xiaoting; Zhou, Xiang; Chai, Wenzhao; Liu, Dawei

2016-06-01

To explore whether extravascular lung water (EVLW) provides a valuable prognostic tool guiding fluid therapy in septic shock patients after initial resuscitation. We performed a retrospective study of septic shock patients who achieved adequate initial fluid resuscitation with extended hemodynamic monitoring, analyzing the prognostic value of EVLW and whether fluid therapy for 24 (T24) or 24-48 hours (T24-48) after initial resuscitation with a recommended value of EVLW yielded a 28-day mortality advantage. One hundred five patients with septic shock were included in this study, 60 (57.1%) of whom died after 28 days. For 48 hours after initial resuscitation, the daily fluid balance (DFB; T24: 2494 ± 1091 vs 1965 ± 964 mL [P = .011] and T24-48: 2127 ± 783 vs 1588 ± 665 mL [P < .001]) and daily maximum values of the EVLW index (EVLWImax; T24: 13.9 ± 3.7 vs 11.5 ± 3.2 mL/kg [P < .001] and T24-48: 14.4 ± 5.3 vs 12.0 ± 4.4 mL/kg [P < .001]) were significantly higher in nonsurvivors than in survivors. In multivariate regression analysis, the DFB (T24: odds ratio [OR] 1.001 [P = .016] and T24-48: OR 1.001 [P = .008]), EVLWImax (T24: OR 2.158 [P = .002] and T24-48: OR 3.277 [P = .001]), blood lactate (T24: OR 1.368 [P = .021] and T24-48: OR 4.112 [P < .001]), and central venous blood oxygen saturation (T24: OR 0.893 [P = .013] and T24-48: OR 0.780 [P = .004]) were all independently associated with the 28-day mortality. A receiver operating characteristic analysis revealed that area under the curve values of 0.82 (95% confidence interval, 0.74-0.91; P < .001) and 0.90 (95% confidence interval, 0.83-0.96; P < .001) for EVLWImax ≥ 12.5 mL/kg (T24 and T24-48) predicted a 28-day mortality with sensitivities of 88% (80%-96%) and 95% (90%-100%) and specificities of 60% (46%-74%) and 76% (63%-89%).The EVLWImax was correlated with DFB with Spearman ρ values of 0.497 (T24: P < .001) and 0.650 (T24-48: P < .001). Cox survival and regression analyses demonstrated that EVLWImax ≥ 12.5 mL/kg (T24 and T24-48) was associated with higher risk and increased mortality, with adjusted ORs of 4.77 (P < .001) and 10.86 (P < .001). A higher EVLW in septic shock patients after initial resuscitation was associated with a more positive fluid balance and increased mortality, which is an independent predictor of the 28-day mortality in septic shock patients after initial resuscitation. Copyright © 2016 Elsevier Inc. All rights reserved.

Changing Definitions of Sepsis

PubMed Central

Gül, Fethi; Arslantaş, Mustafa Kemal; Cinel, İsmail; Kumar, Anand

2017-01-01

Sepsis is one of the main causes of morbidity and mortality in critically ill patients despite the use of modern antibiotics and resuscitation therapies. Outcomes in sepsis have improved overall, probably because of an enhanced focus on early diagnosis and other improvements in supportive care, but mortality rates still remain unacceptably high. The diagnosis and definition of sepsis is a critical problem due to the heterogeneity of this disease process. Although it is apparent that much more needs to be done to advance our understanding, sepsis and related terms remain difficult to define. A 1991 consensus conference developed initial definitions that systemic inflammatory response syndrome (SIRS) to infection would be called sepsis. Definitions of sepsis and septic shock were revised in 2001 to incorporate the threshold values for organ damage. In early 2016, the new definitions of sepsis and septic shock have changed dramatically. Sepsis is now defined as life-threatening organ dysfunction caused by a dysregulated host response to infection. The consensus document describes organ dysfunction as an acute increase in total Sequential Organ Failure Assessment (SOFA) score two points consequently to the infection. A significant change in the new definitions is the elimination of any mention of SIRS. The Sepsis-3 Task Force also introduced a new bedside index, called the qSOFA, to identify outside of critical care units patients with suspected infection who are likely to develop sepsis. Recently updated the consensus definitions improved specificity compared with the previous descriptions. PMID:28752002

S100A8/A9 mRNA induction in an ex vivo model of endotoxin tolerance: roles of IL-10 and IFNγ.

PubMed

Fontaine, Mathieu; Planel, Séverine; Peronnet, Estelle; Turrel-Davin, Fanny; Piriou, Vincent; Pachot, Alexandre; Monneret, Guillaume; Lepape, Alain; Venet, Fabienne

2014-01-01

Septic syndromes are the leading cause of death in intensive care units. They are characterized by the development of immune dysfunctions such as endotoxin tolerance (ET), whose intensity and duration are associated with increased risk of nosocomial infections and mortality. Alarmins S100A8 and S100A9 have been shown to be increased after septic shock. Importantly, a delayed S100A9 mRNA increase predicts hospital-acquired infection in patients. The aim of this study was to investigate the regulation of S100A8 and S100A9 mRNA expression in an ex vivo model of ET. ET was reproduced ex vivo by priming healthy peripheral blood mononuclear cells (number of donors  = 9 to 10) with low-dose endotoxin (2 ng/ml) before stimulation with high dose endotoxin (100 ng/ml). S100A8 and S100A9 mRNA levels were measured by quantitative real-time polymerase chain reactions. ET was established by observing decreased TNFα and increased IL-10 transcriptomic responses to two subsequent endotoxin challenges. Interestingly, ET was associated with increased S100A8 and S100A9 mRNA expression ex vivo. We showed that IL-10 played a role in this process, since S100A8 and S100A9 mRNA increases were significantly abrogated by IL-10 blockade in the model. Conversely, treatment with rIFN-γ, a pro-inflammatory and immunostimulating molecule known to block ET induction, was able to restore normal S100A8 and S100A9 mRNA in this model. In this ex vivo model, we observed that S100A8 and S100A9 mRNA expression was significantly increased during ET. This reproduced ex vivo the observations we had previously made in septic shock patients. Interestingly, IL-10 blockade and rIFN-γ treatment partially abrogated S100A8/A9 mRNA increases in this model. Pending confirmation in larger, independent clinical studies, these preliminary results suggest that S100A8 and S100A9 mRNA levels might be used as surrogate markers of ET and as stratification tools for personalized immunotherapy in septic shock patients.

Bench-to-bedside review: Toll-like receptors and their role in septic shock

PubMed Central

Opal, Steven M; Huber, Christian E

2002-01-01

The Toll-like receptors (TLRs) are essential transmembrane signaling receptors of the innate immune system that alert the host to the presence of a microbial invader. The recent discovery of the TLRs has rapidly expanded our knowledge of molecular events that initiate host–pathogen interactions. These functional attributes of the cellular receptors provide insights into the nature of pattern recognition receptors that activate the human antimicrobial defense systems. The fundamental significance of the TLRs in the generation of systemic inflammation and the pathogenesis of septic shock is reviewed. The potential clinical implications of therapeutic modulation of these recently characterized receptors of innate immunity are also discussed. PMID:11983038

The Role of Adjunctive Therapies in Septic Shock by Gram Negative MDR/XDR Infections.

PubMed

Busani, Stefano; Roat, Erika; Serafini, Giulia; Mantovani, Elena; Biagioni, Emanuela; Girardis, Massimo

2017-01-01

Patients with septic shock by multidrug resistant microorganisms (MDR) are a specific sepsis population with a high mortality risk. The exposure to an initial inappropriate empiric antibiotic therapy has been considered responsible for the increased mortality, although other factors such as immune-paralysis seem to play a pivotal role. Therefore, beyond conventional early antibiotic therapy and fluid resuscitation, this population may benefit from the use of alternative strategies aimed at supporting the immune system. In this review we present an overview of the relationship between MDR infections and immune response and focus on the rationale and the clinical data available on the possible adjunctive immunotherapies, including blood purification techniques and different pharmacological approaches.

The role of milrinone in children with cardiovascular compromise: review of the literature.

PubMed

Meyer, Sascha; Gortner, Ludwig; Brown, Kate; Abdul-Khaliq, Hashim

2011-04-01

Cardiovascular instability is a common complication in children after cardiac surgery and in various forms of shock. Systematic literature review. Four randomized controlled trials (RCTs) were included in this systematic literature review. In children after corrective surgery for congenital heart disease milrinone significantly reduced the risk of development of LCOS compared with placebo. In another study in children with high pulmonary vascular resistance and impaired oxygenation after Fontan operation, inhalation of NO with milrinone led to the most significant reduction of pulmonary vascular resistance and improvement of oxygenation. When only milrinone was given these changes were less pronounced. In non-hyperdynamic septic shock, CI, SVI, and DO₂ significantly increased while SVRI significantly decreased after milrinone when compared to placebo. There are a limited number of RCTs in children that suggest a beneficial effect of milrinone in the optimization of cardiovascular function after cardiac surgery and in septic shock.

Major publications in the critical care pharmacotherapy literature: January-December 2017.

PubMed

Hammond, Drayton A; Baumgartner, Laura; Cooper, Craig; Donahey, Elisabeth; Harris, Serena A; Mercer, Jessica M; Morris, Mandy; Patel, Mona K; Plewa-Rusiecki, Angela M; Poore, Alia A; Szaniawski, Ryan; Horner, Deanna

2018-06-01

To summarize selected meta-analyses and trials related to critical care pharmacotherapy published in 2017. The Critical Care Pharmacotherapy Literature Update (CCPLU) Group screened 32 journals monthly for impactful articles and reviewed 115 during 2017. Two meta-analyses and eight original research trials were reviewed here from those included in the monthly CCPLU. Meta-analyses on early, goal-directed therapy for septic shock and statin therapy for acute respiratory distress syndrome were summarized. Original research trials that were included evaluate thrombolytic therapy in severe stroke, hyperoxia and hypertonic saline in septic shock, intraoperative ketamine for prevention of post-operative delirium, intravenous ketorolac dosing regimens for acute pain, angiotensin II for vasodilatory shock, dabigatran reversal with idarucizumab, bivalirudin versus heparin monotherapy for myocardial infarction, and balanced crystalloids versus saline fluid resuscitation. This clinical review provides perspectives on impactful critical care pharmacotherapy publications in 2017. Copyright © 2018 Elsevier Inc. All rights reserved.

High Serum sTREM-1 Correlates With Myocardial Dysfunction and Predicts Prognosis in Septic Patients.

PubMed

Li, Zhenyu; Zhang, Enyuan; Hu, Yipeng; Liu, Yi; Chen, Bing

2016-06-01

This study aimed to evaluate the predictive and prognostic value of soluble triggering receptor expressed on myeloid cells-1 (sTREM-1) in patients with myocardial dysfunction induced by severe sepsis and septic shock. A total of 84 patients with severe sepsis and septic shock were enrolled between May 2013 and December 2014.The patients were monitored by pulse indicator continuous cardiac output system and divided into myocardial depression group (cardiac function index [CFI] < 4.1/minute, n = 37) and nonmyocardial depression group (CFI ≥ 4.1/minute, n = 47 ). Additionally, the patients were divided into survival group (n = 40) and nonsurvival group (n = 44) based on 28-day mortality. Hemodynamic parameters and serum sTREM-1, B-type natriuretic peptide (BNP) and cardiac troponin I (cTnI) levels were collected on days 1, 3 and 5 after admission to intensive care unit. (1) The serum values of sTREM-1, BNP and cTnI in myocardial depression group were higher than those in nonmyocardial depression group (P < 0.01); and CFI, cardiac index, stroke volume, global ejection fraction and left ventricular contractility index (dpmax) in myocardial depression group were lower than those in nonmyocardial depression group on day 1 (P < 0.05); (2) serum sTREM-1 negatively correlated with left ventricular ejection fraction, CFI, cardiac index, global ejection fraction and dpmax, and it positively correlated with BNP and cTnI (P < 0.01); (3) the area under the receiver operating characteristics curve for sTREM-1 in the prediction of myocardial depression was 0.671 with a sensitivity of 83.8% and a specificity of 46.8% when cutoff point was 174.5ng/mL, the power of predicting septic depression for sTREM-1 was lower than that of BNP; logistic regression analysis showed that serum sTREM-1 was not an independent predictor of septic myocardial depression; the area under the receiver operating characteristics curve was 0.773 for sTREM-1 in predicting outcome with a sensitivity of 86.4% and a specificity of 80% when cutoff point was 182.3ng/mL, the power of predicting prognosis for sTREM-1 was superior to those of BNP and cTnI; (4) there was a decrease trend for sTREM-1 levels and an increasing trend for CFI in the survival group (P < 0.05). Myocardial dysfunction is common in patients with severe sepsis and septic shock and high serum levels of sTREM-1 correlates with myocardial dysfunction to some extent but is not an independent predictor, which more importantly showed prognostic value for septic shock outcome. Copyright © 2016 Southern Society for Clinical Investigation. Published by Elsevier Inc. All rights reserved.

Red blood cell transfusion in the resuscitation of septic patients with hematological malignancies.

PubMed

Mirouse, Adrien; Resche-Rigon, Matthieu; Lemiale, Virginie; Mokart, Djamel; Kouatchet, Achille; Mayaux, Julien; Vincent, François; Nyunga, Martine; Bruneel, Fabrice; Rabbat, Antoine; Lebert, Christine; Perez, Pierre; Renault, Anne; Meert, Anne-Pascale; Benoit, Dominique; Hamidfar, Rebecca; Jourdain, Mercé; Darmon, Michaël; Azoulay, Elie; Pène, Frédéric

2017-12-01

Indications for red blood cell (RBC) transfusion in septic acute circulatory failure remain unclear. We addressed the practices and the prognostic impact of RBC transfusion in the early resuscitation of severe sepsis and septic shock in patients with hematological malignancies. We performed a retrospective analysis of a prospectively collected database of patients with hematological malignancies who required intensive care unit (ICU) admission in 2010-2011. Patients with a main admission diagnosis of severe sepsis or septic shock were included in the present study. We assessed RBC transfusion during the first two days as part of initial resuscitation. Among the 1011 patients of the primary cohort, 631 (62.4%) were admitted to the ICU for severe sepsis (55%) or septic shock (45%). Among them, 210 (33.3%) patients received a median of 2 [interquartile 1-3] packed red cells during the first 48 h. Hemoglobin levels were lower in transfused patients at days 1 and 2 and became similar to those of non-transfused patients at day 3. Early RBC transfusion was more likely in patients with myeloid neoplasms and neutropenia. Transfused patients displayed more severe presentations as assessed by higher admission SOFA scores and blood lactate levels and the further requirements for organ failure supports. RBC transfusion within the first two days was associated with higher day 7 (20.5 vs. 13.3%, p = 0.02), in-ICU (39 vs. 25.2%, p < 0.001) and in-hospital (51 vs. 36.6%, p < 0.001) mortality rates. RBC transfusion remained independently associated with increased in-hospital mortality in multivariate logistic regression (OR 1.52 [1.03-2.26], p = 0.03) and propensity score-adjusted (OR 1.64 [1.05-2.57], p = 0.03) analysis. RBC transfusion is commonly used in the early resuscitation of septic patients with hematological malignancies. Although it was preferentially provided to the most severe patients, we found it possibly associated with an increased risk of death.

Coagulation phenotypes in septic shock as evaluated by calibrated automated thrombography.

PubMed

Perrin, Julien; Charron, Cyril; François, Jean-Hugues; Cramer-Bordé, Elisabeth; Lévy, Bruno; Borgel, Delphine; Vieillard-Baron, Antoine

2015-01-01

Sepsis induces alterations of coagulation suggesting both hypercoagulable or hypocoagulable features. The result of their combination remains unknown, making it difficult to predict whether one prevails over the other. Thrombin generation tests (TGTs) stand as an interesting tool to establish an integrative phenotype of coagulation. It has been reported that septic patients display a hypocoagulable trait using TGT. However, protein C (PC) system response was not evaluated. We aimed at describing the thrombin generation profile in patients with septic shock under conditions that are sensitive to PC system to evaluate the net results of coagulation abnormalities and to determine whether hypercoagulable or hypocoagulable traits coexist within a given individual. Thrombin generation was studied in plasma from patients presenting with septic shock at diagnosis and 6 h after a conventional therapeutic management using calibrated automated thrombography with or without thrombomodulin (TM) addition. Patients exhibit clear alterations of TGT that present as both consumption-related hypocoagulability (evidenced without TM addition) but also hypercoagulability by decreased sensitivity to the PC system evidenced with TM addition. No difference could be demonstrated between survivors and nonsurvivors at Day 28, but patients who do not respond to therapeutics at 6 h seem to be more hypercoagulable. More importantly, if our results evidence heterogeneity between patients, we show that alterations of coagulation result in an equilibrium in the majority of patients, thus suggesting "normocoagulability"; but, in the presence of a biological imbalance between baseline thrombin generation and sensitivity to TM, the global effect mostly tends toward hypercoagulability. Thus, TGT may help identify distinct biological coagulation phenotypes in the complex alterations induced by sepsis.

Prognosis Biomarkers of Severe Sepsis and Septic Shock by 1H NMR Urine Metabolomics in the Intensive Care Unit

PubMed Central

Modesto-Alapont, Vicente; Gonzalez-Marrachelli, Vannina; Vento-Rehues, Rosa; Jorda-Miñana, Angela; Blanquer-Olivas, Jose; Monleon, Daniel

2015-01-01

Early diagnosis and patient stratification may improve sepsis outcome by a timely start of the proper specific treatment. We aimed to identify metabolomic biomarkers of sepsis in urine by 1H-NMR spectroscopy to assess the severity and to predict outcomes. Urine samples were collected from 64 patients with severe sepsis or septic shock in the ICU for a 1H NMR spectra acquisition. A supervised analysis was performed on the processed spectra, and a predictive model for prognosis (30-days mortality/survival) of sepsis was constructed using partial least-squares discriminant analysis (PLS-DA). In addition, we compared the prediction power of metabolomics data respect the Sequential Organ Failure Assessment (SOFA) score. Supervised multivariate analysis afforded a good predictive model to distinguish the patient groups and detect specific metabolic patterns. Negative prognosis patients presented higher values of ethanol, glucose and hippurate, and on the contrary, lower levels of methionine, glutamine, arginine and phenylalanine. These metabolites could be part of a composite biopattern of the human metabolic response to sepsis shock and its mortality in ICU patients. The internal cross-validation showed robustness of the metabolic predictive model obtained and a better predictive ability in comparison with SOFA values. Our results indicate that NMR metabolic profiling might be helpful for determining the metabolomic phenotype of worst-prognosis septic patients in an early stage. A predictive model for the evolution of septic patients using these metabolites was able to classify cases with more sensitivity and specificity than the well-established organ dysfunction score SOFA. PMID:26565633

Leukemia inhibitory factor levels are elevated in septic shock and various inflammatory body fluids.

PubMed Central

Waring, P; Wycherley, K; Cary, D; Nicola, N; Metcalf, D

1992-01-01

Leukemia inhibitory factor (LIF) has many biological actions which parallel those of IL-1, IL-6 and tumor necrosis factor-alpha, but its role in the pathogenesis of human disease is unknown. A specific radioreceptor competition assay capable of detecting LIF at concentrations above 1 ng/ml (45 pM) was developed. To identify disease states in which LIF might be involved, a cross-sectional survey of serum and body fluids from approximately 1,500 subjects with a variety of diseases was performed using the LIF radioreceptor competition assay. Serum LIF concentrations were transiently elevated (2-200 ng/ml) in six subjects with meningococcal or Gram-negative septic shock, and in a subject with idiopathic fulminant hepatic failure. Moderately elevated LIF concentrations (> 10 ng/ml) were detected in cerebrospinal fluid from subjects with bacterial meningitis, in effusions associated with pneumonia and peritonitis, and in amniotic fluid from a woman with chorioamnionitis. Low LIF concentrations (1-10 ng/ml) were present in synovial fluid from subjects with inflammatory arthritis, amniotic fluid from women in labor, and some reactive, chronic inflammatory and malignant effusions and cyst fluids, but rarely in transudates. These initial findings suggest that LIF might be involved in the pathogenesis of inflammation and septic shock. PMID:1430224

Initial fractal exponent of heart-rate variability is associated with success of early resuscitation in patients with severe sepsis or septic shock: a prospective cohort study

PubMed Central

Brown, Samuel M.; Tate, Quinn; Jones, Jason P.; Knox, Daniel; Kuttler, Kathryn G.; Lanspa, Michael; Rondina, Matthew T.; Grissom, Colin K.; Behera, Subhasis; Mathews, V.J.; Morris, Alan

2013-01-01

Introduction Heart-rate variability reflects autonomic nervous system tone as well as the overall health of the baroreflex system. We hypothesized that loss of complexity in heart-rate variability upon ICU admission would be associated with unsuccessful early resuscitation of sepsis. Methods We prospectively enrolled patients admitted to ICUs with severe sepsis or septic shock from 2009 to 2011. We studied 30 minutes of EKG, sampled at 500 Hz, at ICU admission and calculated heart-rate complexity via detrended fluctuation analysis. Primary outcome was vasopressor independence at 24 hours after ICU admission. Secondary outcome was 28-day mortality. Results We studied 48 patients, of whom 60% were vasopressor independent at 24 hours. Five (10%) died within 28 days. The ratio of fractal alpha parameters was associated with both vasopressor independence and 28-day mortality (p=0.04) after controlling for mean heart rate. In the optimal model, SOFA score and the long-term fractal alpha parameter were associated with vasopressor independence. Conclusions Loss of complexity in heart rate variability is associated with worse outcome early in severe sepsis and septic shock. Further work should evaluate whether complexity of heart rate variability (HRV) could guide treatment in sepsis. PMID:23958243

[Septic shock due to community-acquired complicated intra-abdominal infection treated with ertapenem: outcome in 25 cases].

PubMed

Maseda, E; Lillo, M; Fernández, L; Villagrán, M J; Gómez-Rice, A; Ramasco, F

2008-04-01

To assess the effectiveness of ertapenem in patients admitted to a surgical intensive care unit with septic shock due to community-acquired complicated intra-abdominal infection. Patients undergoing emergency surgery for community-acquired complicated intra-abdominal infection were enrolled prospectively. All patients were given intravenous ertapenem at a rate of 1 g/24 h and the guidelines of the Surviving Sepsis Campaign were applied. Outcome measures were duration of antibiotic therapy, mean length of stay in the surgical intensive care unit (ICU), antibiotic failure, and death while in the surgical ICU. Twenty-five patients with a mean (SD) age of 74 (14) years were enrolled. The origin of infection was the colon in 56% of the cases; most patients (76%) had generalized peritonitis. The mean stay in the surgical ICU was 10 (7) days. The mean duration of antibiotic therapy was 5.8 (1.26) days. Antibiotic failure occurred in 12%. Mortality in the surgical ICU was 28%. Our findings suggest that patients with community-acquired intra-abdominal infection and septic shock have a good chance of survival when treated according to the guidelines of the Surviving Sepsis Campaign. Ertapenem seems to give good results when used in this setting.

Adrenergic support in septic shock: a critical review.

PubMed

Póvoa, Pedro; Carneiro, António H

2010-02-01

The definition of septic shock includes sepsis-induced hypotension despite adequate fluid resuscitation, along with the presence of organ perfusion abnormalities, and ultimately cell dysfunction. To restore adequate organ perfusion and cell homeostasis, cardiac output should be restored with volume infusion plus vasopressor agents as indicated. Appropriate arterial pressure for each individual patient and proper arterial oxygen content are key elements to restoring perfusion. Tissue perfusion can be monitored by markers of organ and mitochondrial function, namely urine output, level of consciousness, peripheral skin perfusion, central or mixed venous oxygen saturation, and lactate. The hemodynamic effects of the different vasopressor agents depend on the relative affinity to adrenergic receptors. Those with predominant alpha-agonist activity produce more vasoconstriction (inoconstrictors) while those with predominant beta-agonist stimulation increase cardiac performance (inodilators). The debate about whether one vasopressor agent is superior to another is still ongoing. The Surviving Sepsis Campaign guidelines refer to either norepinephrine or dopamine as the first-choice vasopressor agent to correct hypotension in septic shock. However, recent data from observational and controlled trials have challenged these recommendations concerning different adrenergic agents. As a result, our view on the prescription of vasopressors has changed from a probably oversimplified "one-size-fits-all" approach to a multimodal approach in vasopressor selection.

Mortality prediction in patients with severe septic shock: a pilot study using a target metabolomics approach.

PubMed

Ferrario, Manuela; Cambiaghi, Alice; Brunelli, Laura; Giordano, Silvia; Caironi, Pietro; Guatteri, Luca; Raimondi, Ferdinando; Gattinoni, Luciano; Latini, Roberto; Masson, Serge; Ristagno, Giuseppe; Pastorelli, Roberta

2016-02-05

Septic shock remains a major problem in Intensive Care Unit, with high lethality and high-risk second lines treatments. In this preliminary retrospective investigation we examined plasma metabolome and clinical features in a subset of 20 patients with severe septic shock (SOFA score >8), enrolled in the multicenter Albumin Italian Outcome Sepsis study (ALBIOS, NCT00707122). Our purpose was to evaluate the changes of circulating metabolites in relation to mortality as a pilot study to be extended in a larger cohort. Patients were analyzed according to their 28-days and 90-days mortality. Metabolites were measured using a targeted mass spectrometry-based quantitative metabolomic approach that included acylcarnitines, aminoacids, biogenic amines, glycerophospholipids, sphingolipids, and sugars. Data-mining techniques were applied to evaluate the association of metabolites with mortality. Low unsaturated long-chain phosphatidylcholines and lysophosphatidylcholines species were associated with long-term survival (90-days) together with circulating kynurenine. Moreover, a decrease of these glycerophospholipids was associated to the event at 28-days and 90-days in combination with clinical variables such as cardiovascular SOFA score (28-day mortality model) or renal replacement therapy (90-day mortality model). Early changes in the plasma levels of both lipid species and kynurenine associated with mortality have potential implications for early intervention and discovering new target therapy.

Mortality prediction in patients with severe septic shock: a pilot study using a target metabolomics approach

PubMed Central

Ferrario, Manuela; Cambiaghi, Alice; Brunelli, Laura; Giordano, Silvia; Caironi, Pietro; Guatteri, Luca; Raimondi, Ferdinando; Gattinoni, Luciano; Latini, Roberto; Masson, Serge; Ristagno, Giuseppe; Pastorelli, Roberta

2016-01-01

Septic shock remains a major problem in Intensive Care Unit, with high lethality and high-risk second lines treatments. In this preliminary retrospective investigation we examined plasma metabolome and clinical features in a subset of 20 patients with severe septic shock (SOFA score >8), enrolled in the multicenter Albumin Italian Outcome Sepsis study (ALBIOS, NCT00707122). Our purpose was to evaluate the changes of circulating metabolites in relation to mortality as a pilot study to be extended in a larger cohort. Patients were analyzed according to their 28-days and 90-days mortality. Metabolites were measured using a targeted mass spectrometry-based quantitative metabolomic approach that included acylcarnitines, aminoacids, biogenic amines, glycerophospholipids, sphingolipids, and sugars. Data-mining techniques were applied to evaluate the association of metabolites with mortality. Low unsaturated long-chain phosphatidylcholines and lysophosphatidylcholines species were associated with long-term survival (90-days) together with circulating kynurenine. Moreover, a decrease of these glycerophospholipids was associated to the event at 28-days and 90-days in combination with clinical variables such as cardiovascular SOFA score (28-day mortality model) or renal replacement therapy (90-day mortality model). Early changes in the plasma levels of both lipid species and kynurenine associated with mortality have potential implications for early intervention and discovering new target therapy. PMID:26847922

Augmented renal clearance is not a risk factor for mortality in Enterobacteriaceae bloodstream infections treated with appropriate empiric antimicrobials.

PubMed

Burnham, Jason P; Micek, Scott T; Kollef, Marin H

2017-01-01

The main objective of the study was to assess whether augmented renal clearance was a risk factor for mortality in a cohort of patients with Enterobacteriaceae sepsis, severe sepsis, or septic shock that all received appropriate antimicrobial therapy within 12 hours. Using a retrospective cohort from Barnes-Jewish Hospital, a 1,250-bed teaching hospital, we collected data on individuals with Enterobacteriaceae sepsis, severe sepsis, and septic shock who received appropriate initial antimicrobial therapy between June 2009 and December 2013. Clinical outcomes were compared according to renal clearance, as assessed by Modification of Diet in Renal Disease (MDRD) and Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formulas, sepsis classification, demographics, severity of illness, and comorbidities. We identified 510 patients with Enterobacteriaceae bacteremia and sepsis, severe sepsis, or septic shock. Sixty-seven patients (13.1%) were nonsurvivors. Augmented renal clearance was uncommon (5.1% of patients by MDRD and 3.0% by CKD-EPI) and was not associated with increased mortality. Our results are limited by the absence of prospective determination of augmented renal clearance. However, in this small cohort, augmented renal clearance as assessed by MDRD and CKD-EPI does not seem to be a risk factor for mortality in patients with Enterobacteriaceae sepsis. Future studies should assess this finding prospectively.

Gas gangrene without wound: both lower extremities affected simultaneously.

PubMed

Lu, Jun; Wu, Xiao-Tao; Kong, Xiang-Fei; Tang, Wen-Hao; Cheng, Jian-Ming; Wang, Hai-Liang

2008-10-01

Gas gangrene is a necrotizing soft tissue infection characterized by muscular necrosis and gas formation. It develops quickly and can cause septic shock and death. In adults, gas gangrene used to be a well-known complication of war wounds. Recently, cases of spontaneous or nontraumatic gas gangrene have been reported in both adults and children. We report a case of nontraumatic gas gangrene involving both the lower extremities simultaneously. Pathogenesis of this fatal soft tissue infection is discussed.We also review the diagnosis and treatment aspects of this entity.

