Lansing, Allan M.
Septic shock may be defined as hypotension caused by bacteremia and accompanied by decreased peripheral blood flow, evidenced by oliguria. Clinically, a shaking chill is the warning signal. The immediate cause of hypotension is pooling of blood in the periphery, leading to decreased venous return: later, peripheral resistance falls and cardiac failure may occur. Irreversible shock is comparable to massive reactive hyperemia. Reticuloendothelial failure, histamine release, and toxic hypersensitivity may be factors in the pathogenesis of septic shock. Adrenal failure does not usually occur, but large doses of corticosteroid are employed therapeutically to counteract the effect of histamine release or hypersensitivity to endotoxin. The keys to successful therapy are time, antibiotics, vasopressors, cortisone and correction of acidosis. PMID:14063936
Delmas, Anne; Leone, Marc; Rousseau, Sébastien; Albanèse, Jacques; Martin, Claude
Vasopressin (antidiuretic hormone) is emerging as a potentially major advance in the treatment of septic shock. Terlipressin (tricyl-lysine-vasopressin) is the synthetic, long-acting analogue of vasopressin, and has comparable pharmacodynamic but different pharmacokinetic properties. Vasopressin mediates vasoconstriction via V1 receptor activation on vascular smooth muscle. Septic shock first causes a transient early increase in blood vasopressin concentrations; these concentrations subsequently decrease to very low levels as compared with those observed with other causes of hypotension. Infusions of 0.01–0.04 U/min vasopressin in septic shock patients increase plasma vasopressin concentrations. This increase is associated with reduced need for other vasopressors. Vasopressin has been shown to result in greater blood flow diversion from nonvital to vital organ beds compared with adrenaline (epinephrine). Of concern is a constant decrease in cardiac output and oxygen delivery, the consequences of which in terms of development of multiple organ failure are not yet known. Terlipressin (one or two boluses of 1 mg) has similar effects, but this drug has been used in far fewer patients. Large randomized clinical trials should be conducted to establish the utility of these drugs as therapeutic agents in patients with septic shock. PMID:15774080
Maloney, Patrick J
Early recognition of sepsis and septic shock in children relies on obtaining an attentive clinical history, accurate vital signs, and a physical examination focused on mental status, work of breathing, and circulatory status. Laboratory tests may support the diagnosis but are not reliable in isolation. The goal of septic shock management is reversal of tissue hypoperfusion. The therapeutic end point is shock reversal. Mortality is significantly better among children when managed appropriately. Every physician who cares for children must strive to have a high level of suspicion and keen clinical acumen for recognizing the rare but potentially seriously ill child.
Bouletreau, P; Petit, P; Latarjet, J
According to the data in the literature, the authors attempted to sum-up present attitudes on the value of corticoids in the treatment of septic shock. If their cardiovascular effects after a period of enthusiasm, are presently rather controversial, their cellular and sub-cellular actions, on the lysosomal membranes, capillary permeability and perhaps the intimate mechanisms of cellular oxygenation seem to be more real. However, the contra-indications which persist in the results of clinical works have resulted in the fact that the exact place of cortico-steroids in the therapeutic arsenal of septic shock still remains to be specified.
Tønnesen, Else; Larsen, Kim
Sepsis, severe sepsis and septic shock are syndromes. The incidence of sepsis is as high as 35% and with mortality rates in the intensive care unit from 27% to 54% in sepsis and septic shock, respectively. Many new treatments have been tested but only few have been implemented in clinical practise. The treatment of severe sepsis and septic shock is based on the Surviving Sepsis Campaign guidelines developed by an international expert panel. Early diagnosis, optimization of haemodynamics, rapid identification of focus and adequate antibiotic treatment are the most important strategies.
Cawcutt, Kelly A; Peters, Steve G
Sepsis is among the oldest themes in medicine; however, despite modern advances, it remains a leading cause of death in the United States. Every clinician should be able to recognize the signs and symptoms of sepsis, along with early management strategies, to expeditiously provide appropriate care and decrease resultant morbidity and mortality. This review addresses the definitions, pathogenesis, clinical manifestations, management, and outcomes of patients with sepsis, severe sepsis, and septic shock.
Vucić, N; Pilas, V
The authors compare, in this prospective study, the accuracy of their own clinical assessment of hemodynamic parameters and severity of disease with the findings obtained by right heart catheterization in 50 patients with septic shock. The purpose of the study was to determine whether Swan-Ganz catheter insertion was necessary in all patients with septic shock. As soon as the diagnosis was established, the value of pulmonary capillary wedge pressure was estimated, as well as presence or absence of pathological uptake/supply dependency in all patients. The latter is an excellent indicator of severity of disease. The accurate assessment was noted in 27 (54%) patients (1. investigator), and in 30 (60%) patients (2. investigator). The sensitivity of detection of pathological uptake/supply dependency amounted to 53% and 65%; specificity was 73% and 79%, respectively. The therapy was altered in 21 patients (42%) after catheter insertion. The results were tested with chi2-test (p < 0.01). The findings of this study warrant catheter insertion in patients with septic shock.
Alavi-Moghaddam, Mostafa; Anvari, Ali; Soltani Delgosha, Reaza; Kariman, Hamid
Introduction: Although significant development in the field of medicine is achieved, sepsis is still a major issue threatening humans’ lives. This study was aimed to audit the management of severe sepsis and septic shock patients in emergency department (ED) according to the present standard guidelines. Method: This is a prospective audit on approaching adult septic patients who were admitted to ED. The audit checklist was created based on the protocols of Surviving Sepsis Campaign and British Royal College recommendations. The mean knowledge score and the compliance rate of studied measures regarding standard protocols were calculated using SPSS version 21. Results: 30 emergency medicine residents were audited (63.3% male). The mean knowledge score of studied residents regarding standard guidelines were 5.07 ± 1.78 (IQR = 2) in pre education and 8.17 ± 1.31 (IQR = 85) in post education phase (p < 0.001). There was excellent compliance with standard in 4 (22%) studied measures, good in 2 (11%), fair in 1 (6%), weak in 2 (11%), and poor in 9 (50%). 64% of poor compliance measures correlated to therapeutic factors. After training, score of 5 measures including checking vital signs in < 20 minute, central vein pressure measurement in < 1 hour, blood culture request, administration of vasopressor agents, and high flow O2 therapy were improved clinically, but not statistically. Conclusion: The protocol adherence in management of severe sepsis and septic shock for urine output measurement, central venous pressure monitoring, administration of inotrope agents, blood transfusion, intravenous antibiotic and hydration therapy, and high flow O2 delivery were disappointingly low. It seems training workshops and implementation of Clinical audit can improve residents’ adherence to current standard guidelines regarding severe sepsis and septic shock. PMID:28286823
Colomina-Climent, Francisco; Giménez-Esparza, Carola; Portillo-Requena, Cristina; Allegue-Gallego, José Manuel; Galindo-Martínez, María; Mollà-Jiménez, Cristina; Antón-Pascual, José Luis; Rodríguez-Serra, Manuel; Martín-Ruíz, José Luis; Fernández-Arroyo, Pablo Juan; Blasco-Císcar, Eugenia María; Cánovas-Robles, José; Herrera-Murillo, Miguel; González-Hernández, Enrique; Sánchez-Morán, Fernando; Solera-Suárez, Manuel; Torres-Tortajada, Jesús; Nuñez-Martínez, José María; Martín-Langerwerf, David; Herrero-Gutiérrez, Eugenio; Sebastián-Muñoz, Isabel; Palazón-Bru, Antonio; Gil-Guillén, Vicente Francisco
Introduction There is a lack of evidence in the efficacy of the coupled plasma filtration adsorption (CPFA) to reduce the mortality rate in septic shock. To fill this gap, we have designed the ROMPA study (Mortality Reduction in Septic Shock by Plasma Adsorption) to confirm whether treatment with an adequate dose of treated plasma by CPFA could confer a clinical benefit. Methods and analysis Our study is a multicentric randomised clinical trial with a 28-day and 90-day follow-up and allocation ratio 1:1. Its aim is to clarify whether the application of high doses of CPFA (treated plasma ≥0.20 L/kg/day) in the first 3 days after randomisation, in addition to the current clinical practice, is able to reduce hospital mortality in patients with septic shock in intensive care units (ICUs) at 28 and 90 days after initiation of the therapy. The study will be performed in 10 ICUs in the Southeast of Spain which follow the same protocol in this disease (based on the Surviving Sepsis Campaign). Our trial is designed to be able to demonstrate an absolute mortality reduction of 20% (α=0.05; 1−β=0.8; n=190(95×2)). The severity of the process, ensuring the recruitment of patients with a high probability of death (50% in the control group), will be achieved through an adequate stratification by using both severity scores and classical definitions of severe sepsis/septic shock and dynamic parameters. Our centres are fully aware of the many pitfalls associated with previous medical device trials. Trying to reduce these problems, we have developed a training programme to improve the CPFA use (especially clotting problems). Ethics and dissemination The protocol was approved by the Ethics Committees of all the participant centres. The findings of the trial will be disseminated through peer-reviewed journals, as well as national and international conference presentations. Trial registration number NCT02357433; Pre-results. PMID:27406647
Edwards, J D
There have been important advances in the resuscitation of patients in septic shock in recent years. Survival can be improved by earlier recognition and therefore eradication of the sepsis combined with logical supportive measures. As with any acutely ill patient consultation with intensive care unit staff may be useful. Consultation with the intensive care unit does not necessarily imply the need for admission and mechanical ventilation; helpful advice may be forthcoming. Equally, referral to the intensive care unit does not mean an admission of failure but merely a recognition that additional skills and technical facilities are necessary for the patient's survival. PMID:8324438
Llor, J; Parret, L; Stucki, P; Cotting, J
Septic shock is a frequent admission cause in intensive care unit. In spite of the important progresses in the understanding of his physiopathology, mortality due to septic shock is about 20%. Recently, it has been demonstrated that an early goal-directed therapy permitted to improve the patient prognosis. With a good hemodynamic management and early antibiotherapy, mortality could be reduced.
Val-Flores, Luis Silva; Fior, Alberto; Santos, Ana; Reis, Luís; Bento, Luís
The authors report a rare case of shock in a patient without significant clinical history, admitted to the intensive care unit for suspected septic shock. The patient was initially treated with fluid therapy without improvement. A hypothesis of systemic capillary leak syndrome was postulated following the confirmation of severe hypoalbuminemia, hypotension, and hemoconcentration--a combination of three symptoms typical of the disease. The authors discussed the differential diagnosis and also conducted a review of the diagnosis and treatment of the disease.
Val-Flores, Luis Silva; Fior, Alberto; Santos, Ana; Reis, Luís; Bento, Luís
The authors report a rare case of shock in a patient without significant clinical history, admitted to the intensive care unit for suspected septic shock. The patient was initially treated with fluid therapy without improvement. A hypothesis of systemic capillary leak syndrome was postulated following the confirmation of severe hypoalbuminemia, hypotension, and hemoconcentration - a combination of three symptoms typical of the disease. The authors discussed the differential diagnosis and also conducted a review of the diagnosis and treatment of the disease. PMID:25607273
Hellerud, Bernt C; Olstad, Ole K; Nielsen, Erik W; Trøseid, Anne-Marie S; Skadberg, Øyvind; Thorgersen, Ebbe B; Vege, Åshild; Mollnes, Tom E; Brandtzæg, Petter
Fulminant meningococcal sepsis is characterized by a massive growth of bacteria in the circulation, regarded as the primary inflammatory site, with no specific solid organ focus. Here we aimed to study the local inflammatory response in organs using a porcine model of fulminant meningococcal septic shock challenged with exponentially increasing doses of heat inactivated Neisseria meningitidis. The results were compared with those obtained in organs post mortem from three patients with lethal meningococcal septic shock. Nine patients with lethal pneumococcal disease and 14 patients with sudden infant death syndrome served as controls. Frozen tissue were thawed, homogenized and prepared for quantification of bacterial DNA by real-time polymerase chain reaction, and key inflammatory mediators were measured by ELISA in the pig material and by multiplex in the human material. In addition, gene expression assayed by Affymetrix gene expression profiling was performed in the pig study. The porcine model revealed a major influx of N. meningitidis in lungs, liver, spleen, and kidneys accompanied with major production of cardinal inflammatory mediators including tumor necrosis factor, interleukin (IL)-1β, IL-6, and IL-8, far exceeding the amount detected in blood. Genes encoding for these mediators revealed a similar profile. By comparing the wild-type with a lipopolysaccharide (LPS) deficient meningococcal strain, we documented that LPS was the dominant group of molecules inducing organ inflammation and was required for IL-8 production. IL-10 production was predominantly stimulated by non-LPS molecules. The massive organ inflammation in the porcine model was present in the three patients dying of meningococcal shock and differed markedly from the patients with lethal pneumococcal infections and sudden infant death syndrome. In conclusion, in meningococcal sepsis, a massive local inflammatory response occurs in specific organs.
Livigni, Sergio; Bertolini, Guido; Rossi, Carlotta; Ferrari, Fiorenza; Giardino, Michele; Pozzato, Marco; Remuzzi, Giuseppe
Objectives Coupled plasma filtration adsorption (CPFA, Bellco, Italy), to remove inflammatory mediators from blood, has been proposed as a novel treatment for septic shock. This multicenter, randomised, non-blinded trial compared CPFA with standard care in the treatment of critically ill patients with septic shock. Design Prospective, multicenter, randomised, open-label, two parallel group and superiority clinical trial. Setting 18 Italian adult, general, intensive care units (ICUs). Participants Of the planned 330 adult patients with septic shock, 192 were randomised to either have CPFA added to the standard care, or not. The external monitoring committee excluded eight ineligible patients who were erroneously included. Interventions CPFA was to be performed daily for 5 days, lasting at least 10 h/day. Primary and secondary outcome measures The primary endpoint was mortality at discharge from the hospital at which the patient last stayed. Secondary endpoints were: 90-day mortality, new organ failures and ICU-free days within 30 days. Results There was no statistical difference in hospital mortality (47.3% controls, 45.1% CPFA; p=0.76), nor in secondary endpoints, namely the occurrence of new organ failures (55.9% vs 56.0%; p=0.99) or free-ICU days during the first 30 days (6.8 vs 7.5; p=0.35). The study was terminated on the grounds of futility. Several patients randomised to CPFA were subsequently found to be undertreated. An a priori planned subgroup analysis showed those receiving a CPFA dose >0.18 L/kg/day had a lower mortality compared with controls (OR 0.36, 95% CI 0.13 to 0.99). Conclusions CPFA did not reduce mortality in patients with septic shock, nor did it positively affect other important clinical outcomes. A subgroup analysis suggested that CPFA could reduce mortality, when a high volume of plasma is treated. Owing to the inherent potential biases of such a subgroup analysis, this result can only be viewed as a hypothesis generator and
Maravitsa, Panagiota; Adamopoulou, Maria; Pistiki, Aikaterini; Netea, Mihai G; Louis, Konstantinos; Giamarellos-Bourboulis, Evangelos J
In order to investigate the role of T-helper 17 (Th17) cell activation in acute kidney injury (AKI) after septic shock, a two-stage approach was used. Firstly, peripheral blood mononuclear cells (PBMCs) and CD4-lymphocytes were isolated the first 24h after septic shock from 26 patients with AKI and 18 patients with chronic renal disease (CRD) without AKI and stimulated for the release of tumour necrosis factor-alpha (TNFα), interleukin (IL)-10, IL-17, IL-22 and interferon-gamma (IFNγ). Results were compared with 15 healthy volunteers and 13 patients with uncomplicated sepsis. Secondly, a murine model of multiple organ dysfunction (MODS) complicated with AKI and bacterial gut translocation was studied, and IL-10, IL-17, IL-22 and IFNγ were measured in kidney homogenates. IL-17 was the only cytokine produced at greater quantities from PBMCs and CD4-lymphocytes of patients with septic shock and AKI than comparators. When PBMCs of patients with septic shock and AKI were ex-vivo stimulated, intracellular staining for IL-17 was greater in CD3(+)/CD4(+)/CD196(+) cells compared to patients with septic shock and CRD. IL-17 was released at greater amounts from PBMCs of non-survivors by septic shock and AKI but not of septic shock and CRD. In the murine model of MODS, a gradual decrease of IL-17, but not of IL-10, IL-22 and IFNγ, of kidney homogenates was found indicating over-consumption. These results suggest that AKI after septic shock is driven through IL-17 release by Th17 cells; this is gradually consumed in the kidney.
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
Dumont, Tiffany; Francis-Frank, Lyndave; Chong, Josebelo; Balaan, Marvin R
Sepsis and septic shock are major health conditions in the United States, with a high incidence and mortality. The Surviving Sepsis Campaign, which was formed in 2002, formulates guidelines for the management of severe sepsis and septic shock and has actually demonstrated a reduction in mortality with institution of "sepsis bundles." Despite this, some elements of the guidelines have been questioned, and recent data suggest that strict compliance with bundles and protocols may not be necessary. Still, prompt recognition and treatment of sepsis and septic shock remain of utmost importance.
Garretson, Sharon; Malberti, Shelly
Shock is a complex physiological syndrome. If it is not detected and treated promptly, it can lead to death. This article reviews and summarises the latest findings, treatment and nursing and medical interventions for three of the most common forms of shock, namely, hypovolaemic, cardiogenic and septic shock.
Lee, En-Pei; Hsia, Shao-Hsuan; Lin, Jainn-Jim; Chan, Oi-Wa; Lee, Jung; Lin, Chia-Ying
Septic shock and cardiogenic shock are the two most common types of shock in children admitted to pediatric intensive care units (PICUs). The aim of the study was to investigate which hemodynamic variables were associated with mortality in children with shock. We retrospectively analyzed 50 children with shock (37 septic shock cases and 13 cardiogenic shock cases) in the PICU and monitored their hemodynamics using transpulmonary thermodilution from 2003 to 2016. Clinical factors were analyzed between the patients with septic and cardiogenic shock. In addition, hemodynamic parameters associated with mortality were analyzed. The 28-day mortality was significantly higher in the septic group than in the cardiogenic group (p = 0.016). Initially, the parameters of cardiac output and cardiac contractility were higher in the septic group (p < 0.05) while the parameters of preload and afterload were all higher in the cardiogenic group (p < 0.05). Cardiac index was significantly lower in the nonsurvivors of cardiogenic shock at the time of initial admission and after the first 24 hours (both p < 0.05), while systemic vascular resistance index (SVRI) was significantly lower in the nonsurvivors of septic shock (p < 0.001). Therefore, during the first 24 hours after intensive care, SVRI and cardiac index are the most important hemodynamic parameters associated with mortality.
Kneyber, Martin C J; van Heerde, Marc; Henneveld, Hetty Th
Paediatric shock is common. Hypovolaemic and septic shock are the main forms. Early and rapid results-oriented therapy of paediatric septic shock has a favourable effect on survival. There is an international guideline for the primary management of paediatric shock during the first hour after presentation of the patient. The goal of treatment is to prevent oxygen debt and consequently organ failure. The main symptoms of paediatric shock are tachycardia and reduced consciousness. In a child in shock, the clinical picture should be recognized within 15 minutes and an attempt should be made to reverse the situation by rapid fluid infusion. If the shock persists after 15 minutes, vasoactive medication should be given and the child should be transferred to a local paediatric intensive care unit. Intubation and mechanical ventilation are then also required.
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
Corrêa, Thiago Domingos; Cavalcanti, Alexandre Biasi; de Assunção, Murillo Santucci Cesar
Timely fluid administration is crucial to maintain tissue perfusion in septic shock patients. However, the question concerning which fluid should be used for septic shock resuscitation remains a matter of debate. A growing body of evidence suggests that the type, amount and timing of fluid administration during the course of sepsis may affect patient outcomes. Crystalloids have been recommended as the first-line fluids for septic shock resuscitation. Nevertheless, given the inconclusive nature of the available literature, no definitive recommendations about the most appropriate crystalloid solution can be made. Resuscitation of septic and non-septic critically ill patients with unbalanced crystalloids, mainly 0.9% saline, has been associated with a higher incidence of acid-base balance and electrolyte disorders and might be associated with a higher incidence of acute kidney injury. This can result in greater demand for renal replacement therapy and increased mortality. Balanced crystalloids have been proposed as an alternative to unbalanced solutions in order to mitigate their detrimental effects. Nevertheless, the safety and effectiveness of balanced crystalloids for septic shock resuscitation need to be further addressed in a well-designed, multicenter, pragmatic, randomized controlled trial. PMID:28099643
Park, Dae Won; Chun, Byung Chul; Kim, June Myung; Sohn, Jang Wook; Peck, Kyong Ran; Kim, Yang Soo; Choi, Young Hwa; Choi, Jun Yong; Kim, Sang Il; Eom, Joong Sik; Kim, Hyo Youl; Song, Joon Young; Song, Young Goo; Choi, Hee Jung; Kim, Min Ja
A prospective multicenter observational study was performed to investigate the epidemiology and outcomes of community-acquired severe sepsis and septic shock. Subjects included 1,192 adult patients admitted to the 22 participating intensive care units (ICUs) of 12 university hospitals in the Korean Sepsis Registry System from April, 2005 through February, 2009. Male accounted for 656 (55%) patients. Mean age was 65.0 ± 14.2 yr. Septic shock developed in 740 (62.1%) patients. Bacteremia was present in 422 (35.4%) patients. The 28-day and in-hospital mortality rates were 23.0% and 28.0%, respectively. Men were more likely to have comorbid illnesses and acute organ dysfunctions, and had higher mortality and clinical severity compared to women. While respiratory sources of sepsis were common in men, urinary sources were predominant in women. In the multivariate logistic regression analysis, cancer (odds ratio 1.89; 95% confidence interval 1.13-3.17), urinary tract infection (0.25; 0.13-0.46), APACHE II score (1.05; 1.02-1.09), SOFA score on day 1 (1.13; 1.06-1.21) and metabolic dysfunction (2.24, 1.45-3.45) were independent clinical factors for gender-related in-hospital mortality. This study provided epidemiological and clinical characteristics of community-acquired severe sepsis and septic shock in ICUs in Korea, and demonstrated the impact of clinical factors on gender difference in mortality.
Liang, Stephen Y; Kumar, Anand
Mortality and morbidity in severe sepsis and septic shock remain high despite significant advances in critical care. Efforts to improve outcome in septic conditions have focused on targeted, quantitative resuscitation strategies utilizing intravenous fluids, vasopressors, inotropes, and blood transfusions to correct disease-associated circulatory dysfunction driven by immune-mediated systemic inflammation. This review explores an alternate paradigm of septic shock in which microbial burden is identified as the key driver of mortality and progression to irreversible shock. We propose that clinical outcomes in severe sepsis and septic shock hinge upon the optimized selection, dosing, and delivery of highly potent antimicrobial therapy.
Liang, Stephen Y.
Mortality and morbidity in severe sepsis and septic shock remain high despite significant advances in critical care. Efforts to improve outcome in septic conditions have focused on targeted, quantitative resuscitation strategies utilizing intravenous fluids, vasopressors, inotropes, and blood transfusions to correct disease-associated circulatory dysfunction driven by immune-mediated systemic inflammation. This review explores an alternate paradigm of septic shock in which microbial burden is identified as the key driver of mortality and progression to irreversible shock. We propose that clinical outcomes in severe sepsis and septic shock hinge upon the optimized selection, dosing, and delivery of highly potent antimicrobial therapy. PMID:26031965
Steiner, Alexandre A
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.
Ramzi, Jeddi; Mohamed, Zarrouk; Yosr, Benabdennebi; Karima, Kacem; Raihane, Benlakhal; Lamia, Aissaoui; Hela, Ben Abid; Zaher, Belhadjali; Balkis, Meddeb
Neutropenia is a major risk factor for developing a serious infection. Bacteremia still causes significant mortality among neutropenic patients with cancer. The purpose of this study was to identify risk factors for septic shock and for mortality in neutropenic patients with leukemia and bacteremia. Consecutive samples from 20 patients with acute myeloid leukemia and bacteremia were studied during a 1 year period (January-December 2003). All patients received empirical antibiotic therapies for febrile episodes using ceftazidime plus amikacin. About 110 neutropenic febrile episodes were noted: clinically documented 14.54%, microbiologically documented 16.36% and fever of unknown origin 69.09%. Gram-negative organism caused eight febrile episodes: Pseudomonas (5), Klebsiella (3). Gram-positive organism caused 10 episodes: Staphylococcus (6), Streptococci (2), Enterococci (2). Pulmonary infection accounted for 25% of clinically documented infections. About 14 of the 110 febrile episodes were associated with septic shock causing mortality in 7 patients. In a univariate analysis variables associated with septic shock were: pulmonary infection (OR = 17, p = 0.001), serum bicarbonate < 17 mmol/l (OR = 68, p < 0.001) and serum lactate >3 mmol/l (OR = 62, p < 0.001). Variables associated with mortality were: pulmonary infection (OR = 83, p < 0.001) and serum bicarbonate < 17 mmol/l (OR = 61, p < 0.001). In a multivariate analysis two variables were associated with septic shock: pulmonary infection (OR = 5, p = 0.043) and serum lactate >3 mmol/l (OR = 10, p = 0.003). An elevated serum lactate (>3 mmol/l) and low serum bicarbonate ( < 17 mmol/l) at the onset of bacteremia are useful biomarkers in predicting septic shock and mortality in neutropenic patients.
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
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
Nagaratnam, Nages; Brakoulias, Vlasios; Ng, Kevin
A 60-year-old female in septic shock developed neurological signs and symptoms. She had left-sided hemiparesis, left homonymous hemianopia, bimanual coordination disorder, a language dysfunction of anomic aphasic type and a non-aphasic right hemispheric communication disorder. Computer tomography demonstrated bilateral anterior and posterior watershed as well as territorial infarctions. Risk factors included chronic airways limitation, cardiac failure and heavy smoking. Carotid duplex studies were normal. The mechanisms can be explained by flow changes and thrombus formation.
Yamashita, Chizuru; Hara, Yoshitaka; Kuriyama, Naohide; Nakamura, Tomoyuki; Nishida, Osamu
Polymyxin B-immobilized fiber column direct hemoperfusion (PMX-DHP) therapy is widely used for the treatment of severe sepsis and septic shock, and is generally performed for 2 h. Although previous studies demonstrated the efficacy of PMX-DHP therapy, it currently remains unclear whether its optimal duration is 2 h. This retrospective study analyzed 37 patients with septic shock who showed a poor clinical response to 2 h of PMX-DHP, and underwent a longer duration of this therapy. The mean duration of PMX-DHP therapy was 15.8 ± 7.9 h, and none of the patients developed adverse events, which enabled the therapy to be performed safely. The pressure catecholamine index [CAIP = catecholamine index/mean arterial pressure; catecholamine index = dopamine + dobutamine + (adrenaline + noradrenaline) × 100 μg/kg per min], as an indicator of hemodynamics, improved significantly in the survival group in the period between the start and 24 h after the end of PMX-DHP therapy (P < 0.01), and between 2 h after the start of and the end of this therapy (P < 0.05). In addition, the P/F ratio improved significantly in the group of surviving patients with acute respiratory distress syndrome (ARDS) in the period between the start and 24 h after the end of PMX-DHP therapy (P < 0.01), and between 2 h after the start of and the end of this therapy (P < 0.01). These results suggest that a longer duration of PMX-DHP therapy can be expected to improve the hemodynamics and pulmonary oxygenation capacity of patients with severe sepsis/septic shock. Strict prospective studies are needed in the future.
Dettmer, Matthew; Holthaus, Christopher V; Fuller, Brian M
Monitoring in the setting of critical illness must be linked to beneficial therapy to affect clinical outcome. Elevated serum lactate is associated with an increase in mortality in emergency department (ED) patients with severe sepsis and septic shock. The reduction of lactate levels toward normal during acute resuscitation is associated with improved clinical outcomes. The majority of data demonstrating the interventions used to achieve a reduction in lactate levels and the associated clinical outcomes have been obtained during protocolized randomized trials. We therefore conducted a retrospective observational cohort study of 243 adult patients with severe sepsis and septic shock to assess the interventions associated with nonprotocolized serial lactate monitoring and to assess clinical outcomes. A multivariable model was used to assess outcome differences between the serial lactate (SL) and no serial lactate (NL) cohorts. The SL group received more crystalloid resuscitation (3.6 L vs. 2.5 L; P < 0.01), central venous oxygen saturation monitoring (30% vs. 12%; P < 0.01), and central venous pressure monitoring (23.5% vs. 11.8%; P = 0.02). By day 28, a total of 31 patients in the SL group (23.5%) and 44 in the NL group (39.6%) had died. Multivariable logistic regression analysis demonstrated that the lack of serial lactate monitoring was independently associated with mortality (adjusted odds ratio, 2.09; 95% confidence interval [CI], 1.12 - 3.89; P = 0.02). The SL group also showed greater improvement in 24-h Sequential Organ Failure Assessment scores (1.16 vs. 0.19; P = 0.03), decreased intensive care unit length of stay in days (4.6 vs. 6.0; P = 0.04), and more ventilator-free (19.9 vs. 16; P = 0.05) and vasopressor-free (21.6 vs. 17.9; P = 0.02) days. In the setting of routine clinical care, serial lactate monitoring is associated with an increase in crystalloid administration, resuscitation interventions, and improved clinical outcomes in ED patients with
Martin, Kelly; Weiss, Scott L.
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
Chong, Josebelo; Dumont, Tiffany; Francis-Frank, Lyndave; Balaan, Marvin
Sepsis and septic shock are a continuum of disease resulting from a complex host response to infection. They are major health issues in the United States, causing significant financial burden to the health care system in addition to multisystem morbidity and high rates of mortality. In recent decades, landmark trials in sepsis management have demonstrated improved mortality. Although the value of protocol-driven care is currently under question, it is clear that early recognition, prompt resuscitation, and timely use of antibiotics are of utmost importance.
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
Fayssoil, A; Checinski, A
Septic shock is a severe sepsis associated with cardio-circulatory failure and tissular hypoperfusion. Echocardiography-Doppler remains essential for the assessment of myocardial function in septic shock. This ultrasound procedure helps clinicians for the analysis of left ventricular systolic function, left ventricular diastolic function, right ventricular function and cardiac filling.
Arabi, Yaseen M; Dara, Saqib I; Memish, Ziad; Al Abdulkareem, Abdulmajeed; Tamim, Hani M; Al-Shirawi, Nehad; Parrillo, Joseph E; Dodek, Peter; Lapinsky, Stephen; Feinstein, Daniel; Wood, Gordon; Dial, Sandra; Zanotti, Sergio; Kumar, Anand
It is unclear whether practice-related aspects of antimicrobial therapy contribute to the high mortality from septic shock among patients with cirrhosis. We examined the relationship between aspects of initial empiric antimicrobial therapy and mortality in patients with cirrhosis and septic shock. This was a nested cohort study within a large retrospective database of septic shock from 28 medical centers in Canada, the United States, and Saudi Arabia by the Cooperative Antimicrobial Therapy of Septic Shock Database Research Group between 1996 and 2008. We examined the impact of initial empiric antimicrobial therapeutic variables on the hospital mortality of patients with cirrhosis and septic shock. Among 635 patients with cirrhosis and septic shock, the hospital mortality was 75.6%. Inappropriate initial empiric antimicrobial therapy was administered in 155 (24.4%) patients. The median time to appropriate antimicrobial administration was 7.3 hours (interquartile range, 3.2-18.3 hours). The use of inappropriate initial antimicrobials was associated with increased mortality (adjusted odds ratio [aOR], 9.5; 95% confidence interval [CI], 4.3-20.7], as was the delay in appropriate antimicrobials (aOR for each 1 hour increase, 1.1; 95% CI, 1.1-1.2). Among patients with eligible bacterial septic shock, a single rather than two or more appropriate antimicrobials was used in 226 (72.9%) patients and was also associated with higher mortality (aOR, 1.8; 95% CI, 1.0-3.3). These findings were consistent across various clinically relevant subgroups. Conclusion: In patients with cirrhosis and septic shock, inappropriate and delayed appropriate initial empiric antimicrobial therapy is associated with increased mortality. Monotherapy of bacterial septic shock is also associated with increased mortality. The process of selection and implementation of empiric antimicrobial therapy in this high-risk group should be restructured. (Hepatology 2012;56:2305–2315) PMID:22753144
In a previous issue of Critical Care, researchers have focused on the venous-to-arterial carbon dioxide difference (Pv-aCO2) as a surrogate marker for systemic perfusion in patients with septic shock. Although the complex mechanisms responsible for an increased Pv-aCO2 in septic shock need to be further unraveled, the potential prognostic value of Pv-aCO2 seems clinically relevant and useful in daily practice in view of its easy availability. PMID:24602317
van Beest, Paul A; Spronk, Peter E
In a previous issue of Critical Care, researchers have focused on the venous-to-arterial carbon dioxide difference (Pv-aCO2) as a surrogate marker for systemic perfusion in patients with septic shock. Although the complex mechanisms responsible for an increased Pv-aCO2 in septic shock need to be further unraveled, the potential prognostic value of Pv-aCO2 seems clinically relevant and useful in daily practice in view of its easy availability.
Vazquez-Grande, Gloria; Kumar, Anand
There has been little improvement in septic shock mortality in the past 70 years, despite ever more broad-spectrum and potent antimicrobials. In the past, resuscitative elements have been the primary area of clinical septic shock management and research. The question of the optimal use of antimicrobial therapy was relatively ignored in recent decades. This review explores the pathophysiology of sepsis in an attempt to produce a better understanding and define key determinants of antimicrobial therapy response in septic shock. Optimizing existing antimicrobials delivery can drive significant improvements in the outcome of sepsis and septic shock. Inappropriate antimicrobial selection and dosing or delays in the administration substantially increase mortality and morbidity in life-threatening infections. Definitive combination therapy (where a pathogen known to be susceptible to a given agent is additionally covered by another agent) remains controversial. Although some in vitro studies, animal models, and clinical studies of infection including endocarditis, gram-negative bacteremia, and neutropenic infections have supported combination therapy, the potential clinical benefit in other severe infections has been questioned. Several meta-analyses have failed to demonstrate improvement of outcome with combination therapy in immunocompetent patients with sepsis and/or gram-negative bacteremia. These meta-analyses did not undertake subgroup analyses of the septic shock population. This article reviews the existing evidence supporting combination therapy for severe infections, sepsis, and septic shock.
Hynes-Gay, Patricia; Lalla, Patti; Leo, Maria; Merrill-Bell, Audrey; Nicholson, Marjorie; Villaruel, Elizabeth
Sepsis remains the leading cause of death in non-coronary ICU patients, despite improvements in supportive treatment modalities such as antimicrobial drugs and ventilation therapy. Further, the incidence of sepsis is projected to increase in years to come, related to factors including a rise in immunosuppressed patient populations and more widespread use of invasive lines and procedures. In this article, the authors seek to advance nurses' understanding of sepsis by reviewing the SIRS to septic shock paradigm and using a case study to illustrate how a patient progressed along the continuum. The role of the critical care nurse is an important aspect of the care of these patients. Early identification of patients at risk for, or who are developing, sepsis is crucial in order to improve patient outcomes.
Schmittinger, Christian A; Wurzinger, Bettina; Deutinger, Martina; Wohlmuth, Christoph; Knotzer, Hans; Torgersen, Christian; Dünser, Martin W; Hasibeder, Walter R
Heart failure is a well-recognized manifestation of organ failure in sepsis and septic shock. The pathophysiology of septic heart failure is complex and currently believed to involve several mechanisms. So far, the contributory role of high plasma catecholamine levels has not been investigated. In this manuscript, we present a hypothesis suggesting that excessive catecholamine production and exogenous administration of catecholamines may relevantly contribute to the development of heart failure and cardiovascular collapse in patients suffering from septic shock. Substantially elevated plasma catecholamine levels were measured during critical illness and sepsis or septic shock. There is a growing body of clinical and experimental evidence demonstrating that high catecholamine plasma levels exert direct toxic effects on the heart. The pathophysiologic mechanisms involved in catecholamine-induced cardiomyocyte toxicity may involve a combination of inflammation, oxidative stress, and abnormal calcium handling resulting in myocardial stunning, apoptosis and necrosis. Clinical signs of catecholamine-induced heart failure can present with a wide range of symptoms reaching from subtle histological changes with preserved myocardial pump function to severe heart failure exhibiting a distinctive echocardiographic pattern which became known as "Takotsubo"-like cardiomyopathy or the left ventricular apical ballooning syndrome. In a medical intensive care unit patient population, presence of sepsis was the only variable associated with the development of left ventricular apical ballooning. Since several therapeutic interventions influence catecholamine plasma levels in septic shock patients, treatment strategies aiming at the reduction of endogenous or exogenous catecholamine exposure may protect the heart during septic shock and could facilitate patient survival.
Kourelis, Taxiarchis; Kannan, Subramanian; Foley, Raymond J
Capnocytophaga canimorsus is a gram-negative rod that is a normal inhabitant of the oral flora of most dogs, cats and other animals. Clinically significant infections of humans by this common organism are extremely rare. We present a case of an 87-year-old woman who presented with septic shock and multiorgan system failure. Blood cultures were positive for a gram-negative rod that five days after admission was identified as C. canimorsus. She was treated aggressively with intravenous fluid resuscitation, vasopressors and parenteral antibiotics and recovered. The epidemiology, virulence factors, and treatment options for C. canimorsus are discussed.
Yu, Xuezhong; Guo, Shigong; Ji, Xu; Sun, Tongwen; Lan, Chao; Lavergne, Valery; Ghannoum, Marc; Li, Li
Introduction Platelet indices, including mean platelet volume (MPV), are readily available blood tests, although their prognostic value in patients with septic shock has not been fully explored. Current evidence has found contradictory results. This study aims to explore the behavior of platelet indices in septic shock and their clinical prognostic value. Methods Charts of septic shock patients from January to December 2012 in a tertiary medical center in Northern China were reviewed retrospectively. Platelet indices were recorded during the first five consecutive days after admission, as well as the penultimate and the last day of hospital stay. The data were compared between surviving and non-surviving patients. Results A total of 124 septic shock patients were enrolled. Thirty-six of the patients survived and 88 of them expired. MPV in the non-survivor group was higher than that of the survivor group, especially on the last day. PDW and PLCR showed increased trends, while PCT and PLT decreased in the non-survivor group. Among the PLT indices, MPV had the highest area under the receiver operating characteristic curve (0.81) with a precision rate of 75.6% at a cut-off of 10.5.Compared with other more usual septic shock prognostic markers, MPV is second only to lactate for the highest area under the curve. Conclusion A statistically significant difference was seen between survivors and non-survivors for platelet indices which make them easily available and useful prognostic markers for patients in septic shock. PMID:25118886
Huber, Wolfgang; Nierhaus, Axel; Kluge, Stefan; Reuter, Daniel A.; Wagner, Julia Y.
In patients with sepsis and septic shock, the hemodynamic management in both early and later phases of these “organ dysfunction syndromes” is a key therapeutic component. It needs, however, to be differentiated between “early goal-directed therapy” (EGDT) as proposed for the first 6 hours of emergency department treatment by Rivers et al. in 2001 and “hemodynamic management” using advanced hemodynamic monitoring in the intensive care unit (ICU). Recent large trials demonstrated that nowadays protocolized EGDT does not seem to be superior to “usual care” in terms of a reduction in mortality in emergency department patients with early identified septic shock who promptly receive antibiotic therapy and fluid resuscitation. “Hemodynamic management” comprises (a) making the diagnosis of septic shock as one differential diagnosis of circulatory shock, (b) assessing the hemodynamic status including the identification of therapeutic conflicts, and (c) guiding therapeutic interventions. We propose two algorithms for hemodynamic management using transpulmonary thermodilution-derived variables aiming to optimize the cardiocirculatory and pulmonary status in adult ICU patients with septic shock. The complexity and heterogeneity of patients with septic shock implies that individualized approaches for hemodynamic management are mandatory. Defining individual hemodynamic target values for patients with septic shock in different phases of the disease must be the focus of future studies. PMID:27703980
Suntharesan, Janani; Wijesekara, Dimuthu Saraji
Kawasaki disease is diagnosed when fever lasts for more than 5 days with the presence of four out of five of the following clinical features: bilateral conjunctival congestion, changes in the lips and oral cavity, polymorphous exanthem, changes in peripheral extremities, and acute nonpurulent cervical lymphadenopathy (Nakamura et al., 2012). The average age of onset is 2 years and 90% of patients are below 5 years of age. Boys are more affected than girls (Cox and Sallis, 2009). This case report describes an adolescent female who was initially managed as having septic shock and subsequently found to have Kawasaki shock syndrome. PMID:28101385
Shock, defined at a cellular level, is a condition in which oxygen delivery to the cells is not sufficient to sustain cellular activity and support organ function. The central role of microcirculation in providing oxygen to the cells makes it of prime importance in determining organ function. In sepsis and septic shock, macrocirculatory alterations and microcirculatory dysfunction participate concurrently in the pathophysiology of organ failure. Haemodynamic coherence in shock is a condition in which normalization of systemic haemodynamic variables results in simultaneous amelioration in the perfusion of the microcirculation and restoration of tissue oxygenation as a final result. Septic shock is most frequently characterized by a lack of microcirculatory recruitment despite of macrocirculatory successful resuscitation. The lack of haemodynamic coherence between macrocirculation and microcirculation in septic patients results in treatment failure and increased mortality. The monitoring of microcirculation and the effects of its changes are an important area of future clinical research and treatment modification.
Meyer, Sascha; Gottschling, Sven; Baghai, Ali; Wurm, Donald; Gortner, Ludwig
Introduction The aim of this study was to assess the efficacy of arginine-vasopressin (AVP) as a rescue therapy in catecholamine-refractory septic and non-septic shock in extremely low birth weight (ELBW) infants with acute renal injury. Methods Prospective assessment of AVP therapy in three ELBW infants with catecholamine-refractory septic shock and acute renal injury (mean birth weight 600 ± 30 g) and three ELBW infants with non-septic shock and acute renal injury (mean birth weight 770 ± 110 g) at a University hospital. The main outcome measures were restoration of blood pressure with adequate organ perfusion and survival at discharge. Results In all three ELBW infants with catecholamine-resistant septic shock, systemic arterial blood pressure increased substantively with restoration of urine output after AVP administration (dosage, 0.035 to 0.36 U/kg/h; length, 70 ± 21 hours). In the three ELBW infants with non-septic shock, only a transient stabilization in mean arterial pressure with restoration of urine output was observed after AVP therapy (dosage, 0.01 to 0.36 U/kg/h; length, 30 ± 16 hours). The mortality rate was 1/3 in the sepsis group versus 3/3 in the non-septic group. Conclusion AVP may be a promising rescue therapy in catecholamine-resistant shock in ELBW infants with acute renal injury. Larger prospective clinical trials are warranted to assess the efficacy and safety of AVP as a pressor adjunct in septic versus non-septic shock in ELBW infants. PMID:16677425
Riachy, Moussa Albert
The authors present the case of a 43-year-old male who presented at the emergency department, with a mean arterial pressure of 48 mm of Hg, a sinus tachycardia of 142/min and shallow breathing at 30/min. Two days previously, he started a high-grade fever with a concomitant reddish and painful left knee and right elbow, without any treatment. Septic shock was diagnosed and the patient was started on empiric antibiotics combining ceftriaxone and vancomycin and vasopressors (norepinephrine). The painful knee and elbow joints were aspirated and cultures grew Streptococcus pneumoniae. The patient’s clinical condition improved progressively and after investigation, the diagnosis of multiple myeloma was concluded. Pneumococcal septic arthritis, an extraordinary cause of septic arthritis, is a manifestation of an underlying disease and can be responsible for septic shock. Its diagnosis should direct further investigations. It can occur in patients with joint disease but should emphasise the search of systemic immunosuppression. PMID:22694889
Arriagada S, Daniela; Donoso F, Alejandro; Cruces R, Pablo; Díaz R, Franco
Essential therapeutic principles in children with septic shock persist over time, although some new concepts have been recently incorporated, and fully awareness of pediatricians and intensivists is essential. Fluid resuscitation is a fundamental intervention, but the kind of ideal fluid has not been established yet, as each of these interventions has specific limitations and there is no evidence supportive of the superiority of one type of fluid. Should septic shock persists despite adequate fluid resuscitation, the use of inotropic medication and/or vasopressors is indicated. New vasoactive drugs can be used in refractory septic shock caused by vasopressors, and the use of hydrocortisone should be considered in children with suspected adrenal insufficiency, as it reduces the need for vasopressors. The indications for red blood cells transfusion or the optimal level of glycemia are still controversial, with no consensus on the threshold value for the use of these blood products or the initiation of insulin administration, respectively. Likewise, the use of high-volume hemofiltration is a controversial issue and further study is needed on the routine recommendation in the course of septic shock. Nutritional support is crucial, as malnutrition is a serious complication that should be properly prevented and treated. The aim of this paper is to provide update on the most recent advances as concerns the treatment of septic shock in the pediatric population.
Pozzato, Marco; Ferrari, Fiorenza; Livigni, Sergio; Quarello, Francesco
Acute kidney injury (AKI) occurs in 5-45% of critically ill patients, and renal replacement therapy (RRT) is required in 4-10% of patients with AKI. AKI has long been considered to be hemodynamic damage from low blood flow resulting in shock, and efforts have been made to prevent and cure it by increasing the renal blood flow and improving the cardiac output and perfusion pressure. In recent years, new experimental studies on patients with septic AKI have shown that the renal blood flow remains unaltered or even increases in septic shock. An important mechanism in the pathophysiology of sepsis and septic shock appears to be apoptosis rather than ischemic necrosis. The type of treatment as well as the dose and timing of initiation of RRT seem to have strategic importance in the recovery of AKI in patients admitted to the ICU. In critically ill (often postsurgical and septic) patients with acute renal failure the use of new anticoagulation strategies has permitted to perform treatments for a sufficient number of hours to achieve the correct level of purification by minimizing the downtime and the bleeding risk. In our center the use of protocols for different methods and different types of anticoagulants has simplified the treatment of all patients with AKI and septic shock admitted to the ICU.
Vela-Vásquez, R S; Grigorov-Tzenkov, I; Aguilar, J L
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.
Dicpinigaitis, Peter V.; De Aguirre, Manuel; Divito, Joseph
Infection with Enterococcus hirae has rarely been reported in humans but is not uncommon in mammals and birds. We describe a case of Enterococcus hirae bacteremia associated with acute pancreatitis, acute cholecystitis, and septic shock responsive to antibiotic therapy and supportive critical care management. Unique aspects of this case of Enterococcus hirae bacteremia are its association with acute pancreatitis and its geographical origin. To our knowledge, this is the first report of Enterococcus hirae bacteremia occurring in a patient in the United States. Although human infection with this organism appears to be rare, all cases reported to date describe bacteremia associated with severe and life-threatening illness. Thus, physicians need to be cognizant of the clinical significance of this heretofore little recognized pathogen. PMID:26417465
Corrêa, Thiago Domingos; Rocha, Leonardo Lima; Pessoa, Camila Menezes Souza; Silva, Eliézer; de Assuncao, Murillo Santucci Cesar
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. PMID:26313437
Cardoso, Cristina Padre; de Oliveira, Argenil José de Assis; Botoni, Fernando Antônio; Rezende, Isabela Cristina Porto; Alves-Filho, Jose Carlos; Cunha, Fernando de Queiroz; Estanislau, Juliana de Assis Silva Gomes; Magno, Luiz Alexandre Viana; Rios-Santos, Fabricio
Despite major improvements in its treatment and diagnosis, sepsis is still a leading cause of death and admittance to the intensive care unit (ICU). Failure to identify patients at high risk of developing septic shock contributes to an increase in the sepsis burden and rapid molecular tests are currently the most promising avenue to aid in patient risk determination and therapeutic anticipation. The primary goal of this study was to evaluate the genetic susceptibility that affects sepsis outcome in 72 sepsis patients admitted to the ICU. Seven polymorphisms were genotyped in key inflammatory response genes in sepsis, including tumour necrosis factor-α, interlelukin (IL)-1β, IL-10, IL-8, Toll-like receptor 4, CXCR1 and CXCR2. The primary finding showed that patients who were homozygous for the major A allele in IL-10 rs1800896 had almost five times higher chance to develop septic shock compared to heterozygotes. Similarly, selected clinical features and CXCR2 rs1126579 single nucleotide polymorphisms modulated septic shock susceptibility without affecting survival. These data support the hypothesis that molecular testing has clinical usefulness to improve sepsis prognostic models. Therefore, enrichment of the ICU portfolio by including these biomarkers will aid in the early identification of sepsis patients who may develop septic shock. PMID:26038959
Desrochers, André; Francoz, David
Synovial fluid, ultrasound, and radiographic imaging are common diagnostic tools for septic arthritis. Mycoplasma septic arthritis is suspected in calves with clinical signs of otitis and pneumonia. Commonly affected joints are carpus, stifle, and tarsus. Treatment strategy must include long-term antibiotics, anti-inflammatories, and joint lavage. Knowledge of communication and boundaries for commonly affected joints is essential to perform joint lavage and arthrotomy.
Lissac, J; Kayal, S
This review is going on to emphasize recent advances of the pathophysiology of septic shock (SS) which goes-between the systemic inflammatory response syndrome (SIRS) and the multisystem organ failure (MOF). By several recent studies, our knowledge of the cellular and molecular pathophysiology of the SS has dramatically increased. Bacterial products, immunocompetent cells, soluble mediators, and cell-cell interactions between blood cells and endothelium have been reviewed. The metabolic disorders following SS can also be observed during SIRS. Still further, these abnormalities do not accurately predict prognosis, except some of them. A wealth of pre-clinical data suggests the efficacy and potentially useful therapeutic strategies like specific immunotherapy (anti-endotoxin, antimediators). Discrepancies between animals models and unexpected and disappointing clinical trial results during SS are discussed. Blocking simultaneously the hole metabolic patterns of SS which is a complex, multisystem, and multifactorial pathologic process seems to be a utopian situation. Furthermore SS occuring more frequently as a complication of nosocomial infection, the high cost of such a novel therapeutic strategy has to be taken into account.
E . coli endotoxin or live E . coli organisms were evaluated during a 24-hour period or until death. Results suggest significant differences between the two shock models: large dosages of endotoxin on contrast to those used in the canine species were required to elicit lethality characteristics. Hypoglycemia and hypoinsulinemia were regularly observed in live E . coli organism induced shock; however, hyperglycemia was a consistent hallmark in the endotoxin infused model. Renal fibrin thrombi were presented only after E .
Wong, Hector R.; 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; Hall, Mark; Gedeit, Rainer; Freishtat, Robert J.; Nowak, Jeffrey; Raj, Shekhar S.; Gertz, Shira; Howard, Kelli; Harmon, Kelli; Lahni, Patrick; Frank, Erin; Hart, Kimberly W.; Lindsell, Christopher J.
The temporal version of the pediatric sepsis biomarker risk model (tPERSEVERE) estimates the risk of a complicated course in children with septic shock based on biomarker changes from days 1 to 3 of septic shock. We validated tPERSEVERE performance in a prospective cohort, with an a priori plan to redesign tPERSEVERE if it did not perform well. Biomarkers were measured in the validation cohort (n = 168) and study subjects were classified according to tPERSEVERE. To redesign tPERSEVERE, the validation cohort and the original derivation cohort (n = 299) were combined and randomly allocated to training (n = 374) and test (n = 93) sets. tPERSEVERE was redesigned using the training set and CART methodology. tPERSEVERE performed poorly in the validation cohort, with an area under the curve (AUC) of 0.67 (95% CI: 0.58–0.75). Failure analysis revealed potential confounders related to clinical characteristics. The redesigned tPERSEVERE model had an AUC of 0.83 (0.79–0.87) and a sensitivity of 93% (68–97) for estimating the risk of a complicated course. Similar performance was seen in the test set. The classification tree segregated patients into two broad endotypes of septic shock characterized by either excessive inflammation or immune suppression. PMID:26844289
Pascual-Ramírez, J; Aguirre Sánchez-Covisa, M; Araujo, F; Gil Trujillo, S; Collar, L G; Bocharán, S
Safety in the use of small volumes of hypertonic saline solution for hypovolaemic shock and in the treatment of intracranial hypertension has been demonstrated in studies in the field of resuscitation. There is little experience of this for septic shock in humans. Beneficial immunomodulatory effects have been detected in pre-clinical studies. Interactions with the pituitary-adrenal axis and with the secretion of anti-diuretic hormone are varied and suggestive, but are not sufficiently understood. On the other hand, vasopressin has cardiovascular, osmoregulatory, and coagulation effects, and also acts on the hypothalamic-pituitary-adrenal axis. There is a relative deficit of vasopressin in septic shock. Its use in these patients does not seem to have any advantages as regards mortality, but may be beneficial in patients at risk from acute renal failure, or those who receive corticosteroids. Terlipressin is a vasopressin analogue that has also been studied. The synergy between vasopressin and hypertonic saline is a hypothesis that is mainly supported in pre-clinical studies. The use of hypertonic saline solution in septic shock, although promising, is still experimental, and must be restricted to the field of controlled clinical trials.
Tamme, Kadri; Kruusat, Rein; Ehrlich, Hans-Erik; Viirelaid, Mirjam
Background. High volumes of haemofiltration are used in septic patients to control systemic inflammation and improve patient outcomes. We aimed to clarify if extended intermittent high volume online haemodiafiltration (HVHDF) influences patient haemodynamics and cytokines profile and/or has effect upon sublingual microcirculation in critically ill septic shock patients. Methods. Main haemodynamic and clinical variables and concentrations of cytokines were evaluated before and after HVHDF in 19 patients with septic shock requiring renal replacement therapy due to acute kidney injury. Sublingual microcirculation was assessed in 9 patients. Results. The mean (SD) time of HVHDF was 9.4 (1.8) hours. The median convective volume was 123 mL/kg/h. The mean (SD) dose of norepinephrine required to maintain mean arterial pressure at the target range of 70–80 mmHg decreased from 0.40 (0.43) μg/kg/min to 0.28 (0.33) μg/kg/min (p = 0.009). No significant changes in the measured cytokines or microcirculatory parameters were observed before and after HVHDF. Conclusions. The single-centre study suggests that extended HVHDF results in decrease of norepinephrine requirement in patients with septic shock. Haemodynamic improvement was not associated with decrease in circulating cytokine levels, and sublingual microcirculation was well preserved. PMID:26064875
Emamifar, Amir; Asmussen Andreasen, Rikke; Skaarup Andersen, Nanna; Jensen Hansen, Inger Marie
Vibrio vulnificus is a rare but potential fatal bacterium that can cause severe infections. Wound infections, primary sepsis and gastroenteritis are the most common clinical features. Septic arthritis caused by V. vulnificus is an atypical presentation that has been reported in only two case reports; however, it has not been previously noted in Denmark. The authors report a case of septic arthritis caused by V. vulnificus in an immunocompromised patient. The disease progressed to severe sepsis and subsequent death within 10 h of admission.
Jacobs, R.; Kaliner, M.; Shelhamer, J.H.; Parrillo, J.E.
Histamine has been suggested as an important mediator of the cardiovascular abnormalities during septic shock. To determine if blood histamine levels were increased during human sepsis and septic shock, plasma histamine was measured using a very sensitive radioenzyme assay employing histamine N-methyltransferase (HNMT) in the following patient groups: normal controls (n = 76), nonseptic critically ill (n = 12), nonseptic shock (n = 2), sepsis without shock (n = 28), and septic shock (n = 41). Using this enzyme binding assay, all these groups had similar, normal plasma histamine concentrations, except those patients with septic shock whose mean histamine measurements were significantly reduced (p less than .002). This decrease was found to be due to an artifact of the assay: plasma contained a circulating inhibitor that falsely lowered the measured histamine level. Fractionation of septic shock plasma using molecular exclusion membranes and gel filtration revealed a 5000 MW inhibitory factor. After removal of this inhibitor from plasma, septic shock plasma histamine levels were normal. Thus, septic shock patients may have a circulating inhibitor of the HNMT enzyme, but plasma histamine concentrations are normal. Histaminemia is unlikely to play an important role in the pathogenesis of septic shock in humans.
Varghese, Julie M; Roberts, Jason A; Lipman, Jeffrey
Antimicrobial pharmacokinetics (PK) and pharmacodynamics (PD) are important considerations, particularly in critically ill patients with severe sepsis and septic shock. The pathophysiologic changes that occur in these conditions can have a major effect on pharmacokinetic parameters, which in turn could result in failure to achieve pharmacodynamic targets for antimicrobials thus adversely affecting clinical outcome. This paper discusses the pathophysiologic changes that occur during severe sepsis and septic shock and the consequent effects on antimicrobial PK and PD. The effect of PK/PD on specific antimicrobial classes is discussed and a rational framework for antimicrobial dosing is provided. Knowledge of PK/PD properties of antimicrobials can be used to personalize dosing regimens not only to maximize antimicrobial activity but also to minimize toxicity and reduce the development of antimicrobial resistance.
Alp, E; Erdem, H; Rello, J
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.
Although early and appropriate antibiotic therapy remains the most important intervention for successful treatment of septic shock, data guiding optimization of beta-lactam prescription in critically ill patients prescribed with continuous renal replacement therapy (CRRT) are still limited. Being small hydrophilic molecules, beta-lactams are likely to be cleared by CRRT to a significant extent. As a result, additional variability may be introduced to the per se variable antibiotic concentrations in critically ill patients. This article aims to describe the current clinical scenario for beta-lactam dosing in critically ill patients with septic shock and CRRT, to highlight the sources of variability among the different studies that reduce extrapolation to clinical practice, and to identify the opportunities for future research and improvement in this field. Three frequently prescribed beta-lactams (meropenem, piperacillin and ceftriaxone) were chosen for review. Our findings showed that present dosing recommendations are based on studies with drawbacks limiting their applicability in the clinical setting. In general, current antibiotic dosing regimens for CRRT follow a one-size-fits-all fashion despite emerging clinical data suggesting that drug clearance is partially dependent on CRRT modality and intensity. Moreover, some studies pool data from heterogeneous populations with CRRT that may exhibit different pharmacokinetics (for example, admission diagnoses different to septic shock, such as trauma), which also limit their extrapolation to critically ill patients with septic shock. Finally, there is still no consensus regarding the %T>MIC (percentage of dosing interval when concentration of the antibiotic is above the minimum inhibitory concentration of the pathogen) value that should be chosen as the pharmacodynamic target for antibiotic therapy in patients with septic shock and CRRT. For empirically optimized dosing, during the first day a loading dose is required
Ulldemolins, Marta; Vaquer, Sergi; Llauradó-Serra, Mireia; Pontes, Caridad; Calvo, Gonzalo; Soy, Dolors; Martín-Loeches, Ignacio
Although early and appropriate antibiotic therapy remains the most important intervention for successful treatment of septic shock, data guiding optimization of beta-lactam prescription in critically ill patients prescribed with continuous renal replacement therapy (CRRT) are still limited. Being small hydrophilic molecules, beta-lactams are likely to be cleared by CRRT to a significant extent. As a result, additional variability may be introduced to the per se variable antibiotic concentrations in critically ill patients. This article aims to describe the current clinical scenario for beta-lactam dosing in critically ill patients with septic shock and CRRT, to highlight the sources of variability among the different studies that reduce extrapolation to clinical practice, and to identify the opportunities for future research and improvement in this field. Three frequently prescribed beta-lactams (meropenem, piperacillin and ceftriaxone) were chosen for review. Our findings showed that present dosing recommendations are based on studies with drawbacks limiting their applicability in the clinical setting. In general, current antibiotic dosing regimens for CRRT follow a one-size-fits-all fashion despite emerging clinical data suggesting that drug clearance is partially dependent on CRRT modality and intensity. Moreover, some studies pool data from heterogeneous populations with CRRT that may exhibit different pharmacokinetics (for example, admission diagnoses different to septic shock, such as trauma), which also limit their extrapolation to critically ill patients with septic shock. Finally, there is still no consensus regarding the %T>MIC (percentage of dosing interval when concentration of the antibiotic is above the minimum inhibitory concentration of the pathogen) value that should be chosen as the pharmacodynamic target for antibiotic therapy in patients with septic shock and CRRT. For empirically optimized dosing, during the first day a loading dose is required
Oyama, Yoshimasa; Goto, Koji; Yamamoto, Shunsuke; Kusaka, Jyunya; Hidaka, Seigo; Shingu, Chihiro; Noguchi, Takayuki
Septic shock is an adverse clinical condition resulting in multiple organ failure from global tissue hypoxia. The importance of initial treatment is widely recognized. Thus, guidelines for septic shock recommend early goal-directed therapy (EGDT) during the first six hours of treatment. Central venous oxygen saturation monitoring is useful to maintain adequate tissue oxygen delivery. A newly developed central venous oximetry catheter (PreSep Oximetery Catheter, Edwards Lifesciences) allows continuous and easy monitoring of central venous oxygen saturation. This report shows the usefulness of this catheter in a patient who developed septic shock during an emergency operation for perforated bowel. By using EGDT perioperatively with continuous central venous oximetry, multiple organ failure might be successfully avoided.
Keegan, Joshua; Wira, Charles R
Severe sepsis and septic shock have great relevance to Emergency Medicine physicians because of their high prevalence, morbidity, and mortality. Treatment is time-sensitive, depends on early identification risk stratification, and has the potential to significantly improve patient outcomes. In this article, we review the pathophysiology of, and evidence basis for, the emergency department management of severe sepsis and septic shock.
