Death In Severe Sepsis Research Articles

Abstract 15505: Cardiac-Specific Jarid2 Deficiency, Results in Improved Survival and Myocardial Function Following Experimental Sepsis

Introduction: Myocardial depression and associated hemodynamic collapse are among the major causes of death in severe sepsis. Management of severe sepsis is largely supportive. Hypothesis: Emerging evidence suggests that the transcriptional repressor Jarid2 may play a regulatory role in sepsis; however, the functional role of Jarid2 in sepsis-induced myocardial dysfunction remains uninvestigated. Methods: Using both in in vivo (murine model of cecum ligation and puncture (CLP) in 12-week-old C57-wild type (WT) and cardiac specific Jarid2(knock-out, KO)) and in vitro (lipopolysaccharide, LPS) treatment of cultured murine cardiac myocytes) approaches we determined whether Jarid2 is a putative novel target for sepsis. Results: In response to CLP for 48hrs, WT displayed >60% mortality, survivors developed bacterial peritonitis, a marked inflammatory response (3-5-fold increases in serum and left ventricular (LV) interleukin (IL)-1beta, IL-6 and tumor necrosis factor (TNF)-alpha), myocardial dysfunction (20-35% decreases in dp/dt and echo-derived % ejection fraction (EF) and % fractional shortening (FS)), and a 40-50% decrease in LV Jarid2mRNA and protein compared to WT-sham. Jarid2KO mice showed resistance to CLP-induced bacterial peritonitis resulting in improved cardiac function (10-15% decrease in %EF and %FS), and survival (>90%) despite an exacerbated (10-15-fold increase in LV) inflammatory response compared to WT mice. In adult cultured cardiac myocytes derived from WT and Jarid2KO mice, treatment with the endotoxin LPS (1 microgram/mL) for 24 hrs, resulted in an 8-10-fold and 20-35-fold increase respectively, in the inflammatory cytokines TNF-alpha, IL-1beta and IL-6. Conclusions: These findings reveal that the loss of Jarid2 enhances bacterial clearance and despite an enhanced inflammatory response, resulted in improved myocardial function and survival following CLP-induced sepsis. As such, Jarid2 may be a novel therapeutic target in the treatment of sepsis-induced myocardial dysfunction.

Nurse Influence in Meeting Compliance With the Centers for Medicare and Medicaid Services Quality Measure

Increased mortality has been identified as the sepsis cascade progresses from sepsis to severe sepsis to septic shock. Estimates reflect sepsis death rates ranging from 10% to 20%, severe sepsis death rates of 20% to 50%, and septic shock fatality rates of 40% to 80%. The high rates of morbidity, mortality, and Medicare costs prompted the Centers for Medicare and Medicaid Services to implement bundled care and public reporting of the Early Management Bundle, Severe Sepsis/Septic Shock (SEP-1) quality measure in 2015. Sepsis care bundles were identified to be beneficial since the 1990s as the bundle facilitates efficient, effective, and timely delivery of care to support quality improvement. The SEP-1 measure can be challenging and requires the nurse's active participation. Nurses need increased knowledge of the sepsis cascade and treatments as defined in the SEP-1 quality measure. Increased knowledge and application of bundle elements are lifesaving and can influence postdischarge outcomes. This article discusses the nurse's role in meeting the specific elements of each bundle and strategies to improve bundle compliance.

Toll-Like Receptor 4 and NLRP3 Caspase 1- Interleukin-1β-Axis are Not Involved in Colon Ascendens Stent Peritonitis-Associated Heart Disease.

Hemodynamic collapse and myocardial dysfunction are among the major causes of death in severe sepsis. The purpose of this study was to assess the role played by toll-like receptor 4 and by the NLRP3 inflammasome in the cardiac dysfunction that occurs after high-grade polymicrobial sepsis. We performed the colon ascendens stent peritonitis (CASP) surgery in Tlr4, Nlrp3, and caspase-1 mice. We also assessed for the first time the electrical heart function in the colon ascendens stent peritonitis (CASP) model. The QJ interval was increased in wild-type C57BL/6J mice after CASP when compared with sham controls, a result paralleled by an increase in the cardiac action potential (AP) duration (APD). The decreases in ejection fraction (EF), left ventricle end diastolic volume, stroke volume, and cardiac output found after CASP were similar among all groups of mice. Similar heart response was found when Nlrp3 mice were submitted to high-grade cecal ligation and puncture. Despite developing cardiac dysfunction similar to wild types after CASP, Nlrp3 mice had reduced circulating levels of interleukin (IL)-1β, IL-6 and tumor necrosis factor-α. Our results demonstrate that the genetic ablation of Tlr4, Nlrp3, and caspase-1 does not prevent the cardiac dysfunction, despite preventing the increase in pro-inflammatory cytokines, indicating that these are not feasible targets to therapy in high-grade sepsis.