A small 'lick' will sink a great ship: fulminant septicaemia after dog saliva wound treatment in an asplenic patient.

PubMed

Morandi, Evi M; Pauzenberger, Reinhard; Tasch, Christoph; Rieger, Ulrich M; Pierer, Gerhard; Djedovic, Gabriel

2017-12-01

Capnocytophaga canimorsus is a bacterium transmitted through the saliva of dogs. An infection can cause severe sepsis with acral necrosis and is potentially fatal. Here, we report the case of a 41-year-old man who was infected through a wound that was licked by his dog. He went into septic shock with disseminated intravascular coagulation and subsequently lost both lower legs, his nose and all the fingers on both hands. © 2017 Medicalhelplines.com Inc and John Wiley & Sons Ltd.

Effect of Early Vasopressin vs Norepinephrine on Kidney Failure in Patients With Septic Shock: The VANISH Randomized Clinical Trial.

PubMed

Gordon, Anthony C; Mason, Alexina J; Thirunavukkarasu, Neeraja; Perkins, Gavin D; Cecconi, Maurizio; Cepkova, Magda; Pogson, David G; Aya, Hollmann D; Anjum, Aisha; Frazier, Gregory J; Santhakumaran, Shalini; Ashby, Deborah; Brett, Stephen J

2016-08-02

Norepinephrine is currently recommended as the first-line vasopressor in septic shock; however, early vasopressin use has been proposed as an alternative. To compare the effect of early vasopressin vs norepinephrine on kidney failure in patients with septic shock. A factorial (2×2), double-blind, randomized clinical trial conducted in 18 general adult intensive care units in the United Kingdom between February 2013 and May 2015, enrolling adult patients who had septic shock requiring vasopressors despite fluid resuscitation within a maximum of 6 hours after the onset of shock. Patients were randomly allocated to vasopressin (titrated up to 0.06 U/min) and hydrocortisone (n = 101), vasopressin and placebo (n = 104), norepinephrine and hydrocortisone (n = 101), or norepinephrine and placebo (n = 103). The primary outcome was kidney failure-free days during the 28-day period after randomization, measured as (1) the proportion of patients who never developed kidney failure and (2) median number of days alive and free of kidney failure for patients who did not survive, who experienced kidney failure, or both. Rates of renal replacement therapy, mortality, and serious adverse events were secondary outcomes. A total of 409 patients (median age, 66 years; men, 58.2%) were included in the study, with a median time to study drug administration of 3.5 hours after diagnosis of shock. The number of survivors who never developed kidney failure was 94 of 165 patients (57.0%) in the vasopressin group and 93 of 157 patients (59.2%) in the norepinephrine group (difference, -2.3% [95% CI, -13.0% to 8.5%]). The median number of kidney failure-free days for patients who did not survive, who experienced kidney failure, or both was 9 days (interquartile range [IQR], 1 to -24) in the vasopressin group and 13 days (IQR, 1 to -25) in the norepinephrine group (difference, -4 days [95% CI, -11 to 5]). There was less use of renal replacement therapy in the vasopressin group than in the norepinephrine group (25.4% for vasopressin vs 35.3% for norepinephrine; difference, -9.9% [95% CI, -19.3% to -0.6%]). There was no significant difference in mortality rates between groups. In total, 22 of 205 patients (10.7%) had a serious adverse event in the vasopressin group vs 17 of 204 patients (8.3%) in the norepinephrine group (difference, 2.5% [95% CI, -3.3% to 8.2%]). Among adults with septic shock, the early use of vasopressin compared with norepinephrine did not improve the number of kidney failure-free days. Although these findings do not support the use of vasopressin to replace norepinephrine as initial treatment in this situation, the confidence interval included a potential clinically important benefit for vasopressin, and larger trials may be warranted to assess this further. clinicaltrials.gov Identifier: ISRCTN 20769191.

Effects of high doses of selenium, as sodium selenite, in septic shock: a placebo-controlled, randomized, double-blind, phase II study

PubMed Central

Forceville, Xavier; Laviolle, Bruno; Annane, Djillali; Vitoux, Dominique; Bleichner, Gérard; Korach, Jean-Michel; Cantais, Emmanuel; Georges, Hugues; Soubirou, Jean-Louis; Combes, Alain; Bellissant, Eric

2007-01-01

Introduction Sepsis is associated with the generation of oxygen free radicals and (lacking) decreased selenium plasma concentrations. High doses of sodium selenite might reduce inflammation by a direct pro-oxidative effect and may increase antioxidant cell capacities by selenium incorporation into selenoenzymes. We investigated the effects of a continuous administration of high doses of selenium in septic shock patients. Methods A prospective, multicentre, placebo-controlled, randomized, double-blind study was performed with an intention-to-treat analysis in severe septic shock patients with documented infection. Patients received, for 10 days, selenium as sodium selenite (4,000 μg on the first day, 1,000 μg/day on the nine following days) or matching placebo using continuous intravenous infusion. The primary endpoint was the time to vasopressor therapy withdrawal. The duration of mechanical ventilation, the mortality rates in the intensive care unit, at hospital discharge, and at 7, 14, 28 and 180 days and 1 year after randomization, and adverse events were recorded. Results Sixty patients were included (placebo, n = 29; selenium, n = 31). The median time to vasopressor therapy withdrawal was 7 days in both groups (95% confidence interval = 5–8 and 6–9 in the placebo and selenium groups, respectively; log-rank, P = 0.713). The median duration of mechanical ventilation was 14 days and 19 days in the placebo and selenium groups, respectively (P = 0.762). Mortality rates did not significantly differ between groups at any time point. Rates of adverse events were similar in the two groups. Conclusion Continuous infusion of selenium as sodium selenite (4,000 μg on the first day, 1,000 μg/day on the nine following days) had no obvious toxicity but did not improve the clinical outcome in septic shock patients. Trial Registration = NCT00207844. PMID:17617901

The Prevalence and Clinical Significance of Low Procalcitonin Levels Among Patients With Severe Sepsis or Septic Shock in the Emergency Department.

PubMed

Choe, Eun A; Shin, Tae Gun; Jo, Ik Joon; Hwang, Sung Yeon; Lee, Tae Rim; Cha, Won Chul; Sim, Min Seob

2016-07-01

The aims of this study were to evaluate the prevalence of low procalcitonin (PCT) levels among patients with severe sepsis or septic shock, and to investigate clinical characteristics and outcomes associated with low PCT levels. We analyzed data from the sepsis registry for patients with severe sepsis or septic shock in the emergency department. Based on a specific PCT cutoff value, patients were classified into two groups: a low PCT group, PCT <0.25 ng/mL; and a high PCT group, PCT ≥0.25 ng/mL. The primary endpoint was 28-day mortality. A multivariable logistic regression model was used to evaluate independent factors associated with low PCT and 28-day mortality. A total of 1,212 patients were included. Of the eligible patients, 154 (12.7%) were assigned to the low PCT group, and 1,058 (87.3%) to the high PCT group. The 28-day mortality was 4.6% in the low PCT group and 13.5% in the high PCT group (P < 0.01). The adjusted odds ratio of the low PCT group for 28-day mortality was 0.43 (95% CI 0.19-0.98; P = 0.04). There was no trend of increasing mortality among higher PCT level patients. In a logistic regression model, factors associated with low PCT were pneumonia, lower C-reactive protein levels, lower lactate levels, the absence of bacteremia, and the absence of organ failure. Intra-abdominal infection and obesity were associated with high PCT. Initial low PCT levels were common among patients diagnosed with severe sepsis or septic shock in the emergency department, suggesting favorable outcomes. The prevalence of low PCT levels was significantly different according to obesity, the source of infection, C-reactive protein levels, lactate levels, bacteremia, and organ failure.

Evaluation of Vasopressin for Septic Shock in Patients on Chronic Renin-Angiotensin-Aldosterone System Inhibitors.

PubMed

Erwin, Beth L; Denaburg, Michael A; Barker, Andrew B; McArdle, Philip J; Windham, Samuel T; Morgan, Charity J

2017-12-01

To compare the hemodynamic response in septic shock patients receiving vasopressin who were on chronic renin-angiotensin-aldosterone system inhibitor therapy with those who were not. Single-center, retrospective cohort study. Medical and surgical ICUs at a 1,100-bed academic medical center. Medical and surgical ICU patients with septic shock who received vasopressin infusion added to at least one concomitant vasopressor agent between January 2014 and December 2015, then divided into two cohorts: 1) patients who were on chronic renin-angiotensin-aldosterone system inhibitor therapy as outpatients and 2) patients who were not on chronic renin-angiotensin-aldosterone system inhibitor therapy as outpatients. None. Mean arterial pressure at 6 hours was 72.2 mm Hg in the renin-angiotensin-aldosterone system inhibitor group versus 69.7 mm Hg in the non-renin-angiotensin-aldosterone system inhibitor group (p = 0.298). There was no difference in mean arterial pressure at 1, 24, or 48 hours between groups. Total concomitant vasopressor requirements, based on norepinephrine equivalents excluding vasopressin, were significantly lower at 24 hours in the renin-angiotensin-aldosterone system inhibitor group versus the non-renin-angiotensin-aldosterone system inhibitor group (10.7 vs 18.1 µg/min, respectively; p = 0.007), but no significant differences were seen at the other time points assessed. There were no significant differences in ICU or hospital length of stay or mortality. There was no significant difference in the primary outcome of 6-hour mean arterial pressure in septic shock patients receiving vasopressin who were on chronic renin-angiotensin-aldosterone system inhibitor therapy versus those receiving vasopressin who were not on chronic renin-angiotensin-aldosterone system inhibitor therapy. Renin-angiotensin-aldosterone system inhibitor patients had lower total concomitant vasopressor requirements at 24 hours compared with non-renin-angiotensin-aldosterone system inhibitor patients.

Delay Within the 3-Hour Surviving Sepsis Campaign Guideline on Mortality for Patients With Severe Sepsis and Septic Shock.

PubMed

Pruinelli, Lisiane; Westra, Bonnie L; Yadav, Pranjul; Hoff, Alexander; Steinbach, Michael; Kumar, Vipin; Delaney, Connie W; Simon, Gyorgy

2018-04-01

To specify when delays of specific 3-hour bundle Surviving Sepsis Campaign guideline recommendations applied to severe sepsis or septic shock become harmful and impact mortality. Retrospective cohort study. One health system composed of six hospitals and 45 clinics in a Midwest state from January 01, 2011, to July 31, 2015. All adult patients hospitalized with billing diagnosis of severe sepsis or septic shock. Four 3-hour Surviving Sepsis Campaign guideline recommendations: 1) obtain blood culture before antibiotics, 2) obtain lactate level, 3) administer broad-spectrum antibiotics, and 4) administer 30 mL/kg of crystalloid fluid for hypotension (defined as "mean arterial pressure" < 65) or lactate (> 4). To determine the effect of t minutes of delay in carrying out each intervention, propensity score matching of "baseline" characteristics compensated for differences in health status. The average treatment effect in the treated computed as the average difference in outcomes between those treated after shorter versus longer delay. To estimate the uncertainty associated with the average treatment effect in the treated metric and to construct 95% CIs, bootstrap estimation with 1,000 replications was performed. From 5,072 patients with severe sepsis or septic shock, 1,412 (27.8%) had in-hospital mortality. The majority of patients had the four 3-hour bundle recommendations initiated within 3 hours. The statistically significant time in minutes after which a delay increased the risk of death for each recommendation was as follows: lactate, 20.0 minutes; blood culture, 50.0 minutes; crystalloids, 100.0 minutes; and antibiotic therapy, 125.0 minutes. The guideline recommendations showed that shorter delays indicates better outcomes. There was no evidence that 3 hours is safe; even very short delays adversely impact outcomes. Findings demonstrated a new approach to incorporate time t when analyzing the impact on outcomes and provide new evidence for clinical practice and research.

Predictive Value of Soluble Programmed Death-1 for Severe Sepsis and Septic Shock During the First Week in an Intensive Care Unit.

PubMed

Zhao, Yongzhen; Jia, Yumei; Li, Chunsheng; Shao, Rui; Fang, Yingying

2018-04-26

Programmed death-1 (PD-1)/programmed death ligand-1 (PD-L1) exists in both membrane-bound and soluble forms. In this study, we evaluated the predictive value of soluble PD-1 (sPD-1) for severity and 28-day mortality in patients with severe sepsis and septic shock during the first week in an intensive care unit (ICU). In this prospective cohort study, patients were classified into the severe sepsis group or the septic shock group according to the severity of their condition on ICU admission. All patients were also separated into the survivor or nonsurvivor groups according to their 28-day outcomes. Peripheral blood sPD-1 and soluble PD-L1 (sPD-L1) levels, PD-1 expression on CD4 and CD8 T cells, and PD-L1 expression on monocytes were measured and compared between the groups on days 1 and 7 after ICU admission. In all, 45 healthy volunteers and 112 patients were recruited. Serum sPD-1 levels were positively correlated with the severity of sepsis, sPD-L1 levels, PD-1 expression on CD4 or CD8 T cells, and PD-L1 expression on monocytes. The sPD-1 was an independent predictive factor for 28-day mortality both on day 1 and day 7. The area under the curve (AUC) of the sPD-1 on day 7 (0.871) was higher than that on day 1 (0.785) (P < 0.05), and better than the AUC of the percentages of PD-L1 on monocytes (0.770) on day 7 (P < 0.05). Serum sPD-1 shows valuable predictive ability for the severity and 28-day mortality of severe sepsis and septic shock during the first week of ICU treatment.

Early lactate clearance is associated with biomarkers of inflammation, coagulation, apoptosis, organ dysfunction and mortality in severe sepsis and septic shock

PubMed Central

2010-01-01

Background Lactate clearance, a surrogate for the magnitude and duration of global tissue hypoxia, is used diagnostically, therapeutically and prognostically. This study examined the association of early lactate clearance with selected inflammatory, coagulation, apoptosis response biomarkers and organ dysfunction scores in severe sepsis and septic shock. Methods Measurements of serum arterial lactate, biomarkers (interleukin-1 receptor antagonist, interleukin-6, interleukin-8, interleukin-10, tumor necrosis factor-alpha, intercellular adhesion molecule-1, high mobility group box-1, D-Dimer and caspase-3), and organ dysfunction scores (Acute Physiology and Chronic Health Evaluation II, Simplified Acute Physiology Score II, Multiple Organ Dysfunction Score, and Sequential Organ Failure Assessment) were obtained in conjunction with a prospective, randomized study examining early goal-directed therapy in severe sepsis and septic shock patients presenting to the emergency department (ED). Lactate clearance was defined as the percent change in lactate levels after six hours from a baseline measurement in the ED. Results Two-hundred and twenty patients, age 65.0 +/- 17.1 years, were examined, with an overall lactate clearance of 35.5 +/- 43.1% and in-hospital mortality rate of 35.0%. Patients were divided into four quartiles of lactate clearance, -24.3 +/- 42.3, 30.1 +/- 7.5, 53.4 +/- 6.6, and 75.1 +/- 7.1%, respectively (p < 0.01). The mean levels of all biomarkers and organ dysfunction scores over 72 hours were significantly lower with higher lactate clearance quartiles (p < 0.01). There was a significant decreased in-hospital, 28-day, and 60-day mortality in the higher lactate clearance quartiles (p < 0.01). Conclusions Early lactate clearance as a surrogate for the resolution of global tissue hypoxia is significantly associated with decreased levels of biomarkers, improvement in organ dysfunction and outcome in severe sepsis and septic shock. PMID:20181046

Targeting matrix metalloproteinases with intravenous doxycycline in severe sepsis--A randomised placebo-controlled pilot trial.

PubMed

Nukarinen, Eija; Tervahartiala, Taina; Valkonen, Miia; Hynninen, Marja; Kolho, Elina; Pettilä, Ville; Sorsa, Timo; Backman, Janne; Hästbacka, Johanna

2015-09-01

An overwhelming inflammatory process is the hallmark of severe sepsis and septic shock. Matrix metalloproteinases (MMPs)-8 and -9 are released from neutrophils and activated in sepsis to participate in inflammation in several ways. High levels of MMP-8 may associate with increased ICU mortality. The activity of MMP-8 and -9 is regulated by a natural inhibitor, tissue inhibitor of metalloproteinases-1 (TIMP-1). Moreover, MMPs are chemically inhibited by tetracycline-group antibiotics, such as doxycycline. We therefore aimed to study plasma concentration and MMP inhibition after intravenous doxycycline in critically ill patients with severe sepsis and septic shock in a prospective, randomised, placebo-controlled double-blinded pilot trial. Twenty-four patients with severe sepsis or septic shock were randomised in 3 groups. Group 1 received 200, 100 and 100mg, group 2 100, 50 and 50mg of intravenous doxycycline and group 3 placebo on three consecutive days. We measured doxycycline concentrations from baseline up to day 5. MMPs and TIMP-1 concentrations were measured from baseline up to day 10 of study and we compared their changes over time from baseline to 72 h and from baseline to 120 h. Data from 23 patients were analysed. At 72 h all patients in group 1 showed doxycycline concentrations >1 mg/l, whereas none in group 2 did. No serious adverse effects of the drug were recorded. We observed no differences over time up to 72 or up to 120 h in the concentrations or activities of MMP-8, -9 or TIMP-1 in any of the groups. We found intravenous doxycycline 100, 50 and 50mg to be adequate to achieve a sub-antimicrobial concentration in patients with severe sepsis or septic shock but having no impact on MMP-8, -9 or TIMP-1 concentrations or activities. Copyright © 2015 Elsevier Ltd. All rights reserved.

Predictive value of N-terminal pro-brain natriuretic peptide in severe sepsis and septic shock.

PubMed

Varpula, Marjut; Pulkki, Kari; Karlsson, Sari; Ruokonen, Esko; Pettilä, Ville

2007-05-01

The aim of this study was to evaluate the predictive value of N-terminal pro-brain natriuretic peptide (NT-proBNP) on mortality in a large, unselected patient population with severe sepsis and septic shock. Prospective observational cohort study about incidence and prognosis of sepsis in 24 intensive care units in Finland (the FINNSEPSIS study). A total of 254 patients with severe sepsis or septic shock. After informed consent, the blood tests for NT-proBNP analyses were drawn on the day of admission and 72 hrs thereafter. Patients' demographic data were collected, and intensive care unit and hospital mortality and basic hemodynamic and laboratory data were recorded daily. NT-proBNP levels at admission were significantly higher in hospital nonsurvivors (median, 7908 pg/mL) compared with survivors (median, 3479 pg/mL; p = .002), and the difference remained after 72 hrs (p = .002). The receiver operating characteristic curves of admission and 72-hr NT-proBNP levels for hospital mortality resulted in area under the curve values of 0.631 (95% confidence interval, 0.549-0.712; p = .002) and 0.648 (95% confidence interval, 0.554-0.741; p = .002), respectively. In logistic regression analyses, NT-proBNP values at 72 hrs after inclusion and Simplified Acute Physiology Score for the first 24 hrs were independent predictors of hospital mortality. Pulmonary artery occlusion pressure (p < .001), plasma creatinine clearance (p = .001), platelet count (p = .03), and positive blood culture (p = .04) had an independent effect on first-day NT-proBNP values, whereas after 72 hrs, only plasma creatinine clearance (p < .001) was significant in linear regression analysis. NT-proBNP values are frequently increased in severe sepsis and septic shock. Values are significantly higher in nonsurvivors than survivors. NT-proBNP on day 3 in the intensive care unit is an independent prognostic marker of mortality in severe sepsis.

Salivary Cortisol Can Replace Free Serum Cortisol Measurements in Patients With Septic Shock

PubMed Central

Orlander, Philip R.

2011-01-01

Background: There is a renewed interest in adrenal function during severe sepsis. Most studies have used total serum cortisol levels; however, only free serum cortisol is biologically active. The aim of this study was to determine the validity of salivary cortisol levels as a surrogate for free serum cortisol levels during septic shock. Methods: Fifty-seven patients with septic shock were studied to determine the correlation between total serum cortisol and salivary cortisol to free serum cortisol levels. Thirty-eight patients were included in the salivary to free serum cortisol correlation. Salivary cortisol level was tested by enzyme immunoassay. Serum total cortisol, free cortisol, and cortisol-binding globulin (CBG) levels were determined by liquid chromatography-mass spectrometry, equilibrium analysis, and radioimmunoassay, respectively. Results: The mean ± SD age was 56.6 ± 18.5 years. Fifty-seven percent were women. APACHE (Acute Physiology and Chronic Health Evaluation) II score median was 26, Simplified Acute Physiology Score II median was 61, and Sequential Organ Failure Assessment median was 13. The correlation between salivary and free serum cortisol levels was 0.79 (95% CI, 0.63-0.89; P < .0001). The correlation between free serum cortisol and total serum cortisol levels was 0.86 (95% CI, 0.78-0.92; P < .0001). The mean ± SD free serum cortisol level was 2.27 ± 1.64 μg/dL. The mean ± SD salivary cortisol level was 2.60 ± 2.69 μg/dL. The mean ± SD total serum cortisol level was 21.56 ± 8.71 μg/dL. The mean ± SD CBG level was 23.54 ± 8.33 mg/dL. Conclusions: Salivary cortisol level can be used as a surrogate of free serum cortisol level in patients with septic shock with very good correlation. Salivary cortisol testing is noninvasive, easy to perform, and can be conducted daily. Trial registry: ClinicalTrials.gov; No.: NCT00523198; URL: www.clinicaltrials.gov PMID:21816912

Validation of a simple method of estimating plasma free cortisol: role of cortisol binding to albumin.

PubMed

Dorin, Richard I; Pai, Hemanth K; Ho, Jui T; Lewis, John G; Torpy, David J; Urban, Frank K; Qualls, Clifford R

2009-01-01

To develop, optimize, and validate a generalized mass action, equilibrium solution that incorporates measured concentrations of albumin as well as cortisol binding globulin (CBG) to estimate free cortisol. Free cortisol was estimated by Coolens method or by cubic equilibrium equation and compared to measured free cortisol, determined by ultrafiltration method, in subjects with septic shock (n=45), sepsis (n=19), and healthy controls (n=10) at 0, 30, and 60 min following administration of cosyntropin (250 mcg). The data set also included repeat testing in 30 subjects following recovery from sepsis/septic shock. The equilibrium dissociation constant for cortisol binding to albumin (K(A)) was optimized by non-linear regression. The cubic equilibrium solution was also used to model the influence of cortisol, CBG, and albumin concentration on free cortisol. Compared to measured free cortisol, the cubic solution, using an optimized K(A) of 137,800 nM, was less biased than Coolens solution, with mean percent error of -23.0% vs. -41.1% (paired t test, P<0.001). Standard deviation values were also significantly lower (Wilks' test, P<0.001) for the cubic solution (SD 35.8% vs. 40.8% for cubic vs. Coolens, respectively). Modeling studies using the cubic solution suggest an interaction effect by which low concentrations of CBG and albumin contribute to a greater increase in free cortisol than the sum of their independent effects. Mass action solutions that incorporate the measured concentration of albumin as well as CBG provide a reasonably accurate estimate of free cortisol that generalizes to conditions of health as well as a setting of hypercortisolism and low CBG and albumin concentrations associated with septic shock. Modeling studies emphasize the significant contribution of albumin deficiency and albumin-bound cortisol under conditions of CBG-deficiency, and identify a synergistic effect by which combined CBG and albumin deficiency contribute to elevation of free cortisol in septic shock.

Role of Admission Troponin-T and Serial Troponin-T Testing in Predicting Outcomes in Severe Sepsis and Septic Shock.

PubMed

Vallabhajosyula, Saraschandra; Sakhuja, Ankit; Geske, Jeffrey B; Kumar, Mukesh; Poterucha, Joseph T; Kashyap, Rahul; Kashani, Kianoush; Jaffe, Allan S; Jentzer, Jacob C

2017-09-09

Troponin-T elevation is seen commonly in sepsis and septic shock patients admitted to the intensive care unit. We sought to evaluate the role of admission and serial troponin-T testing in the prognostication of these patients. This was a retrospective cohort study from 2007 to 2014 on patients admitted to the intensive care units at the Mayo Clinic with severe sepsis and septic shock. Elevated admission troponin-T and significant delta troponin-T were defined as ≥0.01 ng/mL and ≥0.03 ng/mL in 3 hours, respectively. The primary outcome was in-hospital mortality. Secondary outcomes included 1-year mortality and lengths of stay. During this 8-year period, 944 patients met the inclusion criteria with 845 (90%) having an admission troponin-T ≥0.01 ng/mL. Serial troponin-T values were available in 732 (78%) patients. Elevated admission troponin-T was associated with older age, higher baseline comorbidity, and severity of illness, whereas significant delta troponin-T was associated with higher severity of illness. Admission log 10 troponin-T was associated with unadjusted in-hospital (odds ratio 1.6; P =0.003) and 1-year mortality (odds ratio 1.3; P =0.04), but did not correlate with length of stay. Elevated delta troponin-T and log 10 delta troponin-T were not significantly associated with any of the primary or secondary outcomes. Admission log 10 troponin-T remained an independent predictor of in-hospital mortality (odds ratio 1.4; P =0.04) and 1-year survival (hazard ratio 1.3; P =0.008). In patients with sepsis and septic shock, elevated admission troponin-T was associated with higher short- and long-term mortality. Routine serial troponin-T testing did not add incremental prognostic value in these patients. © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

Effect of early goal-directed therapy on mortality in patients with severe sepsis or septic shock: a meta-analysis of randomised controlled trials

PubMed Central

Yu, Hong; Chi, Dongmei; Wang, Siyang; Liu, Bin

2016-01-01

Objective To determine whether patients with severe sepsis or septic shock could benefit from a strict and early goal-directed therapy (EGDT) protocol recommended by Surviving Sepsis Campaign (SSC) Guidelines. Methods MEDLINE/PubMed, EMBASE/OVID and Cochrane Central Register of Controlled Trials (CENTRAL) were searched between March 1983 and March 2015. Eligible studies evaluated the outcomes of EGDT versus usual care or standard therapy in patients with severe sepsis or septic shock. The primary outcomes were mortality within 28 days, 60 days and 90 days. Included studies must report at least one metric of mortality. Results 5 studies that enrolled 4303 patients with 2144 in the EGDT group and 2159 in the control group were included in this meta-analysis. Overall, there were slight decreases of mortality within 28 days, 60 days and 90 days in the random-effect model in patients with severe sepsis or septic shock receiving EGDT resuscitation. However, none of the differences reached statistical significance (RR=0.86; 95% CI 0.69 to 1.06; p=0.16; p for heterogeneity=0.008, I2=71%; RR=0.94; 95% CI 0.81 to 1.10; p=0.46; p for heterogeneity=0.16, I2=43%; RR=0.98; 95% CI 0.88 to 1.10; p=0.75; p for heterogeneity=0.87, I2=0%, respectively). Conclusions The current meta-analysis pooled data from five RCTs and found no survival benefit of EGDT in patients with sepsis. However, the included trials are not sufficiently homogeneous and potential confounding factors in the negative trials (ProCESS, ARISE and ProMISe) might bias the results and diminish the treatment effect of EGDT. Further well-designed studies should eliminate all potential source of bias to determine if EGDT has a mortality benefit. PMID:26932135

Positive fluid balance as a major predictor of clinical outcome of patients with sepsis/septic shock after ICU discharge.

PubMed

Brotfain, Evgeni; Koyfman, Leonid; Toledano, Ronen; Borer, Abraham; Fucs, Lior; Galante, Ori; Frenkel, Amit; Kutz, Ruslan; Klein, Moti

2016-11-01

Sepsis and septic shock continue to be syndromes that carry a high mortality rate worldwide. Early aggressive fluid and vasopressor support have resulted in significant improvement in patient outcomes. The prognostic clinical significance of a positive fluid balance in septic intensive care unit (ICU) patients remains undetermined. We collected data from 297 septic patients hospitalized in our general and medical ICUs at Soroka Medical Center between January 2005 and June 2011 and divided the 4 study groups into the following 4 fluid balances: group 1, patients with fluid balance at discharge from ICU (FBD) less than 10 L; group 2, patients with an FBD of 10 to 20 L; group 3, patients with an FBD of 20 to 30 L; and group 4, patients with FBD in excess of 30 L. The ICU and in-hospital mortality rate was also significantly higher in groups 2 to 4 as compared with group 1 (P < .001 for both ICU and in-hospital mortality). The positive cumulative FBD was found to be an independent predictor of ICU mortality (odds ratio [OR], 1.04; 95% confidence interval [CI], 1.02-1.06; P < .001; Table 3) and in-hospital mortality (OR, 1.06; 95% CI, 1.03-1.08; P < .001; Table 5) and also to constitute a risk factor for new organ system dysfunction at hospital discharge (OR, 1.01; 95% CI, 1.01-1.013; P < .001; Table 6) in critically ill patients with severe sepsis/septic shock. Although it is a monocentric retrospective study, we suggest that positive cumulative fluid balance is one of the major factors that can predict the clinical outcome of critically ill patients during their ICU stay and after their discharge from the ICU. Copyright © 2016 Elsevier Inc. All rights reserved.