Morelli, Andrea; Ertmer, Christian; Rehberg, Sebastian; Lange, Matthias; Orecchioni, Alessandra; Laderchi, Amalia; Bachetoni, Alessandra; D'Alessandro, Mariadomenica; Van Aken, Hugo; Pietropaoli, Paolo; Westphal, Martin
Introduction Previous findings suggest that a delayed administration of phenylephrine replacing norepinephrine in septic shock patients causes a more pronounced hepatosplanchnic vasoconstriction as compared with norepinephrine. Nevertheless, a direct comparison between the two study drugs has not yet been performed. The aim of the present study was, therefore, to investigate the effects of a first-line therapy with either phenylephrine or norepinephrine on systemic and regional hemodynamics in patients with septic shock. Methods We performed a prospective, randomized, controlled trial in a multidisciplinary intensive care unit in a university hospital. We enrolled septic shock patients (n = 32) with a mean arterial pressure below 65 mmHg despite adequate volume resuscitation. Patients were randomly allocated to treatment with either norepinephrine or phenylephrine infusion (n = 16 each) titrated to achieve a mean arterial pressure between 65 and 75 mmHg. Data from right heart catheterization, a thermodye dilution catheter, gastric tonometry, acid-base homeostasis, as well as creatinine clearance and cardiac troponin were obtained at baseline and after 12 hours. Differences within and between groups were analyzed using a two-way analysis of variance for repeated measurements with group and time as factors. Time-independent variables were compared with one-way analysis of variance. Results No differences were found in any of the investigated parameters. Conclusions The present study suggests there are no differences in terms of cardiopulmonary performance, global oxygen transport, and regional hemodynamics when phenylephrine was administered instead of norepinephrine in the initial hemodynamic support of septic shock. Trial registration ClinicalTrial.gov NCT00639015 PMID:19017409
Ranzani, Otavio Tavares; Monteiro, Mariana Barbosa; Ferreira, Elaine Maria; Santos, Sergio Ricardo; Machado, Flavia Ribeiro; Noritomi, Danilo Teixeira
Objective The current definition of severe sepsis and septic shock includes a heterogeneous profile of patients. Although the prognostic value of hyperlactatemia is well established, hyperlactatemia is observed in patients with and without shock. The present study aimed to compare the prognosis of septic patients by stratifying them according to two factors: hyperlactatemia and persistent hypotension. Methods The present study is a secondary analysis of an observational study conducted in ten hospitals in Brazil (Rede Amil - SP). Septic patients with initial lactate measurements in the first 6 hours of diagnosis were included and divided into 4 groups according to hyperlactatemia (lactate >4mmol/L) and persistent hypotension: (1) severe sepsis (without both criteria); (2) cryptic shock (hyperlactatemia without persistent hypotension); (3) vasoplegic shock (persistent hypotension without hyperlactatemia); and (4) dysoxic shock (both criteria). Results In total, 1,948 patients were analyzed, and the sepsis group represented 52% of the patients, followed by 28% with vasoplegic shock, 12% with dysoxic shock and 8% with cryptic shock. Survival at 28 days differed among the groups (p<0.001). Survival was highest among the severe sepsis group (69%, p<0.001 versus others), similar in the cryptic and vasoplegic shock groups (53%, p=0.39), and lowest in the dysoxic shock group (38%, p<0.001 versus others). In the adjusted analysis, the survival at 28 days remained different among the groups (p<0.001) and the dysoxic shock group exhibited the highest hazard ratio (HR=2.99, 95%CI 2.21-4.05). Conclusion The definition of sepsis includes four different profiles if we consider the presence of hyperlactatemia. Further studies are needed to better characterize septic patients, to understand the etiology and to design adequate targeted treatments. PMID:24553507
Zhao, Guang-ju; Li, Dong; Zhao, Qian; Song, Jia-xing; Chen, Xiao-rong; Hong, Guang-liang; Li, Meng-fang; Wu, Bing; Lu, Zhong-qiu
Secondary infection in septic patients has received widespread attention, although clinical data are still lacking. The present study was performed on 476 patients with septic shock. Time trends for mortality were analyzed using Spearman’s rank correlation test. Risk factors for secondary infection were investigated by binary logistic regression. The extended Cox model with time-varying covariates and hazard ratios (HR) was performed to determine the impact of secondary infection on mortality. Differences in hospital length of stay (LOS) between patients with and without secondary infection were calculated using a multistate model. Thirty-nine percent of septic shock patients who survived the early phase of the disease developed secondary infection. There was a statistically significant increased odds ratio for secondary infection in older patients and patients with a longer LOS in the intensive care unit (ICU), a higher Sequential Organ Failure Assessment (SOFA) score, and endotracheal intubation. Secondary infection significantly reduced the rate of discharge (HR 5.607; CI95 3.612–8.704; P < 0.001) and was associated with an increased hospital LOS of 5.46 days. The present findings represent a direct description of secondary infection in septic shock patients and highlight the influence of this condition on septic shock outcomes. PMID:27924831
Malleshappa, P; Ranganath, R; Chaudhari, A P; Singhai, P; Aghariya, M; Shah, A B
Direct hemoperfusion using polymyxin B-immobilized fiber (PMX-DHP) is an established treatment method for septic shock caused by Gram-negative infections. Here we report one instance in which PMX-DHP therapy has been used successfully in a patient with septic shock from urosepsis. After antibiotic therapy, direct hemoperfusion using polymyxin B helped in cardiovascular stability. The patient recovered from the shock within a few days after treatment with polymyxin-B hemoperfusion. As far as we are aware, this is the first reported case of effective treatment of urosepsis complicated by septic shock using PMX-DHP therapy in India.
de Assuncao, Murillo Santucci Cesar; Corrêa, Thiago Domingos; Bravim, Bruno de Arruda; Silva, Eliézer
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
Qian, Yun; Wong, Chi-Chun; Lai, San-Chuan; Lin, Zheng-Hua; Zheng, Wei-Liang; Zhao, Hui; Pan, Kong-Han; Chen, Shu-Jie; Si, Jian-Min
We present a rare case of invasive liver abscess syndrome due to Klebsiella pneumoniae (K. pneumoniae) with metastatic meningitis and septic shock. A previously healthy, 55-year-old female patient developed fever, liver abscess, septic shock, purulent meningitis and metastatic hydrocephalus. Upon admission, the clinical manifestations, laboratory and imaging examinations were compatible with a diagnosis of K. pneumoniae primary liver abscess. Her distal metastasis infection involved meningitis and hydrocephalus, which could flare abruptly and be life threatening. Even with early adequate drainage and antibiotic therapy, the patient's condition deteriorated and she ultimately died. To the best of our knowledge, this is the first case of K. pneumoniae invasive liver abscess syndrome with septic meningitis reported in mainland China. Our findings reflect the need for a better understanding of the epidemiology, risk factors, complications, comorbid medical conditions and treatment of this disease.
Qian, Yun; Wong, Chi-Chun; Lai, San-Chuan; Lin, Zheng-Hua; Zheng, Wei-Liang; Zhao, Hui; Pan, Kong-Han; Chen, Shu-Jie; Si, Jian-Min
We present a rare case of invasive liver abscess syndrome due to Klebsiella pneumoniae (K. pneumoniae) with metastatic meningitis and septic shock. A previously healthy, 55-year-old female patient developed fever, liver abscess, septic shock, purulent meningitis and metastatic hydrocephalus. Upon admission, the clinical manifestations, laboratory and imaging examinations were compatible with a diagnosis of K. pneumoniae primary liver abscess. Her distal metastasis infection involved meningitis and hydrocephalus, which could flare abruptly and be life threatening. Even with early adequate drainage and antibiotic therapy, the patient’s condition deteriorated and she ultimately died. To the best of our knowledge, this is the first case of K. pneumoniae invasive liver abscess syndrome with septic meningitis reported in mainland China. Our findings reflect the need for a better understanding of the epidemiology, risk factors, complications, comorbid medical conditions and treatment of this disease. PMID:26973425
Adamik, Barbara; Zielinski, Stanislaw; Smiechowicz, Jakub; Kübler, Andrzej
To evaluate the effectiveness of endotoxin elimination with an adsorption column in patients with septic shock and endotoxemia. The elimination therapy was guided by a new bedside method of measuring endotoxin activity (EA). Intensive care unit (ICU) patients with septic shock and suspected Gram-negative infection were consecutively added to the study group within the first 24 h. Endotoxin elimination was performed using hemoperfusion with the Alteco LPS Adsorber. The primary endpoint was improvement in organ function within the first 24 h of treatment. A secondary objective was to assess the usefulness of a new method of measuring EA to help guide endotoxin elimination therapy. Out of 64 patients 18 had a high baseline EA [0.70 EA units (0.66-0.77)]. Those patients had endotoxin elimination treatment in addition to conventional medical therapy. At 24 h after endotoxin elimination, the EA had decreased to 0.56 EA units (0.43-0.77), (p = 0.005); MAP increased from 69 (62-80) to 80 mm Hg (68-88), (p = 0.002), and noradrenaline use decreased from 0.28 (0.15-0.80) to 0.1 μg/kg/min (0.00-0.70) at the same time (p = 0.04). The SOFA score had decreased from 11 (9-15) to 9 (7-14) points 24 h after endotoxin elimination (p = 0.01) with a median delta SOFA -2 points. Endotoxin elimination did not have a significant effect on the ICU length of stay or ICU mortality. Effective endotoxin elimination resulted in a significant improvement in hemodynamic parameters and of organ function. The application of the EA assay was useful for the bedside monitoring of endotoxemia in critically ill ICU patients.
Tichit, R; Saumet, L; Marchandin, H; Haouy, S; Latry, P; Sirvent, N
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.
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.
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
Silverman, Adam M
Septic shock is a relatively rare but life-threatening condition in pediatric patients that can often be difficult to recognize in the emergency department. Once recognized, the emphasis of therapy is to reverse deficits in cellular respiration by increasing oxygen and other substrate delivery to tissue beds. Providing oxygen, improving tissue perfusion through augmentation of cardiac output, and administering antibiotics in a timely manner have all been shown to significantly improve outcomes in children with septic shock. Goal-directed therapy is relatively straightforward, emphasizes the need for effective surveillance and timely recognition of this disease process, and has the potential to significantly reduce morbidity and mortality. This review discusses how to identify specific populations at the greatest risk for septic shock, lays out the essential components of goal-directed therapy, examines potential pitfalls in management, and distinguishes additional ways that emergency clinicians can avoid the devastating consequences of septic shock in pediatric patients.
Ito, Hiroyasu; Koide, Naoki; Hassan, Ferdaus; Islam, Shamima; Tumurkhuu, Gantsetseg; Mori, Isamu; Yoshida, Tomoaki; Kakumu, Shinichi; Moriwaki, Hisataka; Yokochi, Takashi
The effect of alpha-galactosylceramide (alpha-GalCer) on lipopolysaccharide (LPS)-mediated lethality was examined. Administration of LPS killed all mice pretreated with alpha-GalCer, but not untreated control mice. The lethal shock in alpha-GalCer-sensitized mice was accompanied by severe pulmonary lesions with marked infiltration of inflammatory cells and massive cell death. On the other hand, hepatic lesions were focal and mild. A number of cells in pulmonary and hepatic lesions underwent apoptotic cell death. alpha-GalCer sensitization was ineffective for the development of the systemic lethal shock in Valpha14-positive natural killer T cell-deficient mice. Sensitization with alpha-GalCer led to the circulation of a high level of interferon (IFN)-gamma and further augmented the production of tumor necrosis factor (TNF)-alpha in response to LPS. The lethal shock was abolished by the administration of anti-IFN-gamma or TNF-alpha antibody. Further, the lethal shock did not occur in TNF-alpha-deficient mice. Taken together, alpha-GalCer sensitization rendered mice very susceptible to LPS-mediated lethal shock, and IFN-gamma and TNF-alpha were found to play a critical role in the preparation and execution of the systemic lethal shock, respectively. The LPS-mediated lethal shock using alpha-GalCer sensitization might be useful for researchers employing experimental models of sepsis and septic shock.
Zelenitsky, Sheryl; Rubinstein, Ethan; Ariano, Robert; Iacovides, Harris; Dodek, Peter; Mirzanejad, Yazdan; Kumar, Anand
Given the lack of clinical data to guide optimal dosing of vancomycin in critically ill patients with life-threatening infections, the objective was to characterise vancomycin pharmacodynamics in MRSA-associated septic shock. Cases were extracted from an observational, multicentre study in Canadian Intensive Care Units and included 35 adult patients with MRSA-associated septic shock who received vancomycin and had a measured serum concentration within the first 72 h of therapy. Univariate and multivariate analyses were used to assess variables predictive of in-hospital mortality. Patients who survived were significantly younger and had better renal function, lower probability of chronic obstructive pulmonary disease, higher probability of intravenous drug use, lower probability of healthcare-associated infection and lower APACHE II score. Survivors also received higher vancomycin doses and had higher serum troughs and AUC₂₄/MIC values. The survival rate was 2.5-fold greater in patients who had vancomycin troughs ≥15 mg/L [70.6% (12/17) vs. 27.8% (5/18); P=0.001]. Two significant AUC₂₄/MIC thresholds for survival, ≥451 (P=0.006) and ≥578 (P=0.012), were identified by CART analysis. Only younger age (P=0.028) and higher vancomycin AUC₂₄/MIC (P=0.045) were significant in multivariate analyses of survival. This study of vancomycin in critically ill patients supports the current recommendation for serum troughs of at least 15 mg/L and, in patients with septic shock, an AUC₂₄/MIC threshold higher than the conventional 400. Improved survival was observed with the attainment of these pharmacodynamic targets.
Vattanavanit, Veerapong; Kawla-ied, Jarernporn; Bhurayanontachai, Rungsun
Background Septic shock resuscitation bundles have poor compliance worldwide partly due to a lack of knowledge and clinical skills. High-fidelity simulation-based training is a new teaching technology in our faculty which may improve the performance of medical students in the resuscitation process. However, since the efficacy of this training method in our institute is limited, we organized an extra class for this evaluation. Purpose The aim was to evaluate the effect on medical students’ knowledge and confidence levels after the high-fidelity medical simulation training in septic shock management. Methods A retrospective study was performed in sixth year medical students during an internal medicine rotation between November 2015 and March 2016. The simulation class was a 2-hour session of a septic shock management scenario and post-training debriefing. Knowledge assessment was determined by a five-question pre-test and post-test examination. At the end of the class, the students completed their confidence evaluation questionnaire. Results Of the 79 medical students, the mean percentage score ± standard deviation (SD) of the post-test examination was statistically significantly higher than the pre-test (66.83%±19.7% vs 47.59%±19.7%, p<0.001). In addition, the student mean percentage confidence level ± SD in management of septic shock was significantly better after the simulation class (68.10%±12.2% vs 51.64%±13.1%, p<0.001). They also strongly suggested applying this simulation class to the current curriculum. Conclusion High-fidelity medical simulation improved the students’ knowledge and confidence in septic shock resuscitation. This simulation class should be included in the curriculum of the sixth year medical students in our institute. PMID:28053558
Ferrario, Manuela; Cambiaghi, Alice; Brunelli, Laura; Giordano, Silvia; Caironi, Pietro; Guatteri, Luca; Raimondi, Ferdinando; Gattinoni, Luciano; Latini, Roberto; Masson, Serge; Ristagno, Giuseppe; Pastorelli, Roberta
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
Background The decision of when to stop septic shock resuscitation is a critical but yet a relatively unexplored aspect of care. This is especially relevant since the risks of over-resuscitation with fluid overload or inotropes have been highlighted in recent years. A recent guideline has proposed normalization of central venous oxygen saturation and/or lactate as therapeutic end-points, assuming that these variables are equivalent or interchangeable. However, since the physiological determinants of both are totally different, it is legitimate to challenge the rationale of this proposal. We designed this study to gain more insights into the most appropriate resuscitation goal from a dynamic point of view. Our objective was to compare the normalization rates of these and other potential perfusion-related targets in a cohort of septic shock survivors. Methods We designed a prospective, observational clinical study. One hundred and four septic shock patients with hyperlactatemia were included and followed until hospital discharge. The 84 hospital-survivors were kept for final analysis. A multimodal perfusion assessment was performed at baseline, 2, 6, and 24 h of ICU treatment. Results Some variables such as central venous oxygen saturation, central venous-arterial pCO2 gradient, and capillary refill time were already normal in more than 70% of survivors at 6 h. Lactate presented a much slower normalization rate decreasing significantly at 6 h compared to that of baseline (4.0 [3.0 to 4.9] vs. 2.7 [2.2 to 3.9] mmol/L; p < 0.01) but with only 52% of patients achieving normality at 24 h. Sublingual microcirculatory variables exhibited the slowest recovery rate with persistent derangements still present in almost 80% of patients at 24 h. Conclusions Perfusion-related variables exhibit very different normalization rates in septic shock survivors, most of them exhibiting a biphasic response with an initial rapid improvement, followed by a much slower trend
Picard, W.; Bazin, F.; Clouzeau, B.; Bui, H.-N.; Soulat, M.; Guilhon, E.; Vargas, F.; Hilbert, G.; Bouchet, S.; Gruson, D.; Moore, N.
To assess the risk of acute kidney injury (AKI) attributable to aminoglycosides (AGs) in patients with severe sepsis or septic shock, we performed a retrospective cohort study in one medical intensive care unit (ICU) in France. Patients admitted for severe sepsis/septic shock between November 2008 and January 2010 were eligible. A propensity score for AG administration was built using day 1 demographic and clinical characteristics. Patients still on the ICU on day 3 were included. Patients with renal failure before day 3 or endocarditis were excluded. The time window for assessment of renal risk was day 3 to day 15, defined according to the RIFLE (risk, injury, failure, loss, and end-stage renal disease) classification. The AKI risk was assessed by means of a propensity-adjusted Cox proportional hazards regression analysis. Of 317 consecutive patients, 198 received AGs. The SAPS II (simplified acute physiology score II) score and nosocomial origin of infection favored the use of AGs, whereas a preexisting renal insufficiency and the neurological site of infection decreased the propensity for AG treatment. One hundred three patients with renal failure before day 3 were excluded. AGs were given once daily over 2.6 ± 1.1 days. AKI occurred in 16.3% of patients in a median time of 6 (interquartile range, 5 to 10) days. After adjustment to the clinical course and exposure to other nephrotoxic agents between day 1 and day 3, a propensity-adjusted Cox proportional hazards regression analysis showed no increased risk of AKI in patients receiving AGs (adjusted relative risk = 0.75 [0.32 to 1.76]). In conclusion, in critically septic patients presenting without early renal failure, aminoglycoside therapy for less than 3 days was not associated with an increased risk of AKI. PMID:25288085
Karapetsa, Maria; Pitsika, Marina; Goutzourelas, Nikos; Stagos, Dimitrios; Tousia Becker, Aphrodite; Zakynthinos, Epaminondas
The aim of this pilot study was to investigate variability of oxidative stress during sepsis evolution. ICU patients with the diagnosis of septic shock were included. Thiobarbituric-acid reactive substances, total antioxidant capacity, protein carbonyls in plasma, reduced, oxidized glutathione and catalase activity in erythrocyte lysate were assessed in the 1st, 3rd, 5th and 8th day after sepsis appearance. A total of 17 patients were divided in two groups: survivors (n=7) and non-survivors (n=10). APACHE II was 11.5 ± 5.4 and 19.9 ± 4.97 in survivors and non-survivors respectively (p=0.005), while mean age and SOFA score at sepsis diagnosis, were similar between the two groups. GSH levels, catalase activity and protein carbonyls presented significant different course in time between survivors and non-survivors (p<0.05). Catalase activity was significantly higher in survivors (238.8 ± 51.5) than non-survivors (166.4 ± 40.2; p=0.005), while protein carbonyls levels were significantly lower in survivors (0.32 ± 0.09) than non-survivors (0.48 ± 0.16; p=0.036) on the 1st day. Yet, non-survivors exhibited a declining course in GSH levels during time, while GSH levels were maintained in survivors. Conclusively, a longstanding antioxidant deficiency in non-surviving patients was noted. This phenomenon was clearly prominent in patients' erythrocytes.
Alvarez, J; Mar, J; Varela-Ledo, E; Garea, M; Matinez-Lamas, L; Rodriguez, J; Regueiro, B
Antibiotic treatment for septic shock is generally prescribed on an empirical basis using broad-spectrum antibiotics. Molecular diagnostic techniques can detect the presence of microbial DNA in blood within a few hours and facilitate early, targeted treatment. The aim of this study was to evaluate the economic impact of a real-time polymerase chain reaction technique, LightCycler SeptiFast (LSC), in patients with sepsis. A cost-minimisation study was carried out in patients admitted with a diagnosis of severe sepsis or septic shock to the intensive care unit of a university hospital. The stay in the intensive care unit, hospital admission, 28-day and six-month mortality, and the economic cost of the clinical process were also evaluated. The study involved 48 patients in the LSC group and 54 patients in the control group. The total cost was €42,198 in the control group versus €32,228 in the LCS group with statistically significant differences (P <0.05), giving rise to an average net saving of €9970 per patient. The mortality rate was similar in both groups. The main finding of this study was the significant economic saving afforded by the use of the LCS technique, due to the shortening of intensive care unit stay and the use of fewer antibiotics.
Doughty, Lesley A.; Carlton, Stacey; Galen, Benjamin; Cooma-Ramberan, Indranie; Chung, Chung-Shiang; Ayala, Alfred
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
Introduction Septic syndromes remain the leading cause of mortality in intensive care units (ICU). Septic patients rapidly develop immune dysfunctions, the intensity and duration of which have been linked with deleterious outcomes. Decreased mRNA expressions of major histocompatibility complex (MHC) class II-related genes have been reported after sepsis. We investigated whether their mRNA levels in whole blood could predict mortality in septic shock patients. Methods A total of 93 septic shock patients were included. On the third day after shock, the mRNA expressions of five MHC class II-related genes (CD74, HLA-DRA, HLA-DMB, HLA-DMA, CIITA) were measured by qRT-PCR and monocyte human leukocyte antigen-DR (mHLA-DR) by flow cytometry. Results A significant correlation was found among MHC class II related gene expressions. Among mRNA markers, the best prognostic value was obtained for CD74 (HLA-DR antigen-associated invariant chain). For this parameter, the area under the receiver operating characteristic curve (AUC) was calculated (AUC = 0.67, 95% confidence interval (CI) = 0.55 to 0.79; P = 0.01) as well as the optimal cut-off value. After stratification based on this threshold, survival curves showed that a decreased CD74 mRNA level was associated with increased mortality after septic shock (Log rank test, P = 0.0043, Hazard Ratio = 3.0, 95% CI: 1.4 to 6.5). Importantly, this association remained significant after multivariate logistic regression analysis including usual clinical confounders (that is, severity scores, P = 0.026, Odds Ratio = 3.4, 95% CI: 1.2 to 9.8). Conclusion Decreased CD74 mRNA expression significantly predicts 28-day mortality after septic shock. After validation in a larger multicentric study, this biomarker could become a robust predictor of death in septic patients. PMID:24321376
Cruz, Marília Galvão; Dantas, João Gabriel Athayde de Oliveira; Levi, Talita Machado; Rocha, Mário de Seixas; de Souza, Sérgio Pinto; Boa-Sorte, Ney; de Moura, Carlos Geraldo Guerreiro; Cruz, Constança Margarida Sampaio
Objective This study aimed to describe and compare the characteristics and clinical outcomes of patients with septic and non-septic acute kidney injury. Methods This study evaluated an open cohort of 117 critically ill patients with acute kidney injury who were consecutively admitted to an intensive care unit, excluding patients with a history of advanced-stage chronic kidney disease, kidney transplantation, hospitalization or death in a period shorter than 24 hours. The presence of sepsis and in-hospital death were the exposure and primary variables in this study, respectively. A confounding analysis was performed using logistic regression. Results No significant differences were found between the mean ages of the groups with septic and non-septic acute kidney injury [65.30±21.27 years versus 66.35±12.82 years, respectively; p=0.75]. In the septic and non-septic acute kidney injury groups, a predominance of females (57.4% versus 52.4%, respectively; p=0.49) and Afro-descendants (81.5% versus 76.2%, respectively; p=0.49) was observed. Compared with the non-septic patients, the patients with sepsis had a higher mean Acute Physiology and Chronic Health Evaluation II score [21.73±7.26 versus 15.75±5.98; p<0.001)] and a higher mean water balance (p=0.001). Arterial hypertension (p=0.01) and heart failure (p<0.001) were more common in the non-septic patients. Septic acute kidney injury was associated with a greater number of patients who required dialysis (p=0.001) and a greater number of deaths (p<0.001); however, renal function recovery was more common in this group (p=0.01). Sepsis (OR: 3.88; 95%CI: 1.51-10.00) and an Acute Physiology and Chronic Health Evaluation II score >18.5 (OR: 9.77; 95%CI: 3.73-25.58) were associated with death in the multivariate analysis. Conclusion Sepsis was an independent predictor of death. Significant differences were found between the characteristics and clinical outcomes of patients with septic versus non-septic acute kidney
Krzystek-Korpacka, Malgorzata; Mierzchala, Magdalena; Neubauer, Katarzyna; Durek, Grazyna; Gamian, Andrzej
The objective of the study was to evaluate whether severe sepsis and septic shock are related to alterations in midkine concentrations, to identify disease-related factors associated with these alterations, and to initially appraise whether midkine might serve as a biomarker in sepsis. Prospective observational cross-sectional study with 5-day follow-up. Circulating midkine was measured (enzyme-linked immunosorbent assay) in 38 septic (13 with severe sepsis, 25 with septic shock), 82 active inflammatory bowel disease (IBD) (26 with systemic inflammatory response syndrome [SIRS]) patients, and 87 healthy subjects. Midkine significantly increased along with a sequence: health-inflammation (IBD)-systemic inflammation (IBD-SIRS)-severe sepsis/septic shock. High midkine levels (>1,000 ng/L) were found in 63% of septic and in 19% of IBD-SIRS patients, whereas extremely high concentrations (>5,000 ng/L) were found in 16% vs. 4%. Although not different at admission, midkine gradually decreased in severe sepsis and remained high in shock. Similarly, persistently high midkine was observed in patients with cardiovascular insufficiency (CVI) and in mechanically ventilated as compared with normalizing levels in patients without CVI and not requiring ventilation. The differences in devised simple rates (Δ5th-1st) were significant in all these cases. Accordingly, admission midkine was higher in patients with metabolic acidosis. Concerning pathogen, gram-positive infections were associated with the highest midkine levels. In conclusion, sepsis and septic shock are associated with midkine elevation, substantially more pronounced than in inflammation, even systemic, revealing a new potential mediator of deregulation of neutrophil migration. Sepsis-related global hypoxia seems to contribute to midkine elevation. Our results substantiate further research on possible midkine application as a sepsis biomarker: in differentiating SIRS from sepsis and identifying gram-positive sepsis and
Du, Wei; Wang, Xiao-Ting; Long, Yun; Liu, Da-Wei
Background: Previous studies have suggested that β1-receptor blockers benefit septic shock patients. This study aimed to determine whether β1-receptor blockers benefit tissue perfusion in sepsis and to identify parameters to reduce the risk of this drug in sepsis. Methods: Consecutive septic shock patients were recruited from the Intensive Care Unit of Peking Union Medical College Hospital within 48 h of diagnosis. All patients were hemodynamically stable and satisfactorily sedated with a heart rate (HR) ≥100 beats/min. Esmolol therapy achieved the target HR of 10–15% lower than the baseline HR. Clinical and physiological data of patients were collected prospectively within 1 h prior to esmolol therapy and 2 h after achieving the targeted HR. Results: Sixty-three patients were recruited. After esmolol therapy, blood pressure was unaltered, whereas stroke volume (SV) was increased compared with before esmolol therapy (43.6 ± 22.7 vs. 49.9 ± 23.7 ml, t = −2.3, P = 0.047). Tissue perfusion, including lactate levels (1.4 ± 0.8 vs. 1.1 ± 0.6 mmol/L, t = 2.6, P = 0.015) and the central venous-to-arterial carbon dioxide difference (5.6 ± 3.3 vs. 4.3 ± 2.2 mmHg, t = 2.6 P = 0.016), was also significantly decreased after esmolol therapy. For patients with increased SV (n = 42), cardiac efficiency improved, and esmolol therapy had a lower risk for a decrease in cardiac output (CO). Therefore, pretreatment cardiac systolic and diastolic parameters with (n = 42)/without (n = 21) an increase in SV were compared. Mitral lateral annular plane systolic excursion (MAPSElat) in patients with increased SV was significantly higher than that in those without increased SV (1.3 ± 0.3 vs. 1.1 ± 0.2 cm, t = 2.4, P = 0.034). Conclusions: SV of septic shock patients is increased following esmolol therapy. Although CO is also decreased with HR, tissue perfusion is not worse. MAPSElat can be used to predict an increase in SV before esmolol use. Trial Registration: Clinical
Wilson, Stephen J; Mehta, Saurabh S; Bellamy, Mark C
Sepsis remains a significant problem and cause of morbidity and mortality in intensive care. Vasopressin infusions are currently used as rescue therapy for the treatment of vasodilatory, catecholamine-resistant septic shock. At present, there are no large randomised, controlled trials in the literature investigating vasopressin in this role, although two such studies are currently ongoing in Canada. This review outlines the pathophysiology of sepsis and that of vasopressin in sepsis and reviews the available evidence for the use of vasopressin in sepsis and septic shock. A review of the safety data for vasopressin in this indication is included. Recommendations for the use of vasopressin in septic shock, along with suggestions for the direction of further work in the field are presented.
Mishra, Shakti Bedanta; Singh, Ratender Kumar; Baronia, Arvind Kumar; Poddar, Banani; Azim, Afzal; Gurjar, Mohan
Aim of the Study: Acute kidney injury (AKI) in septic shock has poor outcomes. Sustained low-efficiency dialysis (SLED) is increasingly replacing continuous renal replacement therapy as the preferred modality in Intensive Care Units (ICUs). However, the essential aspects of hemodynamic tolerability and efficacy of SLED in septic shock AKI has been minimally studied. Patients and Methods: We describe hemodynamic tolerability using modified vasopressor index (VI) and vasopressor dependency (VD) and efficacy using a combination of Kt/v, correction of acidosis, electrolyte, and fluid overload. Adult ICU patients of septic shock in AKI requiring SLED were included in this study. Results: One hundred and twenty-four patients of septic shock AKI requiring SLED were enrolled in the study. There were 74 nonsurvivors (NSs). Approximately, 56% (278/498) of the sessions in which vasopressors were required were studied. Metabolic acidosis (49%) was the predominant indication for the initiation of SLED in these patients. Baseline characteristics between survivors and NSs were comparable, except for age, severity scores, AKI stage, and coexisting illness. VI and VD prior to the initiation of SLED and delta VI and VD during SLED were significantly higher in NSs. Hemodynamic tolerability and efficacy of SLED was achievable only at lower vasopressor doses. Conclusion: VI, VD, and combination of Kt/v together with correction of acidosis, electrolyte, and fluid overload can be used to describe hemodynamic tolerability and efficacy of SLED in septic shock AKI. However, at higher vasopressor doses in septic shock, hemodynamic tolerability and efficacy of SLED requires further evidence. PMID:28149027
Katip, Wasan; Jaruratanasirikul, Sutep; Pattharachayakul, Sutthiporn; Wongpoowarak, Wibul; Jitsurong, Arnurai; Lucksiri, Aroonrut
Objective To characterize the pharmacokinetics (PK) of vancomycin in patients in the initial phase of septic shock. Methods Twelve patients with septic shock received an intravenous infusion of vancomycin 30 mg/kg over 2 h. The vancomycin PK study was conducted during the first 12 h of the regimen. Serum vancomycin concentration–time data were analyzed using the standard model-independent analysis and the compartment model. Results For the noncompartment analysis the mean values ± standard deviation (SD) of the estimated clearance and volume of distribution of vancomycin at steady state were 6.05±1.06 L/h and 78.73±21.78 L, respectively. For the compartmental analysis, the majority of vancomycin concentration–time profiles were best described by a two-compartment PK model. Thus, the two-compartmental first-order elimination model was used for the analysis. The mean ± SD of the total clearance (3.70±1.25 L/h) of vancomycin was higher than that obtained from patients without septic shock. In contrast, the volume of the central compartment (8.34±4.36 L) and volume of peripheral compartment (30.99±7.84 L) did not increase when compared with patients without septic shock. Conclusion The total clearance of vancomycin was increased in septic shock patients. However, the volume of the central compartment and peripheral compartment did not increase. Consequently, a loading dose of vancomycin should be considered in all patients with septic shock. PMID:27920562
David, S; Hoeper, M M; Kielstein, J T
Sepsis is defined as a systemic inflammatory response of the body to an infection. Besides anti-infective drugs and removal of the site of infection, no specific therapeutics that target the overwhelming host response are available. Clinical researchers are currently evaluating the extracorporeal elimination of circulating cytokines. Modern adsorbing techniques have increasingly been used for this purpose allowing an unselective but highly effective removal of the vast majority of circulating cytokines but also fail to replace used protective factors in patients' plasma. Therapeutic plasma exchange (TPE) however might represent a novel method to remove pathologically elevated cytokines and simultaneously to replace protective plasmatic factors. Here we report the case of a septic shock patient treated with TPE and review the available literature with respect to TPE as an adjunctive therapy in sepsis.
Smeding, Lonneke; Plötz, Frans B; Groeneveld, A B Johan; Kneyber, Martin C J
Cardiovascular dysfunction is common in severe sepsis or septic shock. Although functional alterations are often described, the elevated serum levels of cardiac proteins and autopsy findings of myocardial immune cell infiltration, edema, and damaged mitochondria suggest that structural changes to the heart during severe sepsis and septic shock may occur and may contribute to cardiac dysfunction. We explored the available literature on structural (versus functional) cardiac alterations during experimental and human endotoxemia and/or sepsis. Limited data suggest that the structural changes could be prevented, and myocardial function improved by (pre-)treatment with platelet-activating factor, cyclosporin A, glutamine, caffeine, simvastatin, or caspase inhibitors.
Montini, Florent; Grenouillet, Frederic; Capellier, Gilles; Piton, Gaël
We report a case of invasive strongyloidiasis in a patient from the French Antilles who had been living in France for many years, with no history of immunosuppression, and who was hospitalised in the intensive care unit for septic shock with multimicrobial hypoxaemia pneumonia and exudative enteropathy. Initiation of systemic corticosteroid therapy for septic shock seems to have precipitated onset of the parasitic infection, with recurrence of hypoxaemic pneumonia complicated by hypoxic cardiac arrest. The diagnosis was confirmed after roundworm larvae were found on bronchoalveolar lavage. Treatment with ivermectin was initiated, but the patient died in a context of postanoxic encephalopathy. PMID:25819827
Although Plesiomonas shigelloides, a water-borne bacterium of the Enterobacteriaceae family, usually causes self-limiting gastroenteritis with diarrhea, several cases of sepsis have been reported. We report the case of a 43-year-old male patient with hemochromatosis, pyruvate kinase deficiency, and asplenia via splenectomy who developed septic shock caused by P. shigelloides complicated by respiratory failure, renal failure, liver failure, and disseminated intravascular coagulation. Early aggressive antimicrobial therapy and resuscitation measures were unsuccessful and the patient passed away. We kindly suggest clinicians to implement early diagnosis of septic shock, empirical coverage with antibiotics, and prompt volume resuscitation based on the high mortality rate of P. shigelloides bacteremia. PMID:27610253
Ruiz-Bailén, Manuel; Ramos-Cuadra, Jose Angel; Aragón-Extremera, Victor Manuel; Rucabado-Aguilar, Luis
We report the case of a 45-year-old woman who developed severe shock with multiorgan failure requiring admission to intensive care. Endomyocardial biopsy was performed and she was diagnosed with sepsis secondary to left ventricular thrombus abscess. Surgery was contraindicated and the patient received exclusively medical treatment; the clinical course was satisfactory and the patient is alive one year later. An apical thrombus may rarely be complicated by infection. Although management normally requires surgical excision, medical management may be effective in situations in which surgery is contraindicated.
Khan, M. M.; Shibuya, Y.; Kambara, T.; Yamamoto, T.
An essential role of alpha-2-macroglobulin (alpha 2M) was revealed in the prevention of septic shock induced in guinea-pigs by an elastase producing strain (IFO-3455) of Pseudomonas aeruginosa. When bacterial peritonitis was induced by inoculating fibrin-thrombin clot containing viable bacteria at a dose of 10(9) c.f.u./kg body weight, the guinea-pigs (n = 6) died within 7-8 hours due to septic shock. Prior to the shock, consumption of two-thirds of the circulating alpha 2M was observed. When circulating alpha 2M was depleted 4 hours after the bacterial inoculation, the guinea-pigs immediately developed shock and died within one hour. This shock was prevented either with a specific elastase inhibitor, HONHCOCH(CH2C6H5)CO-Ala-Gly-NH2, zincov (6 microM), or with human alpha 2M. Simultaneous depletion of circulating Hageman factor also prevented shock in the alpha 2M-depleted animals. These results indicate that septic shock was induced through activation of the Hageman factor dependent system by the bacteria-produced elastase which survived alpha 2M in the circulation. PMID:7537522
Maybauer, Dirk M.; Maybauer, Marc O.; Szabó, Csaba; Cox, Robert A.; Westphal, Martin; Kiss, Levente; Horvath, Eszter M.; Traber, Lillian D.; Hawkins, Hal K.; Salzman, Andrew L.; Southan, Garry J.; Herndon, David N.; Traber, Daniel L.
Systemic inflammatory response syndrome (SIRS) is associated with excessive production of nitric oxide (NO•) and superoxide (O2−), forming peroxynitrite (ONOO−), which in turn, acts as a terminal mediator of cellular injury by producing cell necrosis and apoptosis. We examined the effect of the ONOO− decomposition catalyst WW-85 in a sheep model of acute lung injury (ALI) and septic shock. Eighteen sheep were operatively prepared and randomly allocated, either to the sham, control, or WW-85 group (n=6 each). Following a tracheotomy, ALI was produced in the control and WW-85 group by insufflation of four sets of 12 breaths of cotton smoke. Then, a 30 mL suspension of live Pseudomonas aeruginosa bacteria (containing 2–5×1011 cfu) was instilled into the lungs according to an established protocol. The sham group received only the vehicle (30 mL saline). The sheep were studied in awake state for 24 hrs and ventilated with 100% oxygen. WW-85 was administered 1 h post injury as bolus infusion (0.1 mg/kg), followed by a continuous infusion of 0.02 mg•kg−1•h−1 until the end of the 24-h experimental period. Compared to injured but untreated controls, WW-85-treated animals had significantly improved gas exchange, reductions in airway obstruction, shunt formation, lung myeloperoxidase-, lung malondialdehyde-, lung 3-nitrotyrosine concentrations, and plasma nitrate-to-nitrite (NOx) levels. Animals treated with WW-85 exhibited less microvascular leakage and improvements in pulmonary function. These results provide evidence that blockade of the nitric oxide - peroxynitrite pathway improves disturbances from septic shock, as demonstrated in a clinically relevant ovine experimental model. PMID:20577150
Maybauer, Dirk M; Maybauer, Marc O; Szabó, Csaba; Cox, Robert A; Westphal, Martin; Kiss, Levente; Horvath, Eszter M; Traber, Lillian D; Hawkins, Hal K; Salzman, Andrew L; Southan, Garry J; Herndon, David N; Traber, Daniel L
Systemic inflammatory response syndrome is associated with excessive production of nitric oxide (NO·) and superoxide (O2), forming peroxynitrite, which in turn, acts as a terminal mediator of cellular injury by producing cell necrosis and apoptosis. We examined the effect of the peroxynitrite decomposition catalyst, WW-85, in a sheep model of acute lung injury and septic shock. Eighteen sheep were operatively prepared and randomly allocated to the sham, control, or WW-85 group (n = 6 each). After a tracheotomy, acute lung injury was produced in the control and WW-85 groups by insufflation of four sets of 12 breaths of cotton smoke. Then, a 30-mL suspension of live Pseudomonas aeruginosa bacteria (containing 2 - 5 × 10¹¹ colony-forming units) was instilled into the lungs according to an established protocol. The sham group received only the vehicle (30 mL saline). The sheep were studied in awake state for 24 h and ventilated with 100% oxygen. WW-85 was administered 1 h after injury as bolus infusion (0.1 mg/kg), followed by a continuous infusion of 0.02 mg·kg⁻¹·h⁻¹ until the end of the 24-h experimental period. Compared with injured but untreated controls, WW-85-treated animals had significantly improved gas exchange, reductions in airway obstruction, shunt formation, lung myeloperoxidase concentrations, lung malondialdehyde concentrations, lung 3-nitrotyrosine concentrations, and plasma nitrate-to-nitrite levels. Animals treated with WW-85 exhibited less microvascular leakage and improvements in pulmonary function. These results provide evidence that blockade of the nitric oxide-peroxynitrite pathway improves disturbances from septic shock, as demonstrated in a clinically relevant ovine experimental model.
Giacomini, Matheus Gomes; Lopes, Márcia Valéria Caldeira Angelucci; Gandolfi, Joelma Villafanha; Lobo, Suzana Margareth Ajeje
Objective To assess the causes and factors associated with the death of patients between intensive care unit discharge and hospital discharge. Methods The present is a pilot, retrospective, observational cohort study. The records of all patients admitted to two units of a public/private university hospital from February 1, 2013 to April 30, 2013 were assessed. Demographic and clinical data, risk scores and outcomes were obtained from the Epimed monitoring system and confirmed in the electronic record system of the hospital. The relative risk and respective confidence intervals were calculated. Results A total of 581 patients were evaluated. The mortality rate in the intensive care unit was 20.8% and in the hospital was 24.9%. Septic shock was the cause of death in 58.3% of patients who died after being discharged from the intensive care unit. Of the patients from the public health system, 73 (77.6%) died in the intensive care unit and 21 (22.4%) died in the hospital after being discharged from the unit. Of the patients from the Supplementary Health System, 48 (94.1%) died in the intensive care unit and 3 (5.9%) died in the hospital after being discharged from the unit (relative risk, 3.87%; 95% confidence interval, 1.21 - 12.36; p < 0.05). The post-discharge mortality rate was significantly higher in patients with intensive care unit hospitalization time longer than 6 days. Conclusion The main cause of death of patients who were discharged from the intensive care unit and died in the ward before hospital discharge was septic shock. Coverage by the public healthcare system and longer hospitalization time in the intensive care unit were factors associated with death after discharge from the intensive care unit. PMID:25909313
Arriagada S, Daniela; Donoso F, Alejandro; Cruces R, Pablo; Díaz R, Franco
New and important concepts have emerged for the advanced management of the child with septic shock in the recent decades. Attending physicians in the Pediatric intensive care unit must be fully aware of them to improve patient care in the critical care unit. It should be considered the use of immune therapy only in selected groups of patients. Continuous renal replacement therapies are well tolerated and their early use prevents deleterious fluid overload. Removal of inflammatory mediators by using high volume hemofiltration may play a role in hyperdynamic septic patients. The use of plasmapheresis is recommended in patients with thrombocytopenia-associated multiple organ failure. Extracorporeal support use should be considered in those with refractory septic shock despite goals directed therapy. The immunoparalysis has been associated with nosocomial infections and late mortality. The information from genetic markers may allow early intervention and preventive genomics-based medicine.
Schefold, Joerg C
Sepsis is associated with failure of multiple organs, including failure of the immune system. The resulting 'sepsis-associated immunosuppression' resembles a state of immunological anergy that is characterized by repeated 'infectious hits', prolonged multiple-organ failure, and death. As a consequence, adjunctive treatment approaches using measures of immunostimulation with colony-stimulating factors (CSFs) were tested in animal experiments and clinical trials. Herein, data from randomized clinical trials will be discussed in the context of a recently published meta-analysis investigating the effects of granulocyte- and granulocyte-macrophage colony-stimulating factor therapy in patients with severe sepsis and septic shock.
Mizuno, Ju; Tsujikawa, Tetsuya; Wakuta, Akiko; Matsuki, Michiko; Morita, Tsubasa; Gouda, Yoshinori
We report a case of septic shock associated with pyogenic liver abscess rescued with percutaneous transhepatic abscess drainage (PTAD). A 70-year-old male patient was admitted to our outpatient department of internal medicine with general fatigue, dullness of bilateral shoulders and extremities, appetite loss, weight loss, headache, and vertigo. Laboratory tests showed severe inflammatory indications, anemia, and high values of hepatobiliary enzymes and blood sugar. Abdominal ultrasonography and enhanced CT showed a pyogenic liver abscess of 10 cm in diameter at S 6-7 in the right hepatic lobe. The patient's condition deteriorated suddenly that night. From the results of abdominal ultrasonography and enhanced CT, we made diagnosis of septic shock associated with pyogenic liver abscess. Emergency abdominal ultrasound-guided PTAD was performed under local anesthetic. Postoperatively, the antibiotic was infused daily through a PTAD tube into the liver abscess space. He recovered and his laboratory tests improved gradually. On abdominal ultrasonography and enhanced CT, the liver abscess disappeared by 19th postoperative day, and PTAD tube was removed. There was no complication during PTAD treatment. We conclude that patients in septic shock should undergo further examinations immediately and treatment of the infected tissue should be started as soon as possible. PTAD may be an additional effective procedure for pyogenic liver abscess in septic shock. Furthermore, local antibiotic lavage through a PTAD tube into the liver abscess space may be an important supplementary method in the management of the illness.
Nantais, Jordan; Dumbarton, Tristan C; Farah, Nizam; Maxan, Alexander; Zhou, Juan; Minor, Samuel; Lehmann, Christian
Methylene blue (MB) has been used with some success as a treatment for the vasoplegia of vasopressor-refractory septic shock. The putative mechanism of action of MB is the inhibition of endothelial nitric oxide within the microvasculature and improved responsiveness to endogenous catecholamines (norepinephrine (NE)). However, to date, no study has demonstrated the microcirculatory effect of methylene blue in septic shock. The objective of this randomized, controlled, animal study was to show, in an experimentally-induced, septic shock model in rats, the effects of MB and NE on global hemodynamics and the microcirculation. Mean arterial pressure (MAP) was drastically reduced following bacterial endotoxin (lipopolysaccharide, LPS) administration in animals not receiving vasopressors. Only the combination of NE + MB restored MAP to control levels by the end of the three hour experiment. Intravital microscopy of the microcirculation was performed in the terminal ileum in order to examine functional capillary density in intestinal muscle layers and the mucosa, as well as leukocyte activation in venules (rolling, adhesion to the endothelium). Untreated LPS animals showed a significant increase in leukocyte adhesion and a decrease in capillary perfusion in the intestinal microcirculation. In groups receiving NE or NE+MB, we observed a significant decrease in leukocyte adhesion and improved functional capillary density, indicating that microvasculature function was improved. This study suggests that methylene blue may be able to improve hemodynamics while preserving microvascular function in septic shock.
Rollé, Amélie; Schepers, Kinda; Cassadou, Sylvie; Curlier, Elodie; Madeux, Benjamin; Hermann-Storck, Cécile; Fabre, Isabelle; Lamaury, Isabelle; Tressières, Benoit; Thiery, Guillaume; Hoen, Bruno
During a 2014 outbreak, 450 patients with confirmed chikungunya virus infection were admitted to the University Hospital of Pointe-à-Pitre, Guadeloupe. Of these, 110 were nonpregnant adults; 42 had severe disease, and of those, 25 had severe sepsis or septic shock and 12 died. Severe sepsis may be a rare complication of chikungunya virus infection.
Bridey, Céline; Mathieu, Soulène; Steiger, Magali; Trari, Vanessa; Lavoivre, Christine; Ducrocq, Nicolas; Levy, Bruno; Gérard, Alain; Augros, Johann
A significant number of intubated, ventilated and sedated patients suffering from septic shock develop acute respiratory distress syndrome (ARDS). The supervision by a multidisciplinary team optimises both the management of ventilation and the sedation analgesia of the patient. The nursing supervision and care related to this pathology are specific.
Maruccio, Gianfranco; Montanaro, Alessio; Schiavone, Palmira; Fumarola, Martino; Flores, Antonio; Strippoli, Paolo; Caretto, Vincenzo; Paladini, Daniele; Ramunni, Alfonso
Coupled plasma filtration absorption (CPFA) can increase blood pressure in septic shock and reduce fever during and after treatment. It is not able to stop the activation of intravascular coagulation and does not reduce the need for dialysis or the overall mortality.
de Oliveira, Cláudio Flauzino
In the whole world, around 29,000 children younger than 5 years die every day, and sepsis is the most common cause of death. Whereas in adult patients vasomotor paralysis represents the predominant cause of mortality, death in pediatric sepsis is associated with severe hypovolemia and low cardiac output. The purpose of this article was to review the recent evidence on early treatment of pediatric severe sepsis and septic shock. Although current American College of Critical Care Medicine-Pediatric Advanced Life Support guidelines represent best practice, stronger evidences are lacking to confirm the components of these recommendations. Retrospective studies showed, at the same time, the positive effects arising from the utilization of American College of Critical Care Medicine-Pediatric Advanced Life Support guidelines and the existing barriers to its implementation. And one randomized control trial paralleled the results observed in adult patients and revealed that early goal-directed therapy in children is one of the few therapeutic interventions that proved to be beneficial in septic shock treatment. Early goal-directed therapy in pediatric septic shock is a successful method to optimize and parameterize treatment, but there is still a long way to turn septic shock resuscitation simpler and more widely spread.
We have succeeded in developing the first effective therapy to prevent death from septic shock induced by a 100% lethal dose of live E . coli organisms...sodium succinate, and the aminoglycoside antibiotic, gentamicin sulfate. Application of the therapy soon after initiation of E . coli administration
Kim, Moo Hyun; Jeong, Woo Yong; Jung, In Young; Oh, Dong Hyun; Kim, Yong Chan; Kim, Eun Jin; Jeong, Su Jin; Ku, Nam Su; Kim, June Myung
Background Septic shock remains a leading cause of death, despite advances in critical care management. The Surviving Sepsis Campaign (SSC) has reduced morbidity and mortality. This study evaluated risk factors for mortality in patients with septic shock who received treatment following the SSC bundles. Materials and Methods This retrospective cohort study included patients with septic shock who received treatments following SSC bundles in an urban emergency department between November 2007 and November 2011. Primary and secondary endpoints were all-cause 7- and 28-day mortality. Results Among 436 patients, 7- and 28-day mortality rates were 7.11% (31/436) and 14% (61/436), respectively. In multivariate analysis, high lactate level (odds ratio [OR], 1.286; 95% confidence interval [CI], 1.016–1.627; P=0.036) and low estimated glomerular filtration rate (OR, 0.953; 95% CI, 0.913–0.996; P=0.032) were independent risk factors for 7-day mortality. Risk factors for 28-day mortality were high lactate level (OR, 1.346; 95% CI, 1.083–1.673; P=0.008) and high Acute Physiology and Chronic Health Evaluation II score (OR, 1.153; 95% CI, 1.029–1.293; P=0.014). Conclusion The risk of mortality of septic shock patients remains high in patients with high lactate levels and acute kidney injury. PMID:27659434
Alves, Fernanda Sampaio; Freitas, Flavio Geraldo Resende; Bafi, Antonio Tonete; Azevedo, Luciano Cesar Pontes; Machado, Flavia Ribeiro
Objectives To evaluate the serum concentrations of vitamin D and their variations in patients with severe sepsis or septic shock and in control subjects upon admission and after 7 days of hospitalization in the intensive care unit and to correlate these concentrations with the severity of organ dysfunction. Methods This case-control, prospective, observational study involved patients aged > 18 years with severe sepsis or septic shock paired with a control group. Serum vitamin D concentrations were measured at inclusion (D0) and on the seventh day after inclusion (D7). Severe deficiency was defined as vitamin D levels < 10ng/ml, deficiency as levels between 10 and 20ng/ml, insufficiency as levels between 20 and 30ng/ml, and sufficiency as levels ≥ 30ng/mL. We considered a change to a higher ranking, together with a 50% increase in the absolute concentration, to represent an improvement. Results We included 51 patients (26 with septic shock and 25 controls). The prevalence of vitamin D concentration ≤ 30ng/ml was 98%. There was no correlation between the serum concentration of vitamin D at D0 and the SOFA score at D0 or D7 either in the general population or in the group with septic shock. Patients with improvement in vitamin D deficiency had an improved SOFA score at D7 (p = 0.013). Conclusion In the population studied, patients with septic shock showed improvement in the serum concentrations of vitamin D on the seventh day compared with the controls. We also found a correlation between higher vitamin D concentrations and a greater decrease in the severity of organ dysfunction. PMID:26761476
Stenzel, Tatjana; Weidgang, Clair; Wagner, Katja; Wagner, Florian; Gröger, Michael; Weber, Sandra; Stahl, Bettina; Wachter, Ulrich; Vogt, Josef; Calzia, Enrico; Denk, Stephanie; Georgieff, Michael; Huber-Lang, Markus; Radermacher, Peter; McCook, Oscar
Septic shock-related kidney failure is characterized by almost normal morphological appearance upon pathological examination. Endothelial barrier disrupture has been suggested to be of crucial importance for septic shock-induced organ dysfunction. Therefore, in murine resuscitated cecal ligation and puncture (CLP)-induced septic shock, we tested the hypothesis whether there is a direct relationship between the kidney endothelial barrier injury and renal dysfunction. Anesthetized mice underwent CLP, and 15 h later, were anesthetized again and surgically instrumented for a 5-h period of intensive care comprising lung-protective mechanical ventilation, fluid resuscitation, continuous i.v. norepinephrine to maintain target hemodynamics, and measurement of creatinine clearance (CrCl). Animals were stratified according to low or high CrCl. Nitrotyrosine formation, expression of the inducible isoform of the nitric oxide synthase, and blood cytokine (tumor necrosis factor, interleukin-6, interleukin-10) and chemokine (monocyte chemoattractant protein-1, keratinocyte-derived chemokine) levels were significantly higher in animals with low CrCl. When plotted against CrCl and neutrophil gelatinase-associated lipocalin levels, extravascular albumin accumulation, and tissue expression of the vascular endothelial growth factor and angiopoietin-1 showed significant mathematical relationships related to kidney (dys)function. Preservation of the constitutive expression of the hydrogen sulfide producing enzyme cystathione-γ-lyase was associated with maintenance of organ function. The direct quantitative relation between microvascular leakage and kidney (dys)function may provide a missing link between near-normal tissue morphology and septic shock-related renal failure, thus further highlighting the important role of vascular integrity in septic shock-related renal failure.
Introduction Diastolic dysfunction as demonstrated by tissue Doppler imaging (TDI), particularly E/e' (peak early diastolic transmitral/peak early diastolic mitral annular velocity) is common in critical illness. In septic shock, the prognostic value of TDI is undefined. This study sought to evaluate and compare the prognostic significance of TDI and cardiac biomarkers (B-type natriuretic peptide (BNP); N-terminal proBNP (NTproBNP); troponin T (TnT)) in septic shock. The contribution of fluid management and diastolic dysfunction to elevation of BNP was also evaluated. Methods Twenty-one consecutive adult patients from a multidisciplinary intensive care unit underwent transthoracic echocardiography and blood collection within 72 hours of developing septic shock. Results Mean ± SD APACHE III score was 80.1 ± 23.8. Hospital mortality was 29%. E/e' was significantly higher in hospital non-survivors (15.32 ± 2.74, survivors 9.05 ± 2.75; P = 0.0002). Area under ROC curves were E/e' 0.94, TnT 0.86, BNP 0.78 and NTproBNP 0.67. An E/e' threshold of 14.5 offered 100% sensitivity and 83% specificity. Adjustment for APACHE III, cardiac disease, fluid balance and grade of diastolic function, demonstrated E/e' as an independent predictor of hospital mortality (P = 0.019). Multiple linear regression incorporating APACHE III, gender, cardiac disease, fluid balance, noradrenaline dose, C reactive protein, ejection fraction and diastolic dysfunction yielded APACHE III (P = 0.033), fluid balance (P = 0.001) and diastolic dysfunction (P = 0.009) as independent predictors of BNP concentration. Conclusions E/e' is an independent predictor of hospital survival in septic shock. It offers better discrimination between survivors and non-survivors than cardiac biomarkers. Fluid balance and diastolic dysfunction were independent predictors of BNP concentration in septic shock. PMID:20331902
Introduction The chemokine CXCL10 is produced during infection and inflammation to activate the chemokine receptor CXCR3, an important regulator of lymphocyte trafficking and activation. The goal of this study was to assess the contributions of CXCL10 to the pathogenesis of experimental septic shock in mice. Methods Septic shock was induced by cecal ligation and puncture (CLP) in mice resuscitated with lactated Ringer’s solution and, in some cases, the broad spectrum antibiotic Primaxin. Studies were performed in CXCL10 knockout mice and mice treated with anti-CXCL10 immunoglobulin G (IgG). Endpoints included leukocyte trafficking and activation, core body temperature, plasma cytokine concentrations, bacterial clearance and survival. Results CXCL10 was present at high concentrations in plasma and peritoneal cavity during CLP-induced septic shock. Survival was significantly improved in CXCL10 knockout (CXCL10KO) mice and mice treated with anti-CXCL10 IgG compared to controls. CXCL10KO mice and mice treated with anti-CXCL10 IgG showed attenuated hypothermia, lower concentrations of interleukin-6 (IL-6) and macrophage inhibitory protein-2 (MIP-2) in plasma and lessened natural killer (NK) cell activation compared to control mice. Compared to control mice, bacterial burden in blood and lungs was lower in CXCL10-deficient mice but not in mice treated with anti-CXCL10 IgG. Treatment of mice with anti-CXCL10 IgG plus fluids and Primaxin at 2 or 6 hours after CLP significantly improved survival compared to mice treated with non-specific IgG under the same conditions. Conclusions CXCL10 plays a role in the pathogenesis of CLP-induced septic shock and could serve as a therapeutic target during the acute phase of septic shock. PMID:24890566
Background Over the last few years, accumulating data have implicated a role for ferritin as a signaling molecule and direct mediator of the immune system. Hyperferritinemia is associated with a multitude of clinical conditions and with worse prognosis in critically ill patients. Discussion There are four uncommon medical conditions characterized by high levels of ferritin, namely the macrophage activation syndrome (MAS), adult onset Still’s disease (AOSD), catastrophic antiphospholipid syndrome (cAPS) and septic shock, that share a similar clinical and laboratory features, and also respond to similar treatments, suggesting a common pathogenic mechanism. Ferritin is known to be a pro-inflammatory mediator inducing expression of pro-inflammatory molecules, yet it has opposing actions as a pro-inflammatory and as an immunosuppressant. We propose that the exceptionally high ferritin levels observed in these uncommon clinical conditions are not just the product of the inflammation but rather may contribute to the development of a cytokine storm. Summary Here we review and compare four clinical conditions and the role of ferritin as an immunomodulator. We would like to propose including these four conditions under a common syndrome entity termed “Hyperferritinemic Syndrome”. PMID:23968282
Dickinson, John D; Kollef, Marin H
Severe sepsis and septic shock are conditions that pose difficult challenges to physicians and the health care system. In the past 10 years, a number of retrospective and prospective observational studies have shed light on the importance of a rapid and systematic approach to treatment of these conditions. A key component is early and appropriate use of antibiotics. Delay of even 6 h can dramatically increase hospital mortality. In addition, multivariate analyses have demonstrated that inappropriate initial antibiotics lead to worse outcomes. The treating physician can rapidly identify risk factors for initial inappropriate antibiotics at the bedside, such as recent antibiotic therapy or recent hospitalization. Organized antibiotic order sets have been shown to significantly improve timely appropriate antibiotic administration in septic patients. Finally, emerging laboratory data suggest that early in the course of septic shock, the pharmacokinetics of common broad spectrum antibiotics may be significantly altered due to increased volumes of distribution having dosing implications for antibiotics in septic shock.
Oliva-Martin, Maria Jose; Sanchez-Abarca, Luis Ignacio; Rodhe, Johanna; Carrillo-Jimenez, Alejandro; Vlachos, Pinelopi; Herrera, Antonio Jose; Garcia-Quintanilla, Albert; Caballero-Velazquez, Teresa; Perez-Simon, Jose Antonio; Joseph, Bertrand; Venero, Jose Luis
In septic patients, the onset of septic shock occurs due to the over-activation of monocytes. We tested the therapeutic potential of directly targeting innate immune cell activation to limit the cytokine storm and downstream phases. We initially investigated whether caspase-8 could be an appropriate target given it has recently been shown to be involved in microglial activation. We found that LPS caused a mild increase in caspase-8 activity and that the caspase-8 inhibitor IETD-fmk partially decreased monocyte activation. Furthermore, caspase-8 inhibition induced necroptotic cell death of activated monocytes. Despite inducing necroptosis, caspase-8 inhibition reduced LPS-induced expression and release of IL-1β and IL-10. Thus, blocking monocyte activation has positive effects on both the pro and anti-inflammatory phases of septic shock. We also found that in primary mouse monocytes, caspase-8 inhibition did not reduce LPS-induced activation or induce necroptosis. On the other hand, broad caspase inhibitors, which have already been shown to improve survival in mouse models of sepsis, achieved both. Thus, given that monocyte activation can be regulated in humans via the inhibition of a single caspase, we propose that the therapeutic use of caspase-8 inhibitors could represent a more selective alternative that blocks both phases of septic shock at the source. PMID:27250033
It is the nurse's responsibility to assess the critically ill patient and to interpret data so that therapy can be directed to optimally treat that individual. Shock is a complex progressive syndrome that includes specific types, such as cardiogenic, septic, anaphylactic, and hypovolemic. Clinical and hemodynamic parameters provide clues to the specific type of shock and its clinical progress. The progression of the shock state must be monitored by critical care nurses who are knowledgeable of and proficient in clinical assessment skills and the acquisition and interpretation of significant hemodynamic data.
This review surveys investigations of membrane ion transport in animals in hemorrhagic, endotoxic, or bacteremic shock. The focus of the review is on ion transport studies in the skeletal muscle and liver. Skeletal muscle Na/sup +/-K/sup +/ transport alterations have been shown during the induction of shock via hemorrhage, endotoxin, or live Gram-negative bacteria in the rodent, canine, and primate species. These alterations include impairment of active cellular K/sup +/ accumulation, increased permeability to /sup 24/Na/sup +/ and Cl/sup -/, and membrane depolarization. The ion transport alterations in the skeletal muscle are compatible with movement of extracellular fluid into the intracellular compartment. Such fluid movements can potentially lead to decreases in circulating plasma volume and thus to circulatory deficits in shock. Studies in the liver of rats subjected to hemorrhagic or endotoxic shock indicated the failure of electrogenic Na/sup +/ pump. Although the hepatic cellular membrane permeability to Na/sup +/ relative to permeability to K/sup +/ appeared unaltered in hemorrhagic shock, endotoxic shock caused an increase in permeability to Na/sup +/. Hepatic cellular /sup 45/Ca/sup +/ regulation also appeared to be adversely affected during endotoxic shock. Alterations in hepatic Na/sup +/-K/sup +/ transport and Ca/sup +/ regulation could contribute to impairment in hepatic glucose production during shock. Although mechanisms of altered membrane ion transport during shock states remain unknown, such changes could occur prior to any substantial loss of cellular metabolic energy.
Kee, C; Cheong, K Y; Pham, K; Waterer, G W; Temple, S E L
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.
Öbrink-Hansen, Kristina; Juul, Rasmus Vestergaard; Storgaard, Merete; Thomsen, Marianne Kragh; Hardlei, Tore Forsingdal; Brock, Birgitte; Kreilgaard, Mads; Gjedsted, Jakob
Antibiotic dosing in septic shock patients poses a challenge for clinicians due to the pharmacokinetic (PK) variability seen in this patient population. Piperacillin-tazobactam is often used for empirical treatment, and initial appropriate dosing is crucial for reducing mortality. Accordingly, we determined the pharmacokinetic profile of piperacillin (4 g) every 8 h, during the third consecutive dosing interval, in 15 patients treated empirically for septic shock. We developed a population pharmacokinetic model to assess empirical dosing and to simulate alternative dosing regimens and modes of administration. Time above the MIC (T>MIC) predicted for each patient was evaluated against clinical breakpoint MIC for Pseudomonas aeruginosa (16 mg/liter). Pharmacokinetic-pharmacodynamic (PK/PD) targets evaluated were 50% fT>4×MIC and 100% fT>MIC. A population PK model was developed using NONMEM, and data were best described by a two-compartment model. Central and intercompartmental clearances were 3.6 liters/h (relative standard error [RSE], 15.7%) and 6.58 liters/h (RSE, 16.4%), respectively, and central and peripheral volumes were 7.3 liters (RSE, 11.8%) and 3.9 liters (RSE, 9.7%), respectively. Piperacillin plasma concentrations varied considerably between patients and were associated with levels of plasma creatinine. Patients with impaired renal function were more likely to achieve predefined PK/PD targets than were patients with preserved or augmented renal function. Simulations of alternative dosing regimens showed that frequent intermittent bolus dosing as well as dosing by extended and continuous infusion increases the probability of attaining therapeutic plasma concentrations. For septic shock patients with preserved or augmented renal function, dose increment or prolonged infusion of the drug needs to be considered. (This study has been registered at ClinicalTrials.gov under registration no. NCT02306928.).
Kerstein, M.D.; Kohler, J.; Gould, S.; Moseley, P.
The effect of live Escherichia coli on the pulmonary extraction of the biogenic amines /sup 14/C 5-hydroxytryptamine, (5-HT) and /sup 3/H-epinephrine was investigated. The labeled isotopes were injected into a central venous catheter and collected from an aortic catheter. One hundred per cent of the labeled epinephrine was recovered in the control and septic state. Only 32.8 +/- 3.6% SEM of the 5-hydroxytryptamine was recovered before sepsis and 42.5 +/- 4.9% SEM after sepsis. During sepsis, mean arterial pressure fell to 58 mm Hg from 121 mm Hg. Pulmonary shunt increased from .7 +/- .05 SEM to .33 +/- .09 SEM.