Utilidad del lactato sérico elevado como factor pronóstico de muerte en sepsis severa

Objective: To determine the usefulness of lactate as a prognostic factor of death in severe sepsis. Setting: Hospital Regional Docente de Trujillo. La Libertad. Perú. Material and Methods: A case control study nested in a cohort. We studied a total of 82 adult patients with severe sepsis during the period from June 2012 to April 2013 in whom we determined the usefulness of the lactate level by calculating the Positive and Negative Likelihood Ratio, Relative Risk, Positive and Negative Predictive Value, Sensibility and Specificity. The exposed cohort was constituted by those patients who presented a lactate > 2 mmol/l and the unexposed cohort by those with lactate < 2 mmol/l. Results: Overall mortality was of 54.9 % of the patients, being 92.7% in the group of cases and 17.1% in the group of controls respectively. We found a Sensitivity of 84.4% (CI: 72.7 - 96.1), a Specificity of 91.9% (CI:81.7 - 100.0), a Positive Predictive Value of 92.68% (CI: 83.5 - 100-0), a Negative Predictive Value of 82.9 (CI: 70.2 - 95.7), a Positive Likelihood Ratio of 10.4 (CI: 3.5 - 31.0), a Negative Likelihood Ratio of 0.2 (CI: 01 - 0.3) and a Relative Risk of 5.4 (CI: 2.8 - 10.7). Conclusion: Cancer, COPD, peripheral arterial disease, diabetes, heart failure, impaired baseline functional status; and overall burden of comorbidity are the main risk factors associated with hospital complications in older adults.

Elevated pregnancy-associated plasma protein A predicts myocardial dysfunction and death in severe sepsis

Pregnancy-associated plasma protein A (PAPPA) is an emerging biomarker used in various medical fields but has yet to be evaluated in critical care medicine. This study evaluates the value of PAPPA as a biomarker in predicting myocardial dysfunction and 28-day mortality in patients with severe sepsis. Serum concentrations of PAPPA and traditional cardiac biomarkers including cardiac troponin I (cTnI) and B-type natriuretic peptide (BNP) were measured on admission in 118 severely septic patients. The value of PAPPA for the diagnosis of sepsis-related myocardial dysfunction (SRMD) and for the prediction of 28-day mortality was subsequently evaluated using statistical methods. PAPPA was elevated (≥4.5 ng/mL) in 76 (64.4%) patients; patients with elevated PAPPA were more likely to have SRMD (76.3% vs. 38.1%, P < 0.001). By comparison of the area under the curve (AUC) in receiver operating characteristics analysis, PAPPA had comparable value (AUC 0.661, P = 0.003) to conventional biomarkers (BNP: AUC 0.699, P < 0.001; cTnI: AUC 0.647, P = 0.007) in the diagnosis of SRMD and offered superior value (AUC 0.771, P < 0.001) over them (all AUC<0.7, P > 0.05) in the prediction of 28-day death. Increased PAPPA (≥5.4 ng/mL) was associated with lower 28-day survival (χ(2) = 19.78, P < 0.001) and independently predicted 28-day mortality in septic patients. Serum PAPPA concentration frequently increases in patients with severe sepsis and appears to be associated with SRMD. PAPPA can be used as a novel biomarker for the diagnosis of SRMD and the prediction of outcomes in critically ill patients.

Assessment of hemodynamic efficacy and safety of 6% hydroxyethylstarch 130/0.4 vs. 0.9% NaCl fluid replacement in patients with severe sepsis: The CRYSTMAS study