Co-infection of Influenza B and Streptococci causing severe pneumonia and septic shock in healthy women

PubMed Central

2010-01-01

Background Since the Influenza A pandemic in 1819, the association between the influenza virus and Streptococcus pneumoniae has been well described in literature. While a leading role has been so far attributed solely to Influenza A as the primary infective pathogen, Influenza B is generally considered to be less pathogenic with little impact on morbidity and mortality of otherwise healthy adults. This report documents the severe synergistic pathogenesis of Influenza B infection and bacterial pneumonia in previously healthy persons not belonging to a special risk population and outlines therapeutic options in this clinical setting. Case Presentation During the seasonal influenza epidemic 2007/2008, three previously healthy women presented to our hospital with influenza-like symptoms and rapid clinical deterioration. Subsequent septic shock due to severe bilateral pneumonia necessitated intensive resuscitative measures including the use of an interventional lung assist device. Microbiological analysis identified severe dual infections of Influenza B with Streptococcus pyogenes in two cases and Streptococcus pneumoniae in one case. The patients presented with no evidence of underlying disease or other known risk factors for dual infection such as age (< one year, > 65 years), pregnancy or comorbidity. Conclusions Influenza B infection can pose a risk for severe secondary infection in previously healthy persons. As patients admitted to hospital due to severe pneumonia are rarely tested for Influenza B, the incidence of admission due to this virus might be greatly underestimated, therefore, a more aggressive search for influenza virus and empirical treatment might be warranted. While the use of an interventional lung assist device offers a potential treatment strategy for refractory respiratory acidosis in addition to protective lung ventilation, the combined empiric use of a neuraminidase-inhibitor and antibiotics in septic patients with pulmonary manifestations during an epidemic season should be considered. PMID:20979628

Septic/unsafe abortion: a preventable tragedy.

PubMed

Sultana, Ruqqia; Noor, Shehla; Fawwad, Ali; Abbasi, Nasreen; Bashir, Rubina

2012-01-01

Unsafe abortion is one of the greatest neglected problems of health care in developing countries like Pakistan. In countries where abortions are restricted women have to resort to clandestine interventions to have an unwanted pregnancy terminated. The study was conducted to find out the prevalence of septic induced abortion and the associated morbidity and mortality and to highlight the measures to reduce it. This cross-sectional descriptive study was carried out in Obs/Gyn B Unit, Ayub Teaching Hospital, Abbottabad from January 2007 to December 2011. During this period all the patients presenting with pyrexia lower abdominal pain, vaginal bleeding, acute abdomen, septic or hypovolaemic shock after undergoing some sort of intervention for abortion outside the hospital were included. After thorough history, examination and detailed investigations including high vaginal and endocervical swabs for culture and sensitivity and pelvic ultrasound supportive management was given followed by antibiotics, surgical evacuation of uterus/ major laparotomy in collaboration with surgeon as required. Patients with DIC or multiple system involvement were managed in High Dependency Unit (HDU) by multidisciplinary team. During the study period out of a total 6,906 admissions 968 presented with spontaneous abortion. There were 110 cases (11.36%) of unsafe abortion, 56.4% presented with vaginal discharge, 34.5% with vaginal bleeding, 21.8% with acute abdomen, while 18.9% in shock and 6.8% with DIC. Forty-nine percent patients used termination as a method of contraception. Mortality rate was 16.36%, leading cause being septicaemia. Death and severe morbidity from unsafe abortions and its complications is avoidable through health education, effective contraception, early informed recognition and management of the problem once it occurs.

The effect of ex vivo CDDO-Me activation on nuclear factor erythroid 2-related factor 2 pathway in white blood cells from patients with septic shock.

PubMed

Noel, Sanjeev; Zheng, Laura; Navas-Acien, Ana; Fuchs, Ralph J

2014-11-01

Nuclear factor erythroid 2-related factor 2 (NRF2) has been shown to protect against experimental sepsis in mice and lipopolysaccharide (LPS)-induced inflammation in ex vivo white blood cells from healthy subjects by upregulating cellular antioxidant genes. The objective of this study was to test the hypothesis that ex vivo methyl 2-cyano-3,12-dioxoolean-1,9-dien-28-oate (CDDO-Me) activates NRF2-regulated antioxidant genes in white blood cells from patients with septic shock and protects against LPS-induced inflammation and reactive oxidative species production. Peripheral blood was collected from 18 patients with septic shock who were being treated in medical and surgical intensive care units. Real-time polymerase chain reaction was used to quantify the expression of NRF2 target genes (NQO1, HO-1, GCLM, and FTL) and IL-6 in peripheral blood mononuclear cells (PBMCs), monocytes, and neutrophils after CDDO-Me treatment alone or after subsequent LPS exposure. Superoxide anion (O2) was measured to assess the effect of CDDO-Me pretreatment on subsequent LPS exposure. Treatment with CDDO-Me increased the gene expression of NQO1 (P = 0.04) and decreased the expression of HO-1 (P = 0.03) in PBMCs from patients with septic shock. Purified monocytes exhibited significant increases in the expression of NQO1 (P = 0.01) and GCLM (P = 0.003) after CDDO-Me treatment. Levels of other NRF2 target genes (HO-1 and FTL) remained similar to those of vehicle-treated cells. Peripheral blood mononuclear cells showed a trend toward increased IL-6 gene expression after CDDO-Me treatment, whereas purified monocytes showed a trend toward decreased IL-6. There was no discernible trend in the IL-6 expression subsequent to LPS treatment in either vehicle-treated or CDDO-Me-treated PBMCs and monocytes. Treatment with CDDO-Me significantly increased O2 production in PBMCs (P = 0.04). Although CDDO-Me pretreatment significantly attenuated O2 production to subsequent LPS exposure (P = 0.03), the change was comparable to that observed in vehicle-treated PBMCs. Pretreatment with CDDO-Me followed by LPS exposure had no significant effect on O2 levels in purified monocytes. These data suggest that the NRF2 pathway is differentially responsive to CDDO-Me activation in peripheral blood cells from patients with septic shock and results in increased O2 production. The data may also suggest a suppressed NRF2 pathway in white blood cells from critically ill patients.

[The clinical significance of microcirculation and oxygen metabolism evaluation in acute kidney injury assessment in patients with septic shock after resuscitation].

PubMed

Yu, C; Liu, D W; Wang, X T; He, H W; Pan, P; Xing, Z Q

2018-02-01

Objective: To evaluate the value of microcirculation and oxygen metabolism evaluation (MicrOME) in acute kidney injury(AKI) evaluation in patients with septic shock after resuscitation. Methods: Consecutive patients with septic shock after resuscitation and mechanical ventilation were enrolled from October 2016 to February 2017 in ICU at Peking Union Medical College Hospital.Patients were divided into 3 groups based on 10 min transcutaneous oxygen challenge test transcutaneous partial pressure of oxygen(PtcO(2))and venoarterial pressure of carbon dioxide difference (Pv-aCO(2)) /arteriovenous O(2) content difference (Ca-vO(2)) by blood gas analysis, i.e. group A [ΔPtcO(2)>66 mmHg(1 mmHg=0.133 kPa) and Pv-aCO(2)/Ca-vO(2)≤1.23], group B (ΔPtcO(2)≤66 mmHg), group C (ΔPtcO(2)>66 mmHg and Pv-aCO(2)/Ca-vO(2)>1.23). Heart rate,mean arterial pressure,central venous pressure,noradrenaline dose,lactate,Pv-aCO(2),Ca-vO(2), lactate clearance, central venous oxygen saturation(ScvO(2)) and liquid equilibrium were assessed after resuscitation.AKI staging based on Kidney Disease Global Improving Outcomes (KDIGO) clinical practice guideline was analyzed. The predictive value of lactate, ScvO(2), Pv-aCO(2)/Ca-vO(2) to progression of AKI after resuscitation was determined using receiver operating characteristic(ROC)curve analysis. Results: A total of 49 septic shock patients were enrolled including 30 males and 19 females with mean age of (61.10±17.10)years old.There were 19 patients in group A,21 patients in group B, and 9 patients in group C. Acute physiology and chronic health evaluation Ⅱ score was 20.92±7.19 and sequential organ failure assessment score 12.02±3.28. There were 4 patients with AKI and 1 progressed in group A, 11 patients with AKI and 2 progressed in group B, 6 patients with AKI and 4 progressed in group C. The cutoff value of Pv-aCO(2)/Ca-vO(2) was equal or more than 2.20 for predicting progression of AKI, resulting in a sensitivity of 85.7% and a specificity of 73.8%. Conclusion: MicrOME is a significant parameter to predict the progression of AKI in patients with septic shock after resuscitation. Pv-aCO(2)/Ca-vO(2) is also a good predictive factor.

Clinical Features, Short-Term Mortality, and Prognostic Risk Factors of Septic Patients Admitted to Internal Medicine Units

PubMed Central

Mazzone, Antonino; Dentali, Francesco; La Regina, Micaela; Foglia, Emanuela; Gambacorta, Maurizia; Garagiola, Elisabetta; Bonardi, Giorgio; Clerici, Pierangelo; Concia, Ercole; Colombo, Fabrizio; Campanini, Mauro

2016-01-01

Abstract Only a few studies provided data on the clinical history of sepsis within internal Medicine units. The aim of the study was to assess the short-term mortality and to evaluate the prognostic risk factors in a large cohort of septic patients treated in internal medicine units. Thirty-one internal medicine units participated to the study. Within each participating unit, all admitted patients were screened for the presence of sepsis. A total of 533 patients were included; 78 patients (14.6%, 95%CI 11.9, 18.0%) died during hospitalization; mortality rate was 5.5% (95% CI 3.1, 9.6%) in patients with nonsevere sepsis and 20.1% (95%CI 16.2, 28.8%) in patients with severe sepsis or septic shock. Severe sepsis or septic shock (OR 4.41, 95%CI 1.93, 10.05), immune system weakening (OR 2.10, 95%CI 1.12, 3.94), active solid cancer (OR 2.14, 95% CI 1.16, 3.94), and age (OR 1.03 per year, 95% CI 1.01, 1.06) were significantly associated with an increased mortality risk, whereas blood culture positive for Escherichia coli was significantly associated with a reduced mortality risk (OR 0.46, 95%CI 0.24, 0.88). In-hospital mortality of septic patients treated in internal medicine units appeared similar to the mortality rate obtained in recent studies conducted in the ICU setting. PMID:26825876

Prospective evaluation of an automated method to identify patients with severe sepsis or septic shock in the emergency department.

PubMed

Brown, Samuel M; Jones, Jason; Kuttler, Kathryn Gibb; Keddington, Roger K; Allen, Todd L; Haug, Peter

2016-08-22

Sepsis is an often-fatal syndrome resulting from severe infection. Rapid identification and treatment are critical for septic patients. We therefore developed a probabilistic model to identify septic patients in the emergency department (ED). We aimed to produce a model that identifies 80 % of sepsis patients, with no more than 15 false positive alerts per day, within one hour of ED admission, using routine clinical data. We developed the model using retrospective data for 132,748 ED encounters (549 septic), with manual chart review to confirm cases of severe sepsis or septic shock from January 2006 through December 2008. A naïve Bayes model was used to select model features, starting with clinician-proposed candidate variables, which were then used to calculate the probability of sepsis. We evaluated the accuracy of the resulting model in 93,733 ED encounters from April 2009 through June 2010. The final model included mean blood pressure, temperature, age, heart rate, and white blood cell count. The area under the receiver operating characteristic curve (AUC) for the continuous predictor model was 0.953. The binary alert achieved 76.4 % sensitivity with a false positive rate of 4.7 %. We developed and validated a probabilistic model to identify sepsis early in an ED encounter. Despite changes in process, organizational focus, and the H1N1 influenza pandemic, our model performed adequately in our validation cohort, suggesting that it will be generalizable.

Clinical Features, Short-Term Mortality, and Prognostic Risk Factors of Septic Patients Admitted to Internal Medicine Units: Results of an Italian Multicenter Prospective Study.

PubMed

Mazzone, Antonino; Dentali, Francesco; La Regina, Micaela; Foglia, Emanuela; Gambacorta, Maurizia; Garagiola, Elisabetta; Bonardi, Giorgio; Clerici, Pierangelo; Concia, Ercole; Colombo, Fabrizio; Campanini, Mauro

2016-01-01

Only a few studies provided data on the clinical history of sepsis within internal Medicine units. The aim of the study was to assess the short-term mortality and to evaluate the prognostic risk factors in a large cohort of septic patients treated in internal medicine units. Thirty-one internal medicine units participated to the study. Within each participating unit, all admitted patients were screened for the presence of sepsis. A total of 533 patients were included; 78 patients (14.6%, 95%CI 11.9, 18.0%) died during hospitalization; mortality rate was 5.5% (95% CI 3.1, 9.6%) in patients with nonsevere sepsis and 20.1% (95%CI 16.2, 28.8%) in patients with severe sepsis or septic shock. Severe sepsis or septic shock (OR 4.41, 95%CI 1.93, 10.05), immune system weakening (OR 2.10, 95%CI 1.12, 3.94), active solid cancer (OR 2.14, 95% CI 1.16, 3.94), and age (OR 1.03 per year, 95% CI 1.01, 1.06) were significantly associated with an increased mortality risk, whereas blood culture positive for Escherichia coli was significantly associated with a reduced mortality risk (OR 0.46, 95%CI 0.24, 0.88). In-hospital mortality of septic patients treated in internal medicine units appeared similar to the mortality rate obtained in recent studies conducted in the ICU setting.

The Temporal Kinetics of Circulating Angiopoietin Levels in Children with Sepsis

PubMed Central

Giuliano, John S.; Tran, Kevin; Li, Fang-yong; Northrup, Veronika; Tala, Joana A.; Bhandari, Vineet

2013-01-01

Objective Capillary integrity continues to challenge critical care physicians worldwide when treating children with sepsis. Vascular growth factors, specifically angiopoietin (angpt)-1 and angpt-2, play opposing roles in capillary stabilization in septic patients, respectively. We aim to determine whether pediatric patients with severe sepsis/shock have persistently high angpt-2/1 ratios when compared to non-septic pediatric intensive care unit (PICU) patients over a 7-day period. Design Prospective, observational study. Patients were classified within 24h of admission into: non-systemic inflammatory response syndrome (non-SIRS), SIRS/sepsis, or severe sepsis/shock. Plasma levels of angpt-1 and angpt-2 were measured via ELISA. The angpt-2/1 ratio was graphically plotted and determined whether patients fell into ‘constant’ or ‘variable’ patterns. Setting Tertiary care center PICU. Patients Critically ill pediatric patients with varying sepsis severity. Interventions None Measurements and Main Results Forty five patients were enrolled (n=9 non-SIRS, n=19 SIRS/sepsis, and n=17 severe sepsis/shock). Gender, age, weight, comorbidities and PICU length of stay were not significantly different between the groups. Admission pediatric risk stratification scores and net fluid ins/outs were significantly elevated in the severe sepsis/shock group when compared (all p<0.05). Admission angpt-2 levels and angpt-2/1 ratios were significantly different in the severe sepsis/shock group when all groups were compared (both p<0.05). Additionally, the latter were significantly elevated in the severe sepsis/shock group at multiple time points (all p≤0.05) with the peak occurring on day 2 of illness. In a separate analysis, 32% of SIRS/sepsis and 82% of severe sepsis/shock had ‘variable’ angpt-2/1 ratio patterns compared to none in the control group (p<0.001). Conclusions Pediatric patients with severe sepsis and septic shock possess significantly elevated angpt-2/1 ratios during their first 3 days of illness which peak at day 2 of illness. A subset of these patients demonstrated ‘variable’ angpt-2/1 ratio patterns. PMID:24141659

Use of cryopoor plasma for albumin replacement and continuous antimicrobial infusion for treatment of septic peritonitis in a dog.

PubMed

Ropski, Meaghan K; Guillaumin, Julien; Monnig, Andrea A; Townsend, Katy; McLoughlin, Mary A

2017-05-01

To report the successful management of a dog with septic peritonitis and septic shock secondary to enterectomy dehiscence using novel techniques for identification of intestinal dehiscence and for septic shock treatment. A 5-year-old castrated male Bernese Mountain Dog presented for lethargy 6 days following enterotomy for foreign body obstruction. Septic peritonitis was identified due to dehiscence of the enterotomy site, and resection and anastomosis were performed using a gastrointestinal anastomosis and thoracoabdominal stapling device. Postoperatively the patient experienced severe hypotension, which responded to norepinephrine constant rate infusion (CRI) after failing to improve with fluid therapy or dopamine CRI. Further treatment included antimicrobial CRI and supportive care including careful fluid therapy. Due to low effective circulating volume paired with intersititial fluid overload and large volume abdominal effusion, fluid therapy consisted of a combination of human serum albumin, canine albumin, synthetic colloids, and isotonic crystalloids. Cryopoor plasma (CPP) was used as a source of canine albumin and intravascular volume. On Day 4, food dye was given through a nasogastric tube due to suspicion of dehiscence of the anastomosis site. Dehiscence was confirmed during abdominal exploratory, and a second resection and anastomosis was performed. Abdominal partial closure with vacuum-assisted closure device was performed. Supportive care was continued with CPP CRI and imipenem CRI. Planned relaparotomy to change the vacuum-assisted closure device was performed 48 hours later, with abdominal closure 96 hours after anastomosis. The patient was discharged on Day 15. Recheck 12 months later was normal. This case includes novel techniques such food dye via nasogastric tube to identify anastomosis dehiscence, use of CPP as a source of canine albumin, and antimicrobial CRI in a dog with septic peritonitis. © Veterinary Emergency and Critical Care Society 2017.

The ability of endotoxin adsorption during a longer duration of direct hemoperfusion with a polymyxin B-immobilized fiber column in patients with septic shock.

PubMed

Shimizu, Tomoharu; Obata, Toru; Sonoda, Hiromichi; Akabori, Hiroya; Tabata, Takahisa; Eguchi, Yutaka; Endo, Yoshihiro; Tani, Tohru

2013-12-01

The patients' hemodynamic conditions of septic shock due to intra-abdominal infection were improved by the longer duration of direct hemoperfusion with a polymyxin B-immobilized fiber column (PMX), reducing plasma endotoxins measured by the novel endotoxin detection method, named endotoxin scattering photometry (ESP) method; however, turbidimetric method could not detect endotoxins. We also observed the reduction in the endotoxin after passing through column by ESP method even after the longer duration of PMX. ESP method may more sensitively detect endotoxins than the ordinary turbidimetric method. Moreover, we demonstrated the ability of endotoxin adsorption in spite of the longer duration of PMX. Copyright © 2013 Elsevier Ltd. All rights reserved.

Ebola virus: the role of macrophages and dendritic cells in the pathogenesis of Ebola hemorrhagic fever.

PubMed

Bray, Mike; Geisbert, Thomas W

2005-08-01

Ebola hemorrhagic fever is a severe viral infection characterized by fever, shock and coagulation defects. Recent studies in macaques show that major features of illness are caused by effects of viral replication on macrophages and dendritic cells. Infected macrophages produce proinflammatory cytokines, chemokines and tissue factor, attracting additional target cells and inducing vasodilatation, increased vascular permeability and disseminated intravascular coagulation. However, they cannot restrict viral replication, possibly because of suppression of interferon responses. Infected dendritic cells also secrete proinflammatory mediators, but cannot initiate antigen-specific responses. In consequence, virus disseminates to these and other cell types throughout the body, causing multifocal necrosis and a syndrome resembling septic shock. Massive "bystander" apoptosis of natural killer and T cells further impairs immunity. These findings suggest that modifying host responses would be an effective therapeutic strategy, and treatment of infected macaques with a tissue-factor inhibitor reduced both inflammation and viral replication and improved survival.

[Experience in management of trauma-related acute abdomen at the "General Ignacio Zaragoza" Regional Hospital in Mexico City].

PubMed

Senado-Lara, Isaac; Castro-Mendoza, Antonio; Palacio-Vélez, Fernando; Vargas-Avila, Arcenio Luis

2004-01-01

To know the current state of surgical management of patients with abdominal trauma. We carried out a retrospective, observational, transversal study involving patients with abdominal trauma with clinical files wtih trauma who required surgery during the period of April 1, 1998 through March 30, 2003. There were 72 cases including nine male and 33 female patients. Mechanism of lesion was divided into closed and penetrating trauma, the latter group of patients divided into individuals with blunt wounds or with gunshot wounds. Most frequent early postoperative complication was hemorrhage, while most frequent late postoperative complication was acute renal failure. Causes of death were hypovolemic shock in four patients followed by two cases each with the following pathologies: acute respiratory insufficiency syndrome; myocardial infarct, and septic shock. Abdominal trauma is a frequent pathology in our environment, males the most affected patients, with penetrating trauma main lesion cause. Prolonged surgical time required hemotransfusions, and infectious processes together with processes related with tissular hypoxia are the most common cause of complications and death.

Survival After Shock Requiring High-Dose Vasopressor Therapy

PubMed Central

Lanspa, Michael J.; Jones, Jason P.; Kuttler, Kathryn G.; Li, Yao; Carlson, Rick; Miller, Russell R.; Hirshberg, Eliotte L.; Grissom, Colin K.; Morris, Alan H.

2013-01-01

Background: Some patients with hypotensive shock do not respond to usual doses of vasopressor therapy. Very little is known about outcomes after high-dose vasopressor therapy (HDV). We sought to characterize survival among patients with shock requiring HDV. We also evaluated the possible utility of stress-dose corticosteroid therapy in these patients. Methods: We conducted a retrospective study of patients with shock requiring HDV in the ICUs of five hospitals from 2005 through 2010. We defined HDV as receipt at any point of ≥ 1 μg/kg/min of norepinephrine equivalent (calculated by summing norepinephrine-equivalent infusion rates of all vasopressors). We report survival 90 days after hospital admission. We evaluated receipt of stress-dose corticosteroids, cause of shock, receipt of CPR, and withdrawal or withholding of life support therapy. Results: We identified 443 patients meeting inclusion criteria. Seventy-six (17%) survived. Survival was similar (20%) among the 241 patients with septic shock. Among the 367 nonsurvivors, 254 (69%) experienced withholding/withdrawal of care, and 115 (31%) underwent CPR. Stress-dose corticosteroid therapy was associated with increased survival (P = .01). Conclusions: One in six patients with shock survived to 90 days after HDV. The majority of nonsurvivors died after withdrawal or withholding of life support therapy. A minority of patients underwent CPR. Additionally, stress-dose corticosteroid therapy appears reasonable in patients with shock requiring HDV. PMID:22911566

[The influence of lactate Ringer solution versus hydroxyethyl starch on coagulation and fibrinolytic system in patients with septic shock].

PubMed

Lv, Jie; Zhao, Hui-ying; Liu, Fang; An, You-zhong

2012-01-01

To investigate the influence of lactate Ringer solution (RL) versus hydroxyethyl starch 130/0.4 (HES130/0.4) solution on coagulation and fibrinolytic system in the patients with septic shock. Forty-two consecutive patients with septic shock diagnosed between September 2009 and June 2011 were randomized to two study groups: RL resuscitation group (RL group) with 20 patients, and HES130/0.4 resuscitation group (HES group) with 22 patients. In all of them peripheral blood was collected at four points of time: before resuscitation, 6, 12, 24 hours after resuscitation, and then prothrombin time (PT), activated partial thromboplastin time (APTT) and levels of plasma tissue plasminogen activator (t-PA), and plasminogen activator inhibitor (PAI) were determined. Meanwhile, the patients' outcome and the length of intensive care unit stay (ICU-LOS) were recorded. ICU-LOS (days) in HES group was significantly shorter than the RL group (12.5 ± 8.8 vs. 17.1 ± 16.6, P < 0.01). Meanwhile, the volume of fluid (L: 2.77 ± 0.59) as well as vasoactive drugs [μg×kg(-1)×min(-1): 0.56 ± 0.15] used in the HES group were significantly lower than RL group (3.46 ± 0.73, 0.81 ± 0.41, both P < 0.01). In RL group, 12 patients died and 8 patients survived, while in HES group, 7 patients died and 15 patients survived, showing no difference between two groups. PT, APTT and the levels of t-PA showed no significant differences between two groups at different time points, but the levels of plasma PAI (μg/L) of the HES group decreased gradually, and was significantly lower than that before resuscitation and RL group at 24 hours after resuscitation (41.76 ± 25.95 vs. 89.11 ± 14.27, 55.08 ± 35.43, both P < 0.05). Both RL and HES130/0.4 fluid resuscitation did not affect the outcome of the patients with septic shock, but the resuscitation efficiency of HES130/0.4 is much better than RL. Both type of fluids did not show the effect on coagulability of the septic patients, but colloid fluid resuscitation may protect the vascular endothelial cell, reduce the inhibition of fibrinolytic system, and alleviate hypercoagulability state of patients in early stage.

Structural diversity of Burkholderia pseudomallei lipopolysaccharides affects innate immune signaling

PubMed Central

Norris, Michael H.; Schweizer, Herbert P.

2017-01-01

Burkholderia pseudomallei (Bp) causes the disease melioidosis. The main cause of mortality in this disease is septic shock triggered by the host responding to lipopolysaccharide (LPS) components of the Gram-negative outer membrane. Bp LPS is thought to be a weak inducer of the host immune system. LPS from several strains of Bp were purified and their ability to induce the inflammatory mediators TNF-α and iNOS in murine macrophages at low concentrations was investigated. Innate and adaptive immunity qPCR arrays were used to profile expression patterns of 84 gene targets in response to the different LPS types. Additional qPCR validation confirmed large differences in macrophage response. LPS from a high-virulence serotype B strain 576a and a virulent rough central nervous system tropic strain MSHR435 greatly induced the innate immune response indicating that the immunopathogenesis of these strains is different than in infections with strains similar to the prototype strain 1026b. The accumulation of autophagic vesicles was also increased in macrophages challenged with highly immunogenic Bp LPS. Gene induction and concomitant cytokine secretion profiles of human PBMCs in response to the various LPS were also investigated. MALDI-TOF/TOF was used to probe the lipid A portions of the LPS, indicating substantial structural differences that likely play a role in host response to LPS. These findings add to the evolving knowledge of host-response to bacterial LPS, which can be used to better understand septic shock in melioidosis patients and in the rational design of vaccines. PMID:28453531

[Infected subdural hematoma having a surgery of chronic subdural hematoma 1 year ago:a case report].

PubMed

Nagao, Takaaki; Miyazaki, Chikao; Ando, Shunpei; Haga, Daisuke; Kuroki, Takao; Sugo, Nobuo; Nagao, Takeki

2015-02-01

We report a case of an infected subdural hematoma that occurred 1 year after burr-hole irrigation for chronic subdural hematoma. A 78-year-old woman who had developed left hemiparesis was admitted to our hospital. A computed tomography(CT)scan revealed the presence of a chronic subdural hematoma in the right hemisphere. Her clinical symptoms improved immediately after emergency burr-hole irrigation, which allowed her discharge from the hospital. One year after the initial surgery, she developed an infection of the urinary tract infection, which led to severe pyelonephritis and septic shock. Treatment of the urological symptoms eliminated the systemic inflammation. One month after the urinary infection, the patient was readmitted to the hospital in a comatose state. A CT scan showed regrowth of a residual subdural hematoma surrounded by a thick capsule, causing a midline shift in the brain. An emergency operation for removal of the subdural hematoma by burr-hole irrigation was performed, and pus was drained from the subdural mass. Microbiological cultures of the abscess revealed the presence of Proteus mirabilis. After surgery, the patient was administered an antibiotic treatment for three weeks and she was discharged with no neurological deficits. Cultures of blood from the septic shock as well as from the abscess both revealed the presence of Proteus mirabilis. Therefore, a diagnosis of infected subdural hematoma, which was caused by hematogenous infection, was made. We conclude that attention should be paid to the risk of infection of the hematoma capsule in subdural hematomas.

Endotoxins and other sepsis triggers.

PubMed

Opal, Steven M

2010-01-01

Endotoxin, or more accurately termed bacterial lipopolysaccharide (LPS), is recognized as the most potent microbial mediator implicated in the pathogenesis of sepsis and septic shock. Yet despite its discovery well over a century ago, the fundamental role of circulating endotoxin in the blood of most patients with septic shock remains enigmatic and a subject of considerable controversy. LPS is the most prominent 'alarm molecule' sensed by the host's early warning system of innate immunity presaging the threat of invasion of the internal milieu by Gram-negative bacterial pathogens. In small doses within a localized tissue space, LPS signaling is advantageous to the host in orchestrating an appropriate antimicrobial defense and bacterial clearance mechanisms. Conversely, the sudden release of large quantities of LPS into the bloodstream is clearly deleterious to the host, initiating the release of a dysregulated and potentially lethal array of inflammatory mediators and procoagulant factors in the systemic circulation. The massive host response to this single bacterial pattern recognition molecule is sufficient to generate diffuse endothelial injury, tissue hypoperfusion, disseminated intravascular coagulation and refractory shock. Numerous attempts to block endotoxin activity in clinical trials with septic patients have met with inconsistent and largely negative results. Yet the groundbreaking discoveries within the past decade into the precise molecular basis for LPS-mediated cellular activation and tissue injury has rekindled optimism that a new generation of therapies that specifically disrupt LPS signaling might succeed. Other microbial mediators found in Gram-positive bacterial and viral and fungal pathogens are now appreciated to activate many of the same host defense networks induced by LPS. This information is providing novel interventions in the continuing effots to improve the care of septic patients. Copyright 2010 S. Karger AG, Basel.

Shock-induced neutrophil mediated priming for acute lung injury in mice: divergent effects of TLR-4 and TLR-4/FasL deficiency.

PubMed

Ayala, Alfred; Chung, Chun-Shiang; Lomas, Joanne L; Song, Grace Y; Doughty, Lesley A; Gregory, Stephen H; Cioffi, William G; LeBlanc, Brian W; Reichner, Jonathan; Simms, H Hank; Grutkoski, Patricia S

2002-12-01

Acute lung injury (ALI) leading to respiratory distress is a common sequela of shock/trauma, however, modeling this process in mice with a single shock or septic event is inconsistent. One explanation is that hemorrhage is often just a "priming insult," thus, secondary stimuli may be required to "trigger" ALI. To test this we carried out studies in which we assessed the capacity of hemorrhage alone or hemorrhage followed by septic challenge (CLP) to induce ALI. Lung edema, bronchoalveolar lavage interleukin (IL)-6, alveolar congestion, as well as lung IL-6, macrophage inflammatory protein (MIP)-2, and myeloperoxidase (MPO) activity were all increased in mice subjected to CLP at 24 but not 72 hours following hemorrhage. This was associated with a marked increase in the susceptibility of these mice to septic mortality. Peripheral blood neutrophils derived from 24 hours post-hemorrhage, but not Sham animals, exhibited an ex vivo decrease in apoptotic frequency and an increase in respiratory burst capacity, consistent with in vivo "priming." Subsequently, we observed that adoptive transfer of neutrophils from hemorrhaged but not sham-hemorrhage animals to neutropenic recipients reproduce ALI when subsequently septically challenged, implying that this priming was mediated by neutrophils. We also found marked general increases in lung IL-6, MIP-2, and MPO in mice deficient for toll-like receptor (TLR-4) or the combined lack of TLR-4/FasL. However, the TLR-4 defect markedly attenuated neutrophil influx into the lung while not altering the change in local cytokine/chemokine expression. Alternatively, the combined loss of FasL and TLR-4 did not inhibit the increase in MPO and exacerbated lung IL-6/MIP-2 levels even further.