Saugel, Bernd; Trepte, Constantin J; Heckel, Kai; Wagner, Julia Y; Reuter, Daniel A
Septic shock is a life-threatening condition in both critically ill medical patients and surgical patients during the perioperative phase. In septic shock, specific alterations in global cardiovascular dynamics (i.e., the macrocirculation) and in the microcirculatory blood flow (i.e., the microcirculation) have been described. However, the presence and degree of microcirculatory failure are in part independent from systemic macrohemodynamic variables. Macrocirculatory and microcirculatory failure can independently induce organ dysfunction. We review current diagnostic and therapeutic approaches for the assessment and optimization of both the macrocirculation and the microcirculation in septic shock. There are various technologies for the determination of macrocirculatory hemodynamic variables. We discuss the data on early goal-directed therapy for the resuscitation of the macrocirculation. In addition, we describe the concept of "individualized goal-directed hemodynamic therapy." Technologies to assess the local microcirculation are also available. However, adequate resuscitation goals for the optimization of the microcirculation still need to be defined. At present, we are not ready to specifically monitor and target the microcirculation in clinical routine outside studies. In the future, concepts for an integrative approach for individualized hemodynamic management of the macrocirculation and in parallel the microcirculation might constitute a huge opportunity to define additional resuscitation end points in septic shock.
Myc, Lukasz A; Stine, Jonathan G; Chakrapani, Rinita; Kadl, Alexandra; Argo, Curtis K
AIM To examine patient-centered outcomes with vasopressin (AVP) use in patients with cirrhosis with catecholamine-refractory septic shock. METHODS We conducted a single center, retrospective cohort study enrolling adult patients with cirrhosis treated for catecholamine-resistant septic shock in the intensive care unit (ICU) from March 2011 through December 2013. Other etiologies of shock were excluded. Multivariable regression models were constructed for seven and 28-d mortality comparing AVP as a second-line therapy to a group of all other vasoactive agents. RESULTS Forty-five consecutive patients with cirrhosis were treated for catecholamine-resistant septic shock; 21 received AVP while the remaining 24 received another agent [phenylephrine (10), dopamine (6), norepinephrine (4), dobutamine (2), milrinone (2)]. In general, no significant differences in baseline demographics, etiology of cirrhosis, laboratory values, vital signs or ICU mortality/severity of illness scores were observed with the exception of higher MELD scores in the AVP group (32.4, 95%CI: 28.6-36.2 vs 27.1, 95%CI: 23.6-30.6, P = 0.041). No statistically significant difference was observed in unadjusted 7-d (52.4% AVP vs 58.3% and P = 0.408) or 28-d mortality (81.0% AVP vs 87.5% non-AVP, P = 0.371). Corticosteroid administration was associated with lower 28-d mortality (HR = 0.37, 95%CI: 0.16-0.86, P = 0.021) independent of AVP use. CONCLUSION AVP is similar in terms of patient centered outcomes of seven and 28-d mortality, in comparison to all other vasopressors when used as a second line vasoactive agent in catecholamine resistant septic shock. Large-scale prospective study would help to refine current consensus standards and provide further support to our findings. PMID:28144392
Mukhopadhyay, Samanwoy; Thatoi, Pravat K; Pandey, Abhay D; Das, Bidyut K; Ravindran, Balachandran; Bhattacharjee, Samsiddhi; Mohapatra, Saroj K
Septic shock is a major medical problem with high morbidity and mortality and incompletely understood biology. Integration of multiple data sets into a single analysis framework empowers discovery of new knowledge about the condition that may have been missed by individual analysis of each of these datasets. Electronic search was performed on medical literature and gene expression databases for selection of transcriptomic studies done in circulating leukocytes from human subjects suffering from septic shock. Gene-level meta-analysis was conducted on the six selected studies to identify the genes consistently differentially expressed in septic shock. This was followed by pathway-level analysis using three different algorithms (ORA, GSEA, SPIA). The identified up-regulated pathway, Osteoclast differentiation pathway (hsa04380) was validated in two independent cohorts. Of the pathway, 25 key genes were selected that serve as an expression signature of Septic Shock.
Mukhopadhyay, Samanwoy; Thatoi, Pravat K.; Pandey, Abhay D.; Das, Bidyut K.; Ravindran, Balachandran; Bhattacharjee, Samsiddhi; Mohapatra, Saroj K.
Septic shock is a major medical problem with high morbidity and mortality and incompletely understood biology. Integration of multiple data sets into a single analysis framework empowers discovery of new knowledge about the condition that may have been missed by individual analysis of each of these datasets. Electronic search was performed on medical literature and gene expression databases for selection of transcriptomic studies done in circulating leukocytes from human subjects suffering from septic shock. Gene-level meta-analysis was conducted on the six selected studies to identify the genes consistently differentially expressed in septic shock. This was followed by pathway-level analysis using three different algorithms (ORA, GSEA, SPIA). The identified up-regulated pathway, Osteoclast differentiation pathway (hsa04380) was validated in two independent cohorts. Of the pathway, 25 key genes were selected that serve as an expression signature of Septic Shock. PMID:28199355
Huet, Olivier; Ramsey, Debbie; Miljavec, Sandra; Jenney, Adam; Aubron, Cecile; Aprico, Andrea; Stefanovic, Nada; Balkau, Beverley; Head, Geoff A; de Haan, Judy B; Chin-Dusting, Jaye P F
With animal models, death as an intentional end point is ethically unacceptable. However, in the study of septic shock, death is still considered the only relevant end point. We defined eight humane end points into four stages of severity (from healthy to moribund) and used to design a clinically relevant scoring tool, termed "the mouse clinical assessment score for sepsis" (M-CASS). The M-CASS was used to enable a consistent approach to the assessment of disease severity. This allowed an ethical and objective assessment of disease after which euthanasia was performed, instead of worsening suffering. The M-CASS displayed a high internal consistency (Cronbach α = 0.97) with a high level of agreement and an intraclass correlation coefficient equal to 0.91. The plasma levels of cytokines and markers of oxidative stress were all associated with the M-CASS score (Kruskal-Wallis test, P < 0.05). The M-CASS allows tracking of disease progression and animal welfare requirements.
Ng, Kevin; Schorr, Christa; Reboli, Annette C; Zanotti, Sergio; Tsigrelis, Constantine
In this incidence study, of 16 074 patients admitted to the intensive care unit (ICU) from 1/1/2003 to 7/31/2011, 161 cases of candidemia were identified. The incidence of sepsis (27%), severe sepsis (31%), and septic shock (40%) was remarkably high in these cases of candidemia, as was the all-cause in-hospital mortality for sepsis (30%), severe sepsis (44%), and septic shock (65%).
Pugni, Lorenza; Ronchi, Andrea; Bizzarri, Bianca; Consonni, Dario; Pietrasanta, Carlo; Ghirardi, Beatrice; Fumagalli, Monica; Ghirardello, Stefano; Mosca, Fabio
Septic shock, occurring in about 1% of neonates hospitalized in neonatal intensive care unit (NICU), is a major cause of death in the neonatal period. In the 1980s and 90s, exchange transfusion (ET) was reported by some authors to be effective in the treatment of neonatal sepsis and septic shock. The main aim of this retrospective study was to compare the mortality rate of neonates with septic shock treated only with standard care therapy (ScT group) with the mortality rate of those treated with ScT and ET (ET group). All neonates with septic shock admitted to our NICU from 2005 to 2015 were included in the study. Overall, 101/9030 (1.1%) neonates had septic shock. Fifty neonates out of 101 (49.5%) received one or more ETs. The mortality rate was 36% in the ET group and 51% in the ScT group (p = 0.16). At multivariate logistic regression analysis, controlling for potentially confounding factors significantly associated with death (gestational age, serum lactate, inotropic drugs, oligoanuria), ET showed a marked protective effect (Odds Ratio 0.21, 95% Confidence Interval: 0.06–0.71; p = 0.01). The lack of observed adverse events should encourage the use of this procedure in the treatment of neonates with septic shock. PMID:27171076
Pugni, Lorenza; Ronchi, Andrea; Bizzarri, Bianca; Consonni, Dario; Pietrasanta, Carlo; Ghirardi, Beatrice; Fumagalli, Monica; Ghirardello, Stefano; Mosca, Fabio
Septic shock, occurring in about 1% of neonates hospitalized in neonatal intensive care unit (NICU), is a major cause of death in the neonatal period. In the 1980s and 90s, exchange transfusion (ET) was reported by some authors to be effective in the treatment of neonatal sepsis and septic shock. The main aim of this retrospective study was to compare the mortality rate of neonates with septic shock treated only with standard care therapy (ScT group) with the mortality rate of those treated with ScT and ET (ET group). All neonates with septic shock admitted to our NICU from 2005 to 2015 were included in the study. Overall, 101/9030 (1.1%) neonates had septic shock. Fifty neonates out of 101 (49.5%) received one or more ETs. The mortality rate was 36% in the ET group and 51% in the ScT group (p = 0.16). At multivariate logistic regression analysis, controlling for potentially confounding factors significantly associated with death (gestational age, serum lactate, inotropic drugs, oligoanuria), ET showed a marked protective effect (Odds Ratio 0.21, 95% Confidence Interval: 0.06-0.71; p = 0.01). The lack of observed adverse events should encourage the use of this procedure in the treatment of neonates with septic shock.
Adler, Adam C; Cestero, Cesar; Brown, Robert B
Pasteurella multocida is a gram-negative organism categorized morphologically as a coccobacillus. P. multocida is a natural inhabitant found in the nasopharynx and oropharynx of numerous animal hosts, but serves as an opportunistic pathogen in humans. Pasturella multocida has multiple subspecies; when identified as the cause of infection they are broadly termed pasturelloses. Infections involving P. multocida are typically reported to occur in immune-compromised patients. Few cases in the literature identify pasturellosis as the causative agent of septic shock, especially in cirrhotic patients. Our patient's underlying cirrhosis and past splenectomy place her in the higher risk category for developing invasive Pasturella infection. We report a patient who presented with septic shock that was initially thought to be related to a urinary tract infection. It was later revealed that the patient's condition was caused by a recent cat bite leading to Pasturella bacteremia compounded by hepatic cirrhosis and previous splenectomy.
Decreased organ failure in patients with severe SIRS and septic shock treated with the platelet-activating factor antagonist TCV-309: a prospective, multicenter, double-blind, randomized phase II trial. TCV-309 Septic Shock Study Group.
Poeze, M; Froon, A H; Ramsay, G; Buurman, W A; Greve, J W
Sepsis and organ failure remain the main cause of death on the ICU. Sepsis is characterized by a severe inflammatory response, in which platelet-activating factor (PAF) is considered to play an important role. This study investigated whether treatment with the PAF-antagonist TCV-309 reduces morbidity and mortality in patients with septic shock. The study was conducted as a double-blind, randomized, placebo controlled multicenter study. The included patients had to fulfill the SIRS criteria with a clinical suspicion of infection, an admission APACHE II score greater than 15, and shock, defined as a mean arterial pressure <70 mmHg and/or a decrease > or =40 mmHg despite adequate fluid resuscitation. Patients received 1.0 mg/kg TCV-309 or placebo, twice daily, intravenously during 14 days. The prospectively set goals were MOF score, recovery from shock, mortality, and assessment of the safety of the medication. A total of 98 patients were included of which 97 were analyzed on an intention-to-treat basis. The overall survival at day 56 of TCV-309 treated patients was similar compared to placebo treated patients (51.0% vs. 41.7%, P = 0.47). In contrast, the mean percentage of failed organs per patient present after 14 days in the TCV-309 treated patients was significantly lower compared to the placebo treated patients (11.9% vs. 25.1%, P = 0.04), leading to a reduced need for vasopressors, dialysis, and ventilatory support. Furthermore, the mean APACHE-II score during treatment with TCV-309 was significantly lower and the number of patients recovered from shock after day 14 was significantly higher in the TCV-309 treated patient group (2/32 vs. 9/29, P = 0.01). The number of adverse events was not significantly different between the TCV-309 and placebo treated patients. TCV-309 did not change overall mortality of septic shock, however a substantial reduction in organ dysfunction and morbidity, frequently associated with septic shock was achieved, without significant
Zabet, Mohadeseh Hosseini; Mohammadi, Mostafa; Ramezani, Masoud; Khalili, Hossein
Objective: Effects of ascorbic acid on hemodynamic parameters of septic shock were evaluated in nonsurgical critically ill patients in limited previous studies. In this study, the effect of high-dose ascorbic acid on vasopressor drug requirement was evaluated in surgical critically ill patients with septic shock. Methods: Patients with septic shock who required a vasopressor drug to maintain mean arterial pressure >65 mmHg were assigned to receive either 25 mg/kg intravenous ascorbic acid every 6 h or matching placebo for 72 h. Vasopressor dose and duration were considered as the primary outcomes. Duration of Intensive Care Unit (ICU) stay and 28-day mortality has been defined as secondary outcomes. Findings: During the study period, 28 patients (14 in each group) completed the trial. Mean dose of norepinephrine during the study period (7.44 ± 3.65 vs. 13.79 ± 6.48 mcg/min, P = 0.004) and duration of norepinephrine administration (49.64 ± 25.67 vs. 71.57 ± 1.60 h, P = 0.007) were significantly lower in the ascorbic acid than the placebo group. No statistically significant difference was detected between the groups regarding the length of ICU stay. However, 28-day mortality was significantly lower in the ascorbic acid than the placebo group (14.28% vs. 64.28%, respectively; P = 0.009). Conclusion: High-dose ascorbic acid may be considered as an effective and safe adjuvant therapy in surgical critically ill patients with septic shock. The most effective dose of ascorbic acid and the best time for its administration should be determined in future studies. PMID:27162802
Chalkias, Athanasios; Spyropoulos, Vaios; Koutsovasilis, Anastasios; Papalois, Apostolos; Kouskouni, Evaggelia; Xanthos, Theodoros
Cardiopulmonary resuscitation in patients with severe sepsis and septic shock is challenging and usually unsuccessful. The aim of the present study is to describe our swine model of cardiac arrest and resuscitation in severe sepsis and septic shock. In this prospective randomized animal study, 10 healthy female Landrace-Large White pigs with an average weight of 20 ± 1 kg (aged 19 - 21 weeks) were the study subjects. Septicemia was induced by an intravenous infusion of a bolus of 20-mL bacterial suspension in 2 min, followed by a continuous infusion during the rest of the experiment. After septic shock was confirmed, the animals were left untreated until cardiac arrest occurred. All animals developed pulseless electrical activity between the fifth and sixth hours of septicemia, whereas five (50%) of 10 animals were successfully resuscitated. Coronary perfusion pressure was statistically significantly different between surviving and nonsurviving animals. We found a statistically significant correlation between mean arterial pressure and unsuccessful resuscitation (P = 0.046), whereas there was no difference in end-tidal carbon dioxide (23.05 ± 1.73 vs. 23.56 ± 1.70; P = 0.735) between animals with return of spontaneous circulation and nonsurviving animals. During the 45-min postresuscitation monitoring, we noted a significant decrease in hemodynamic parameters, although oxygenation indices and lactate clearance were constantly increased (P = 0.001). This successful basic swine model was for the first time developed and may prove extremely useful in future studies on the periarrest period in severe sepsis and septic shock.
Siami, Shidasp; Polito, Andrea; Porcher, Raphael; Hissem, Tarik; Blanchard, Anne; Boucly, Catherine; Carlier, Robert; Annane, Djillali; Haymann, Jean-Philippe; Sharshar, Tarek
Objective Vasopressin (AVP) secretion during an osmotic challenge is frequently altered in the immediate post-acute phase of septic shock. We sought to determine if this response is still altered in patients recovering from septic shock. Design Prospective interventional study Setting Intensive care unit (ICU) at Raymond Poincaré and Etampes Hospitals. Patients Normonatremic patients at least 5 days post discontinuation of catecholamines given for a septic shock. Intervention Osmotic challenge involved infusing 500 mL of hypertonic saline solution (with cumulative amount of sodium not exceeding 24 g) over 120 minutes. Measurements and main results Plasma AVP levels were measured 15 minutes before the infusion and then every 30 minutes for two hours. Non-responders were defined as those with a slope of the relation between AVP and plasma sodium levels less than < 0.5 ng/mEq. Among the 30 included patients, 18 (60%) were non-responders. Blood pressure and plasma sodium and brain natriuretic peptide levels were similar in both responders and non-responders during the course of the test. Critical illness severity, hemodynamic alteration, electrolyte disturbances, treatment and outcome did not differ between the two groups. Responders had more severe gas exchange abnormality. Thirst perception was significantly diminished in non-responders. The osmotic challenge was repeated in 4 non-responders several months after discharge and the abnormal response persisted. Conclusion More than half of patients recovering from septic shock have an alteration of osmoregulation characterised by a dramatic decrease in vasopressin secretion and thirst perception during osmotic challenge. The mechanisms of this alteration but also of the relationship between haematosis and normal response remain to be elucidated. PMID:24223220
Troskot, Rosana; Šimurina, Tatjana; Žižak, Mirza; Majstorović, Karolina; Marinac, Ivana; Šutić, Ines Mrakovčić
Aim To investigate the changes in the venoarterial carbon-dioxide gradient (V-a Pco2) and its prognostic value for survival of patients with severe sepsis and septic shock. Methods The study was conducted in General Hospital Holy Spirit from January 2004 to December 2007 and included 71 conveniently sampled adult patients (25 women and 46 men), who fulfilled the severe sepsis and septic shock criteria and were followed for a median of 8 days (interquartile range, 12 days). The patients were divided in two groups depending on whether or not they had been mechanically ventilated. Both groups of patients underwent interventions with an aim to achieve hemodynamic stability. Mechanical ventilation was applied in respiratory failure. Venoarterial carbon dioxide gradient was calculated from the difference between the partial pressure of arterial CO2 and the partial pressure of mixed venous CO2, which was measured with a pulmonary arterial Swan-Ganz catheter. The data were analyzed using Kaplan-Meier survival analysis, along with a calculation of the hazard ratios. Results There was a significant difference between non-ventilated and ventilated patients, with almost 4-fold greater hazard ratio for lethal outcome in ventilated patients (3.85; 95% confidence interval, 1.64-9.03). Furthermore, the pattern of changes of many other variables was also different in these two groups (carbon dioxide-related variables, variables related to acid-base status, mean arterial pressure, systemic vascular resistance, lactate, body mass index, Acute Physiology and Chronic Health Evaluation II, Simplified Acute Physiology II Score, and Sepsis-related Organ Failure Assessment score). Pco2 values (with a cut-off of 0.8 kPa) were a significant predictor of lethal outcome in non-ventilated patients (P = 0.015) but not in ventilated ones (P = 0.270). Conclusion V-a Pco2 was a significant predictor of fatal outcome only in the non-ventilated group of patients. Ventilated patients are more
Mari, Arnaud; Vallée, Fabrice; Bedel, Jérome; Riu, Béatrice; Ruiz, Jean; Sanchez-Verlaan, Pascale; Geeraerts, Thomas; Génestal, Michèle; Silva, Stein; Fourcade, Olivier
Transcutaneous oxygen pressure (PtcO2) value in response to an increase of FiO2 or oxygen challenge test (OCT) in ventilated patients has been reported to be related to peripheral perfusion and outcome during septic shock. However, patients with sepsis-related acute respiratory distress syndrome could demonstrate compromised arterial oxygenation with OCT impairment decoupled to circulatory failure. The aims of this study were to confirm the prognostic value of OCT and to explore the influence of respiratory status on OCT results. This was a prospective study set in an intensive care unit of a tertiary teaching hospital. Fifty-six mechanically ventilated patients with septic shock criteria were studied. Transcutaneous oxygen pressure was measured at baseline and after OCT, at intensive care unit admittance (T0), and 24 h later (T24). Survival at day 28 and hemodynamic and respiratory parameters were analyzed and compared according to outcome and respiratory status. Central hemodynamic parameters or static transcutaneous data did not differ between survivors and nonsurvivors at enrollment. The OCT was statistically different at T24 according to outcome (P < 0.001), but sensitivity was low (53%). Moreover, patients with low OCT results at T24 exhibited more severe respiratory failure (P < 0.01). The OCT at T24 is related to outcome but is influenced by the severity of respiratory failure. Our results suggest considering with caution hemodynamic management based on OCT in septic shock patients with altered pulmonary function.
Kitayama, Hiromitsu; Sugiyama, Junko; Hirayama, Michiaki; Onada, Yosihiro; Tsuji, Yasushi
Background As a symptom of pyomyositis, sepsis usually follows local inflammation signs. Here, we report pyomyositis with lymphedema of upper extremity in which septic shock and poor local findings initially presented during chemotherapy for breast cancer. Case Report An 80-year-old woman presented with chronic right shoulder pain during chemotherapy for the recurrent disease. She had a history of postmastectomy lymphedema, diabetes mellitus, and repeated hyaluronic acid injections to the shoulder joint. The pain suddenly worsened with septic shock and no apparent local signs. Magnetic resonance imaging revealed myonecrosis, and no pus was yielded by ultrasound-guided needle aspiration. After 2 weeks of recovery by conservative medical management, surgical drainage was performed. Late formulated massive intramuscular pus showed severe neutrophil infiltration and myonecrosis. Conclusion Pyomyositis can develop into septic shock with poor local signs. Myelosuppression after chemotherapy can cause myonecrosis without macroabscess, and magnetic resonance imaging was useful for the diagnosis of this condition. When unspecified local pain appears during cancer chemotherapy we should consider this disease, too. PMID:27920709
Background Sepsis-associated brain dysfunction has been linked to white matter lesions (leukoencephalopathy) and ischemic stroke. Our objective was to assess the prevalence of brain lesions in septic shock patients requiring magnetic resonance imaging (MRI) for an acute neurologic change. Method Seventy-one septic shock patients were included in a prospective observational study. Patients underwent daily neurological examination. Brain MRI was obtained in patients who developed focal neurological deficit, seizure, coma, or delirium. Electroencephalogy was performed in case of coma, delirium, or seizure. Leukoencephalopathy was graded and considered present when white matter lesions were either confluent or diffuse. Patient outcome was evaluated at 6 months with the Glasgow Outcome Scale (GOS). Results We included 71 patients with median age of 65 years (56 to 76) and SAPS II at admission of 49 (38 to 60). MRI was indicated on focal neurological sign in 13 (18%), seizure in 7 (10%), coma in 33 (46%), and delirium in 35 (49%). MRI was normal in 37 patients (52%) and showed cerebral infarcts in 21 (29%), leukoencephalopathy in 15 (21%), and mixed lesions in 6 (8%). EEG malignant pattern was more frequent in patients with ischemic stroke or leukoencephalopathy. Ischemic stroke was independently associated with disseminated intravascular coagulation (DIC), focal neurologic signs, increased mortality, and worse GOS at 6 months. Conclusions Brain MRI in septic shock patients who developed acute brain dysfunction can reveal leukoencephalopathy and ischemic stroke, which is associated with DIC and increased mortality. PMID:24047502
Sepsis is a common disorder associated with high morbidity and mortality. It is now defined as an abnormal host response to infection, resulting in life-threatening dysfunction of organs. There is evidence from in vitro and in vivo experiments in various animal models and in patients that endotoxin or sepsis may directly and indirectly alter the hypothalamic–pituitary–adrenal response to severe infection. These alterations may include necrosis or hemorrhage or inflammatory mediator-mediated decreased ACTH synthesis, steroidogenesis, cortisol delivery to tissues, clearance from plasma, and decreased sensitivity of tissues to cortisol. Disruption of the hypothalamic–pituitary–adrenal axis may translate in patients with sepsis into cardiovascular and other organ dysfunction, and eventually an increase in the risk of death. Exogenous administration of corticosteroids at moderate dose, i.e., <400 mg of hydrocortisone or equivalent for >96 h, may help reversing sepsis-associated shock and organ dysfunction. Corticosteroids may also shorten the duration of stay in the ICU. Except for increased blood glucose and sodium levels, treatment with corticosteroids was rather well tolerated in the context of clinical trials. The benefit of treatment on survival remains controversial. Based on available randomized controlled trials, the likelihood of survival benefit is greater in septic shock versus sepsis patients, in sepsis with acute respiratory distress syndrome or with community-acquired pneumonia versus patients without these conditions, and in patients with a blunted cortisol response to 250 μg of ACTH test versus those with normal response. PMID:27379022
Adamik, Barbara; Smiechowicz, Jakub; Jakubczyk, Dominika; Kübler, Andrzej
To examine the effect of endotoxemia on the procalcitonin (PCT) serum levels and mortality rates of adult patients with septic shock diagnosed on the day of admission to the intensive care unit (ICU).A retrospective observational study was performed over a 2-year period. Levels of PCT were compared for septic shock patients with and without endotoxemia on admission to the ICU. Endotoxemia was identified with an Endotoxin Activity Assay.One hundred fifty-seven patients with septic shock were enrolled into the study. Group 1 consisted of patients with elevated endotoxin activity (EA) (n = 95, EA = 0.57 endotoxin activity unit [EAU] [0.46-0.67]) and Group 2 consisted of patients with low EA (n = 62, EA = 0.27 EAU [0.17-0.36]). Acute Physiology And Chronic Health Evaluation II (APACHE II) score and SOFA score were similar in both groups (APACHE II = 23 [16-29] and 19 [16-25]; Sequential Organ Failure Assessment [SOFA] = 10 [7-13] and 11 [8-12] in Groups 1 and 2, respectively) (nonsignificant). The PCT level was 6 times higher in Group 1 than in Group 2 (19.6 ng/mL vs. 3.1 ng/mL, P < 0.001). There was a strong correlation between EA and serum PCT (P < 0.001, R = 0.5). The presence of endotoxemia on admission to the ICU was associated with an increased mortality rate: 52% in the group of patients with endotoxemia and 25% in the group without endotoxemia. EA in survivors was 0.39 EAU (0.26-0.57) and 0.53 EAU (0.4-0.61) in nonsurvivors (P = 0.004). The median PCT level in survivors was 6.7 ng/mL (2.3-28.0), compared with 16.7 ng/mL (5.3-31.0) in nonsurvivors (P = 0.04).This observational study revealed that endotoxemia in patients with septic shock on admission to the ICU was frequently found and was associated with an elevated PCT level and a high mortality rate. Endotoxemia was a common occurrence in patients with septic shock, regardless of the infecting microorganism.
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
Průcha, M; Zazula, R; Herold, I; Dostál, M; Hyánek, T; Bellingan, G
In this retrospective study we assessed the frequency of hypogammaglobulinemia in 708 patients with SIRS, severe sepsis and septic shock. We evaluated the relationship between hypogammaglobulinemia IgG, IgM and 28 day mortality. Total of 708 patients and 1,513 samples were analyzed. In the three subgroups we investigated, patients met the criteria of SIRS, severe sepsis and septic shock. IgG hypogammaglobulinemia was demonstrated in 114 patients with severe sepsis (25.2%), 11 septic shock patients (24.4%), and in 29 SIRS patients (13.9%). IgM hypogammaglobulinemia was documented in 55 patients with severe sepsis (12.2%), 6 septic shock patients (13.3%), and in 17 SIRS patients (8.1%). Mortality of patients with severe sepsis and normal IgG levels was significantly lower (111 patients; 32.8%) compared with those with IgG hypogammaglobulinemia (49 patients; 43.0%; p=0.001). Mortality of patients with septic shock and IgG hypogammaglobulinemia (n=5) was significantly higher compared with those with normal IgG levels (45.5% vs. 38.2%; p=0.001). Mortality of patients with severe sepsis and IgM hypogammaglobulinemia did not differ from that of patients with normal IgM levels (37.0 vs. 41.8%). Mortality of patients with septic shock and IgM hypogammaglobulinemia was significantly higher compared with those with normal IgM levels (50% vs. 38.5%; p=0.0001). This study documented relatively high incidence of hypogammaglobulinemia IgG and IgM in patients with severe sepsis, septic shock and SIRS respectively. The presence of IgG hypogammaglobulinemia in patients with severe sepsis is independent factor of mortality.
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
Kushawaha, Anurag; Brown, Mark; Martin, Ismael; Evenhuis, Walther
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
Miguel, C; Gonçalves, I; Matos, Maria L; Coelho, Paulo Clemente
We report the clinical case of a 76 years-old woman with a subacute trochanteric inflammatory pain with low-grade fever and laboratory markers of acute inflammation, associated with the ultrasonographic evidence of bursitis and radiologic evidence of femoral erosions, that resolved after intravenous antibiotherapy. Although rare, the infectious etiology should be considered in patients with clinical manifestations of bursitis and signs of systemic involvement.
Li, Jia; Li, Ming; Su, Longxiang; Wang, Huijuan; Xiao, Kun; Deng, Jie; Jia, Yanhong; Han, Gencheng; Xie, Lixin
Circulating lymphocyte number was significantly decreased in patients with sepsis. However, it remains unknown which severity phase (sepsis, severe sepsis, and septic shock) does it develop and what happen on each subpopulation. Eight patients with differing severities of sepsis (31 sepses, 33 severe sepses, and 16 septic shocks) were enrolled. Quantitative real-time polymerase chain reaction (RT-PCR) of Th1, Th2, and Th17; regulatory T (Treg) cell-specific transcription factor T-bet; GATA-3; RORgammat (RORγt); forkhead box P3 (FOXP3); and IL-17 mRNA were performed, and the enzyme-linked immunosorbent assay (ELISA) was used to detect serum interferon (IFN)-γ, IL-4, and IL-10. In this study, the Th1, Th2, Treg transcription factors, and related cytokines IFN-γ, IL-4, and IL-10 levels of sepsis and severe sepsis patients in peripheral blood were significantly higher than those of the normal controls. Except for IL-17, the T-bet, GATA-3, and IFN-γ levels of septic shock patients were lower than those of sepsis patients. We also observed that the proportions of Th17/Treg in the sepsis and septic shock groups were inversed. From the above, the inflammatory response especially the adaptive immune response is still activated in sepsis and severe sepsis, but significant immunosuppression was developed in septic shock. In addition, the proportion of Th17/Treg inversed may be associated with the illness aggravation of patients with sepsis.
Fischer, Doris; Nold, Marcel F; Nold-Petry, Claudia A; Furlan, Antonio; Veldman, Alex
Objectives Sepsis remains a disease with a high mortality in neonates. Microcirculatory impairment plays a pivotal role in the development of multiorgan failure in septic newborns. The hemodynamic effects of recombinant activated protein C (rhAPC) were tested in an animal model of neonatal septic shock focusing on intestinal microcirculation. Materials and methods Endotoxic shock was triggered by intravenous application of Escherichia coli lipopolysaccarides in newborn piglets. Thereafter, five animals received a continuous infusion of 24 μg/kg/h rhAPC, and five received vehicle for control. Over the course of three hours, intestinal microcirculation was assessed by intravital microscopy every 30 min. Macrocirculation and blood counts were monitored simultaneously. Results After a short hypotensive period in all animals, the arterial blood pressure returned to baseline in the rhAPC-treated piglets, whereas the hypotension became increasingly severe in the controls. By 90 min, mean blood pressure in the controls was significantly lower than in the treatment group. Similar observations were made regaring microcirculation. After an early impairment in all study animals, functional capillary density and intestinal microcirculatory red blood cell velocity and red blood cell flow recovered in the rhAPC group, but deteriorated further in the control piglets. Conclusion Recombinant activated protein C protects macro- and microcirculation from endotoxic shock. PMID:19774219
Tomino, Atsutoshi; Tsuda, Masanobu; Aoki, Ruri; Kajita, Yuka; Hashiba, Masamitsu; Terajima, Tsuguaki; Kano, Hideki
Sepsis causes impairment of innate and adaptive immunity by multiple mechanisms, including depletion of immune effector cells and T cell exhaustion. Although lymphocyte dysfunction is associated with increased mortality and potential reactivation of latent viral infection in patients with septic shock, the relation between viral reactivation and lymphocyte dysfunction is obscure. The objectives of this study were 1) to determine the relation of lymphocyte dysfunction to viral reactivation and mortality, and 2) to evaluate recovery of lymphocyte function during septic shock, including T cell receptor (TCR) diversity and the expression of programmed death 1 (PD-1). In 18 patients with septic shock and latent cytomegalovirus (CMV) infection, serial blood samples were obtained on days 1, 3, and 7 after the onset of shock, and immune cell subsets and receptor expression were characterized by flow cytometry. TCR diversity of peripheral blood mononuclear cells was analyzed by Multi-N-plex PCR, and CMV DNA was quantified using a real-time PCR kit. A decrease of TCR diversity and monocyte HLA-DR expression were observed in the early stage of septic shock, while CD4+ T cells displayed an increase of PD-1 expression. Significant lymphopenia persisted for at least 7 days following the onset of septic shock. Normalization of TCR diversity and PD-1 expression was observed by day 7, except in patients who died. CMV reactivation was detected in 3 of the 18 patients during the first week of their ICU stay and all 3 patients died. These changes are consistent with the early stage of immune cell exhaustion and indicate the importance of normal lymphocyte function for recovery from septic shock. Ongoing lymphocyte dysfunction is associated with CMV reactivation and dissemination, as well as with unfavorable outcomes. PMID:28072859
Shimizu, Tomoharu; Obata, Toru; Sonoda, Hiromichi; Akabori, Hiroya; Miyake, Tohru; Yamamoto, Hiroshi; Tabata, Takahisa; Eguchi, Yutaka; Tani, Tohru
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.
Mesquida, Jaume; Gruartmoner, Guillem; Martínez, Maria Luisa; Masip, Jordi; Sabatier, Caroline; Espinal, Cristina; Artigas, Antonio; Baigorri, Francisco
This prospective study was aimed to test the hypothesis that tissue hemoglobin oxygen saturation (StO₂) measured noninvasively using near-infrared spectroscopy is a reliable indicator of global oxygen delivery (DO₂) measured invasively using a pulmonary artery catheter (PAC) in patients with septic shock. The study setting was a 26-bed medical-surgical intensive care unit at a university hospital. Subjects were adult patients in septic shock who required PAC hemodynamic monitoring for resuscitation. Interventions included transient ischemic challenge on the forearm. After blood pressure normalization, hemodynamic and oximetric PAC variables and, simultaneously, steady-state StO₂ and its changes from ischemic challenge (deoxygenation and reoxygenation rates) were measured. Fifteen patients were studied. All the patients had a mean arterial pressure above 65 mmHg. The DO₂ index (iDO₂) range in the studied population was 215 to 674 mL O₂/min per m. The mean mixed venous oxygen saturation value was 61% ± 10%, mean cardiac index was 3.4 ± 0.9 L/min per m, and blood lactate level was 4.6 ± 2.7 mmol/L. Steady-state StO₂ significantly correlated with iDO₂, arterial and venous O₂ content, and O₂ extraction ratio. A StO₂ cutoff value of 75% predicted iDO₂ below 450, with a sensitivity of 0.9 and a specificity of 0.9. In patients in septic shock and normalized MAP, low StO₂ reflects extremely low iDO₂. Steady-state StO₂ does not correlate with moderately low iDO₂, indicating poor sensitivity of StO₂ to rule out hypoperfusion.
El-Solh, Ali A; Abou Jaoude, Philippe; Porhomayon, Jahan
The use of supplemental sodium bicarbonate for the treatment of patients with septic shock and elevated blood lactate levels remains a controversial therapy. We conducted a retrospective study between March 2004 and February 2009 of 36 consecutive patients diagnosed with septic shock who received continuous infusion of bicarbonate therapy. A control group was matched 1:1 for age, site of infection, and predicted mortality by APACHE II. All patients were managed according to standard protocols. The median time until reversal of shock did not achieve statistical significance between the bicarbonate group (44.5 h [95% confidence interval [CI] 34-54] and the control group (55.0 h [95% CI 39-60] (p = 0.09). The median time to liberation of mechanical ventilation was significantly reduced in the bicarbonate group (10 days [95% CI 5.0-13.0] compared to the control group (14 days [95% CI 9.0-19.0], p = 0.02). The length of intensive care unit (ICU) stay was also shorter in the surviving patients who received bicarbonate compared to controls (median 11.5 days (95% CI 6.0-16.0) vs. 16.0 days (95% CI 13.5-19.0), respectively; p = 0.01). However, there was no difference in 28-day mortality between the two study groups (28%; 95% CI 14-45% vs. 33%; 95% CI 19-51%, respectively; p = 0.79). Infusion of sodium bicarbonate in septic patients with arterial hyperlactatemia may facilitate weaning from mechanical ventilation and reduce length of ICU stay.
Choudhary, Richa; Sitaraman, Sadasivan; Choudhary, Anita
Context: 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. Aims: To evaluate the predictive value of lactate clearance and to determine the optimal cut-off value for predicting outcome in children with septic shock. Settings and Design: A prospective observational study was performed on children with septic shock admitted to pediatric Intensive Care Unit (PICU). Subjects and Methods: 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. Results: 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). Conclusions: 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. PMID:28367008
Wu, Yifen; Zhang, Ning; Wu, Yifu; Zheng, Yanping; You, Xiaoen; Cao, Zhuo; Xu, Yaqi
The effect of different vasoactive drugs on the pH [intracellular pH (pHi)] of gastric mucosa in patients with septic shock was evaluated in the present study. According to the vasoactive drugs applied, 48 patients with septic shock were divided into 3 groups: A, B and C, with 16 cases each. Cases of group A were treated with dopamine, those of group B with norepinephrine while those of group C were treated with norepinephrine plus dobutamine. The changes of pH of gastric mucosa were observed before treatment (baseline) and 6, 12, 24 and 48 h after treatment, and the hemodynamic indicators were observed before treatment (baseline) and 6 h after administration. The gastric mucosal pH was not significantly different between two of the three groups before treatment (each at P>0.05). The gastric mucosal pH of group A did not change 6, 12, 24 and 48 h after treatment with drugs compared with the baseline (all at P>0.05), while the gastric mucosal pH in groups B and C were each statistically higher at the time points of 6, 12, 24 and 48 h after treatment with drugs compared with the respective baselines (all at P<0.05). Following treatment with drugs, the gastric mucosal pH of group C at all the time points of 6, 12, 24 and 48 h after treatment were significantly higher than those of groups A and B at the same time points after treatment, while there were some statistical differences between groups A and B at these time points (6, 12, 24 and 48 h after treatment; P<0.05). The hemodynamic indicators of the patients before treatment were not significantly different between two of the three groups (all at P>0.05). Compared with the baseline values, the mean arterial pressure and the cardiac index of each group after treatment were significantly increased, the pulmonary capillary wedge pressure and the central venous pressure of groups B and C significantly increased (all at P<0.05) and the heart rate of group A was significantly increased (P<0.05). In conclusion, the
Graham, D I; Behan, P O; More, I A
The neuropathological findings in six patients who developed neurological signs after the onset of "septic shock" caused by Gram-negative septicaemia are described. The changes in the brains were characteristic of acute haemorrhagic leucoencephalitis, and there was evidence, particularly in the kidneys, of disseminated intravascular coagulation with tubular necrosis and, in some, appearances indistinguishable from membrano-proliferative glomerulonephritis. It is agreed that acute haemorrhagic leucoencephalitis is another manifestation of a generalised Shwartzman reaction, and it is suggested that activation of complement is the final common pathway that produces tissue damage in the brain and kidney. Images PMID:762582
Carlier, Mieke; Taccone, Fabio S; Beumier, Majorie; Seyler, Lucie; Cotton, Frédéric; Jacobs, Frédérique; Roberts, Jason A
The aim of this study was to describe the population pharmacokinetics of cefepime in septic shock patients requiring continuous renal replacement therapy and to determine whether current or alternative dosing regimens can achieve PK/PD targets. In this observational PK study, 62 samples from 13 patients were analysed using non-linear mixed-effects modelling. Different dosing regimens were evaluated using Monte Carlo simulations with ultrafiltration flow rates (UFRs) of 1000, 1500 and 2000 mL/h. The probability of target attainment was calculated against a conservative (60% T(>MIC)) and a higher PK/PD target (100% T(>MIC)) against an MIC of 8 mg/L, the clinical susceptibility breakpoint for Pseudomonas aeruginosa. A one-compartment model with between-subject variability (BSV) on clearance and volume of distribution (V(d)) described the data adequately. UFR was supported as a covariate on both parameters. Typical values for clearance and V(d) were 4.4L/h (BSV 37%) and 40.9L (BSV 20%), respectively. Dosing simulations showed failure to achieve both a conservative and a higher PK/PD target using a dose of 1g q12h for patients treated with a high UFR (≥1500 mL/h). The dose of 2g q8h or 1g q6h leads to optimal target attainment for high UFR. One gram q8h is optimal for low UFR (≤1000 mL/h). We found important variability in PK parameters. Dosing simulations show that a dose of 2g q8h or 1g q6h is needed to ensure rapid achievement of adequate levels if the UFR is ≥1500 mL/h and 1g q8h for low UFR (≤1000 mL/h).
Ibarra-Estrada, Miguel A; Chávez-Peña, Quetzalcóatl; Reynoso-Estrella, Claudia I; Rios-Zermeño, Jorge; Aguilera-González, Pável E; García-Soto, Miguel A; Aguirre-Avalos, Guadalupe
AIM To characterize the prescribing patterns for hydrocortisone for patients with septic shock and perform an exploratory analysis in order to identify the variables associated with better outcomes. METHODS This prospective cohort study included 59 patients with septic shock who received stress-dose hydrocortisone. It was performed at 2 critical care units in academic hospitals from June 1st, 2015, to July 31st, 2016. Demographic data, comorbidities, medical management details, adverse effects related to corticosteroids, and outcomes were collected after the critical care physician indicated initiation of hydrocortisone. Univariate comparison between continuous and bolus administration of hydrocortisone was performed, including multivariate analysis, as well as Kaplan-Meier analysis to compare the proportion of shock reversal at 7 d after presentation. Receiver operating characteristic (ROC) curves determined the best cut-off criteria for initiation of hydrocortisone associated with the highest probability of shock reversal. We addressed the effects of the taper strategy for discontinuation of hydrocortisone, noting risk of shock relapse and adverse effects. RESULTS All-cause 30-d mortality was 42%. Hydrocortisone was administered as a continuous infusion in 54.2% of patients; time to reversal of shock was 49 h longer in patients who were given a bolus administration [59 h (range, 47.5-90.5) vs 108 h (range, 63.2-189); P = 0.001]. The maximal dose of norepinephrine after initiation of hydrocortisone was lower in patients on continuous infusion [0.19 μg/kg per minute (range, 0.11-0.28 μg)] compared with patients who were given bolus [0.34 μg/kg per minute (range, 0.16-0.49); P = 0.004]. Kaplan-Meier analysis revealed a higher proportion of shock reversal at 7 d in patients with continuous infusion compared to those given bolus (83% vs 63%; P = 0.004). There was a good correlation between time to initiation of hydrocortisone and time to reversal of shock (r = 0
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
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. Trial registration: University Hospital Medical Information Network Clinical
Johansson, Daniel; Ekström, Helena; Beronius, Ellen; Rasmussen, Magnus
The reliability of official registers of diagnosis depends on proper adherence to guidelines for diagnosis and diagnosis coding. Such guidelines for severe sepsis and septic shock have changed over the years, reflecting improved knowledge of these serious conditions. In order to investigate the compliance to current Swedish guidelines for diagnosis and coding of severe sepsis and septic shock, we studied the medical records from 300 patients with Escherichia coli bacteremia and 300 patients with Staphylococcus aureus bacteremia. Our study showed that out of 161 patients who fulfilled the criteria for either severe sepsis or septic shock, only 29 (18%) received an accurate diagnosis code. Thus, severe sepsis appears to be underappreciated in official registers of diagnosis in Sweden. It is important to improve the adherence to the present diagnosis guidelines in order for the registers to be reliable.
Meyns, E; Vermeersch, N; Ilsen, B; Hoste, W; Delooz, H; Hubloue, I
Gas gangrene of the liver is a rare clinical syndrome associated with a high rate of mortality. It is mostly associated with malignancy and immunosuppression. We report on a male patient who presented at the department of emergency medicine with high fever but no localised complaints. CT scan revealed a cavitary lesion filled with air in the liver. Clostridium perfringens was proved to be present in the hepatic lesion and the blood, and clostridium perfringens sepsis with gas gangrene of the liver was diagnosed. Despite early diagnosis and treatment the patient died. The importance of "an aggressive treatment policy" in this kind of life-threatening disease is emphasised.
Kase, Yoichi; Obata, Toru; Okamoto, Yasuhisa; Iwai, Kenichi; Saito, Keita; Yokoyama, Keitaro; Takinami, Masanori; Tanifuji, Yasumasa
Arachidonylethanolamide (AEA) and 2-arachidonylglycerol (2-AG) are endocannabinoids involved in septic shock, and 8-epi prostaglandin F2alpha (F2-isoprostane) is a biomarker of oxidative stress in biological systems. Because the antibiotic polymyxin B absorbs endocannabinoids as well as endotoxins, direct hemoperfusion therapy with polymyxin B-immobilized fibers (PMX-DHP) decreases serum levels of endocannabinoids. To investigate the features of sepsis and determine the proper use of PMX-DHP, we measured the changes in levels of endocannabinoids and F2-isoprostane in patients with septic shock. Twenty-six patients with septic shock, including those with septic shock induced by peritonitis, underwent laparotomy for drainage. Endocannabinoids absorption with PMX-DHP was examined in two groups of patients: patients whose mean arterial blood pressure (mABP) had increased more than 20 mm Hg (responder group; N = 13); and patients iwhose mABP did not increase or had increased no more than 20 mm Hg (non-responder group; N = 13). Levels of AEA did not change after PMX-DHP in either the non-responder or responder groups, whereas levels of 2-AG decreased significantly after PMX-DHP in the responder group, but not in the non-responder group. F2-isoprostane gradually increased after PMX-DHP treatment; on the other hand, levels of F2-isoprostane remained constant in the responder group. Patients with septic shock are under considerable oxidative stress, and 2-AG plays an important role in the cardiovascular status of these patients. The removal of 2-AG by PMX-DHP benefits patients with septic shock by stabilizing cardiovascular status and decreasing long-term oxidative stress.
Gil, Julio; Antunes, Hugo; Marmelo, Bruno; Abreu, Luis; Goncalves, Maria Luisa; dos Santos, Luis Ferreira; Cabral, Jose Costa
Pseudoaneurysm of the mitral-aortic intervalvular fibrosa (P-MAIVF) is a rare complication of infective endocarditis and trauma, particularly of aortic valve surgery. Clinical symptoms are usually unspecific and generally due to complications. Transesophageal echocardiography (TEE) is the most commonly used exam to diagnose P-MAIVF. The main echocardiographic feature is the presence of a cavity communicating with the left ventricular outflow tract that expands during systole and collapses during diastole. Most frequent complications are formation of a fistulous tract and compression of adjacent structures. Surgical correction is usually the treatment of choice. The authors describe a case of a female patient with a septic shock of unclear origin. After antibiotic therapy and organ-supporting measures without apparent improvements, a TEE revealed infective endocarditis, complicated with P-MAIVF. Despite adequate treatment, the patient did not survive for long enough to be submitted to surgical repair. PMID:28179972
Ko, Young Hwii; Ji, Yoon Seob; Park, Sin-Youl; Kim, Su Jin; Song, Phil Hyun
ABSTRACT Introduction: To investigate the role of initial procalcitonin (PCT) level as an early predictor of septic shock for the patient with sepsis induced by acute pyelonephritis (APN) secondary to ureteral calculi. Materials and Methods: The data from 49 consecutive patients who met criteria of sepsis due to APN following ureteral stone were collected and divided into two groups: with (n=15) or without (n=34) septic shock. The clinical variables including PCT level for this outcome were retrospectively compared by univariate analysis, followed by multivariable logistic regression model. Results: All subjects had hydronephrosis, and were hospitalized with the mean of 11.8 days (3–42 days). The mean size of the ureteral stones was 7.5mm (3–30mm), and 57% were located in upper ureter. At univariate analysis, patients with septic shock were significantly older, a higher proportion had hypertension, lower platelet count and serum albumin level, higher CRP and PCT level, and higher positive blood culture rate. Multivariate models indicated that lower platelet count and higher PCT level are independent risk factors (p=0.043 and 0.046, respectively). In ROC curve, the AUC was significantly wider in PCT (0.929), compared with the platelet count (0.822, p=0.004). At the cut-off of 0.52ng/mL, the sensitivity and specificity were 86.7% and 85.3%. Conclusion: Our study demonstrated elevated initial PCT levels as an early independent predictor to progress into septic shock in patients with sepsis associated with ureteral calculi. PMID:27256181
Fujii, Tomoko; Ganeko, Riki; Kataoka, Yuki; Featherstone, Robin; Bagshaw, Sean M
Introduction Polymyxin-B immobilised haemoperfusion (PMX-HP) is a promising adjuvant strategy for the treatment of sepsis and septic shock. PMX-HP therapy works by clearing circulating endotoxin through binding to polymyxin-immobilised fibres during haemoperfusion. Small clinical trials have shown that PMX-HP therapy is associated with improved haemodynamic profile, oxygenation and survival. However, clear inferences have been largely inconclusive due to limitations in study design (eg, small, unblinded) and generalisability. We therefore propose to perform an up-to-date systematic review and evidence synthesis to describe the efficacy, safety and effectiveness of PMX-HP for adult patients with sepsis or septic shock. Methods and analysis We will search the following databases from 1946 to 2016 MEDLINE (Ovid), EMBASE (Ovid), Cochrane Library, Health Technology Assessment Database (HTA), Cumulative Index to Nursing and Allied Health Literature (CINAHL), PubMed and ‘Igaku Chuo Zasshi’ (ICHUSHI) for randomised controlled trials of PMX-HP in critically ill patients with sepsis or septic shock. There will be no language restrictions in the electronic search for studies. Two reviewers will extract data and appraise the quality of each study independently. The primary outcome will be the pooled risk ratio of 28-day all-cause mortality. Serious adverse events and changes in organ dysfunction scores will also be evaluated. The secondary outcomes will be 90-day all-cause mortality, changes in haemodynamic profile and endotoxin levels, and health services use. Ethics and dissemination Our systematic review will synthesise the evidence on use of the PMX-HP as an adjuvant therapy in sepsis/septic shock to improve patient-centred, physiological and health services outcomes. Research ethics is not required for this review. The study will be disseminated by peer-reviewed publication and conference presentation. Trial registration number CRD42016038356. PMID:27872122
Vänskä, Matti; Koivula, Irma; Hämäläinen, Sari; Pulkki, Kari; Nousiainen, Tapio; Jantunen, Esa; Juutilainen, Auni
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
Background In order to develop clinical reasoning, medical students must be able to integrate knowledge across traditional subject boundaries and multiple disciplines. At least two dimensions of integration have been identified: horizontal integration, bringing together different disciplines in considering a topic; and vertical integration, bridging basic science and clinical practice. Much attention has been focused on curriculum overhauls, but our approach is to facilitate horizontal and vertical integration on a smaller scale through an interdisciplinary case study discussion and then to assess its utility. Methods An interdisciplinary case study discussion about a critically ill patient was implemented at the end of an organ system-based, basic sciences module at New York University School of Medicine. Three clinical specialists—a cardiologist, a pulmonologist, and a nephrologist—jointly led a discussion about a complex patient in the intensive care unit with multiple medical problems secondary to septic shock. The discussion emphasized the physiologic underpinnings behind the patient’s presentation and the physiologic considerations across the various systems in determining proper treatment. The discussion also highlighted the interdependence between the cardiovascular, respiratory, and renal systems, which were initially presented in separate units. After the session students were given a brief, anonymous three-question free-response questionnaire in which they were asked to evaluate and freely comment on the exercise. Results Students not only took away physiological principles but also gained an appreciation for various thematic lessons for bringing basic science to the bedside, especially horizontal and vertical integration. The response of the participants was overwhelmingly positive with many indicating that the exercise integrated the material across organ systems, and strengthened their appreciation of the role of physiology in understanding
Osborn, Tiffany M
Between 2014 and 2015, 3 independent, multicenter, randomized controlled trials evaluated early goal-directed therapy (EGDT) in severe sepsis and septic shock: Protocolized Care for Early Septic Shock (ProCESS) from the United States; Australasian Resuscitation in Sepsis Evaluation (ARISE), and Protocolised Management in Sepsis (ProMISe) in the United Kingdom. All 3 trials confirmed that there was no survival benefit of EGDT compared to usual resuscitation. How should we define usual care for sepsis given these study findings? Furthermore, the definition of sepsis has now been updated. This article reviews key findings of these 3 trials and discusses these important issues in sepsis management.
Herzum, I; Renz, H
Despite great advancement in the understanding of the pathophysiology and in the development of novel therapeutic approaches, mortality of sepsis still remains unacceptably high. Adequate laboratory diagnostics represents a major requirement for the improvement of this situation. For a better understanding of the immunological dysregulation in this disease, several markers are now available for routine diagnostics in the clinical laboratory. They include the cytokines interleukin (IL) -6, IL-8, procalcitonin and the LPS-binding protein (LBP). These novel markers will be compared to the conventional procedure of diagnosing inflammatory and infectious disease, such as measurements of C-reactive protein (CRP) as a major acute phase protein and differential blood counting. Important questions addressed in this review are the usefulness of these markers for early diagnosis, their role as prognostic markers and in the risk assessment of patients. Furthermore, we will discuss whether these parameters are to differentiate between systemic inflammatory response syndrome (SIRS) and sepsis at its different degrees. In the case of an infectious nature of the disease, it is important to differentiate between viral or bacterial origin and to monitor the responsiveness of antibiotic therapies. The literature was analysed with focus on the evidence for diagnostic and analytical performance. For this purpose international definition and staging criteria were used in context of criteria for assay performance including sensitivity, specificity, negative and positive predictive values, ROC analysis and other analytical criteria.
Procalcitonin has been proposed as a specific biomarker of bacterial infections and has been related to the severity of sepsis. The prognostic ability of the initial concentrations of procalcitonin in sepsis is controversial. Some studies find higher initial concentrations in non-survivors but others find no differences. Prognostic assessment based on follow-up of procalcitonin levels may be better than evaluation of the initial levels of procalcitonin. The persistence of elevated procalcitonin levels is indicative of poor prognosis and is associated with mortality. Procalcitonin kinetics could be a tool for assessing the evolution of severe sepsis and sepsis shock. Procalcitonin should find its place as a biomarker for predicting treatment failure of severe sepsis and septic shock. PMID:24004571
Boisramé-Helms, Julie; Meyer, Grégory; Degirmenci, Su Emmanuelle; Burban, Mélanie; Schini-Kerth, Valérie; Cynober, Luc; De Bandt, Jean-Pascal; Hasselmann, Michel; Meziani, Ferhat
Background Immunonutrition in sepsis, including n-3 poly-unsaturated fatty acids (PUFAs) or L-arginine supplementation, is a controversial issue that has yielded a great number of studies for the last thirty-five years, and the conclusions regarding the quantity and quality of this support in patients are deceiving. The aim of the present experimental study is to investigate the effects of a pretreatment with enteral nutrition enriched with n-3 PUFAs or L-arginine on vascular dysfunctions, inflammation and oxidative stress during septic shock in rats. Design Rats were fed with enteral Peptamen® HN (HN group), Peptamen® AF containing n-3 PUFAs (AF group) or Peptamen® AF enriched with L-arginine (AFA group). On day 4, peritonitis by cecal ligation and puncture (CLP) was performed. Rats were resuscitated (H18) once septic shock was established. After a 4-hour resuscitation, vessels and organs were harvested to assess inflammation, superoxide anion, nitric oxide and prostacyclin levels. Ex-vivo vascular reactivity was also performed. Results Compared to CLP-AF or CLP-HN groups, 47.6% of CLP-AFA rats died before the beginning of hemodynamic measurements (vs. 8.0% and 20.0% respectively, p<0.05). AF and AFA rats required significantly increased norepinephrine infusion rates to reach the mean arterial pressure objective, compared to CLP-HN rats. Both CLP-AF and CLP-AFA reduced mesenteric resistance arterial contractility, decreased vascular oxidative stress, but increased NF-κB (0.40±0.15 in CLP-AF and 0.69±0.06 in CLP-AFA vs. 0.09±0.03 in SHAM rats and 0.30±0.06 in CLP-HN, ß-actin ratio, p<0.05) and pIκB expression (0.60±0.03 in CLP-AF and 0.94±0.15 in CLP-AFA vs. 0.04±0.01 in SHAM rats and 0.56±0.07 in CLP-HN, ß-actin ratio, p<0.05), nitric oxide and prostacyclin production in septic rats. Conclusions Although n-3 PUFAs or L-arginine supplementation exhibited an antioxidant effect, it worsened the septic shock-induced vascular dysfunction. Furthermore
He, Xinrong; Su, Fuhong; Taccone, Fabio Silvio; Laporte, Régent; Kjølbye, Anne Louise; Zhang, Jing; Xie, Keliang; Moussa, Mouhamed Djahoum; Reinheimer, Torsten Michael
interleukin-6 and nitrite/nitrate levels. Selepressin-treated animals survived longer than the other animals. Conclusions: In this clinically relevant model, selepressin, a selective V1A receptor agonist, was superior to arginine vasopressin and to norepinephrine in the treatment of septic shock, especially when administered early. PMID:26496451
Van Amersfoort, Edwin S.; Van Berkel, Theo J. C.; Kuiper, Johan
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. PMID:12857774
Li, Xiaofan; Chen, Jianhui
Bacterial infection is a common complication after Hematopoietic Stem Cell Transplantation (HSCT). Morganella morganii is ubiquitous Gram-negative facultative anaerobe, which may cause many kinds of opportunistic infection. Herein we report a case of a 55-year-old man who presented with frequent urination, urgency, and mild pain that comes and goes low in the abdomen and around the anus. The patient had a medical history of chronic prostatitis for 4 years. He received HLA-matched sibling allo-HSCT because of angioimmunoblastic T-cell lymphoma 29 months ago. The routine examination of prostatic fluid showed increased leukocytes and the culture of prostatic fluid showed Morganella morganii subsp. morganii. The patient developed chills and fever 18 hours after examination. Both urine culture and blood culture showed Morganella morganii subsp. morganii. The patient was successfully treated with antibiotic therapy and septic shock management. Taken together, Morganella morganii should be considered a possible pathogen when immunocompromised patients develop prostatitis. Also, prostatic massage could be a possible trigger of septic shock induced by Morganella morganii subsp. morganii in a posttransplantation patient. PMID:26798544
Brachelente, Chiara; Wiener, Dominique; Malik, Yasminda; Huessy, Daniela
A 4-year-old, neutered female, domestic shorthair cat admitted to the animal hospital for recurrent constipation presumed to be due to post-traumatic injuries, went into shock with signs including fever and ataxia followed by stupor. On the fifth day of hospitalization, the cat developed severe, diffuse oedema of the ventral abdomen with multifocal to coalescing erythematous areas and small vesicle formation. The results of bacteriological cultures of liver, spleen and kidney specimens led to the diagnosis of Acinetobacter baumannii sepsis. Histopathological findings of skin samples taken during necropsy showed an extensive epidermal and dermal necrosis with septic vasculitis and numerous intralesional gram-negative bacteria. Detection of the bla(OXA-51-like) gene specific for A. baumannii by PCR, performed retrospectively on samples of the deep layers of the skin, confirmed the presence of A. baumannii also in the cutaneous lesions. To our knowledge this is the first report of a necrotizing fasciitis with septic shock in a cat caused by A. baumannii.
Prasad, Karothu Durga; Trinath, Jamma; Biswas, Ansuman; Sekar, Kanagaraj; Balaji, Kithiganahalli N.; Guru Row, Tayur N.
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.
Cheng, Allen C; Stephens, Dianne P; Anstey, Nicholas M; Currie, Bart J
Melioidosis, caused by the intracellular pathogen Burkholderia pseudomallei, is endemic in northern Australia and Southeast Asia. Risk factors for this infection have also been associated with functional neutrophil defects. Because of this, granulocyte colony-stimulating factor (G-CSF) was adopted for use in patients with septic shock due to melioidosis in December 1998. We compared the mortality rates from before and after the introduction of G-CSF therapy at the Royal Darwin Hospital (Darwin, Australia) during the period of 1989-2002. The mortality rate decreased from 95% to 10% after the introduction of G-CSF. Risk factors, the duration of illness before presentation, and the severity of illness were similar in both groups. A smaller decrease in mortality among patients in the intensive care unit who did not have melioidosis was observed, suggesting that other changes in management did not account for the magnitude of the benefit seen. We conclude that G-CSF may have contributed to the reduction in the mortality rate among patients with septic shock due to melioidosis.
... look for pneumonia or fluid in the lungs (pulmonary edema) A urine sample to look for infection Additional studies, such as blood cultures , may not become positive for several days after the blood has been taken, ... MD, MHS, Associate Professor of Medicine, Pulmonary, Allergy, and Critical Care, Perelman School of Medicine, ...
Walkey, Allan J.; Soylemez-Wiener, Renda; Lindenauer, Peter K.
Objective In 2001 a randomized trial showed decreased mortality with early, goal-directed therapy in septic shock, a strategy later recommended by the Surviving Sepsis Campaign. Placement of a central venous catheter (CVC) is necessary to administer goal-directed therapy. We sought to evaluate nationwide trends in: 1) CVC utilization and 2) the association between early CVC insertion and mortality in patients with septic shock. Design We retrospectively analyzed the proportion of septic shock cases receiving an early (day of admission) CVC and the odds of hospital mortality associated with receiving early CVC from years 1998-2001 compared with 2002-2009. Setting Non-federal acute care hospitalizations from the Nationwide Inpatient Sample, 1998-2009. Interventions None Patients 203,481 (population estimate: 999,545) cases admitted through an emergency department with principal diagnosis of septicemia and secondary diagnosis of shock. Measurements and Main Results From 1998-2009 population-adjusted rates of septic shock increased from 12.6 cases per 100,000 US adults to 78 cases per 100,000. During this time age-adjusted hospital mortality associated with septic shock declined from 40.4% to 31.4%. Early CVC insertion increased from 5.7% (95% CI 5.1-6.3%) to 19.2% (95% CI 18.7-19.5%) cases with septic shock, with an increased rate of early CVC placement identified after 2007. The rate of decline in age-adjusted hospital mortality was significantly greater for patients who received an early CVC (-4.2% per year, 95% CI -3.2, -4.2%) as compared with no CVC (-2.9% per year, 95% CI -2.3, -3.5%), p=0.016. Hospital mortality associated with early CVC insertion significantly decreased from a multivariable-adjusted odds ratio of 1.29 (95% CI 1.14-1.45) prior to 2001 to an adjusted odds ratio of 0.87 (95% CI 0.84-0.90) after 2001. Conclusions Placement of a CVC early in septic shock has increased 3-fold since 1998. The mortality associated with early CVC insertion decreased
Ospina-Tascón, Gustavo Adolfo; García Marín, Alberto Federico; Echeverri, Gabriel J; Bermúdez, William Fernando; Madriñán Navia, Humberto José; Valencia, Juan David; Quiñones, Edgardo; Rodríguez, Fernando; Marulanda, Angela; Arango Davila, César Augusto; Bruhn, Alejandro; Hernández, Glenn; De Backer, Daniel
Derangements of microvascular blood flow distribution might contribute to disturbing oxygen extraction by peripheral tissues. We evaluated the dynamic relationships between the mesenteric oxygen extraction ratio (mes-ERO2) and the heterogeneity of microvascular blood flow at the gut and sublingual mucosa, during the development and resuscitation of septic shock in a swine model of fecal peritonitis. Jejunal-villi and sublingual microcirculation were evaluated using a portable intravital-microscopy technique. Simultaneously, we obtained arterial, mixed-venous and mesenteric blood gases, and jejunal-tonometric measurements. During resuscitation, pigs were randomly allocated to fixed-dose of dobutamine (5 µgr/kg/min) or placebo, while three sham models with identical monitoring served as controls. At the time-of-shock, we observed a significant decreased proportion of perfused intestinal-villi (villi-PPV) and sublingual percentage of perfused small-vessels (SL-PPV), paralleling an increase in mes-ERO2 in both dobutamine and placebo groups. After starting resuscitation, villi-PPV and SL-PPV significantly increased in the dobutamine group with subsequent improvement of functional capillary density, while mes-ERO2 exhibited a corresponding significant decrease (repeated-measures ANOVA, p=0.02 and p=0.04 for time*group-interactions and inter-group differences for villi-PPV and mes-ERO2, respectively). Variations in villi-PPV were paralleled by variations in mes-ERO2 (R(2)=0.88, p<0.001) and these, in turn, by mesenteric lactate changes (R(2)=0.86, p<0.001). There were no significant differences in cardiac output and systemic oxygen delivery throughout the experiment. In conclusion, dynamic changes in microvascular blood flow heterogeneity at jejunal mucosa are closely related to the mesenteric oxygen extraction ratio, suggesting a crucial role for microvascular blood flow distribution on oxygen uptake during development and resuscitation from septic shock.