IntroductionInadequate initial treatment and delayed hemodynamic stabilization (HDS) may be associated with increased risk of death in severe sepsis patients.MethodsIn order to compare the hemodynamic efficacy and safety of 6% HES 130/0.4 and NaCl 0.9% for HDS in patients with severe sepsis, we designed a prospective, multicenter, active-controlled, double-blind, randomized study in intensive care units.Results174 out of 196 patients reached HDS (88 and 86 patients for HES and NaCl, respectively). Significantly less HES was used to reach HDS vs. NaCl (1,379 ±886 ml in the HES group and 1,709 ±1,164 ml in the NaCl group (mean difference = -331± 1,033, 95% CI -640 to -21, P = 0.0185). Time to reach HDS was 11.8 10.1 hours vs. 14.3 ±11.1 hours for HES and NaCl, respectively. Total quantity of study drug infused over four consecutive days, ICU and hospital LOS, and area under the curve of SOFA score were comparable. Acute renal failure occurred in 24 (24.5%) and 19 (20%) patients for HES and NaCl, respectively (P = 0.454). There was no difference between AKIN and RIFLE criteria among groups and no difference in mortality, coagulation, or pruritus up to 90 days after treatment initiation.ConclusionSignificantly less volume was required to achieve HDS for HES vs. NaCl in the initial phase of fluid resuscitation in severe sepsis patients without any difference for adverse events in both groups.ClinicalTrials.govNCT00464204

Free hemoglobin concentration in severe sepsis: methods of measurement and prediction of outcome

IntroductionHemolysis can be induced in sepsis via various mechanisms, its pathophysiological importance has been demonstrated in experimental sepsis. However, no data on free hemoglobin concentrations in human sepsis are available. In the present study we measured free hemoglobin in patients with severe sepsis as well as in postoperative patients using four methods. It was our aim to determine the potential value of free hemoglobin as a biomarker for diagnosis and outcome of severe sepsis in critical illness.MethodsPlasma concentration of free hemoglobin was determined in patients with severe sepsis (n = 161) and postoperative patients (n = 136) on day 1 of diagnosis and surgery. For the measurement of free hemoglobin, an enzyme linked immunosorbent assay and three spectrophotometric algorithms were used. Moreover, SAPS II- and SOFA scores as well as procalcitonin concentration and outcome were determined. Kaplan-Meier analysis was performed and odds ratios were determined after classification of free hemoglobin concentrations in a high and low concentration group according to the median. For statistical evaluation the Mann-Whitney test and logistic regression analysis were used.ResultsIn non-survivors of severe sepsis, free hemoglobin concentration was twice the concentration compared to survivors. Thirty-day survival of patients, as evidenced by Kaplan-Meier analysis, was markedly lower in patients with high free hemoglobin concentration than in patients with low free hemoglobin concentration. Best discrimination of outcome was achieved with the spectrophotometric method of Harboe (51.3% vs. 86.4% survival, p < 0.001; odds ratio 6.1). Multivariate analysis including free hemoglobin, age, SAPS II- and SOFA-score and procalcitonin demonstrated that free hemoglobin, as determined by all 4 methods, was the best and an independent predictor for death in severe sepsis (p = 0.022 to p < 0.001). Free hemoglobin concentrations were not significantly different in postoperative and septic patients in three of four assays. Thus, free hemoglobin can not be used to diagnose severe sepsis in critical illness.ConclusionsFree hemoglobin is an important new predictor of survival in severe sepsis.

Severe protein C deficiency predicts early death in severe sepsis.

To explore the relationship between measures of baseline disease severity and survival time in patients with severe sepsis. A retrospective evaluation of the placebo group from a large placebo-controlled phase III clinical trial (PROWESS) comprising a total of 840 patients with severe sepsis from 164 medical centers. Data collected included baseline demographics and disease severity measurements, baseline protein C and interleukin-6 levels, 28-day and in-hospital survival rates, and cause of death to 28 days. The survival curve for the placebo patients can be divided into three segments during which the rate of death seemed to be different: the rapid alpha phase (day 0 to day 5), the beta phase (day 6 through day 15), and the gamma phase (day 16 to day 28). The risk of death during each phase was statistically significantly different. More patients died of refractory shock during the alpha phase than in the beta and gamma phases, whereas more patients died of respiratory failure during the beta and gamma phases than during the alpha phase. Multiple organ failure was a frequent cause of death during all phases. Protein C levels at the start of each time interval were highly predictive of outcome within that phase, with continued protein C deficiency being associated with mortality. Patients who died during either the alpha or beta phases had higher interleukin-6 levels at baseline than those who died later or who eventually survived. The rate and cause of death for patients with severe sepsis differs during the 28-day postdiagnosis period. Severe protein C deficiency (<40% of the level of protein C in pooled normal human plasma) and high interleukin-6 levels were associated with early death that resulted predominantly from refractory shock and multiple organ dysfunction.