The epidemiology of adults with severe sepsis and septic shock in Scottish emergency departments.

PubMed

Gray, Alasdair; Ward, Kirsty; Lees, Fiona; Dewar, Colin; Dickie, Sarah; McGuffie, Crawford

2013-05-01

The Surviving Sepsis Campaign (SSC) promotes a bundle approach to the care of septic patients to improve outcome. Some have questioned the capability of delivering the bundle in emergency departments (EDs). The authors report the epidemiology and 6 h bundle compliance of patients with severe sepsis/septic shock presenting to Scottish EDs. Analysis of the previously reported Scottish Trauma Audit Group sepsis database was performed including 20 mainland Scottish EDs. A total of 308,910 attendances were screened (between 2 March and 31 May 2009), and 5285 of 27,046 patients were identified after case note review and included on the database. This analysis includes patients who had severe sepsis/septic shock before leaving the ED. Epidemiological, severity of illness criteria, and ED management data were analysed. 626 patients (median age 73; M/F ratio 1:1; 637 presentations) met entrance criteria. The median number of cases per site was 16 (range 3-103). 561 (88.1%) patients arrived by ambulance. The most common source of infection was the respiratory tract (n=411, 64.5%) The most common physiological derangements were heart rate (n=523, 82.1%), respiratory rate (n=452, 71%) and white cell count (n=432, 67.8%). The median hospital stay was 9 days (IQR 4-17 days). 201 (31.6%) patients were admitted to critical care within 2 days, 130 (20.4%) directly from the ED. 180 patients (28.3%) died. There was poor compliance with all aspect of the SSC resuscitation bundle. Sepsis presentations are of variable frequency but have typical epidemiology and clinical outcomes. SSC bundle resuscitation uptake is poor in Scottish EDs.

Persisting high levels of plasma pentraxin 3 over the first days after severe sepsis and septic shock onset are associated with mortality.

PubMed

Mauri, Tommaso; Bellani, Giacomo; Patroniti, Nicolo'; Coppadoro, Andrea; Peri, Giuseppe; Cuccovillo, Ivan; Cugno, Massimo; Iapichino, Gaetano; Gattinoni, Luciano; Pesenti, Antonio; Mantovani, Alberto

2010-04-01

Pentraxin 3 (PTX3) is an inflammatory mediator produced by neutrophils, macrophages, myeloid dendritic and endothelial cells. During sepsis a massive inflammatory activation and coagulation/fibrinolysis dysfunction occur. PTX3, as a mediator of inflammation, may represent an early marker of severity and outcome in sepsis. This study is based on a prospective trial regarding the impact of glycemic control on coagulation in sepsis. Ninety patients admitted to three general intensive care units were enrolled when severe sepsis or septic shock was diagnosed. At enrollment, we recorded sepsis signs, disease severity, coagulation activation [prothrombin fragments 1 + 2 (F(1+2))] and fibrinolysis inhibition [plasminogen activator inhibitor-1 (PAI-1)]. We measured plasma PTX3 levels at enrollment, everyday until day 7, then at days 9, 11, 13, 18, 23 and 28. Mortality was recorded at day 90. Although not different on day 1, PTX3 remained significantly higher in non-survivors than in survivors over the first 5 days (p = 0.002 by general linear model). On day 1, PTX3 levels were higher in septic shock than in severely septic patients (p = 0.029). Day 1 PTX3 was significantly correlated with platelet count (p < 0.001), SAPS II score (p = 0.006) and SOFA score (p < 0.001). Day 1 PTX3 was correlated with F(1+2) concentration and with PAI-1 activity and concentration (p < 0.05 for all). Persisting high levels of circulating PTX3 over the first days from sepsis onset may be associated with mortality. PTX3 correlates with severity of sepsis and with sepsis-associated coagulation/fibrinolysis dysfunction.

Correlation of left ventricular systolic dysfunction determined by low ejection fraction and 30-day mortality in patients with severe sepsis and septic shock: a systematic review and meta-analysis.

PubMed

Sevilla Berrios, Ronaldo A; O'Horo, John C; Velagapudi, Venu; Pulido, Juan N

2014-08-01

The prognostic implications of myocardial dysfunction in patients with sepsis and its association with mortality are controversial. Several tools have been proposed to evaluate cardiac function in these patients, but their usefulness beyond guiding therapy is unclear. We review the value of echocardiographic estimate of left ventricular ejection fraction (LVEF) in the setting of severe sepsis and/or septic shock and its correlation with 30-day mortality. We conducted a systematic review and meta-analysis to evaluate the prognostic functionality of newly diagnosed LV systolic dysfunction by transthoracic echocardiography on critical ill patients admitted to the intensive care unit with severe sepsis or septic shock. A search of EMBASE and PubMed, Ovide MEDLINE, and Cochrane CENTRAL medical databases yielded 7 studies meeting inclusion criteria reporting on a total of 585 patients. The pooled sensitivity of depressed LVEF for mortality was 52% (95% confidence interval [CI], 29%-73%), and pooled specificity was 63% (95% CI, 53%-71%). Summary receiver operating characteristic curve showed an area under the curve of 0.62 (95% CI, 0.58-0.67). The overall mortality diagnostic odd ratio for septic patients with LV systolic dysfunction was 1.92 (95% CI, 1.27-2.899). Statistical heterogeneity of studies was moderate. The presence of new LV systolic dysfunction associated with sepsis and defined as low LVEF is neither a sensitive nor a specific predictor of mortality. These findings are limited because of the heterogeneity and underpower of the studies. Further research into this method is warranted. Copyright © 2014 Elsevier Inc. All rights reserved.

Validation of cardiac output studies from the Mostcare compared to a pulmonary artery catheter in septic patients.

PubMed

Gopal, S; Do, T; Pooni, J S; Martinelli, G

2014-03-01

The Mostcare monitor is a non-invasive cardiac output monitor. It has been well validated in cardiac surgical patients but there is limited evidence on its use in patients with severe sepsis and septic shock. The study included the first 22 consecutive patients with severe sepsis and septic shock in whom the floatation of a pulmonary artery catheter was deemed necessary to guide clinical management. Cardiac output measurements including cardiac output, cardiac index and stroke volume were simultaneously calculated and recorded from a thermodilution pulmonary artery catheter and from the Mostcare monitor respectively. The two methods of measuring cardiac output were compared by Bland-Altman statistics and linear regression analysis. A percentage error of less than 30% was defined as acceptable for this study. Bland-Altman analysis for cardiac output showed a Bias of 0.31 L.min-1, precision (=SD) of 1.97 L.min-1 and a percentage error of 62.54%. For Cardiac Index the bias was 0.21 L.min-1.m-2, precision of 1.10 L.min-1.m-2 and a percentage error of 64%. For stroke volume the bias was 5 mL, precision of 24.46 mL and percentage error of 70.21%. Linear regression produced a correlation coefficient r2 for cardiac output, cardiac index, and stroke volume, of 0.403, 0.306, and 0.3 respectively. Compared to thermodilution cardiac output, cardiac output studies obtained from the Mostcare monitor have an unacceptably high error rate. The Mostcare monitor demonstrated to be an unreliable monitoring device to measure cardiac output in patients with severe sepsis and septic shock on an intensive care unit.

Fatal streptococcal toxic shock syndrome from an intrauterine device.

PubMed

Cho, Elizabeth E; Fernando, Dinali

2013-04-01

The occurrence of toxic shock syndrome from an intrauterine device (IUD) is very rare. To raise awareness of the risk of toxic shock syndrome caused by an IUD, to educate others about when to suspect this complication, and to provide treatment recommendations. A 49-year-old woman presented to the Emergency Department in septic shock after complaining of 5 days of nausea, vomiting, and diarrhea. Physical examination findings included a diffusely tender and rigid abdomen with free fluid on bedside sonogram. She was found, on computed tomography of her abdomen and pelvis, to have an IUD with moderate ascites. The IUD was removed, and both her IUD and her blood cultures grew out group A Streptococcus. Despite aggressive medical management, which included multiple vasopressors and broad-spectrum antibiotics, she died from group A streptococcal sepsis, with the IUD as her most likely source. Her clinical presentation and laboratory findings meet the Centers for Disease Control and Prevention diagnostic criteria for streptococcal toxic shock syndrome. Her diagnosis was confirmed by autopsy. IUDs should be considered as a possible source of infection in patients with an IUD who present with symptoms consistent with toxic shock syndrome. These patients need to be aggressively managed with early surgical intervention. Copyright © 2013. Published by Elsevier Inc.

Intraosseous and intravenous administration of antibiotics yields comparable plasma concentrations during experimental septic shock

PubMed Central

Strandberg, G; Larsson, A; Lipcsey, M; Michalek, J; Eriksson, M

2015-01-01

Background We aimed to investigate whether comparable antibiotic concentrations could be reached with intraosseous and intravenous administration during septic shock. Methods In this randomized, prospective experimental study conducted at an animal research laboratory at the University Hospital of Uppsala, eight anesthetized pigs, weighing 21.2 to 29.1 kg (mean: 25.2 ± 2.3 kg), received endotoxin infusion at 4 μg/kg/h for 6 h. At the onset of clinical shock, alternatively after 3 h of endotoxemia, they received 75 mg/kg of cefotaxime and 7 mg/kg of gentamicin either in a proximal tibial intraosseous catheter or in a peripheral intravenous catheter. Mixed venous samples were taken after 5, 15, 30, 60, 120 and 180 min and analyzed for antibiotic concentrations. Results For both antibiotics, plasma concentrations after intraosseous and intravenous administration followed similar curves throughout the observation period, and peak concentrations were comparable. Mean concentration area under the curve (AUC mg × h/l) for cefotaxime was 108.1 ± 19.5 after intraosseous and 116.5 ± 11.1 after intravenous administration; ratio 0.93, (95% CI 0.71–1.19). Mean AUC for gentamicin was 28.1 ± 6.8 for intraosseous and 32.2 ± 3.5 for intravenous administration; ratio 0.87 (95% CI 0.62–1.19). Conclusions In this porcine septic shock model, intraosseous and intravenous administration of gentamicin and cefotaxime yielded comparable concentrations. In an emergency, intraosseous administration of these antibiotics may be considered in severe infections when venous access is difficult. PMID:25557933

Sepsis

MedlinePlus

... pressure drops and the heart weakens, leading to septic shock. Anyone can get sepsis, but the risk is higher in People with weakened immune systems Infants and children The elderly People with chronic ...

Protection by mTOR Inhibition on Zymosan-Induced Systemic Inflammatory Response and Oxidative/Nitrosative Stress: Contribution of mTOR/MEK1/ERK1/2/IKKβ/IκB-α/NF-κB Signalling Pathway.

PubMed

Sahan-Firat, Seyhan; Temiz-Resitoglu, Meryem; Guden, Demet Sinem; Kucukkavruk, Sefika Pinar; Tunctan, Bahar; Sari, Ayse Nihal; Kocak, Zumrut; Malik, Kafait U

2018-02-01

Mammalian target of rapamycin (mTOR), a serine/threonine kinase regulate variety of cellular functions including cell growth, differentiation, cell survival, metabolism, and stress response, is now appreciated to be a central regulator of immune responses. Because mTOR inhibitors enhanced the anti-inflammatory activities of regulatory T cells and decreased the production of proinflammatory cytokines by macrophages, mTOR has been a pharmacological target for inflammatory diseases. In this study, we examined the role of mTOR in the production of proinflammatory and vasodilator mediators in zymosan-induced non-septic shock model in rats. To elucidate the mechanism by which mTOR contributes to non-septic shock, we have examined the activity of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase system caused by mTOR/mitogen-activated protein kinase kinase (MEK1)/extracellular signal-regulated kinase (ERK1/2)/inhibitor κB kinase (IKKβ)/inhibitor of κB (IκB-α)/nuclear factor-κB (NF-κB) signalling pathway activation. After 1 h of zymosan (500 mg/kg, i.p.) administration to rats, mean arterial blood pressure (MAP) was decreased and heart rate (HR) was increased. These changes were associated with increased expression and/or activities of ribosomal protein S6, MEK1, ERK1/2, IKKβ, IκB-α and NF-κB p65, and NADPH oxidase system activity in cardiovascular and renal tissues. Rapamycin (1 mg/kg, i.p.), a selective mTOR inhibitor, reversed these zymosan-induced changes in these tissues. These observations suggest that activation of mTOR/MEK1/ERK1/2/IKKβ/IκB-α/NF-κB signalling pathway with proinflammatory and vasodilator mediator formation and NADPH oxidase system activity contributes to systemic inflammation in zymosan-induced non-septic shock. Thus, mTOR may be an optimal target for the treatment of the diseases characterized by the severe systemic inflammatory response.

The Theory is Out There: The Use of ALPHA-2 Agonists in Treatment of Septic Shock.

PubMed

Ferreira, Jason

2018-04-01

The sympathetic nervous system plays an important role in the initial response to sepsis. This response enables the host to respond to invading pathogens; however, prolonged activation can become pathological. The potential for unregulated sympathetic tone to become detrimental in the septic patient has fueled interest in the role and impact of sympathetic manipulation, including the selective inhibition of sympathetic tone to return and augment vascular reactivity. While conventional understanding of alpha 2 agonists activity is depletion of sympathetic outflow, novel evidence suggests mitigation rather than depletion. The mechanism by which these agents exert these properties remains controversial and appears to be condition-specific. The hypothesis by which alpha agonists affect the pathology of sepsis is multifactorial, but includes influence on inflammatory regulation, coagulopathy, dynamic flow, as well as vascular responsiveness and integrity. Theory and basic science evidence supports the use of α agonists in the septic population. The clinical evidence shedding light on this topic is limited and confounded by intention or trial design. Future evidence should focus on adjuvant therapy in patients progressing to or at high risk of shock development.

Principles of fluid management and stewardship in septic shock: it is time to consider the four D's and the four phases of fluid therapy.

PubMed

Malbrain, Manu L N G; Van Regenmortel, Niels; Saugel, Bernd; De Tavernier, Brecht; Van Gaal, Pieter-Jan; Joannes-Boyau, Olivier; Teboul, Jean-Louis; Rice, Todd W; Mythen, Monty; Monnet, Xavier

2018-05-22

In patients with septic shock, the administration of fluids during initial hemodynamic resuscitation remains a major therapeutic challenge. We are faced with many open questions regarding the type, dose and timing of intravenous fluid administration. There are only four major indications for intravenous fluid administration: aside from resuscitation, intravenous fluids have many other uses including maintenance and replacement of total body water and electrolytes, as carriers for medications and for parenteral nutrition. In this paradigm-shifting review, we discuss different fluid management strategies including early adequate goal-directed fluid management, late conservative fluid management and late goal-directed fluid removal. In addition, we expand on the concept of the "four D's" of fluid therapy, namely drug, dosing, duration and de-escalation. During the treatment of patients with septic shock, four phases of fluid therapy should be considered in order to provide answers to four basic questions. These four phases are the resuscitation phase, the optimization phase, the stabilization phase and the evacuation phase. The four questions are "When to start intravenous fluids?", "When to stop intravenous fluids?", "When to start de-resuscitation or active fluid removal?" and finally "When to stop de-resuscitation?" In analogy to the way we handle antibiotics in critically ill patients, it is time for fluid stewardship.

Ventilator Dependence Risk Score for the Prediction of Prolonged Mechanical Ventilation in Patients Who Survive Sepsis/Septic Shock with Respiratory Failure.

PubMed

Chang, Ya-Chun; Huang, Kuo-Tung; Chen, Yu-Mu; Wang, Chin-Chou; Wang, Yi-Hsi; Tseng, Chia-Cheng; Lin, Meng-Chih; Fang, Wen-Feng

2018-04-04

We intended to develop a scoring system to predict mechanical ventilator dependence in patients who survive sepsis/septic shock with respiratory failure. This study evaluated 251 adult patients in medical intensive care units (ICUs) between August 2013 to October 2015, who had survived for over 21 days and received aggressive treatment. The risk factors for ventilator dependence were determined. We then constructed a ventilator dependence (VD) risk score using the identified risk factors. The ventilator dependence risk score was calculated as the sum of the following four variables after being adjusted by proportion to the beta coefficient. We assigned a history of previous stroke, a score of one point, platelet count less than 150,000/μL a score of one point, pH value less than 7.35 a score of two points, and the fraction of inspired oxygen on admission day 7 over 39% as two points. The area under the curve in the derivation group was 0.725 (p < 0.001). We then applied the VD risk score for validation on 175 patients. The area under the curve in the validation group was 0.658 (p = 0.001). VD risk score could be applied to predict prolonged mechanical ventilation in patients who survive sepsis/septic shock.

A history of adjunctive glucocorticoid treatment for pediatric sepsis: moving beyond steroid pulp fiction toward evidence-based medicine.

PubMed

Zimmerman, Jerry J

2007-11-01

To review the history of clinical use of corticosteroids with particular reference to adjunctive therapy for severe pediatric sepsis and, in this context, to provide an overview of what is known, what is not known, and what research questions are particularly relevant at this time. Literature review using PubMed, cross-referenced article citations, and the Internet. The history of corticosteroid use in clinical medicine has been colorful, noisy, and always controversial. Therapeutic corticosteroid indications that initially seemed rational have frequently been refuted on closer, rigorous clinical trial inspection. Although it may be prudent to provide stress-dose steroids to children with septic shock who are clinically at risk for adrenal insufficiency (chronic or recent steroid use, purpura fulminans, etomidate or ketoconazole administration, hypothalamic, pituitary, adrenal disease), the safety and efficacy of stress-dose steroids as general adjunctive therapy for pediatric septic shock have not been established. Glucocorticoid administration does add potential risk to critically ill children. In particular, although adjunctive corticosteroids may hasten resolution of unstable hemodynamics in septic shock, this may occur at the metabolic cost of hyperglycemia. Clinical practice that fosters innovative therapy (off-label use) over research probably represents bad medical and social policy. Accordingly, pediatric critical care researchers have a responsibility to generate pediatric-specific evidence-based medicine for adjunctive corticosteroid therapy for severe sepsis in children.

Biomarker discovery and development in pediatric critical care medicine

PubMed Central

Kaplan, Jennifer M.; Wong, Hector R.

2010-01-01

Objective To frame the general process of biomarker discovery and development, and to describe a proposal for the development of a multi-biomarker based risk model for pediatric septic shock. Data Source Narrative literature review and author generated data. Main Results Biomarkers can be grouped into four broad classes, based on the intended function: diagnostic, monitoring, surrogate, and stratification. Biomarker discovery and development requires a rigorous process, which is frequently not well followed in the critical care medicine literature. Very few biomarkers have successfully transitioned from the candidate stage to the true biomarker stage. There is great interest in developing diagnostic and stratification biomarkers for sepsis. Procalcitonin is currently the most promising diagnostic biomarker for sepsis. Recent evidence suggests that interleukin-8 can be used to stratify children with septic shock having a high likelihood of survival with standard care. Currently, there is a multi-institutional effort to develop a multi-biomarker based sepsis risk model intended to predict outcome and illness severity for individual children with septic shock. Conclusions Biomarker discovery and development is an important portion of the pediatric critical care medicine translational research agenda. This effort will require collaboration across multiple institutions and investigators. Rigorous conduct of biomarker-focused research holds the promise of transforming our ability to care for individual patients and our ability to conduct clinical trials in a more effective manner. PMID:20473243

Recurrent SDSE bacteraemia resulting in streptococcal toxic shock syndrome in a patient with Noonan syndrome.

PubMed

Suzuki, Kei; Nakamura, Akiko; Ishikura, Ken; Imai, Hiroshi

2016-08-02

A 19-year-old man with chronic lymphoedema due to Noonan syndrome presented at our hospital with septic shock and pain in his lower leg. Blood cultures were positive for Streptococcus dysgalactiae subsp equisimilis (SDSE), resulting in a diagnosis of cellulitis with toxic involvement. He was treated with ampicillin for 3 weeks. Although he did well for 6 weeks, septic shock recurred. Blood culture again revealed SDSE, with the strain being identical to the first episode, suggesting that this infection had relapsed. He was treated with ampicillin for 6 weeks and prophylactically with trimethoprim-sulfamethoxazole for 12 months. Although SDSE bacteraemia occurs commonly in elderly patients, findings in this patient showed that it can also develop in younger persons with predisposing factors. This case also indicates that SDSE has the potential to recur, despite generally sufficient antibiotic administration, and that patients who experience recurrent episodes may require prolonged treatment with antibiotics, including prophylaxis. 2016 BMJ Publishing Group Ltd.

DUSP3 genetic deletion confers M2-like−macrophage-dependent tolerance to septic shock

PubMed Central

Singh, Pratibha; Dejager, Lien; Amand, Mathieu; Theatre, Emilie; Vandereyken, Maud; Zurashvilli, Tinatin; Singh, Maneesh; Mack, Matthias; Timmermans, Steven; Musumeci, Lucia; Dejardin, Emmanuel; Mustelin, Tomas; Van Ginderachter, Jo A.; Moutschen, Michel; Oury, Cécile; Libert, Claude; Rahmouni, Souad

2015-01-01

DUSP3 is a small dual-specificity protein phosphatase with an unknown physiological function. We report that DUSP3 is strongly expressed in human and mouse monocytes and macrophages and that its deficiency in mice promotes tolerance to lipopolysaccharide (LPS)-induced endotoxin shock and to polymicrobial septic shock following cecal ligation and puncture. By using adoptive transfer experiments, we demonstrate that resistance to endotoxin is macrophage-dependent and transferable and that this protection is associated with a striking increase of M2-like macrophages in DUSP3−/− mice in both the LPS and cecal ligation and puncture models. We show that the altered response of DUSP3−/− mice to sepsis is reflected in decreased TNF production and impaired ERK1/2 activation. Our results demonstrate that DUSP3 plays a key and non-redundant role as a regulator of innate immune responses by mechanisms involving the control of ERK1/2 activation, TNF secretion and macrophage polarization. PMID:25876765

The Epidemiology of Hospital Death Following Pediatric Severe Sepsis: When, Why, and How Children With Sepsis Die.

PubMed

Weiss, Scott L; Balamuth, Fran; Hensley, Josey; Fitzgerald, Julie C; Bush, Jenny; Nadkarni, Vinay M; Thomas, Neal J; Hall, Mark; Muszynski, Jennifer

2017-09-01

The epidemiology of in-hospital death after pediatric sepsis has not been well characterized. We investigated the timing, cause, mode, and attribution of death in children with severe sepsis, hypothesizing that refractory shock leading to early death is rare in the current era. Retrospective observational study. Emergency departments and ICUs at two academic children's hospitals. Seventy-nine patients less than 18 years old treated for severe sepsis/septic shock in 2012-2013 who died prior to hospital discharge. None. Time to death from sepsis recognition, cause and mode of death, and attribution of death to sepsis were determined from medical records. Organ dysfunction was assessed via daily Pediatric Logistic Organ Dysfunction-2 scores for 7 days preceding death with an increase greater than or equal to 5 defined as worsening organ dysfunction. The median time to death was 8 days (interquartile range, 1-12 d) with 25%, 35%, and 49% of cumulative deaths within 1, 3, and 7 days of sepsis recognition, respectively. The most common cause of death was refractory shock (34%), then multiple organ dysfunction syndrome after shock recovery (27%), neurologic injury (19%), single-organ respiratory failure (9%), and nonseptic comorbidity (6%). Early deaths (≤ 3 d) were mostly due to refractory shock in young, previously healthy patients while multiple organ dysfunction syndrome predominated after 3 days. Mode of death was withdrawal in 72%, unsuccessful cardiopulmonary resuscitation in 22%, and irreversible loss of neurologic function in 6%. Ninety percent of deaths were attributable to acute or chronic manifestations of sepsis. Only 23% had a rise in Pediatric Logistic Organ Dysfunction-2 that indicated worsening organ dysfunction. Refractory shock remains a common cause of death in pediatric sepsis, especially for early deaths. Later deaths were mostly attributable to multiple organ dysfunction syndrome, neurologic, and respiratory failure after life-sustaining therapies were limited. A pattern of persistent, rather than worsening, organ dysfunction preceded most deaths.

Purulent pericarditis and pneumonia caused by Streptococcus equi subsp. zooepidemicus.

PubMed

Held, Jürgen; Schmitz, Roland; van der Linden, Mark; Nührenberg, Thomas; Häcker, Georg; Neumann, Franz-Josef

2014-02-01

Purulent pericarditis is a life-threatening disease that usually manifests following bacteraemia or through spreading from an intrathoracic focus. Only a few cases of this disease have been reported with Lancefield group C streptococci as aetiological agents, and the primary focus in these infections remains unknown. We report a case of purulent pericarditis with septic and cardiogenic shock, caused by Streptococcus equi subsp. zooepidemicus (group C) in a 51-year-old patient. The pathogen was possibly contracted through contact with horses. Most probably, it caused initially pneumonia before spreading to the pericardium, either directly or via the bloodstream. A combined therapeutic approach, consisting of antibiotic therapy and repeated pericardial drainage, was necessary to ensure a clinical cure. After discharge, long-term follow-up for development of constrictive pericarditis is considered mandatory.

Fluids and sepsis: changing the paradigm of fluid therapy: a case report.

PubMed

Hariyanto, Hori; Yahya, Corry Quando; Widiastuti, Monika; Wibowo, Primartanto; Tampubolon, Oloan Eduard

2017-02-04

Over the past 16 years, sepsis management has been guided by large-volume fluid administration to achieve certain hemodynamic optimization as advocated in the Rivers protocol. However, the safety of such practice has been questioned because large-volume fluid administration is associated with fluid overload and carries the worst outcome in patients with sepsis. Researchers in multiple studies have declared that using less fluid leads to increased survival, but they did not describe how to administer fluids in a timely and appropriate manner. An 86-year-old previously healthy Sundanese man was admitted to the intensive care unit at our institution with septic shock, acute kidney injury, and respiratory distress. Standard care was implemented during his initial care in the high-care unit; nevertheless, his condition worsened, and he was transferred to the intensive care unit. We describe the timing of fluid administration and elaborate on the amount of fluids needed using a conservative fluid regimen in a continuum of resuscitated sepsis. Because fluid depletion in septic shock is caused by capillary leak and pathologic vasoplegia, continuation of fluid administration will drive intravascular fluid into the interstitial space, thereby producing marked tissue edema and disrupting vital oxygenation. Thus, fluids have the power to heal or kill. Therefore, management of patients with sepsis should entail early vasopressors with adequate fluid resuscitation followed by a conservative fluid regimen.

Early and innovative interventions for severe sepsis and septic shock: taking advantage of a window of opportunity

PubMed Central

Rivers, Emanuel P.; McIntyre, Lauralyn; Morro, David C.; Rivers, Kandis K.

2005-01-01

The pathogenic, diagnostic and therapeutic landscape of sepsis is no longer confined to the intensive care unit: many patients from other portals of entry to care, both outside and within the hospital, progress to severe disease. Approaches that have led to improved outcomes with other diseases (e.g., acute myocardial infarction, stroke and trauma) can now be similarly applied to sepsis. Improved understanding of the pathogenesis of severe sepsis and septic shock has led to the development of new therapies that place importance on early identification and aggressive management. This review emphasizes approaches to the early recognition, diagnosis and therapeutic management of sepsis, giving the clinician the most contemporary and practical approaches with which to treat these patients. PMID:16247103

Large Lipomatous Hypertrophy of the Interventricular Septum

PubMed Central

Ak, Koray; Isbir, Selim; Kepez, Alper; Turkoz, Kemal; Elci, Emre; Arsan, Sinan

2014-01-01

We present the case of a 58-year-old woman who had large lipomatous hypertrophy of the interventricular septum, a condition that is reported very infrequently. Preoperative cardiac magnetic resonance images revealed an inhomogeneous, infiltrating mass that was suppressed in fat-suppression mode. The extensive mass was causing right ventricular dysfunction, so we excised it through a right ventricular approach. The findings on histologic analysis of the mass were consistent with lipomatous hypertrophy. The patient died of septic shock on the 28th postoperative day. In addition to the patient's case, we discuss the characteristics and diagnosis of this rare entity. PMID:24808791

Neutropenic Fever.

PubMed

White, Lindsey; Ybarra, Michael

2017-12-01

Fever is a common presenting complaint among adult or pediatric patients in the emergency department setting. Although fever in healthy individuals does not necessarily indicate severe illness, fever in patients with neutropenia may herald a life-threatening infection. Therefore, prompt recognition of patients with neutropenic fever is imperative. Serious bacterial illness is a significant cause of morbidity and mortality for neutropenic patients. Neutropenic fever should trigger the initiation of a rapid work-up and the administration of empiric systemic antibiotic therapy to attenuate or avoid the progression along the spectrum of sepsis, severe sepsis, septic shock syndrome, and death. Copyright © 2017 Elsevier Inc. All rights reserved.

[Clinical study on sepsis in 2 pediatric intensive care units in Beijing].