Xu, Xiao-Jun; Tang, Yong-Min; Song, Hua; Yang, Shi-Long; Xu, Wei-Qun; Shi, Shu-Wen; Zhao, Ning; Liao, Chan
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.
Fernández-Valencia, Jenaro A; García, Sebastian; Prat, Salvio
Pasteurella multocida, a gram-negative coccobacillus, is a commensal in the nasopharynx of many animals. P. multocida infections most commonly involve the skin, soft tissues, and respiratory tract, particularly in immunosuppressed patients. The present case illustrates a severe articular infection caused by this bacterium, leading to septic shock, in an elderly, otherwise healthy woman, after a simple scratch of a cat.
de Carvalho, Mônica Andrade; Freitas, Flávio Geraldo Rezende; Silva Junior, Hélio Tedesco; Bafi, Antônio Toneti; Machado, Flávia Ribeiro; Pestana, José Osmar Medina
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
Huang, Ying; Wang, Shu-Ren; Yi, Cheng; Ying, Ming-Ying; Lin, Ying; Zhi, Mao-Hui
AIM: To investigate the therapeutic effects of recombinant human growth hormone (rhGH) on rat septic shock with intraabdominal infection by E. coli and its possible mechanism. METHODS: 76 SD rats were divided into 3 groups randomly: control group (group C, n = 16) without any special treatment, septic shock group (group S, n = 30) received bolus injection of E.coli (1 × 1010 cfu·L-1,15 mL·kg-1, ip), treated group (group T, n = 30) received bolus injection of E.coli, and then followed by rhGH injection (2.25 U·kg-1·d-1, im). Group S and group T were further divided into 1d and 3d subgroups, respectively (n = 15 each). Mean arterial pressure (MAP), levels of plasma TNFα and endotoxin and leukocyte count were determined on 1st day and 3rd day after E.coli injection. Another 39 SD rats were divided into groups C, S and T (n = 13 each) just for observing survival rate within 1 week. RESULTS: (1) On 1st and 3rd day, MAP in group S decreased markedly, and MAP on 1st day lowered more than that of 3rd day (P < 0.01), while MAP in group T just decreased slightly. The survival rate within 1 week was much higher in group T (84.6%) than in group S (46.2%) (P < 0.01). (2)On 1st day, plasma TNFα and endotoxin elevated significantly in group S and group T (P < 0.05), and endotoxin in group S had more increase (P < 0.01). On 3rd day, TNFα in group S returned to the level of group C (P > 0.05),while TNFα in group T went down below the level of group C(P < 0.01). On 3rd day, endotoxin in group S declined, but was still higher than that of group C (P < 0.01), endotoxin in group T returned to the level of group C (P > 0.05). (3) On 1st day, neutrophil ratio in total leukocyte count in both group S and group T increased significantly (P < 0.05 vs group C). CONCLUSION: rhGH showed beneficial effects on rat septic shock. The possible mechanisms may involve the attenuation of bacteria/endotoxin translocation and decreased systemic endotoxin level; inhibition of the production and
Elbaradey, Ghada F.; Elshmaa, Nagat Sayed; Hodeib, Hossam
Background and Aims: The aim of this study is to assess the effect of atrial natriuretic peptide (ANP) on intestinal ischemia-reperfusion injury in septic shock. Material and Methods: A prospective randomized controlled, observer-blinded study was carried out in surgical Intensive Care Unit (ICU), University Hospital. Forty adult patients in septic shock were randomly divided into two groups, control group (Group C) received normal saline and ANP group (Group A) patients received ANP in the form of 1.5 mg vial added to 250 ml solvent in plastic bag (1 ml = 6 micg) given at 2 mcg/kg intravenous bolus over 1 min followed by 0.01 mcg/kg/min for 24 h. The primary outcome measurements were blood marker of intestinal hypoperfusion in form of intestinal fatty acid binding protein (I-FABP), malondialdehyde (MDA), myloperoxidase enzyme activity (MPO), protein carbonyl (PC), and glutathione peroxidase activity (GPA) measured before start of ANP infusion, 6 h, 12 h, and 24 h after start of infusion. The secondary outcome measurements were the duration of noradrenaline infusion, duration of ICU stay, hospital mortality rate, and complications related to ANP. Results: In comparison with Group C, Group A showed a significant decrease (P < 0.05) in serum level of MPO, MDA, PC, and I-FABP, with a significant increase (P < 0.05) in serum level of GPA, 6 h, 12 h, and 24 h after the start of ANP infusion. There was significant decrease (P < 0.05) in mean duration of noradrenaline infusion, the length of ICU stay and mortality rate in Group A in comparison with Group C. In Group A, seven patients had mean arterial blood pressure < 65 mmHg but respond to volume resuscitation, three patients serum sodium was 125–130 mmol/L. Conclusion: In cases of septic shock, concomitant administration of ANP with noradrenaline may have a protective effect against intestinal injury through a decrease in the level of intestinal hypoperfusion owing to its anti-inflammatory and antioxidant effect. PMID
Plasma levels of antithrombin III, alpha 2-macroglobulin and inter-alpha-trypsin inhibitor, as well as those of various clotting, complement and other plasma factors, were significantly decreased in 18 patients suffering from hyperdynamic septic shock. A similar statistically significant reduction of the concentrations of several plasma factors (prothrombin and antithrombin III, plasminogen and alpha 2-plasmin inhibitor, complement factor C3 and clotting factor XIII) was observed in experimental endotoxaemia. In this model the reduction in the plasma levels of these factors was considerably diminished by the intravenous injection of a granulocytic elastase--cathepsin G inhibitor of lower molecular weight from soybeans. The results of both studies indicate that consumption of plasma factors in the course of Gram-negative sepsis proceeds not only via the classical routes (by activation of the clotting, fibrinolytic and complement cascades by system-specific proteinases such as thrombokinase or the plasminogen activator) but also to an appreciable degree of unspecific degradation of plasma factors by neutral proteinases such as elastase and cathepsin G. The endotoxin-induced release of both sorts of proteinases, the system-specific ones and the unspecific lysosomal proteinases from leucocytes and other cells, is likely to be mainly responsible for the consumption of antithrombin III and alpha-2-macroglobulin via complex formation (followed by elimination of the complexes) and the increased turnover of the inter-alpha-trypsin inhibitor as observed in the clinical study. The therapeutic use of an exogenous elastase--cathepsin G inhibitor in the experimental model was stimulated by the observation that human mucous secretions contain and acid-stable inhibitor of the neutral granulocytic proteinases, called HUSI-I or antileucoproteinase. This inhibitor protects mucous membranes and soluble proteins against proteolytic attack by leucocytic proteinases released in the
Ranjit, Suchitra; Natraj, Rajeswari; Kandath, Sathish Kumar; Kissoon, Niranjan; Ramakrishnan, Balasubramaniam; Marik, Paul E.
Aims: We previously reported that vasodilatation was common in pediatric septic shock, regardless of whether they were warm or cold, providing a rationale for early norepinephrine (NE) to increase venous return (VR) and arterial tone. Our primary aim was to evaluate the effect of smaller fluid bolus plus early-NE versus the American College of Critical Care Medicine (ACCM) approach to more liberal fluid boluses and vasoactive-inotropic agents on fluid balance, shock resolution, ventilator support and mortality in children with septic shock. Secondly, the impact of early NE on hemodynamic parameters, urine output and lactate levels was assessed using multimodality-monitoring. Methods: In keeping with the primary aim, the early NE group (N-27) received NE after 30ml/kg fluid, while the ACCM group (N-41) were a historical cohort managed as per the ACCM Guidelines, where after 40-60ml/kg fluid, patients received first line vasoactive-inotropic agents. The effect of early-NE was characterized by measuring stroke volume variation(SVV), systemic vascular resistance index (SVRI) and cardiac function before and after NE, which were monitored using ECHO + Ultrasound-Cardiac-Output-Monitor (USCOM) and lactates. Results: The 6-hr fluid requirement in the early-NE group (88.9+31.3 to 37.4+15.1ml/kg), and ventilated days [median 4 days (IQR 2.5-5.25) to 1day (IQR 1-1.7)] were significantly less as compared to the ACCM group. However, shock resolution and mortality rates were similar. In the early NE group, the overall SVRI was low (mean 679.7dynes/sec/cm5/m2, SD 204.5), and SVV decreased from 23.8±8.2 to 18.5±9.7, p=0.005 with NE infusion suggesting improved preload even without further fluid loading. Furthermore, lactate levels decreased and urine-output improved. Conclusion: Early-NE and fluid restriction may be of benefit in resolving shock with less fluid and ventilator support as compared to the ACCM approach. PMID:27829710
Le Tulzo, Yves; Pangault, Celine; Amiot, Laurence; Guilloux, Valérie; Tribut, Olivier; Arvieux, Cédric; Camus, Christophe; Fauchet, Renée; Thomas, Rémi; Drénou, Bernard
Monocyte deactivation has been identified as a major factor of immunosuppression in sepsis and is associated with a loss of surface human leukocyte antigen-DR (HLA-DR) expression on circulating monocytes. Using flow cytometry, quantitative reverse transcription-polymerase chain reaction, we investigated this phenomenon in septic patients. We confirmed the early loss of monocyte HLA-DR expression in all infected patients and demonstrated that this persistent lowered expression at Day 6 correlated with severity scores, secondary infection, and death. This phenomenon occurred at a transcriptional level via a decrease in the class II transactivator A (CIITA) transcription. Furthermore, these abnormalities correlated with the high cortisol levels observed in sepsis and not with those of other putative factors such as catecholamines or interleukin-10. Finally, in vitro studies evidenced that glucocorticoids decrease HLA-DR expression at a transcriptional level via a decrease in CIITA mRNA levels, mainly by down modulating its isoforms I and III. We conclude that in human sepsis, the loss of HLA-DR expression on circulating monocytes is associated with a poor outcome. We suggest that the high endogenous cortisol level observed in septic shock may be a possible new factor involved in the loss of HLA-DR expression on monocytes via its effect on HLA-DR and CIITA transcription.
Røsjø, Helge; Varpula, Marjut; Hagve, Tor-Arne; Karlsson, Sari; Ruokonen, Esko; Pettilä, Ville
Purpose To assess the clinical utility of a recently developed highly sensitive cardiac troponin T (hs-cTnT) assay for providing prognostic information on patients with sepsis. Methods cTnT levels were measured by the novel hs-cTnT assay at two time points (inclusion and 72 h thereafter) in a subgroup of patients from the FINNSEPSIS study and associations with clinical outcomes were examined. Results for the hs-cTnT assay were compared to those of the established fourth-generation cTnT assay. Results cTnT measured by the fourth-generation and hs-cTnT assay was detectable in 124 (60%) and 207 (100%) patients, respectively, on inclusion in this study. hs-cTnT levels on inclusion correlated with several indices of risk in sepsis, including the simplified acute physiology score (SAPS) II and sequential organ failure assessment (SOFA) scores. The level of hs-cTnT on inclusion was higher in hospital non-survivors (n = 47) than survivors (n = 160) (median 0.054 [Q1–3, 0.022–0.227] versus 0.035 [0.015–0.111] μg/L, P = 0.047), but hs-cTnT level was not an independent predictor of in-hospital mortality. hs-cTnT levels on inclusion were also higher in patients with septic shock during the hospitalization (0.044 [0.024–0.171] versus 0.033 [0.012–0.103] μg/L, P = 0.03), while this was not the case for the fourth-generation cTnT assay or NT-proBNP levels. Conclusions Circulating hs-cTnT is present in patients with severe sepsis and septic shock, associates with disease severity and survival, but does not add to SAPS II score for prediction of mortality. hs-cTnT measurement could still have a role in sepsis as an early marker of shock. Electronic supplementary material The online version of this article (doi:10.1007/s00134-010-2051-x) contains supplementary material, which is available to authorized users. PMID:20938765
Herzig, Daniela S.; Driver, Brandon R.; Fang, Geping; Toliver-Kinsky, Tracy E.; Shute, Eric N.
Rationale: Lymphocytes have been shown to facilitate systemic inflammation and physiologic dysfunction in experimental models of severe sepsis. Our previous studies show that natural killer (NK) cells migrate into the peritoneal cavity during intraabdominal sepsis, but the trafficking of NKT and T lymphocytes has not been determined. The factors that regulate lymphocyte trafficking during sepsis are currently unknown. Objectives: To ascertain the importance of CXC chemokine receptor 3 (CXCR3) as a regulator of lymphocyte trafficking during sepsis and determine the contribution of CXCR3-mediated lymphocyte trafficking to the pathogenesis of septic shock. Methods: Lymphocyte trafficking was evaluated in control and CXCR3-deficient mice using flow cytometry during sepsis caused by cecal ligation and puncture (CLP). Survival, core temperature, cytokine production, and bacterial clearance were measured as pathobiological endpoints. Measurements and Main Results: This study shows that concentrations of the CXCR3 ligands CXCL9 (monokine induced by interferon γ, MIG) and CXCL10 (interferon γ–induced protein 10, IP-10) increase in plasma and the peritoneal cavity after CLP, peak at 8 hours after infection, and are higher in the peritoneal cavity than in plasma. The numbers of CXCR3+ NK cells progressively decreased in spleen after CLP with a concomitant increase within the peritoneal cavity, a pattern that was ablated in CXCR3-deficient mice. CXCR3-dependent recruitment of T cells was also evident at 16 hours after CLP. Treatment of mice with anti-CXCR3 significantly attenuated CLP-induced hypothermia, decreased systemic cytokine production, and improved survival. Conclusions: CXCR3 regulates NK- and T-cell trafficking during sepsis and blockade of CXCR3 attenuates the pathogenesis of septic shock. PMID:22135342
Rimmelé, Thomas; Wey, Pierre-François; Bernard, Nicolas; Monchi, Mehran; Semenzato, Nicolas; Benatir, Farida; Boselli, Emmanuel; Etienne, Jérôme; Goudable, Joëlle; Chassard, Dominique; Bricca, Giampiero; Allaouchiche, Bernard
High-volume hemofiltration (HVHF) has been suggested as an adjuvant treatment of septic shock because of its capacities to remove inflammatory mediators from blood. Nevertheless, HVHF presents some important drawbacks, such as the depletion of low molecular weight molecules (nutriments, vitamins, trace elements and antibiotics) due to the high ultrafiltration rate, or the significant financial cost and nursing workload due to the frequent changes of large amounts of expensive sterile substitution fluids. A new hemofiltration system called "Cascade" has been developed, allowing very high ultrafiltration rates (120 mL/kg/h) limiting these drawbacks by using a special extracorporeal circuit. The objective of this study was to assess the technical feasibility of the Cascade system and to compare its hemodynamic impact to that of the standard HVHF system. Twenty sepsis-induced pigs were randomized in two groups: one group was hemofiltered with the standard HVHF system and the other with the Cascade system during a six-hour session. No technical problems were observed with the Cascade system during the experiment. At the end of the experiment, colloid requirements (989 +/- 355 mL vs. 1913 +/- 538 mL, P = 0.006), epinephrine requirements (0.82 +/- 0.42 mg vs. 3.27 +/- 3.02 mg, P < 0.001), lactic acidosis (pH = 7.33 +/- 0.08 vs. 7.10 +/- 0.07, P < 0.001) and mean pulmonary arterial pressure were less pronounced in the Cascade group. These results suggest that Cascade hemofiltration is technically feasible and safe. Moreover, compared with standard HVHF, it can reduce the severity of porcine septic shock.
Jazrawi, Allan; Miller, Jan; Baigi, Amir; Chew, Michelle
Introduction Although metabolic alkalosis is a common occurrence in intensive care units (ICUs), no study has evaluated its prevalence or outcomes in patients with severe sepsis or septic shock. Methods This is a retrospective cohort study of critically ill patients suffering from severe sepsis and septic shock admitted to the ICUs of Halmstad and Varberg County hospitals. From 910 patient records, 627 patients met the inclusion criteria. We investigated the relationship between metabolic alkalosis and mortality. Further, we studied the relationship between metabolic alkalosis and ICU length of stay (LOS). Results Metabolic alkalosis was associated with decreased 30-day and 12-month mortalities. This effect was however lost when a multivariate analysis was conducted, correcting for age, gender, pH on admission, base excess (BE) on admission, Simplified Acute Physiology Score III (SAPS III) and acute kidney injury (AKI). We then analyzed for any dose-response effect between the severity of metabolic alkalosis and mortality and found no relationship. Bivariate analysis showed that metabolic alkalosis had a significant effect on the length of ICU stay. When adjusting for age, sex, pH at admission, BE at admission, SAPS III and AKI in a multivariate analysis, metabolic alkalosis significantly contributed to prolonged ICU length of stay. In two separate sensitivity analyses pure metabolic alkalosis and late metabolic alkalosis (time of onset >48 hours) were the only significant predictor of increased ICU length of stay. Conclusion Metabolic alkalosis did not have any effect on 30-day and 12-month mortalities after adjusting for age, sex, SAPS III-score, pH and BE on admission and AKI in a multivariate analysis. The presence of metabolic alkalosis was independently associated with an increased ICU length of stay. PMID:28045915
Gutierrez, Guillermo; Reines, H David; Wulf-Gutierrez, Marian E
This review addresses the pathophysiology and treatment of hemorrhagic shock – a condition produced by rapid and significant loss of intravascular volume, which may lead sequentially to hemodynamic instability, decreases in oxygen delivery, decreased tissue perfusion, cellular hypoxia, organ damage, and death. Hemorrhagic shock can be rapidly fatal. The primary goals are to stop the bleeding and to restore circulating blood volume. Resuscitation may well depend on the estimated severity of hemorrhage. It now appears that patients with moderate hypotension from bleeding may benefit by delaying massive fluid resuscitation until they reach a definitive care facility. On the other hand, the use of intravenous fluids, crystalloids or colloids, and blood products can be life saving in those patients who are in severe hemorrhagic shock. The optimal method of resuscitation has not been clearly established. A hemoglobin level of 7–8 g/dl appears to be an appropriate threshold for transfusion in critically ill patients with no evidence of tissue hypoxia. However, maintaining a higher hemoglobin level of 10 g/dl is a reasonable goal in actively bleeding patients, the elderly, or individuals who are at risk for myocardial infarction. Moreover, hemoglobin concentration should not be the only therapeutic guide in actively bleeding patients. Instead, therapy should be aimed at restoring intravascular volume and adequate hemodynamic parameters. PMID:15469601
Rodchuae, Muchima; Ruangpin, Chonlada; Katchamart, Wanruchada
Septic arthritis of the sternoclavicular joint (SCJ) is an atypical and rarely seen clinical condition. The prognosis for patients with SCJ septic arthritis is often poor. The objective of this study was to compare clinical characteristics between SCJ and non-sternoclavicular joint (NSCJ) septic arthritis and to identify independent risk factors for SCJ septic arthritis. A total of 450 adult patients diagnosed with septic arthritis during the January 2002 to December 2013 study period were included in this retrospective cohort study. Patient characteristics, clinical manifestations, and treatment outcomes were examined. Univariate and multivariate analysis was performed to identify potential risk factors for SCJ septic arthritis. Thirty-three (7.3%) of 450 patients had SCJ septic arthritis and the remaining 417 patients had NSCJ. Oligoarthritis or polyarthritis were seen more often in SCJ patients than in NSCJ patients (55 vs. 19%; p < 0.05). Abscess formation and bacteremia were more commonly found at presentation in the SCJ group than in the NSCJ group (18 vs. 8%; p < 0.05 for abscess formation; and, 53.1 vs. 26.6%; p < 0.05 for bacteremia). In multivariate analysis, extra-articular infection (OR 2.7, 95% CI 1.2-6.4; p = 0.02), cirrhosis (OR 1.9, 95% CI 1.1-3.3; p = 0.02), and malignancy (OR 3, 95% CI 1.1-7.8; p = 0.03) were independent risk factors for SCJ septic arthritis. SCJ septic arthritis is an uncommon septic arthritis that frequently presents with local and systemic complications. Factors found to be significantly associated with SCJ septic arthritis were extra-articular infection and immunocompromised host. A high index of suspicion in high-risk patients is the key to achieving improved outcomes.
A circulating myocardial depressant substance in humans with septic shock. Septic shock patients with a reduced ejection fraction have a circulating factor that depresses in vitro myocardial cell performance.
Parrillo, J E; Burch, C; Shelhamer, J H; Parker, M M; Natanson, C; Schuette, W
We have previously described a subpopulation of patients with septic shock who had a reversible depression of radionuclide-determined left ventricular ejection fraction (EF). To investigate the mechanism of this myocardial depression, an in vitro model of mammalian myocardial cell performance was established employing primary spontaneously beating rat myocardial cells. The contraction of a single cardiac cell was quantitated by recording the changes in area occupied by the cell during contraction and relaxation. In 20 septic shock patients during the acute phase, the mean left ventricular EF was decreased (mean = 0.33, normal mean = 0.50), and serum obtained during this acute phase induced a mean (+/- standard error of the mean) 33 +/- 4% decrease in extent and 25 +/- 4% decrease in velocity of myocardial cell shortening during contraction (P less than 0.001). In contrast, serum obtained from 11 of these same patients before shock (n = 2) or after recovery (n = 9) of the left ventricular EF (mean = 0.50) showed a return toward normal in extent and velocity of shortening (P less than 0.001). Sera from 17 critically ill nonseptic patients, from 10 patients with structural heart disease as a cause for a depressed EF, and from 12 healthy laboratory personnel, induced no significant changes in in vitro myocardial cell performance. In 20 patients during the acute phase of septic shock, the decreased EF in vivo demonstrated a significant correlation (r = +0.52, P less than 0.01) with a decrease in the extent of myocardial cell shortening in vitro. The quantitative and temporal correlation between the decreased left ventricular EF and this serum myocardial depressant substance argues for a pathophysiologic role for this depressant substance in producing the reversible cardiomyopathy seen during septic shock in humans. Images PMID:4056039
Boyer, Alexandre; Gruson, Didier; Bouchet, Stéphane; Clouzeau, Benjamin; Hoang-Nam, Bui; Vargas, Frédéric; Gilles, Hilbert; Molimard, Mathieu; Rogues, Anne-Marie; Moore, Nicholas
Aminoglycoside nephrotoxicity has been reported in patients with sepsis, and several risk factors have been described. Once-daily dosing and shorter treatment have reduced nephrotoxicity risk, and simplified aminoglycoside monitoring. This review focuses on nephrotoxicity associated with aminoglycosides in the subset of patients with septic shock or severe sepsis. These patients are radically different from those with less severe sepsis. They may have, for instance, renal impairment due to the shock per se, sepsis-related acute kidney injury, frequent association with pre-existing risk factors for renal failure such as diabetes, dehydration and other nephrotoxic treatments. In this category of patients, these risk factors might modify substantially the benefit-risk ratio of aminoglycosides. In addition, aminoglycoside administration in critically ill patients with sepsis is complicated by an extreme inter- and intra-individual variability in drug pharmacokinetic/pharmacodynamic characteristics: the volume of distribution (Vd) is frequently increased while the elimination constant can be either increased or decreased. Consequently, and although its effect on nephrotoxicity has not been explored, a different administration schedule, i.e. a high-dose once daily (HDOD), and several therapeutic drug monitoring (TDM) options have been proposed in these patients. This review describes the historical perspective of these different options, including those applying to subsets of patients in which aminoglycoside administration is even more complex (obese intensive care unit [ICU] patients, patients needing continuous or discontinuous renal replacement therapy [CRRT/DRRT]). A simple linear dose adjustment according to aminoglycoside serum concentration can be classified as low-intensity TDM. Nomograms have also been proposed, based on the maximum (peak) plasma concentration (Cmax) objectives, weight and creatinine clearance. The Sawchuk and Zaske method (based on the
Weiss, M; Fischer, G; Barth, E; Boneberg, E; Schneider, E M; Georgieff, M; Hartung, T
Over a 6 month period, in 192 patients admitted to the intensive care unit (ICU), a longitudinal analysis of whole blood lipopolysaccharide (LPS)-induced ex vivo cytokine production was performed on a daily basis until discharge from the ICU or death. Twenty-one patients with proven infections were in septic shock for the first time and for at least 3 days' duration. Ex vivo LPS-inducible release of granulocyte colony-stimulating factor (G-CSF) was upregulated and that of TNF-alpha was downregulated in patients with septic shock, regardless whether they survived or died. In conclusion, LPS-induced ex vivo TNF-alpha and G-CSF cytokine release by monocytes is regulated differentially in patients with septic shock. Since upregulation of LPS-induced production of G-CSF occurred earlier in survivors than in non-survivors, rapidly elevated and sustained G-CSF responsiveness may contribute to survival in septic shock.
Karjagin, J; Lefeuvre, S; Oselin, K; Kipper, K; Marchand, S; Tikkerberi, A; Starkopf, J; Couet, W; Sawchuk, R J
Our objective was to describe the pharmacokinetics of meropenem in the peritoneal fluid (PF) of six patients with severe peritonitis and septic shock and to relate measured concentrations to the minimum inhibitory concentration of bacteria. Microdialysis catheters were placed into the peritoneal space during surgery. Meropenem concentrations in plasma and in PF were analyzed using compartmental modeling. Meropenem areas under the concentration-time curve were lower in PF than in plasma (average ratio, 73.8+/-15%) because of degradation confirmed ex vivo. Compartment modeling with elimination from a peripheral compartment described the data adequately, and was used to simulate steady-state concentration profiles in plasma and PF during various dosing regimens. At the currently recommended dosing regimen of 1 g infused over 20 min every 8 h, PF concentrations of meropenem in patients with severe peritonitis associated with septic shock reach values sufficient for antibacterial effects against susceptible, but not always against intermediately susceptible, bacteria.
Pea, Federico; Viale, Pierluigi
Appropriate antibiotic therapy in patients with severe sepsis and septic shock should mean prompt achievement and maintenance of optimal exposure at the infection site with broad-spectrum antimicrobial agents administered in a timely manner. Once the causative pathogens have been identified and tested for in vitro susceptibility, subsequent de-escalation of antimicrobial therapy should be applied whenever feasible. The goal of appropriate antibiotic therapy must be pursued resolutely and with continuity, in view of the ongoing explosion of antibiotic-resistant infections that plague the intensive care unit setting and of the continued decrease in new antibiotics emerging. This article provides some principles for the correct handling of antimicrobial dosing regimens in patients with severe sepsis and septic shock, in whom various pathophysiological conditions may significantly alter the pharmacokinetic behaviour of drugs.
Vol. 110 (4): 453-460, 2015. p. 453. "Interleukin-10 rs2227307 and CXCR2 rs1126579 polymorphisms modulate the predisposition to septic shock" should read: "Interleukin-10 rs1800896 and CXCR2 rs1126579 polymorphisms modulate the predisposition to septic shock". == Vol. 110 (6): 797-800, 2015 .p. 797. "Financial support: IOC/FIOCRUZ, PAPESIV/VPPDT/FIOCRUZ, FAPERJ-APQ1 (E-26/110.497/2011), CNPq (458858/2014-5)" should read: "Financial support: IOC/FIOCRUZ, PAPESIV/VPPDT/FIOCRUZ, FAPERJ-APQ1 (E-26/110.497/2011), CNPq (458858/2014-5),FAPEAM/CNPq/PPP-FAPEAM (010/2011), MCT/CNPq (014/2011)"
Westover, Angela J.; Buffington, Deborah A.; Johnston, Kimberly A.; Smith, Peter L.; Pino, Christopher J.; Humes, H. David
Renal cell therapy using the hollow fiber based renal assist device (RAD) improved survival time in an animal model of septic shock (SS) through the amelioration of cardiac and vascular dysfunction. Safety and ability of the RAD to improve clinical outcomes was demonstrated in a Phase II clinical trial, in which patients had high prevalence of sepsis. Even with these promising results, clinical delivery of cell therapy is hampered by manufacturing hurdles, including cell sourcing, large-scale device manufacture, storage and delivery. To address these limitations, the bioartificial renal epithelial cell system (BRECS) was developed. The BRECS contains human renal tubule epithelial cells derived from adult progenitor cells using enhanced propagation techniques. Cells were seeded onto trabeculated disks of niobium-coated carbon, held within cryopreservable, perfusable, injection-molded polycarbonate housing. The study objective was to evaluate the BRECS in a porcine model of SS to establish conservation of efficacy after necessary cell sourcing and design modifications; a pre-clinical requirement to move back into clinical trials. SS was incited by peritoneal injection of E. coli simultaneous to insertion of BRECS (n=10) or control (n=15), into the ultrafiltrate biofeedback component of an extracorporeal circuit. Comparable to RAD, prolonged survival of the BRECS cohort was conveyed through stabilization of cardiac output and vascular leak. In conclusion, the demonstration of conserved efficacy with BRECS therapy in a porcine SS model represents a crucial step toward returning renal cell therapy to the clinical setting, initially targeting ICU patients with acute kidney injury requiring continuous renal replacement therapy. PMID:25424193
Bermejo, C; Maseda, E; Salgado, P; Gabilondo, G; Gilsanz, F
The epidemiology of Clostridium difficile infection has changed in the past decade. The incidence rate of community acquired cases has increased in patients with no typical risk factors. We present a patient who was diagnosed with community-acquired Clostridium difficile infection who presented with acute abdominal pain, and subsequently developed acute renal failure and septic shock. We describe the diagnosis, treatment and outcome and brief review of the literature.
Molderez, A.; Trine, H.
We report the case of a patient admitted to our intensive care unit in the course of a septic shock, secondary to cholangitis. After rapid hemodynamic stabilization, antibiotherapy, and endoscopic extraction of bile ducts stones, she appeared to have developed flaccid paraplegia. The suspected diagnosis of medullar ischemia was confirmed by typical MRI findings. This case stresses the potential pathogenic role of hypotension in medullar ischemia and the place of magnetic resonance imaging (MRI) as a reliable diagnostic tool. PMID:28316845
Mazza, Bruno Franco; Freitas, Flavio Geraldo Rezende; Barros, Melca Maria Oliveira; Azevedo, Luciano Cesar Pontes; Machado, Flavia Ribeiro
Objective To evaluate the immediate effects of red blood cell transfusion on central venous oxygen saturation and lactate levels in septic shock patients with different transfusion triggers. Methods We included patients with a diagnosis of septic shock within the last 48 hours and hemoglobin levels below 9.0g/dL Patients were randomized for immediate transfusion with hemoglobin concentrations maintained above 9.0g/dL (Group Hb9) or to withhold transfusion unless hemoglobin felt bellow 7.0g/dL (Group Hb7). Hemoglobin, lactate, central venous oxygen saturation levels were determined before and one hour after each transfusion. Results We included 46 patients and 74 transfusions. Patients in Group Hb7 had a significant reduction in median lactate from 2.44 (2.00 - 3.22) mMol/L to 2.21 (1.80 - 2.79) mMol/L, p = 0.005, which was not observed in Group Hb9 [1.90 (1.80 - 2.65) mMol/L to 2.00 (1.70 - 2.41) mMol/L, p = 0.23]. Central venous oxygen saturation levels increased in Group Hb7 [68.0 (64.0 - 72.0)% to 72.0 (69.0 - 75.0)%, p < 0.0001] but not in Group Hb9 [72.0 (69.0 - 74.0)% to 72.0 (71.0 - 73.0)%, p = 0.98]. Patients with elevated lactate or central venous oxygen saturation < 70% at baseline had a significant increase in these variables, regardless of baseline hemoglobin levels. Patients with normal values did not show a decrease in either group. Conclusion Red blood cell transfusion increased central venous oxygen saturation and decreased lactate levels in patients with hypoperfusion regardless of their baseline hemoglobin levels. Transfusion did not appear to impair these variables in patients without hypoperfusion. ClinicalTrials.gov NCT01611753 PMID:25909311
Mallat, Jihad; Lemyze, Malcolm; Tronchon, Laurent; Vallet, Benoît; Thevenin, Didier
The mixed venous-to-arterial carbon dioxide (CO2) tension difference [P (v-a) CO2] is the difference between carbon dioxide tension (PCO2) in mixed venous blood (sampled from a pulmonary artery catheter) and the PCO2 in arterial blood. P (v-a) CO2 depends on the cardiac output and the global CO2 production, and on the complex relationship between PCO2 and CO2 content. Experimental and clinical studies support the evidence that P (v-a) CO2 cannot serve as an indicator of tissue hypoxia, and should be regarded as an indicator of the adequacy of venous blood to wash out the total CO2 generated by the peripheral tissues. P (v-a) CO2 can be replaced by the central venous-to-arterial CO2 difference (ΔPCO2), which is calculated from simultaneous sampling of central venous blood from a central vein catheter and arterial blood and, therefore, more easy to obtain at the bedside. Determining the ΔPCO2 during the resuscitation of septic shock patients might be useful when deciding when to continue resuscitation despite a central venous oxygen saturation (ScvO2) > 70% associated with elevated blood lactate levels. Because high blood lactate levels is not a discriminatory factor in determining the source of that stress, an increased ΔPCO2 (> 6 mmHg) could be used to identify patients who still remain inadequately resuscitated. Monitoring the ΔPCO2 from the beginning of the reanimation of septic shock patients might be a valuable means to evaluate the adequacy of cardiac output in tissue perfusion and, thus, guiding the therapy. In this respect, it can aid to titrate inotropes to adjust oxygen delivery to CO2 production, or to choose between hemoglobin correction or fluid/inotrope infusion in patients with a too low ScvO2 related to metabolic demand. The combination of P (v-a) CO2 or ΔPCO2 with oxygen-derived parameters through the calculation of the P (v-a) CO2 or ΔPCO2/arteriovenous oxygen content difference ratio can detect the presence of global anaerobic metabolism.
Mallat, Jihad; Lemyze, Malcolm; Tronchon, Laurent; Vallet, Benoît; Thevenin, Didier
The mixed venous-to-arterial carbon dioxide (CO2) tension difference [P (v-a) CO2] is the difference between carbon dioxide tension (PCO2) in mixed venous blood (sampled from a pulmonary artery catheter) and the PCO2 in arterial blood. P (v-a) CO2 depends on the cardiac output and the global CO2 production, and on the complex relationship between PCO2 and CO2 content. Experimental and clinical studies support the evidence that P (v-a) CO2 cannot serve as an indicator of tissue hypoxia, and should be regarded as an indicator of the adequacy of venous blood to wash out the total CO2 generated by the peripheral tissues. P (v-a) CO2 can be replaced by the central venous-to-arterial CO2 difference (ΔPCO2), which is calculated from simultaneous sampling of central venous blood from a central vein catheter and arterial blood and, therefore, more easy to obtain at the bedside. Determining the ΔPCO2 during the resuscitation of septic shock patients might be useful when deciding when to continue resuscitation despite a central venous oxygen saturation (ScvO2) > 70% associated with elevated blood lactate levels. Because high blood lactate levels is not a discriminatory factor in determining the source of that stress, an increased ΔPCO2 (> 6 mmHg) could be used to identify patients who still remain inadequately resuscitated. Monitoring the ΔPCO2 from the beginning of the reanimation of septic shock patients might be a valuable means to evaluate the adequacy of cardiac output in tissue perfusion and, thus, guiding the therapy. In this respect, it can aid to titrate inotropes to adjust oxygen delivery to CO2 production, or to choose between hemoglobin correction or fluid/inotrope infusion in patients with a too low ScvO2 related to metabolic demand. The combination of P (v-a) CO2 or ΔPCO2 with oxygen-derived parameters through the calculation of the P (v-a) CO2 or ΔPCO2/arteriovenous oxygen content difference ratio can detect the presence of global anaerobic metabolism
Yang, Su-Xian; Chen, Yun-Xiu; Xu, Jing; Yang, Zhao-Hui
Background The aim of this study was to investigate the value of plasma intermedin (IMD) in assessing severity and treatment efficacy of septic shock. Material/Methods Healthy male Sprague-Dawley (SD) rats were chosen and divided into a normal control group (n=15) and a shock model group (n=27) that received intravenous injection of lipopolysaccharide (LPS). Then, 3 specimens were taken from each group. The shock model group rats were divided into an LPS group and a treatment group with 12 rats each. The treatment group received intravenous injection of compound sodium lactate solution. Plasma IMD and IMD1-47 mRNA expressions were compared and analyzed. Results Mean arterial pressure (MAP) was lower while white blood cell count and TNF-α were higher in the shock model group than in the normal control group (P<0.05). After 10 h and 20 h, the treatment group had lower plasma IMD and IMD1-47 mRNA expressions compared with the LPS group (P<0.05). Plasma IMD and IMD1-47 mRNA expressions in the LPS group after 20 h were significantly higher than after 10 h (P<0.05). IMD was positively correlated with interleukins (IL-3, IL-6, and IL-8), white blood cell count, and body temperature (all P<0.05), but were negatively correlated with systolic pressure (r=−0.8474, P=0.0040). Conclusions Plasma IMD level can effectively reflect the severity of septic shock and can be used as an important indicator of septic shock treatment effectiveness. PMID:27999422
Palomba, Henrique; Corrêa, Thiago Domingos; Silva, Eliézer; Pardini, Andreia; de Assuncao, Murillo Santucci Cesar
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
Starr, Anna; Sand, Claire A; Heikal, Lamia; Kelly, Peter D; Spina, Domenico; Crabtree, Mark; Channon, Keith M; Leiper, James M; Nandi, Manasi
Overproduction of nitric oxide (NO) by inducible NO synthase contributes toward refractory hypotension, impaired microvascular perfusion, and end-organ damage in septic shock patients. Tetrahydrobiopterin (BH4) is an essential NOS cofactor. GTP cyclohydrolase 1 (GCH1) is the rate-limiting enzyme for BH4 biosynthesis. Under inflammatory conditions, GCH1 activity and hence BH4 levels are increased, supporting pathological NOS activity. GCH1 activity can be controlled through allosteric interactions with GCH1 feedback regulatory protein (GFRP). We investigated whether overexpression of GFRP can regulate BH4 and NO production and attenuate cardiovascular dysfunction in sepsis. Sepsis was induced in mice conditionally overexpressing GFRP and wild-type littermates by cecal ligation and puncture. Blood pressure was monitored by radiotelemetry, and mesenteric blood flow was quantified by laser speckle contrast imaging. Blood biochemistry data were obtained using an iSTAT analyzer, and BH4 levels were measured in plasma and tissues by high-performance liquid chromatography. Increased BH4 and NO production and hypotension were observed in all mice, but the extents of these pathophysiological changes were attenuated in GFRP OE mice. Perturbations in blood biochemistry were similarly attenuated in GFRP OE compared with wild-type controls. These results suggest that GFRP overexpression regulates GCH1 activity during septic shock, which in turn limits BH4 bioavailability for iNOS. We conclude that the GCH1-GFRP axis is a critical regulator of BH4 and NO production and the cardiovascular derangements that occur in septic shock.
Intercellular adhesion molecule 1 (ICAM-1) is one of three immunoglobulin superfamily members that bind to the integrins lymphocyte function associated 1 (LFA-1) and Mac-1 on leukocytes. We have generated mice that are genetically and functionally deficient in ICAM-1. These mice have elevated numbers of circulating neutrophils and lymphocytes, as well as diminished allogeneic T cell responses and delayed type hypersensitivity. Mutant mice are resistant to lethal effects of high doses of endotoxin (lipopolysaccharide [LPS]), and this correlates with a significant decrease in neutrophil infiltration in the liver. Production of inflammatory cytokines such as tumor necrosis factor alpha or interleukin 1 is normal in ICAM-1-deficient mice, and thus protection appears to be related to a diminution in critical leukocyte-endothelial interactions. After sensitization with D- galactosamine (D-Gal), ICAM-1-deficient mice are resistant to the lethal effect of low doses of exotoxin (Staphylococcus aureus enterotoxin B [SEB]), which has been shown to mediate its toxic effects via the activation of specific T cells. In this model, ICAM-1-mediated protection against SEB lethality correlates with a decrease in the systemic release of inflammatory cytokines, as well as with prevention of extensive hepatocyte necrosis and hemorrhage. ICAM-1-deficient mice sensitized with D-Gal, however, are not protected from lethality when challenged with low doses of endotoxin (LPS). These studies show that the different contribution of ICAM-1 in the activation of either T cells or macrophages is decisive for the fatal outcome of the shock in these two models. This work suggests that anti-ICAM-1 therapy may be beneficial in both gram-positive and -negative septic shock, either by reducing T cell activation or by diminishing neutrophil infiltration. PMID:7911822
Lv, Sihan; Qiu, Xinchen; Li, Jian; Li, Weida; Zhang, Chao; Zhang, Zhen-Ning; Luan, Bing
Although hypoglycemia has been documented as a major cause of high mortality in the setting of septic shock, the mechanism of hypoglycemia in infection has not been clearly determined. Hepatic gluconeogenesis serves as an important mechanism to maintain glucose levels under physiological conditions and CREB coactivator CRTC2 plays an important role in regulating gluconeogenic gene expression. Here, we show that triggering of the Toll-like receptor 4 pathway in response to endotoxin lipopolysaccharide (LPS) inhibits gluconeogenic gene expression and hepatic glucose output by blocking CRTC2 activation. Interleukin-1β (IL-1β) is found to disrupt gluconeogenic gene expression via the activation of the E3 ubiquitin ligase TRAF6, a key component of the Toll-like receptor 4 signaling pathway that associates with and ubiquitinates CRTC2. TRAF6 promotes the K63-linked ubiquitination of CRTC2, a modification that blocks binding of calcineurin at an adjacent calcineurin-binding site, thereby disrupting CRTC2 dephosphorylation in response to glucagon signals. Mutation of TRAF6-binding sites or ubiquitination site in CRTC2 rescues hepatic gluconeogenesis in LPS-challenged mice. These results suggest that pro-inflammatory signals intersect with the CRTC2 pathway in liver, thus contributing to hypoglycemia caused by infection. PMID:27990298
Tamme, Kadri; Oselin, Kersti; Kipper, Karin; Low, Kaywei; Standing, Joseph F; Metsvaht, Tuuli; Karjagin, Juri; Herodes, Koit; Kern, Hartmut; Starkopf, Joel
Pharmacokinetics (PK) of doripenem was determined during high volume hemodiafiltration (HVHDF) in patients with septic shock. A single 500 mg dose of doripenem was administered as a 1 hour infusion during HVHDF to 9 patients. Arterial blood samples were collected before and at 30 or 60 minute intervals over 8 hours (12 samples) after study drug administration. Doripenem concentrations were determined by ultrahigh performance liquid chromatography-tandem mass spectrometry. Population PK analysis and Monte Carlo simulation of 1,000 subjects were performed. The median convective volume of HVHDF was 10.3 L/h and urine output during the sampling period was 70 mL. The population mean total doripenem clearance on HVHDF was 6.82 L/h, volume of distribution of central compartment 10.8 L, and of peripheral compartment 12.1 L. Doses of 500 mg every 8 hours resulted in 88.5% probability of attaining the target of 50% time over MIC for bacteria with MIC = 2 µg/mL at 48 hours, when doubling of MIC during that time was assumed. Significant elimination of doripenem occurs during HVHDF. Doses of 500 mg every 8 hours are necessary for treatment of infections caused by susceptible bacteria during extended HVHDF.
Zhao, Ting; Pan, Baihong; Alam, Hasan B.; Liu, Baoling; Bronson, Roderick T.; Deng, Qiufang; Wu, Erxi; Li, Yongqing
Production of innate and adaptive immune cells from hematopoietic stem cells, and maturation of T lymphocytes are effective immune responses to fight severe microbial infection. In sepsis, this emergency myelopoiesis is damaged, leading to failure of bacterial clearance, and excessive stress-induced steroids cause immature T-lymphocyte apoptosis in thymus. We recently found that Cl-amidine, a peptidylarginine deiminase (PAD) inhibitor, improves survival in a mouse model of cecal ligation and puncture (CLP)-induced septic shock. In the present study we investigated how Cl-amidine promotes survival, focusing on protective effects of Cl-amidine on immune response. We confirmed survival-improving effect of Cl-amidine and are the first to explore the role of Cl-amidine in immune response. CLP caused bone marrow (BM) and thymus atrophy, decreased innate immune cells in BM. CLP increased levels of cytokines (IL-1β, IL-6, and TNF-α) and bacteria load in blood/liver. In primary splenocyte culture, lipopolysaccharide increased TNF-α production. In contrast, Cl-amidine attenuated these CLP and lipopolysaccharide-induced alterations. Moreover, Cl-amidine increased circulating monocytes. Collectively, our results demonstrate Cl-amidine plays protective roles by significantly decreasing BM and thymus atrophy, restoring innate immune cells in BM, increasing blood monocytes and blood/liver bacteria clearance, and attenuating pro-inflammatory cytokine production in a murine model of lethal sepsis. PMID:27819302
Maybauer, Dirk M; Maybauer, Marc O; Szabó, Csaba; Westphal, Martin; Traber, Lillian D; Salzman, Andrew L; Herndon, David N; Traber, Daniel L
This prospective, randomized, controlled experimental study examined the effects of the peroxynitrite decomposition catalyst WW-85 on global hemodynamics and regional microvascular blood flow (RMBF) in an established ovine model of septic shock following severe smoke inhalation injury. Twenty-one sheep were randomized into a sham group (no injury), a control group (smoke/sepsis), and a treatment group (smoke/sepsis/WW-85; n=7 each). WW-85 was administered 1h after injury as a bolus (0.1 mg/kg), followed by a continuous infusion of 0.02 mg/kg/h RMBF was analyzed using colored microspheres. All control animals developed a hypotensive, hyperdynamic circulation and increased plasma levels of nitrate/-nitrite (NOx). All hemodynamic variables and NOx levels were significantly improved in the treatment group. In visceral organs of controls, blood flow to trachea, ileum, and spleen significantly increased (p<0.05). Blood flow to kidneys and pancreas significantly decreased (p<0.05). Treatment with WW-85 stabilized blood flow to ileum, spleen, and kidneys on baseline levels and was significantly improved compared to controls (p<0.05). Cerebral blood flow deteriorated in controls, but was significantly improved in cerebral cortex, cerebellum, pons, medulla oblongata, and thalamus (p<0.05) by WW-85. These results provide evidence that WW-85 blocks NO production, thereby improving cardiovascular function and microcirculation.
Maybauer, Dirk M.; Maybauer, Marc O.; Szabó, Csaba; Westphal, Martin; Traber, Lillian D.; Salzman, Andrew L.; Herndon, David N.; Traber, Daniel L.
This prospective, randomized, controlled experimental study looks at the effects of the peroxynitrite decomposition catalyst WW-85 on global hemodynamics and regional microvascular blood flow (RMBF) in an established ovine model of septic shock following severe smoke inhalation injury. Twenty-one sheep were randomized into a sham group (no injury), a control group (smoke/sepsis), and a treatment group (smoke/sepsis/WW-85; n=7 each). WW-85 was administered 1h post injury as bolus (0.1 mg/kg), followed by a continuous infusion of 0.02 mg/kg/h RMBF was analyzed using colored microspheres. All control animals developed a hypotensive, hyperdynamic circulation and increased plasma levels of nitrate/-nitrite (NOx). All hemodynamic variables and NOx levels were significantly improved in the treatment group. In visceral organs of controls, blood flow to trachea, ileum, and spleen significantly increased (p<0.05). Blood flow to kidneys and pancreas significantly decreased (p<0.05). Treatment with WW-85 stabilized blood flow to ileum, spleen, and kidneys on baseline levels and was significantly improved compared to controls (p<0.05). Cerebral blood flow deteriorated in controls, but was significantly improved in cerebral cortex, cerebellum, pons, medulla oblongata, and thalamus (p<0.05) by WW-85. These results provide evidence that WW-85 blocks NO production, thereby improving cardiovascular function and microcirculation. PMID:21345593
Menegueti, Mayra Goncalves; Machado-Viana, Jaciara; Gaspar, Gilberto Gambero; Nicolini, Edson Antonio; Basile-Filho, Anibal; Auxiliadora-Martins, Maria
Haemophilus parainfluenzae, which belongs to the HACEK (Haemophilus ssp, Actinobacillus actinomycetemcomitans, Cardiobacterium hominis, Eikenella corrodens, and Kingella kingae) group, is a rare cause of subacute endocarditis and may lead to ischemic stroke. A 65-year-old female patient previously diagnosed with rheumatic valve disease was submitted to surgical mitral valve repair in 1996. Physical examination did not reveal any murmurs; physical examination of the lungs and abdomen was normal. The patient was admitted to hospital with progressive dyspnea, dry cough, and fever. Transesophageal echocardiogram revealed an approximately 8-mm filamentous image with chaotic motion in the ventricular face of the anterior mitral valve leaflet compatible with vegetation. Treatment with ceftriaxone and gentamicin was initiated. Haemophilus parainfluenzae grew in five blood culture samples. Along the hospital stay, the patient’s level of consciousness decreased, and she was diagnosed with ischemic stroke of cardioembolic etiology. The patient developed septic shock refractory to the prescribed treatment and died 12 days after admission. Even though the patient started being treated for endocarditis before the infectious agent was identified, the prompt use of antimicrobials hindered the growth of Haemophilus parainfluenzae and made its isolation difficult. PMID:27924179
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.
Objective To determine if intravenous thiamine would reduce lactate in patients with septic shock. Design Randomized, double-blind, placebo-controlled trial. Setting Two US hospitals. Patients Adult patients with septic shock and elevated (> 3 mmol/L) lactate between 2010 and 2014. Interventions Thiamine 200 mg or matching placebo twice daily for 7 days or until hospital discharge. Measurements and Main Results 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). Conclusion 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. PMID:26771781
Zhang, Xinchao; Lin, Peihong; Wei, Jie; Cao, Yu; Pan, Shuming; Walline, Joseph; Qian, Chuanyun; Shan, Zhigang
The effect of Shenfu on biochemical parameters and survival during resuscitation in patients with septic shock was examined. This was a multicenter, controlled, randomized, open-label trial carried out in 210 patients with septic shock from seven medical centers in China. They were randomized to Shenfu or saline. The primary outcome was lactate clearance. The secondary outcomes were shock index normalization, dose of vasopressors, ICU stay, hospital stay, and mortality. A total of 199 patients completed the trial. Blood pressure, heart rate, and other routine lab tests showed no difference between the groups. Lactate levels and lactate clearance were similar between the two groups. Hospital and ICU stay were similar between the two groups. When considering all patients, the 7- and 28-day mortality were similar between the two groups, but when considering only patients with lactate levels ≥4.5 mmol/L, the Shenfu group showed a better 7-day survival than the control group (7 days: 83.3% versus 54.5%, P = 0.034; 28 days: 72.7% versus 47.6%, P = 0.092). Shenfu may improve the 7-day survival in patients with impaired lactate clearance (≥4.5 mmol/L), but the mechanism for this effect is unclear. Additional studies are necessary to characterize the hemodynamic changes after Shenfu infusion. This trial is registered with ChiCTR-TRC-11001369. PMID:27446222
Starr, Anna; Sand, Claire A.; Heikal, Lamia; Kelly, Peter D.; Spina, Domenico; Crabtree, Mark; Channon, Keith M.; Leiper, James M.; Nandi, Manasi
ABSTRACT Overproduction of nitric oxide (NO) by inducible NO synthase contributes toward refractory hypotension, impaired microvascular perfusion, and end-organ damage in septic shock patients. Tetrahydrobiopterin (BH4) is an essential NOS cofactor. GTP cyclohydrolase 1 (GCH1) is the rate-limiting enzyme for BH4 biosynthesis. Under inflammatory conditions, GCH1 activity and hence BH4 levels are increased, supporting pathological NOS activity. GCH1 activity can be controlled through allosteric interactions with GCH1 feedback regulatory protein (GFRP). We investigated whether overexpression of GFRP can regulate BH4 and NO production and attenuate cardiovascular dysfunction in sepsis. Sepsis was induced in mice conditionally overexpressing GFRP and wild-type littermates by cecal ligation and puncture. Blood pressure was monitored by radiotelemetry, and mesenteric blood flow was quantified by laser speckle contrast imaging. Blood biochemistry data were obtained using an iSTAT analyzer, and BH4 levels were measured in plasma and tissues by high-performance liquid chromatography. Increased BH4 and NO production and hypotension were observed in all mice, but the extents of these pathophysiological changes were attenuated in GFRP OE mice. Perturbations in blood biochemistry were similarly attenuated in GFRP OE compared with wild-type controls. These results suggest that GFRP overexpression regulates GCH1 activity during septic shock, which in turn limits BH4 bioavailability for iNOS. We conclude that the GCH1-GFRP axis is a critical regulator of BH4 and NO production and the cardiovascular derangements that occur in septic shock. PMID:25046538
Garg, Manjri; Sen, Jyotsna; Goyal, Sandeep; Chaudhry, Dhruva
Objective: Fluid infusion, the most critical step in the resuscitation of patients with septic shock, needs preferably continuous invasive hemodynamic monitoring. The study was planned to evaluate the efficacy of ultrasonographically measured inferior vena cava collapsibility index (IVC CI) in comparison to central venous pressure (CVP) in predicting fluid responsiveness in septic shock. Materials and Methods: Thirty-six patients of septic shock requiring ventilatory support (invasive/noninvasive) were included. Patients with congestive heart failure, raised intra-abdominal pressure, and poor echo window were excluded from the study. They were randomly divided into two groups based on mode of fluid resuscitation – Group I (CVP) and Group II (IVC CI). Primary end-points were mean arterial pressure (MAP) of ≥65 mmHg and CVP >12 mmHg or IVC CI <20% in Groups I and II, respectively. Patients were followed till achievement of end-points or maximum of 6 h. Outcome variables (pulse rate, MAP, urine output, pH, base deficit, and ScvO2 ) were serially measured till the end of the study. Survival at 2 and 4 weeks was used as secondary end-point. Results: Primary end-point was reached in 31 patients (15 in Group I and 16 in Group II). Fluid infusion, by either method, had increased CVP and decreased IVC CI with resultant negative correlation between them (Pearson correlation coefficient –0.626). There was no significant difference in the amount of fluid infused and time to reach end-point in two groups. Comparison in outcome variables at baseline and end-point showed no significant difference including mortality. Conclusion: CVP and IVC CI are negatively correlated with fluid resuscitation, and both methods can be used for resuscitation, with IVC CI being noninferior to CVP. PMID:28149028
Basmaci, R; Ilharreborde, B; Bonacorsi, S; Kahil, M; Mallet, C; Aupiais, C; Doit, C; Dugué, S; Lorrot, M
Septic arthritis has to be suspected in children with joint effusion and fever so as to perform joint aspiration, which will confirm the diagnosis by bacteriological methods, and to perform surgical treatment by joint lavage. Since development of current molecular methods, such as real-time PCR, Kingella kingae has become the first microbial agent of osteoarticular infections in young children, whereas Staphylococcus aureus is second. C-reactive protein (CRP) is an aid used to diagnose septic arthritis, but its elevation could be moderate. In a previous study, conducted at our hospital, 10% of children hospitalized for S. aureus or K. kingae septic arthritis had a CRP level<10 mg/L. To determine if diagnosis of septic arthritis could be made by other parameters, we analyzed the clinical and biologic features of these patients and compared them to those of children hospitalized for septic arthritis with initial CRP ≥10 mg/L. Among the 89 children with septic arthritis, 10% (n=9) had initial CRP<10 mg/L (K. kingae, n=5/63 ; S. aureus, n=4/26). Initial temperature and fibrinogen were significantly lower in the CRP<10 mg/L group than in the other (37.3°C vs. 37.9°C, P=0.039 and 4.19 vs. 5.72 g/L, P=0.003, respectively). Age, symptom duration before diagnosis, as well as leukocyte and platelet counts were similar in both groups. Two children (2/89=2.2%) with S. aureus septic arthritis had no fever, CRP elevation, or fibrinogen elevation. In the CRP-negative group, three of four children with S. aureus arthritis and one of five with K. kingae arthritis had a high CRP level (34, 40, 61, and 13 mg/L, respectively) 3 days after surgery and antibiotic treatment. One child with K. kingae septic arthritis and initial CRP<10 mg/L needed a second surgical drainage because of relapse of arthritis. In the S. aureus arthritis group, none of the children with initial CRP<10 mg/L experienced complications, while six of those with initial CRP≥10 mg/L needed a second surgical act
Ginsburg, Isaac; van Heerden, Peter Vernon; Koren, Erez
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
Roberts, Jason A; Roberts, Darren M
Dosing antibiotics in critically ill patients to achieve therapeutic concentrations is a significant challenge. The presence of septic shock and prescription of continuous renal replacement therapy introduces further complexities for the clinician. Unfortunately, this is a dilemma encountered daily by intensivists. Although small pharmacokinetic studies are emerging to provide data to help address this problem, the variability in results from these studies is profound. As such, effective antibiotic dosing guidelines for critically ill patients who have septic shock and who receive continuous renal replacement therapy are not available. Dosing flowcharts and therapeutic drug monitoring represent the best available options for clinicians to optimize antibiotic dosing.
Gotes, Jose; Kasian, Krika; Jacobs, Hans; Cheng, Zhao-Qin; Mink, Steven N
In septic shock (SS), cardiovascular collapse is caused by the release of inflammatory mediators. We previously found that lysozyme-c (Lzm-S), released from leukocytes, contributed to systemic vasodilation in a canine model of SS. We then delineated the pathway by which this occurs in a canine carotid artery organ bath preparation (CAP). We showed that Lzm-S could intrinsically generate hydrogen peroxide (H(2)O(2)) and that H(2)O(2) subsequently reacted with endogenous catalase to form compound I, an oxidized form of catalase. In turn, compound I led to an increase in cyclic guanosine 3',5'-monophosphate to produce vasodilation. However, it was not clear from previous studies whether it is necessary for Lzm-S to bind to the vasculature to cause vasodilation or, alternatively, whether the generation of H(2)O(2) by Lzm-S in the surrounding medium is all that is required. We examined this question in the present study in which we used multiple preparations. In a partitioned CAP, we found that when we added Lzm-S to a partitioned space in which a semipermeable membrane prevented diffusion of Lzm-S to the carotid artery tissue, vasodilation still occurred because of diffusion of H(2)O(2). On the other hand, we found that Lzm-S could accumulate within the vascular smooth muscle layer (VSML) after 7 h of SS in a canine model. We also determined that when Lzm-S was located in close proximity to vascular smooth muscle cells, it could generate H(2)O(2) to produce lengthening in a human cell culture preparation. We conclude that there are two mechanisms by which Lzm-S can cause vasodilation in SS. In one instance, H(2)O(2) generated by Lzm-S in plasma diffuses to the VSML to cause vasodilation. In a second mechanism, Lzm-S directly binds to the VSML, where it generates H(2)O(2) to produce vasodilation.
Song, Xue-Min; Li, Jian-Guo; Wang, Yan-Lin; Hu, Zheng-Fang; Zhou, Qing; Du, Zhao-Hui; Jia, Bao-Hui
To investigate the effects of the cholinergic anti-inflammatory pathway on hemodynamics, blood biochemistry, the plasma TNF-alpha level, and the nuclear factor-kappaB (NF-kappaB) activation during septic shock, male Sprague-Dawley rats were subjected to cecal ligation and puncture (CLP, a model of polymicrobial sepsis) or sham operation. Forty-eight rats were randomly assigned into six equal groups: sham CLP group; CLP group; VGX group was subjected to bilateral cervical vagotomy after CLP; STM group was subjected to bilateral cervical vagotomy after CLP plus the left vagus nerve trunk electrical stimulation; THA group was administered tetrahydroaminoacridine after CLP and bilateral cervical vagotomy; and alpha-BGT group was administered alpha-bungarotoxin before electrical stimulation of the vagus nerve. The right carotid artery was cannulated to monitor MAP. The plasma TNF-alpha level was measured using enzyme-linked immunosorbent assays. The hepatic NF-kappaB activation was determined by Western blotting. Cecal ligation and puncture produced progressive hypotension. Serum aspartate transaminase and alanine transaminase levels significantly increased after CLP challenge. The plasma TNF-alpha level and the hepatic NF-kappaB activation significantly increased after CLP alone or with bilateral cervical vagotomy compared with sham-operated group. Application of constant voltage pulses to the caudal vagus trunk significantly prevented the development of CLP-induced hypotension, alleviated the hepatic damage, and reduced the plasma TNF-alpha production, but electrical stimulation had no effect on the hepatic NF-kappaB activation. Tetrahydroaminoacridine administration after bilateral cervical vagotomy reversed hypotension and attenuated the plasma TNF-alpha response; in addition, it had no effect on the hepatic NF-kappaB activation. alpha-Bungarotoxin pretreatment significantly reversed the inhibitory effect of vagal electrical stimulation, but it had no effect on the
Shock, regardless of etiology, is characterized by decreased tissue perfusion resulting in cell death, organ dysfunction, and poor survival. Current therapies largely focus on restoring tissue perfusion through resuscitation but have failed to address the specific cellular dysfunction caused by shock. Acetylation is rapidly emerging as a key mechanism that regulates the expression of numerous genes (epigenetic modulation through activation of nuclear histone proteins), as well as functions of multiple cytoplasmic proteins involved in key cellular functions such as cell survival, repair/healing, signaling, and proliferation. Cellular acetylation can be increased immediately through the administration of histone deacetylase inhibitors (HDACI). A series of studies have been performed using: (1) cultured cells; (2) single-organ ischemia-reperfusion injury models; (3) rodent models of lethal septic and hemorrhagic shock; (4) swine models of lethal hemorrhagic shock and multi-organ trauma; and (5) tissues from severely injured trauma patients, to fully characterize the changes in acetylation that occur following lethal insults and in response to treatment with HDACI. These data demonstrate that: (1) shock causes a decrease in acetylation of nuclear and cytoplasmic proteins; (2) hypoacetylation can be rapidly reversed through the administration of HDACI; (3) normalization of acetylation prevents cell death, decreases inflammation, attenuates activation of pro-apoptotic pathways, and augments pro-survival pathways; (4) the effect of HDACI significantly improves survival in lethal models of septic shock, hemorrhagic shock, and complex poly-trauma without need for conventional fluid resuscitation or blood transfusion; and (5) improvement in survival is not due to better resuscitation but due to an enhanced ability of cells to tolerate lethal insults. As different models of hemorrhagic or septic shock have specific strengths and limitations, this chapter will summarize our
Garcia-Simon, Monica; Morales, Jose M; Modesto-Alapont, Vicente; Gonzalez-Marrachelli, Vannina; Vento-Rehues, Rosa; Jorda-Miñana, Angela; Blanquer-Olivas, Jose; Monleon, Daniel
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 (1)H-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 (1)H 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.