PubMed

2012-03-01

To investigate the incidence, mortality, causes and risk factors of sepsis in children in pediatric intensive care units (PICU) in Beijing through large sample prospective clinical research. From 1st November 2008 to 31st December 2009, all patients aged from 29 days to 18 years admitted to PICU of the two children's hospitals in Beijing were surveyed. Patients who met the conditions of Chinese pediatric critical illness score (PCIS) < 90 or American guidelines for PICU admission were defined as critically ill cases. According to the definitions of sepsis of 2005 international pediatric sepsis consensus conference and 2006 Chinese Medical Association meeting, sepsis, sever sepsis, and septic shock cases were selected from these critically ill patients. The qualified subjects were surveyed by questionnaire until discharge or death the data were analyzed by SPSS. A total of 1531 of PICU admissions were enrolled within a 14-month period, of whom 1250 met the criteria of critically ill case; 486 developed sepsis, of whom 55 died. The morbidity of sepsis for all in critically ill patients in PICU was 38.9% (486/1250) and the mortality was 11.3% (55/486). The morbidity of sepsis, severe sepsis and septic shock in these PICU was 25.5% (319/1250), 10.3% (129/1250), 3.0% (38/1250) and the mortality was 2.2% (7/319), 23.3% (30/129), and 47.4% (18/38), respectively. The proportion of less than 3 years old was 75.5% (367/486). Respiratory system diseases (71.8%), such as pneumonia (63.6%), were the underlying primary infectious diseases of sepsis. Bacterial etiology accounted for 64.1% of the cases with sepsis with definite etiological test results. The proportion of gram-positive bacteria and gram-negative bacteria were 46.1% and 53.9%, respectively. PCIS and disease severity were negatively correlated (r = -0.583, P < 0.01). Multiple stepwise logistic regression analysis showed that depressed PCIS and use of mechanical ventilation were the risk factors for death. Average medical costs per patient in PICU with severe sepsis and septic shock were 2.3 times and 1.3 times higher than those of critically ill patients. Sepsis with the characteristics of high morbidity, mortality and cost was one of the critical illnesses in PICU in two pediatric hospitals in Beijing. Patients younger than 3 years were more susceptible to develop sepsis. Main infectious cause was pneumonia and bacteria was the main pathogen bacterial pneumonia. Risk factors for death were depressed PCIS and use of mechanical ventilation.

Comparison of Cross-Linked Hemoglobin Solution to Lactated Ringers and 5% Albumin in Resuscitation of a Rat Model of escherichia coli Septic Shock

DTIC Science & Technology

1993-08-01

and 0M. in BHI (0). 35 36 7 II I "I -. I 4I I .0 Z 2 L 0 1 2 3 4 5 6 7 Time (hours) Figure 10. Death Rate The Death Rates of 3 septic groups receiving...There were insufficient numbers of animals in each group to make statistical conclusions regarding death rates between groups. 37 38 7 _! 5 S o 2.0 Z 2...0 0 1 2 3 4 5 6 7 Time (hours) Figure 11. Death Rate Death rates of 3 septic groups receiving 40 cc/kg intravenous boluses of either 7

THE IMPACT OF AGE ON THE INNATE IMMUNE RESPONSE AND OUTCOMES AFTER SEVERE SEPSIS/SEPTIC SHOCK IN TRAUMA AND SURGICAL INTENSIVE CARE UNIT PATIENTS.

PubMed

Brakenridge, Scott C; Efron, Philip A; Stortz, Julie A; Ozrazgat-Baslanti, Teczan; Ghita, Gabriela; Wang, Zhongkai; Bihorac, Azra; Mohr, Alicia M; Brumback, Babette A; Moldawer, Lyle L; Moore, Frederick A

2018-04-02

Advancing age is a strong risk factor for adverse outcomes across multiple disease processes. However, septic surgical and trauma patients are unique in they incur two or more inflammatory insults. The effects of advanced age on sepsis pathophysiology and outcomes remain unclear. We performed a single center, prospective observational cohort study of Surgical ICU patients with severe sepsis/septic shock. Peripheral blood was collected for genomic, cytokine and biomarker analysis at 0.5, 1, 4, 7, 14, 21 and 28 days after sepsis onset. Based on sensitivity analysis, cohorts were defined as "young" (<55 years) and "aged" (≥55 years). We compared age-defined cohorts to determine differences in patient characteristics, biomarker profiles and clinical outcomes. The cohort included 173 patients with severe sepsis (n=93; 53.8%) or septic shock (n=80; 46.2%), with a mean age of 60.9 (±14.5) years. Intra-abdominal sepsis was the leading source (n=81; 46.8%), followed by NSTI (n=33, 19.1%) and pneumonia (n=30; 17.3%). Aged patients had a higher comorbidity burden, but were otherwise similar to the young cohort. The aged cohort had a higher severity of early physiologic derangement (median APACHE II, 23 vs 18, p=0.002), greater incidence of multiple organ failure (MOF; 64.3% vs 40.4%, p=0.006), and hospital mortality (15.9% vs 2.1%, p=0.016). Six-month mortality was significantly higher in the aged as compared to young cohort (31% vs 9%, p=0.003). Aged septic patients biomarker trajectories suggestive of persistent immunosuppression (Absolute lymphocyte count, sPDL-1) and catabolism (Urine 3MH-Cr ratio, IGF, IGF1BP3, albumin) out to 28 days after sepsis. Aged, critically ill surgical patients have greater organ dysfunction, and incidence of adverse clinical outcomes after sepsis. Biomarker profiles suggest an immunophenotype of persistent immunosuppression and catabolism. Advanced age may necessitate novel therapeutic strategies to promote multi-system organ recovery and improve survival after sepsis. Level II, prognostic.

Mortality predictors in renal transplant recipients with severe sepsis and septic shock.

PubMed

de Carvalho, Mônica Andrade; Freitas, Flávio Geraldo Rezende; Silva Junior, Hélio Tedesco; Bafi, Antônio Toneti; Machado, Flávia Ribeiro; Pestana, José Osmar Medina

2014-01-01

The growing number of renal transplant recipients in a sustained immunosuppressive state is a factor that can contribute to increased incidence of sepsis. However, relatively little is known about sepsis in this population. The aim of this single-center study was to evaluate the factors associated with hospital mortality in renal transplant patients admitted to the intensive care unit (ICU) with severe sepsis and septic shock. Patient demographics and transplant-related and ICU stay data were retrospectively collected. Multiple logistic regression was conducted to identify the independent risk factors associated with hospital mortality. A total of 190 patients were enrolled, 64.2% of whom received kidneys from deceased donors. The mean patient age was 51 ± 13 years (males, 115 [60.5%]), and the median APACHE II was 20 (16-23). The majority of patients developed sepsis late after the renal transplantation (2.1 [0.6-2.3] years). The lung was the most common infection site (59.5%). Upon ICU admission, 16.4% of the patients had ≤ 1 systemic inflammatory response syndrome criteria. Among the patients, 61.5% presented with ≥ 2 organ failures at admission, and 27.9% experienced septic shock within the first 24 hours of ICU admission. The overall hospital mortality rate was 38.4%. In the multivariate analysis, the independent determinants of hospital mortality were male gender (OR = 5.9; 95% CI, 1.7-19.6; p = 0.004), delta SOFA 24 h (OR = 1.7; 95% CI, 1.2-2.3; p = 0.001), mechanical ventilation (OR = 30; 95% CI, 8.8-102.2; p<0.0001), hematologic dysfunction (OR = 6.8; 95% CI, 2.0-22.6; p = 0.002), admission from the ward (OR = 3.4; 95% CI, 1.2-9.7; p = 0.02) and acute kidney injury stage 3 (OR = 5.7; 95% CI,1.9-16.6; p = 0.002). Hospital mortality in renal transplant patients with severe sepsis and septic shock was associated with male gender, admission from the wards, worse SOFA scores on the first day and the presence of hematologic dysfunction, mechanical ventilation or advanced graft dysfunction.

Association of Microcirculation, Macrocirculation, and Severity of Illness in Septic Shock: A Prospective Observational Study to Identify Microcirculatory Targets Potentially Suitable for Guidance of Hemodynamic Therapy.

PubMed

Sturm, Timo; Leiblein, Julia; Schneider-Lindner, Verena; Kirschning, Thomas; Thiel, Manfred

2018-04-01

Clinically unapparent microcirculatory impairment is common and has a negative impact on septic shock, but specific therapy is not established so far. This prospective observational study aimed at identifying candidate parameters for microcirculatory-guided hemodynamic therapy. ClinicalTrials.gov : NCT01530932. Microcirculatory flow and postcapillary venous oxygen saturation were detected during vaso-occlusive testing (VOT) on days 1 (T0), 2 (T24), and 4 (T72) in 20 patients with septic shock at a surgical intensive care unit using a laser Doppler spectrophotometry system (O2C). Reperfusional maximal venous capillary oxygen saturation (SvcO 2 max) showed negative correlations with Simplified Acute Physiology Score II (SAPSII)/Sequential Organ Failure Assessment (SOFA) score, norepinephrine dosage, and lactate concentration and showed positive correlations with cardiac index (CI). At T24 and T72, SvcO 2 max was also inversely linked to fluid balance. With respect to any predictive value, SvcO 2 max and CI determined on day 1 (T0) were negatively correlated with SAPS II/SOFA on day 4 (T72). Moreover, SvcO 2 max measured on day 1 or day 2 was negatively correlated with cumulated fluid balance on day 4 ( r= -.472, P < .05 and r = -.829, P < .001). By contrast, CI neither on day 1 nor on day 2 was correlated with cumulated fluid balance on day 4 ( r = -.343, P = .17 and r = -.365, P = .15). In patients with septic shock, microcirculatory reserve as assessed by SvcO 2 max following VOT was impaired and negatively correlated with severity of illness and fluid balance. In contrast to CI, SvcO 2 max determined on day 1 or day 2 was significantly negatively correlated with cumulative fluid balance on day 4. Therefore, early microcirculatory measurement of SvcO 2 max might be superior to CI in guidance of sepsis therapy to avoid fluid overload. This has to be addressed in future clinical studies.

[The predictive value of dynamic arterial elastance in arterial pressure response after norepinephrine dosage reduction in patients with septic shock].

PubMed

Liang, F M; Yang, T; Dong, L; Hui, J J; Yan, J

2017-05-01

Objective: To assess whether dynamic arterial elastance(Ea(dyn))can be used to predict the reduction of arterial pressure after decreasing norepinephrine (NE) dosage in patients with septic shock. Methods: A prospective observational cohort study was conducted. Thirty-two patients with septic shock and mechanical ventilationwere enrolledfrom January 2014 to December 2015 in ICU of Wuxi People's Hospital of Nanjing Medical University. Hemodynamic parameters were recorded by pulse contour cardiac output(PiCCO)monitoring technology before and after decreasing norepinephrine dosage. Ea(dyn) was defined as the ratio of pulse pressure variation (PPV) to stroke volume variation (SVV). Mean arterial pressure(MAP) variation was calculated after decreasing the dose of NE. Response was defined as a ≥15% decrease of MAP. AUC was plotted to assess the value of Ea(dyn) in predicting MAP response. Results: A total of 32 patients were enrolled in our study, with 13 responding to NE dose decrease where as the other 19 did not. Ea(dyn) was lower in responders than in nonresponders (0.77±0.13 vs 1.09±0.31, P <0.05). Baseline Ea(dyn) was positively correlated with systolic blood pressure variation, diastolic blood pressure variation, systemic vascular resistance variation and MAP variation( r =0.621, P =0.000; r =0.735, P =0.000; r =0.756, P =0.000; r =0.568, P =0.000 respectively). However, stoke volume variation, baseline level of systemic vascular resistance and NE baseline dose were not correlated with Ea(dyn) baseline value( r =0.264, P =0.076; r =0.078, P =0.545; r =0.002, P =0.987 respectively). Ea(dyn)≤0.97 predicted a decrease of MAP when decreasing NE dose, with an area under the receiver-operating characteristic curve of 0.85.The sensitivity was 100.0% and specificity was 73.7%. Conclusions: In septic shock patients treated with NE, Ea(dyn) is an index to predict the decrease of arterial pressure in response to NE dose reduction.

Long-term outcomes in patients with septic shock transfused at a lower versus a higher haemoglobin threshold: the TRISS randomised, multicentre clinical trial.

PubMed

Rygård, Sofie L; Holst, Lars B; Wetterslev, Jørn; Winkel, Per; Johansson, Pär I; Wernerman, Jan; Guttormsen, Anne B; Karlsson, Sari; Perner, Anders

2016-11-01

We assessed the predefined long-term outcomes in patients randomised in the Transfusion Requirements in Septic Shock (TRISS) trial. In 32 Scandinavian ICUs, we randomised 1005 patients with septic shock and haemoglobin of 9 g/dl or less to receive single units of leuko-reduced red cells when haemoglobin level was 7 g/dl or less (lower threshold) or 9 g/dl or less (higher threshold) during ICU stay. We assessed mortality rates 1 year after randomisation and again in all patients at time of longest follow-up in the intention-to-treat population (n = 998) and health-related quality of life (HRQoL) 1 year after randomisation in the Danish patients only (n = 777). Mortality rates in the lower- versus higher-threshold group at 1 year were 53.5 % (268/501 patients) versus 54.6 % (271/496) [relative risk 0.97; 95 % confidence interval (CI) 0.85-1.09; P = 0.62]; at longest follow-up (median 21 months), they were 56.7 % (284/501) versus 61.0 % (302/495) (hazard ratio 0.88; 95 % CI 0.75-1.03; P = 0.12). We obtained HRQoL data at 1 year in 629 of the 777 (81 %) Danish patients, and mean differences between the lower- and higher-threshold group in scores of physical HRQoL were 0.4 (95 % CI -2.4 to 3.1; P = 0.79) and in mental HRQoL 0.5 (95 % CI -3.1 to 4.0; P = 0.79). Long-term mortality rates and HRQoL did not differ in patients with septic shock and anaemia who were transfused at a haemoglobin threshold of 7 g/dl versus a threshold of 9 g/dl. We may reject a more than 3 % increased hazard of death in the lower- versus higher-threshold group at the time of longest follow-up.

Clinical course of sepsis, severe sepsis, and septic shock in a cohort of infected patients from ten Colombian hospitals

PubMed Central

2013-01-01

Background Sepsis has several clinical stages, and mortality rates are different for each stage. Our goal was to establish the evolution and the determinants of the progression of clinical stages, from infection to septic shock, over the first week, as well as their relationship to 7-day and 28-day mortality. Methods This is a secondary analysis of a multicenter cohort of inpatients hospitalized in general wards or intensive care units (ICUs). The general estimating equations (GEE) model was used to estimate the risk of progression and the determinants of stages of infection over the first week. Cox regression with time-dependent covariates and fixed covariates was used to determine the factors related with 7-day and 28-day mortality, respectively. Results In 2681 patients we show that progression to severe sepsis and septic shock increases with intraabdominal and respiratory sources of infection [OR = 1,32; 95%IC = 1,20-1,46 and OR = 1.21, 95%CI = 1,11-1,33 respectively], as well as according to Acute Physiology and Chronic Health Evaluation II (APACHE II) [OR = 1,03; 95%CI = 1,02-1,03] and Sequential Organ Failure Assessment (SOFA) [OR = 1,16; 95%CI = 1,14-1,17] scores. The variables related with first-week mortality were progression to severe sepsis [HR = 2,13; 95%CI = 1,13-4,03] and septic shock [HR = 3,00; 95%CI = 1,50-5.98], respiratory source of infection [HR = 1,76; 95%IC = 1,12-2,77], APACHE II [HR = 1,07; 95% CI = 1,04-1,10] and SOFA [HR = 1,09; 95%IC = 1,04-1,15] scores. Conclusions Intraabdominal and respiratory sources of infection, independently of SOFA and APACHE II scores, increase the risk of clinical progression to more severe stages of sepsis; and these factors, together with progression of the infection itself, are the main determinants of 7-day and 28-day mortality. PMID:23883312

Age-related differences in biomarkers of acute inflammation during hospitalization for sepsis.

PubMed

Ginde, Adit A; Blatchford, Patrick J; Trzeciak, Stephen; Hollander, Judd E; Birkhahn, Robert; Otero, Ronny; Osborn, Tiffany M; Moretti, Eugene; Nguyen, H Bryant; Gunnerson, Kyle J; Milzman, David; Gaieski, David F; Goyal, Munish; Cairns, Charles B; Rivers, Emanuel P; Shapiro, Nathan I

2014-08-01

The authors aimed to evaluate age-related differences in inflammation biomarkers during the first 72 h of hospitalization for sepsis. This was a secondary analysis of a prospective observational cohort of adult patients (n = 855) from 10 urban academic emergency departments with confirmed infection and two or more systemic inflammatory response syndrome criteria. Six inflammation-related biomarkers were analyzed-chemokine (CC-motif) ligand-23, C-reactive protein, interleukin-1 receptor antagonist, neutrophil gelatinase-associated lipocalin (NGAL), peptidoglycan recognition protein, and tumor necrosis factor receptor-1a (TNFR-1a)-measured at presentation and 3, 6, 12, 24, 48, or 72 h later. The median age was 56 (interquartile range, 43 - 72) years, and sepsis severity was 38% sepsis, 16% severe sepsis without shock, and 46% septic shock; the overall 30-day mortality was 12%. Older age was associated with higher sepsis severity: 41% of subjects aged 18 to 34 years had severe sepsis or septic shock compared with 71% for those aged 65 years or older (P < 0.001). In longitudinal models adjusting for demographics, comorbidities, and infection source, older age was associated with higher baseline values for chemokine (CC-motif) ligand-23, interleukin-1 receptor antagonist, NGAL, and TNFR-1a (all P < 0.05). However, older adults had higher mean values during the entire 72-h period only for NGAL and TNFR-1a and higher final 72-h values only for TNFR-1a. Adjustment or stratification by sepsis severity did not change the age-inflammation associations. Although older adults had higher levels of inflammation at presentation and an increased incidence of severe sepsis and septic shock, these age-related differences in inflammation largely resolved during the first 72 h of hospitalization.

Native valve endocarditis caused by Kocuria rosea complicated by peripheral mycotic aneurysm in an elderly host

PubMed Central

Gunaseelan, P; Suresh, G; Raghavan, V; Varadarajan, S

2017-01-01

Infective endocarditis still remains a dreaded illness among treating physicians because of the disease course, its need for meticulous antibiotic management, complications, and overall morbidity. Peripheral mycotic aneurysms are a rarely reported complication of infective endocarditis. Mycotic aneurysms occur in about 5%–10% of cases of infective endocarditis, and most of them involve the intracranial vessels. Here, we report a case of native valve endocarditis in a 74-year-old man caused by Kocuria rosea. He presented with septic shock and acute kidney injury. His illness was complicated by a right popliteal artery mycotic aneurysm. He was treated with intravenous ceftriaxone and vancomycin. The mycotic aneurysm needed aneurysmectomy and anastomosis with a graft. PMID:28397739

Endotoxin-induced shock in the rat. A role for C5a.

PubMed Central

Smedegård, G.; Cui, L. X.; Hugli, T. E.

1989-01-01

Administration of endotoxin from gram-negative bacteria to rats results in systemic hypotension, an increased hematocrit, and decreased numbers of circulating leukocytes (polymorphonuclear), monocytes, and platelets. These potentially lethal physiologic changes may be partially attributed to complement activation and generation of anaphylatoxins by the endotoxin (LPS). We demonstrated an elevation in the plasma levels of both C3a and C5a in LPS-treated rats. Injection of 5 micrograms C5ades Arg (rat) into rats produced effects similar to those induced by LPS, including decreased mean arterial pressure (systemic hypotension) and decreased numbers of circulating polymorphonuclear leukocytes, monocytes, and platelets. Unlike the response to LPS, C5a did not increase the hematocrit, indicating little effect on vascular permeability at the doses used. When LPS-treated animals were pretreated with F(ab')2 fragments of rabbit anti-rat C5a, no changes were measured in the circulating cell counts compared with LPS alone; however a significant improvement in the mean arterial pressure and a decrease in hematocrit was observed. We conclude that LPS-induced (septic) shock in the rat may result, in part, from the effects of complement activation and particularly from the generation of C5a. The influence of C5a on the LPS effect in the rat appears to enhance both the hypotensive (mean arterial pressure) and vascular permeability (hematocrit) responses. These results appear to support and confirm earlier observations that anti-human C5a increased survival in a septic-shock monkey model by eliminating circulating C5a and presumably thereby reducing the effects of endotoxin on blood pressure. Our results demonstrate that C5a plays a significant role in the hemodynamic changes associated with endotoxin-induced shock. Neutralization of C5a with specific antibodies may reduce the hypotensive response to endotoxin sufficiently to prevent lethal septic shock both in animals and in man. PMID:2789475

Toxic Shock Syndrome: Still a Timely Diagnosis.

PubMed

Gossack-Keenan, Kira L; Kam, April J

2017-10-16

Toxic shock syndrome (TSS) is an acute, severe, toxin-mediated disease, characterized by fever, hypotension, and multiorgan system involvement. Toxic shock syndrome has made headlines because of its high associated morbidity and mortality rate in previously healthy young females. Incidence peaked in the early 1980s owing to increased usage of ultra-absorbent tampons. After improved patient education and tampon labeling, the incidence of menstrual TSS has declined. A previously healthy 14-year-old girl presented to an urgent care center with a 2-day history of fever, erythematous maculopapular rash, vomiting, diarrhea, and malaise. She was found to be tachycardic and hypotensive. Investigations revealed thrombocytopenia, an elevated white count and lactate, and acute kidney injury, consistent with septic shock. Recent tampon usage with menstruation was reported, and a pelvic examination revealed purulent vaginal discharge. The patient was transferred to a pediatric intensive care unit for antibiotic and vasopressor therapy. Vaginal swabs later tested positive for Staphylococcus aureus and TSS toxin-1. Although the incidence of TSS has decreased in recent years, it is crucial that clinicians rapidly recognize and treat this life-threatening condition. Emergency physicians should always have a high index of suspicion for TSS in young females presenting without another obvious cause of shock. A pelvic examination should always be completed in these cases.

Septic and non-septic olecranon bursitis in the accident and emergency department--an approach to management.

PubMed Central

Stell, I M

1996-01-01

Olecranon bursitis is relatively common. One third of episodes are septic. Most of the remainder are non-septic, with occasional rheumatological causes. Trauma can cause both septic and non-septic olecranon bursitis. Clinical features are helpful in separating septic from non-septic olecranon bursitis, but there may be local erythema in both. Aspiration should be carried out in all cases, and if the presence of infection is still in doubt, microscopy, Gram staining, and culture of the aspirate will resolve the issue. Septic olecranon bursitis should be treated by aspiration, which may need to be repeated, and a long course of antibiotics. Some cases will need admission, and a few will need surgical treatment. Non-septic olecranon bursitis can be managed with aspiration alone. Non-steroidal anti-inflammatory drugs probably hasten symptomatic improvement. Intrabursal corticosteroids produce a rapid resolution but concern remains over their long term local effects. Recovery from septic olecranon bursitis can take months. PMID:8894865

Ebola haemorrhagic fever

PubMed Central

Feldmann, Heinz; Geisbert, Thomas W

2012-01-01

Ebola viruses are the causative agents of a severe form of viral haemorrhagic fever in man, designated Ebola haemorrhagic fever, and are endemic in regions of central Africa. The exception is the species Reston Ebola virus, which has not been associated with human disease and is found in the Philippines. Ebola virus constitutes an important local public health threat in Africa, with a worldwide effect through imported infections and through the fear of misuse for biological terrorism. Ebola virus is thought to also have a detrimental effect on the great ape population in Africa. Case-fatality rates of the African species in man are as high as 90%, with no prophylaxis or treatment available. Ebola virus infections are characterised by immune suppression and a systemic inflammatory response that causes impairment of the vascular, coagulation, and immune systems, leading to multiorgan failure and shock, and thus, in some ways, resembling septic shock. PMID:21084112

Severe soft tissue infections.

PubMed

Napolitano, Lena M

2009-09-01

Severe skin and soft tissue infections (SSTIs) frequently require management in the ICU, in part related to associated septic shock or toxic shock syndrome or associated organ failure. Four fundamental management principles are key to a successful outcome in caring for patients who have severe SSTIs, including (1) early diagnosis and differentiation of necrotizing versus nonnecrotizing SSTI, (2) early initiation of appropriate empiric broad-spectrum antimicrobial therapy with consideration of risk factors for specific pathogens and mandatory coverage for methicillin-resistant Staphylococcus aureus (MRSA), (3) source control (ie, early aggressive surgical intervention for drainage of abscesses and debridement of necrotizing soft tissue infections), and (4) pathogen identification and appropriate de-escalation of antimicrobial therapy. MRSA has emerged as the most common identifiable cause of severe SSTIs; therefore, initiation of empiric anti-MRSA antimicrobials is warranted in all cases of severe SSTIs. In addition, appropriate critical care management-including fluid resuscitation, organ support and nutritional support-is a necessary component in treating severe SSTIs.

CLOSTRIDIAL PARAPROCTITIS WITH GAS GANGRENE OF FRONT-LATERAL ABDOMINAL WALLS AND NECROTIC FASCIO-MYOSITIS (CASE REPORT).

PubMed

Didbaridze, N; Lomidze, N; Abuladze, T; Qiliptari, G; Didbaridze, T; Gvasalia, I; Mkervalishvili, Z; Gogokhia, N

2016-09-01

Anaerobic clostridial infection is the most severe form of paraproctitis. The incubation period is very short, from 3 to 6 hours, sometimes lasting for 1-2 days. Clostridial infection spreads rapidly and induces gas gangrene, causes destruction of cells and other intermediate substances, and impedes blood circulation. This paper presents a case study of an extremely severe form of anaerobic infection with spontaneous gas gangrene, cellulitis, fasciomyositic necrosis, severe intoxication and septic shock on the abdominal front and lateral surfaces. This patient presented as infected with Clostridium septicum, a rare and highly toxic Gram-positive, spore-forming, obligate anaerobic bacillus that progresses and migrates rapidly, affecting all soft tissues (muscle, fascia), and produces four toxins which cause gas gangrene, intravascular hemolysis, tissue necrosis, and septic shock. The mortality rate is typically 80%. In this case study, a positive clinical outcome was achieved by aggressive identification of the microbe, appropriate and immediate therapy, and vigorous surgical intervention. Specifically, immediate surgery was conducted to ensure a wide excision of damaged tissues, necrectomy, curettage, wide drainage, readjustment, oxygenation through drainages, further additional surgical corrections through CT control with wide bandages in the operating area. Further, the diagnostic workup was thorough, identifying the microbe through a properly constructed diagnostic algorithm, ultrasound and CT studies, infectious agent assessments, and bacteriological monitoring carried out on the 1st-2nd-5th-7th-12th-15th-21st-25th days. Rational antibiotic therapy with permanent susceptibility testing informed the selection of an appropriate agent. Finally, markers for the evaluation of severity (Apache scale) were assessed, as they were for stage of infection (prokalcitonin), inflammation (CRP) and other indicators.

Prehospital triage of septic patients at the SAMU regulation: Comparison of qSOFA, MRST, MEWS and PRESEP scores.

PubMed

Jouffroy, R; Saade, A; Ellouze, S; Carpentier, A; Michaloux, M; Carli, P; Vivien, B

2018-05-01

A couple of scoring systems have been developed for risk stratification of septic patients. Their performance in the management of out-of-hospital initial care delivery is not documented. This study try to evaluate the predictive ability of Quick Sequential Organ Failure Assessment (qSOFA), Robson Screening Tool (RST), Modified Early Warning Score (MEWS) and Prehospital Early Sepsis Detection (PRESEP) scores on out of-hospital triage of septic patients, to predict intensive care unit (ICU) admission. A retrospective study using call records received by the SAMU 15 regulation call centre including all patients with presumed septic shock was performed. The primary outcome was the admission to the ICU. Among the 47 000 reports received, 37 patients with presumed septic shock were included. Twenty-two patients (59%) were admitted to ICU. AUCs of qSOFA, RST, MEWS and PRESEP scores were respectively 0.40 [0.22-0.59], 0.60 [0.43-0.78], 0.66 [0.47-0.85] and 0.67 [0.51-0.84]. RST outperformed PRESEP, MEWS and qSOFA for sensitivity (1, 0.92, 0.85 and 0.62 respectively). MEWS showed better specificity than PRESEP, MRST and qSOFA (0.33, 0.29, 0.16 and 0.16). MEWS showed comparable positive predictive value than PRESEP and outperformed MRST and qSOFA (0.41, 0.41, 0.39 and 0.29 respectively). Negative predictive value of MRST outperformed PRESEP, MEWS and qSOFA (1, 0.88, 0.80 and 0.44 respectively). Our findings suggest that screening patients at SAMU 15 regulation call centre using qSOFA, MRST, MEWS and PRESEP scores to predict ICU admission is irrelevant. Development of a specific scoring system for out-of-hospital triage of septic patients is needed. Copyright © 2017 Elsevier Inc. All rights reserved.

Lower initial central venous pressure in septic patients from long-term care facilities than in those from the community.

PubMed

Lin, Chun-Yu; Chen, Tun-Chieh; Lu, Po-Liang; Chen, Hui-Juan; Bojang, Kebba S; Chen, Yen-Hsu

2014-10-01

The cornerstone of emergency management of severe sepsis and septic shock is early (within 6 hours) goal-directed therapy, including maintenance of central venous pressure (CVP) at 8-12 mmHg. It is unclear whether there is a difference in initial (baseline) CVP between septic patients who are referred from the community and those who come from long-term care facilities (LTCFs) in Taiwan. We designed this study to investigate the difference in hemodynamic parameters between these two groups. Every patient with severe sepsis or septic shock who had a central venous catheter inserted via the internal jugular or subclavian vein at Kaohsiung Medical University Hospital between April 2007 and October 2007 was enrolled. CVP was measured immediately at the emergency department. Patient demographics, including residence, were retrospectively recorded and analyzed. There were 166 evaluable patients; 125 (75.3%) came from the community and 41 (24.7%) from LTCFs. There were no significant differences in age, sex, initial body temperature, heart rate, blood pressure, or leukocyte count between the two groups. However, patients who were referred from LTCFs had a significantly lower initial CVP than those from the community (5.0 ± 4.5 mmHg vs. 7.0 ± 4.8 mmHg, p = 0.023). The difference was more significant between mechanically ventilated patients from LTCFs and those from the community (5.0 ± 3.0 mmHg vs. 8.1 ± 5.6 mmHg, p = 0.006). Severely septic patients referred from LTCFs may require more aggressive fluid resuscitation within the first 6 hours of the diagnostic criteria met at the emergency department to achieve the CVP target of early goal-directed therapy. Copyright © 2013. Published by Elsevier B.V.

Evaluation of the delta neutrophil index from an automated blood cell analyser in septic dogs.

PubMed

Troìa, R; Agnoli, C; Calipa, S; Segalina, S; Murgia, E; Gruarin, M; Dondi, F; Giunti, M

2017-12-01

Immature granulocytes (IG) are a marker of severe inflammatory states in human beings and animals, and have been linked to a diagnosis of sepsis and poor prognosis. The delta neutrophil index (DNI), automatically calculated by a haematological analyser, provides an estimate of circulating IG. In particular, an increased DNI value has been associated with the severity of sepsis, and mortality, in critically ill human beings. The aims of this study were to determine the DNI reference interval (RI) in healthy dogs, and to evaluate its diagnostic and prognostic significance in dogs with sepsis. A total of 118 dogs with sepsis undergoing a complete blood cell count (CBC) at the time of hospital admission were included retrospectively. Dogs with sepsis were compared to 20 dogs with primary immune-mediated haemolytic anaemia (IMHA) and 99 healthy controls. The DNI RI was set from 0 to 9.2%. The DNI was significantly higher in dogs with sepsis compared to dogs with IMHA and healthy dogs (P<0.001), and significantly higher in dogs with septic shock compared to septic dogs without circulatory failure (P<0.03). No differences were detected between survivors (78/118) and non-survivors (40/118). Septic dogs with a DNI above the RI had significantly higher frequencies of IG and toxic neutrophil changes on manual blood smear evaluation (P=0.03 and P<0.001, respectively). The DNI had a fair performance in identifying dogs with sepsis in this population and predicted septic shock. Larger prospective studies are needed to validate DNI measurement in dogs and to test its clinical utility. Copyright © 2017 Elsevier Ltd. All rights reserved.

Impact of echinocandin on prognosis of proven invasive candidiasis in ICU: A post-hoc causal inference model using the AmarCAND2 study.

PubMed

Bailly, Sébastien; Leroy, Olivier; Azoulay, Elie; Montravers, Philippe; Constantin, Jean-Michel; Dupont, Hervé; Guillemot, Didier; Lortholary, Olivier; Mira, Jean-Paul; Perrigault, Pierre-François; Gangneux, Jean-Pierre; Timsit, Jean-François

2017-04-01

guidelines recommend first-line systemic antifungal therapy (SAT) with echinocandins in invasive candidiasis (IC), especially in critically ill patients. This study aimed at assessing the impact of echinocandins compared to azoles as initial SAT on the 28-day prognosis in adult ICU patients. From the prospective multicenter AmarCAND2 cohort (835 patients), we selected those with documented IC and treated with echinocandins (ECH) or azoles (AZO). The average causal effect of echinocandins on 28-day mortality was assessed using an inverse probability of treatment weight (IPTW) estimator. 397 patients were selected, treated with echinocandins (242 patients, 61%) or azoles (155 patients, 39%); septic shock: 179 patients (45%). The median SAPSII was higher in the ECH group (48 [35; 62] vs. 43 [31; 58], p = 0.01). Crude mortality was 34% (ECH group) vs. 25% (AZO group). After adjustment on baseline confounders, no significant association emerged between initial SAT with echinocandins and 28-day mortality (HR: 0.95; 95% CI: [0.60; 1.49]; p = 0.82). However, echinocandin tended to benefit patients with septic shock (HR: 0.46 [0.19; 1.07]; p = 0.07). Patients who received echinocandins were more severely ill. Echinocandin use was associated with a non-significant 7% decrease of 28-day mortality and a trend to a beneficial effect for patient with septic shock. Copyright © 2017 The British Infection Association. Published by Elsevier Ltd. All rights reserved.

Derivation and Validation of a Biomarker-Based Clinical Algorithm to Rule Out Sepsis From Noninfectious Systemic Inflammatory Response Syndrome at Emergency Department Admission: A Multicenter Prospective Study.

PubMed

Mearelli, Filippo; Fiotti, Nicola; Giansante, Carlo; Casarsa, Chiara; Orso, Daniele; De Helmersen, Marco; Altamura, Nicola; Ruscio, Maurizio; Castello, Luigi Mario; Colonetti, Efrem; Marino, Rossella; Barbati, Giulia; Bregnocchi, Andrea; Ronco, Claudio; Lupia, Enrico; Montrucchio, Giuseppe; Muiesan, Maria Lorenza; Di Somma, Salvatore; Avanzi, Gian Carlo; Biolo, Gianni

2018-05-07

To derive and validate a predictive algorithm integrating a nomogram-based prediction of the pretest probability of infection with a panel of serum biomarkers, which could robustly differentiate sepsis/septic shock from noninfectious systemic inflammatory response syndrome. Multicenter prospective study. At emergency department admission in five University hospitals. Nine-hundred forty-seven adults in inception cohort and 185 adults in validation cohort. None. A nomogram, including age, Sequential Organ Failure Assessment score, recent antimicrobial therapy, hyperthermia, leukocytosis, and high C-reactive protein values, was built in order to take data from 716 infected patients and 120 patients with noninfectious systemic inflammatory response syndrome to predict pretest probability of infection. Then, the best combination of procalcitonin, soluble phospholypase A2 group IIA, presepsin, soluble interleukin-2 receptor α, and soluble triggering receptor expressed on myeloid cell-1 was applied in order to categorize patients as "likely" or "unlikely" to be infected. The predictive algorithm required only procalcitonin backed up with soluble phospholypase A2 group IIA determined in 29% of the patients to rule out sepsis/septic shock with a negative predictive value of 93%. In a validation cohort of 158 patients, predictive algorithm reached 100% of negative predictive value requiring biomarker measurements in 18% of the population. We have developed and validated a high-performing, reproducible, and parsimonious algorithm to assist emergency department physicians in distinguishing sepsis/septic shock from noninfectious systemic inflammatory response syndrome.

Puerperal and intrapartum group A streptococcal infection.

PubMed Central

Anteby, E Y; Yagel, S; Hanoch, J; Shapiro, M; Moses, A E

1999-01-01

OBJECTIVE: To determine the demographic and clinical variables characteristic of non-epidemic intrapartum or puerperal group A streptococcal (GAS) infection. METHODS: The records of 47 patients diagnosed with intrapartum or puerperal GAS infection over a 6 1/2 year period at Hadassah-University Hospital-Mt. Scopus, Jerusalem were reviewed. Data regarding 25,811 women, the general population of women that delivered during that period, were obtained from their computerized medical records. Frequency distributions, t-test, chi-square, and Spearman's Rank Correlation were used, as appropriate, to analyze and compare demographic and clinical variables associated with development of GAS infection, its clinical course and subsequent development of septic shock. RESULTS: Mean age of mothers with GAS infection was higher than that of our general pregnant population (30.4 versus 27.4 years, P = 0.0019), and a higher proportion of GAS infected patients (30% versus 12%, P < 0.005) experienced PROM. Thirty-one (66%) women had fever as their sole presenting symptom, eight (17%) had fever and abdominal pain, seven (15%) had fever and abnormal vaginal bleeding, and one patient (2%) presented with a rash. Three patients (6%) developed a septic shock. Two of these patients presented with symptoms more than 14 days after delivery. CONCLUSIONS: We describe the characteristics of non-epidemic intrapartum or puerperal GAS infection. Data from our study and review of the literature suggest that some patients who develop septic shock may present later in the puerperium than patients with an uncomplicated GAS infection. PMID:10598916

Imbalances in serum angiopoietin concentrations are early predictors of septic shock development in patients with post chemotherapy febrile neutropenia

PubMed Central

2010-01-01

Background Febrile neutropenia carries a high risk of sepsis complications, and the identification of biomarkers capable to identify high risk patients is a great challenge. Angiopoietins (Ang -) are cytokines involved in the control microvascular permeability. It is accepted that Ang-1 expression maintains endothelial barrier integrity, and that Ang-2 acts as an antagonizing cytokine with barrier-disrupting functions in inflammatory situations. Ang-2 levels have been recently correlated with sepsis mortality in intensive care units. Methods We prospectively evaluated concentrations of Ang-1 and Ang-2 at different time-points during febrile neutropenia, and explored the diagnostic accuracy of these mediators as potential predictors of poor outcome in this clinical setting before the development of sepsis complications. Results Patients that evolved with septic shock (n = 10) presented higher levels of Ang-2 measured 48 hours after fever onset, and of the Ang-2/Ang-1 ratio at the time of fever onset compared to patients with non-complicated sepsis (n = 31). These levels correlated with sepsis severity scores. Conclusions Our data suggest that imbalances in the concentrations of Ang-1 and Ang-2 are independent and early markers of the risk of developing septic shock and of sepsis mortality in febrile neutropenia, and larger studies are warranted to validate their clinical usefulness. Therapeutic strategies that manipulate this Ang-2/Ang-1 imbalance can potentially offer new and promising treatments for sepsis in febrile neutropenia. PMID:20509945

Factors associated with postoperative complications and mortality in perforated peptic ulcer.

PubMed

Montalvo-Javé, Eduardo Esteban; Corres-Sillas, Omar; Athié-Gutiérrez, César

2011-01-01

Elective surgery for uncomplicated peptic ulcer has shown a significant decrease; however, complications such as perforation and obstruction persist and require urgent surgical management. The aim of this study was to identify factors associated with early postoperative complications and mortality of patients admitted to the emergency department with perforated peptic ulcer. We performed a clinical, retrospective, cross-sectional and descriptive study of patients who were treated at the General Hospital of Mexico with a diagnosis of perforated peptic ulcer from January 2006 to December 2008. Thirty patients were included in the study. We studied several clinical findings upon admission to the emergency department and intraoperative patient findings in order to determine the association of those with early postoperative complications and mortality. We studied 30 patients with an average age of 57.07 years (± 14.2 years). The male:female ratio was 2:1. We found that the risk of developing postoperative complications was 66.7% and is significantly influenced by time of onset of abdominal pain prior to admission, bloating, septic shock and blood type O positive. Mortality was 16.7% and was correlated with the presence of septic shock on admission. The surgical procedure performed was primary closure with Graham patch in 86.6%. Average hospital stay was 12.8 days. The presence of early postoperative complications is associated with time of onset of abdominal pain before admission, abdominal distension, blood type O positive and the presence of septic shock on admission.

Shock in the Nonhuman Primate. Volume 2. Abstracts of the Published Literature, 1974-1977

DTIC Science & Technology

1977-06-01

primates from hemorrhagic and septic shock. Trunkey, D., J. Holcroft, and M. A. Carpenter ... ........... .... 42 Calcium flux during hemorrhagic...virtually absent. In vitro endotoxin-leukocyte interaction reproduced all changes seen in sequestered PMN-leukocytes with the exception of leukocyte...Although there is no pre- sently known clinical state referable to lead-endotoxin interaction and since our experimental conditions were not

The big bang of hemofiltration: the beginning of a new era in the third millennium for extra-corporeal blood purification!

PubMed

Honore', P M; Joannes-Boyau, O; Merson, L; Boer, W; Piette, V; Galloy, A-C; Janvier, G

2006-07-01

Since the last decade, hemofiltration and especially high volume hemofiltration has rapidly evolved from a somewhat experimental treatment towards a potentially effective 'adjunctive' therapy in severe septic shock and especially refractory or catecholamine resistant hypodynamic septic shock. Nevertheless, this approach lacks prospective randomized studies (PRT'S) evaluating the critical role of early hemofiltration in sepsis. An important step forward which could be called the 'big bang' in term of hemofiltration was the publication of a PRT in patients with acute renal failure (ARF) (1). Before this study (2), nobody believed that hemofiltration could change the survival rate in intensive care. Since that big bang, many physicians consider that hemofiltration at a certain dose can change the survival rate in intensive care. So the world of hemofiltration in ICU is not a definitive world, it is still in expansion. Indeed, we now have to try to define what will be the exact dose we need in septic acute renal failure. This dose might well be 'higher' than 35 ml/kg/hour in the septic acute renal failure 'group' as suggested by many studies (2-5). At present, it is the issue of continuous dose of high volume hemofiltration that has to be tested in future randomized studies. Since the Vicenza study (2) has shown that 35 ml/kg/h is the best dose in terms of survival, dealing with non septic acute renal failure in ICU, several studies from different groups have shown that, in septic acute renal failure, a higher dose might correlate with better survival. This has also been shown in some way by the study of the 'Vicenza group' but not with a statistically significant value (2). New PRT'S have just started in Europe like the IVOIRE study (hIgh VOlume in Intensive caRE) (6) and the RENAL study. Another large study is looking more basically at dose in non septic acute renal failure in Australasia and is led by the group of Rinaldo Bellomo in Melbourne (7) as well as the ATN study (8) led by Palevsky and colleagues in the USA, also testing the importance of dose in the treatment for ARF. Nevertheless, 'early goal-directed hemofiltration therapy' like early goal directed therapy (9) has to be studied in our critical ill patients. Regarding this issue, fewer studies, mainly retrospective exist, but again the IVOIRE study (6) will address this issue by studying septic patients with acute renal injury according to the Rifle classification (10). So, this review focuses on the early application and on the adequate dose of continuous high volume hemofiltration in septic shock in order to improve not only hemodynamics, but survival in this very severely ill cohort of patients. This could well be called the 'big bang of hemofiltration' as one could never have anticipated that an adequate dose of hemofiltration could markedly influence the survival rate of ICU-septic acute renal failure patients. On top of the use of early and adequate dose of hemofiltration in sepsis, a higher dose could also provide better renal recovery rate and reduce the risk of associate chronic dialysis in these patients. Furthermore, this paper also reviews 'brand' new theories regarding the rationale for hemofiltration in sepsis. Finally, this paper also addresses the so-called negative studies as well anticipated side effects.

Severe group A streptococcal infection and streptococcal toxic shock syndrome.

PubMed

Baxter, F; McChesney, J

2000-11-01

To review the literature on group A streptococcal toxic shock syndrome, (STSS). Medline and EMBASE searches were conducted using the key words group A streptococcal toxic shock syndrome, alone and in combination with anesthesia; and septic shock, combined with anesthesia. Medline was also searched using key words intravenous immunoglobulin, (IVIG) and group A streptococcus, (GAS); and group A streptococcus and antibiotic therapy. Other references were included in this review if they addressed the history, microbiology, pathophysiology, incidence, mortality, presentation and management of invasive GAS infections. Relevant references from the papers reviewed were also considered. Articles on the foregoing topics were included regardless of study design. Non-English language studies were excluded. Literature on the efficacy of IVIG and optimal antibiotic therapy was specifically searched. Reports of invasive GAS infections have recently increased. Invasive GAS infection is associated with a toxic shock syndrome, (STSS), in 8-14% of cases. The STSS characteristically results in shock and multi-organ failure soon after the onset of symptoms, and is associated with a mortality of 33-81%. Many of these patients will require extensive soft tissue debridement or amputation in the operating room, on an emergency basis. The extent of tissue debridement required is often underestimated before skin incision. Management of STSS requires volume resuscitation, vasopressor/inotrope infusion, antibiotic therapy and supportive care in an intensive care unit, usually including mechanical ventilation. Intravenous immunoglobulin infusion has been recommended. Further studies are needed to define the role of IVIG in STSS management and to determine optimal anesthetic management of patients with septic shock.

A rational approach to fluid therapy in sepsis.

PubMed

Marik, P; Bellomo, R

2016-03-01

Aggressive fluid resuscitation to achieve a central venous pressure (CVP) greater than 8 mm Hg has been promoted as the standard of care, in the management of patients with severe sepsis and septic shock. However recent clinical trials have demonstrated that this approach does not improve the outcome of patients with severe sepsis and septic shock. Pathophysiologically, sepsis is characterized by vasoplegia with loss of arterial tone, venodilation with sequestration of blood in the unstressed blood compartment and changes in ventricular function with reduced compliance and reduced preload responsiveness. These data suggest that sepsis is primarily not a volume-depleted state and recent evidence demonstrates that most septic patients are poorly responsive to fluids. Furthermore, almost all of the administered fluid is sequestered in the tissues, resulting in severe oedema in vital organs and, thereby, increasing the risk of organ dysfunction. These data suggest that a physiologic, haemodynamically guided conservative approach to fluid therapy in patients with sepsis would be prudent and would likely reduce the morbidity and improve the outcome of this disease. © The Author 2015. Published by Oxford University Press on behalf of the British Journal of Anaesthesia. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Clozapine-induced acute gastrointestinal necrosis: a case report.

PubMed

Osterman, Mark T; Foley, Caitlin; Matthias, Isaac

2017-09-23

Clozapine is known to cause fecal impaction and ileus with resultant colonic necrosis due to compression of colonic mucosa. There are rare reports of clozapine causing necrosis of other portions of the gastrointestinal tract unrelated to constipation. We describe a case of acute necrosis of the upper gastrointestinal tract and small bowel to due to clozapine and quetiapine. A 66-year-old white man with a past medical history of schizophrenia, maintained on clozapine and quetiapine, presented with hypoxic respiratory failure caused by aspiration of feculent emesis due to impacted stool throughout his colon. His constipation resolved with discontinuation of clozapine and quetiapine, and his clinical condition improved. These medicines were restarted after 2 weeks, resulting in acute gastrointestinal necrosis from the mid esophagus through his entire small bowel. He died due to septic shock with Gram-negative rod bacteremia. Clozapine may cause acute gastrointestinal necrosis.

[Flesh-eating bacteria infection of an immunocompromised patient].

PubMed

Slavei, K; Hauser, B; Pénzes, I; Ondrejka, P; Faller, J

2001-10-01

After years of steadily declining morbidity and mortality due to group A streptococcal infections, a resurgence of severe, invasive disease has been ongoing since 1980, leading to the recognition of streptococcal shock syndrome (STSS), necrotizing fasciitis, the most severe form of invasive infection. The patients suffer from rapid local deep soft tissue destruction, severe septic shock and multi organ failure. The increased incidence of these infections has been accompanied by remarkable vigor in virulence and severity of the disease. The reason for this impressive change in the epidemiology and clinical manifestation of group A streptococcal infections remains unknown. The possible etiological factor is changing in virulence factor or the lack of protective immunity of the population (immunocompromise) against the invasive strains. We describe a severe necrotizing fasciitis of a 41-year-old previously immunocompromised woman. The patient developed severe septic shock, multi organ failure and perineal and lower abdominal skin, fat and fascia necrosis due to mixed GAS (aerob, anaerob) infection of the perineum and the Bartholini glands. After an aggressive surgical debridement, antibiotic and supportive therapy the generalised and local infection was treated.

Protocolised Management In Sepsis (ProMISe): a multicentre randomised controlled trial of the clinical effectiveness and cost-effectiveness of early, goal-directed, protocolised resuscitation for emerging septic shock.

PubMed

Mouncey, Paul R; Osborn, Tiffany M; Power, G Sarah; Harrison, David A; Sadique, M Zia; Grieve, Richard D; Jahan, Rahi; Tan, Jermaine C K; Harvey, Sheila E; Bell, Derek; Bion, Julian F; Coats, Timothy J; Singer, Mervyn; Young, J Duncan; Rowan, Kathryn M

2015-11-01

Early goal-directed therapy (EGDT) is recommended in international guidance for the resuscitation of patients presenting with early septic shock. However, adoption has been limited and uncertainty remains over its clinical effectiveness and cost-effectiveness. The primary objective was to estimate the effect of EGDT compared with usual resuscitation on mortality at 90 days following randomisation and on incremental cost-effectiveness at 1 year. The secondary objectives were to compare EGDT with usual resuscitation for requirement for, and duration of, critical care unit organ support; length of stay in the emergency department (ED), critical care unit and acute hospital; health-related quality of life, resource use and costs at 90 days and at 1 year; all-cause mortality at 28 days, at acute hospital discharge and at 1 year; and estimated lifetime incremental cost-effectiveness. A pragmatic, open, multicentre, parallel-group randomised controlled trial with an integrated economic evaluation. Fifty-six NHS hospitals in England. A total of 1260 patients who presented at EDs with septic shock. EGDT (n = 630) or usual resuscitation (n = 630). Patients were randomly allocated 1 : 1. All-cause mortality at 90 days after randomisation and incremental net benefit (at £20,000 per quality-adjusted life-year) at 1 year. Following withdrawals, data on 1243 (EGDT, n = 623; usual resuscitation, n = 620) patients were included in the analysis. By 90 days, 184 (29.5%) in the EGDT and 181 (29.2%) patients in the usual-resuscitation group had died [p = 0.90; absolute risk reduction -0.3%, 95% confidence interval (CI) -5.4 to 4.7; relative risk 1.01, 95% CI 0.85 to 1.20]. Treatment intensity was greater for the EGDT group, indicated by the increased use of intravenous fluids, vasoactive drugs and red blood cell transfusions. Increased treatment intensity was reflected by significantly higher Sequential Organ Failure Assessment scores and more advanced cardiovascular support days in critical care for the EGDT group. At 1 year, the incremental net benefit for EGDT versus usual resuscitation was negative at -£725 (95% CI -£3000 to £1550). The probability that EGDT was more cost-effective than usual resuscitation was below 30%. There were no significant differences in any other secondary outcomes, including health-related quality of life, or adverse events. Recruitment was lower at weekends and out of hours. The intervention could not be blinded. There was no significant difference in all-cause mortality at 90 days for EGDT compared with usual resuscitation among adults identified with early septic shock presenting to EDs in England. On average, costs were higher in the EGDT group than in the usual-resuscitation group while quality-adjusted life-years were similar in both groups; the probability that it is cost-effective is < 30%. The ProMISe (Protocolised Management In Sepsis) trial completes the planned trio of evaluations of EGDT across the USA, Australasia and England; all have indicated that EGDT is not superior to usual resuscitation. Recognising that each of the three individual, large trials has limited power for evaluating potentially important subgroups, the harmonised approach adopted provides the opportunity to conduct an individual patient data meta-analysis, enhancing both knowledge and generalisability. Current Controlled Trials ISRCTN36307479. This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 19, No. 97. See the NIHR Journals Library website for further project information.

Novel hybrid technology for early diagnostics of sepsis

NASA Astrophysics Data System (ADS)

Saknite, Inga; Grabovskis, Andris; Kazune, Sigita; Rubins, Uldis; Marcinkevics, Zbignevs; Volceka, Karina; Kviesis-Kipge, Edgars; Spigulis, Janis

2017-02-01

Sepsis is a potentially fatal disease with mortality rate as high as 50% in patients with septic shock; mortality rate can increase by 7.6% per hour if appropriate treatment is not started. Internationally accepted guidelines for diagnosis of sepsis rely on vital sign monitoring and laboratory tests in order to recognize organ failure. This pilot study aims to explore the potential of hyperspectral and thermal imaging techniques to identify and quantify early alterations in skin oxygenation and perfusion induced by sepsis. The study comprises both physiological model experiments on healthy volunteers in a laboratory environment, as well as screening case series of patients with septic shock in the intensive care department. Hyperspectral imaging is used to determine one of the main characteristic visual signs of skin oxygenation abnormalities - skin mottling, whereas changes in peripheral perfusion have been visualized by thermal imaging as heterogeneous skin temperature areas. In order to mimic septic skin mottling in a reproducible way in laboratory environment, arterial occlusion provocation test was utilized on healthy volunteers. Visualization of oxygen saturation by hyperspectral imaging allows diagnosing microcirculatory alterations induced by sepsis earlier than visual assessment of mottling. Thermal images of sepsis patients in the clinic clearly reveal hotspots produced by perforating arteries, as well as cold regions of low blood supply. The results of this pilot study show that thermal imaging in combination with hyperspectral imaging allows the determination of oxygen supply and utilization in critically ill septic patients.

The New York Sepsis Severity Score: Development of a Risk-Adjusted Severity Model for Sepsis.

PubMed

Phillips, Gary S; Osborn, Tiffany M; Terry, Kathleen M; Gesten, Foster; Levy, Mitchell M; Lemeshow, Stanley

2018-05-01

In accordance with Rory's Regulations, hospitals across New York State developed and implemented protocols for sepsis recognition and treatment to reduce variations in evidence informed care and preventable mortality. The New York Department of Health sought to develop a risk assessment model for accurate and standardized hospital mortality comparisons of adult septic patients across institutions using case-mix adjustment. Retrospective evaluation of prospectively collected data. Data from 43,204 severe sepsis and septic shock patients from 179 hospitals across New York State were evaluated. Prospective data were submitted to a database from January 1, 2015, to December 31, 2015. None. Maximum likelihood logistic regression was used to estimate model coefficients used in the New York State risk model. The mortality probability was estimated using a logistic regression model. Variables to be included in the model were determined as part of the model-building process. Interactions between variables were included if they made clinical sense and if their p values were less than 0.05. Model development used a random sample of 90% of available patients and was validated using the remaining 10%. Hosmer-Lemeshow goodness of fit p values were considerably greater than 0.05, suggesting good calibration. Areas under the receiver operator curve in the developmental and validation subsets were 0.770 (95% CI, 0.765-0.775) and 0.773 (95% CI, 0.758-0.787), respectively, indicating good discrimination. Development and validation datasets had similar distributions of estimated mortality probabilities. Mortality increased with rising age, comorbidities, and lactate. The New York Sepsis Severity Score accurately estimated the probability of hospital mortality in severe sepsis and septic shock patients. It performed well with respect to calibration and discrimination. This sepsis-specific model provides an accurate, comprehensive method for standardized mortality comparison of adult patients with severe sepsis and septic shock.

Prediction about severity and outcome of sepsis by pro-atrial natriuretic peptide and pro-adrenomedullin.

PubMed

Wang, Rui-lan; Kang, Fu-xin

2010-06-01

Measurement of biomarkers is a potential approach to early prediction of the risk of mortality in patients with sepsis. The aim of the present study was to evaluate the prognostic value of pro-atrial natriuretic peptide (pro-ANP) and pro-adrenomedullin (pro-ADM) levels in a cohort of medical intensive care patients and to compare it with that of other known biomarkers and physiological scores. Blood samples of 51 consecutive critically ill patients admitted to the intensive care unit and 53 age-matched healthy control people were evaluated in this prospective study. The prognostic value of pro-ANP and pro-ADM levels was compared with that of acute physiology and chronic health evaluation (APACHE) II scores and various biomarkers such as C-reactive protein, interleukin-6 and procalcitonin. Pro-ANP and pro-ADM were detected by a new sandwich immunoassay. On admission, 25 patients had systemic inflammatory response syndrome (SIRS), 12 sepsis, 9 severe sepsis and 5 septic shock. At that time, the median levels (ng/ml) of pro-ANP and pro-ADM were 87.22 and 0.34 respectively in patients with SIRS, 1533.30 and 2.23 in those with sepsis, 1098.73 and 4.57 in those with severe sepsis, and 1933.94 and 8.21 in those with septic shock. With the increasing severity of disease, the levels of pro-ANP and pro-ADM were gradually increased. On admission, the circulating levels of pro-ANP and pro-ADM in patients with sepsis, severe sepsis, or septic shock were significantly higher in non-survivors than in survivors (P less than 0.05). In a receiver operating characteristic curve analysis for the survival of patients with sepsis, the areas under the curve (AUCs) for pro-ANP and pro-ADM were 0.89 and 0.87 respectively, which was similar to the AUCs for procalcitonin and APACHE II scores. Pro-ANP and pro-ADM are valuable biomarkers for prediction of severity of septic patients.

Computer-controlled closed-loop drug infusion system for automated hemodynamic resuscitation in endotoxin-induced shock.

PubMed

Uemura, Kazunori; Kawada, Toru; Zheng, Can; Li, Meihua; Sugimachi, Masaru

2017-10-23

Hemodynamic resuscitation in septic shock requires aggressive fluid replacement and appropriate use of vasopressors to optimize arterial pressure (AP) and cardiac output (CO). Because responses to these drugs vary between patients and within patient over time, strict monitoring of patient condition and repetitive adjustment of drug dose are required. This task is time and labor consuming, and is associated with poor adherence to resuscitation guidelines. To overcome this issue, we developed a computer-controlled closed-loop drug infusion system for automated hemodynamic resuscitation in septic shock, and evaluated the performance of the system in a canine model of endotoxin shock. Our system monitors AP, CO and central venous pressure, and computes arterial resistance (R), stressed blood volume (V) and Frank-Starling slope of left ventricle (S). The system controls R with noradrenaline (NA), and V with Ringer's acetate solution (RiA), thereby controlling AP and CO. In 4 dogs, AP and CO were measured invasively. In another 4 dogs, AP and CO were measured less invasively using clinically acceptable modalities, aiming to make the system clinically feasible. In all 8 dogs, endotoxin shock was induced by injecting Escherichia coli lipopolysaccharide, which significantly decreased AP from 95 (91-108) to 43 (39-45) mmHg, and CO from 112 (104-142) to 62 (51-73) ml·min -1 ·kg -1 . The system was then connected to the dogs, and activated. System performance was observed over a period of 4 h. Our system immediately started infusions of NA and RiA. Within 40 min, RiA increased V to target level, and NA maintained R at target level, while S was concomitantly increased. These resulted in restoration of AP to 70 (69-71) mmHg and CO to 130 (125-138) ml·min -1 ·kg -1 . Median of absolute performance error, an index of precision of control, was small in AP [2.5 (2.1-4.5) %] and CO [2.4 (1.4-5.5) %], which were not increased even when the variables were measured less invasively. In a canine model of endotoxin shock, our system automatically improved and maintained AP and CO at their target values with small performance error. Our system is potentially an attractive clinical tool for rescuing patients with septic shock.