Modesto-Alapont, Vicente; Gonzalez-Marrachelli, Vannina; Vento-Rehues, Rosa; Jorda-Miñana, Angela; Blanquer-Olivas, Jose; Monleon, Daniel
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
Huang, Min-Yi; Chen, Chun-Yu; Chien, Ju-Huei; Wu, Kun-Hsi; Chang, Yu-Jun; Wu, Kang-Hsi; Wu, Han-Ping
We evaluated the tendency of the plasma concentration and procalcitonin (PCT) clearance (PCTc) to act as biomarkers of prognosis in patients with severe sepsis and septic shock. From 2011 to 2013, we prospectively analyzed patients with sepsis admitted to the intensive care unit (ICU). The serum PCT was evaluated at the time of sepsis diagnosis and again after 48 h (day 3) and 96 h (day 5). PCTc after 48 h (PCTc-day 3) and 96 h (PCTc-day 5) was also calculated to evaluate the prognostic value for survival in patients with sepsis. A total of 48 patients were included. Overall mortality was 16.7% (8 patients). PCTc was higher in survivors than in nonsurvivors, with significant differences on day 3 and day 5 (p = 0.033; p = 0.002, resp.); however, serum PCT levels on day 1, day 3, and day 5 were not significant prognostic factors for survival. The prognosis of patients with severe sepsis and septic shock may be associated with PCTc. Dynamic changes of PCT reflected as PCTc at 48 h (day 3) and 96 h (day 5) after admission to the ICU may serve as a predictor of survival in critically ill patients with severe sepsis.
Huang, Min-Yi; Chen, Chun-Yu; Chien, Ju-Huei; Wu, Kun-Hsi; Chang, Yu-Jun; Wu, Han-Ping
We evaluated the tendency of the plasma concentration and procalcitonin (PCT) clearance (PCTc) to act as biomarkers of prognosis in patients with severe sepsis and septic shock. From 2011 to 2013, we prospectively analyzed patients with sepsis admitted to the intensive care unit (ICU). The serum PCT was evaluated at the time of sepsis diagnosis and again after 48 h (day 3) and 96 h (day 5). PCTc after 48 h (PCTc-day 3) and 96 h (PCTc-day 5) was also calculated to evaluate the prognostic value for survival in patients with sepsis. A total of 48 patients were included. Overall mortality was 16.7% (8 patients). PCTc was higher in survivors than in nonsurvivors, with significant differences on day 3 and day 5 (p = 0.033; p = 0.002, resp.); however, serum PCT levels on day 1, day 3, and day 5 were not significant prognostic factors for survival. The prognosis of patients with severe sepsis and septic shock may be associated with PCTc. Dynamic changes of PCT reflected as PCTc at 48 h (day 3) and 96 h (day 5) after admission to the ICU may serve as a predictor of survival in critically ill patients with severe sepsis. PMID:27088084
Artigas, Antonio; Piccinni, Pasquale
Sepsis is a major health problem and remains an important cause of death worldwide. The failure to convert advances in our understanding of the biologic features of sepsis into effective new therapies questions the current approach to the development of sepsis drugs, and suggests a need for newer and better clinical trial design. Blood purification for sepsis is a promising therapeutic strategy to improve survival and reduce organ failure in patients with severe sepsis and septic shock.
Ahmed, Wasim; Memon, Javed I; Rehmani, Rifat; Al Juhaiman, Abdulmajeed
Acute kidney injury (AKI) in the intensive care unit (ICU) is commonly caused by severe sepsis and septic shock. There is limited data regarding the incidence and outcomes of patients developing AKI treated with early goal-directed therapy (EGDT). Our aim was to observe the incidence and outcomes of patients with AKI in severe sepsis and septic shock, treated with EGDT as compared with historic controls. Study subjects included all adults admitted to the ICU with a diagnosis of severe sepsis and septic shock prior to (historic controls) and after introduction of EGDT (intervention group). Two groups were compared for incidence of AKI, length of ICU and hospital stay, incidence and requirement for renal replacement therapy, serum creatinine at discharge, maximum RIFLE (Risk, injury, failure, loss, end stage) in each group and 28-day mortality. Two groups were well matched for age, sex, (April 16, 2014) and acute physiological and chronic health evaluation (APACHE) II scores. We found no significant difference in the incidence of AKI (51% vs. 46%). There was no statistical difference in any of the above outcomes, including 28-day mortality in historic controls versus patients treated with EGDT. Septic AKI is a complex syndrome. The incidence and outcomes have not improved despite advances in sepsis management and EGDT. Very early detection of septic AKI and targeted therapies may improve outcomes.
Klouche, Kada; Pommet, Stephane; Amigues, Laurent; Bargnoux, Anne Sophie; Dupuy, Anne Marie; Machado, Sonia; Serveaux-Delous, Marianne; Morena, Marion; Jonquet, Olivier; Cristol, Jean Paul
The aim of this study was to evaluate and compare brain natriuretic peptide (BNP) and cardiac troponin I (cTnI) levels as mortality prognosticator and predictor for myocardial dysfunction in severe sepsis and septic shock. Baseline clinical and biological variables were collected from 47 patients with severe sepsis or septic shock. Ventricular systolic function assessed by echocardiography was measured over a 5-day period. Both cTnI and BNP plasmatic levels were determined at intensive care unit (ICU) admission and during the following 15 days. At admission, cTnI and BNP levels were compared to those of 12 control critically ill nonseptic patients. The plasma levels of BNP and cTnI in patients with sepsis were elevated at admission and significantly higher than in the controls. Among patients with sepsis, BNP levels were significantly more elevated in nonsurvivors compared to survivors at admission and 1 day later. The cTnI levels were also significantly more elevated in nonsurvivors compared to survivors, but only at admission. From admission to day 5, patients with sepsis with left ventricular systolic dysfunction had higher BNP plasmatic concentrations than those without; differences were significant at days 3 and 4. In contrast, plasma cTnI levels were similar between the 2 groups. In critically ill patients, sepsis induces significant increase in BNP and cTnI levels. High BNP and cTnI plasma levels during ICU admission appear to be associated with poor outcome of sepsis. Time course of BNP levels seems helpful to discriminate between surviving and nonsurviving patients with sepsis and to detect myocardial dysfunction where troponin levels fail to do so.
Sethuraman, Vinoth K; Balasubramanian, Kavitha; Aghoram, Rajeswari
Adult onset Still’s disease is uncommon in middle-aged and elderly individuals and can rarely present with shock; shock is usually associated with disseminated intravascular coagulation, multiorgan dysfunction syndrome or acute respiratory distress syndrome. We report a post-menopausal woman with arthritis, fever, pneumonitis and hypotension which was managed as septic shock. Steroids were inadvertently missed during the second day of hospitalization in the intensive care unit. Persistence of hypotension on inotropes, with normal renal, hepatic and neurological function and recurrence of fever when steroids were skipped, led to suspicion of an inflammatory disorder. A diagnosis of Still’s disease may be entertained in postmenopausal women with polyarthritis, rash, and fever with leukocytosis. Sepsis is mimicked, and multiple antibiotics use is common before the diagnosis of such an entity is made. Shock is rare in adult onset Still’s disease and is not necessarily associated with disseminated intravascular coagulation, acute respiratory distress syndrome, or multiorgan dysfunction. PMID:28191382
Seghezzi, Michela; Vavassori, Mauro; Dominoni, Paola; Apassiti Esposito, Sara; Manenti, Barbara; Mecca, Tommaso; Marchesi, Gianmariano; Castellucci, Enrico; Azzarà, Giovanna; Ottomano, Cosimo; Lippi, Giuseppe
Background This study evaluated the clinical significance of cell population data (CPD) parameters obtained on Sysmex XN-9000 in septic patients admitted to intensive care unit (ICU) and stratified according to liver function. Methods The study population consisted in 84 patients, 44 of whom did not develop sepsis (NS), whereas the remaining 40 developed sepsis (SE) (n=24) or septic shock (SS) (n=16). Two hundred ostensibly healthy blood donors [healthy subjects (HS)], undergoing routine blood testing before a regular blood donation, were studied. Results Except for neutrophils and lymphocytes cell size (NE-FCS and LY-Z), all other CPD values were significantly different in ICU patients compared to HS. Neutrophils and monocytes fluorescence intensity (NE-SFL and MO-X) values were significantly higher in SS compared to sepsis and not develop sepsis patients. The value of many parameters was also different according to liver function. Overall, MO-X and neutrophils fluorescence intensity (NE-SFL) exhibited the best performance for diagnosing sepsis in all patients (AUC, 0.75 and 0.72), as well as in those with (AUC, 0.95 and 0.89) or without (AUC, 0.72 for both) liver impairment. These parameters were also significantly correlated with Sequential Organ Failure Assessment (SOFA) score. Conclusions This study suggested that some novel CPD parameters (namely NE-SFL and MO-X) may provide useful information for diagnosis and management of sepsis. PMID:27942509
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
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
Introduction Venous-to-arterial carbon dioxide difference (Pv-aCO2) may reflect the adequacy of blood flow during shock states. We sought to test whether the development of Pv-aCO2 during the very early phases of resuscitation is related to multi-organ dysfunction and outcomes in a population of septic shock patients resuscitated targeting the usual oxygen-derived and hemodynamic parameters. Methods We conducted a prospective observational study in a 60-bed mixed ICU in a University affiliated Hospital. 85 patients with a new septic shock episode were included. A Pv-aCO2 value ≥ 6 mmHg was considered to be high. Patients were classified in four predefined groups according to the Pv-aCO2 evolution during the first 6 hours of resuscitation: (1) persistently high Pv-aCO2 (high at T0 and T6); (2) increasing Pv-aCO2 (normal at T0, high at T6); (3) decreasing Pv-aCO2 (high at T0, normal at T6); and (4) persistently normal Pv-aCO2 (normal at T0 and T6). Multiorgan dysfunction at day-3 was compared for predefined groups and a Kaplan Meier curve was constructed to show the survival probabilities at day-28 using a log-rank test to evaluate differences between groups. A Spearman-Rho was used to test the agreement between cardiac output and Pv-aCO2. Finally, we calculated the mortality risk ratios at day-28 among patients attaining normal oxygen parameters but with a concomitantly increased Pv-aCO2. Results Patients with persistently high and increasing Pv-aCO2 at T6 had significant higher SOFA scores at day-3 (p < 0.001) and higher mortality rates at day-28 (log rank test: 19.21, p < 0.001) compared with patients who evolved with normal Pv-aCO2 at T6. Interestingly, a poor agreement between cardiac output and Pv-aCO2 was observed (r2 = 0.025, p < 0.01) at different points of resuscitation. Patients who reached a central venous saturation (ScvO)2 ≥ 70% or mixed venous oxygen saturation (SvO2) ≥ 65% but with concomitantly high Pv-aCO2 at different developmental points (i
Lei, Ming; Liu, Xin-Xin
The vagus nerve and the released acetylcholine exert anti-inflammatory effects and inhibit septic shock. However, their detailed mechanisms remain to be elucidated. The present study aimed to investigate the effects of vagus nerve electrical stimulation on serum S100A8 levels in septic shock rats. A total of 36 male Sprague-Dawley rats were randomly divided into six equal groups: i) Sham group, receiving sham operation; ii) CLP group, subjected to cecal ligation and puncture (CLP) to establish a model of polymicrobial sepsis; iii) VGX group, subjected to CLP and bilateral cervical vagotomy; iv) STM group, subjected to CLP, bilateral cervical vagotomy and electrical stimulation on the left vagus nerve trunk; v) α‑bungarotoxin (BGT) group was administered α‑BGT prior to electrical stimulation; vi) Anti‑receptor for advanced glycation end products (RAGE) group, administered intraperitoneal injection of anti‑RAGE antibody prior to electrical stimulation. The right carotid artery was cannulated to monitor mean artery pressure (MAP). The serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels were measured to assess the liver function. Serum S100A8 and advanced glycation end product (AGE) levels were measured using enzyme‑linked immunosorbent assays. The expression of hepatic RAGE was determined by western blotting. The present study revealed that Sprague‑Dawley rats exhibited progressive hypotension and significantly increased serum AST and ALT levels following CLP challenge compared with the sham group. The levels of S100A8 and AGEs, and the protein expression of hepatic RAGE were significantly increased following CLP compared with the sham group. Vagus nerve electrical stimulation significantly prevented the development of CLP‑induced hypotension, alleviated the hepatic damage, reduced serum S100A8 and AGEs production, and reduced the expression of hepatic RAGE. The inhibitory effect of vagus nerve electrical
Introduction This prospective, randomized, controlled, experimental animal study looks at the effects of recombinant human activated protein C (rhAPC) on global hemodynamics and microcirculation in ovine acute lung injury (ALI) and septic shock, resulting from smoke inhalation injury. Methods Twenty-one sheep (37 ± 2 kg) were operatively prepared for chronic study and randomly allocated to either the sham, control, or rhAPC group (n = 7 each). The control and rhAPC groups were subjected to insufflation of four sets of 12 breaths of cotton smoke followed by instillation of live Pseudomonas aeruginosa into both lung lobes, according to an established protocol. Healthy sham animals were not subjected to the injury and received only four sets of 12 breaths of room air and instillation of the vehicle (normal saline). rhAPC (24 μg/kg/hour) was intravenously administered from 1 hour post injury until the end of the 24-hour experiment. Regional microvascular blood flow was analyzed using colored microspheres. All sheep were mechanically ventilated with 100% oxygen, and fluid resuscitated with lactated Ringer's solution to maintain hematocrit at baseline levels. Results The rhAPC-associated reduction in heart malondialdehyde (MDA) and heart 3-nitrotyrosine (a reliable indicator of tissue injury) levels occurred parallel to a significant increase in mean arterial pressure and to a significant reduction in heart rate and cardiac output compared with untreated controls that showed a typical hypotensive, hyperdynamic response to the injury (P < 0.05). In addition, rhAPC significantly attenuated the changes in microvascular blood flow to the trachea, kidney, and spleen compared with untreated controls (P < 0.05 each). Blood flow to the ileum and pancreas, however, remained similar between groups. The cerebral blood flow as measured in cerebral cortex, cerebellum, thalamus, pons, and hypothalamus, was significantly increased in untreated controls, due to a loss of cerebral
Markota, Andrej; Seme, Katja; Golle, Andrej; Poljak, Mario; Sinkovič, Andreja
Several studies have been performed investigating the role of a real-time multiplex polymerase chain reaction assay LightCycler SeptiFast with inconsistent results. In prospective evaluation of adult patients with severe sepsis or septic shock SeptiFast assay and blood culture results were compared regarding concordance, the impact of SeptiFast assay on antimicrobial therapy adjustment, time to results and the role of SeptiFast assay as a marker of disease severity. 63 blood sample sets were collected from 57 patients. 51 (80.9%) results were concordant negative and 7 (11.1%) concordant posi- tive. In one (1.6%) sample set blood culture was positive and SeptiFast assay negative, in three (4.8%) sample sets with negative blood cultures pathogens were detected by SeptiFast assay and in one (1.6%)patient an additional pathogen was detected by SeptiFast assay. If blood culture is considered as "gold standard", 1 (1.6%) SeptiFast false negative and 4 (6.3%) false positive results were identified (sensitivity 87.5%, specificity 92.6%, negative predictive value 97.8%). Antibiotic treatment was adjusted according to SeptiFast assay in 4 (6.3%) cases. Time to final results was significantly shorter with SeptiFast assay (32 +/- 23 h vs. 97 +/- 28 h, p < 0.0001). Positive SeptiFast assay was not associated with higher mortality, C-reactive protein orprocalcitonin (p = 0.74, p = 0.44 and p = 0.12, respectively). According to our results SeptiFast assay can be used as a valuable add-on to blood culture in diagnostic workup ofpatients with severe sepsis and septic shock but it cannot replace the blood culture.
Bonanno, Fabrizio Giuseppe
The clinical aspects of shock syndromes are described from their inception as compensated physiology to a stage of decompensation. The clinical significance of hypotension, fluid-responsive and non fluid-responsive hypotension, is discussed. Untimely or inadequate treatment leads to persistent subclinical shock despite adjustments of the macrohemodynamic variables, which evolves in a second hit of physiological deterioration if not aggressively managed. Irreversible shock ensues as consequence of direct hit or as result of inadequate or delayed treatment and is characterized by drug-resistant hypotension. PMID:21769211
Mazzone, Antonino; Dentali, Francesco; La Regina, Micaela; Foglia, Emanuela; Gambacorta, Maurizia; Garagiola, Elisabetta; Bonardi, Giorgio; Clerici, Pierangelo; Concia, Ercole; Colombo, Fabrizio; Campanini, Mauro
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.
Hsu, Jong-Hau; Yang, Rei-Cheng; Lin, Shih-Jen; Liou, Shu-Fen; Dai, Zen-Kong; Yeh, Jwu-Lai; Wu, Jiunn-Ren
It has been recently demonstrated that intracellular heat shock cognate protein 70 (HSC70) can be released into extracellular space with physiologic effects. However, its extracellular function in sepsis is not clear. In this study, we hypothesize that extracellular HSC70 can protect against lipopolysaccharide (LPS)-induced myocardial and hepatic dysfunction because of its anti-inflammatory actions. In Wistar rats, septic shock developed with hypotension, tachycardia, and myocardial and hepatic dysfunction at 4 h following LPS administration (10 mg/kg, i.v.). Pretreatment with recombinant bovine HSC70 (20 μg/kg, i.v.) attenuated LPS-induced hypotension and tachycardia by 21% and 23%, respectively (P < 0.05), improved myocardial dysfunction (left ventricular systolic pressure: 33%; max dP/dt: 20%; min dP/dt: 33%, P < 0.05), and prevented hepatic dysfunction (glutamic-oxaloacetic transaminase: 81 vs. 593 IU/L; glutamic-pyruvic transaminase: 15 vs. 136 IU/L, P < 0.05) compared with LPS-treated rats at 4 h. Heat shock cognate protein 70 also prevented LPS-induced hypoglycemia (217 vs. 59 mg/dL, P < 0.05) and elevated lactate dehydrogenase (1,312 vs. 6,301 IU/L, P < 0.05). Furthermore, HSC70 decreased LPS-induced elevation of circulating tumor necrosis factor α and nitrite/nitrate, and tissue expression of inducible nitric oxide synthase, cyclooxygenase 2, and matrix metalloproteinase 9 in the heart and liver. To investigate underlying mechanisms, we found that HSC70 attenuated LPS-induced nuclear translocation of nuclear factor κB subunit p65 by blocking the phosphorylation of inhibitor of nuclear factor κB. Finally, we showed that HSC70 repressed the activation of MAPKs caused by LPS. These results demonstrate that in LPS-induced septic shock, extracellular HSC70 conveys pleiotropic protection on myocardial, hepatic, and systemic derangements, with associated inhibition of proinflammatory mediators including tumor necrosis factor α, nitric oxide, cyclooxygenase 2
Pilas, V; Cubrilo, M; Bakula, V; Vranjkovic, S; Bakula, B; Bilic, A
In 31 patients with sepsis and multiple organic dysfunction, changes in the systemic oxygen consumption (VO2) during reanimation were observed in order to discover more objective indicators of the course and prognosis of the disease. In a prospective randomized study, 21 live (Group 1) and 11 dead patients (Group 2) were included. The investigation was based upon the application of the invasive tracing of oxygen hemodynamics and transport. The findings of the initially hypovolemic status were compared with those of the stabile normovolemic status obtained by the application of infusions and the blood volume substitute. In the early phase of the disease there were no significant differences in the clinical finding of the circulatory shock and the volume deficit of the circulated blood between these two groups of patients. Group 1 patients had lower values of the cardiac index (CI) and the systemic oxygen transport (DO2). In them there was a greater frequency of acute organic insufficiency, especially pulmonal, renal and hepatal. In the initial status VO2 decreased. In the normovolemic status of Group 1, a significant VO2 was found, while in Group 2 in spite of a DO2 increase and hemodynamics improvement, a more significant VO2 increase was not obtained. As VO2 is an objective indicator of oxidative metabolic reactions of the organism and the circulatory system, the authors maintain that by the VO2 tracing, a better insight into the seriousness and course of the disease is obtained, and that an inadequate VO2 finding during the therapeutic treatment requires a revision of the treatment.
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).
Cornejo, Rodrigo; Romero, Carlos; Ugalde, Diego; Bustos, Patricio; Diaz, Gonzalo; Galvez, Ricardo; Llanos, Osvaldo; Tobar, Eduardo
We report the successful treatment of two patients with aneurismal subarachnoid hemorrhage complicated by severe respiratory failure and refractory septic shock using simultaneous prone position ventilation and high-volume hemofiltration. These rescue therapies allowed the patients to overcome the critical situation without associated complications and with no detrimental effects on the intracranial and cerebral perfusion pressures. Prone position ventilation is now an accepted therapy for severe acute respiratory distress syndrome, and high-volume hemofiltration is a non-conventional hemodynamic support that has several potential mechanisms for improving septic shock. In this manuscript, we briefly review these therapies and the related evidence. When other conventional treatments are insufficient for providing safe limits of oxygenation and perfusion as part of basic neuroprotective care in subarachnoid hemorrhage patients, these rescue therapies should be considered on a case-by-case basis by an experienced critical care team. PMID:25028955
Release of melanotroph- and corticotroph-type proopiomelanocortin derivatives into blood after administration of corticotropin-releasing hormone in patients with septic shock without adrenocortical insufficiency.
Matejec, Reginald; Löcke, Gudrun; Mühling, Jörg; Harbach, Heinz-Walter; Langefeld, Tanja-Wiebke; Bödeker, Rolf-Hasso; Hempelmann, Gunter
The aim of the study was to assess the adequacy of pituitary function by determining the plasma concentrations of corticotroph-type (corticotropin, beta-endorphin immunoreactive material [beta-END IRM], authentic beta-END, and beta-lipotropin IRM) as well as melanotroph-type (alpha-melanocyte-stimulating hormone [alpha-MSH] and N-acetyl-beta-END [Nac-beta-END] IRM) proopiomelanocortin (POMC) derivatives in patients under septic shock upon administration of corticotropin-releasing hormone (CRH). The objectives were to assess whether an insufficient release of corticotroph- or melanotroph-type POMC derivatives from the pituitary into the cardiovascular compartment correlates with the 28-day mortality rate. Seventeen patients with septic shock but without adrenocortical insufficiency and 16 healthy volunteers were enrolled in the study, and CRH stimulation tests were performed with an i.v. bolus injection of 100 microg human CRH. After treatment with CRH, plasma concentrations of corticotroph-type POMC derivatives increased in survivors and nonsurvivors, melanotroph-type POMC derivatives such as alpha-MSH or Nac-beta-END IRM increased only in survivors in contrast to nonsurvivors. The release of alpha-MSH and Nac-beta-END IRM was suppressed by dexamethasone in survivors but not in nonsurvivors. In patients with septic shock, the response of the pituitary to CRH stimulation in terms of alpha-MSH or Nac-beta-END IRM release was impaired in nonsurvivors compared with survivors or controls. Reduced responses of alpha-MSH or Nac-beta-END IRM to CRH and the invalid suppression by dexamethasone reflect a state of dysfunction of the melanotroph-type POMC system in nonsurvivors. Considering anticytokine and anti-inflammatory effects of alpha-MSH, this dysfunction may increase the risk of death in patients with septic shock.
Ala-Kokko, Tero I; Mutt, Shivaprakash J; Nisula, Sara; Koskenkari, Juha; Liisanantti, Janne; Ohtonen, Pasi; Poukkanen, Meri; Laurila, Jouko J; Pettilä, Ville; Herzig, Karl-Heinz
Introduction Low levels of vitamin D have been associated with increased mortality in patients that are critically ill. This study explored whether vitamin D levels were associated with 90-day mortality in severe sepsis or septic shock. Methods Plasma vitamin D levels were measured on admission to the intensive care unit (ICU) in a prospective multicentre observational study. Results 610 patients with severe sepsis were included; of these, 178 (29%) had septic shock. Vitamin D deficiency (<50 nmol/L) was present in 333 (55%) patients. The 90-day mortality did not differ among patients with or without vitamin D deficiency (28.3% vs. 28.5%, p = 0.789). Diabetes was more common among patients deficient compared to those not deficient in vitamin D (30% vs. 18%, p < 0.001). Hospital-acquired infections at admission were more prevalent in patients with a vitamin D deficiency (31% vs. 16%, p < 0.001). A multivariable adjusted Cox regression model showed that low vitamin D levels could not predict 90-day mortality (<50 nmol/L: hazard ratio (HR) 0.99 (95% CI: 0.72-1.36), p > 0.9; and <25 nmol/L: HR 0.44 (95% CI: 0.22-0.87), p = 0.018). Conclusions Vitamin D deficiency detected upon ICU admission was not associated with 90-day mortality in patients with severe sepsis or septic shock. Key messages In severe sepsis and septic shock, a vitamin D deficiency upon ICU admission was not associated with increased mortality. Compared to patients with sufficient vitamin D, patients with deficient vitamin D more frequently exhibited diabetes, elevated C-reactive protein levels, and hospital-acquired infections upon ICU admission, and they more frequently developed acute kidney injury.
Festti, Josiane; Grion, Cintia Magalhães Carvalho; Festti, Luciana; Mazzuco, Tânia Longo; Lima-Valassi, Helena Pantelion; Brito, Vinícius Nahime; Barbosa, Décio Sabbatini; Carrilho, Alexandre José Faria
Relative adrenal insufficiency in sepsis has been extensively debated on; however, accurate diagnosis and therapeutic intervention remain controversial. The authors aimed to evaluate adrenocorticotropic hormone (ACTH), salivary cortisol, total cortisol and estimated plasma-free cortisol, cholesterol, and lipoproteins as predictors of adrenal insufficiency in patients within 24 h of septic shock diagnosis. This prospective study evaluated all hospitalized patients older than 18 years who developed septic shock and were using vasoactive drugs within 24 h of diagnosis. Blood and saliva samples were drawn at baseline and 60 min (T60) after 250 μg tetracosactide intravenous injection. Patients were divided into two groups: responders (Δ [T60 minus baseline] total cortisol >9 μg/dL) and nonresponders (Δ total cortisol ≤ 9 μg/dL or baseline total cortisol <10 μg/dL). The latter group was considered to have adrenal insufficiency. A total of 7,324 hospitalized patients were monitored, and 34 subjects with septic shock were included in the analysis. Adrenal insufficiency was found in 32.4%. Total cholesterol, high-density lipoprotein cholesterol, triglycerides, and salivary cortisol did not differ between groups. Estimated plasma-free cortisol was not better than total plasma cortisol in estimating adrenal function. Baseline endogenous ACTH was higher in nonresponders than responders (55.5 pg/mL vs. 18.3 pg/mL, respectively; P = 0.01). The cutoff ACTH value that discriminated patients with adrenal insufficiency was 31.5 pg/mL. Thus, endogenous ACTH measured within 24 h of septic shock diagnosis could predict adrenal response to tetracosactide.
Ulldemolins, Marta; Soy, Dolors; Llaurado-Serra, Mireia; Vaquer, Sergi; Castro, Pedro; Rodríguez, Alejandro H; Pontes, Caridad; Calvo, Gonzalo; Torres, Antoni; Martín-Loeches, Ignacio
Meropenem dosing in critically ill patients with septic shock and continuous renal replacement therapy (CRRT) is complex, with the recommended maintenance doses being 500 mg to 1,000 mg every 8 h (q8h) to every 12 h. This multicenter study aimed to describe the pharmacokinetics (PKs) of meropenem in this population to identify the sources of PK variability and to evaluate different dosing regimens to develop recommendations based on clinical parameters. Thirty patients with septic shock and CRRT receiving meropenem were enrolled (153 plasma samples were tested). A population PK model was developed with data from 24 patients and subsequently validated with data from 6 patients using NONMEM software (v.7.3). The final model was characterized by CL = 3.68 + 0.22 · (residual diuresis/100) and V = 33.00 · (weight/73)(2.07), where CL is total body clearance (in liters per hour), residual diuresis is the volume of residual diuresis (in milliliters per 24 h), and V is the apparent volume of distribution (in liters). CRRT intensity was not identified to be a CL modifier. Monte Carlo simulations showed that to maintain concentrations of the unbound fraction (fu ) of drug above the MIC of the bacteria for 40% of dosing interval T (referred to as 40% of the ƒ uT >MIC), a meropenem dose of 500 mg q8h as a bolus over 30 min would be sufficient regardless of the residual diuresis. If 100% of the ƒ uT >MIC was chosen as the target, oligoanuric patients would require 500 mg q8h as a bolus over 30 min for the treatment of susceptible bacteria (MIC < 2 mg/liter), while patients with preserved diuresis would require the same dose given as an infusion over 3 h. If bacteria with MICs close to the resistance breakpoint (2 to 4 mg/liter) were to be treated with meropenem, a dose of 500 mg every 6 h would be necessary: a bolus over 30 min for oligoanuric patients and an infusion over 3 h for patients with preserved diuresis. Our results suggest that residual diuresis may be an easy and
Maybauer, Dirk M; Maybauer, Marc O; Traber, Lillian D; Westphal, Martin; Nakano, Yoshimitsu Y; Enkhbaatar, Perenlei; Morita, Naoki; Herndon, David N; Traber, Daniel L
This prospective, randomized, controlled experimental study looks at the effects on global and regional microvascular blood flow (RMBF) in an ovine model of septic shock after severe smoke inhalation injury. Sixteen sheep were randomized into two groups, a control group (no injury, n = 8) and a smoke/sepsis (SS) group (n = 8), which received an insufflation of 4 sets of 12 breaths of cotton smoke (<40 degrees C) followed by instillation of live Pseudomonas aeruginosa into both lung lobes, according to an established protocol. All sheep were mechanically ventilated with 100% oxygen, and fluid resuscitated with lactated Ringer's solution for the entire duration of the 24-h experimental period to maintain hematocrit at baseline (BL) levels. Healthy control animals were not subjected to the injury and received only 4 x 12 breaths of room air and instillation of the vehicle (normal saline). Blood flow was analyzed using colored microspheres. Control animals remained hemodynamically stable and had no statistical changes from BL in visceral or cerebral blood flow during the entire experimental period. All SS animals developed a hypotensive, hyperdynamic circulation, characterized by a significant increase in heart rate and cardiac output with a simultaneous significant fall in mean arterial pressure, which, in combination, led to a fall in systemic vascular resistance index versus BL (P < 0.001, each). In visceral organs, the trachea showed a significant increase in RMBF (P < 0.001). In addition, skeletal muscle significantly increased versus BL and versus controls over time (P < 0.01). Whereas the pancreas displayed a significant drop in RMBF versus BL and controls (P < 0.05), no statistical differences occurred in the renal cortex, spleen, and ileum. All investigated cerebral structures, such as the cortex cerebri, basal ganglia, thalamus, hippocampus, pons, medulla oblongata, and cerebellum showed a significant increase in RMBF versus BL and versus control animals (P
Baldwin, Lee N; Smith, Sally A; Fender, Veronica; Gisby, Sharon; Fraser, Jayne
Severe sepsis and septic shock are syndromes resulting in a systemic inflammatory response and the dysfunction of one or more organs following infection. The Surviving Sepsis Campaign is an international effort to reduce mortality in severe sepsis and septic shock by 25% by 2009 using a care bundle approach. It comprises evidenced-based interventions to be carried out within 6h of onset of sepsis. We conducted a prospective observational audit of 32 consecutive adult patients with severe sepsis or septic shock admitted via the A&E of a district general hospital. The compliance rate against each element, and overall compliance to the 6-h bundle were obtained. Patients' ages ranged from 55 to 75 years with 53% being male. Overall compliance was 19%. Arterial lactate was undertaken 100% of the time, and only just over half received an appropriate fluid challenge. Administration of an antibiotic was also very slow. Local recommendations include improvements to the track and trigger scoring system in A&E to improve recognition of sick patients, ensuring the doctor responsible for prescribing the antibiotic will administer it, and increasing awareness of the surviving sepsis campaign via education and training of all A&E staff. Given current evidence greater compliance to the care bundle may well improve patient outcomes for this client group.
Carnio, E C; Moreto, V; Giusti-Paiva, A; Antunes-Rodrigues, J
Septic shock is a major cause of death following trauma and a persistent problem in surgical patients. It is a challenge to the critical care medicine specialist and carries an unacceptably high mortality rate, despite adequate antibiotic and vasopressor therapy. The prevalent hypothesis regarding its mechanism is that the syndrome is caused by an excessive defensive and inflammatory response. During the acute phase some signalling mechanisms are activated, particularly hormone release, which function to restore the host homeostasis that has been disturbed by the infection. Since the neuroendocrine and immune systems are functionally related, so the exposure to antigens induces a synchronized response, which allows the organism to successfully endure immunology changes. An important characteristic of this communication includes the appearance of proteins released into the circulation by activated immune cells. These proteins, called cytokines can enter the circulation and reach neuroendocrine organs, where they act either themselves or through the release of intermediates such as prostaglandin, catecholamines and nitric oxide. The synthesis of nitric oxide may be induced in brain as a consequence of infection and may alter the function of the hypothalamic-pituitary axis. In this review we discuss the physiologic roles of the nitric oxide in central nervous system controlling the regulation of vasopressin and oxytocin during the pathophysiology of sepsis.
Huang, Chun-Ta; Tsai, Yi-Ju; Tsai, Pi-Ru; Yu, Chong-Jen; Ko, Wen-Je
Severe sepsis remains the leading cause of mortality in the critically ill. Local epidemiological studies on sepsis are of paramount importance to increase our knowledge about sepsis features and to improve patient care and prognosis.Adult patients (≥20 years) admitted to the surgical intensive care units with severe sepsis or septic shock from 2009 to 2010 were retrospectively retrieved and analyzed. The primary outcome of interest was 28-day mortality.Of 7795 admissions, 536 (6.9%) patients had severe sepsis. The most common sites of infection were the respiratory tract (38%) and abdomen (33%). Gram-negative bacteria, particularly Klebsiella pneumoniae (8.6%) and Escherichia coli (6.0%), were the major infecting micro-organisms, responsible for approximately two-thirds of the severe sepsis episodes. The overall 28-day mortality rate was 61%, and a higher sequential organ failure assessment score and the use of mechanical ventilation were independently associated with a worse outcome.Admissions with severe sepsis are not uncommon and are associated with substantial 28-day mortality in surgical intensive care units in northern Taiwan. Establishment and optimization of each institutional sepsis care standard to improve the outcome of sepsis are warranted.
Sarrias, Maria-Rosa; Farnós, Montserrat; Mota, Rubén; Sánchez-Barbero, Fernando; Ibáñez, Anna; Gimferrer, Idoia; Vera, Jorge; Fenutría, Rafael; Casals, Cristina; Yélamos, José; Lozano, Francisco
CD6 is a lymphocyte receptor that belongs to the scavenger receptor cysteine-rich superfamily. Because some members of the scavenger receptor cysteine-rich superfamily act as pattern recognition receptors for microbial components, we studied whether CD6 shares this function. We produced a recombinant form of the ectodomain of CD6 (rsCD6), which was indistinguishable (in apparent molecular mass, antibody reactivity, and cell binding properties) from a circulating form of CD6 affinity-purified from human serum. rsCD6 bound to and aggregated several Gram-positive and -negative bacterial strains through the recognition of lipoteichoic acid and LPS, respectively. The Kd of the LPS–rsCD6 interaction was 2.69 ± 0.32 × 10−8 M, which is similar to that reported for the LPS–CD14 interaction. Further experiments showed that membrane CD6 also retains the LPS-binding ability, and it results in activation of the MAPK signaling cascade. In vivo experiments demonstrated that i.p. administration of rsCD6 before lethal LPS challenge significantly improved mice survival, and this was concomitant with reduced serum levels of the proinflammatory cytokines TNF-α, IL6, and IL-1β. In conclusion, our results illustrate the unprecedented bacterial binding properties of rsCD6 and support its therapeutic potential for the intervention of septic shock syndrome or other inflammatory diseases of infectious origin. PMID:17601777
Morichika, Daisuke; Sato-Hisamoto, Akiko; Hotta, Katsuyuki; Takata, Katsuyoshi; Iwaki, Noriko; Uchida, Koji; Minami, Daisuke; Kubo, Toshio; Tanimoto, Mitsune; Kiura, Katsuyuki
Invasive candidiasis has increased as nosocomial infection recently in cancer patients who receive systemic chemotherapy, and the timely risk assessment for developing such specific infection is crucial. Especially in those concomitantly with hypopituitarism, febrile neutropenia with candidiasis can cause severe stress and lead potentially to sudden fatal outcome when the temporal steroid coverage for the adrenal insufficiency is not fully administered. We report a 72-year-old male case diagnosed as non-small-cell lung cancer, Stage IIIA. He had received a steroid replacement therapy for the prior history of hypophysectomy due to pituitary adenoma with hydrocortisone of 3.3 mg/day, equivalent to prednisolone of 0.8 mg/day. This very small dosage of steroid was hardly supposed to weaken his immune system, but rather potentially led to an inappropriate supplementation of his adrenal function, assuming that the serum sodium and chlorine levels decreased. On Day 6 of second cycle of chemotherapy with carboplatin and paclitaxel, he developed sudden febrile neutropenia, septic shock and ileus, leading to death. After his death, the venous blood culture on Day 7 detected Candida albicans. Autopsy findings showed a massive necrotizing enterocolitis with extensive Candida invasion into submucous tissue. In conclusion, this case may suggest that (i) immediate initiation of antifungal therapy soon after the careful risk assessment of Candida infection and (ii) adequate administration of both basal steroid replacement therapy and temporal steroid coverage for febrile neutropenia might have improved his fatal outcome.
In the middle of a busy shift, a patient arrives by ambulance from a local long-term care facility with a report of altered mental status. You enter the room to find a chronically ill-appearing 85-year-old man with fever, tachycardia, and hypotension, and it is instantly apparent that this patient is septic. What is not clear is what the source is, what modifications in treatment might be necessary based on preexisting microbial resistance, and which of the array of invasive resuscitation techniques are appropriate when meaningful recovery is questionable and efforts may not be desired by the patient and family. You order IV fluids and broad-spectrum antibiotics; send lab tests, including lactate and cultures of blood, urine, and sputum; and begin to review his extensive history to discuss goals of care with his family and primary doctor. While reviewing these issues, a 54-year-old woman with a history of asthma is brought straight back from triage with respiratory distress. You listen to her lungs, expecting wheezes, but hear decreased lung sounds at the right base, preserved air movement elsewhere, and her skin radiates heat. Now, on the monitor, she has a heart rate of 135 beats per minute, blood pressure of 90/60 mm Hg, O2 saturation of 86%, and a temperature of 39.4 degrees C (103 degrees F). You again identify sepsis and instruct your team that you will be using your department's severe sepsis protocol. Equipment for monitoring and procedures is assembled, your staff provides preprinted order and monitoring flow sheets, and the ICU is alerted. Within an hour, the patient is intubated, has a central line placed, and has received IV fluids, broad-spectrum antibiotics and norepinephrine, and you are pleased to see a MAP of 67 mm Hg, a lactate decreasing from an initial value of 7.0, CVP of 10, and ScvO2 of 78%.
Helito, Camilo Partezani; Teixeira, Paulo Renan Lima; de Oliveira, Priscila Rosalba; de Carvalho, Vladimir Cordeiro; Pécora, José Ricardo; Camanho, Gilberto Luis; Demange, Marco Kawamura; Lima, Ana Lucia Munhoz
OBJECTIVES: To clinically and epidemiologically characterize a population diagnosed with and treated for septic arthritis of the knee, to evaluate the treatment results and to analyze the differences between patients with positive and negative culture results, patients with Gram-positive and Gram-negative bacterial isolates and patients with S. aureus- and non-S. aureus-related infections. METHODS: One hundred and five patients with septic knee arthritis were included in this study. The clinical and epidemiological data were evaluated. Statistical analysis was performed to compare patients with and without an isolated causative agent, patients with Gram-positive and Gram-negative pathogens and patients with S. aureus-related and non S. aureus-related infections. RESULTS: Causative agents were isolated in 81 patients. Gram-positive bacteria were isolated in 65 patients and Gram-negative bacteria were isolated in 16 patients. The most commonly isolated bacterium was S. aureus. Comparing cases with an isolated pathogen to cases without an isolated pathogen, no differences between the studied variables were found except for the longer hospital stays of patients in whom an etiological agent was identified. When comparing Gram-positive bacteria with Gram-negative bacteria, patients with Gram-positive-related infections exhibited higher leukocyte counts. Patients with S. aureus-related infections were more frequently associated with healthcare-related environmental encounters. CONCLUSION: S. aureus is the most common pathogen of septic knee arthritis. Major differences were not observed between infections with isolated and non-isolated pathogens and between infections with Gram-positive and Gram-negative bacteria. S. aureus infections were more likely to be associated with a prior healthcare environment exposure. PMID:28076516
Rivers, Emanuel P; Jaehne, Anja Kathrin; Nguyen, H Bryant; Papamatheakis, Demosthenes G; Singer, Daniel; Yang, James J; Brown, Samantha; Klausner, Howard
Improving time to diagnosis and intervention has positively impacted outcomes in acute myocardial infarction, stroke, and trauma through elucidating the early pathogenesis of those diseases. This insight may partly explain the futility of time-insensitive immunotherapy trials for severe sepsis and septic shock. The aim of this study was to examine the early natural history of circulatory biomarker activity in sepsis, relative to previous animal and human outcome trials. We conducted a literature search using PubMed, MEDLINE, and Google Scholar to identify outcome trials targeting biomarkers with emphasis on the timing of therapy. These findings were compared with the biomarker activity observed over the first 72 h of hospital presentation in a cohort of severe sepsis and septic shock patients. Biomarker levels in animal and human research models are elevated within 30 min after exposure to an inflammatory septic stimulus. Consistent with these findings, the biomarker cascade is activated at the most proximal point of hospital presentation in our patient cohort. These circulatory biomarkers overlap; some have bimodal patterns and generally peak between 3 and 36 h while diminishing over the subsequent 72 h of observation. When this is taken into account, prior outcome immunotherapy trials have generally enrolled patients after peak circulatory biomarker concentrations. In previous immunotherapy sepsis trials, intervention was delayed after the optimal window of peak biomarker activity. As a result, future studies need to recalibrate the timing of enrollment and administration of immunotherapy agents that still may hold great promise for this deadly disease.
Groeneveld, A.B.; den Hollander, W.; Straub, J.; Nauta, J.J.; Thijs, L.G. )
We studied the therapeutic effects of continuously infused N-acetylcysteine, an O2 radical scavenger (N, n = 6), and terbutaline, a beta 2-agonist (T, n = 6), versus dextrose (controls C, N = 6) on hemodynamics and regional albumin extravasation in porcine septic shock. After instrumentation, injection of 99mTc-labeled red blood cells, and baseline measurements, pigs received a 90 min infusion of 11 +/- 9 X 10(8).kg-1 live Escherichia coli bacteria. Thereafter, therapy was started, and 131I human serum albumin was injected. Images were obtained hourly using a gamma camera and a computer until 5 hours after baseline. Regions of interest were drawn in the 99mTc images, yielding regional 131I/99mTc radioactivity ratios, with blood samples as reference. From these ratios, an albumin leak index, a rate constant of transvascular albumin transport, was calculated. Control pigs developed pulmonary hypertension, arterial hypotension, hemoconcentration, and lactic acidemia. In spite of tachycardia and unchanged filling pressures, cardiac output fell. In arterial blood, white cell count, PO2, albumin level, and colloid osmotic pressure fell. The albumin leak index (X10(-3).min-1) measured 1.56 +/- 0.59 over the lungs and 2.87 +/- 1.19 over the abdomen in C, confirming previously found increased albumin flux in both lung and abdomen, the latter exceeding the former. Neither N nor T significantly affected hemodynamic and biochemical changes. The drugs neither decreased the regional albumin leak index nor attenuated the formation of albumin-rich ascites found at autopsy. However, the lung albumin index obtained at autopsy was significantly reduced with N (P less than .01 vs. C), at similar gravimetrically determined extravascular lung water (EVLW). EVLW positively correlated with pulmonary albumin extravasation in C and T but not in N.
Castro, Isabel; Quisenberry, Leah; Calvo, Rosa-Maria; Obregon, Maria-Jesus; Lado-Abeal, Joaquin
Non-thyroidal illness syndrome (NTIS) is part of the neuroendocrine response to stress, but the significance of this syndrome remains uncertain. The aim of this study was to investigate the effect of lipopolysaccharide (LPS)-induced NTIS on thyroid hormone (TH) levels and TH molecular targets, as well as the relationship between septic shock nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kB) activation and TH receptor β (THRB) gene expression at a multi-tissue level in a pig model. Prepubertal domestic pigs were given i.v. saline or LPS for 48 h. Serum and tissue TH was measured by chemiluminescence and RIA. Expression of THRs and cofactors was measured by real-time PCR, and deiodinase (DIO) activity was measured by enzyme assays. Tissue NF-kB nuclear binding activity was evaluated by EMSA. LPS-treated pigs had decreased TH levels in serum and most tissues. DIO1 expression in liver and kidney and DIO1 activity in kidney decreased after LPS. No changes in DIO2 activity were observed between groups. LPS induced an increase in hypothalamus, thyroid, and liver DIO3 activity. Among the other studied genes, monocarboxylate transporter 8 and THRB were the most commonly repressed in endotoxemic pigs. LPS-induced NF-kB activation was associated with a decrease in THRB gene expression only in frontal lobe, adrenal gland, and kidney cortex. We conclude that LPS-induced NTIS in pigs is characterized by hypothyroidism and tissue-specific reduced TH sensitivity. The role of NF-kB in regulating THRB expression during endotoxemia, if any, is restricted to a limited number of tissues.
Wawrzeniak, Iuri Christmann; Loss, Sergio Henrique; Moraes, Maria Cristina Martins; De La Vega, Fabiane Lopes; Victorino, Josue Almeida
Context: Sepsis is a disease with high incidence and mortality. Among the interventions of the resuscitation bundle, the early goal-directed therapy (EGDT) is recommended. Aims: The aim was to evaluate outcomes in patients with severe sepsis and septic shock using EGDT in real life compared with patients who did not undergo it in the Intensive Care Unit (ICU) setting. Settings and Design: retrospective and observational cohort study at tertiary hospital. Subjects and Methods: All the patients admitted to ICU were screened for severe sepsis or septic shock and included in a registry and followed. The patients were allocated in two groups according to submission or not to EGDT. Results: A total of 268 adult patients with severe sepsis or septic shock were included. EGDT was employed in 97/268 patients. The general mortality was higher in no early goal-directed therapy (no-EGDT) then in EGDT groups (49.7% vs. 37.1% [P = 0.04] in hospital and 40.4% vs. 29.9% [P = 0.08] in the ICU, respectively. The general length of stay [LOS] in the no-EGDT and EGDT groups was 45.0 ± 59.8 vs. 29.1 ± 30.1 days [P = 0.002] in hospital and 17.4 ± 19.4 vs. 9.1 ± 9.8 days [P < 0.001] in the ICU, respectively). Conclusions: Our study shows reduced mortality and LOS in patients submitted to EGDT in the ICU setting. A simplified EGDT without central venous oxygen saturation is an important tool for sepsis management. PMID:25810612
Noel, Sanjeev; Zheng, Laura; Navas-Acien, Ana; Fuchs, Ralph J
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
Shimizu, Tomoharu; Obata, Toru; Sonoda, Hiromichi; Akabori, Hiroya; Tabata, Takahisa; Eguchi, Yutaka; Endo, Yoshihiro; Tani, Tohru
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.
Faust, Jeremy S; Weingart, Scott D
SEP-1, the new national quality measure on sepsis, resulted from an undertaking to standardize care for severe sepsis and septic shock regardless of the size of the emergency department where the patient is being treated. SEP-1 does not necessarily follow the best current evidence available. Nevertheless, a thorough understanding of SEP-1 is crucial because all hospitals and emergency providers will be accountable for meeting the requirements of this measure. SEP-1 is the first national quality measure on early management of sepsis care. This article provides a review of SEP-1 and all its potential implications on sepsis care in the United States.
Plante, Lauren A
The incidence of sepsis is increasing in the United States, both in the general adult population and among pregnant and postpartum women. Neither infection nor bacteremia are synonymous with sepsis: it is a dysregulated host response to a pathogen in which organ dysfunction is key. New clinical criteria have been released. Cornerstones of management are early suspicion and recognition, effective fluid resuscitation, and appropriate antimicrobial therapy.
Papachristos, Ioannis C.; Daliakopoulos, Stavros I.; Chatzoulis, Kostas; Lampridis, Savvas; Svarnas, Grigorios; Katsiadramis, Ioannis
Diaphragmatic rupture (DR) after thoracoabdominal trauma has a reported rate of 0.8% to 5% and up to 30% of diaphragmatic hernias are accompanied with delayed diagnosis. The DR occurs after high-energy blunt or penetrating (stab or gunshot wounds) trauma. The purpose of this article is to analyze the DR, its clinical presentation, complications and possible causes of the delay in diagnosis, whilst recording a rare interesting case. A 44-year old moribund male with a fifteen years history of paraplegia, came to the emergency department with a clinical presentation of extremely severe respiratory distress. Chest X-ray showed the colon present in the left hemithorax. The onset of symptoms was 48 hours before, resulting in hemodynamic instability and severe sepsis condition. Emergency left thoracotomy and laparotomy were carried out. A rupture of the left hemidiaphragm was found as well as intrathoracic presence of colon, incarcerated and perforated, feces and omentum, also incarcerated and necrotic. There were dense adhesions between the ectopic viscera and the thoracic structures. The necrotic parts of the colon and the omentum were mobilized, and then resected. The viable parts of the colon were laboriously reintroduced into the intraperitoneal cavity. We conclude that early diagnosis is crucial to the morbidity and mortality after DR. The course and the kinetic energy of bullets determine the extent of the wound and the size of the DR. The diagnosis of rupture of the diaphragm after penetrating trauma is sometimes difficult and delay can lead to life threatening complications. PMID:24255791
Kim, Ye-Ram; Koh, Hyun-Jung; Kim, Jae-Sung; Yun, Jin-Seung; Jang, Kiseok; Lee, Joo-Youn; Jung, Jae U; Yang, Chul-Su
Sepsis is a clinical syndrome that complicates severe infection and is characterized by the systemic inflammatory response syndrome (SIRS), is a life threatening disease characterized by inflammation of the entire body. Upon microbial infection, p22phox-gp91phox NADPH oxidase (NOX) complexes produce reactive oxygen species (ROS) that are critical for the elimination of invading microbes. However, excess production of ROS represents a key element in the cascade of deleterious processes in sepsis. We have previously reported direct crosstalk between autophagy and phagocytosis machineries by demonstrating that the Rubicon protein interacts with p22phox upon microbial infection, facilitating phagosomal trafficking of the p22phox-gp91phox NOX complex to induce a ROS burst, inflammatory cytokine production, and thereby, potent anti-microbial activities. Here, we showed N8 peptide, an N-terminal 8-amino acid peptide derived from p22phox, was sufficient for Rubicon interaction and thus, capable of robustly blocking the Rubicon-p22phox interaction and profoundly suppressing ROS and inflammatory cytokine production. Consequently, treatment with the Tat-N8 peptide or a N8 peptide-mimetic small-molecule dramatically reduced the mortality associated with Cecal-Ligation-and-Puncture-induced polymicrobial sepsis in mice. This study demonstrates a new anti-sepsis therapeutic strategy by blocking the crosstalk between autophagy and phagocytosis innate immunity machineries, representing a potential paradigm shift for urgently needed therapeutic intervention against this life-threatening SIRS.
Level, Claude; Chauveau, Philippe; Guisset, Olivier; Cazin, Marie Cécile; Lasseur, Catherine; Gabinsky, Claude; Winnock, Stéphane; Montaudon, Danièle; Bedry, Régis; Nouts, Caroline; Pillet, Odile; Benissan, Georges Gbikpi; Favarel-Guarrigues, Jean Claude; Castaing, Yves
Objectives To measure the mass transfer and clearance of procalcitonin (PCT) in patients with septic shock during continuous venovenous hemofiltration (CVVH), and to assess the mechanisms of elimination of PCT. Setting The medical department of intensive care. Design A prospective, observational study. Patients Thirteen critically ill patients with septic shock and oliguric acute renal failure requiring continuous venovenous postdilution hemofiltration with a high-flux membrane (AN69 or polyamide) and a 'conventional' substitution volume (< 2.5 l/hour). Measurements and main results PCT was measured with the Lumitest PCT Brahms® in the prefilter and postfilter plasma, in the ultrafiltrate at the beginning of CVVH (T0) and 15 min (T15'), 60 min (T60') and 6 hours (T6h) after setup of CVVH, and in the prefilter every 24 hours during 4 days. Mass transfer was determined and the clearance and the sieving coefficient were calculated according to the mass conservation principle. Plasma and ultrafiltrate clearances, respectively, at T15', T60' and T6h were 37 ± 8.6 ml/min (not significant) and 1.8 ± 1.7 ml/min (P < 0.01), 34.7 ± 4.1 ml/min (not significant) and 2.3 ± 1.8 ml/min (P < 0.01), and 31.5 ± 7 ml/min (not significant) and 5 ± 2.3 ml/min (P < 0.01). The sieving coefficient significantly increased from 0.07 at T15' to 0.19 at T6h, with no difference according to the nature of the membrane. PCT plasma levels were not significantly modified during the course of CCVH. Conclusions We conclude that PCT is removed from the plasma of patients with septic shock during CCVH. Most of the mass is eliminated by convective flow, but adsorption also contributes to elimination during the first hours of CVVH. The effect of PCT removal with a conventional CVVH substitution fluid rate (<2.5 l/hour) on PCT plasma concentration seems to be limited, and PCT remains a useful diagnostic marker in these septic patients. The impact of high-volume hemofiltration on the PCT clearance
Jeon, Kyeongman; Shin, Tae Gun; Sim, Min Seob; Suh, Gee Young; Lim, So Yeon; Song, Hyoung Gon; Jo, Ik Joon
The objectives of this study were to determine whether an educational program could improve compliance with resuscitation bundles and the outcomes of patients with severe sepsis or septic shock and to evaluate which resuscitation bundle end points were associated with in-hospital mortality. This was a retrospective observational study of 366 patients (163 of historical controls and 203 of treatment patients) with severe sepsis or septic shock who presented to the emergency department between May 2007 and July 2009. Compliance with resuscitation bundles and achievement of the corresponding end points were compared before and after the 3-month educational program. Compliance with central line insertion and monitoring of central venous pressure (29% vs. 67%, P < 0.001) and central venous oxygen saturation (ScvO₂) (25% vs. 68%, P < 0.001) was significantly improved after the educational program. The achievement of target ScvO₂ within the first 6 h was significantly improved (62% vs. 88%, P < 0.001). In-hospital mortality was independently associated with adequate fluid challenge (odds ratio [OR], 0.161; 95% confidence interval [CI], 0.046-0.559) and the achievement of target mean arterial pressure (OR, 0.056; 95% CI, 0.008-0.384) and ScvO₂ (OR, 0.251; 95% CI, 0.072-0.875) among the five sepsis resuscitation bundles. In conclusion, an educational program can improve compliance with resuscitation bundles and achievement of their corresponding end points.
Natanson, C; Danner, R L; Elin, R J; Hosseini, J M; Peart, K W; Banks, S M; MacVittie, T J; Walker, R I; Parrillo, J E
Using different types of bacteria and a canine model simulating human septic shock, we investigated the role of endotoxin in cardiovascular dysfunction and mortality. Either Escherichia coli (a microorganism with endotoxin) or Staphylococcus aureus (a microorganism without endotoxin) were placed in an intraperitoneal clot in doses of viable or formalin-killed bacteria. Cardiovascular function of conscious animals was studied using simultaneous radionuclide heart scans and thermodilution cardiac outputs. Serial plasma endotoxin levels were measured. S. aureus produced a pattern of reversible cardiovascular dysfunction over 7-10 d that was concordant (P less than 0.01) with that of E. coli. Although this cardiovascular pattern was not altered by formalin killing (S. aureus and E. coli), formalin-killed organisms produced a lower mortality and less myocardial depression (P less than 0.01). S. aureus, compared to E. coli, produced higher postmortem concentrations of microorganisms and higher mortality (P less than 0.025). E. coli produced significant endotoxemia (P less than 0.01), though viable organisms (versus nonviable) resulted in higher endotoxin blood concentrations (P less than 0.05). Significant endotoxemia did not occur with S. aureus. Thus, in the absence of endotoxemia, S. aureus induced the same cardiovascular abnormalities of septic shock as E. coli. These findings indicate that structurally and functionally distinct microorganisms, with or without endotoxin, can activate a common pathway resulting in similar cardiovascular injury and mortality. PMID:2642920
Sakamoto, Yuichiro; Mashiko, Kunihiro; Obata, Toru; Yokota, Hiroyuki
The limulus test, which has been established as a test for endotoxin measurement, is associated with problems, including that posed by the presence of a response inhibitor factor and the longer time needed for the measurement of low concentrations. On the other hand, the technique of direct hemoperfusion with a polymyxin B immobilized fiber column (DHP-PMX) was developed in Japan in 1994 and has been used for the control of endotoxemia in septic shock. The limulus test, which is a common endotoxin measurement test, has several problems with regard to sensitivity. Therefore, this test is no longer used to determine the effectiveness of DHP-PMX. Here, we describe a patient presenting with colonic perforation who recovered from septic shock with DHP-PMX. This treatment effect was reflected by a decrease in plasma endotoxin levels as demonstrated more readily with endotoxin scattering photometry assay than with the standard limulus test. We conclude that endotoxin measurement with endotoxin scattering photometry is superior to nephelometry in patients with endotoxemia.
Sukhavasi, Sowmya; Jothimuthu, Pretha; Papautsky, Ian; Beyette, Fred R
In the Unites States Pediatric septic shock is a major health problem with about 42,000 cases per y ear and a mortality rate of about 10% . Studies have indicated that children with pediatric septic shock have demonstrated critically low levels of serum z inc (Zn) and supplementation of Zn is being suggested as a therapeutic strategy. However, to protect patient safety, it is vital that Z n levels be monitored during supplementation to insure the Zn concentration levels remain at or near physiologic normal levels. Currently Atomic Absorption Spectroscopy (AAS) is used to quantify Zn levels in serum samples. Unfortunately, AAS frequently involves sending serum samples to external laboratory facilities which yields measurement turnaround time that range from hours to days. Thus, timely monitoring of Zn levels is critical to preventing over supplementation that could result in critical conditions such as heavy metal (Zn) toxicity. This paper reports on the development of a Point-of-Care device for rap id electrochemical measurement of Zn. The prototype device is able to accurately quantify Zn in serum with a turn-around time of about 30 minutes. The devices is based on a three electrode sensor which uses Anodic stripping voltammetry (ASV) for sensing Zn levels. The ASV electrode sensor is read using a reader that has be en developed using commercially available embedded system components and custom analog circuitry.
Purpose To describe and compare the design of three independent but collaborating multicenter trials of early goal-directed resuscitation for severe sepsis and septic shock. Methods We reviewed the three current trials, one each in the USA (ProCESS: protocolized care for early septic shock), Australasia (ARISE: Australasian resuscitation in sepsis evaluation), and the UK (ProMISe: protocolised management in sepsis). We used the 2010 CONSORT (consolidated standards of reporting trials) statement and the 2008 CONSORT extension for trials assessing non-pharmacologic treatments to describe and compare the underlying rationale, commonalities, and differences. Results All three trials conform to CONSORT guidelines, address the same fundamental questions, and share key design elements. Each trial is a patient-level, equal-randomized, parallel-group superiority trial that seeks to enroll emergency department patients with inclusion criteria that are consistent with the original early goal-directed therapy (EGDT) trial (suspected or confirmed infection, two or more systemic inflammatory response syndrome criteria, and refractory hypotension or elevated lactate), is powered to detect a 6–8 % absolute mortality reduction (hospital or 90-day), and uses trained teams to deliver EGDT. Design differences appear to primarily be driven by between-country variation in health care context. The main difference between the trials is the inclusion of a third, alternative resuscitation strategy arm in ProCESS. Conclusions Harmonization of study design and methods between severe sepsis trials is feasible and may facilitate pooling of data on completion of the trials. PMID:23958738
Wong, Hector R.; Cvijanovich, Natalie Z.; Anas, Nick; Allen, Geoffrey L.; Thomas, Neal J.; Bigham, Michael T.; Weiss, Scott L.; Fitzgerald, Julie; Checchia, Paul A.; Meyer, Keith; Shanley, Thomas P.; Quasney, Michael; Hall, Mark; Gedeit, Rainer; Freishtat, Robert J.; Nowak, Jeffrey; Raj, Shekhar S.; Gertz, Shira; Dawson, Emily; Howard, Kelli; Harmon, Kelli; Lahni, Patrick; Frank, Erin; Hart, Kimberly W.; Lindsell, Christopher J.
Objective The development of acute kidney injury in patients with sepsis is associated with worse outcomes. Identifying those at risk for septic acute kidney injury could help to inform clinical decision making. We derived and tested a multibiomarker-based model to estimate the risk of septic acute kidney injury in children with septic shock. Design Candidate serum protein septic acute kidney injury biomarkers were identified from previous transcriptomic studies. Model derivation involved measuring these biomarkers in serum samples from 241 subjects with septic shock obtained during the first 24 hours of admission and then using a Classification and Regression Tree approach to estimate the probability of septic acute kidney injury 3 days after the onset of septic shock, defined as at least two-fold increase from baseline serum creatinine. The model was then tested in a separate cohort of 200 subjects. Setting Multiple PICUs in the United States. Interventions None other than standard care. Measurements and Main Results The decision tree included a first-level decision node based on day 1 septic acute kidney injury status and five subsequent biomarker-based decision nodes. The area under the curve for the tree was 0.95 (CI95, 0.91–0.99), with a sensitivity of 93% and a specificity of 88%. The tree was superior to day 1 septic acute kidney injury status alone for estimating day 3 septic acute kidney injury risk. In the test cohort, the tree had an area under the curve of 0.83 (0.72–0.95), with a sensitivity of 85% and a specificity of 77% and was also superior to day 1 septic acute kidney injury status alone for estimating day 3 septic acute kidney injury risk. Conclusions We have derived and tested a model to estimate the risk of septic acute kidney injury on day 3 of septic shock using a novel panel of biomarkers. The model had very good performance in a test cohort and has test characteristics supporting clinical utility and further prospective evaluation
Rumbus, Zoltan; Matics, Robert; Hegyi, Peter; Zsiboras, Csaba; Szabo, Imre; Illes, Anita; Petervari, Erika; Balasko, Marta; Marta, Katalin; Miko, Alexandra; Parniczky, Andrea; Tenk, Judit; Rostas, Ildiko; Solymar, Margit
Background Sepsis is usually accompanied by changes of body temperature (Tb), but whether fever and hypothermia predict mortality equally or differently is not fully clarified. We aimed to find an association between Tb and mortality in septic patients with meta-analysis of clinical trials. Methods We searched the PubMed, EMBASE, and Cochrane Controlled Trials Registry databases (from inception to February 2016). Human studies reporting Tb and mortality of patients with sepsis were included in the analyses. Average Tb with SEM and mortality rate of septic patient groups were extracted by two authors independently. Results Forty-two studies reported Tb and mortality ratios in septic patients (n = 10,834). Pearson correlation analysis revealed weak negative linear correlation (R2 = 0.2794) between Tb and mortality. With forest plot analysis, we found a 22.2% (CI, 19.2–25.5) mortality rate in septic patients with fever (Tb > 38.0°C), which was higher, 31.2% (CI, 25.7–37.3), in normothermic patients, and it was the highest, 47.3% (CI, 38.9–55.7), in hypothermic patients (Tb < 36.0°C). Meta-regression analysis showed strong negative linear correlation between Tb and mortality rate (regression coefficient: -0.4318; P < 0.001). Mean Tb of the patients was higher in the lowest mortality quartile than in the highest: 38.1°C (CI, 37.9–38.4) vs 37.1°C (CI, 36.7–37.4). Conclusions Deep Tb shows negative correlation with the clinical outcome in sepsis. Fever predicts lower, while hypothermia higher mortality rates compared with normal Tb. Septic patients with the lowest (< 25%) chance of mortality have higher Tb than those with the highest chance (> 75%). PMID:28081244
Perkins, G; Ainsworth, D M; Erb, H N; Del Piero, F; Miller, M; Wilkins, P A; Palmer, J; Frazer, M
A retrospective multicentre study comparing historical, clinical, haematological, acid-base and biochemical findings of foals with Equine herpesvirus-1 (EHV-1) infection, septicaemia or prematurity was performed to determine if early diagnosis of EHV-1 foals was possible. Fifty-three foals were studied and were assigned to one of 2 groups: herpes positive (n = 14) or herpes negative (n = 39). The latter group included 20 septic, 11 premature, and 8 premature and septic foals. The presence of herpes antigen was confirmed by immunoperoxidase histochemical staining of tissues from necropsied foals. A nonparametric statistical analysis followed by a backwards elimination logistic regression was performed to establish a model at a P value of <0.05. All herpes positive foals died, while 47% (9/19) of the septic foals survived. Based upon our analysis, herpes positive foals were more likely to have total white blood cell counts less than 3 x 10(9)/l and to be icteric as compared to the septic and premature foals. Despite profound hepatic necrosis in the herpes positive foals, liver enzymes were not elevated and were not significantly different from the controls.
Hoffman, W D; Danner, R L; Quezado, Z M; Banks, S M; Elin, R J; Hosseini, J M; Natanson, C
We investigated whether the severity of septic shock is determined by virulence factors associated with or the levels of endotoxemia produced by two Escherichia coli strains. Canines were challenged intraperitoneally with an E. coli strain (O6:H1:K2) that has virulence factors associated with human disease or with an equal dose of a nonvirulent strain (O86:H8) that lacks these factors. Both strains were administered in viable, heat-killed, and purified endotoxin forms. Median survival times with the virulent strain compared with the nonvirulent strain were shorter with viable bacteria (5 x 10(10) CFU/kg) (144 h versus > 672 h; Wilcoxon, P = 0.03), longer with heat-killed bacteria (5 x 10(9) CFU/kg) ( > 676 h versus 26 h; P = 0.03), and similar with purified endotoxin (15 mg/kg) (28 h versus 48 h; P = 0.71). However, whether the challenge contained viable bacteria, heat-killed bacteria, or purified endotoxin, the virulent strain produced less endotoxemia (P = 0.001). Hence, the changing outcomes with differing forms of the two strains cannot be attributed solely to endotoxin levels. The viable virulent strain caused less endotoxemia but more harm, and this does not appear to be explained by a more potent endotoxin or other heat-stable component. This study suggests that circulating endotoxin levels per se are less important in the outcome of septic shock than virulence factors associated with E. coli strains. Furthermore, the data call into question the significance of the endotoxin concentration in the blood in predicting the severity of shock and the lethality of gram-negative infections. PMID:8550184
Cantara, Giulio; Sechtem, Udo; Athanasiadis, Anastasios
Early appropriate anti-microbial therapy is necessary to improve outcomes of septic patients. We describe 20 case histories of patients with severe bacterial sepsis regarding kinetics of several biomarkers. We found that interleukin-6 is able to predict survival and might be able to evaluate appropriateness of anti-microbial therapy. PMID:27103972
Laub, Melissa; Fraser, Robert; Kurche, Jonathan; Lara, Abigail; Kiser, Tyree H; Reynolds, Paul M
Patients presenting with infections while receiving disease-modifying antirheumatic agents (DMARD) may be predisposed to a higher degree illness due to immunosuppression. This can be particularly problematic in patients who are receiving DMARDs with prolonged pharmacokinetic profiles. Leflunomide is a DMARD that has a prolonged half-life due to enterohepatic recirculation. We report a case of a patient with severe septic shock secondary to a prosthetic joint infection in which therapeutic levels of leflunomide were discovered, despite the patient ceasing therapy several weeks prior to admission. An orogastric cholestyramine washout was given to the patient to expedite the removal of the drug. Serum levels rapidly declined over the next several days, corresponding with resolution of her sepsis. A review of the literature relevant to the incidence of DMARD-related infections was conducted as well as discussion regarding the role of leflunomide drug monitoring and cholestyramine-facilitated removal of the drug in episodes of acute infectious syndromes.
Immune complexes containing human gamma (g)1 or murine g2a antibodies generate secondary effector mechanisms via Fc receptor binding or complement activation, whereas those containing human g4 or murine g1 antibodies generally do not. Therefore, isotype selection of therapeutic antibodies may have important clinical consequences. In a rabbit model of human tumor necrosis factor (rhuTNF)-induced pyrexia, a murine/human chimeric g4 anti-human TNF-alpha monoclonal antibody (mAb) (cCB0011) showed a dose-dependent inhibition of pyrexia, whereas a g1 isotype variant of the same mAb gave a marked pyrexia that was seen at all doses indicative of an immune complex-mediated response. To investigate whether isotype difference could influence mAb efficacy in pathological disease states, hamster/murine chimeric g1 and g2a anti- murine TNF-alpha mAbs (TN3g1, TN3g2a) were studied in experimental shock in mice and rats. In lipopolysaccharide-induced shock in mice, treatment with TN3g1 mAb at 30 and 3 mg/kg resulted in 90% survival by 72 h (p < or = 0.004), and prolonged survival to 45 h (p < or = 0.05), respectively, compared with 100% mortality by 27 h in controls. In contrast, a g2a isotype variant of the same mAb (30 mg/kg) resulted in only 10% survival by 72 h (p < or = 0.05). In a neutropenic sepsis model in rats there was greater survival in animals receiving the g1 isotype of TN3 compared with g2a isotype variant (70 vs. 27%; p < or = 0.005) with 100% mortality in the controls. These differences were not due to the pharmacokinetic profiles of the mAbs. In models of experimental shock antibody isotype can affect outcome with inactive isotypes (human g4 and murine g1) being more efficacious than active isotypes (human g1 and murine g2a). PMID:8113678
Zhong, Jixin; Yang, Ping; Muta, Kenjiro; Dong, Robert; Marrero, Mario; Gong, Feili; Wang, Cong-Yi
Given the importance of Jak2 in cell signaling, a critical role for Jak2 in immune cells especially dendritic cells (DCs) has long been proposed. The exact function for Jak2 in DCs, however, remained poorly understood as Jak2 deficiency leads to embryonic lethality. Here we established Jak2 deficiency in adult Cre(+/+)Jak2(fl/fl) mice by tamoxifen induction. Loss of Jak2 significantly impaired DC development as manifested by reduced BMDC yield, smaller spleen size and reduced percentage of DCs in total splenocytes. Jak2 was also crucial for the capacity of DCs to mediate innate immune response. Jak2(-/-) DCs were less potent in response to inflammatory stimuli and showed reduced capacity to secrete proinflammatory cytokines such as TNFalpha and IL-12. As a result, Jak2(-/-) mice were defective for the early clearance of Listeria after infection. However, their potency to mediate adaptive immune response was not affected. Unlike DCs, Jak2(-/-) macrophages showed similar capacity secretion of proinflammatory cytokines, suggesting that Jak2 selectively modulates innate immune response in a DC-dependent manner. Consistent with these results, Jak2(-/-) mice were remarkably resistant to lethal dose of LPS-induced septic shock, a deadly sepsis characterized by the excessive innate immune response, and adoptive transfer of normal DCs restored their susceptibility to LPS-induced septic shock. Mechanistic studies revealed that Jak2/SATA5 signaling is pivotal for DC development and maturation, while the capacity for DCs secretion of proinflammatory cytokines is regulated by both Jak2/STAT5 and Jak2/STAT6 signaling.
Nubaum, Benedikt L; Vogt, Josef; Wachter, Ulrich; McCook, Oscar; Wepler, Martin; Matallo, José; Calzia, Enrico; Gröger, Michael; Georgieff, Michael; Wood, Mark E; Whiteman, Matthew; Radermacher, Peter; Hafner, Sebastian
Decreased levels of endogenous hydrogen sulfide (H2S) contribute to atherosclerosis, whereas equivocal data are available on H2S effects during sepsis. Moreover, H2S improved glucose utilization in anaesthetized, ventilated, hypothermic mice, but normothermia and/or sepsis blunted this effect. The metabolic effects of H2S in large animals are controversial. Therefore, we investigated the effects of the H2S donor GYY4137 during resuscitated, fecal peritonitis-induced septic shock in swine with genetically and diet-induced coronary artery disease (CAD). 12 and 18 hours after peritonitis induction, pigs received either GYY4137 (10 mg kg, n = 9) or vehicle (n = 8). Before, at 12 and 24 hours of sepsis, we assessed left ventricular (pressure-conductance catheters) and renal (creatinine clearance, blood NGAL levels) function. Endogenous glucose production and glucose oxidation were derived from the plasma glucose isotope and the expiratory CO2/CO2 enrichment during continuous i.v. 1,2,3,4,5,6-C6-glucose infusion. GYY4137 significantly increased aerobic glucose oxidation, which coincided with higher requirements of exogenous glucose to maintain normoglycemia, as well as significantly lower arterial pH and decreased base excess. Apart from significantly lower cardiac eNOS expression and higher troponin levels, GYY4137 did not significantly influence cardiac and kidney function or the systemic inflammatory response. During resuscitated septic shock in swine with CAD, GYY4137 shifted metabolism to preferential carbohydrate utilization. Increased troponin levels are possibly due to reduced local NO availability. Cautious dosing, the timing of GYY4137 administration and interspecies differences most likely account for the absence of any previously described anti-inflammatory or organ-protective effects of GYY4137 in this model.
Jaruratanasirikul, Sutep; Thengyai, Suriyan; Wongpoowarak, Wibul; Wattanavijitkul, Thitima; Tangkitwanitjaroen, Kanyawisa; Sukarnjanaset, Waroonrat; Jullangkoon, Monchana; Samaeng, Maseetoh
Pathophysiological changes during the early phase of severe sepsis and septic shock in critically ill patients, resulting in altered pharmacokinetic (PK) patterns for antibiotics, are important factors influencing therapeutic success. The aims of this study were (i) to reveal the population PK parameters and (ii) to assess the probability of target attainment (PTA) for meropenem. The PK studies were carried out following administration of 1 g of meropenem every 8 h during the first 24 h of severe sepsis and septic shock in nine patients, and a Monte Carlo simulation was performed to determine the PTA of achieving 40% exposure time during which the free plasma drug concentration remains above the MIC (fT>MIC) and 80% fT>MIC. The volume of distribution (V) and total clearance (CL) of meropenem in these patients were 23.7 liters and 7.82 liters/h, respectively. For pathogens with MICs of 4 μg/ml, the PTAs of 40% fT>MIC following administration of meropenem as a 1-h infusion of 1 g every 8 h and a 4-h infusion of 0.5 g every 8 h were 92.52% and 90.29%, respectively. For pathogens with MICs of 2 μg/ml in immunocompromised hosts, the PTAs of 80% fT>MIC following administration of 1-h and 4-h infusions of 2 g of meropenem every 8 h were 84.32% and 94.72%, respectively. These findings indicated that the V of meropenem was greater and the CL of meropenem was lower than the values obtained in a previous study with healthy subjects. The maximum recommended dose, i.e., 2 g of meropenem every 8 h, may be required for treatment of life-threatening infections in this patient population.
Objective. To investigate the effects of 72-hour early-initiated continuous venovenous hemofiltration (ECVVH) treatment in patients with septic-shock-induced acute respiratory distress syndrome (ARDS) (not acute kidney injury, AKI) with regard to serum E-selectin and measurements of lung function and hemodynamic stability. Methods. This prospective nonblinded single institutional randomized study involved 51 patients who were randomly assigned to receive or not receive ECVVH, an ECVVH group (n = 24) and a non-ECVVH group (n = 27). Besides standard therapies, patients in ECVVH group underwent CVVH for 72 h. Results. At 0 and 24 h after initiation of treatment, arterial partial pressure of oxygen/fraction of inspired oxygen (PaO2/FiO2) ratio, extravascular lung water index (EVLWI), and E-selectin level were not significantly different between groups (all P > 0.05). Compared to non-ECVVH group, PaO2/FiO2 is significantly higher and EVLWI and E-selectin level are significantly lower in ECVVH group (all P < 0.05) at 48 h and 72 h after initiation of treatment. The lengths of mechanical ventilation and stay in intensive care unit (ICU) were shorter in ECVVH group (all P < 0.05), but there was no difference in 28-day mortality between two groups. Conclusions. In patients with septic-shock-induced ARDS (not AKI), treatment with ECVVH in addition to standard therapies improves endothelial function, lung function, and hemodynamic stability and reduces the lengths of mechanical ventilation and stay in ICU. PMID:28044135
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
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.
Chen, Chao-Ming; Lin, Hsi-Hsien; Hung, Shih-Chieh; Huang, Tung-Fu; Chen, Wei-Ming; Liu, Chien-Lin; Chen, Tain-Hsiung
Septic arthritis is the most rapidly destructive joint disease, but its early diagnosis remains challenging; delayed or inadequate treatment, even by expert physicians, can lead to irreversible joint destruction. Between 25% and 50% of patients develop irreversible loss of joint function, which is especially concerning in elderly patients. To understand the factors influencing the outcome of septic arthritis, the authors reviewed patients aged older than 50 years who had undergone debridement surgery for primary septic arthritis at their institution between 1998 and 2008. Ninety-two patients (92 knees) were enrolled in the study; 14 did not meet inclusion criteria and were excluded from the final analysis. Of the 78 included patients, 7 underwent arthrodesis, 22 underwent total knee arthroplasty, 19 were indicated for total knee arthroplasty for severe knee joint osteoarthritis but did not undergo surgery by the end of this study, and the remaining 30 had no or mild symptoms of osteoarthrosis and did not receive any surgical procedure. Staphylococcus aureus was the most common pathogenic agent (38%), followed by mixed bacterial infection (10%). Several factors negatively influenced the final clinical outcome, including delayed treatment, advanced macroscopic staging made during debridement surgery, performing multiple debridement surgeries, and a larger Lysholm score difference pre- and posttreatment. More antibiotics administered, longer duration of antibiotic treatment, and more pathogenic agents present were also significantly correlated with poor outcome. These findings shed new light on the management of septic arthritis. Accurate diagnoses and effective treatments are important for the clinical outcome of knee joint bacterial infection in elderly patients.
Le Turnier, Paul; Boutoille, David; Joyau, Caroline; Veyrac, Gwenaelle; Asseray, Nathalie
Nonsteroidal anti-inflammatory drugs (NSAIDs) are widely consumed. Some authors suggested a relationship between more severe infections and NSAIDs exposure, especially skin and soft tissue infections (SSTI). However, their impact during bacterial infections remains unclear. The aim of the study was to report the severity features of patients having bacterial infection who were exposed to NSAIDs prior to their hospitalisation. Cases of infected patients with these characteristics declared to the pharmacovigilance department of a French university hospital from 1 January 2011 to 31 December 2013 were retrospectively reviewed. Forty-one patients were included, mainly male (61%). Median age was 37years. No underlying disease was noted for 68% of cases. Ibuprofen was the most frequent drug (63%). Self-medication concerned 61% of cases. Respiratory tract, osteoarticular and SSTI were the most frequent infected sites. Patients suffered septic complications: dissemination of infection to more than one site (51%), suppuration (59%), and requirement for invasive procedures (32%). Eleven patients (27%) had severity criteria as usually defined (10 severe sepsis and 1 septic shock) and 30 did not. There was no significant difference regarding the rate of septic complications between the severe and non-severe group. Septic complications frequently occurred in patients with NSAIDs exposure, whether or not there was severe sepsis or shock. Further studies investigating the impact of NSAIDs in bacterial infections should consider the septic complications depicted here as clinically relevant endpoints. Moreover, clinicians should seek those complications in case of bacterial infections and NSAIDs use.
Peretz, Dwight I.; McGregor, Maurice; Dossetor, John B.
A study was made of the metabolic acidosis of hypotensive shock in 25 patients in an attempt to elucidate its etiology and to determine if the degree of acidosis might be a good parameter for the evaluation of treatment and prognosis. Blood lactate was elevated (> 1.3 mEq./l.) in 24 of 25 patients in hypotensive shock. There was a good correlation (r= 0.83, p < 0.01) between rising blood lactate and decrease in serum bicarbonate and arterial pH, early in shock. These data indicate that the metabolic acidosis of early shock is largely due to lactate ion. Evidence is presented that high blood lactate levels early in shock are indicative of poor prognosis. ImagesFig. 3 PMID:14127378
Munigangaiah, Sudarshan; O’Sullivan, Theresa A.; Lenehan, Brian
Osteoarthritis of knee is one of the common problems in elderly population. Intraarticular corticosteroid injection is a conservative management modality in osteoarthritis of knee. Septic arthritis is an infective complication of intraarticular corticosteroid injection. Septic arthritis in rheumatoid arthritis patients have worse prognosis because of delay in diagnosis. A higher rate of infectious complications following intraarticular injection is expected in immunocompromised and rheumatoid patients. We would like to report an extremely rare case of simultaneous bilateral knee septic arthritis after bilateral knee intraarticular steroid injection in a rheumatoid arthritis patient. Patient was treated successfully with multiple bilateral knee arthroscopic washouts and long-term intravenous antibiotics. This case report emphasizes the increased risk of infection in rheumatoid arthritis patients and a risk benefit assessment on individual basis before carrying out intraarticular steroid injection. Patient should be aware of this increased risk of infection. PMID:25097444
Kim, Sang Min; Ko, Byuk Sung; Kim, Ji Yeon; Ha, Sang Ook; Ahn, Shin; Sohn, Chang Hwan; Seo, Dong Woo; Kim, Tae-Bum; Kim, Won Young
The aim of this study was to investigate the time interval between radiocontrast media (RCM) administration and the development of anaphylactic shock, and risk factors associated with RCM-induced anaphylactic shock. We reviewed the medical records of 154 patients with RCM-induced anaphylaxis presenting to the emergency department of a tertiary care hospital between January 2005 and December 2014. Clinical features of RCM-induced anaphylaxis were analyzed, and patients were categorized into shock and non-shock groups to identify associated factors in affected patients. Of the 154 cases of RCM-induced anaphylaxis, 101 (65.9%) patients experienced shock. The median time between RCM exposure and the onset of shock was 11 min (interquartile range, 7.0-18.8). In patients with RCM-induced anaphylaxis accompanying shock, the median time from RCM to the first symptom onset was 6 min (interquartile range, 5.0-10.0). In the multivariate analysis, age, neurological manifestations, and allergy history except RCM were associated with the development of shock. RCM-induced anaphylaxis was commonly accompanied with shock, and the time interval between RCM exposure and the onset of shock was short. Physicians should pay attention to the development of potential cardiovascular collapse in anaphylaxis patients of old age and with neurologic manifestations.
Wang, Teresa KF; Wong, Samson SY
Background Streptobacillus moniliformis is a zoonotic agent associated with rodent contacts. Although it is more commonly reported to cause rat-bite fever with reactive arthritides, it can also lead to pyogenic infection of the joints. Case presentation We present a lady with past history of osteoarthritis developing streptobacillary septic arthritides of the right knee and left wrist, and required antibiotic and arthrotomy for treatment. We also review 11 previously reported cases of streptobacillary septic arthritis to discuss the characteristics, treatment, prognosis of the infection, and illustrates the differences between streptobacillary rat-bite fever and septic arthritis. Among this patient population, most patients had potential contact with rats (91.6%). The knee is the most commonly affected joint (58.3%), and 83.3% patients having polyarticular involvement. As opposed to rat-bite fever, fever and rash was only present in 58.3% and 16.7% of patients respectively. S. moniliformis bacteremia is uncommon (8.4%) and the prognosis is good. Conclusion Arthrocentesis is useful in distinguishing streptobacillary septic arthritis from reactive arthritis of rat-bite fever. The sole use of commercial media containing sodium polyanethol sulfonate may render the bacterial culture negative. A detailed history of possible exposure to rodents should be elicited from patients with arthritis in order to facilitate microbiologic diagnosis. PMID:17561996
... septic arthritis. Knees are most commonly affected, but septic arthritis also can affect hips, shoulders and other joints. The infection can quickly and severely damage the cartilage and bone within the joint, so prompt treatment is crucial. Treatment involves draining the joint with ...
Sasko, Benjamin; Butz, Thomas; Prull, Magnus Wilhelm; Liebeton, Jeanette; Christ, Martin; Trappe, Hans-Joachim
Background: Early assessment and aggressive hemodynamic treatment have been shown to increase the survival of patients in septic shock. Current and past sepsis guidelines recommend a resuscitation protocol including central venous pressure (CVP), mean arterial blood pressure (MAP), urine output and central venous oxygen saturation (ScvO2) for resuscitation within the first six hours. Currently, the established severity score systems like APACHE II score, SOFA score or SAPS II score predict the outcome of critically ill patients on the bases of variables obtained only after the first 24 hours. The present study aims to evaluate the risk of short-term mortality for patients with septic shock by the earliest possible assessment of hemodynamic parameters and cardiac biomarkers as well as their role for the prediction of the adverse outcome. Methods: 52 consecutive patients treated for septic shock in the intensive care unit of one centre (Marien Hospital Herne, Ruhr University Bochum, Germany) were prospectively enrolled in this study. Hemodynamic parameters (MAP, CVP, ScvO2, left ventricular ejection fraction, Hematocrit) and cardiac biomarkers (Troponin I) at the ICU admission were evaluated in regard to their influence on mortality. The primary endpoint was all-cause mortality within 28 days after the admission. Results: A total of 52 patients (31 male, 21 female) with a mean age of 71.4±8.5 years and a mean APACHE II score of 37.0±7.6 were enrolled in the study. 28 patients reached the primary endpoint (mortality 54%). Patients presenting with hypotension (MAP <65 mmHg) at ICU admission had significantly higher rates of 28-day mortality as compared with the group of patients without hypotension (28-day mortality rate 74 % vs. 32 %, p<0.01). Furthermore, the patients in the hypotension present group had significantly higher lactate concentration (p=0.002), higher serum creatinin (p=0.04), higher NTproBNP (p=0.03) and after the first 24 hours higher APACHE II
Khan, M. M.; Shibuya, Y.; Nakagaki, T.; Kambara, T.; Yamamoto, T.
An intravenous injection of 1.2 mg/kg of Pseudomonas aeruginosa elastase induces immediate lethal shock in guinea-pigs. In the present study, alpha-2-macroglobulin (alpha 2M) was shown to be the major factor in guinea-pig plasma that inhibits the enzymatic activity of elastase in vitro. Depletion of circulating alpha 2M by injecting anti-guinea-pig alpha 2M rabbit IgG F(ab')2 rendered the animals sensitive to a dose of elastase of 0.05 mg/kg. When the alpha 2M-depleted guinea-pigs were reconstituted with human alpha 2M, this sensitivity was reversed. Lethal shock did not occur in alpha 2M-depleted animals even at an elastase dose of 0.2 mg/kg when Hageman factor was simultaneously depleted, indicating that elastase induces shock through activation of the Hageman factor-dependent system. Similar results were obtained when the culture supernatants of an elastase-producing strain, IFO-3455, were used instead of the purified elastase, whereas no cardiovascular changes occurred, even in the alpha 2M-depleted guinea-pigs, when the culture supernatants were pretreated with an elastase specific inhibitor (zincov) or when the culture supernatants of an elastase non-producing strain, PA-103 were used. PMID:7524612
Szabó, C; Southan, G J; Thiemermann, C
Enhanced formation of nitric oxide (NO) by both the constitutive and the inducible isoforms of NO synthase (NOS) has been implicated in the pathophysiology of a variety of diseases, including circulatory shock. Non-isoform-selective inhibition of NO formation, however, may lead to side effects by inhibiting the constitutive isoform of NOS and, thus, the various physiological actions of NO. S-Methylisothiourea sulfate (SMT) is at least 10- to 30-fold more potent as an inhibitor of inducible NOS (iNOS) in immunostimulated cultured macrophages (EC50, 6 microM) and vascular smooth muscle cells (EC50, 2 microM) than NG-methyl-L-arginine (MeArg) or any other NOS inhibitor yet known. The effect of SMT on iNOS activity can be reversed by excess L-arginine in a concentration-dependent manner. SMT (up to 1 mM) does not inhibit the activity of xanthine oxidase, diaphorase, lactate dehydrogenase, monoamine oxidase, catalase, cytochrome P450, or superoxide dismutase. SMT is equipotent with MeArg in inhibiting the endothelial, constitutive isoform of NOS in vitro and causes increases in blood pressure similar to those produced by MeArg in normal rats. SMT, however, dose-dependently reverses (0.01-3 mg/kg) the hypotension and the vascular hyporeactivity to vasoconstrictor agents caused by endotoxin [bacterial lipopolysaccharide (LPS), 10 mg/kg, i.v.] in anesthetized rats. Moreover, therapeutic administration of SMT (5 mg/kg, i.p., given 2 hr after LPS, 10 mg/kg, i.p.) attenuates the rises in plasma alanine and aspartate aminotransferases, bilirubin, and creatinine and also prevents hypocalcaemia when measured 6 hr after administration of LPS. SMT (1 mg/kg, i.p.) improves 24-hr survival of mice treated with a high dose of LPS (60 mg/kg, i.p.). Thus, SMT is a potent and selective inhibitor of iNOS and exerts beneficial effects in rodent models of septic shock. SMT, therefore, may have considerable value in the therapy of circulatory shock of various etiologies and other
Ebner, H; Gebhart, W
Septic gonococcal complications consist in intermittent fever, arthralgia and skin lesions. In recent years predominantly females suffering from this disease were observed. This diagnosis is made by the demonstration of gonococcal infection combined with the above mentioned clinical symptoms. A further confirmation is possible by blood culture and the demonstration of gonococci in skin lesions or joint fluid.
Houston, M C
Shock is an acute widespread reduction in effective tissue perfusion that invokes an imbalance of oxygen supply and demand, anaerobic metabolism, lactic acidosis, cellular and organ dysfunction, metabolic abnormalities, and, if prolonged, irreversible damage and death. The pathophysiologic events in the various types of shock are different and complex with hemodynamic and oxygenation changes, alterations in the composition of the fluid compartments, and various mediators. Shock results from a change in one or a combination of the following: intravascular volume, myocardial function, systemic vascular resistance, or distribution of blood flow. The clinical types of shock include hypovolemic, cardiogenic, distributive (septic), and obstructive. An understanding of the pathophysiologic changes, rapid diagnosis, appropriate monitoring, and appropriate therapy can reduce the high morbidity and mortality in shock states.
Omar, Shahed; Ali, Ahmad; Atiya, Yahya; Mathivha, Rudo Lufuno; Dulhunty, Joel M.
Context: Severe sepsis or septic shock. Aims: The aim of this study is to examine the effect of a fluid challenge on the B-type natriuretic peptide (BNP) and the hemodynamic state. Settings and Design: This observational study was conducted in an intensivist-led academic, mixed medical-surgical Intensive Care Unit. Subjects and Methods: Focused transthoracic echocardiogram, plasma BNP, and hemodynamic measurements were recorded at baseline and following a 500 ml fluid challenge in thirty patients. Independent predictors of the percentage (%) change in stroke volume (SV) were sought. Next, these independent predictors were assessed for a relationship with the percentage change in BNP. Statistical Analysis Used: Multiple linear regressions, Wilcoxon rank-sum test, t-test, and Pearson's correlation were used. Data analysis was carried out using SAS. The 5% significance level was used. Results: Using a multiple regression models, the percentage increase in SV was independently predicted by the percentage increase in mean arterial pressure, left ventricular end-diastolic volume/dimension (LVEDV/LVEDd), ejection fraction, and a decrease in Acute Physiology and Chronic Health Evaluation II score (P < 0.0001). Preload, measured using LVEDV1 (before the fluid challenge) was significantly larger in the fluid nonresponders (%SV increase <15%) vs. the responders (%SV increase ≥15%). Finally, the percentage change in BNP was positively correlated with left ventricular size at end diastole LVEDd, r = 0.4, P < 0.035). Conclusions: An increase in BNP soon after a fluid challenge may have some predictive utility of a large LVEDd, which in turn can be used to independently predict the SV response to a fluid challenge.
Fazio, V W; Wu, J S; Lavery, I C
OBJECTIVE: To evaluate the outcome of repeat ileal pouch-anal anastomosis (IPAA) for septic complications of pelvic pouch surgery; to assess the relationship between diagnosis and outcome; to assess quality of life after surgery. SUMMARY BACKGROUND DATA: Pelvic and perineal sepsis due to ileal pouch-anal anastomotic leaks frequently results in pouch loss. Many surgeons believe that pelvic sepsis and/or dense pelvic fibrosis makes salvage surgery unsafe or that pouches salvaged under these circumstances may not function well. As a result, there are few studies of pouch salvage procedures for septic indications. METHODS: The authors reviewed records of Cleveland Clinic Foundation patients who had undergone repeat IPAA surgery after septic complications from previous pelvic pouch surgery and who had completed at least 6 months of follow-up. Final diagnoses included ulcerative colitis (n = 22), Crohn's disease (n = 10), indeterminate colitis (n = 1), and familial polyposis (n = 2). Patients with functioning pouches were interviewed about functional problems and quality of life using an in-house questionnaire and the validated SF-36 Health Survey. RESULTS: Of 35 patients, 30 (86%) had a functioning pouch 6 months after repeat IPAA. In 4 patients, complications led to pouch removal or fecal diversion. One patient declined stoma closure. Of the patients with mucosal ulcerative colitis (MUC), 95% (21/22) had a functioning pouch 6 months after surgery. For patients with Crohn's disease (CD) 60% (6/10) have maintained a functioning pouch. Of the 30 patients with functioning pouches, 17 (57%) rated their quality of life as either "good" or "excellent," the remaining 13 (43%) selected "fair" or "poor." All said they would choose repeat IPAA surgery again. An SF-36 Health Survey completed by all patients with a functioning pouch at follow-up showed a mean physical component scale of 46.4 and a mean mental component scale of 47.6, scores well within the normal limit. CONCLUSIONS
Stubblefield, P G; Grimes, D A
Abortion-related deaths, which account for 47% of total maternal mortality in the world, result primarily from sepsis and are widespread in developing countries where abortion is illegal or inaccessible. Septic abortion offers opportunities for prevention on the primary, secondary, and tertiary level of medial care. Primary prevention of septic abortion encompasses the provision of effective contraception, provision of safe and legal abortion in cases of contraceptive failure, and appropriate medical management of abortion. Secondary prevention involves the prompt diagnosis of endometriosis and effective treatment to avert more serious infection. The diagnosis of septic abortion should be considered when women of reproductive age present to health facilities with vaginal bleeding, lower abdominal pain, and fever. Tertiary prevention is aimed at avoiding the serious complications of postabortal infection, including hysterectomy and death. Women with high fever, pelvic peritonitis, and tachycardia should undergo uterine evacuation and parental antibiotic therapy. Supportive care for cardiovascular system and other organs may be essential. The medical technology needed to avert serious complications and deaths from septic abortion is available. Lacking is a political commitment on the part of many governments and health care agencies to address this avoidable contributor to maternal morbidity and mortality.
Morgan, D S; Fisher, D; Merianos, A; Currie, B J
A retrospective study of 191 cases of septic arthritis was undertaken at Royal Darwin Hospital in the tropical north of Australia. Incidence was 9.2 per 100,000 overall and 29.1 per 100,000 in Aboriginal Australians (RR 6.6; 95% CI 5.0-8.9). Males were affected more than females (RR 1.6; 95% CI 1.2-2.1). There was no previous joint disease or medical illness in 54%. The commonest joints involved were the knee (54%) and hip (13%). Significant age associations were infected hips in those under 15 years and infected knees in those over 45 years. Seventy two percent of infections were haematogenous. Causative organisms included Staphylococcus aureus (37%), Streptococcus pyogenes (16%) and Neisseria gonorrhoeae (12%). Unusual infections included three melioidosis cases. Polyarthritis occurred in 17%, with N. gonorrhoeae (11/23) more likely to present as polyarthritis than other organisms (22/168) (OR 6.0; 95% CI 2.1-16.7). Univariate and multivariate analysis showed the hip to be at greater risk for S. aureus than other joints. Open arthrotomy was a more successful treatment procedure than arthroscopic washout or needle aspiration.
Shirtliff, Mark E; Mader, Jon T
Acute septic arthritis may develop as a result of hematogenous seeding, direct introduction, or extension from a contiguous focus of infection. The pathogenesis of acute septic arthritis is multifactorial and depends on the interaction of the host immune response and the adherence factors, toxins, and immunoavoidance strategies of the invading pathogen. Neisseria gonorrhoeae and Staphylococcus aureus are used in discussing the host-pathogen interaction in the pathogenesis of acute septic arthritis. While diagnosis rests on isolation of the bacterial species from synovial fluid samples, patient history, clinical presentation, laboratory findings, and imaging studies are also important. Acute nongonococcal septic arthritis is a medical emergency that can lead to significant morbidity and mortality. Therefore, prompt recognition, rapid and aggressive antimicrobial therapy, and surgical treatment are critical to ensuring a good prognosis. Even with prompt diagnosis and treatment, high mortality and morbidity rates still occur. In contrast, gonococcal arthritis is often successfully treated with antimicrobial therapy alone and demonstrates a very low rate of complications and an excellent prognosis for full return of normal joint function. In the case of prosthetic joint infections, the hardware must be eventually removed by a two-stage revision in order to cure the infection.
Puskarich, Michael A.; Kline, Jeffrey A.; Watts, John A.; Shirey, Kristin; Hosler, Jonathan; Jones, Alan E.
Introduction To determine if changes platelet mitochondrial function in patients with sepsis are present early following presentation, and the association of these changes with clinical outcomes and systemic metabolic function. Materials and Methods Prospective observational cohort study of a convenience sample of patients with severe sepsis. Mitochondrial function of intact, non-permeabilized platelets suspended in their own plasma was estimated using high resolution respirometry. Unstimulated basal respiration, oligomycin-induced state 4 (state 4o) and maximal respiratory rate following serial titrations of FCCP were measured. Organ failure was estimated using SOFA score, and patients were followed until 28 days to determine survival. Lactate levels were measured in all patients, and a subset of patients had lactate:pyruvate ratios measured. Results 28 patients were enrolled, 21 of whom survived. Initial SOFA score and lactate levels were 8.5 (IQR 6, 10) and 2.3 (IQR 1.2, 3.5) respectively, while the median L/P ratio was 23.4 (IQR 15.2, 38). Basal and maximal respiratory rates were significantly higher among non-survivors compared to survivors (p=0.02 and 0.04), while oligomycin-induced state 4 respiration was not statistically different between groups (p = 0.15). We found a significant association between maximal respiration and organ failure (p = 0.03), and both basal and maximal rates with initial lactate level (p = 0.04, 0.02), but not with lactate:pyruvate ratio. Conclusions Differences in platelet mitochondrial function between survivors and non-survivors are present very early in the hospital course and are associated with organ failure and lactate. PMID:26511963
Khan, Naushad Ahmad; Singh, Harpreet; Chhoda, Ankit; Mattoo, Sahil; Gupta, Basant Kumar
Introduction Sepsis is the leading cause of mortality in non-coronary Intensive Care Units (ICUs). Oxidative stress is one of the important features in pathogenesis of sepsis. Aim This study was undertaken to evaluate levels of oxidants and antioxidants in patients with sepsis admitted to ICU. Study Design: This was a non-interventional clinical case-control study undertaken at a tertiary level teaching hospital in New Delhi, India. Materials and Methods Forty-six consecutive non-pediatric patients admitted to ICU with sepsis were included and subjected to detailed history, physical examination and investigations. Blood samples were drawn to evaluate oxidant Malondialdehyde (MDA) and antioxidant (alpha-tocopherol) levels. Acute Physiology and Chronic Health Evaluation II (APACHE II) and Organ Dysfunction and/or Infection (ODIN) scores were calculated and patients followed up for outcomes. Twenty age and sex matched healthy subjects served as controls. Results Mean levels of malondialdehyde were higher in patients than controls (17.2±3.8nm/ml versus 4.6±1.6nm/ml, p<0.001) while levels of alpha-tocopherol were lower (3.2±1.3μg/ml versus 9.9±2.0μg/ml, p<0.001). The mean APACHE II and ODIN scores were 18.1±9.3 and 1.7±1.3 respectively in patients. These scores were two to three fold higher in non survivor patients (n=22) in comparison with survivors (n=18) (p<0.001). There was no significant difference between the two groups in oxidants and antioxidants levels (p>0.05). However, a significant and positive correlation was observed between oxidant -antioxidant levels and APACHE II, ODIN and International Normalized Ratio (INR) scores in septic patients overall. Conclusion The oxidants in septic patients were significantly higher while antioxidants were significantly lower than healthy controls. There was also a significant correlation with APACHE II and ODIN scores. A large patient population based study may draw more specific conclusions. PMID:27656484
Makki, Daoud; Watson, Alex James
Trochanteric bursitis, whether septic or inflammatory in origin, is a condition that affects middle-aged patients. Here we report the rare case of an adolescent with septic trochanteric bursitis (treated successfully with intravenous antibiotics), review the available literature on septic bursitis, illustrate the importance of prompt recognition and treatment of this condition in any age group, and describe the clinical presentation and the radiologic findings.
Introduction The effect of parenteral fish oil in septic patients is not widely studied. This study investigated the effects of parenteral fish oil on plasma phospholipid fatty acids, inflammatory mediators, and clinical outcomes. Methods Twenty-five patients with systemic inflammatory response syndrome or sepsis, and predicted to need parenteral nutrition were randomized to receive either a 50:50 mixture of medium-chain fatty acids and soybean oil or a 50:40:10 mixture of medium-chain fatty acids, soybean oil and fish oil. Parenteral nutrition was administrated continuously for five days from admission. Cytokines and eicosanoids were measured in plasma and in lipopolysaccharide-stimulated whole blood culture supernatants. Fatty acids were measured in plasma phosphatidylcholine. Results Fish oil increased eicosapentaenoic acid in plasma phosphatidylcholine (P < 0.001). Plasma interleukin (IL)-6 concentration decreased significantly more, and IL-10 significantly less, in the fish oil group (both P < 0.001). At Day 6 the ratio PO2/FiO2 was significantly higher in the fish oil group (P = 0.047) and there were fewer patients with PO2/FiO2 <200 and <300 in the fish oil group (P = 0.001 and P = 0.015, respectively). Days of ventilation, length of intensive care unit (ICU) stay and mortality were not different between the two groups. The fish oil group tended to have a shorter length of hospital stay (22 ± 7 vs. 55 ± 16 days; P = 0.079) which became significant (28 ± 9 vs. 82 ± 19 days; P = 0.044) when only surviving patients were included. Conclusions Inclusion of fish oil in parenteral nutrition provided to septic ICU patients increases plasma eicosapentaenoic acid, modifies inflammatory cytokine concentrations and improves gas exchange. These changes are associated with a tendency towards shorter length of hospital stay. Trials Registration Clinical Trials Registration Number ISRCTN89432944 PMID:20085628
To assess and correlate the microbiology of neonatal septic arthritis with the clinical presentation, we reviewed the records of nine infants with neonatal septic arthritis (NSA) diagnosed at Edmonton hospitals between 1964 and 1981, and evaluated 92 other cases reported in the English literature since 1960. Our analysis revealed that the microbiology of NSA seemed to be dependent on whether it was hospital or community acquired. In the hospital-acquired cases, staphylococci were the predominant isolates (62%), followed by Candida species (17%) and gram-negative enteric bacilli (15%). Community-acquired arthritis was caused most often by streptococci (52%), followed by staphylococci (26%) and gonococci (17%). Since 1970, the relative infrequency of staphylococcal (5%) in favor of streptococcal (75%) isolates in community-acquired NSA is even more pronounced.
... Many organs can be damaged as a result. Shock requires immediate treatment and can get worse very rapidly. As many 1 in 5 people who suffer shock will die from it. Considerations The main types ...
Araya, I; Fasce, G; Núñez, E; Opazo, J L; Saez, E; Hurtado, V; Contreras, S; Quiñones, L A
The present study is a non-inferiority study based on a descriptive and comparative case series for comparison of generic vs. original intravenous antimicrobials in septic oncology patients at an oncology private ICU. 1906 cancer patients admitted to Arturo Lopez Perez Foundation, Chile, were included in this study. After recruitment, a first retrospective group of 206 septic cancer patients recorded from 1st January, 2008 until July 14th, 2010, treated with original antibiotics (cefoperazone-sulbactam, imipenem-cilastatin, piperacillin-tazobactam) were included for analyses and a second prospective group of 143 septic cancer patients recorded from July 15th, 2010 until January 02, 2013, treated with the same but generic antibiotics were also included for comparisons. The trial protocol was developed in accordance with Helsinki and Good Clinical Practices recommendations. The results of this study showed no significant differences between the 2 groups in days of treatment, rate of success and lab test determinations (white cell count, PCR and procalcitonin), with lower, but not significant, total bed days and CPU bed days for generic antibiotics. Therefore, we conclude that the safety and efficacy of the generic antibiotics cefactam®, imipen® and Piperazam® are not inferior to original antibiotics for the treatment of severe sepsis in hospitalised patients at the Arturo Lopez Perez Foundation.
Liu, M; Zhang, X; Chen, H; Wang, G; Zhang, J; Dong, P; Liu, Y; An, S; Wang, L
We aimed to find the correlation between serum sPD-L1 (soluble programmed cell death L-1 ligand) and sepsis. Totally 91 consecutive patients with sepsis were performed in a 15-bed medical intensive care unit (ICU) of the second affiliated hospital, Xi'an Jiaotong University in Xi'an, China, between February 2015 and May 2016. Healthy controls (HC) consisted of 29 healthy volunteer. Baseline demographic data were recorded. Blood samples were collected through an indwelling central venous or by peripheral venipuncture. Serum sPD-L1 and sPD-1 levels were determined with enzyme-linked immunosorbent assay kits (Elabscience Biotechnology Co. Ltd, Wuhan, China). SPSS19.0 software (SPSS Inc., Chicago, Illinois, USA) was used for statistical analysis. Kaplan-Meier survival analysis and Cox regression analysis were also performed. Serum sPD-L1 levels and sPD-1 levels were significantly increased in septic patients compared with HC (P = 0.000). Serum sPD-L1 levels were significantly increased in non-survivors compared with survivors (P < 0.05), but there was no statistically difference on serum sPD-1 levels between non-survivors and survivors (P > 0.05). Serum sPD-L1 levels were correlated with absolute lymphocyte (ALC), platelets and SOFA scores. Serum sPD-L1/sPD-1 levels were negatively correlated with ALC and platelets, and SOFA scores. The prognostic accuracy of the sPD-L1 level to predict 28-day mortality was similar to that of the APACHE-II scores and SOFA scores. Cox regression analysis showed that sPD-L1 was an independent prognostic factor. Serum sPD-L1 is upregulated in sepsis and may reflect disease severity and clinical outcomes in patients. Serum sPD-L1 may be an independent prognostic factor for sepsis.
Bello, G; Di Muzio, F; Maviglia, R; Antonelli, M
Severe sepsis and septic shock are still the leading cause of mortality and morbidity in the intensive care unit. The inflammatory response to infection is associated with an impressive, systemic release of pro- and anti-inflammatory mediators, which results in generalized endothelial damage, multiple organ failure and altered cellular immunological responsiveness. Over the last years, the substantial advances in the understanding of sepsis have led to the development of a large number of new approaches and technologies in the management of septic patients. Extracorporeal blood purification techniques using various membrane materials have been proposed to modulate multiple inflammatory mediators, and seem to be a potential adjuvant in the treatment of sepsis. However, the use of extracorporeal blood purification techniques during sepsis still remains controversial, thus precluding any definitive recommendations on the benefit of these methods. More data are needed to better recognize septic patients who are most likely to benefit from blood purification treatments, and clarify the optimal timing, duration, and number of applications of these techniques in the daily clinical practice.
Clements, J; Dinneen, A; Heilpern, G
Septic arthritis is an uncommon condition with an incidence of 2-3/100,000. It is clinically notable, however, as it is a rapidly destructive joint disease with significant associated morbidity and mortality. Polyarticular septic arthritis has an estimated incidence of 15% of all cases of infectious arthritis. We report a case of polyarticular septic arthritis with involvement of bilateral shoulders and wrist to highlight the importance of early diagnosis and treatment as well as the high mortality rates associated with this condition. Bilateral septic shoulder arthritis poses a challenge to treat, and its significance should not be underestimated as even with early surgical intervention and aggressive antibiotic and fluid resuscitation death is a sad but perhaps not uncommon outcome. It is therefore imperative that the diagnosis of polyarticular septic arthritis is kept prominent in the physician's mind when confronted with a patient with symptomatic polyarthralgia.
Sundberg, S.B.; Savage, J.P.; Foster, B.K. )
The technetium phosphate bone scans of 106 children with suspected septic arthritis were reviewed to determine whether the bone scan can accurately differentiate septic from nonseptic arthropathy. Only 13% of children with proved septic arthritis had correct blind scan interpretation. The clinically adjusted interpretation did not identify septic arthritis in 30%. Septic arthritis was incorrectly identified in 32% of children with no evidence of septic arthritis. No statistically significant differences were noted between the scan findings in the septic and nonseptic groups and no scan findings correlated specifically with the presence or absence of joint sepsis.
Cardiovascular devices; reclassification of intra-aortic balloon and control systems for acute coronary syndrome, cardiac and non-cardiac surgery, or complications of heart failure; effective date of requirement for premarket approval for intra-aortic balloon and control systems for septic shock or pulsatile flow generation. Final order.
The Food and Drug Administration (FDA) is issuing a final order to reclassify intra-aortic balloon and control system (IABP) devices when indicated for acute coronary syndrome, cardiac and non-cardiac surgery, or complications of heart failure, a preamendments class III device, into class II (special controls), and to require the filing of a premarket approval application (PMA) or a notice of completion of a product development protocol (PDP) for IABPs when indicated for septic shock or pulsatile flow generation.
Wacker, David A; Winters, Michael E
Critically ill patients with undifferentiated shock are complex and challenging cases in the ED. A systematic approach to assessment and management is essential to prevent unnecessary morbidity and mortality. The simplified, systematic approach described in this article focuses on determining the presence of problems with cardiac function (the pump), intravascular volume (the tank), or systemic vascular resistance (the pipes). With this approach, the emergency physician can detect life-threatening conditions and implement time-sensitive therapy.
Ruthrauff, Cassandra M; Smith, Julie; Glerum, Leigh
The purpose of this paper is to describe the signalment, clinical signs, laboratory results, culture results, and response to treatment for primary septic peritonitis in cats. This is a retrospective study of 12 client-owned animals. Medical records were reviewed for clinical findings, laboratory results, microbial culture results, radiographic findings, diagnosis, treatment, and outcome. The overall mortality rate for this group of cats was 31%, consistent with previous reports of septic peritonitis in cats. All cats that were both bradycardic and hypothermic on presentation did not survive. Other clinicopathological findings were consistent with previously reported cases of septic peritonitis in cats. Results suggest that clinicopathological findings and outcomes in cats with primary septic peritonitis are similar to those in cats with septic peritonitis from a determined cause. A specific mechanism of inoculation has yet to be determined, but an oral source of bacteria is suggested for cats with primary bacterial septic peritonitis.
Silva, S.C.; Baggio-Zappia, G.L.; Brunialti, M.K.C.; Assunçao, M.S.C.; Azevedo, L.C.P.; Machado, F.R.; Salomao, R.
Recognition of pathogens is performed by specific receptors in cells of the innate immune system, which may undergo modulation during the continuum of clinical manifestations of sepsis. Monocytes and neutrophils play a key role in host defense by sensing and destroying microorganisms. This study aimed to evaluate the expression of CD14 receptors on monocytes; CD66b and CXCR2 receptors on neutrophils; and TLR2, TLR4, TLR5, TLR9, and CD11b receptors on both cell types of septic patients. Seventy-seven septic patients (SP) and 40 healthy volunteers (HV) were included in the study, and blood samples were collected on day zero (D0) and after 7 days of therapy (D7). Evaluation of the cellular receptors was carried out by flow cytometry. Expression of CD14 on monocytes and of CD11b and CXCR2 on neutrophils from SP was lower than that from HV. Conversely, expression of TLR5 on monocytes and neutrophils was higher in SP compared with HV. Expression of TLR2 on the surface of neutrophils and that of TLR5 on monocytes and neutrophils of SP was lower at D7 than at D0. In addition, SP who survived showed reduced expression of TLR2 and TLR4 on the surface of neutrophils at D7 compared to D0. Expression of CXCR2 for surviving patients was higher at follow-up compared to baseline. We conclude that expression of recognition and cell signaling receptors is differentially regulated between SP and HV depending on the receptor being evaluated. PMID:24728213
Corbucci, G G; Loche, F
Following our previous work on biochemical and clinical aspects of cardiogenic shock, we carried out an open study on 27 patients hospitalized in shock condition and investigated for the entire period of permanence in intensive care units (ICU). The subjects were treated with high doses of L-carnitine following previous results on the use of this molecule in conditions of oxidative damage due to acute cellular hypoxia. When compared with the data reported in the literature, the results obtained in this study show a surprisingly positive trend for the carnitine-treated patients in terms of survival rate to the cardiogenic shock. This finding and statistical analysis of the clinical parameters confirm the suggestion that L-carnitine could be credited with a new and interesting role in the therapy of cardiogenic shock.
Treatment with granulocyte-macrophage colony-stimulating factor is associated with reduced indoleamine 2,3-dioxygenase activity and kynurenine pathway catabolites in patients with severe sepsis and septic shock.
Schefold, Joerg C; Zeden, Jan-Philip; Pschowski, Rene; Hammoud, Ben; Fotopoulou, Christina; Hasper, Dietrich; Fusch, Gerhard; Von Haehling, Stephan; Volk, Hans-Dieter; Meisel, Christian; Schütt, Christine; Reinke, Petra
The immunoregulatory enzyme indoleamine 2,3-dioxygenase (IDO) controls tryptophan metabolism and is induced by pro-inflammatory stimuli. We investigated whether immunostimulatory treatment with granulocyte-macrophage colony-stimulating factor (GM-CSF) influences IDO activity and tryptophan metabolism in sepsis. Thirty-six patients with severe sepsis/septic shock and sepsis-associated immunosuppression (assessed using monocytic human leukocyte antigen-DR (mHLA-DR) expression) were assessed in a controlled trial of GM-CSF or placebo treatment for 8 days. Using tandem mass spectrometry, levels of tryptophan, kynurenine, kynurenic acid, quinolinic acid, 5-hydroxytryptophan, serotonin, and estimated IDO activity were determined in a blinded fashion over a 9-day interval. At baseline, tryptophan and metabolite levels did not differ between the study groups. Although tryptophan levels were unchanged in both groups over the treatment interval (all p>0.8), IDO activity was markedly reduced after GM-CSF treatment (35.4 +/- 21.0 vs 21.6 +/-9.9 (baseline vs day 9), p = 0.02). IDO activity differed significantly between the 2 groups after therapy (p = 0.03). Metabolites downstream of IDO (kynurenine, quinolinic acid, kynurenic acid) were all induced in sepsis and declined in the GM-CSF group, but not in controls. Serotonin pathway metabolites remained unchanged in both groups (all p>0.15). Moreover, IDO activity correlated with procalcitonin (p< 0.0001, r = 0.56) and mHLA-DR levels (p = 0.005, r = -0.28) in the overall samples group. Thus, GM-CSF therapy is associated with decreased IDO activity and reduced kynurenine pathway catabolites in sepsis. This may be due to an improved antibacterial defence.
Song, Xin yu; Li, Shan; Cao, Jian; Xu, Kai; Huang, Hui; Xu, Zuo jun
Abstract Based on the source of the embolus, septic pulmonary embolism (SPE) can be classified as cardiac, peripheral endogenous, or exogenous. Cardiac SPEs are the most common. We conducted a retrospective analysis of 20 patients with cardiac SPE hospitalized between 1991 and 2013 at a Chinese tertiary referral hospital. The study included 14 males and 6 females with a median age of 38.1 years. Fever (100%), cough (95%), hemoptysis (80%), pleuritic chest pain (80%), heart murmur (80%), and moist rales (75%) were common clinical manifestations. Most patients had a predisposing condition: congenital heart disease (8 patients) and an immunocompromised state (5 patients) were the most common. Staphylococcal (8 patients) and Streptococcal species (4 patients) were the most common causative pathogens. Parenchymal opacities, nodules, cavitations, and pleural effusions were the most common manifestations observed via computed tomography (CT). All patients exhibited significant abnormalities by echocardiography, including 15 patients with right-sided vegetations and 4 with double-sided vegetations. All patients received parenteral antimicrobial therapy as an initial treatment. Fourteen patients received cardiac surgery, and all survived. Among the 6 patients who did not undergo surgery, only 1 survived. Most patients in our cardiac SPE cohort had predisposing conditions. Although most exhibited typical clinical manifestations and radiography, they were nonspecific. For suspected cases of SPE, blood culture, echocardiography, and CT pulmonary angiography (CTPA) are important measures to confirm an early diagnosis. Vigorous early therapy, including appropriate antibiotic treatment and timely cardiac surgery to eradicate the infective source, is critical. PMID:27336870
Murray, P M
Septic arthritis of the hand and wrist is relatively uncommon. The most common cause is penetrating trauma such as a human or animal bite. The most common causative organism is Staphylococcus aureus. Septic arthritis caused by Streptococcal species. Haemophilus influenzae, Pseudomonas aeruginosa, Serratia species, Neisseria gonorrhoeae, Pasteurella multocida, Eikenella corrodens, and Mycobacterium marinum also may occur in specific clinical settings. The best clinical results occur following an accurate diagnosis, prompt surgical drainage, and debridement in concert with appropriate antibiotics and early postoperative range of motion. A delay in diagnosis or treatment is associated with an unsatisfactory outcome.
Obonyo, Nchafatso; Maitland, Kathryn
Management of shock in children with severe malnutrition remains controversial. To date, the evidence supporting either benefit or harm of fluid resuscitation or rehydration is weak. This issue, however, is not unique to children with severe malnutrition; pediatric guidelines worldwide have a weak level of evidence and remain unsupported by appropriate clinical studies. In this review we give an overview of the current recommendations in other pediatric populations and appraise the strength of evidence supporting these. We summarize results from the only controlled trial ever undertaken, FEAST (Fluid Expansion As Supportive Therapy), which was conducted in resource-poor hospitals involving 3,141 African children with severe febrile illnesses and shock, including large subgroups with sepsis and malaria but excluding children with severe malnutrition. This high-quality trial provided robust evidence that fluid resuscitation increased the risk of death, leading to an excess mortality of 3 in every 100 children receiving fluid boluses, compared with controls receiving no boluses. These findings may have particular relevance to management of septic shock in children with severe malnutrition. However, they cannot be extrapolated to children with gastroenteritis, since this condition was not included in the trial. Current observational studies under way in East Africa may provide insights into myocardial and hemodynamic function in severe malnutrition, including responses to fluid challenge in those complicated by gastroenteritis. Such studies are an essential step for setting the research agenda regarding fluid management of shock in severe malnutrition.
A collection of septic systems case studies to help community planners, elected officials, health department staff, state officials, and interested citizens explore alternatives for managing their decentralized wastewater treatment systems.
Arian, Mahdieh; Kamali, Azadeh; Tabatabaeichehr, Mahbubeh; Arashnia, Parisa
Introduction Septic cavernous sinus thrombosis (CST) is a rare condition that can result in high mortality and morbidity rates if not treated immediately. CST may be aseptic or septic. Less common primary sites of infection include the tonsils, soft palate, middle ear, and orbit. Reported cases of middle ear infection are very rare, and response to treatment is poor. Case Presentation The present study is a case report of acute otitis media which led to septic cavernous sinus thrombosis in a 56-year-old woman in Bojnord city, North Khorasan, Iran. Conclusions Findings of laboratory tests and magnetic resonance imaging (MRI) confirmed the clinical diagnosis. Clinical-based medical care led to successful management of the patient with broad spectrum intravenous antibiotics that prevented serious complications. PMID:27781123
Wawrzyńska, L; Meleniewska-Maciszewska, A; Burakowski, J
Disseminated pulmonary infiltrates, cutaneous lesions and diabetes insipidus in a female patients with a history of recurrent pneumothorax and persistent respiratory tract infections suggested the diagnosis of histiocytosis X. The pathological examination of a biopsy lung tissue specimen confirmed that diagnosis. In the course of treatment many dangerous complications were observed. The intensive therapy including artificial ventilation (24 days) was fully effective and settle the beneficial clinical outcome.
Gasparetto, A; Corbucci, G G; De Blasi, R A; Antonelli, M; Bagiella, E; D'Iddio, S; Trevisani, C
The clinical use of acetyl carnitine in circulatory shock has its theoretical basis in the ability of this molecule to restore enzyme activity inhibited by hypoxia, acting as an acetyl donor. Moreover the action of carnitine on an injured myocardium encouraged us to examine the clinical effect of this drug during heart failure. A double-blind clinical study was performed in ten Italian intensive care units on 115 patients with septic, cardiac of traumatic shock, by using acetyl-L-carnitine infusion for 12 hours, with a previous single bolus intravenously. The results showed a good response to the drug in terms of blood oxygenation during the course of sepsis and heart failure. The heart rate as well as right atrial pressure decreased significantly in patients with cardiogenic shock. In septic patients systolic and mean arterial pressures increased also. The present data suggests the use of acetyl-L-carnitine as an adjuvant to the commonly used therapy in hypoxic conditions.
Mittermayr, Rainer; Antonic, Vlado; Hartinger, Joachim; Kaufmann, Hanna; Redl, Heinz; Téot, Luc; Stojadinovic, Alexander; Schaden, Wolfgang
For almost 30 years, extracorporeal shock wave therapy has been clinically implemented as an effective treatment to disintegrate urinary stones. This technology has also emerged as an effective noninvasive treatment modality for several orthopedic and traumatic indications including problematic soft tissue wounds. Delayed/nonhealing or chronic wounds constitute a burden for each patient affected, significantly impairing quality of life. Intensive wound care is required, and this places an enormous burden on society in terms of lost productivity and healthcare costs. Therefore, cost-effective, noninvasive, and efficacious treatments are imperative to achieve both (accelerated and complete) healing of problematic wounds and reduce treatment-related costs. Several experimental and clinical studies show efficacy for extracorporeal shock wave therapy as means to accelerate tissue repair and regeneration in various wounds. However, the biomolecular mechanism by which this treatment modality exerts its therapeutic effects remains unclear. Potential mechanisms, which are discussed herein, include initial neovascularization with ensuing durable and functional angiogenesis. Furthermore, recruitment of mesenchymal stem cells, stimulated cell proliferation and differentiation, and anti-inflammatory and antimicrobial effects as well as suppression of nociception are considered important facets of the biological responses to therapeutic shock waves. This review aims to provide an overview of shock wave therapy, its history and development as well as its current place in clinical practice. Recent research advances are discussed emphasizing the role of extracorporeal shock wave therapy in soft tissue wound healing.
Schmittinger, Christian A; Dünser, Martin W; Haller, Maria; Ulmer, Hanno; Luckner, Günter; Torgersen, Christian; Jochberger, Stefan; Hasibeder, Walter R
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
Berbigier, Marina Carvalho; Pasinato, Valeska Fernandes; Rubin, Bibiana de Almeida; Moraes, Rafael Barberena; Perry, Ingrid Dalira Schweigert
Objective To calculate the values of the phase angle of septic patients using bioelectrical impedance analysis, correlate the values with clinical and biochemical variables, and compare them to reference values. Methods Cohort study conducted with 50 septic patients aged ≥18 years old, admitted to intensive care units, and assessed according to prognostic indexes (APACHE II and SOFA), clinical progression (mortality, severity of sepsis, length of stay in intensive care unit), biochemical parameters (albumin and C-reactive protein), and the phase angle. Results The average age of the sample was 65.6±16.5 years. Most patients were male (58%) and suffering from septic shock (60%). The average APACHE II and SOFA scores were 22.98±7.1 and 7.5±3.4, respectively. The patients who survived stayed nine days on average (five to 13) in the intensive care unit, and the mortality rate was 30%. The average value of the phase angle was 5.4±2.6º in the total sample and was smaller among the females compared with the males (p=0.01). The phase angle measures did not exhibit an association with the severity of the sepsis, mortality, gender, and age or correlate with the length of hospitalization or the biochemical parameters. The participants' phase angle values adjusted per gender and age were 1.1 to 1.9 times lower compared with the values for a normal population. Conclusion The average value of the phase angle of septic patients was lower compared with the reference values for a healthy population. The phase angle measures did not exhibit association with the clinical and biochemical variables, which might be explained by the sample homogeneity. PMID:23887756
Mulon, Pierre-Yves; Desrochers, André; Francoz, David
Lameness related to synovial infection needs to be addressed promptly because rapid degradation of the synovial homeostasis results in permanent cartilage alterations detrimental to complete recovery. Diagnosis is based on clinical signs, synovial fluid analysis, and imaging. Commonly affected joints are the fetlock, carpus, tarsus, and stifle; shoulder, elbow, and hip may also be infected. Knowing the source of infection is essential in cases of remote septic arthritis. Antimicrobials should be administered; local delivery systems may be used. Therapy relies on the removal of inflammatory mediators. Pain management is critical throughout the surgical procedures and the recovery period.
Molina Collada, Juan; Rico Nieto, Alicia; Díaz de Bustamante Ussia, Macarena; Balsa Criado, Alejandro
We describe a case of septic arthritis in a native knee due to Corynebacterium striatum, gram-positive bacilli that are usually commensal organisms of skin and mucosal membranes, but are seldom implicated in native septic arthritis. An 84-year-old man with Corynebacterium striatum septic arthritis of his native left knee and no response to conventional antibiotic therapy. Thus, the patient was allowed to take dalbavancin for compassionate use, with an excellent clinical outcome. This case emphasizes de role of Corynebacterium striatum in native joint infections and highlights the importance of early detection and appropriate treatment in improving the clinical outcome.
Boshuizen, Henny P. A.
One of the processes supposed to take place during development toward medical expertise is knowledge encapsulation. In this process detailed biomedical concepts are gradually clustered together and reorganized under fewer, clinically relevant terms. A large-scale investigation was made of the process of biomedical knowledge application using…
Corbucci, G G; Lettieri, B
Research experiences on the use of L-carnitine in conditions of acute hypoxia underline the protective role of this molecule on the cellular enzymic complex. To obtain unconfutable clinical data at this regard, the survival rate in two groups of patients affected by cardiogeic shock was evaluated. The first group (80 patients) was treated with L-carnitine while the second group (36 patients) received sodium bicarbonate. The results showed a significant response to L-carnitine treatment, indicating the role of this molecule on the metabolic acidosis due to shock. The sum of these data confirmed the role of L-carnitine in the reversible phase of cardiogenic shock in terms of enzymic protection in the course of cellular oxidative damage.
Lavrentieva, Athina; Kontakiotis, Theodore; Bitzani, Militsa
The purpose of this study was to investigate the frequency of enteral feeding intolerance in critically ill septic burn patients, the effect of enteral feeding intolerance on the efficacy of feeding, the correlation between the infection marker (procalcitonin [PCT]) and the nutrition status marker (prealbumin) and the impact of feeding intolerance on the outcome of septic burn patients. From January 2009 to December 2012 the data of all burn patients with the diagnosis of sepsis who were placed on enteral nutrition were analyzed. Septic patients were divided into two groups: group A, septic patients who developed feeding intolerance; group B, septic patients who did not develop feeding intolerance. Demographic and clinical characteristics of patients were analyzed and compared. The diagnosis of sepsis was applied to 29% of all patients. Of these patients 35% developed intolerance to enteral feeding throughout the septic period. A statistically significant increase in mean PCT level and a decrease in prealbumin level was observed during the sepsis period. Group A patients had statistically significant lower mean caloric intake, higher PCT:prealbumin ratio, higher pneumonia incidence, higher Sequential Organ Failure Assessment Maximum Score, a longer duration of mechanical ventilation, and a higher mortality rate in comparison with the septic patients without gastric feeding intolerance. The authors concluded that a high percentage of septic burn patients developed enteral feeding intolerance. Enteral feeding intolerance seems to have a negative impact on the patients' nutritional status, morbidity, and mortality.