Early fluid loading for septic patients: Any safety limit needed?

PubMed

Gong, Yi-Chun; Liu, Jing-Tao; Ma, Peng-Lin

2018-02-01

Early adequate fluid loading was the corner stone of hemodynamic optimization for sepsis and septic shock. Meanwhile, recent recommended protocol for fluid resuscitation was increasingly debated on hemodynamic stability vs risk of overloading. In recent publications, it was found that a priority was often given to hemodynamic stability rather than organ function alternation in the early fluid resuscitation of sepsis. However, no safety limits were used at all in most of these reports. In this article, the rationality and safety of early aggressive fluid loading for septic patients were discussed. It was concluded that early aggressive fluid loading improved hemodynamics transitorily, but was probably traded off with a follow-up organ function impairment, such as worsening oxygenation by reduction of lung aeration, in a part of septic patients at least. Thus, a safeguard is needed against unnecessary excessive fluids in early aggressive fluid loading for septic patients. Copyright © 2017 Daping Hospital and the Research Institute of Surgery of the Third Military Medical University. Production and hosting by Elsevier B.V. All rights reserved.

[THE BLADDER STONE OF CARDINAL PIETRO BASADONNA (1617-1684) IN THE WORDS OF HIS PHYSICIAN ROMOLO SPEZIOLI (1642-1723)].

PubMed

Santi, Raffaella; Franza, Annarita; Nesi, Gabriella

2014-01-01

At the death of Cardinal Pietro Basadonna in 1684, his personal physician Romolo Spezioli wrote a report describing the disease, circumstances of death and autopsy findings of the illustrious prelate. This document, kept in the Biblioteca Civica at Jesi, is a significant attestation of the medical terminology and diagnostic and therapeutic procedures of the time. Even with the constraints that interpretation of a clinical account dating back over 300 years inevitably imposes, perusal of this report suggests that Cardinal Basadonna's demise could have been due to septic shock, consequent to a urinary infection caused by a bulky bladder stone.

Cavitary Pulmonary Sporotrichosis: Case Report and Literature Review.

PubMed

Rojas, Florencia D; Fernández, Mariana S; Lucchelli, Juan Manuel; Lombardi, Dora; Malet, José; Vetrisano, María Eugenia; Cattana, María Emilia; Sosa, María de Los Ángeles; Giusiano, Gustavo

2017-12-01

A case of cavitary pulmonary sporotrichosis without mucocutaneous involvement caused by Sporothrix schenckii is reported in a sexagenarian woman with a long smoking history. The patient was hospitalized for septic shock with multiorgan failure from a respiratory focus. The diagnosis was delayed due to the fungal etiological agent was not initially considered in the differential diagnosis. A good clinical and radiological evolution was obtained with the antifungal therapy. Occasional cases of primary pulmonary sporotrichosis have been reported in the literature. Due to its low incidence, this is a less-known and underestimated clinical form. Both clinical suspicion and microbiological studies are needed to reach pulmonary sporotrichosis diagnosis.

Experimental Septic Shock: Models and Mechanisms

DTIC Science & Technology

1976-06-14

the renal, hepatic, and pulmonary systems with severe pathophysiological effects on the liver circulation and metabolism (7,9,11,17,18,20). The...was sustained at values between 40 and 60 nmHg. Mean plasm glucose increased for the first several hours, then progressively fell to hypoglycemic...when the state of shock is severe and when death is imminent. On the other hand, hyperglycemia con- comitantly occurring with hypoinsulinemia, termed

Infectious Adverse Events Following Acupuncture: Clinical Progress and Microbiological Etiology.

PubMed

Kim, Youn-Jung; Kim, Sung-Han; Lee, Hak Jin; Kim, Won Young

2018-06-11

We investigated the clinical progress and bacteriological characteristics of infectious adverse events (AEs) following acupuncture and compared patient characteristics between serious and non-serious outcome groups. A retrospective observational study was conducted in 1,174 patients with infectious complications associated with acupuncture at the emergency department (ED) in a tertiary hospital in Korea between 2010 and 2014. Serious outcome was defined as development of septic shock, admission to intensive care unit (ICU) or attaining permanent morbidity. Forty-eight patients had certain causality and cellulitis, necrotizing fasciitis and osteomyelitis were common in order. Among them, 9 patients (18.8%) were categorized into serious outcome group, and they showed devastating outcomes such as septic shock (n = 2), ICU admission (n = 4), and permanent sequelae (n = 5). The serious group had delayed admission to the ED after acupuncture (30.0 [4.0-55.0] vs. 3.0 [1.0-10.0] days, P = 0.023). Methicillin-sensitive Staphylococcus aureus was the most frequently identified microorganism. The patients in the serious group required longer treatment duration (139.0 [49.0-183.5] vs. 14.0 [7.0-34.0] days, P < 0.001) as well as more operation with local (44.4% vs. 10.3%, P = 0.031) or general anaesthesia (33.3% vs. 2.6%, P = 0.017). The infectious AEs after acupuncture may cause serious outcomes. Patients and primary physicians should be aware of the risk of infectious complications and make efforts to prevent them.

The DISPARITY-II study: delays to antibiotic administration in women with severe sepsis or septic shock.

PubMed

Madsen, Tracy E; Napoli, Anthony M

2014-12-01

Early antibiotics reduce mortality in patients with severe sepsis and septic shock. Recent work demonstrated that women experience greater delays to antibiotic administration, but it is unknown if this relationship remains after adjusting for factors such as source of infection. The objective was to investigate whether gender and/or source of infection are associated with delays to antibiotics in patients with severe sepsis or septic shock. This was a retrospective, observational study in an urban academic emergency department and national Surviving Sepsis Campaign (SSC) database study site. Consecutive patients age 18 years and older admitted to intensive care with severe sepsis or septic shock and entered into the SSC database from October 2005 to March 2012 were included. Two trained research assistants, blinded to the primary outcome, used a standardized abstraction form to obtain patient demographic and clinical data, including the Sequential Organ Failure Assessment (SOFA) scores and comorbidities. Time to first antibiotic and presumed source of infection were extracted from the SSC database. Univariate analyses were performed with Pearson chi-square tests and t-tests. Linear regression was performed with time to first antibiotic as the primary outcome. Covariates, chosen a priori by study authors, included age, race, ethnicity, source of infection, SOFA score, and lactate. A total of 771 patients were included. Women were 45.3% of the sample, the mean age was 66 years (95% confidence interval [CI] = 65.1 to 67.5 years), 19.4% were nonwhite, and 8% were Hispanic. Mean time to first antibiotic was 153 minutes (95% CI = 143 to 163 minutes) for men and 184 minutes (95% CI = 171 to 197 minutes) for women (p < 0.001). The urinary tract was source of infection for 35.2% of women (95% CI = 30.2% to 40.3%) versus 23.7% (95% CI = 19.6% to 27.8%) of men. Pneumonia was present in 46.9% of men (95% CI = 42.1% to 51.7%) versus 35.8% (95% CI = 30.8% to 40.8%) of women. The mean time to antibiotics in women was longer than in men (adjusted odds ratio [aOR] = 1.18, 95% CI = 1.07 to 1.30), even after adjusting for age, race, ethnicity, presumed source of infection, SOFA score, and lactate (p = 0.001). Those with pneumonia compared to other infections received antibiotics faster (aOR = 0.73, 95% CI = 0.66 to 0.81). There was no significant association between other sources of infection and time to antibiotics in either univariate or multivariate analysis. Women experience longer delays to initial antibiotics among patients with severe sepsis or septic shock, even after adjusting for infectious source. Pneumonia was associated with shorter times to antibiotic administration. Future research is necessary to investigate contributors to delayed antibiotic administration in women. © 2014 by the Society for Academic Emergency Medicine.

Fluid administration in severe sepsis and septic shock, patterns and outcomes: an analysis of a large national database.

PubMed

Marik, Paul E; Linde-Zwirble, Walter T; Bittner, Edward A; Sahatjian, Jennifer; Hansell, Douglas

2017-05-01

The optimal strategy of fluid resuscitation in the early hours of severe sepsis and septic shock is controversial, with both an aggressive and conservative approach being recommended. We used the 2013 Premier Hospital Discharge database to analyse the administration of fluids on the first ICU day, in 23,513 patients with severe sepsis and septic shock, who were admitted to an ICU from the emergency department. Day 1 fluid was grouped into categories 1 L wide, starting with 1-1.99 L up to ≥9 L, to examine the effect of day 1 fluids on patient mortality. We built binary response models for hospital mortality and the propensity for receiving more than 5 L of fluids on day 1, using patient age and acute conditions present on admission. Patients were grouped by the requirement for mechanical ventilation and the presence or absence of shock. We assessed trends in the difference between actual and expected mortality, in the low fluid range (1-5 L day 1 fluids) and the high fluid range (5 to ≥9 L day 1 fluids) categories, using weighted linear regression controlling for the effects of sample size and variation within the day 1 fluid category. Day 1 fluid administration averaged 4.4 L being lowest in the group with no mechanical ventilation and no shock (3.6 L) and highest (5.4 L) in the group receiving mechanical ventilation and in shock. The administration of day 1 fluids was remarkably consistent on the basis of hospital size, teaching status, rural/urban location, and region of the country. The hospital mortality in the entire cohort was 25.8%, with a mean ICU and hospital length of stay of 5.1 and 9.1 days, respectively. In the entire cohort, low volume resuscitation (1-4.99 L) was associated with a small but significant reduction in mortality, of -0.7% per litre (95% CI -1.0%, -0.4%; p = 0.02). However, in patients receiving high volume resuscitation (5 to ≥9 L), the mortality increased by 2.3% (95% CI 2.0, 2.5%; p = 0.0003) for each additional litre above 5 L. Total hospital cost increased by $999 for each litre of fluid above 5 L (adjusted R 2  = 92.7%, p = 0.005). The mean amount of fluid administered to patients with severe sepsis and septic shock in the USA during the first ICU day is less than that recommended by the Surviving Sepsis Campaign guidelines. The administration of more than 5 L of fluid during the first ICU day is associated with a significantly increased risk of death and significantly higher hospital costs.

[Beta-blockers in septic shock: a review].

PubMed

Vela-Vásquez, R S; Grigorov-Tzenkov, I; Aguilar, J L

2015-02-01

In septic shock, high adrenergic stress is associated with cardiovascular and systemic adverse effects, which can negatively affect the results. Beta-adrenergic receptor block has been shown to be effective in controlling the disproportionate increase in heart rate, maintaining a favorable hemodynamic profile and apparently improving the efficiency of the cardiovascular system in order to maintain tissue perfusion. They have also been shown to modulate favorably catecholamine-induced immunosuppression and to decrease insulin resistance, protein catabolism, and proinflammatory cytokine expression associated with cardiovascular dysfunction. Selective beta-1 blockers appear to provide better results than non-selective blockers, even suggesting a positive impact on mortality. Future clinical trials are still needed to confirm these findings and define the scope of their benefits. Copyright © 2014 Sociedad Española de Anestesiología, Reanimación y Terapéutica del Dolor. Publicado por Elsevier España, S.L.U. All rights reserved.

Sepsis in general surgery: a deadly complication.

PubMed

Moore, Laura J; Moore, Frederick A; Jones, Stephen L; Xu, Jiaqiong; Bass, Barbara L

2009-12-01

Sepsis is a deadly and potentially preventable complication. A better understanding of sepsis in general surgery patients is needed to help direct resources to those patients at highest risk for death from sepsis. We identified risk factors for sepsis in general surgery patients by using the National Surgical Quality Improvement Project database. Analysis of the database identified 3 major risk factors for both the development of sepsis and death from sepsis in general surgery patients. These risk factors are age older than 60 years, need for emergency surgery, and the presence of comorbid conditions. Risk factors for death from sepsis or septic shock in general surgery patients include age older than 60 years, need for emergency surgery, and the presence of preexisting comorbidities. These findings emphasize the need for early recognition through aggressive sepsis screening and rapid implementation of evidence-based interventions for sepsis and septic shock in general surgery patients with these risk factors.

ShockOmics: multiscale approach to the identification of molecular biomarkers in acute heart failure induced by shock.

PubMed

Aletti, Federico; Conti, Costanza; Ferrario, Manuela; Ribas, Vicent; Bollen Pinto, Bernardo; Herpain, Antoine; Post, Emiel; Romay Medina, Eduardo; Barlassina, Cristina; de Oliveira, Eliandre; Pastorelli, Roberta; Tedeschi, Gabriella; Ristagno, Giuseppe; Taccone, Fabio S; Schmid-Schönbein, Geert W; Ferrer, Ricard; De Backer, Daniel; Bendjelid, Karim; Baselli, Giuseppe

2016-01-28

The ShockOmics study (ClinicalTrials.gov identifier NCT02141607) is a multicenter prospective observational trial aimed at identifying new biomarkers of acute heart failure in circulatory shock, by means of a multiscale analysis of blood samples and hemodynamic data from subjects with circulatory shock. Ninety septic shock and cardiogenic shock patients will be recruited in three intensive care units (ICU) (Hôpital Erasme, Université Libre de Bruxelles, Belgium; Hospital Universitari Mutua Terrassa, Spain; Hôpitaux Universitaires de Genève, Switzerland). Hemodynamic signals will be recorded every day for up to seven days from shock diagnosis (time T0). Clinical data and blood samples will be collected for analysis at: i) T1 < 16 h from T0; ii) T2 = 48 h after T0; iii) T3 = day 7 or before discharge or before discontinuation of therapy in case of fatal outcome; iv) T4 = day 100. The inclusion criteria are: shock, Sequential Organ Failure Assessment (SOFA) score > 5 and lactate levels ≥ 2 mmol/L. The exclusion criteria are: expected death within 24 h since ICU admission; > 4 units of red blood cells or >1 fresh frozen plasma transfused; active hematological malignancy; metastatic cancer; chronic immunodepression; pre-existing end stage renal disease requiring renal replacement therapy; recent cardiac surgery; Child-Pugh C cirrhosis; terminal illness. Enrollment will be preceded by the signature of the Informed Consent by the patient or his/her relatives and by the physician in charge. Three non-shock control groups will be included in the study: a) healthy blood donors (n = 5); b) septic patients (n = 10); c) acute myocardial infarction or patients with prolonged acute arrhythmia (n = 10). The hemodynamic data will be downloaded from the ICU monitors by means of dedicated software. The blood samples will be utilized for transcriptomics, proteomics and metabolomics ("-omics") analyses. ShockOmics will provide new insights into the pathophysiological mechanisms underlying shock as well as new biomarkers for the timely diagnosis of cardiac dysfunction in shock and quantitative indices for assisting the therapeutic management of shock patients.

CytoSorb, a novel therapeutic approach for patients with septic shock: a case report.

PubMed

Hinz, Burkhard; Jauch, Oliver; Noky, Toralf; Friesecke, Sigrun; Abel, Peter; Kaiser, Rolf

2015-08-01

Hemoadsorption using CytoSorb has gained attention as a potential immunotherapy to control systemic inflammation and sepsis. We report on a patient with septic shock, successfully treated with CytoSorb therapy. A 72-year-old male with periodically recurring infectious episodes was admitted with the suspicion of urosepsis. In the following hours his hemodynamic situation deteriorated markedly, exhibiting respiratory-metabolic acidosis, elevated inflammatory marker plasma levels, a severely disturbed coagulation, increased retention parameters, liver dysfunction, and confirmation of bacteria and leucocytes in urine. After admission to the ICU in a state of septic shock the patient received renal support with additional hemoadsorption using CytoSorb. Three CytoSorb sessions were run during the following days. The first and consecutive second session resulted in a reduction of procalcitonin, C-reactive protein and bilirubin and a markedly reduced need for vasopressors while hemodynamics improved significantly (i.e., cardiac index, extravascular lung water). Due to a recurring inflammatory "second hit" episode, another session with CytoSorb was run, resulting in a marked decrease in leukocytosis and liver (dys)function parameters. The rapid hemodynamic stabilization with reduction of vasopressor needs within hours and reduction of the capillary leakage as well as a quick reduction in infection markers were the main conclusions drawn from the use of CytoSorb in this patient. Additionally, treatment appeared to be safe and was well tolerated. Despite the promising results of CytoSorb application in this patient, further studies are necessary to elucidate to what extent these favorable consequences are attributable to the adsorber itself.

Analysis and modelling of septic shock microarray data using Singular Value Decomposition.

PubMed

Allanki, Srinivas; Dixit, Madhulika; Thangaraj, Paul; Sinha, Nandan Kumar

2017-06-01

Being a high throughput technique, enormous amounts of microarray data has been generated and there arises a need for more efficient techniques of analysis, in terms of speed and accuracy. Finding the differentially expressed genes based on just fold change and p-value might not extract all the vital biological signals that occur at a lower gene expression level. Besides this, numerous mathematical models have been generated to predict the clinical outcome from microarray data, while very few, if not none, aim at predicting the vital genes that are important in a disease progression. Such models help a basic researcher narrow down and concentrate on a promising set of genes which leads to the discovery of gene-based therapies. In this article, as a first objective, we have used the lesser known and used Singular Value Decomposition (SVD) technique to build a microarray data analysis tool that works with gene expression patterns and intrinsic structure of the data in an unsupervised manner. We have re-analysed a microarray data over the clinical course of Septic shock from Cazalis et al. (2014) and have shown that our proposed analysis provides additional information compared to the conventional method. As a second objective, we developed a novel mathematical model that predicts a set of vital genes in the disease progression that works by generating samples in the continuum between health and disease, using a simple normal-distribution-based random number generator. We also verify that most of the predicted genes are indeed related to septic shock. Copyright © 2017 Elsevier Inc. All rights reserved.

Thrombopoietin modulates cardiac contractility in vitro and contributes to myocardial depressing activity of septic shock serum.

PubMed

Lupia, Enrico; Spatola, Tiziana; Cuccurullo, Alessandra; Bosco, Ornella; Mariano, Filippo; Pucci, Angela; Ramella, Roberta; Alloatti, Giuseppe; Montrucchio, Giuseppe

2010-09-01

Thrombopoietin (TPO) is a humoral growth factor that has been shown to increase platelet activation in response to several agonists. Patients with sepsis have increased circulating TPO levels, which may enhance platelet activation, potentially participating to the pathogenesis of multi-organ failure. Aim of this study was to investigate whether TPO affects myocardial contractility and participates to depress cardiac function during sepsis. We showed the expression of the TPO receptor c-Mpl on myocardial cells and tissue by RT-PCR, immunofluorescence and western blotting. We then evaluated the effect of TPO on the contractile function of rat papillary muscle and isolated heart. TPO did not change myocardial contractility in basal conditions, but, when followed by epinephrine (EPI) stimulation, it blunted the enhancement of contractile force induced by EPI both in papillary muscle and isolated heart. An inhibitor of TPO prevented TPO effect on cardiac inotropy. Treatment of papillary muscle with pharmacological inhibitors of phosphatidylinositol 3-kinase, NO synthase, and guanilyl cyclase abolished TPO effect, indicating NO as the final mediator. We finally studied the role of TPO in the negative inotropic effect exerted by human septic shock (HSS) serum and TPO cooperation with TNF-alpha and IL-1beta. Pre-treatment with the TPO inhibitor prevented the decrease in contractile force induced by HSS serum. Moreover, TPO significantly amplified the negative inotropic effect induced by TNF-alpha and IL-1beta in papillary muscle. In conclusion, TPO negatively modulates cardiac inotropy in vitro and contributes to the myocardial depressing activity of septic shock serum.

Loss of vagal tone aggravates systemic inflammation and cardiac impairment in endotoxemic rats.

PubMed

Schulte, Astrid; Lichtenstern, Christoph; Henrich, Michael; Weigand, Markus A; Uhle, Florian

2014-05-15

During the course of sepsis, often myocardial depression with hemodynamic impairment occurs. Acetylcholine, the main transmitter of the parasympathetic Nervus vagus, has been shown to be of importance for the transmission of signals within the immune system and also for a variety of other functions throughout the organism. Hypothesizing a potential correlation between this dysfunction and hemodynamic impairment, we wanted to assess the impact of vagal stimulation on myocardial inflammation and function in a rat model of lipopolysaccharide (LPS)-induced septic shock. As the myocardial tissue is (sparsely) innervated by the N. vagus, there might be an important anti-inflammatory effect in the heart, inhibiting proinflammatory gene expression in cardiomyocytes and improving cardiac function. We performed stimulation of the right cervical branch of the N. vagus in vagotomized, endotoxemic (1 mg/kg body weight LPS, intravenously) rats. Hemodynamic parameters were assessed over time using a left ventricular pressure-volume catheter. After the experiments, hearts and blood plasma were collected, and the expression of proinflammatory cytokines was measured using quantitative reverse transcription polymerase chain reaction and enzyme-linked immunosorbent assay. After vagotomy, the inflammatory response was aggravated, measurable by elevated cytokine levels in plasma and ventricular tissue. In concordance, cardiac impairment during septic shock was pronounced in these animals. To reverse both hemodynamic and immunologic effects of diminished vagal tone, even a brief stimulation of the N. vagus was enough during initial LPS infusion. Overall, the N. vagus might play a major role in maintaining hemodynamic stability and cardiac immune homeostasis during septic shock. Copyright © 2014 Elsevier Inc. All rights reserved.

Liberal Versus Restrictive Transfusion Strategy in Critically Ill Oncologic Patients: The Transfusion Requirements in Critically Ill Oncologic Patients Randomized Controlled Trial.

PubMed

Bergamin, Fabricio S; Almeida, Juliano P; Landoni, Giovanni; Galas, Filomena R B G; Fukushima, Julia T; Fominskiy, Evgeny; Park, Clarice H L; Osawa, Eduardo A; Diz, Maria P E; Oliveira, Gisele Q; Franco, Rafael A; Nakamura, Rosana E; Almeida, Elisangela M; Abdala, Edson; Freire, Maristela P; Filho, Roberto K; Auler, Jose Otavio C; Hajjar, Ludhmila A

2017-05-01

To assess whether a restrictive strategy of RBC transfusion reduces 28-day mortality when compared with a liberal strategy in cancer patients with septic shock. Single center, randomized, double-blind controlled trial. Teaching hospital. Adult cancer patients with septic shock in the first 6 hours of ICU admission. Patients were randomized to the liberal (hemoglobin threshold, < 9 g/dL) or to the restrictive strategy (hemoglobin threshold, < 7 g/dL) of RBC transfusion during ICU stay. Patients were randomized to the liberal (n = 149) or to the restrictive transfusion strategy (n = 151) group. Patients in the liberal group received more RBC units than patients in the restrictive group (1 [0-3] vs 0 [0-2] unit; p < 0.001). At 28 days after randomization, mortality rate in the liberal group (primary endpoint of the study) was 45% (67 patients) versus 56% (84 patients) in the restrictive group (hazard ratio, 0.74; 95% CI, 0.53-1.04; p = 0.08) with no differences in ICU and hospital length of stay. At 90 days after randomization, mortality rate in the liberal group was lower (59% vs 70%) than in the restrictive group (hazard ratio, 0.72; 95% CI, 0.53-0.97; p = 0.03). We observed a survival trend favoring a liberal transfusion strategy in patients with septic shock when compared with the restrictive strategy. These results went in the opposite direction of the a priori hypothesis and of other trials in the field and need to be confirmed.

A Computable Definition of Sepsis Facilitates Screening and Performance Improvement Tracking.

PubMed

Alessi, Lauren J; Warmus, Holly R; Schaffner, Erin K; Kantawala, Sajel; Carcillo, Joseph; Rosen, Johanna; Horvat, Christopher M

2018-03-01

Sepsis kills almost 5,000 children annually, accounting for 16% of pediatric health care spending in the United States. We sought to identify sepsis within the Electronic Health Record (EHR) of a quaternary children's hospital to characterize disease incidence, improve recognition and response, and track performance metrics. Methods are organized in a plan-do-study-act cycle. During the "plan" phase, electronic definitions of sepsis (blood culture and antibiotic within 24 hours) and septic shock (sepsis plus vasoactive medication) were created to establish benchmark data and track progress with statistical process control. The performance of a screening tool was evaluated in the emergency department. During the "do" phase, a novel inpatient workflow is being piloted, which involves regular sepsis screening by nurses using the tool, and a regimented response to high risk patients. Screening tool use in the emergency department reduced time to antibiotics (Fig. 1). Of the 6,159 admissions, EHR definitions identified 1,433 (23.3%) between July and December 2016 with sepsis, of which 159 (11.1%) had septic shock. Hospital mortality for all sepsis patients was 2.2% and 15.7% for septic shock (Table 1). These findings approximate epidemiologic studies of sepsis and severe sepsis, which report a prevalence range of 0.45-8.2% and mortality range of 8.2-25% (Table 2). 1-5 . Implementation of a sepsis screening tool is associated with improved performance. The prevalence of sepsis conditions identified with electronic definitions approximates the epidemiologic landscape characterized by other point-prevalence and administrative studies, providing face validity to this approach, and proving useful for tracking performance improvement.

Prescribed targets for titration of vasopressors in septic shock: a retrospective cohort study

PubMed Central

St-Arnaud, Charles; Éthier, Jean-François; Hamielec, Cindy; Bersten, Andrew; Guyatt, Gordon; Meade, Maureen; Zhou, Qi; Leclair, Marc-André; Patel, Alpesh

2013-01-01

Background Without robust clinical evidence to guide titration of vasopressors in septic shock, it is unclear how dosing of these potent medications occurs. We sought to measure the proportion of vasopressor prescriptions for septic shock that were missing explicit targets and to describe the targets that we identified. Methods We conducted a multicentre, retrospective cohort study involving 9 intensive care units (ICUs) located at 3 academic hospitals in Canada and Australia. We reviewed charts of consecutive patients aged 18 years or older who were admitted to the ICU for a presumptive diagnosis of sepsis. Other inclusion criteria were hypotension (systolic arterial pressure ≤ 90 mm Hg or mean arterial pressure [MAP] ≤ 65 mm Hg) and continuous infusion of vasopressors for at least 1 hour within the initial 48 hours of ICU stay, the period of observation for this study. Results We included data from 369 patient charts. At least 1 target was specified in 99% of charts. The most common targets were MAP measurements (73%). The median initial MAP target was 65 (range 55–90) mm Hg. In multivariable regression models, hospital site and older age of the patient, but not comorbidities of the patient, were associated with MAP targets. In 40% of patients, the treating team modified the initial target at least once. Interpretation This study suggests that an explicit blood pressure target accompanies nearly every vasopressor prescription and that patient characteristics have little influence on its value. Identification of a titration strategy that will maximize benefit and minimize harm constitutes a research priority. PMID:25077114

A sense oligonucleotide to inducible nitric oxide synthase mRNA increases the survival rate of rats in septic shock.

PubMed

Okuyama, Tetsuya; Nakatake, Richi; Kaibori, Masaki; Okumura, Tadayoshi; Kon, Masanori; Nishizawa, Mikio

2018-01-30

Natural antisense transcripts (asRNAs) that do not encode proteins are transcribed from rat, mouse, and human genes, encoding inducible nitric oxide synthase (iNOS), which catalyzes the production of the inflammatory mediator nitric oxide (NO). In septic shock, NO is excessively produced in hepatocytes and macrophages. The iNOS asRNA interacts with and stabilizes iNOS mRNA. We found that single-stranded 'sense' oligonucleotides corresponding to the iNOS mRNA sequence reduced iNOS mRNA levels by interfering with the mRNA-asRNA interactions in rat hepatocytes. The iNOS sense oligonucleotides that were substituted with phosphorothioate bonds and locked nucleic acids efficiently decreased the levels of iNOS mRNA and iNOS protein. In this study, the gene expression patterns in the livers of two endotoxemia model rats with acute liver failure were compared. Next, we optimized the sequence and modification of the iNOS sense oligonucleotides in interleukin 1β-treated rat hepatocytes. When a sense oligonucleotide was simultaneously administered with d-galactosamine and bacterial lipopolysaccharide (LPS) to rats, their survival rate significantly increased compared to the rats administered d-galactosamine and LPS alone. In the livers of the sense oligonucleotide-administered rats, apoptosis in the hepatocytes markedly decreased. These results suggest that natural antisense transcript-targeted regulation technology using iNOS sense oligonucleotides may be used to treat human inflammatory diseases, such as sepsis and septic shock. Copyright © 2017 Elsevier Inc. All rights reserved.

Pharmaceutical Approval Update.

PubMed

Kaufman, Michele B

2018-03-01

Zoster vaccine recombinant, adjuvanted (Shingrix) for the prevention of shingles in adults; angiotensin II injection (Giapreza) to increase blood pressure in adults with septic or other distributive shock; and glycopyrrolate inhalation solution (Lonhala Magnair) for the maintenance treatment of chronic obstructive pulmonary disease.

Suppressive effects of lysozyme on polyphosphate-mediated vascular inflammatory responses

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

Chung, Jiwoo; Ku, Sae-Kwang; Lee, Suyeon

Lysozyme, found in relatively high concentration in blood, saliva, tears, and milk, protects us from the ever-present danger of bacterial infection. Previous studies have reported proinflammatory responses of endothelial cells to the release of polyphosphate(PolyP). In this study, we examined the anti-inflammatory responses and mechanisms of lysozyme and its effects on PolyP-induced septic activities in human umbilical vein endothelial cells (HUVECs) and mice. The survival rates, septic biomarker levels, behavior of human neutrophils, and vascular permeability were determined in PolyP-activated HUVECs and mice. Lysozyme suppressed the PolyP-mediated vascular barrier permeability, upregulation of inflammatory biomarkers, adhesion/migration of leukocytes, and activation and/ormore » production of nuclear factor-κB, tumor necrosis factor-α, and interleukin-6. Furthermore, lysozyme demonstrated protective effects on PolyP-mediated lethal death and the levels of the related septic biomarkers. Therefore, these results indicated the therapeutic potential of lysozyme on various systemic inflammatory diseases, such as sepsis or septic shock. -- Highlights: •PolyP is shown to be an important mediator of vascular inflammation. •Lysozyme inhibited PolyP-mediated hyperpermeability. •Lysozyme inhibited PolyP-mediated septic response. •Lysozyme reduced PolyP-induced septic mortality.« less

A randomized trial of protocol-based care for early septic shock.