Bernstein, Anke; Pham, That Minh
Background. Intra-articular infections can rapidly lead to osteoarthritic degradation. The aim of this clinical biomarker analysis was to investigate the influence of inflammation on cartilage destruction and metabolism. Methods. Patients with acute joint infections were enrolled in a prospective clinical trial and the cytokine composition of effusions (n = 76) was analyzed. Characteristics of epidemiology and disease severity were correlated with levels of cytokines with known roles in cartilage turnover and degradation. Results. Higher synovial IL-1β concentrations were associated with clinical parameters indicating a higher disease severity (p < 0.03) excluding the incidence of sepsis. Additionally, intra-articular IL-1β levels correlated with inflammatory serum parameters as leucocyte counts (LC) and C-reactive protein concentrations (p < 0.05) but not with age or comorbidity. Both higher LC and synovial IL-1β levels were associated with increased intra-articular collagen type II cleavage products (C2C) indicating cartilage degradation. Joints with preinfectious lesions had higher C2C levels. Intra-articular inflammation led to increased concentrations of typical cartilage metabolites as bFGF, BMP-2, and BMP-7. Infections with Staphylococcus species induced higher IL-1β expression but less cartilage destruction than other bacteria. Conclusion. Articular infections have bacteria-specific implications on cartilage metabolism. Collagen type II cleavage products reliably mark destruction, which is associated with upregulation of typical cartilage turnover cytokines. This trial is registered with DRKS00003536, MISSinG. PMID:27688601
Modulation of PL mmtabo- lism in ET cells included a faster and higher incorporation of !2-1H] glycerol into phosphatidic acid followd by a shift toward...of the vascular saooth muscle . Therefore, the ability of the endotheliu, to modulate an excitatory signal depends on the efficacy of the agonist...receptor interaction. Endothelium- derived relaxing factor(s) initiate relaxation of the vascular smooth muscle through activation of the guanylate
Agarwal, Anil; Aggarwal, Aditya N
The pathological invasion of a joint and subsequent inflammation is known as septic arthritis. The knee and hip are the most frequently involved joints. Staphylococcus aureus is the most common cause of septic arthritis in children. An acute onset of illness with an inflamed painful joint and restricted movements and inability to use joint (pseudoparalysis) clinically indicates septic arthritis. The diagnosis is difficult in a neonate or young child where refusal to feed, crying, discomfort during change of diaper (if hip is involved) or attempted joint movement may be the only findings. Fever and other systemic signs may also be absent in neonates. Septic arthritis is diagnosed clinically, supported by appropriate radiological and laboratory investigations. The peripheral blood white cell count is frequently raised with a predominance of polymorphonuclear cells. The acute phase reactants such as C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) are often markedly raised. Ultrasonography and MRI are preferred investigations in pediatric septic arthritis. Determination of infecting organism in septic arthritis is the key to the correct antibiotic choice, treatment duration and overall management. Joint aspirate and/or blood culture should be obtained before starting antibiotic treatment. Several effective antibiotic regimes are available for managing septic arthritis in children. Presence of large collections, thick pus, joint loculations and pus evacuating into surrounding soft tissues are main indications for surgical drainage. Joint aspiration can be a practical alternative in case the lesion is diagnosed early, with uncomplicated presentations and superficial joints.
Caldera, Aruna Sanjeewa; Kumanan, Thirunavukarasu; Corea, Enoka
Melioidosis is a pyogenic infection with high mortality caused by the bacterium Burkholderia pseudomallei. As the clinical presentation is not distinctive, a high index of clinical suspicion is required for diagnosis. We present a case of a 50-year-old farmer who was diabetic and a chronic alcoholic, who presented to us with pneumonia, followed by septic arthritis. He was ultimately diagnosed as having melioidosis.
Gay, R M; Lane, T W; Keller, D C
A normal part of the oral flora, Kingella kingae has seldom been recognized as the cause of serious clinical infections. We report a case of documented septic arthritis caused by K. kingae in an otherwise healthy infant. We suggest that it may be more common than thought based on the general unfamiliarity with this organism and the fact that several dozen clinical isolates have been identified by reference laboratories.
Gay, R M; Lane, T W; Keller, D C
A normal part of the oral flora, Kingella kingae has seldom been recognized as the cause of serious clinical infections. We report a case of documented septic arthritis caused by K. kingae in an otherwise healthy infant. We suggest that it may be more common than thought based on the general unfamiliarity with this organism and the fact that several dozen clinical isolates have been identified by reference laboratories. PMID:6826703
Mandell, D C; King, L G
The goal of treatment for all types of shock is the improvement of tissue perfusion and oxygenation. The mainstay of therapy for hypovolemic and septic shock is the expansion of the intravascular volume by fluid administration, including crystalloids, colloids, and blood products. Frequent physical examinations and monitoring enable the clinician to determine the adequacy of tissue oxygenation and thus the success of the fluid therapy.
Keywords: Conference report Vasopressin Shock Cardiac arrest Traumatic brain injury Septic shock Haemorrhagic shock a b s t r a c t The...potential benefits of vasopressin use in shock. 2. Vasopressin deficiency states and shock While a vasopressin infusion has little vasopressor effect in...100pg/ml and restores arterial blood pressure by a direct vasopres- sor effect and by increasing sensitivity to pressor catecholamines. At low doses (1
Wang, Qiaofeng; Zhao, Ze; Xie, Yanan; Ding, Suzhen
This research was aimed at discovering the serological and histological changes in cardiac and hepatic tissue after electric shock. The CK-MB, ALT, and AMS indexes were tested with serological methods. Moreover, the Bcl-2, Bax, and Hsp-60 expression levels were carefully measured. An electrical injury model was established by giving rats electric shocks at 110 V with alternating electric current. Blood samples from the rats were analyzed for the biochemical indexes. The degrees of pathological changes in the heart and liver were evaluated using IHC staining for Bcl-2, Bax, and Hsp-60. The levels of CK-MB in the electrical injury group rapidly peaked at 0.5 hours after the electric shock. Additionally, the levels of Bcl-2, Bax, and Hsp-60 in the cardiac and hepatic tissues changed regularly after the electrical injury and exhibited apparent differences from the levels in the control group. CK-MB, ALT, and AMS were altered regularly after electric shock, and these results provide significant information for clinical and medicolegal practice. This research has shed light on the assessment of electrical injury without obvious electrical burns. Furthermore, the findings obtained for Bcl-2/Bax and Hsp-60 can also facilitate pathological diagnosis and the identification of antemortem and postmortem electrical injury. PMID:27648446
Martínez-Morillo, Melania; Mateo Soria, Lourdes; Riveros Frutos, Anne; Tejera Segura, Beatriz; Holgado Pérez, Susana; Olivé Marqués, Alejandro
Septic pyogenic arthritis of the acromioclavicular joint is a rare entity that occurs in immunosuppressed patients or those with discontinuity of defense barriers. There are only 15 cases described in the literature. The diagnosis is based on clinical features and the isolation of a microorganism in synovial fluid or blood cultures. The evidence of arthritis by imaging (MRI, ultrasound or scintigraphy) may be useful. Antibiotic treatment is the same as in septic arthritis in other locations. Staphylococcus aureus is the microorganism most frequently isolated. Our objective was to describe the clinical features, treatment and outcome of patients diagnosed with septic arthritis of the acromioclavicular joint at a Rheumatology Department. We developed a study with a retrospective design (1989-2012). The medical records of patients with septic arthritis were reviewed (101 patients). Those involving the acromioclavicular joint were selected (6 patients; 6%).
Corey, Sally A; Agger, William A; Saterbak, Andrew T
Acromioclavicular (AC) and sternoclavicular (SC) septic arthritis with contiguous pyomyositis are rare, especially in immunocompetent individuals. We report a case of septic AC joint with pyomyositis of the deltoid and supraspinatus muscles and a separate case with septic SC joint with pyomysitis of the sternocleidomastoid muscle. Both patients had similar presentations of infections with Staphylococcus aureus and were successfully treated with surgical incision and drainage followed by prolonged antibiotic therapy.
Halder, D; Seng, Q B; Malik, A S; Choo, K E
Neonatal septic arthritis has always been considered as separate from its counterpart in older children. The condition is uncommon but serious. Affected neonates usually survive, but with permanent skeletal deformities. Ten cases of neonatal septic arthritis were diagnosed between January 1989 and December 1993 in the neonatal intensive care units of two referral hospitals in the state of Kelantan, Malaysia. All except one neonate was born prematurely. The mean age of presentation was 15.6 days. Joint swelling (10/10), increased warmth (7/10) and erythema of the overlying skin (7/10) were the common presenting signs. Vague constitutional symptoms preceded the definitive signs of septic arthritis in all cases. The total white cell counts were raised with shift to the left. The knee (60%) was not commonly affected, followed by the hip (13%) and ankle (13%). Three neonates had multiple joint involvement. Coexistence of arthritis with osteomyelitis was observed in seven neonates. The commonest organism isolated was methicillin resistant Staphylococcus aureus (9/10). Needle aspiration was performed in nine neonates and one had incision with drainage. Follow up data was available for five neonates and two of these had skeletal morbidity. Early diagnosis by frequent examination of the joints, prompt treatment and control of nosocomial infection are important for management.
Perez, Camilo; Chen, Hong; Matula, Thomas J.; Karzova, Maria; Khokhlova, Vera A.
Extracorporeal shock wave therapy (ESWT) uses acoustic pulses to treat certain musculoskeletal disorders. In this paper the acoustic field of a clinical portable ESWT device (Duolith SD1) was characterized. Field mapping was performed in water for two different standoffs of the electromagnetic head (15 or 30 mm) using a fiber optic probe hydrophone. Peak positive pressures at the focus ranged from 2 to 45 MPa, while peak negative pressures ranged from −2 to −11 MPa. Pulse rise times ranged from 8 to 500 ns; shock formation did not occur for any machine settings. The maximum standard deviation in peak pressure at the focus was 1.2%, indicating that the Duolith SD1 generates stable pulses. The results compare qualitatively, but not quantitatively with manufacturer specifications. Simulations were carried out for the short standoff by matching a Khokhlov-Zabolotskaya-Kuznetzov equation to the measured field at a plane near the source, and then propagating the wave outward. The results of modeling agree well with experimental data. The model was used to analyze the spatial structure of the peak pressures. Predictions from the model suggest that a true shock wave could be obtained in water if the initial pressure output of the device were doubled. PMID:23927207
Pasinato, Valeska Fernandes; Berbigier, Marina Carvalho; Rubin, Bibiana de Almeida; Castro, Kamila; Moraes, Rafael Barberena; Perry, Ingrid Dalira Schweigert
Objective Evaluate the compliance of septic patients' nutritional management with enteral nutrition guidelines for critically ill patients. Methods Prospective cohort study with 92 septic patients, age ≥18 years, hospitalized in an intensive care unit, under enteral nutrition, evaluated according to enteral nutrition guidelines for critically ill patients, compliance with caloric and protein goals, and reasons for not starting enteral nutrition early or for discontinuing it. Prognostic scores, length of intensive care unit stay, clinical progression, and nutritional status were also analyzed. Results The patients had a mean age of 63.4±15.1 years, were predominantly male, were diagnosed predominantly with septic shock (56.5%), had a mean intensive care unit stay of 11 (7.2 to 18.0) days, had 8.2±4.2 SOFA and 24.1±9.6 APACHE II scores, and had 39.1% mortality. Enteral nutrition was initiated early in 63% of patients. Approximately 50% met the caloric and protein goals on the third day of intensive care unit stay, a percentage that decreased to 30% at day 7. Reasons for the late start of enteral nutrition included gastrointestinal tract complications (35.3%) and hemodynamic instability (32.3%). Clinical procedures were the most frequent reason to discontinue enteral nutrition (44.1%). There was no association between compliance with the guidelines and nutritional status, length of intensive care unit stay, severity, or progression. Conclusion Although the number of septic patients under early enteral nutrition was significant, caloric and protein goals at day 3 of intensive care unit stay were met by only half of them, a percentage that decreased at day 7. PMID:23887755
Özgür, Aykut; Tutar, Yusuf
Heat shock protein 90 (Hsp90) is an important member of the chaperone protein family and it is involved in stabilization, regulation, and maintenance of oncogenic client proteins with co-chaperones. Cochaperones regulate the ATPase activity of Hsp90 and its interactions with oncogenic client proteins. Therefore, Hsp90 and its co-chaperones have become significant therapeutic targets for cancer treatment. Many chemical compounds have been evaluated for Hsp90 inhibition as well as significant results were obtained in clinical trials. In this paper, we emphasize on the key roles of Hsp90 and its co-chaperones in tumorigenesis and overview therapeutic strategies of Hsp90 inhibition in oncology.
Revenaugh, Mark S
Veterinarians have begun using extracorporeal shock wave therapy (ESWT) for treatment of osteoarthritis (OA) in horses, although relatively little information has been published about its efficacy or mechanism of action. As a clinician, it can be difficult to know if and when ESWT should be recommended. Case studies in which ESWT is used to treat advanced OA in horses are discussed. ESWTseems to be a valuable adjunct for management of equine OA. It is the purpose of this article to discuss indications and techniques as well as to share clinical experiences using ESWT in the treatment of OA in the horse.
Greenhalgh, David G.; Wilkes, Mahlon M.
Critical appraisal of outcomes after burn shock resuscitation with albumin has previously been restricted to small relatively old randomized trials, some with high risk of bias. Extensive recent data from nonrandomized studies assessing the use of albumin can potentially reduce bias and add precision. The objective of this meta-analysis was to determine the effect of burn shock resuscitation with albumin on mortality and morbidity in adult patients. Randomized and nonrandomized controlled clinical studies evaluating mortality and morbidity in adult patients receiving albumin for burn shock resuscitation were identified by multiple methods, including computer database searches and examination of journal contents and reference lists. Extracted data were quantitatively combined by random-effects meta-analysis. Four randomized and four nonrandomized studies with 688 total adult patients were included. Treatment effects did not differ significantly between the included randomized and nonrandomized studies. Albumin infusion during the first 24 hours showed no significant overall effect on mortality. However, significant statistical heterogeneity was present, which could be abolished by excluding two studies at high risk of bias. After those exclusions, albumin infusion was associated with reduced mortality. The pooled odds ratio was 0.34 with a 95% confidence interval of 0.19 to 0.58 (P < .001). Albumin administration was also accompanied by decreased occurrence of compartment syndrome (pooled odds ratio, 0.19; 95% confidence interval, 0.07–0.50; P < .001). This meta-analysis suggests that albumin can improve outcomes of burn shock resuscitation. However, the scope and quality of current evidence are limited, and additional trials are needed. PMID:25426807
Yusuf, E; Hügle, T; Daikeler, T; Voide, C; Borens, O; Trampuz, A
Current diagnostic methods in differentiating septic from non-septic arthritis are time-consuming (culture) or have limited sensitivity (Gram stain). Microcalorimetry is a novel method that can rapidly detect microorganisms by their heat production. We investigated the accuracy and time to detection of septic arthritis by using microcalorimetry. Patients older than 18 years of age with acute arthritis of native joints were prospectively included. Synovial fluid was aspirated and investigated by Gram stain, culture and microcalorimetry. The diagnosis of septic arthritis and non-septic arthritis were made by experienced rheumatologists or orthopaedic surgeons. Septic arthritis was diagnosed by considering the finding of acute arthritis together with findings such as positive Gram stain or positive culture of synovial fluid or positive blood culture. The sensitivity and specificity for diagnosing septic arthritis and the time to positivity of microcalorimetry were determined. Of 90 patients (mean age 64 years), nine had septic arthritis, of whom four (44 %) had positive Gram stain, six (67 %) positive synovial fluid culture and four (44 %) had positive blood culture. The sensitivity of microcalorimetry was 89 %, the specificity was 99 % and the mean detection time was 5.0 h (range, 2.2-8.0 h). Microcalorimetry is an accurate and rapid method for the diagnosis of septic arthritis. It has potential to be used in clinical practice in diagnosing septic arthritis.
Allen, W R
Acute infectious arthritis is an uncommon disease that is most commonly caused by Neisseria gonorrhoeae or gram-positive cocci. Gram-negative bacteria are an infrequent and highly virulent cause of septic arthritis and most commonly enter the circulation through the urinary tract, as in this case after ureteroneocystostomy. The resulting arthritis carries a mortality of 25% and a morbidity of 80%. Early recognition and treatment with appropriate antibiotics and mechanical drainage is imperative. Needle drainage of the affected joint has been shown superior to open surgical drainage.
Kim, Won-Young; Baek, Moon Seong; Kim, Young Shin; Seo, Jarim; Huh, Jin Won; Lim, Chae-Man; Koh, Younsuck
Background Glucose-insulin-potassium (GIK) demonstrates a cardioprotective effect by providing metabolic support and anti-inflammatory action, and may be useful in septic myocardial depression. The aim of this study was to examine the relationship between GIK and hemodynamic outcomes in septic shock patients with myocardial depression. Methods Between October 2012 and March 2014, 45 patients in the intensive care unit who fulfilled the criteria for severe sepsis/septic shock and were treated with GIK were recruited. Patients were divided into two groups according to echocardiographic findings: hypodynamic (27%) and non-hypodynamic (36%). Results Baseline vasopressor requirements did not differ between both groups. In 12 patients with hypodynamic septic shock with myocardial depression, mean arterial pressure (MAP) increased with the median [interquartile range (IQR)] area under the curve of 16 (8 to 29) mmHg, and the heart rate (HR) decreased with the median (IQR) area under the curve of −9 (−20 to 2)/min during the first 72 h. The total insulin dose correlated with improvement in MAP (r=0.61, P=0.061) and the cardiovascular Sequential Organ Failure Assessment score (r=−0.64, P=0.045) at 72 h, although this phenomenon was not observed in patients with non-hypodynamic septic shock. Serum glucose and potassium levels were within the target ranges in both groups during the 72-h study period. Conclusions Short-term improvement in hemodynamics correlated with GIK administration in septic shock patients with myocardial depression. The use of GIK was well tolerated in all patients. Further studies are required to demonstrate the role of GIK in septic myocardial dysfunction. PMID:28149560
Schlaudraff, Kai-Uwe; Kiessling, Maren C; Császár, Nikolaus BM; Schmitz, Christoph
Background Extracorporeal shock wave therapy has been successfully introduced for the treatment of cellulite in recent years. However, it is still unknown whether the individual clinical outcome of cellulite treatment with extracorporeal shock wave therapy can be predicted by the patient’s individual cellulite grade at baseline, individual patient age, body mass index (BMI), weight, and/or height. Methods Fourteen Caucasian females with cellulite were enrolled in a prospective, single-center, randomized, open-label Phase II study. The mean (± standard error of the mean) cellulite grade at baseline was 2.5±0.09 and mean BMI was 22.8±1.17. All patients were treated with radial extracorporeal shock waves using the Swiss DolorClast® device (Electro Medical Systems, S.A., Nyon, Switzerland). Patients were treated unilaterally with 2 weekly treatments for 4 weeks on a randomly selected side (left or right), totaling eight treatments on the selected side. Treatment was performed at 3.5–4.0 bar, with 15,000 impulses per session applied at 15 Hz. Impulses were homogeneously distributed over the posterior thigh and buttock area (resulting in 7,500 impulses per area). Treatment success was evaluated after the last treatment and 4 weeks later by clinical examination, photographic documentation, contact thermography, and patient satisfaction questionnaires. Results The mean cellulite grade improved from 2.5±0.09 at baseline to 1.57±0.18 after the last treatment (ie, mean δ-1 was 0.93 cellulite grades) and 1.68±0.16 at follow-up (ie, mean δ-2 was 0.82 cellulite grades). Compared with baseline, no patient’s condition worsened, the treatment was well tolerated, and no unwanted side effects were observed. No statistically significant (ie, P<0.05) correlation was found between individual values for δ-1 and δ-2 and cellulite grade at baseline, BMI, weight, height, or age. Conclusion Radial shock wave therapy is a safe and effective treatment option for cellulite. The
Uemura, Takuya; Yagi, Hirohisa; Okada, Mitsuhiro; Yokoi, Takuya; Shintani, Kosuke; Nakamura, Hiroaki
Acute leukemia in children presents with various clinical manifestations that mimic orthopaedic conditions. The association of septic arthritis of the elbow with acute leukemia is very rare, and the correct diagnosis of acute leukemia is often established only after treatment of the septic arthritis. In this article, we present a three-year-old child patient with elbow septic arthritis related to acute leukemia, diagnosed promptly by bone marrow aspiration on the same day as emergency surgical debridement of the septic elbow joint due to the maintenance of a high index of suspicion, and treated with chemotherapy as soon as possible. The emergency physician and orthopaedist must recognize unusual patterns of presentation like this. Since delay in initiating treatment of septic arthritis may result in growth disturbance, elbow septic arthritis associated with pediatric acute leukemia must be treated promptly and appropriately. Early diagnosis is a good prognostic feature of childhood acute leukemia.
Skuhala, Tomislava; Škerk, Višnja; Markotić, Alemka; Bukovski, Suzana; Desnica, Boško
A 20-year-old female patient, 14 weeks pregnant, was admitted to hospital with anamnestic and clinical features of acute pyelonephritis. Clinical signs of septic abortion developed and after obstetric examination the therapy was changed to ampicillin, gentamicin and clindamycin. Campylobacter jejuni was isolated from blood cultures. Pathohistological findings confirmed diagnosis of purulent chorioamnionitis. After 2 weeks of ciprofloxacin administration the patient fully recovered. Campylobacter jejuni was not isolated from stool culture and no signs of acute enteritis were registered during the illness. Invasive forms of Campylobacter disease without enteritis are not unusual in immunocompromised hosts but they are restricted to C. fetus rather than C. jejuni isolates.
Al-Khalisy, Hassan Mahdi; Nikiforov, Ivan; Mansoora, Qurat; Goldman, John; Cheriyath, Pramil
Septic arthritis of the temporomandibular joint (TMJ) is a rare event that has only been reported a few dozen times worldwide. This case is remarkable for septic arthritis of the TMJ joint in an otherwise healthy male. Case Report: A 24-year-old male presented to the emergency department with periauricular swelling, erythema, fever, myalgia's and generalized joint pain. He had previously sought medical attention and was placed on ciprofloxacin. However, he developed facial swelling and a rash and had to discontinue the antibiotic. On physical exam the patient had a large swelling and tenderness in his left periauricular area, with erythema and deviation of the right mandible which limited his ability to open the mouth. A computed tomography showed mild asymmetric soft tissue swelling in the left pharyngeal region but did not show joint effusion. Subsequent magnetic resonance imaging did show effusion of the joint space. The effusion was drained, and the synovial fluid was submitted for gram stain, culture, and sensitivity. The cultures grew menthicillin sensitive Staphyloccocus Aureus. The patient was discharged to complete a two week course of intravenous (IV) Ceftriaxone and IV Vancomycin via home infusion. Conclusion: Septic Arthritis of the TMJ is a rare event with very specific clinical symptoms. Due to the low sensitivity of the computed tomography scan, magnetic resonance imaging should be considered when computed tomography scan is negative for TMJ effusion. PMID:26713295
Ozcan, Ayse; Kaymak, Cetin; Basar, Hulya; Kotanoglu, Mustafa; Kose, Bektas
Introduction The aim of this study is to compare the prognostic value of N-terminal pro-brain natriuretic peptide (NT-proBNP) levels in septic and non-septic intensive care patients. Material and methods Fifty consecutive patients admitted to the intensive care unit (ICU) were enrolled in either the septic or non-septic group according to the criteria in the International Sepsis Definitions Conference in 2001. Demographic and clinical data, procalcitonin and lactate levels at admission, and death within 28 days were registered. Five blood samples were collected from all patients for NT-proBNP measurements. Results Septic patients had higher APACHE II (19 (16.00–24.25) vs. 16 (13.00–18.25)), and SOFA (8 (5–10) vs. 6 (4–7)) scores (p <0.05). Procalcitonin levels were also higher in septic patients (3.33 (1.06–10.96) vs. 0.46 (0.26–1.01) ng/ml) and more patients required vasopressors in this group (9 (36%) vs. 2 (8%)) (p < 0.05). In the septic group, the correlation between mortality and the level of NT-proBNP was significant for each measurement, starting from the admission. In the non-septic group the correlation between mortality and the level of NT-proBNP was significant only at the 120th h. Conclusions We concluded that the level of NT-proBNP at admission is well correlated with 28-day mortality in septic ICU patients. However, single measurement of NT-proBNP levels in non-septic patients does not correlate with the 28-day mortality. Repeated measurements and an increasing trend of the NT-proBNP levels may show a correlation with mortality in non-septic intensive care patients. PMID:28261297
Petrikaitė, Vilma; Matulis, Daumantas
This review describes the recent progress in the field of heat shock protein 90 (Hsp90) inhibitor design. Hsp90 is a heat shock protein with a molecular weight of approximately 90 kDa. Hsp90 is considered a good anticancer target because its inhibition leads to inactivation of its numerous client proteins participating in various signaling and other processes involved in cancer progression. Numerous Hsp90 inhibitors-leads currently tested in clinical trials are presented in this review. Furthermore, this review emphasizes the application of biophysical binding assays in the development of Hsp90 inhibitors. The binding of designed lead compounds to various Hsp90 constructs is measured by isothermal titration calorimetry and thermal shift assay. These assays provide a detailed energetic insight of the binding reaction, including the enthalpy, entropy, heat capacity, and the Gibbs free energy. A detailed description of the binding energetics helps to extend our knowledge of structure-activity relationships in the design of more potent inhibitors. The most active compounds are then tested for their absorption, distribution, metabolism, elimination, toxicity, and activity against cancer cell lines.
Barr, J; Danielsson, D
The overall incidence in gonorrhoea of septic gonococcal dermatitis was found to be 1.9% (3% for the females and 0.7% for the males). In 23 patients the common presenting symptoms were arthritis or arthralgia and bouts of fever, but the characteristic skin lesions served as an early clue to the diagnosis, and Neisseria gonorrhoeae was isolated from the genitourinary tract or from the blood. With the use of immunofluorescent techniques gonococci were also found in smears prepared from the skin lesions. An immune response to gonococci was found with the complement fixation technique in 90% of the patients. The response to treatment with penicillin was prompt, with complete relief from joint pains and fever, usually within two to seven days. The skin lesions faded within a few days, but scars could be observed for up to four weeks.
Higashi, Hiroki; Kanki, Akihiko; Watanabe, Shigeru; Yamamoto, Akira; Noda, Yasufumi; Yasokawa, Kazuya; Higaki, Atsushi; Tamada, Tsutomu; Ito, Katsuyoshi
Hypovolemic shock is often seen in patients with severe blunt trauma who have suffered from blood circulation inadequate to maintain oxygen delivery to multiple organs. The early recognition and prompt management of hypovolemic shock in patients with multiple injuries are mandatory to improving prognosis and patient conditions. The diagnostic accuracy of computed tomography (CT) as a primary diagnostic tool is well established. The abdominal organs show several common and classic appearances on contrast-enhanced CT in patients with trauma. The hypovolemic shock complex is reported in the previous literature as decreased enhancement of the viscera, increased mucosal enhancement and luminal dilation of the small bowel, mural thickening and fluid-filled loops of the small bowel, the halo sign and flattening of the inferior vena cava, reduced aortic diameter, and peripancreatic edema. However, there have been controversial CT reports with contradictory appearances. Physicians understanding these findings could prompt alternative approaches to the early assessment and management of hypovolemic shock. The aim of this article is to illustrate common and well-known abdominal CT features in patients with traumatic hypovolemic shock, to discuss controversial CT signs in the pancreas and adrenal gland, and to describe CT findings' clinical implications when managing hypovolemic shock.
Sakiniene, E; Bremell, T; Tarkowski, A
The aim of the study was to assess the role of the complement system in Staphylococcus aureus arthritis and septicaemia. The murine model of haematogenously acquired septic arthritis was used, injecting intravenously toxic shock syndrome toxin-1 (TSST-1), producing S. aureus LS-1. Complement was depleted using cobra venom factor (CVF). Evaluation of arthritis was performed clinically and histopathologically. In addition, the effect of complement depletion on the phagocytic activity of leucocytes was assessed in vivo and in vitro. Six days after inoculation of S. aureus the prevalence of arthritis in decomplemented mice was three-fold higher than that in controls (91% versus 25%). The clinical severity of arthritis at the end of the experiment, expressed as arthritic index, was 7.3 and 1.9, respectively. These findings were confirmed by histological index of synovitis as well as of cartilage and/or bone destruction being significantly higher in decomplemented mice than in controls (9.8 ± 1.7 versus 4.9 ± 1.2, P < 0.05; and 7.9 ± 1.7 versus 3.0 ± 0.9, P < 0.05, respectively). Also, the septicaemia-induced mortality was clearly higher in decomplemented mice compared with the controls. CVF treatment significantly reduced in vivo polymorphonuclear cell-dependent inflammation induced by subcutaneous injection of olive oil and mirroring the capacity of polymorphonuclear cells (PMNC) to migrate and/or extravasate. Besides, the decomplementation procedure significantly impaired phagocytic activity of peripheral blood leucocytes in vitro, since the number of phagocytes being able to ingest bacteria decreased by 50% when the cells were maintained in decomplemented serum compared with those in intact serum. The conclusion is that complement depletion aggravates the clinical course of S. aureus arthritis and septicaemia, possibly by a combination of decreased migration/extravasation of PMNC and an impairment of phagocytosis. PMID:9933426
Riera, Jaume; Conesa, Xavier; Pisa, Jose; Moreno, Josefa; Siles, Eduard; Novell, Josep
The incidence of infection by Mycobacterium marinum is rising, mainly due to the increasing popularity of home aquariums. The infection typically manifests as skin lesions, with septic arthritis being a rare presentation form. The disease is difficult to diagnose even when there is a high clinical suspicion, as culture in specific media may not yield positive findings. Thus, establishment of appropriate treatment is often delayed. Synovectomy, capsular thinning, and joint drainage together with prolonged, combined antibiotic therapy may be needed to cure the infection.
Tuite, P K
Shock continues to be a challenge for health care professionals because shock is not a single pathologic process but a complex series of interrelated events. After respiratory failure, shock is the second most common cause of death in children. The etiology of shock can be classified into three major categories: hypovolemic, cardiogenic, and distributive shock (septic shock). Despite the etiology of the shock state, if left untreated, the overwhelming response of the body to the inadequate perfusion is death. The key to successful management and treatment of shock is early recognition and rapid intervention.
Wynes, Jacob; Harris, William; Hadfield, Robert A; Malay, D Scot
The clinical presentation of a monoarticular, red, hot, and swollen joint has many possible diagnoses, including septic arthritis, which is 1 of the most devastating. The morbidity associated with this pathologic process involves permanent joint damage and the potential for progression to systemic illness and, even, mortality. The common risk factors for joint sepsis include a history of rheumatoid arthritis, previous joint surgery, joint prosthesis, intravenous drug abuse, alcoholism, diabetes, previous intra-articular steroid use, and cutaneous ulceration. The diagnosis is primarily determined from the culture results after arthrocentesis and correlation with direct visualization, imaging, and various serologies, including synovial analysis. In the present report, a case of an insidious presentation of subtalar joint septic arthritis and its association with a unique patient presentation concomitant with primary immunodeficiency and culture-proven Myocplasma hominis infection is discussed. Septic arthritis has a predilection for the lower extremities and typically is isolated to the hip or knee, with less common involvement of the ankle or metatarsophalangeal joints. Owing to the uncommon nature of primary immunodeficiency disorders and the paucity of studies discussing their association with septic arthridites, we aimed to raise awareness of subtalar joint septic arthritis and to provide a brief overview of the pathogenesis as it presented in a 33-year-old male with X-linked hypogammaglobulinemia/agammaglobulinema.
Gruartmoner, G; Mesquida, J; Ince, C
Microcirculatory alterations play a pivotal role in sepsis-related morbidity and mortality. However, since the microcirculation has been a "black box", current hemodynamic management of septic patients is still guided by macrocirculatory parameters. In the last decades, the development of several technologies has shed some light on microcirculatory evaluation and monitoring, and the possibility of incorporating microcirculatory variables to clinical practice no longer seems to be beyond reach. The present review provides a brief summary of the current technologies for microcirculatory evaluation, and attempts to explore the potential role and benefits of their integration to the resuscitation process in critically ill septic patients.
Faraj, A A; Omonbude, O D; Godwin, P
This study aimed at determining the sensitivity and specificity of Gram staining of synovial fluid as a diagnostic tool in acute septic arthritis. A retrospective study was made of 22 patients who had arthroscopic lavage following a provisional diagnosis of acute septic arthritis of the knee joint. Gram stains and cultures of the knee aspirates were compared with the clinical and laboratory parameters, to evaluate their usefulness in diagnosing acute arthritis. All patients who had septic arthritis had pain, swelling and limitation of movement. CRP was elevated in 90% of patients. The incidence of elevated white blood cell count was higher in the group of patients with a positive Gram stain study (60%) as compared to patients with a negative Gram stain study (33%). Gram staining sensitivity was 45%. Its specificity was however 100%. Gram staining is an unreliable tool in early decision making in patients requiring urgent surgical drainage and washout.
Davis, J M; Peel, M M
The clinical and bacteriological findings in two cases of osteomyelitis and one case of septic arthritis caused by Kingella kingae are presented. This appears to be the first report providing clear evidence for a pathogenic role for this species in bone and joint infections.
Fukada, Tomoko; Kato, Hidehito; Ozaki, Makoto; Yagi, Junji
Sepsis is a serious condition related to systemic inflammation, organ dysfunction, and organ failure. It is a subset of the cytokine storm caused by dysregulation of cytokine production. Morphine influences the severity of infection in vivo and in vitro because it regulates cytokine production. We investigated the immunological function of morphine using a mouse model of septic shock. We treated mice with α-galactosylceramide (2 μg/mouse) to induce lethal endotoxic shock following a challenge with lipopolysaccharide (LPS, 1.5 μg/mouse). This model represents acute lung injury and respiratory failure, and reflects the clinical features of severe septic shock. We evaluated the effect of the timing of morphine (0.8 mg/mouse) administration on the survival rate, cytokine production in vivo, and histological changes of mice with LPS-mediated lethal endotoxic shock. Morphine treatment before LPS challenge suppressed lethal endotoxic shock. In contrast, when we administered after LPS, morphine exacerbated lethal endotoxic shock; hematoxylin and eosin staining revealed a marked increase in the accumulation of infiltrates comprising polymorphonuclear leukocytes and mononuclear cells in the lung; and Elastica van Gieson staining revealed the destruction of alveoli. The plasma levels of tumor necrosis factor-α, interferon-γ, monocyte-chemotactic protein-1, and interleukin-12 in the group treated with morphine after LPS challenge were higher than those treated with morphine before LPS challenge. In conclusion, one of the factors that determine whether morphine exacerbates or inhibits infection is the timing of its administration. Morphine treatment before shock improved the survival rate, and morphine treatment after shock decreased the rate of survival.
Ross, John J
Septic arthritis is a rheumatologic emergency that may lead to disability or death. Prompt evacuation of the joint, either by arthrocentesis at the bedside, open or arthroscopic drainage in the operating room, or imaging-guided drainage in the radiology suite, is mandatory. Methicillin-resistant Staphylococcus aureus (MRSA) has become a major cause of septic arthritis in the United States. MRSA joint infection seems to be associated with worse outcomes. Antibiotic courses of 3 to 4 weeks in duration are usually adequate for uncomplicated bacterial arthritis. Treatment duration should be extended to 6 weeks if there is imaging evidence of accompanying osteomyelitis.
Gündüz, Rukiye; Malas, Fevziye Ünsal; Borman, Pınar; Kocaoğlu, Seher; Özçakar, Levent
The aim of this study was to compare--clinically and ultrasonographically--the therapeutic effects of physical therapy modalities (hot pack, ultrasound therapy, and friction massage), local corticosteroid injection, and extracorporeal shock wave treatment (ESWT) in lateral epicondylitis (LE). Fifty-nine elbows of 59 patients with LE were randomized into three treatment groups receiving either physical therapy, a single corticosteroid injection, or ESWT. Visual analogue scale (VAS) was used to assess pain intensity, Jamar hydraulic dynamometer for grip strength, finger dynamometer for pinch strength (before treatment, on the first, third, and sixth months of treatment). All subjects were also evaluated with ultrasonography before and 6 months after treatment. In all groups, VAS scores of the patients were found to decrease significantly on the first, third, and sixth months of treatment. With respect to grip strength evaluations, the increase after treatment was significant only on the first month in group II; on the first and third months in group I; and on the first, third, and sixth months of treatment in group III. Pinch strength and ultrasonographical findings did not change during follow-up in any group. We imply that physical therapy modalities, corticosteroid injection, and ESWT have favorable effects on pain and grip strength in the early period of LE treatment. The increase in grip strength lasts longer with ESWT. On the other hand, ultrasonographic findings do not change in the first six months of these treatment methods.
Beccati, Francesca; Gialletti, Rodolfo; Passamonti, Fabrizio; Nannarone, Sara; Di Meo, Antonio; Pepe, Marco
Septic arthritis/tenosynovitis in the horse can have life-threatening consequences. The purpose of this cross-sectional retrospective study was to describe ultrasound characteristics of septic arthritis/tenosynovitis in a group of horses. Diagnosis of septic arthritis/tenosynovitis was based on historical and clinical findings as well as the results of the synovial fluid analysis and/or positive synovial culture. Ultrasonographic findings recorded were degree of joint/sheath effusion, degree of synovial membrane thickening, echogenicity of the synovial fluid, and presence of hyperechogenic spots and fibrinous loculations. Ultrasonographic findings were tested for dependence on the cause of sepsis, time between admission and beginning of clinical signs, and the white blood cell counts in the synovial fluid. Thirty-eight horses with confirmed septic arthritis/tenosynovitis of 43 joints/sheaths were included. Degree of effusion was marked in 81.4% of cases, mild in 16.3%, and absent in 2.3%. Synovial thickening was mild in 30.9% of cases and moderate/severe in 69.1%. Synovial fluid was anechogenic in 45.2% of cases and echogenic in 54.8%. Hyperechogenic spots were identified in 32.5% of structures and fibrinous loculations in 64.3%. Relationships between the degree of synovial effusion, degree of the synovial thickening, presence of fibrinous loculations, and the time between admission and beginning of clinical signs were identified, as well as between the presence of fibrinous loculations and the cause of sepsis (P ≤ 0.05). Findings indicated that ultrasonographic findings of septic arthritis/tenosynovitis may vary in horses, and may be influenced by time between admission and beginning of clinical signs.
Hausdorf, Joerg; Jansson, Volkmar; Maier, Markus; Delius, Michael
The molecular events following shock wave treatment of bone are widely unknown. Nevertheless patients with osteonecrosis and non unions are already treated partly successful with shock waves. Concerning the first indication, the question of the permeation of the shock wave into the bone was addressed. Therefore shockwaves were applied to porcine femoral heads and the intraosseous pressure was measured. A linear correlation of the pressure to the intraosseous distance was found. Approximately 50% of the pressure are still measurable 10 mm inside the femoral head. These findings should encourage continued shock wave research on this indication. Concerning the second indication (non union), osteoblasts were subjected to 250 or 500 shock waves at 25 kV. After 24, 48, and 72 h the levels of the bone and vascular growth factors bFGF, TGFbeta1, and VEGF were examined. After 24 h there was a significant increase in bFGF levels (p<0.05) with significant correlation (p<0.05) to the number of impulses. TGFbeta1, and VEGF showed no significant changes. This may be one piece in the cascade of new bone formation following shock wave treatment and may lead to a more specific application of shock waves in orthopedic surgery.
Shah, N S; Billiar, T R
Since the discovery that nitric oxide (.NO) accounts for the biologic activity of endothelial-derived relaxing factor, a torrent of research over the last decade has focused on its role, protective or detrimental, in myriad pathophysiologic conditions. Recently, increasing attention has focused on .NO as a possible mediator of the severe hypotension and impaired vasoreactivity characteristic of circulatory failure. Given the ubiquitous and complex role of .NO in biologic systems, inhibition of .NO synthesis in experimental and clinical studies of shock has yielded mixed, sometimes contradictory, results. Although overproduction of .NO in the vasculature may result in systemic vasodilation, .NO synthesis has also clearly been shown to have a beneficial role in regulating organ perfusion and mediating cytotoxicity. In this review, the pathophysiologic importance of .NO in septic shock and hemorrhagic shock is discussed, and novel therapeutic strategies for manipulation of .NO formation are examined. PMID:9788888
Adams, H A
Hypovolemic shock is not a form of disease and can be subdivided into four special types with varying therapeutic demands. The decisive approach in the therapy of hypovolemic shock is to initially attain normovolemia by rapid administration of volume replacement agents in the sense of controlled hemodilution. This allows an adequate increase in the cardiac output resulting in delivery of sufficient oxygen to tissues. In the following article the limits of intervention will be described and the advantages and disadvantages of these measures for patients suffering from hypovolemic shock will be critically considered.
Sherwin, Catherine M T; Ding, Lili; Kaplan, Jennifer; Spigarelli, Michael G; Vinks, Alexander A
The objective was to demonstrate the methodology and process of optimal sparse sampling pharmacokinetics (PK). This utilized a single daily dose of pioglitazone for pediatric patients with severe sepsis and septic shock based upon adult and minimal adolescent data. Pioglitazone pharmacokinetics were modeled using non-compartment analysis WinNonlin Pro (version 5.1) and population kinetics using NONMEM (version 7.1) with first order conditional estimation method (FOCE) with interaction. The initial model was generated from single- and multiple-dose pioglitazone PK data (15 mg, 30 mg, and 45 mg) in 36 adolescents with diabetes. PK models were simulated and overlaid upon original data to provide a comparison best described by a single compartment, first order model. The optimal design was based on the simulated oral administration of pioglitazone to three groups of pediatric patients, age 3.8 (2-6 years), weight 14.4 (7-28 kg); age 9.6 (6.1-11.9 years), weight 36.5 (28.1-48 kg) and age 15.5 (12-17 years,) weight 61.6 (48.1-80 kg). PFIM (version 3.2) was used to evaluate sample study size. Datasets were compiled using simulation for each dose (15, 30 and 45 mg) for the potential age/weight groups. A target dose of 15 mg daily in the youngest and middle groups was considered appropriate with area under the curve exposure levels (AUC) comparable to studies in adolescents. The final optimal design suggested time points of 0.5, 2, 6 and 21 h for 24 h dosing. This methodology provides a robust method of utilizing adult and limited adolescent data to simulate allometrically scaled, pediatric data sets that allow the optimal design of a pediatric trial. The pharmacokinetics of pioglitazone were described adequately and simulated data estimates were comparable to literature values. The optimal design provided clinically attainable sample times and windows.
Fatima, Farah; Fei, Ying; Ali, Abukar; Mohammad, Majd; Erlandsson, Malin C.; Bokarewa, Maria I.; Nawaz, Muhammad; Valadi, Hadi; Na, Manli
Background Permanent joint dysfunction due to bone destruction occurs in up to 50% of patients with septic arthritis. Recently, imaging technologies such as micro computed tomography (μCT) scan have been widely used for preclinical models of autoimmune joint disorders. However, the radiological features of septic arthritis in mice are still largely unknown. Methods NMRI mice were intravenously or intra-articularly inoculated with S. aureus Newman or LS-1 strain. The radiological and clinical signs of septic arthritis were followed for 10 days using μCT. We assessed the correlations between joint radiological changes and clinical signs, histological changes, and serum levels of cytokines. Results On days 5–7 after intravenous infection, bone destruction verified by μCT became evident in most of the infected joints. Radiological signs of bone destruction were dependent on the bacterial dose. The site most commonly affected by septic arthritis was the distal femur in knees. The bone destruction detected by μCT was positively correlated with histological changes in both local and hematogenous septic arthritis. The serum levels of IL-6 were significantly correlated with the severity of joint destruction. Conclusion μCT is a sensitive method for monitoring disease progression and determining the severity of bone destruction in a mouse model of septic arthritis. IL-6 may be used as a biomarker for bone destruction in septic arthritis. PMID:28152087
Protection against septic shock and suppression of tumor necrosis factor alpha and nitric oxide production on macrophages and microglia by a standard aqueous extract of Mangifera indica L. (VIMANG). Role of mangiferin isolated from the extract.
Garrido, Gabino; Delgado, René; Lemus, Yeny; Rodríguez, Janet; García, Dagmar; Núñez-Sellés, Alberto J
The present study illustrates the effects of a standard aqueous extract, used in Cuba under the brand name of VIMANG, from the stem bark of Mangifera indica L. on the production of tumor necrosis factor alpha (TNFalpha) and nitric oxide (NO) in in vivo and in vitro experiments. In vivo was determined by the action of the extract and its purified glucosylxanthone (mangiferin) on TNFalpha in a murine model of endotoxic shock using Balb/c mice pre-treated with lipopolysaccharide (LPS) 0.125 mg kg(-1), i.p. In vitro, M. indica extract and mangiferin were tested on TNFalpha and NO production in activated macrophages (RAW264.7 cell line) and microglia (N9 cell line) stimulated with LPS (10ng ml(-1)) and interferon gamma (IFNgamma, 2U ml(-1)). M. indica extract reduced dose-dependently TNFalpha production in the serum (ED50 = 64.5 mg kg(-1)) and the TNFalpha mRNA expression in the lungs and livers of mice. Mangiferin also inhibited systemic TNFalpha at 20 mg kg(-1). In RAW264.7, the extract inhibited TNFalpha (IC50 = 94.1 microg ml(-1)) and NO (IC50 = 64.4 microg ml(-1)). In microglia the inhibitions of the extract were IC50 = 76.0 microg ml(-1) (TNFalpha) and 84.0 microg ml(-1) (NO). These findings suggest that the anti-inflammatory response observed during treatment with M. indica extract must be related with inhibition of TNFalpha and NO production. Mangiferin, a main component in the extract, is involved in these effects. The TNFalpha and NO inhibitions by M. indica extract and mangiferin on endotoxic shock and microglia are reported here for the first time.
Lardo, Soroy; Ariane, Anna; Chen, Khie
Septic Pulmonary embolism is a rare condition where there were numerous pulmonary infarcts resulting from blood clot emboli that also contains microorganism. This disorder is insidious onset, Its clinical features usually unspecific and the diagnosis usually difficult to establish. A 43 old woman who underwent an appendicitis surgery, reentered the hospital at the sixth day after surgery presented with fever, pain at the surgical site, progressive severe dyspnea and chest tightness. From the physical examination finding there were tachycardia, tachypneu, wet rough basal rhonki on the right rear and tenderness at right lower region of the abdomen. The thorax-abdomen CT scan result was pleuropneumonial with minimal effusion in the right side. A CT angiography scan of the chest and abdomen showed intralumen emboli in medial lobe segmen of right pulmonary artery, right pleuropneumonia with segmental lession in segmen 10 right lobe and inflammation process along right lateral wall of the abdomen. Laboratory results that also supported diagnosis were D dimer 3442 ng/mL and culture result from surgical site pus showed E. Coli ESBL (+). Base on these findings, this case was established as a septic pulmonary embolism.
Sintek, Marc A.; Gdowski, Mark; Lindman, Brian R.; Nassif, Michael; Lavine, Kory J.; Novak, Eric; Bach, Richard G.; Silvestry, Scott C.; Mann, Douglas L.; Joseph, Susan M.
Objective To characterize the clinical response and identify predictors of clinical stabilization after intra-aortic balloon counterpulsation (IABP) support in patients with chronic systolic heart failure in cardiogenic shock prior to implantation of a left ventricular assist device (LVAD). Background Limited data exist regarding the clinical response to IABP in patients with chronic heart failure in cardiogenic shock. Methods We identified 54 patients supported with IABP prior to LVAD implantation. Criteria for clinical decompensation after IABP insertion and before LVAD included the need for more advanced temporary support, initiation of mechanical ventilation or dialysis, increase in vasopressors/inotropes, refractory ventricular arrhythmias, or worsening acidosis. The absence of these indicated stabilization. Results Clinical decompensation after IABP occurred in 23 (43%) patients. Both patients who decompensated and those who stabilized had similar hemodynamic improvements after IABP support but patients who decompensated required more vasopressors/inotropes. Clinical decompensation after IABP was associated with worse outcomes after LVAD implantation, including a 3-fold longer intensive care unit stay and 5-fold longer time on mechanical ventilation (p<0.01 for both). While baseline characteristics were similar between groups, right and left ventricular cardiac power indices (Cardiac power Index= Cardiac Index × Mean arterial pressure / 451)identified patients who were likely to stabilize (AUC=0.82). Conclusions Among patients with chronic systolic heart failure who develop cardiogenic shock, more than half of patients stabilized with IABP support as a bridge to LVAD. Baseline measures of right and left ventricular cardiac power, both measures of work performed for a given flow and pressure, may allow clinicians to identify patients with sufficient contractile reserve who will be likely to stabilize with an IABP versus those who may need more aggressive
Chang, Enting; Lee, Kuo-Hsien; Yang, Kuang-Yao; Lee, Yu-Chin; Perng, Reury-Perng
Septic pulmonary embolism is an uncommon disease in which septic thrombi are mobilised from an infectious nidus and transported in the vascular system of the lungs. It is usually associated with tricuspid valve vegetation, septic thrombophlebitis or infected venous catheters. We report an immunocompetent young man who presented with fever and pleuritic chest pain. Chest roentgenography and CT showed multiple ill-defined nodules, with central cavitation and feeding vessels. He was found to have a clinically infectious source of methicillin-resistant staphylococcus aureus (MRSA) cultured from the peri-proctal abscess with the same bacteraemia. Pulmonary septic embolism from peri-proctal abscess was diagnosed by image study and bacterial culture correlation. All of the clinical presentations improved after the incision of the peri-proctal abscess and anti-MRSA antibiotics treatment.
Tuff, Taylor; Chrobak, Karen
Septic bursitis (SB) is an important differential diagnosis in athletes presenting with an acute subcutaneous swelling of the elbow or knee. Prompt recognition is essential to minimize recovery time and prevent the spread of infection. Due to the significant overlap in clinical features, it is often difficult to differentiate SB from non-septic bursitis (NSB) without bursal aspirate analysis. SB is commonly not considered unless the bursitis is accompanied by a local skin lesion or fever. This study describes two cases of septic olecranon bursitis and one case of septic prepatellar bursitis in adult hockey players presenting to a sports medicine clinic. None of the cases presented with an observable skin lesion and only one case developed a fever. It is therefore essential that clinicians maintain a high index of suspicion and monitor for signs of progression when presented with an acute bursitis even in the absence of these features. PMID:28065991
Tuff, Taylor; Chrobak, Karen
Septic bursitis (SB) is an important differential diagnosis in athletes presenting with an acute subcutaneous swelling of the elbow or knee. Prompt recognition is essential to minimize recovery time and prevent the spread of infection. Due to the significant overlap in clinical features, it is often difficult to differentiate SB from non-septic bursitis (NSB) without bursal aspirate analysis. SB is commonly not considered unless the bursitis is accompanied by a local skin lesion or fever. This study describes two cases of septic olecranon bursitis and one case of septic prepatellar bursitis in adult hockey players presenting to a sports medicine clinic. None of the cases presented with an observable skin lesion and only one case developed a fever. It is therefore essential that clinicians maintain a high index of suspicion and monitor for signs of progression when presented with an acute bursitis even in the absence of these features.
Kasch, Richard; Merk, Sebastian; Assmann, Grit; Lahm, Andreas; Napp, Matthias; Merk, Harry; Flessa, Steffen
Background The most common intermediate and long-term complications of total knee arthroplasty (TKA) include aseptic and septic failure of prosthetic joints. These complications cause suffering, and their management is expensive. In the future the number of revision TKA will increase, which involves a greater financial burden. Little concrete data about direct costs for aseptic and two-stage septic knee revisions with an in depth-analysis of septic explantation and implantation is available. Questions/Purposes A retrospective consecutive analysis of the major partial costs involved in revision TKA for aseptic and septic failure was undertaken to compare 1) demographic and clinical characteristics, and 2) variable direct costs (from a hospital department’s perspective) between patients who underwent single-stage aseptic and two-stage septic revision of TKA in a hospital providing maximum care. We separately analyze the explantation and implantation procedures in septic revision cases and identify the major cost drivers of knee revision operations. Methods A total of 106 consecutive patients (71 aseptic and 35 septic) was included. All direct costs of diagnosis, surgery, and treatment from the hospital department’s perspective were calculated as real purchase prices. Personnel involvement was calculated in units of minutes. Results Aseptic versus septic revisions differed significantly in terms of length of hospital stay (15.2 vs. 39.9 days), number of reported secondary diagnoses (6.3 vs. 9.8) and incision-suture time (108.3 min vs. 193.2 min). The management of septic revision TKA was significantly more expensive than that of aseptic failure ($12,223.79 vs. $6,749.43) (p <.001). On the level of the separate hospitalizations the mean direct costs of explantation stage ($4,540.46) were lower than aseptic revision TKA ($6,749.43) which were again lower than those of the septic implantation stage ($7,683.33). All mean costs of stays were not comparable as they
Yalcin, E; Keskin Akca, A; Selcuk, B; Kurtaran, A; Akyuz, M
Plantar heel pain, a chronic and disabling foot alignment, occurs in the adult population. Extracorporal shock wave therapy (ESWT) offers a nonsurgical option in addition to stretching exercises, heel cups, NSAI, and corticosteroid injections. This study aimed to investigate the effects of ESWT on calcaneal bone spurs and the correlation between clinical outcomes and radiologic changes. The study involved 108 patients with heel pain and radiologically diagnosed heel spurs. All patients underwent ESWT once a week for 5 weeks at the clinic. Each patient received 2,000 impulses of shock waves, starting with 0.05 mJ/mm2 (1.8 bar) and increasing to 0.4 mJ/mm2 (4.0 bar). Standard radiographies of the affected heels were obtained before and after the therapy. Clinical results demonstrated excellent (no pain) in 66.7% of the cases, good (50% of pain reduced) in 15.7% of the cases, and unsatisfactory (no reduction in pain) in 17.6%. After five ESWT treatments, no patients who received shock wave applications had significant spur reductions, but 19 patients (17.6%) had a decrease in the angle of the spur, 23 patients (21.3%) had a decrease in the dimensions of the spur, and one patient had a broken spur. Therefore, results showed no correlation between clinical outcome and radiologic changes. The present study supports the finding that even with no radiologic change after ESWT therapy, the therapy produces significant effects in reducing patients' complaints about heel spurs.
Bariteau, Jason T; Waryasz, Gregory R; McDonnell, Matthew; Fischer, Staci A; Hayda, Roman A; Born, Christopher T
Management of fungal osteomyelitis and fungal septic arthritis is challenging, especially in the setting of immunodeficiency and conditions that require immunosuppression. Because fungal osteomyelitis and fungal septic arthritis are rare conditions, study of their pathophysiology and treatment has been limited. In the literature, evidence-based treatment is lacking and, historically, outcomes have been poor. The most common offending organisms are Candida and Aspergillus, which are widely distributed in humans and soil. However, some fungal pathogens, such as Histoplasma, Blastomyces, Coccidioides, Cryptococcus, and Sporothrix, have more focal areas of endemicity. Fungal bone and joint infections result from direct inoculation, contiguous infection spread, or hematogenous seeding of organisms. These infections may be difficult to diagnose and eradicate, especially in the setting of total joint arthroplasty. Although there is no clear consensus on treatment, guidelines are available for management of many of these pathogens.
Mays, N.; Challah, S.; Patel, S.; Palfrey, E.; Creeser, R.; Vadera, P.; Burney, P.
STUDY OBJECTIVE: To compare extracorporeal shock wave lithotripsy and percutaneous nephrolithotomy for efficacy in treating renal calculi. DESIGN: Non-randomised multicentre cohort study with 3 month follow up and 13 month data collection period. SETTING: Lithotripter centre in London, tertiary referral hospital, and urological clinics in several secondary and tertiary care centres. PATIENTS: 933 of 1001 patients treated by lithotripsy at the lithotripter centre were compared with 195 treated by nephrolithotomy. Missing patients were due to incomplete collection of data. Age and sex distributions and characteristics of the stones were similar in the two treatment groups. Two patients died in the lithotripsy group. Three month follow up was achieved in about 84% of both groups (783/933 for lithotripsy; 163/195 for nephrolithotomy). INTERVENTIONS: The nephrolithotomy group had surgical nephrolithotomy alone. In the lithotripsy group 83% (774/933) had lithotripsy alone, 11% (103/933) had combined lithotripsy and nephrolithotomy, and 6% (56/933) had lithotripsy plus ureteroscopy. Single and combined lithotripter treatments were analysed as one group and compared with nephrolithotomy. END POINT: Presence of stones three months after treatment. MEASUREMENTS AND MAIN RESULTS: Presence of residual stones was assessed by plain radiography, ultrasonography, or intravenous urography. After adjustment for age and size and position of stone for patients with single stones the likelihood of being free of stones three months after treatment was significantly greater in the nephrolithotomy group than the lithotripsy group (odds ratio 6.6; 95% confidence interval 3.0 to 14.6) and the response was particularly pronounced with staghorn calculi (62% (8/13) v 15% (141/96) patients free of stones after nephrolithotomy and lithotripsy, respectively). OTHER FINDINGS: 19%(146/775) of patients who had had lithotripsy had to be readmitted within three months after treatment compared with 14
Ball, H.L.; Bounds, T.R.
Septic tank effluent pump (STEP) systems are beginning to be recognized as the preferred and most economical method of collecting and transporting partially-treated wastewater to a treatment facility. A conventional septic tank provides pretreatment, removing most settable and floatable solids from the wastewater. Specially designed pumps convey the septic tank effluent under pressure through a network of small diameter plastic piping to a treatment site. Shallow collection lines, following the contours of the terrain, eliminate the need for costly deep excavations. Changes in both vertical and horizontal alignments may be made in the field. The impetus for this rapidly developing technology has come mainly from the western US. Oregon's Department of Environmental Quality, for example, requires engineers to consider STEP systems whenever a new wastewater collection project is contemplated. The success of a STEP system depends primarily on the skill of the engineer in designing and managing the project. Guidelines for designers are discussed and brief descriptions of several successful STEP systems are included.
Host defense and blood coagulation are tightly connected and interacting systems, necessary for the integrity of an organism. Complex mechanisms regulate the intensity of a host response to invading pathogens or other potentially dangerous situations. Under regular conditions, this response is limited in time and located to the site of injury. Sometimes, however, systemic host response is overwhelming and disproportional and causes damage, not cure. Dependent on the genetical predisposition of the host, its current immunocompetence, or the type of injury, the reaction leads to the clinical picture of the different degrees of sepsis. Septic organ dysfunction is caused by intravascular fibrin deposition as a result of coagulation activation, anticoagulant breakdown, and shut down of fibrinolysis. This article describes the major pathophysiologic reactions in these situations and presents www.SepDIC.eu, an online tool on sepsis and associated coagulopathy.
The exact cellular and molecular mechanisms of sepsis-induced encephalopathy remain elusive. The breakdown of the blood-brain barrier (BBB) is considered a focal point in the development of sepsis-induced brain damage. Contributing factors for the compromise of the BBB include cytokines and chemokines, activation of the complement cascade, phagocyte-derived toxic mediators, and bacterial products. To date, we are far from fully understanding the neuropathology that develops as a secondary remote organ injury as a consequence of sepsis. However, recent studies suggest that bacterial proteins may readily cross the functional BBB and trigger an inflammatory response in the subarachnoid space, in absence of a bacterial invasion. A better understanding of the pathophysiological events leading to septic encephalopathy appears crucial to advance the clinical care for this vulnerable patient population. PMID:20565858
Wang, Dingyuan Alvin; Tambyah, Paul Anantharajah
Septic arthritis has long been considered an orthopedic emergency. Historically, Neisseria gonorrhoeae and Staphylococcus aureus have been the most common causes of septic arthritis worldwide but in the modern era of biological therapy and extensive use of prosthetic joint replacements, the spectrum of microbiological causes of septic arthritis has widened considerably. There are also new approaches to diagnosis but therapy remains a challenge, with a need for careful consideration of a combined medical and surgical approach in most cases.
Balthazar, E.J.; Hilton, S.; Naidich, D.; Megibow, A.; Levine, R.
Splenic and perisplenic pathology, demonstrated by CT examination in 14 septic patients, was correlated with the clinical course and with surgical and pathologic findings available. Twelve patients were intravenous drug addicts and two patients developed bacteremia associated with bacterial endocarditis. The CT fingings were divided into three groups: (1) Single wedge-shaped peripherally located defects were seen in five patients; there was good response to medical therapy without other complications. (2) Larger and/or multiple, rounded or oval lesions were present in five patients; two of these patients had splenic abscesses proven on subsequent splenectomy. (3) Multiple splenic lesions and fissures associated with perisplenic and subphrenic fluid collections were seen in four patients; infected splenic infarcts, splenic fractures, and infected perisplenic hemorrhagic fluid collections were found in this group of patients. The CT examination in septic patients can reliably demonstrate splenic and perisplenic pathology, and its appearance contributes greatly to the overall clinical assessment and surgical approach.
McLean, Anthony S
Echocardiography is pivotal in the diagnosis and management of the shocked patient. Important characteristics in the setting of shock are that it is non-invasive and can be rapidly applied.In the acute situation a basic study often yields immediate results allowing for the initiation of therapy, while a follow-up advanced study brings the advantage of further refining the diagnosis and providing an in-depth hemodynamic assessment. Competency in basic critical care echocardiography is now regarded as a mandatory part of critical care training with clear guidelines available. The majority of pathologies found in shocked patients are readily identified using basic level 2D and M-mode echocardiography. A more comprehensive diagnosis can be achieved with advanced levels of competency, for which practice guidelines are also now available. Hemodynamic evaluation and ongoing monitoring are possible with advanced levels of competency, which includes the use of colour Doppler, spectral Doppler, and tissue Doppler imaging and occasionally the use of more recent technological advances such as 3D or speckled tracking.The four core types of shock-cardiogenic, hypovolemic, obstructive, and vasoplegic-can readily be identified by echocardiography. Even within each of the main headings contained in the shock classification, a variety of pathologies may be the cause and echocardiography will differentiate which of these is responsible. Increasingly, as a result of more complex and elderly patients, the shock may be multifactorial, such as a combination of cardiogenic and septic shock or hypovolemia and ventricular outflow obstruction.The diagnostic benefit of echocardiography in the shocked patient is obvious. The increasing prevalence of critical care physicians experienced in advanced techniques means echocardiography often supplants the need for more invasive hemodynamic assessment and monitoring in shock.
Togawa, Atsushi; Toh, Hiromi; Onozawa, Kyoko; Yoshimura, Michinobu; Tokushige, Chiemi; Shimono, Nobuyuki; Takata, Tohru; Tamura, Kazuo
Ninety-four episodes of Klebsiella pneumoniae bloodstream infection were identified at a university hospital in Japan. After excluding extended-spectrum beta lactamase-producing strains, 83 blood isolates from these patients were assayed in terms of their bacterial phenotypes such as the mucoid and hypermucoviscosity phenotypes. Bacterial phenotypes were correlated with the patients' clinical manifestations. The hypermucoviscosity phenotype was significantly associated with septic shock at the onset of infections (odds ratio, 15.92; 95% confidence interval, 1.27-468.12), but was not associated with liver abscess formation. Mortality was determined by the presence of septic shock. RmpA gene was associated with the induction of the hypermucoviscosity phenotype. These results reveal unique roles of bacterial phenotypes on the patient's clinical condition in K. pneumoniae bacteremia.
Zhu, Zaihua; Kang, Yuli; Lin, Zhenlang; Huang, Yanjing; Lv, Huoyang; Li, Yasong
X-linked agammaglobulinemia (XLA) is a primary immunodeficiency disease caused by mutations in the Bruton's tyrosine kinase (BTK) gene. XLA can also present in combination with juvenile idiopathic arthritis (JIA), the major chronic rheumatologic disease in children. We report herein the first known case of a juvenile patient diagnosed with XLA combined with JIA that later developed into invasive Klebsiella pneumoniae polyarticular septic polyarthritis. An additional comprehensive review of XLA combined with JIA and invasive K. pneumoniae septic arthritis is also presented. XLA was identified by the detection of BTK mutations while the diagnosis of JIA was established by clinical and laboratory assessments. Septic arthritis caused by invasive K. pneumoniae was confirmed by culturing of the synovia and gene detection of the isolates. Invasive K. pneumoniae infections can not only result in liver abscesses but also septic arthritis, although this is rare. XLA combined with JIA may contribute to invasive K. pneumoniae infection.
TRAUMATIC HEMORRHAGIC SHOCK CLINICAL TRIALS Edward P. Sloan,* Nora B. Philbin/ Max D. Koenigsberg,* Weihua Gao,§ and DCLHb Traumatic Hemorrhagic...hemorrhagic shock patients included two parallel Address reprint requests to Edward P. Sloan. MD, MPH, Department of Emergency Medicine, University of...human hemoglobin. Crit Care Med 28:2283-2292, 2000. 52. Cheng DC, Mazer CD, Martineau R, Ralph- Edwards A, Karski J, Robblee J, Finegan B, Hall RI
Hassouna, Mohamed E.; Oraby, Samir; Sameh, Wael; El-Abbady, Ahmed
Purpose To assess the effectiveness of a lithotripter (Modularis Vario; Siemens, AG Healthcare, Munich, Germany) in the management of renal and ureteric stones. Patients and methods In all, 1146 adult patients with renal or ureteric stones were treated at one urological centre using the latest model of the Modularis Vario lithotripter. The effectiveness of lithotripsy and re-treatment rate were assessed. Data were obtained on stone location, stone size, shock wave usage, success rate, and complications. Results Between May 2007 and November 2009, 698 patients with renal stones and 448 with ureteric stones underwent extracorporeal shock-wave lithotripsy (ESWL). The mean (SD) renal stone size was 12.8 (3.8) mm; a mean of 1.36 sessions was required, with a mean (SD) number of 3744 (1961) shocks delivered per renal stone. After 3 months, the success rate defined as the patient being stone-free or with residual fragments of <4 mm; for renal stones the rate was 91.1%, with a 6.9% complication rate in the form of steinstrasse and severe renal colic. The mean (SD) ureteric stone size was 10.4 (2.7) mm. A mean of 1.37 sessions was required, with a mean (SD) of 4551 (2467) shocks delivered for each ureteric stone. The success rate for ureteric stones was 89.5%, with a 5.6% complication rate. The overall efficiency quotient was 0.66. Conclusion The Siemens Modularis Vario lithotripter is a safe and effective machine for treating renal and ureteric stones. PMID:26579276
Petrov, Irene Y.; Prough, Donald S.; Kinsky, Michael; Petrov, Yuriy; Petrov, Andrey; Henkel, S. Nan; Seeton, Roger; Salter, Michael G.; Esenaliev, Rinat O.
Circulatory shock is a dangerous medical condition, in which blood flow cannot provide the necessary amount of oxygen to organs and tissues. Currently, its diagnosis and therapy decisions are based on hemodynamic parameters (heart rate, blood pressure, blood gases) and mental status of a patient, which all have low specificity. Measurement of mixed or central venous blood oxygenation via catheters is more reliable, but highly invasive and associated with complications. Our previous studies in healthy volunteers demonstrated that optoacoustic systems provide non-invasive measurement of blood oxygenation in specific vessels, including central veins. Here we report our first results of a clinical study in coronary artery bypass graft (CABG) surgery patients. We used a medical-grade OPO-based optoacoustic system developed in our laboratory to measure in real time blood oxygenation in the internal jugular vein (IJV) of these patients. A clinical ultrasound imaging system (GE Vivid e) was used for IJV localization. Catheters were placed in the IJV as part of routine care and blood samples taken via the catheters were processed with a CO-oximeter. The optoacoustic oxygenation data were compared to the CO-oximeter readings. Good correlation between the noninvasive and invasive measurements was obtained. The results of these studies suggest that the optoacoustic system can provide accurate, noninvasive measurements of central venous oxygenation that can be used for patients with circulatory shock.
Le Quellec, Sandra; Gaillot, Olivier; Chotel, Franck; Freydière, Anne-Marie; Laurent, Frédéric; Vandenesch, François
Since the introduction of type b Haemophilus influenzae vaccination, noncapsulated H. influenzae has become responsible for most cases of invasive H. influenzae diseases. In our two cases of septic arthritis, we isolated strains with β-lactamase-positive amoxicillin-clavulanate resistance (BLPACR). Thus, the increasing prevalence of BLPACR should be taken into account when empirical therapy is chosen for septic arthritis. PMID:23515545
Schaeffeler, Christoph; Sommer, Christoph
Septic arthritis of the pubic symphysis is a potentially severe disease. Athletes are at risk of this form of spontaneous arthritis, as inflammation of the pubic bone due to muscular stress is relatively common. Oedema due to inflammation might predispose to infection through bacteraemia or local bacterial translocation. Suspicion should be raised when an athlete complains of groin pain and has signs of infection (i.e., fever, elevated white blood cell count, and elevated C-reactive protein). Diagnosis is made by imaging showing signs of inflammation combined with positive (blood) cultures. Broad spectrum antibiotics should be started upon suspicion and adjusted according to cultures. An abscess causing clinical deterioration under antibiotic treatment is an indication for invasive intervention (i.e., surgical or image-guided drainage). This is the first case of spontaneous septic arthritis of the pubic symphysis in an athlete requiring surgical and additional image-guided drainage. PMID:27703831
Smits, F Jasmijn; Frima, Herman; Schaeffeler, Christoph; Sommer, Christoph
Septic arthritis of the pubic symphysis is a potentially severe disease. Athletes are at risk of this form of spontaneous arthritis, as inflammation of the pubic bone due to muscular stress is relatively common. Oedema due to inflammation might predispose to infection through bacteraemia or local bacterial translocation. Suspicion should be raised when an athlete complains of groin pain and has signs of infection (i.e., fever, elevated white blood cell count, and elevated C-reactive protein). Diagnosis is made by imaging showing signs of inflammation combined with positive (blood) cultures. Broad spectrum antibiotics should be started upon suspicion and adjusted according to cultures. An abscess causing clinical deterioration under antibiotic treatment is an indication for invasive intervention (i.e., surgical or image-guided drainage). This is the first case of spontaneous septic arthritis of the pubic symphysis in an athlete requiring surgical and additional image-guided drainage.
Zhao, Gang; Wu, Wei; Feng, Qi-ming; Sun, Jian
Objective The objective of the present study was to explore the resuscitative effect of small-volume resuscitation on uncontrolled hemorrhagic shock in emergency. Methods In this study, the resuscitative effects in 200 trauma patients with uncontrolled hemorrhagic shock in emergency were studied. Half of these patients were infused with hypertonic/hyperoncotic fluid (small-volume resuscitation group, n=100), whereas the rest were infused with Hespan and lactated Ringer’s solution (conventional fluid resuscitation group, n=100). The changes in hemodynamics, coagulation function, blood biochemistry, blood hematology, and the average infusion volume in both the groups were comparatively studied. Results It was found that the hemodynamics were improved in both the groups after resuscitation. Interestingly, compared with trauma patients infused with Hespan and lactated Ringer’s solution, the growth rate, range, and time duration of the mean arterial pressure of the patients in small-volume resuscitation group increased significantly, and the shock index decreased progressively; in the 60th min after the resuscitation, blood index including hemoglobin, hematocrit, red blood cells, white blood cells, and platelet declined, whereas prothrombin time and activated partial thromboplastin time were prolonged in both the groups, but these changes were less obvious in the small-volume group. In addition, the average infusion volume of patients in the small-volume group was less than that of patients in conventional fluid resuscitation group. Conclusion Featured with small infusion volume and less influence to coagulation function and homeostasis of human body, small-volume resuscitation possesses a significantly higher resuscitative effect. Therefore, trauma patients may have a better chance to maintain the hemodynamic stability and the survival rate, or recovery speed will be increased when traditional aggressive fluid resuscitation is replaced by small-volume resuscitation
Foster, Glenn; Hubler, Alfred
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.
De Backer, Daniel; Orbegozo Cortes, Diego; Donadello, Katia; Vincent, Jean-Louis
Multiple experimental and human trials have shown that microcirculatory alterations are frequent in sepsis. In this review, we discuss the various mechanisms that are potentially involved in their development and the implications of these alterations. Endothelial dysfunction, impaired inter-cell communication, altered glycocalyx, adhesion and rolling of white blood cells and platelets, and altered red blood cell deformability are the main mechanisms involved in the development of these alterations. Microcirculatory alterations increase the diffusion distance for oxygen and, due to the heterogeneity of microcirculatory perfusion in sepsis, may promote development of areas of tissue hypoxia in close vicinity to well-oxygenated zones. The severity of microvascular alterations is associated with organ dysfunction and mortality. At this stage, therapies to specifically target the microcirculation are still being investigated. PMID:24067428
Ali, Abukar; Na, Manli; Svensson, Mattias N. D.; Magnusson, Malin; Welin, Amanda; Schwarze, Jan-Christoph; Mohammad, Majd; Josefsson, Elisabet; Pullerits, Rille; Jin, Tao
Background Interleukin-1 receptor antagonist (IL-1Ra) is the primary therapy against autoinflammatory syndromes with robust efficacy in reducing systemic inflammation and associated organ injury. However, patients receiving IL-1Ra might be at increased risk of acquiring serious infections. Aims To study whether IL-1Ra treatment deteriorates Staphylococcus aureus (S. aureus) septic arthritis and sepsis in mice. Method NMRI mice were treated with anakinra (IL-1Ra) daily for 7 days before intravenous inoculation with S. aureus strain Newman in both arthritogenic and lethal doses. The clinical course of septic arthritis, histopathological and radiological changes of the joints, as well as the mortality were compared between IL-1Ra treated and control groups. Results IL-1Ra treated mice developed more frequent and severe clinical septic arthritis. Also, the frequency of polyarthritis was significantly higher in the mice receiving IL-1Ra therapy. In line with the data from clinical arthritis, both histological and radiological signs of septic arthritis were more pronounced in IL-1Ra treated group compared to controls. Importantly, the mortality of IL-1Ra treated mice was significantly higher than PBS treated controls. Conclusion IL-1Ra treatment significantly aggravated S. aureus induced septic arthritis and increased the mortality in these mice. PMID:26135738
Löffler, W; Lohse, P; Weihmayr, T; Widenmayer, W
Pyogenic arthritis, pyoderma gangrenosum and acne syndrome was diagnosed in a 42-year-old patient, after an unusual persistency of high synovial cell counts had been noticed. Clinical peculiarities and problems with diagnosing septic versus non-septic arthritis are discussed.
Álvarez, R; Viñas-Castillo, L; Lepe-Jiménez, J A; García-Cabrera, E; Cisneros-Herreros, J M
The time to positivity (TTP) of blood cultures has been associated with increased mortality in bacteremia caused by several microorganisms. The aim of this study is to evaluate the relationship between TTP and prognosis, clinical presentation and extended spectrum B-lactamase (ESBL)-production in patients with Escherichia coli bacteremia. This is a retrospective observational study involving 226 adult patients with E. coli bacteremia. Data collected included underlying diseases, clinical presentation, prognosis factors, TTP, ESBL-production and outcome. Thirty-one (14%) patients had severe sepsis and 29 (13%) septic shock at presentation. Thirty-three (14%) strains were ESBL-producers. Thirty-nine (17%) patients died during admission and 17 (7.5%) within 48 hours. The median TTP was 8.3 hours (range, 0.42–76.5). It was significantly shorter in patients with septic shock (6.23 h, range 1.12–47.29 h vs. 8.51 h, range 0.42–76.50 h; p = 0.018). Rapid growth of E. coli, Pitt index >1.5, non-urinary source and Charlson score >2 were selected as independent risk factors of in-hospital mortality by the multivariate analysis. ESBL-production was not associated with modifications in TTP. Lower TTP is an independent risk factor for septic shock and poor outcome in episodes of E. coli bacteremia. The TTP in E. coli bacteremia is not significantly modified by ESBL-production.
Pääkkönen, Markus; Peltola, Heikki
Acute septic arthritis is a rare, but potentially devastating disease. The treatment is initiated intravenously, but can be safely switched to oral after 2-4 days providing large doses of a well-absorbing antibiotic and, for time-dependent antibiotics, 4 times-a-day administration are used. Empiric treatment should always cover Staphylococcus aureus and common respiratory pathogens, whereas Kingella kingae and Salmonella are important only regionally. Studies conducted by our group have shown that a total course of 10 days may suffice for previously healthy children in a Western setting. Treatment of neonates, patients with immunodeficiency or cases caused by methicillin-resistant S. aureus, may deserve a different approach.
Warkentin, T E; Pai, M
For unknown reasons, a small minority of critically ill patients with septic or cardiogenic shock, multiorgan failure, and disseminated intravascular coagulation develop symmetrical acral (distal extremity) limb loss due to microvascular thrombosis ('limb gangrene with pulses'). Case reports have described preceding 'shock liver' in some critically ill patients who developed such a picture of ischemic limb necrosis. This suggests that profoundly disturbed procoagulant-anticoagulant balance featuring uncontrolled generation of thrombin-resulting from failure of the protein C and antithrombin natural anticoagulant systems due to insufficient hepatic synthesis of these crucial proteins-could explain the microvascular thrombosis and associated limb loss. We hypothesize that shock liver is the key predisposing risk factor underlying ischemic limb necrosis in the majority of patients who develop this complication in the setting of acute disseminated intravascular coagulation complicating septic or cardiogenic shock. As shock liver precedes onset of limb ischemia by several days, therapeutic intervention may be possible.
Gurjar, Rajan S.; Riccardi, Suzannah L.; Johnson, Blair D.; Johnson, Christopher P.; Paradis, Norman A.; Joyner, Michael J.; Wolf, David E.
There is a critical unmet clinical need for a device that can monitor and predict the onset of shock: hemorrhagic shock or bleeding to death, septic shock or systemic infection, and cardiogenic shock or blood flow and tissue oxygenation impairment due to heart attack. Together these represent 141 M patients per year. We have developed a monitor for shock based on measuring blood flow in peripheral (skin) capillary beds using diffuse correlation spectroscopy, a form of dynamic light scattering, and have demonstrated proof-of-principle both in pigs and humans. Our results show that skin blood flow measurement, either alone or in conjunction with other hemodynamic properties such as heart rate variability, pulse pressure variability, and tissue oxygenation, can meet this unmet need in a small self-contained patch-like device in conjunction with a hand-held processing unit. In this paper we describe and discuss the experimental work and the multivariate statistical analysis performed to demonstrate proof-of-principle of the concept.
Shetty, R P; Mathew, M; Smith, J; Morse, L P; Mehta, J A; Currie, B J
Little information is available about several important aspects of the treatment of melioidosis osteomyelitis and septic arthritis. We undertook a retrospective review of 50 patients with these conditions in an attempt to determine the effect of location of the disease, type of surgical intervention and duration of antibiotic treatment on outcome, particularly complications and relapse. We found that there was a 27.5% risk of osteomyelitis of the adjacent bone in patients with septic arthritis in the lower limb. Patients with septic arthritis and osteomyelitis of an adjacent bone were in hospital significantly longer (p = 0.001), needed more operations (p = 0.031) and had a significantly higher rate of complications and re-presentation (p = 0.048). More than half the patients (61%), most particularly those with multifocal bone and joint involvement, and those with septic arthritis and osteomyelitis of an adjacent bone who were treated operatively, needed more visits to theatre.
Septic system maintenance is not complicated, and it does not need to be expensive. Upkeep comes down to four key elements: Inspect and Pump Frequently, Use Water Efficiently, Properly Dispose of Waste and Maintain Your Drainfield.
Creehan, P A
Toxic Shock Syndrome (TSS) is a potentially fatal illness caused by a particular strain of Staphylococcus aureus. The clinical presentation is similar to that of septic shock. The incidence of TSS peaked in the late 1970s and early 1980s, probably as a result of availability of super absorbent tampons. Although most commonly associated with menstruation, the overall incidence of menstrual and nonmenstrual TSS in men and women ranges from 1 to 3 per 100,000. There are almost equal numbers of menstrual and nonmenstrual cases of TSS identified annually. S aureus, the causative microorganism in cases of TSS, has been isolated from many body tissues. Toxic shock syndrome presents as a flu-like illness with high fever, vomiting, diarrhea, general malaise, and muscle weakness. Nursing and medical management focus on controlling or preventing potentially serious complications, such as adult respiratory distress syndrome, renal failure, electrolyte imbalances, disseminated intravascular coagulation, encephalopathy, and cardiomyopathy. Judicious use of tampons and barrier contraceptive devices may decrease the risk of developing TSS.
Jhaveri, Komal; Taldone, Tony; Modi, Shanu; Chiosis, Gabriela
Hsp90 is an ATP dependent molecular chaperone protein which integrates multiple oncogenic pathways. As such, Hsp90 inhibition is a promising anti-cancer strategy. Several inhibitors that act on Hsp90 by binding to its N-terminal ATP pocket have entered clinical evaluation. Robust pre-clinical data suggested anti-tumor activity in multiple cancer types. Clinically, encouraging results have been demonstrated in melanoma, acute myeloid leukemia, castrate refractory prostate cancer, non-small cell lung carcinoma and multiple myeloma. In breast cancer, proof-of-concept was demonstrated by first generation Hsp90 inhibitors in combination with trastuzumab mainly in human epidermal growth factor receptor 2 (HER2) + metastatic breast cancer. There are a multitude of second generation Hsp90 inhibitors currently under investigation. To date, however, there is no FDA approved Hsp90 inhibitor nor standardized assay to ascertain Hsp90 inhibition. This review summarizes the current status of both first and second generation Hsp90 inhibitors based on their chemical classification and stage of clinical development. It also discusses the pharmacodynamic assays currently implemented in clinic as well as other novel strategies aimed at enhancing the effectiveness of Hsp90 inhibitors. Ultimately, these efforts will aid in maximizing the full potential of this class of agents. PMID:22062686
Papadopoulos, Antonios; Karachalios, Theofilos S; Malizos, Constantinos N; Varitimidis, Sokratis
A 75-year-old man presented in shock secondary to septic arthritis of the knee. The patient, with a known history of knee osteoarthritis, was treated elsewhere for mechanical locking symptoms and effusion with arthroscopic debridement, and developed septic arthritis, which disseminated to the leg and foot after a tear in the capsule, and a ruptured pyogenic popliteal cyst. Open debridement of the knee joint, and drainage of the abscesses of the leg and foot, were performed. Antibiotic-loaded cement beads were left in the residual space. Debridement was repeated and cement beads removed after 4 days, and finally the infection was eradicated without any serious consequences for the patient. There is debate over arthroscopic intervention for osteoarthritic knees. The presence of a popliteal cyst, which is a rather common finding in the latter, could be related to a significant number of complications, such as septic arthritis.
Michaels, E K; Pavel, D G; Orellana, P; Montes, A; Olea, E
Patients treated by extracorporeal shock wave lithotripsy (ESWL) are usually evaluated by excretory urography within 1 month after treatment to determine the clearance of stone debris and rule out asymptomatic obstruction. In an attempt to obtain more precise functional information, we used 99mtechnetium-diethylenetriaminepentaacetic acid and 131iodine-hippurate radionuclide renal imaging studies, and a plain abdominal radiograph as the initial followup study after ESWL of 64 kidneys in 55 patients. Of 53 kidneys studied within 60 days after ESWL 42 had abnormal radionuclide renal imaging studies demonstrating pelviocaliceal stasis, excretory delay or poor function, 8 of which required subsequent interventions for obstructing stone debris. Five patients had excretory delay after ESWL that was unexpected based on a pre-ESWL excretory urogram showing normal function without dilation. A subset of 23 patients with large stone burden or anatomical deformity from a prior operation had baseline radionuclide renal imaging studies before ESWL; function improved in 4 and worsened in 5 by radionuclide renal imaging studies after completion of treatment. A total of 19 patients had radionuclide renal imaging studies earlier (within 17 days) after ESWL because of poor function and/or large stone burden, and as expected they had evidence of obstruction from stone debris, which necessitated further followup. Our experience suggests that followup of ESWL by radionuclide renal imaging studies provides specific functional information that is of particular value in the management of patients with obstructing stone debris and/or diminished renal function. Radionuclide renal imaging studies may also reveal unsuspected obstruction or functional impairment after ESWL of uncomplicated stones, and is recommended as routine followup after ESWL.
Zhan, R Z; Fujiwara, N; Shimoji, K
The effect of sepsis on cellular calcium homeostasis in the central nervous system (CNS) was investigated using hippocampal slices of rats in which sepsis was induced by cecal ligation and puncture (CLP). Hippocampal slices were prepared from septic or sham-operated rats at 24 h after abdominal surgery. The basal intracellular calcium ([Ca2+]i) and its response to oxygen-glucose deprivation in hippocampal slices were measured for assessing cellular calcium homeostasis using fura-2 fluorescent imaging technique. The levels of [Ca2+]i were estimated by the fluorescence ratio (R340/380). Twenty-four hours after CLP, spontaneous movement was reduced and plasma lactate was increased in the septic rats in comparison with the sham-operated rats in which laparotomy was performed without CLP. Basal level of R340/380 in the CA4 ara (.72 +/- .07) was significantly higher (p < .001) in the septic group than that in the sham-operated group (.55 +/- (.06). The fluorescence ratio of septic vs. sham-operated in other hippocampal regions were .55 +/- .09 vs. .48 +/- .06 in CA1 (not significant) and .65 +/- .10 vs. .59 +/- .08 (not significant) in CA3, respectively. Increase in [Ca2+]i due to oxygen-glucose deprivation was significant in CA1 and CA3 of the septic group and in all hippocampal regions of sham-operated group. However, it was not significantly increased in CA4 of the septic group. These results suggest that regional deregulation of cellular calcium occurs in the CNS following CLP. Cellular calcium deregulation may be one of the pathogeneses occurred in clinically observed septic encephalopathy.
Shah, Palak; Smith, Sara; Haft, Jonathan W; Desai, Shashank S; Burton, Nelson A; Romano, Matthew A; Aaronson, Keith D; Pagani, Francis D; Cowger, Jennifer A
Temporary circulatory support (TCS) is used to improve hemodynamics in patients with cardiogenic shock as a bridge to durable ventricular assist device (dVAD). Data from dVAD recipients with or without TCS (extracorporeal membranous oxygenation [ECMO], n = 14; TandemHeart [TH], n = 26) were evaluated. Clinical characteristics and hemodynamics were analyzed for patients before and after TCS and compared with profile 1 (n = 29) or profile 2-3 (n = 269) patients without TCS before dVAD. Extracorporeal membranous oxygenation patients had the highest use of preoperative mechanical ventilation, vasopressors, and the highest HeartMate II risk score before dVAD (p < 0.01). Patients receiving TCS before dVAD implant had hemodynamics comparable with patients in Profiles 2-3 and superior to that of Profile 1 patients without TCS. Operative survival after dVAD was lower in patients receiving ECMO (57%) compared with Profile 1 patients receiving TH (88%), Profile 1 without TCS (82%), or Profile 2-3 patients (97%; all p < 0.01). Despite improved clinical stability with TCS, patients bridged to a dVAD have event-free survival that parallels patients in profile 1 without TCS. Our data suggest that patients requiring TCS before dVAD implant should be still classified Interagency Registry for Mechanically Assisted Circulatory Support profile 1.
Chelazzi, Cosimo; Morettini, Elena; Zamidei, Lucia; Valente, Serafina; Caldini, A. Lucia; Zagli, Giovanni; De Gaudio, A. Raffaele; Romagnoli, Stefano
Background Continuous veno-venous hemodialysis with high cut-off membranes (HCO-CVVHD) removes inflammatory mediators involved in organ dysfunction during sepsis. The aim of the present study was to assess the variations in SOFA score and identify early predictors of short-term mortality in a cohort of patients with septic shock, treated with HCO-CVVHD for acute kidney injury (AKI). Methods An observational prospective multicenter cohort study was conducted in four mixed medical-surgical ICUs. Thirty-eight patients with septic shock and AKI (KDIGO stage≥1) treated with HCO-CVVHD have been included in this study. Patients were divided into Survivors and non-Survivors according to mortality observed at 72nd hr of treatment. The variation of SOFA scores and clinical/biochemical parameters were described over time for the entire population and specifically for Survivors and non-Survivors. Similarly, circulating inflammatory mediators (as IL-6, TNF-a and IL-10) were described over time. A logistic regression analysis was used to identify the baseline clinical and biochemical parameters associated with 72 hrs-ICU mortality. Results Overall, the mean SOFA score was 12±3 at baseline, 10.9±3 at 6hrs, 9.8±3 at 12hrs, 8.9±3.3 at 24 hrs, and 8±3.5 at 48 hrs after HCO-CVVHD initiation; and 6.5±2.7 at 24 hrs and 6.6±3 at 48 hrs after HCO-CVVHD discontinuation. In the multivariate regression analysis, baseline serum lactate levels and AKI stage independently correlated with short-term mortality during HCO-CVVHD. A significant reduction was observed in circulating levels of TNFα and IL-6 among Survivors. Conclusions SOFA score significantly decreased early after initiation of HCO-CVVHD in patients with septic AKI. Baseline lactate levels and the AKI stage resulted to be associated to 72 hrs-ICU-mortality. PMID:28207795
Bély, M; Apáthy, A
In the randomized autopsy material of 161 patients with rheumatoid arthritis (RA), a letal, generalized septic infection (GSI) was observed in 22 cases (13.66%). The GSI was accompanied by a pyarthros in 12 (7.45%) and no pyarthros in 10 (6.21%) cases. The clinical parameters of 22 septic RA patients were compared with 139 age and sex matched RA patients without GSI. The average age of septic patients decreased (p < 0.02), with low serum electrophoretic b-globulin level (p < 0.04), and high Waaler-Rose (p < 0.02) and Latex level (p < 0.004). The clinical parameters of 22 septic patients were compared with 76 age and sex matched RA patients without sepsis, vasculitis, or generalized secondary amyloidosis (GSA), and/or miliary epitheloid granulomas of tuberculous type (mT). The differences between the two groups of patients were the same, with a statistically more pronounced age difference (p < 0.005). 29 out of 161 patients (18.01 %) suffered from a clinically manifest diabetes mellitus (in 6 patients accompanied by sepsis), and 11 (6.83 %) from a clinically latent diabetes mellitus (in 2 patients accompanied by sepsis). There was no significant relationship between sepsis and manifest diabetes mellitus. The controlled and treated diabetes mellitus does not influence the frequency of lethal sepsis. Significant correlations were found between sepsis and latent diabetes mellitus (based on the histological detection of amyloid deposition localized to the islets of Langerhans (p < 0.02). 34 out of 161 patients (21.12%) suffered from a generalized secondary amyloidosis (in 3 patients accompanied by sepsis). There was no significant relationship between sepsis and generalized secondary amyloidosis. The thickness of adrenal cortex represents the effect of steroid therapy. Critical random check, using the Mann-Whitney tests, supports significance relationship between the adrenal cortex atrophy and fatal sepsis (p < 0.010). The follicular lymphoid depletion in the spleen
Background The aim of our study is to test procalcitonin (PCT) as surrogate marker of identification of Candida spp. by blood culture (BC) and real-time-polymerase chain reaction (PCR), whether alone or in association with bacteria, in septic patients. Methods We performed a single-centre retrospective study. We reviewed the clinical charts of patients with a diagnosis of severe sepsis or septic shock treated at our general intensive care unit from March 2009 to March 2013. We analysed all diagnostic episodes consisting of BC, real-time PCR assay and dosage of PCT. We registered age, sex, white blood count, sequential organ failure assessment score and type of admission between medical or surgical. When inclusion criteria were met more than once, we registered the new diagnostic episode as subsequent diagnostic episode. The diagnostic performance of PCT to predict Candida spp. identification alone or in mixed infections by either BC or PCR was tested using the receiver-operative characteristic curve. Logistic regression was constructed using presence of Candida spp. as the dependent variable. Results A total of 260 diagnostic episodes met the inclusion criteria. According to BC results classification, a significantly lower value of PCT was observed in Candida spp. BSI (0.99 ng/ml, 0.86 - 1.34) than in BSI caused by bacteria (16.7 ng/ml, 7.65 - 50.2) or in mixed infections (4.76 ng/ml, 2.98 - 6.08). Similar findings were observed considering PCR results. A cut-off of ≤ 6.08 ng/ml for PCT yielded a sensitivity of 86.8%, a specificity of 87.4%, a positive predictive value of 63.9%, a negative predictive value (NPV) of 96.3% and an area under the curve of 0.93 for Candida spp. identification by BC. A similar high NPV for a cut-off ≤ 6.78 ng/ml was observed considering the classification of diagnostic episodes according to PCR results, with an AUC of 0.85. A subsequent diagnostic episode was independently associated with Candida spp. detection either by
Olmos, Carmen; Vilacosta, Isidre; Fernández, Cristina; Sarriá, Cristina; López, Javier; Del Trigo, María; Ferrera, Carlos; Vivas, David; Maroto, Luis; Hernández, Miguel; Rodríguez, Enrique; San Román, José Alberto
Native valve infective endocarditis (IE) in patients with normal valves has increased in the last decades. Whether patients with normal valves present a similar prognosis to those with pathologic valves is unresolved. Our aim is to describe epidemiologic and clinical differences between patients with left-sided IE and normal valves and those with native pathologic valves. We analyzed 945 consecutive episodes of IE, 435 of which involved left-sided nonprosthetic IE. They were classified into 2 groups: episodes in normal valves (normal group, n=173) and episodes in pathologic valves (abnormal group, n=262). Patients in the normal group were younger, Staphylococcus aureus and Streptococcus bovis were more frequently isolated, and vegetations were more frequently found. Heart failure, septic shock, and the need for surgery or death were more common. Multivariate analysis identified the following as factors independently associated with normal valve IE: age<65 years, S bovis, S aureus, heart failure, and vegetation detection. Factors independently associated with in-hospital events included S aureus, periannular complications, heart failure, and septic shock development. In conclusion, compared with patients with abnormal valve IE, patients with IE on normal valves were younger, had a more virulent microbiological profile, developed heart failure and septic shock more frequently, needed more surgical procedures, and had worse prognosis.
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
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
Nafeesah, Abdullah Saleh Al
A case of rarely encountered nontyphoidal Salmonella septic arthritis of the elbow in an infant with no preexisting disease is reported. Salmonella etiology was not suspected in this case, and the diagnosis was made only after bacterial isolation. Aspiration of the infected joint with radiological guidance initially failed to give a good clinical response. Arthrotomy was done with intravenous cefotaxime for 4 weeks followed by 2 weeks oral ciprofloxacin therapy to which the child responded favorably. Up to our knowledge this is the first case of nontyphoidal salmonella elbow septic arthritis in an infant in Saudi Arabia to be reported in the English literature. PMID:26985275
Al Nafeesah, Abdullah Saleh
A case of rarely encountered nontyphoidal Salmonella septic arthritis of the elbow in an infant with no preexisting disease is reported. Salmonella etiology was not suspected in this case, and the diagnosis was made only after bacterial isolation. Aspiration of the infected joint with radiological guidance initially failed to give a good clinical response. Arthrotomy was done with intravenous cefotaxime for 4 weeks followed by 2 weeks oral ciprofloxacin therapy to which the child responded favorably. Up to our knowledge this is the first case of nontyphoidal salmonella elbow septic arthritis in an infant in Saudi Arabia to be reported in the English literature.
Konrads, Christian; Rückl, Kilian; El Tabbakh, Mohammed; Rudert, Maximilian; Kircher, Stefan; Plumhoff, Piet
Introduction: Septic olecranon bursitis due to atypical mycobacteria is rare. An insidious beginning can delay diagnosis and treatment. Antibacterial therapy recommendations are not well-defined for bursitis caused by atypical mycobacteria. We present a rare case of olecranon bursitis caused by Mycobacterium gordonae, reporting our experiences regarding pathogen identification and antibiotic therapy, which differs from regimes used in common septic bursitis mostly caused by staphylococcus aureus. Methods: A 35-year-old male with bursitis olecrani received open bursectomy. Microbiological culture did not reveal bacteria. Due to wound healing complications revision surgery was performed four weeks postoperatively. Finally, Mycobacterium gordonae was identified by PCR and an antibiogram could be developed. A triple antimicrobial combination therapy with Rifampicin, Clarithromycin, and Ethambutol was administered systemically for 12 months. The patient was followed-up for 24 months. Results: After the second operation with pathogen identification and antibiotic combination therapy the wound healed without any additional complications. At last follow-up 24 months after the first surgery with bursectomy and 23 months after revision surgery with debridement, the patient was still pain free with no significant clinical findings or tenderness to touch at the operation site. Elbow range of motion was full. Discussion: As septic bursitis can be caused by many different and sometimes rare and difficult to identify bacteria, intraoperative probes should be taken and histopathological and microbiological analysis should be conducted, including PCR. In a young man with olecranon bursitis due to Mycobacterium gordonae surgical treatment and an antibiotic combination therapy showed a good clinical outcome after one and two years. PMID:27892398
Castellazzi, Luca; Mantero, Marco; Esposito, Susanna
Acute osteomyelitis and septic arthritis are two infections whose frequencies are increasing in pediatric patients. Acute osteomyelitis and septic arthritis need to be carefully assessed, diagnosed, and treated to avoid devastating sequelae. Traditionally, the treatment of acute osteoarticular infection in pediatrics was based on prolonged intravenous anti-infective therapy. However, results from clinical trials have suggested that in uncomplicated cases, a short course of a few days of parenteral antibiotics followed by oral therapy is safe and effective. The aim of this review is to provide clinicians an update on recent controversies and advances regarding the management of acute osteomyelitis and septic arthritis in children. In recent years, the emergence of bacterial species resistant to commonly used antibiotics that are particularly aggressive highlights the necessity for further research to optimize treatment approaches and to develop new molecules able to fight the war against acute osteoarticular infection in pediatric patients. PMID:27258258
Steeil, James; Schumacher, Juergen; Seibert, Rachel; Tobias, Karen
An 8-yr-old intact female African lion (Panthera leo) presented with a 3-day history of lethargy, anorexia, and vomiting. Hematologic and biochemical abnormalities included a leukocytosis, 41,700/microl (4,700-15,300) with a neutrophilia (37,530/microl; 2,000-9,200) and a left shift (1,250/microl bands; 0-300), and mild hypokalemia of 2.1 mEq/L (2.8-4.8). Abdominal radiographs revealed evidence of intestinal ileus, peritonitis, and the presence of effusion. An exploratory laparotomy was performed, and septic peritonitis due to a pyometra was diagnosed. The lion was treated with an ovariohysterectomy, abdominal lavage, fluid therapy, and a subcutaneous injection of cefovecin. The lion recovered, and clinical signs associated with septic peritonitis resolved within 36 hr. It was returned to conspecifics 3 wk later. Three months postoperatively, the lion showed no residual signs of septic peritonitis.
Tanwar, Yashwant Singh; Jaiswal, Atin; Singh, Satyaprakash; Arya, Rajender Kumar; Lal, Hitesh
We present a review of the current literature and the author's opinion regarding Septic arthritis in the pediatric age group. The etiopathogenesis, clinical features, the laboratory parameters for diagnosis and monitoring of treatment, radiological features, are discussed along-with the debatable issues pertaining to the choice of antibiotics, their duration, and the need and mode of surgical drainage and mobilization of the joint.
Bachy, B; Bémer, P; Tortellier, L; Giraudeau, C; Reynaud, A; Corvec, S
Sneathia sanguinegens is an infrequent bacterium in clinical specimens. We describe a case of right elbow septic arthritis due to a Sneathia species most closely related to S. sanguinegens in a young immunocompetent woman. S. sanguinegens has never been implicated in osteoarticular infections.
Olut, Ali Ilgın; Avcı, Meltem; Ozgenç, Onur; Altay, Taşkın; Coşkuner, Seher Ayten; Ozsu Caymaz, Sibel; Havuk, Ayla
The most common microorganisms isolated from septic arthritis are Staphylococcus aureus and streptoccocci. Septic arthritis due to Salmonella spp. are rare and the most commonly isolated species are S.Choleraesuis and S.Typhimurium. However the number of septic arthritis cases due to S.Typhi is low in literature. In this report, septic arthritis of hip due to S.Typhi in a multiple sclerosis patient who was under steroid therapy, was presented. A 25-year-old female patient was admitted to our clinic with the complaints of fever, left hip pain, standing and walking disability for 10 days. Her anamnesis revealed that she had had a multiple sclerosis attack and underwent triple pulse steroid therapy. Laboratory findings were as follows; WBC count: 16.300/mm3 (70% polymorphonuclear leukocyte), hemoglobin: 10.6 g/dl, erythrocyte sedimentation rate: 140 mm/hour, CRP: 28.7 g/L, AST: 86 U/L and ALT: 77 U/L. In lumbosacral magnetic resonance imaging, trochanteric bursitis and generalized myositis were detected in left hip joint compatible with septic arthritis. S.Typhi was isolated from patient's blood and operational tissue samples. Serum Salmonella TO and TH titers were found as 1/400 and 1/200, respectively. Antibiotic susceptibility test was performed by disk diffusion method, and the isolate was found susceptible to ampicillin, chloramphenicol, ceftriaxone, ciprofloxacin and trimethoprim-sulphametoxazole. The patient was treated by surgery and also by two weeks parenteral (2 x 400 mg) and 6 weeks oral (2 x 500 mg) ciprofloxacin treatment. Six months follow-up of the patient revealed that clinical, radiological and laboratory findings were normal. As far as the national literature was considered, this was the first S.Typhi septic arthritis case involving the hip joint and demonstrating bacterial growth both in blood and operational tissue. The presentation of the infection as arthritis plus diffuse myositis and bursitis, is also noteworthy.
Bonfante Ramírez, E; Ahued Ahued, R; García-Benítez, C Q; Bolaños Ancona, R; Callejos, T; Juárez García, L
Shock is one of the most difficult problems an obstetrician can face. Hemorrhage is the main reason of shock. A descriptive and retrospective research was conducted at Instituto Nacional de Perinatología, from January 1992 to May 1996, including all patients admitted to the intensive care unit with diagnosis of shock. There were found 90 cases with diagnosis of shock, 82 were hipovolemic, and 8 cases had the septic kind of shock. The average of age was 32.2 years, with a gestational age between 6.2 to 41.4 weeks . There were 71 healthy patients, hypertension was associated to pregnancy in 9 cases, infertility in two, myomatosis in 2, and diabetes in 2 more patients. Other 5 cases reported different pathologies. The most frequent cause for hipovolemic shock resulted to be placenta acreta (40 cases), followed by uterine tone alterations in 37 patients, ectopic pregnancy in 7, uterine rupture or perforation in 4, and vaginal or cervical lacerations in 2. The estimated blood loss varied from 2200 cc to 6500 cc, and the minimal arterial pressure registered during shock was between 40/20 mmHg to 90/60 mmHg. Medical initial assistance consisted in volume reposition with crystalloids, globular packages, and plasma expansors in 73 patients (81.1%). The rest of the patients received in addition coloids, platelets and cryoprecipitates. A total of 76 patients required surgical intervention consisting in total abdominal hysterectomy. In 5 cases the previous surgical procedure was done and ligation of hypogastric vessels was needed. Salpingectomy was performed in 5 patients, and rupture or perforation repair in 3. The average surgery time was 2 hours and 33 minutes. The observed complications were 7 cases with abscess of the cupula, consumption coagulopathy in 2, 1 vesical quirurgical injury, 1 intestinal occlusion, and 11 vesico-vaginal fistula. The average days of hospitalization resulted to be 5. The most frequent kind of shock seen by obstetricians is the hipovolemic type
Tucker, Adam; Matthews, Scott; Wilson, Alister
Septic arthritis is a debilitating acute orthopedic emergency. Unfortunately, the diagnosis can be delayed or missed in immunocompromised patients with diabetes mellitus, and the result can be catastrophic. These patients are also at risk for atypical infections, including mycotic subtypes, which are more insidious than their more aggressive, more common Staphylococcus counterparts. The result is increased morbidity. In this article, we report a case of Candida albicans septic arthritis in a patient with diabetes mellitus and rheumatoid arthritis. Her case highlights the complexities of this specific disease entity. With early diagnosis, treatment is multimodal, involving surgical débridement and prolonged antifungal therapy.
Altshuler, Angelina E; Kistler, Erik B; Schmid-Schönbein, Geert W
There is currently no effective treatment for multiorgan failure following shock other than supportive care. A better understanding of the pathogenesis of these sequelae to shock is required. The intestine plays a central role in multiorgan failure. It was previously suggested that bacteria and their toxins are responsible for the organ failure seen in circulatory shock, but clinical trials in septic patients have not confirmed this hypothesis. Instead, we review here evidence that the digestive enzymes, synthesized in the pancreas and discharged into the small intestine as requirement for normal digestion, may play a role in multiorgan failure. These powerful enzymes are nonspecific, highly concentrated, and fully activated in the lumen of the intestine. During normal digestion they are compartmentalized in the lumen of the intestine by the mucosal epithelial barrier. However, if this barrier becomes permeable, e.g. in an ischemic state, the digestive enzymes escape into the wall of the intestine. They digest tissues in the mucosa and generate small molecular weight cytotoxic fragments such as unbound free fatty acids. Digestive enzymes may also escape into the systemic circulation and activate other degrading proteases. These proteases have the ability to clip the ectodomain of surface receptors and compromise their function, for example cleaving the insulin receptor causing insulin resistance. The combination of digestive enzymes and cytotoxic fragments leaking into the central circulation causes cell and organ dysfunction, and ultimately may lead to complete organ failure and death. We summarize current evidence suggesting that enteral blockade of digestive enzymes inside the lumen of the intestine may serve to reduce acute cell and organ damage and improve survival in experimental shock.
use of naloxone in human septic shock (10), but the doses of naloxone used were quite low compared to those found to be effective in rodents, dogs (3-6...Lechner, T. Vargish, and 0. G. Reynolds: Dose - dependent naltrexone improvement of cardiovascular function and survival suggests opiate receptors...Reynolds: Cardio- vascular effects of naltrexone in canine hemorrhagic shock are dose dependent. Circ. Shock 13:45-46, 1984. 38. R. B. Lechner, N. J
Poderoso, J J; Carreras, M C; Lisdero, C; Schöpfer, F; Riobó, N; Peralta, J
The shock syndrome has been classically considered as a consequence of both decreased tissue perfusion and O2 supply; however, in some types of shock like septic or traumatic ones, regional blood flows may be increased. A decade ago, mitochondrial alterations consistent with uncoupling of oxidative phosphorylation were reported in either endotoxemic or hemorrhagic experimental shock or in humans. Recently, the discovery of nitric oxide (NO) and its increase in the shock state, has opened new perspectives in the understanding of this problem. Nitric oxide produces vasodilatation and, at the same time, increases the mitochondrial production of O2 active species like superoxide anion. Both radicals react to form a strong oxidant that is able to nitrate the phenolic rings of proteins: peroxynitrite. This effect leads to the impairment of the activities of different mitochondrial enzymes like succinate dehydrogenase and ATPase and the mitochondrial function and finally, to decreased energy levels and to multiorgan failure. The increase in NO release is due to the effects of circulating peptides and of increased adhesion of neutrophils to the endothelium and to the positive effects of inflammatory mediators like TNF-alpha and cytokines on inducible NOS (iNOS) expression in endothelium and tissues. It is suggested that the shock state is the consequence of an imbalance between NO and O2 and their metabolites.
Li, YiQiang; Zhou, QingHe; Liu, YuanZhong; Chen, WeiDong; Li, JingChun; Yuan, Zhe; Yong, BiCheng; Xu, HongWen
Abstract There is still controversy on the management of septic arthritis in neonates. This study aims to investigate the treatment of septic arthritis in neonates. We reviewed 52 neonates (37 males and 15 females) with septic arthritis in our hospital during 2004 to 2015. The mean age at onset of infection was 17.5 ± 7.6 days, mean age at admission was 32.6 ± 10.7 days. A total of 56 joints were involved (22 knees, 18 shoulders, 13 hips, and 3 other joints). Thiryt-six patients underwent surgical drainage, 14 patients were treated nonoperatively, 2 families refused treatment. Forty-four patients (48 joints) were followed for 4.5 ± 1.2 years. Based on treatment, these 48 joints were divided into an operative group and a nonoperative group. Clinical presentations, imaging examination results, treatments, and outcomes were analyzed. Among the patients who were followed-up, the time from onset to treatment in the operatively managed group (12.7 ± 8.1 days) was significantly shorter than that in the conservatively managed group (20.0 ± 8.2 days). There were no significant differences between both groups on the age at onset, age at admission, imaging score, length of hospital stay, WBC counts, and intravenous medication time. Thirty-five sites (72.9%) recovered completely. There was no significant difference on recovery rate between operative and nonoperative group. Only 33.3% of the hips recovered, this was significantly lower than that of knee/ankle (85.0%) and shoulder/elbow (78.9%). Sequels were found in 13 joints. Logistic regression indicated that sex, imaging score, and hip joint involvement were predictors of sequel. One point of imaging score increased the risk of sequels by a factor of 2.960, and hip joint involvement increased the risk of sequels by a factor of 12.712. Females were more likely to have sequels than males. Surgical drainage is recommended for early diagnosed neonatal septic arthritis and hip infections. A conservative
Cesarini, Carla; Macieira, Susana; Girard, Christiane; Drolet, Richard; d’Anjou, Marc-André; Jean, Daniel
The costochondral junction constitutes a potential site of infection in septic foals and it could be favored by thoracic trauma. Standard radiographs and ultrasonography are useful tools for diagnosis of this condition and ultrasound-guided needle aspiration could permit the definitive confirmation of infection. PMID:22210943
Morton, Alison J
Septic arthritis (SA) is a common orthopedic condition encountered in horses that are presented to equine veterinarians. Successful out-come is dependent on prompt and thorough evaluation and treatment. This article briefly reviews the pathophysiology, outlines diagnostics, describes treatment options and prognostics, and discusses current research in diagnosis and treatment of SA.
Kok, Jen; Chen, Sharon C A; Dwyer, Dominic E; Iredell, Jonathan R
The integration of matrix-assisted laser desorption ionisation-time of flight mass spectrometry (MALDI-TOF MS) into many clinical microbiology laboratories has revolutionised routine pathogen identification. MALDI-TOF MS complements and has good potential to replace existing phenotypic identification methods. Results are available in a more clinically relevant timeframe, particularly in bacteraemic septic shock. Novel applications include strain typing and the detection of antimicrobial resistance, but these are not widely used. This review discusses the technical aspects, current applications, and limitations of MALDI-TOF MS.
Saur, M; Distler, O; Müller, N
Clinical signs of acute arthritis are non-specific. An acute painfull joint with effusion of unknown origin needs to be evaluated by puncture. The analysis of the synovial fluid will enable to divide an arthritis into three categories: crystal induced, rheumatological or septic arthritis. A bacterial infection should always be suspected. Cultures from blood, synovia and Gram stain do not reliably exclude a bacterial infection. If gonococcal, mycobacterial, borrelial and non-gonococcal-infective arthritis under antibiotic therapy is suspected, direct DNA-amplification can be helpful. A disseminated gonococcal infection (DGI) must be suspected on appearance of tenosynovitis, polyarthralgia and skin lesions. The clinical picture, diagnosis and therapy of a case with DGI is discussed.
Kim, E.E.; Haynie, T.P.; Podoloff, D.A.; Lowry, P.A.; Harle, T.S. )
Despite controversy over its exact role, radionuclide imaging plays an important role in the evaluation of patients suspected of having osteomyelitis. The differentiation between osteomyelitis and cellulitis is best accomplished by using a three-phase technique using Tc-99m methylene diphosphonate (MDP). Frequently, it is necessary to obtain multiple projections and magnification views to adequately assess suspected areas. It is recommended that a Ga-67 or In-111 leukocyte scan be performed in those cases where osteomyelitis is strongly suspected clinically and the routine bone scan is equivocal or normal. Repeated bone scan after 48 to 72 h may demonstrate increased radioactivity in the case of early osteomyelitis with the initial photon-deficient lesion. In-111 leukocyte imaging is useful for the evaluation of suspected osteomyelitis complicating recent fracture or operation, but must be used in conjunction with clinical and radiographic correlation. The recognition of certain imaging patterns appears helpful to separate osteomyelitis from septic arthritis or cellulitis. 83 references.
Mussap, Michele; Noto, Antonio; Fravega, Marco; Fanos, Vassilios
Several biochemical markers have been proposed over the past years to manage critically ill newborns with acute inflammation and sepsis. The state of the art in diagnosing and monitoring neonatal sepsis, severe sepsis and septic shock consists of the measurement of plasma C-reactive protein (CRP) and procalcitonin (PCT) at the onset and in the course of the disease. CRP and PCT in combination are clinically significant in diagnosing and monitoring septic newborns; however, CRP and PCT have a very limited value for risk stratification and in predicting outcome. The availability of commercial methods for the automated measurement of the soluble CD14 subtype presepsin (sCD14-ST) and lipopolysaccharide binding protein (LBP) represent a challenge for the evaluation in clinical practice of reliable markers of neonatal sepsis, specifically for the very early diagnosis, the classification into class of severity, and the prediction of complications and death.
Lee, Kwang-Hoon; Choi, Sang-Tae; Lee, Soo-Kyung; Lee, Joo-Hyun; Yoon, Bo-Young
Septic arthritis and gout are major diseases that should be suspected in patients with acute monoarthritis. These two diseases are clinically similar and often indistinguishable without the help of synovial fluid analysis. Recently, a novel diagnostic rule for gout without synovial fluid analysis was developed and showed relevant performances. This study aimed to determine whether this diagnostic rule could perform well in distinguishing gout from septic arthritis. The diagnostic rule comprises 7 clinical and laboratory variables, each of which is given a specified score. The probability of gout is classified into 3 groups according to the sum of the scores: high (≥ 8), intermediate (> 4 to < 8) and low probability (≤ 4). In this retrospective study, we applied this diagnostic rule to 136 patients who presented as acute monoarthritis and were subsequently diagnosed as acute gout (n = 82) and septic arthritis (n = 54) based on synovial fluid analysis. The mean sum of scores of acute gout patients was significantly higher than that of those with septic arthritis (8.6 ± 0.2 vs. 3.6 ± 0.32, P < 0.001). Patients with acute gout had significantly more 'high', and less 'low' probabilities compared to those with septic arthritis (Eta[η]: 0.776). The prevalence of acute gouty arthritis, as confirmed by the presence of monosodium crystal, was 95.5% (61/64), 57.5% (19/33), and 5.1% (2/39) in high, intermediate and low probability group, respectively. The recently introduced diagnostic rule properly discriminates acute gout from septic arthritis. It may help physicians diagnose gout in cases difficult to be differentiated from septic arthritis.
Pussayanavin, Tatchai; Koottatep, Thammarat; Eamrat, Rawintra; Polprasert, Chongrak
Septic tanks in most developing countries are constructed without drainage trenches or leaching fields to treat toilet wastewater and /or grey water. Due to the short hydraulic retention time, effluents of these septic tanks are still highly polluted, and there is usually high accumulation of septic tank sludge or septage containing high levels of organics and pathogens that requires frequent desludging and subsequent treatment. This study aimed to reduce sludge accumulation in septic tanks by increasing temperatures of the septic tank content. An experimental study employing two laboratory-scale septic tanks fed with diluted septage and operating at temperatures of 40 and 30°C was conducted. At steady-state conditions, there were more methanogenic activities occurring in the sludge layer of the septic tank operating at the temperature of 40°C, resulting in less total volatile solids (TVS) or sludge accumulation and more methane (CH4) production than in the unit operating at 30°C. Molecular analysis found more abundance and diversity of methanogenic microorganisms in the septic tank sludge operating at 40°C than at 30°C. The reduced TVS accumulation in the 40°C septic tank would lengthen the period of septage removal, resulting in a cost-saving in desluging and septage treatment. Cost-benefit analysis of increasing temperatures in septic tanks was discussed.
Lu, Pei; Wang, Zijie; Song, Rijin; Wang, Xiaolan; Qi, Kai; Dai, Qiying; Zhang, Wei; Gu, Min
The aim was to investigate the clinical efficacy and safety of extracorporeal shock wave lithotripsy (ESWL) in pediatric urolithiasis. A comprehensive systematic review and meta-analysis were performed. PubMed, Embase, and the Cochrane central register of controlled trials (CENTRAL) were searched, and the stone-free rates (SFRs) of various stone sizes and stone positions were extracted from the eligible articles. The quality of the original articles was assessed according to the McHarm Scale. The risk ratios (RRs) and 95% confidential intervals (CIs) were pooled, and the sensitive analysis was performed to evaluate the heterogeneity among all eligible studies. In total, 14 studies with 1842 patients were identified. The pooled RR for the SFR of stones less than 10 mm and greater than 10 mm was 1.14 (95% CI: 1.07, 1.21, P < 0.001); the RR for the SFR of stones in the renal pole calix (PC) and the renal pelvis was 0.95 (95% CI: 0.893, 1.009, P < 0.01); the RR for the SFR of stones in the upper/middle PC and the lower PC was 1.07 (95% CI: 0.997, 1.156, P < 0.061); and the RR for the SFR of stones in the proximal ureter and middle/distal ureter was 1.077 (95% CI: 1.005, 1.154, P = 0.036). Heterogeneity was low in all the analyses. Major complications in ESWL of pediatric urolithiasis were steinstrasse and abdominal colic, the incidences of which were 6.00 and 6.29 %, respectively. The SFR of stones <10 mm was significantly higher than stones >10 mm, and the SFR of stones located in proximal ureter was statistically greater than stones in middle or distal ureter in pediatric urolithiasis, leaving no significant between stones in renal PC and renal pelvis, or between upper/middle PC and lower PC. The use of ESWL in children is highly efficient, with negligible complications; ESWL therapy could be considered the first-line treatment for pediatric urolithiasis.
Alho, A; Jäättelä, A; Lahdensuu, M; Rokkanen, P; Avikainen, V; Karaharju, E; Tervo, T; Lepistö, P
The role of endogenous catecholamines in various clinical shock and stress states is reviewed; the effects, especially on the peripheral circulation, of catecholamine secretion are the same independent of the cause. Risks of using sympathomimetic agents in the treatment of shock are evaluated. A prolonged noradrenaline activity is to be expected in surgical stress states, e.g. multiple injuries, fat embolism syndrome, burns and infections; therapeutic approaches to minimize the sympathoadrenal activity are outlined.
Schell, Wiley A.; Joyce, Maria; Alley, Christopher; Woods, Christopher W.
Introduction: Mucormycosis is a rare fungal infection, but can cause substantial morbidity and mortality in both immunocompromised and immunocompetent patients. Apophysomyces is a mucormycetes species ubiquitous in nature, particularly in soil, decaying wood and other organic matter. Apophysomyces is known to cause cutaneous fungal infections, particularly after penetrating trauma. Septic arthritis is a rare clinical manifestation. Case presentation: We describe a case of Apophysomyces trapeziformis causing septic arthritis of the knee of a patient with multiple myeloma. He was treated multiple times for bacterial septic arthritis with minimal improvement. Surgical tissue specimens finally grew mucoraceous mould, and DNA sequencing and morphological assessment of spores identified the mould as A. trapeziformis. The patient was treated with amphotericin B and posaconazole, but ultimately required an above-the-knee amputation for definitive treatment. Conclusion: This case illustrates the need to evaluate for fungal infection in a persistent septic arthritis that is culture negative and refractory to empiric antibiotics, particularly in an immunocompromised individual. It also shows the importance of a thorough social history and adequate tissue specimens for culture. PMID:28348796
Suzuki, Kei; Nakamura, Akiko; Enokiya, Tomoyuki; Iwashita, Yoshiaki; Tomatsu, Eri; Muraki, Yuichi; Kaneko, Toshihiro; Okuda, Masahiro; Katayama, Naoyuki; Imai, Hiroshi
We herein report the first case of septic arthritis caused by rmpA-positive hypermucoviscous community-acquired K. pneumoniae that followed urosepsis in a 65-year-old Japanese woman. The patient responded well to drainage of the abscesses and treatment with cefazolin. Although this virulent phenotype of K. pneumoniae has been primarily reported in Hong Kong, we confirmed that 18/50 isolates obtained in our hospital over the past five years displayed the hypermucoviscous phenotype. Therefore, clinicians should consider the possibility of an increasing prevalence of rmpA-positive hypermucoviscous K. pneumoniae infection in Japan and be particularly vigilant for invasive clinical manifestations, even in patients with urinary tract infections.
Moraes, Rafael Barberena; Guillén, Julián Alberto Viteri; Zabaleta, William Javier Castillo; Borges, Flavia Kessler
Objective To evaluate the prevalence of antibiotic de-escalation in patients diagnosed with severe sepsis or septic shock at a public academic tertiary hospital and to evaluate antibiotic adequacy and culture positivity. Methods The prevalence of antibiotic de-escalation, the adequacy of antibiotic treatment and the rates of culture positivity were analyzed in patients with severe sepsis and septic shock between April and December 2013 at an intensive care unit in a tertiary university hospital. Results Among the 224 patients included in the study, de-escalation was appropriate in 66 patients (29.4%) but was implemented in 44 patients (19.6%). Among the patients who underwent de-escalation, half experienced narrowing of the antimicrobial spectrum. The mortality rate was 56.3%, with no differences between the patients with or without de-escalation (56.8% versus 56.1%; p = 0.999) nor in the length of hospital stay. Empirical antibiotic therapy was appropriate in 89% of cases. Microorganisms were isolated from total cultures in 30% of cases and from blood cultures in 26.3% of cases. Conclusion The adequacy rate of empirical antibiotic therapy was high, reflecting an active institutional policy of monitoring epidemiological profiles and institutional protocols on antimicrobial use. However, antibiotic de-escalation could have been implemented in a greater number of patients. De-escalation did not affect mortality rates. PMID:27626951
Mackay, Andrew J; Amador, Manuel; Diaz, Annette; Smith, Josh; Barrera, Roberto
Aedes aegypti and Culex quinquefasciatus were found in large numbers emerging from septic tanks in southern Puerto Rico during the dry season. Previous studies suggested that Ae. aegypti uses subterranean aquatic habitats only during dry periods when surface containers do not have water. This research investigated whether septic tanks are alternative aquatic habitats that this mosquito uses during unfavorable times of the year, or whether Ae. aegypti uses this aquatic habitat throughout the year. To assess temporal change, exit traps were used to collect mosquitoes emerging from septic tanks in Playa/Playita, southern Puerto Rico, from November 2006 to October 2007. We also investigated the hypotheses that (1) the production of Ae. aegypti in septic tanks was larger than in surface containers and (2) adult mosquitoes emerging from septic tanks were larger than those emerging from surface containers. This study demonstrated that unsealed septic tanks produced large numbers of Ae. aegypti and Cx. quinquefasciatus throughout the year, without any significant relationship with rainfall. The number of adult Ae. aegypti emerging per day from septic tanks in each community was 3 to 9 times larger than those produced in surface containers. It was also demonstrated that Ae. aegypti emerging from septic tanks were significantly larger than those emerging from surface container habitats. It is recommended that dengue prevention programs include regular inspection and maintenance of septic tanks in communities lacking sewerage.
Honore, Patrick M; Jacobs, Rita; Joannes-Boyau, Olivier; De Regt, Jouke; Boer, Willem; De Waele, Elisabeth; Collin, Vincent; Spapen, Herbert D
Evidence is accumulating showing that septic acute kidney injury (AKI) is different from non-septic AKI. Specifically, a large body of research points to apoptotic processes underlying septic AKI. Unravelling the complex and intertwined apoptotic and immuno-inflammatory pathways at the cellular level will undoubtedly create new and exciting perspectives for the future development (e.g., caspase inhibition) or refinement (specific vasopressor use) of therapeutic strategies. Shock complicating sepsis may cause more AKI but also will render treatment of this condition in an hemodynamically unstable patient more difficult. Expert opinion, along with the aggregated results of two recent large randomized trials, favors continuous renal replacement therapy (CRRT) as preferential treatment for septic AKI (hemodynamically unstable). It is suggested that this approach might decrease the need for subsequent chronic dialysis. Large-scale introduction of citrate as an anticoagulant most likely will change CRRT management in intensive care units (ICU), because it not only significantly increases filter lifespan but also better preserves filter porosity. A possible role of citrate in reducing mortality and morbidity, mainly in surgical ICU patients, remains to be proven. Also, citrate administration in the predilution mode appears to be safe and exempt of relevant side effects, yet still requires rigorous monitoring. Current consensus exists about using a CRRT dose of 25 ml/kg/h in non-septic AKI. However, because patients should not be undertreated, this implies that doses as high as 30 to 35 ml/kg/h must be prescribed to account for eventual treatment interruptions. Awaiting results from large, ongoing trials, 35 ml/kg/h should remain the standard dose in septic AKI, particularly when shock is present. To date, exact timing of CRRT is not well defined. A widely accepted composite definition of timing is needed before an appropriate study challenging this major issue can be
Background Osteopetrosis is a rare, inherited, bone disorder, characterized by osteosclerosis, obliteration of the medullary cavity and calcified cartilage. The autosomal dominant form is compatible with a normal life span, although fractures often result from minimal trauma, due to the pathologic nature of bone. Osteomyelitis is common in patients with osteopetrosis because of a reduced resistance to infection, attributed to the lack of marrow vascularity and impairment of white cell function. Only one case of osteomyelitis of the proximal third of the femur has been previously reported, treated with several repeated debridements and finally with femoral head resection. Here we present for the first time a case of a staged implant of a cementless total hip prosthesis for the treatment of a septic hip in femoral neck nonunion in osteopetrosis. Case presentation A 36-years-old woman, affected by autosomal dominant osteopetrosis was referred to our department because of a septic hip arthritis associated with femoral neck septic non-union, with draining fistulas. The infection occurred early after a plate osteosynthesis for a closed perthrocanteric fracture of the femur and persisted in spite of osteosynthesis removal, surgical debridement and external fixation. In our hospital the patient underwent accurate debridement, femoral head and greater trochanter resection, preparation of the diaphyseal intramedullary canal and implant of an antibiotic-loaded cement spacer. The spacer was exchanged after one month, due to infection recurrence and four months later, a cementless total hip arthroplasty was implanted, with no clinical and laboratory signs of infection recurrence at two years follow-up. Conclusions In case of hip septic arthritis and proximal femur septic non-union, femoral head resection may not be the only option available and staged total hip arthroplasty can be considered. PMID:22472060
Pae, Chi-Un; Drago, Antonio; Kim, Jung-Jin; Mandelli, Laura; De Ronchi, Diana; Serretti, Alessandro
We previously investigated a group of single-nucleotide polymorphisms of a set of genes coding for heat shock proteins (HSPA1A, HSPA1B and HSPA1L) and found a significant association between one HSPA1B variation and schizophrenia (SZ). We now report an association between a set of variations (rs2227956, rs2075799, rs1043618, rs562047 and rs539689) within the same genes and a larger sample of schizophrenic inpatients. A single variation, rs539689 (HSPA1B), was found to be marginally associated with Positive and Negative Syndrome Scale (PANSS) positive scores at discharge, and haplotype analysis revealed a significant association between improvement in PANSS scores with both A-C-G-G and A-C-G-G haplotypes. These findings further support a role of heat shock proteins in the pathophysiology of SZ.