PubMed

Yealy, Donald M; Kellum, John A; Huang, David T; Barnato, Amber E; Weissfeld, Lisa A; Pike, Francis; Terndrup, Thomas; Wang, Henry E; Hou, Peter C; LoVecchio, Frank; Filbin, Michael R; Shapiro, Nathan I; Angus, Derek C

2014-05-01

In a single-center study published more than a decade ago involving patients presenting to the emergency department with severe sepsis and septic shock, mortality was markedly lower among those who were treated according to a 6-hour protocol of early goal-directed therapy (EGDT), in which intravenous fluids, vasopressors, inotropes, and blood transfusions were adjusted to reach central hemodynamic targets, than among those receiving usual care. We conducted a trial to determine whether these findings were generalizable and whether all aspects of the protocol were necessary. In 31 emergency departments in the United States, we randomly assigned patients with septic shock to one of three groups for 6 hours of resuscitation: protocol-based EGDT; protocol-based standard therapy that did not require the placement of a central venous catheter, administration of inotropes, or blood transfusions; or usual care. The primary end point was 60-day in-hospital mortality. We tested sequentially whether protocol-based care (EGDT and standard-therapy groups combined) was superior to usual care and whether protocol-based EGDT was superior to protocol-based standard therapy. Secondary outcomes included longer-term mortality and the need for organ support. We enrolled 1341 patients, of whom 439 were randomly assigned to protocol-based EGDT, 446 to protocol-based standard therapy, and 456 to usual care. Resuscitation strategies differed significantly with respect to the monitoring of central venous pressure and oxygen and the use of intravenous fluids, vasopressors, inotropes, and blood transfusions. By 60 days, there were 92 deaths in the protocol-based EGDT group (21.0%), 81 in the protocol-based standard-therapy group (18.2%), and 86 in the usual-care group (18.9%) (relative risk with protocol-based therapy vs. usual care, 1.04; 95% confidence interval [CI], 0.82 to 1.31; P=0.83; relative risk with protocol-based EGDT vs. protocol-based standard therapy, 1.15; 95% CI, 0.88 to 1.51; P=0.31). There were no significant differences in 90-day mortality, 1-year mortality, or the need for organ support. In a multicenter trial conducted in the tertiary care setting, protocol-based resuscitation of patients in whom septic shock was diagnosed in the emergency department did not improve outcomes. (Funded by the National Institute of General Medical Sciences; ProCESS ClinicalTrials.gov number, NCT00510835.).

Mortality Predictors in Renal Transplant Recipients with Severe Sepsis and Septic Shock

PubMed Central

de Carvalho, Mônica Andrade; Freitas, Flávio Geraldo Rezende; Silva Junior, Hélio Tedesco; Bafi, Antônio Toneti; Machado, Flávia Ribeiro; Pestana, José Osmar Medina

2014-01-01

Introduction The growing number of renal transplant recipients in a sustained immunosuppressive state is a factor that can contribute to increased incidence of sepsis. However, relatively little is known about sepsis in this population. The aim of this single-center study was to evaluate the factors associated with hospital mortality in renal transplant patients admitted to the intensive care unit (ICU) with severe sepsis and septic shock. Methods Patient demographics and transplant-related and ICU stay data were retrospectively collected. Multiple logistic regression was conducted to identify the independent risk factors associated with hospital mortality. Results A total of 190 patients were enrolled, 64.2% of whom received kidneys from deceased donors. The mean patient age was 51±13 years (males, 115 [60.5%]), and the median APACHE II was 20 (16–23). The majority of patients developed sepsis late after the renal transplantation (2.1 [0.6–2.3] years). The lung was the most common infection site (59.5%). Upon ICU admission, 16.4% of the patients had ≤1 systemic inflammatory response syndrome criteria. Among the patients, 61.5% presented with ≥2 organ failures at admission, and 27.9% experienced septic shock within the first 24 hours of ICU admission. The overall hospital mortality rate was 38.4%. In the multivariate analysis, the independent determinants of hospital mortality were male gender (OR = 5.9; 95% CI, 1.7–19.6; p = 0.004), delta SOFA 24 h (OR = 1.7; 95% CI, 1.2–2.3; p = 0.001), mechanical ventilation (OR = 30; 95% CI, 8.8–102.2; p<0.0001), hematologic dysfunction (OR = 6.8; 95% CI, 2.0–22.6; p = 0.002), admission from the ward (OR = 3.4; 95% CI, 1.2–9.7; p = 0.02) and acute kidney injury stage 3 (OR = 5.7; 95% CI,1.9–16.6; p = 0.002). Conclusions Hospital mortality in renal transplant patients with severe sepsis and septic shock was associated with male gender, admission from the wards, worse SOFA scores on the first day and the presence of hematologic dysfunction, mechanical ventilation or advanced graft dysfunction. PMID:25369197

The accuracy of pulse oximetry in emergency department patients with severe sepsis and septic shock: a retrospective cohort study.

PubMed

Wilson, Ben J; Cowan, Hamish J; Lord, Jason A; Zuege, Dan J; Zygun, David A

2010-05-05

Pulse oximetry is routinely used to continuously and noninvasively monitor arterial oxygen saturation (SaO2) in critically ill patients. Although pulse oximeter oxygen saturation (SpO2) has been studied in several patient populations, including the critically ill, its accuracy has never been studied in emergency department (ED) patients with severe sepsis and septic shock. Sepsis results in characteristic microcirculatory derangements that could theoretically affect pulse oximeter accuracy. The purposes of the present study were twofold: 1) to determine the accuracy of pulse oximetry relative to SaO2 obtained from ABG in ED patients with severe sepsis and septic shock, and 2) to assess the impact of specific physiologic factors on this accuracy. This analysis consisted of a retrospective cohort of 88 consecutive ED patients with severe sepsis who had a simultaneous arterial blood gas and an SpO2 value recorded. Adult ICU patients that were admitted from any Calgary Health Region adult ED with a pre-specified, sepsis-related admission diagnosis between October 1, 2005 and September 30, 2006, were identified. Accuracy (SpO2 - SaO2) was analyzed by the method of Bland and Altman. The effects of hypoxemia, acidosis, hyperlactatemia, anemia, and the use of vasoactive drugs on bias were determined. The cohort consisted of 88 subjects, with a mean age of 57 years (19 - 89). The mean difference (SpO2 - SaO2) was 2.75% and the standard deviation of the differences was 3.1%. Subgroup analysis demonstrated that hypoxemia (SaO2 < 90) significantly affected pulse oximeter accuracy. The mean difference was 4.9% in hypoxemic patients and 1.89% in non-hypoxemic patients (p < 0.004). In 50% (11/22) of cases in which SpO2 was in the 90-93% range the SaO2 was <90%. Though pulse oximeter accuracy was not affected by acidoisis, hyperlactatementa, anemia or vasoactive drugs, these factors worsened precision. Pulse oximetry overestimates ABG-determined SaO2 by a mean of 2.75% in emergency department patients with severe sepsis and septic shock. This overestimation is exacerbated by the presence of hypoxemia. When SaO2 needs to be determined with a high degree of accuracy arterial blood gases are recommended.

International pediatric sepsis consensus conference: definitions for sepsis and organ dysfunction in pediatrics.

PubMed

Goldstein, Brahm; Giroir, Brett; Randolph, Adrienne

2005-01-01

Although general definitions of the sepsis continuum have been published for adults, no such work has been done for the pediatric population. Physiologic and laboratory variables used to define the systemic inflammatory response syndrome (SIRS) and organ dysfunction require modification for the developmental stages of children. An international panel of 20 experts in sepsis and clinical research from five countries (Canada, France, Netherlands, United Kingdom, and United States) was convened to modify the published adult consensus definitions of infection, sepsis, severe sepsis, septic shock, and organ dysfunction for children. Consensus conference. This document describes the issues surrounding consensus on four major questions addressed at the meeting: a) How should the pediatric age groups affected by sepsis be delineated? b) What are the specific definitions of pediatric SIRS, infection, sepsis, severe sepsis, and septic shock? c) What are the specific definitions of pediatric organ failure and the validity of pediatric organ failure scores? d) What are the appropriate study populations and study end points required to successfully conduct clinical trials in pediatric sepsis? Five subgroups first met separately and then together to evaluate the following areas: signs and symptoms of sepsis, cell markers, cytokines, microbiological data, and coagulation variables. All conference participants approved the final draft of the proceedings of the meeting. Conference attendees modified the current criteria used to define SIRS and sepsis in adults to incorporate pediatric physiologic variables appropriate for the following subcategories of children: newborn, neonate, infant, child, and adolescent. In addition, the SIRS definition was modified so that either criteria for fever or white blood count had to be met. We also defined various organ dysfunction categories, severe sepsis, and septic shock specifically for children. Although no firm conclusion was made regarding a single appropriate study end point, a novel nonmortality end point, organ failure-free days, was considered optimal for pediatric clinical trials given the relatively low incidence of mortality in pediatric sepsis compared with adult populations. We modified the adult SIRS criteria for children. In addition, we revised definitions of severe sepsis and septic shock for the pediatric population. Our goal is for these first-generation pediatric definitions and criteria to facilitate the performance of successful clinical studies in children with sepsis.

Effect of dextran-70 on outcome in severe sepsis; a propensity-score matching study.

PubMed

Bentzer, Peter; Broman, Marcus; Kander, Thomas

2017-07-06

Albumin may be beneficial in patients with septic shock but availability is limited and cost is high. The objective of the present study was to investigate if the use of dextran-70 in addition to albumin and crystalloids influences organ failure or mortality in patients with severe sepsis or septic shock. Patients with severe sepsis or septic shock (n = 778) admitted to a university hospital intensive care unit (ICU) between 2007 and 2015 that received dextran-70 during resuscitation were propensity score matched to controls at a 1 to 1 ratio. Outcomes were highest acute kidney injury network (AKIN) score the first 10 days in the ICU, use of renal replacement therapy, days alive and free of organ support the first 28 days after admission to ICU, mortality and events of severe bleeding. Outcomes were assessed using paired hypothesis testing. Propensity score matching resulted in two groups of patients with 245 patients in each group. The dextran group received a median volume of 1483 ml (interquartile range, 1000-2000 ml) of dextran-70 during the ICU stay. Highest AKIN score did not differ between the control- and dextran groups (1 (0-3) versus 2 (0-3), p = 0.06). Incidence of renal replacement therapy in the control- and dextran groups was similar (19% versus 22%, p = 0.42, absolute risk reduction -2.9% [95% CI: -9.9 to 4.2]). Days alive and free of renal replacement, vasopressors and mechanical ventilation did not differ between the control- and dextran groups. The 180-day mortality was 50.2% in the control group and 41.6% in the dextran group (p = 0.046, absolute risk reduction 8.6% [-0.2 to 17.4]). Fraction of patients experiencing a severe bleeding in the first 10 days in the ICU did not differ between the control and dextran groups (14% versus 18%, p = 0.21). There is a paucity of high quality data regarding effects of dextran solutions on outcome in sepsis. In the present study, propensity score matching was used in attempt to reduce bias. No evidence to support a detrimental effect of dextran-70 on mortality or on organ failures in patients with severe sepsis or septic shock could be detected.

Surviving Sepsis Campaign: international guidelines for management of severe sepsis and septic shock, 2012.

PubMed

Dellinger, R P; Levy, Mitchell M; Rhodes, Andrew; Annane, Djillali; Gerlach, Herwig; Opal, Steven M; Sevransky, Jonathan E; Sprung, Charles L; Douglas, Ivor S; Jaeschke, Roman; Osborn, Tiffany M; Nunnally, Mark E; Townsend, Sean R; Reinhart, Konrad; Kleinpell, Ruth M; Angus, Derek C; Deutschman, Clifford S; Machado, Flavia R; Rubenfeld, Gordon D; Webb, Steven; Beale, Richard J; Vincent, Jean-Louis; Moreno, Rui

2013-02-01

To provide an update to the "Surviving Sepsis Campaign Guidelines for Management of Severe Sepsis and Septic Shock," last published in 2008. A consensus committee of 68 international experts representing 30 international organizations was convened. Nominal groups were assembled at key international meetings (for those committee members attending the conference). A formal conflict of interest policy was developed at the onset of the process and enforced throughout. The entire guidelines process was conducted independent of any industry funding. A stand-alone meeting was held for all subgroup heads, co- and vice-chairs, and selected individuals. Teleconferences and electronic-based discussion among subgroups and among the entire committee served as an integral part of the development. The authors were advised to follow the principles of the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system to guide assessment of quality of evidence from high (A) to very low (D) and to determine the strength of recommendations as strong (1) or weak (2). The potential drawbacks of making strong recommendations in the presence of low-quality evidence were emphasized. Recommendations were classified into three groups: (1) those directly targeting severe sepsis; (2) those targeting general care of the critically ill patient and considered high priority in severe sepsis; and (3) pediatric considerations. Key recommendations and suggestions, listed by category, include: early quantitative resuscitation of the septic patient during the first 6 h after recognition (1C); blood cultures before antibiotic therapy (1C); imaging studies performed promptly to confirm a potential source of infection (UG); administration of broad-spectrum antimicrobials therapy within 1 h of the recognition of septic shock (1B) and severe sepsis without septic shock (1C) as the goal of therapy; reassessment of antimicrobial therapy daily for de-escalation, when appropriate (1B); infection source control with attention to the balance of risks and benefits of the chosen method within 12 h of diagnosis (1C); initial fluid resuscitation with crystalloid (1B) and consideration of the addition of albumin in patients who continue to require substantial amounts of crystalloid to maintain adequate mean arterial pressure (2C) and the avoidance of hetastarch formulations (1B); initial fluid challenge in patients with sepsis-induced tissue hypoperfusion and suspicion of hypovolemia to achieve a minimum of 30 mL/kg of crystalloids (more rapid administration and greater amounts of fluid may be needed in some patients (1C); fluid challenge technique continued as long as hemodynamic improvement is based on either dynamic or static variables (UG); norepinephrine as the first-choice vasopressor to maintain mean arterial pressure ≥65 mmHg (1B); epinephrine when an additional agent is needed to maintain adequate blood pressure (2B); vasopressin (0.03 U/min) can be added to norepinephrine to either raise mean arterial pressure to target or to decrease norepinephrine dose but should not be used as the initial vasopressor (UG); dopamine is not recommended except in highly selected circumstances (2C); dobutamine infusion administered or added to vasopressor in the presence of (a) myocardial dysfunction as suggested by elevated cardiac filling pressures and low cardiac output, or (b) ongoing signs of hypoperfusion despite achieving adequate intravascular volume and adequate mean arterial pressure (1C); avoiding use of intravenous hydrocortisone in adult septic shock patients if adequate fluid resuscitation and vasopressor therapy are able to restore hemodynamic stability (2C); hemoglobin target of 7-9 g/dL in the absence of tissue hypoperfusion, ischemic coronary artery disease, or acute hemorrhage (1B); low tidal volume (1A) and limitation of inspiratory plateau pressure (1B) for acute respiratory distress syndrome (ARDS); application of at least a minimal amount of positive end-expiratory pressure (PEEP) in ARDS (1B); higher rather than lower level of PEEP for patients with sepsis-induced moderate or severe ARDS (2C); recruitment maneuvers in sepsis patients with severe refractory hypoxemia due to ARDS (2C); prone positioning in sepsis-induced ARDS patients with a PaO (2)/FiO (2) ratio of ≤100 mm Hg in facilities that have experience with such practices (2C); head-of-bed elevation in mechanically ventilated patients unless contraindicated (1B); a conservative fluid strategy for patients with established ARDS who do not have evidence of tissue hypoperfusion (1C); protocols for weaning and sedation (1A); minimizing use of either intermittent bolus sedation or continuous infusion sedation targeting specific titration endpoints (1B); avoidance of neuromuscular blockers if possible in the septic patient without ARDS (1C); a short course of neuromuscular blocker (no longer than 48 h) for patients with early ARDS and a PaO (2)/FI O (2) <150 mm Hg (2C); a protocolized approach to blood glucose management commencing insulin dosing when two consecutive blood glucose levels are >180 mg/dL, targeting an upper blood glucose ≤180 mg/dL (1A); equivalency of continuous veno-venous hemofiltration or intermittent hemodialysis (2B); prophylaxis for deep vein thrombosis (1B); use of stress ulcer prophylaxis to prevent upper gastrointestinal bleeding in patients with bleeding risk factors (1B); oral or enteral (if necessary) feedings, as tolerated, rather than either complete fasting or provision of only intravenous glucose within the first 48 h after a diagnosis of severe sepsis/septic shock (2C); and addressing goals of care, including treatment plans and end-of-life planning (as appropriate) (1B), as early as feasible, but within 72 h of intensive care unit admission (2C). Recommendations specific to pediatric severe sepsis include: therapy with face mask oxygen, high flow nasal cannula oxygen, or nasopharyngeal continuous PEEP in the presence of respiratory distress and hypoxemia (2C), use of physical examination therapeutic endpoints such as capillary refill (2C); for septic shock associated with hypovolemia, the use of crystalloids or albumin to deliver a bolus of 20 mL/kg of crystalloids (or albumin equivalent) over 5-10 min (2C); more common use of inotropes and vasodilators for low cardiac output septic shock associated with elevated systemic vascular resistance (2C); and use of hydrocortisone only in children with suspected or proven "absolute"' adrenal insufficiency (2C). Strong agreement existed among a large cohort of international experts regarding many level 1 recommendations for the best care of patients with severe sepsis. Although a significant number of aspects of care have relatively weak support, evidence-based recommendations regarding the acute management of sepsis and septic shock are the foundation of improved outcomes for this important group of critically ill patients.

Surviving sepsis campaign: international guidelines for management of severe sepsis and septic shock: 2012.

PubMed

Dellinger, R Phillip; Levy, Mitchell M; Rhodes, Andrew; Annane, Djillali; Gerlach, Herwig; Opal, Steven M; Sevransky, Jonathan E; Sprung, Charles L; Douglas, Ivor S; Jaeschke, Roman; Osborn, Tiffany M; Nunnally, Mark E; Townsend, Sean R; Reinhart, Konrad; Kleinpell, Ruth M; Angus, Derek C; Deutschman, Clifford S; Machado, Flavia R; Rubenfeld, Gordon D; Webb, Steven A; Beale, Richard J; Vincent, Jean-Louis; Moreno, Rui

2013-02-01

To provide an update to the "Surviving Sepsis Campaign Guidelines for Management of Severe Sepsis and Septic Shock," last published in 2008. A consensus committee of 68 international experts representing 30 international organizations was convened. Nominal groups were assembled at key international meetings (for those committee members attending the conference). A formal conflict of interest policy was developed at the onset of the process and enforced throughout. The entire guidelines process was conducted independent of any industry funding. A stand-alone meeting was held for all subgroup heads, co- and vice-chairs, and selected individuals. Teleconferences and electronic-based discussion among subgroups and among the entire committee served as an integral part of the development. The authors were advised to follow the principles of the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system to guide assessment of quality of evidence from high (A) to very low (D) and to determine the strength of recommendations as strong (1) or weak (2). The potential drawbacks of making strong recommendations in the presence of low-quality evidence were emphasized. Some recommendations were ungraded (UG). Recommendations were classified into three groups: 1) those directly targeting severe sepsis; 2) those targeting general care of the critically ill patient and considered high priority in severe sepsis; and 3) pediatric considerations. Key recommendations and suggestions, listed by category, include: early quantitative resuscitation of the septic patient during the first 6 hrs after recognition (1C); blood cultures before antibiotic therapy (1C); imaging studies performed promptly to confirm a potential source of infection (UG); administration of broad-spectrum antimicrobials therapy within 1 hr of recognition of septic shock (1B) and severe sepsis without septic shock (1C) as the goal of therapy; reassessment of antimicrobial therapy daily for de-escalation, when appropriate (1B); infection source control with attention to the balance of risks and benefits of the chosen method within 12 hrs of diagnosis (1C); initial fluid resuscitation with crystalloid (1B) and consideration of the addition of albumin in patients who continue to require substantial amounts of crystalloid to maintain adequate mean arterial pressure (2C) and the avoidance of hetastarch formulations (1C); initial fluid challenge in patients with sepsis-induced tissue hypoperfusion and suspicion of hypovolemia to achieve a minimum of 30 mL/kg of crystalloids (more rapid administration and greater amounts of fluid may be needed in some patients) (1C); fluid challenge technique continued as long as hemodynamic improvement, as based on either dynamic or static variables (UG); norepinephrine as the first-choice vasopressor to maintain mean arterial pressure ≥ 65 mm Hg (1B); epinephrine when an additional agent is needed to maintain adequate blood pressure (2B); vasopressin (0.03 U/min) can be added to norepinephrine to either raise mean arterial pressure to target or to decrease norepinephrine dose but should not be used as the initial vasopressor (UG); dopamine is not recommended except in highly selected circumstances (2C); dobutamine infusion administered or added to vasopressor in the presence of a) myocardial dysfunction as suggested by elevated cardiac filling pressures and low cardiac output, or b) ongoing signs of hypoperfusion despite achieving adequate intravascular volume and adequate mean arterial pressure (1C); avoiding use of intravenous hydrocortisone in adult septic shock patients if adequate fluid resuscitation and vasopressor therapy are able to restore hemodynamic stability (2C); hemoglobin target of 7-9 g/dL in the absence of tissue hypoperfusion, ischemic coronary artery disease, or acute hemorrhage (1B); low tidal volume (1A) and limitation of inspiratory plateau pressure (1B) for acute respiratory distress syndrome (ARDS); application of at least a minimal amount of positive end-expiratory pressure (PEEP) in ARDS (1B); higher rather than lower level of PEEP for patients with sepsis-induced moderate or severe ARDS (2C); recruitment maneuvers in sepsis patients with severe refractory hypoxemia due to ARDS (2C); prone positioning in sepsis-induced ARDS patients with a PaO2/FIO2 ratio of ≤ 100 mm Hg in facilities that have experience with such practices (2C); head-of-bed elevation in mechanically ventilated patients unless contraindicated (1B); a conservative fluid strategy for patients with established ARDS who do not have evidence of tissue hypoperfusion (1C); protocols for weaning and sedation (1A); minimizing use of either intermittent bolus sedation or continuous infusion sedation targeting specific titration endpoints (1B); avoidance of neuromuscular blockers if possible in the septic patient without ARDS (1C); a short course of neuromuscular blocker (no longer than 48 hrs) for patients with early ARDS and a Pao2/Fio2 < 150 mm Hg (2C); a protocolized approach to blood glucose management commencing insulin dosing when two consecutive blood glucose levels are > 180 mg/dL, targeting an upper blood glucose ≤ 180 mg/dL (1A); equivalency of continuous veno-venous hemofiltration or intermittent hemodialysis (2B); prophylaxis for deep vein thrombosis (1B); use of stress ulcer prophylaxis to prevent upper gastrointestinal bleeding in patients with bleeding risk factors (1B); oral or enteral (if necessary) feedings, as tolerated, rather than either complete fasting or provision of only intravenous glucose within the first 48 hrs after a diagnosis of severe sepsis/septic shock (2C); and addressing goals of care, including treatment plans and end-of-life planning (as appropriate) (1B), as early as feasible, but within 72 hrs of intensive care unit admission (2C). Recommendations specific to pediatric severe sepsis include: therapy with face mask oxygen, high flow nasal cannula oxygen, or nasopharyngeal continuous PEEP in the presence of respiratory distress and hypoxemia (2C), use of physical examination therapeutic endpoints such as capillary refill (2C); for septic shock associated with hypovolemia, the use of crystalloids or albumin to deliver a bolus of 20 mL/kg of crystalloids (or albumin equivalent) over 5 to 10 mins (2C); more common use of inotropes and vasodilators for low cardiac output septic shock associated with elevated systemic vascular resistance (2C); and use of hydrocortisone only in children with suspected or proven "absolute"' adrenal insufficiency (2C). Strong agreement existed among a large cohort of international experts regarding many level 1 recommendations for the best care of patients with severe sepsis. Although a significant number of aspects of care have relatively weak support, evidence-based recommendations regarding the acute management of sepsis and septic shock are the foundation of improved outcomes for this important group of critically ill patients.

[Central venous-arterial carbon dioxide tension to arterial-central venous oxygen content ratio combined with lactate clearance rate as early resuscitation goals of septic shock].

PubMed

Gao, X H; Li, P J; Cao, W

2018-02-13

Objective: To investigate the prognostic significance of central venous-arterial carbon dioxide tension to arterial-venous oxygen content ratio (Pcv-aCO(2)/Ca-cvO(2)) combined with lactate clearance rate (LCR) as early resuscitation goals of septic shock. Methods: One hundred and forty-five septic shock patients admitted to Second Department of Critical Care Medicine of Lanzhou University Second Hospital from March 2013 to May 2017 were enrolled in this study.All septic shock patients received an initial resuscitation therapy according to early goal-directed therapy.The arterial and central venous blood gases were measured simultaneously at baseline (T0) and 6 hours after resuscitation (T6). Pcv-aCO(2)/Ca-cvO(2) and LCR were calculated.Patients were classified into four groups according to Pcv-aCO(2)/Ca-cvO(2) and LCR at T6: group A, Pcv-aCO(2)/Ca-cvO(2)>1.8 and LCR<30%; group B, Pcv-aCO(2)/Ca-cvO(2)>1.8 and LCR≥30%; group C, Pcv-aCO(2)/Ca-cvO(2)≤1.8 and LCR<30%; group D, Pcv-aCO(2)/Ca-cvO(2)≤1.8 and LCR≥30%.General demographics, hemodynamic parameters, oxygen metabolism parameters, acute physiology and chronic health evaluation (APACHE Ⅱ) scores, sequential organ failure assessment (SOFA) scores, length of intensive care unit (ICU) stay, and 28-day mortality rate were compared among the 4 groups.A Kaplan-Meier curve showed the survival probabilities at day 28 using a log-rank test for multiple comparisons.Parameters were introduced into a Cox's proportional hazards regression model to analyze the prediction of 28-day mortality.Receiver operating characteristics (ROC) curves were constructed to evaluate the ability of Pcv-aCO(2)/Ca-cvO(2), LCR, Pcv-aCO(2)/Ca-cvO(2) combined with LCR at T6 to predict 28-day mortality. Results: Compared with patients in group A, patients from group D had the lower APACHE Ⅱ and SOFA score at day 3 ( t =-2.909, -3.630, both P <0.05), shorter ICU stay ( t =-2.575, P =0.011), and lower mortality rate at day 28 (χ(2)=3.124, P =0.011). Survival curves up to day 28, illustrated by Kaplan-Meier method, showed that group A had the shortest median survival time (χ(2)=10.332, P =0.016), difference between group A and group D was statistically significant (χ(2)=8.304, P =0.004). The Cox regression analysis revealed that Pcv-aCO(2)/Ca-cvO(2) ( RR =3.888, 95% CI : 2.443-6.189, P <0.001) and LCR ( RR =0.073, 95% CI : 0.008-0.640, P =0.018) at T6 were independent predictors of 28-day mortality.The area under ROC curve for Pcv-aCO(2)/Ca-cvO(2) combined with LCR (0.919, 95% CI : 0.862-0.958) was significantly greater than whether Pcv-aCO(2)/Ca-cvO(2) (0.862, 95% CI : 0.795-0.914) or LCR (0.820, 95% CI : 0.748-0.879) alone ( Z =2.032, 2.364, both P <0.05). Conclusion: Combination of Pcv-aCO(2)/Ca-cvO(2) and LCR is better than single parameter to predict the risk of adverse outcomes of septic shock patients, and may provide useful information for assessing the adequacy of resuscitation at early stage of septic shock.

Protective effects of Cinnamomum cassia (Lamaceae) against gout and septic responses via attenuation of inflammasome activation in experimental models.

PubMed

Shin, Woo-Young; Shim, Do-Wan; Kim, Myong-Ki; Sun, Xiao; Koppula, Sushruta; Yu, Sang-Hyeun; Kim, Han-Bi; Kim, Tack-Joong; Kang, Tae-Bong; Lee, Kwang-Ho

2017-06-09

Cinnamomum cassia (C. cassia, Lauraceae family), commonly used for treating dyspepsia, gastritis, blood circulation, and inflammatory diseases is considered as one of the 50 fundamental herbs in traditional Chinese medicine. The anti-inflammatory action of an ethanol extract of C. cassia (CA), and its underlying mechanisms were explored in both in vitro cellular and in vivo murine models. Bone marrow-derived macrophages (BMDMs) were used to study the regulatory effect of CA on inflammasome activation. A lipopolysaccharide (LPS)-induced sepsis mouse model and a monosodium urate (MSU)-induced gout model were employed to study the effect of CA on in vivo efficacy. CA improved the survival rate in the LPS-induced septic shock mouse model and inhibited inflammasome activation including NLRP3, NLRC4, and AIM2, leading to suppression of interleukin-1β secretion. Further, ASC oligomerization and its speck formation in cytosol were attenuated by CA treatment. Furthermore, CA improved both survival rate of LPS-induced septic shock and gout murine model. CA treatment significantly attenuated danger signals-induced inflammatory responses via regulation of inflammasome activation, substantiating the traditional claims of its use in the treatment of inflammation-related disorders. Copyright © 2017. Published by Elsevier B.V.