Outcome Of Severe Sepsis Research Articles

Outcomes of Severe Sepsis and Septic Shock Patients on Chronic Antiplatelet Treatment: A Historical Cohort Study

Background. Sepsis is characterized by dysfunctional activation of platelets, and antiplatelet therapy could improve the outcomes of septic patients. Methods. We performed a retrospective cohort study of severe sepsis or septic shock adult patients. Outcomes of patients on antiplatelet therapy were compared to those that were not taking antiplatelet therapy by univariate analysis followed by a propensity score analysis based on the probability of receiving antiplatelet therapy. Results. Of 651 patients included in the study 272 (42.8%) were on antiplatelet therapy before the development of severe sepsis or septic shock. After adjusting for important confounding variables antiplatelet therapy was not associated with a decreased risk of hospital mortality (odds ratio 0.73, 95% confidence interval 0.46–1.16). Antiplatelet therapy was associated with a decreased incidence of acute respiratory distress syndrome/acute lung injury (odds ratio 0.50, 95% confidence interval 0.35–0.71) and reduced need of mechanical ventilation (odds ratio 0.62, 95% confidence interval 0.45–87). Incidence of acute kidney injury was similar between both groups (odds ratio 1.08, 95% confidence interval 0.73–1.59). Conclusions. The use of antiplatelet therapy before the diagnosis of severe sepsis or septic shock was not associated with decreased hospital mortality. Antiplatelet therapy was associated with a decreased incidence of acute lung injury/acute respiratory distress syndrome.

The NFKB1 Promoter Polymorphism (−94ins/delATTG) Alters Nuclear Translocation of NF-κB1 in Monocytes after Lipopolysaccharide Stimulation and Is Associated with Increased Mortality in Sepsis

Because the nuclear factor-κB (NF-κB) coupled pathway is believed to amplify inflammation prevailing in sepsis, the authors tested the hypotheses that the insertion-deletion polymorphism (-94ins/delATTG) (1) alters nuclear translocation of nuclear factor-κB and activator protein-1 (NF-κB1) in monocytes after lipopolysaccharide stimulation; (2) affects lipopolysaccharide-induced NF-κB1 messenger RNA expression, tumor necrosis factor α concentrations, and tissue factor activity; and (3) may be associated with increased 30-day mortality in patients with sepsis. Nuclear translocation of NF-κB1 in monocytes after lipopolysaccharide stimulation from healthy blood donors was performed with immunofluorescence staining (n = 5 each). Lipopolysaccharide-induced NF-κB1 messenger RNA expression was measured with real-time polymerase chain reaction (PCR; n = 60), tumor necrosis factor α concentrations with a multiplexing system kit (n = 60), and tissue factor activity with thromboelastometry (n = 105). In a prospective study, multivariate proportional hazard analysis tested 30-day mortality in patients with sepsis (n = 143). The homozygous deletion genotype compared with the homozygous insertion genotype was associated with a nearly twofold increase in nuclear translocation of NF-κB1 (P = 0.001), a threefold difference in NF-κB1 messenger RNA expression (P = 0.001), and a twofold increase in tissue factor expression (P = 0.021). The deletion allele in adults with severe sepsis was tested as an independent prognostic factor for 30-day mortality (hazard ratio, 2.3; 95% CI, 1.13-4.8; P = 0.022). Mortality was 25% for homozygous insertion genotypes but 41% for combined heterozygous deletion/homozygous deletion genotypes (P = 0.034). The deletion allele of the NFκB1 insertion-deletion (-94ins/delATTG) polymorphism is associated with increased 30-day mortality in patients with severe sepsis and increased reaction of the innate immune system.

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Introduction: Based on evidence that early antibiotics improve outcomes in severe sepsis, clinical guidelines are often implemented in the emergency department (ED) to expedite therapy. The role of guidelines targeted for children who develop nosocomial sepsis is not known. Hypothesis: For patients transferred to ICU, time from sepsis recognition to antibiotic administration is delayed in hospitalized inpatients compared to ED patients. Methods: We studied 75 consecutive patients with severe sepsis admitted to an academic pediatric ICU from Feb-July 2012 via the ED (n=25) or inpatient floor (n=50). A sepsis guideline was in place in the ED, but not inpatient floors or ICU. Age, chronic illness, and PRISM III-12 score were determined. Median (IQR) times from sepsis recognition to antibiotic order and administration were compared in ED vs hospitalized inpatients using Wilcoxon rank sum test. Achieving the benchmark of antibiotic administration within 60 minutes of sepsis recognition was compared in ED vs inpatient groups using binary logistic regression. Results: Septic patients admitted to ICU from ED and inpatient were similar in age (median, IQR 11.4, 5.2-14.0 vs 8.0, 2.4-18.0 years; p=0.18) and PRISM score (6, 5-12 vs 8, 3-12; p=0.76) but those admitted from ED had less chronic illness (ED 36%, inpatients 76%; p<0.01). Time to antibiotic order was 47 (7-126) for ED vs 87 (5-393) min for inpatients (p=0.18). Time to antibiotic administration was 73 (25-190) for ED vs 134 (58-443) min for inpatients (p<0.001). Delay from antibiotic order to administration was shorter for ED vs inpatients (14, 6-30 vs 62, 28-494 min; p=0.04). Inpatients were less likely to achieve antibiotic administration within 60 minutes (OR 0.29, 95% CI 0.11-0.81). After controlling for chronic illness, inpatients remained less likely to meet this metric, though this was not statistically significant (OR 0.41, 0.15-1.13). Conclusions: For patients transferred to ICU, time from sepsis recognition to antibiotic administration was delayed in hospitalized inpatients treated without a clinical sepsis guideline compared to ED patients treated with a clinical guideline. Guidelines that address barriers to therapy for inpatients who develop sepsis are needed.

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Introduction: Acinetobacter baumanni is a serious nosocomial pathogen worldwide. Cancer patients have been found to be at high risk of developing Acinetobacter-related infections. Hypothesis: We describe the characteristics and outcomes of severe sepsis and septic shock due to Acinetobacter baumannii in cancer patients. We hypothesize that the outcomes of such a serious infection in immunocompromised patients is poor. Methods: The ICU electronic database was used to identify all cancer patients who developed severe sepsis and septic shock due to Acinetobacter baumannii between Jan 1, 2007 and Dec 31, 2010. The demographics of all patients were recorded. In addition, organ failure, the site of positive cultures, type of infection, incidence of drug resistance, length of ICU stay and ICU mortality were determined. Results: Over the study period, 30 patients were identified; mean age was 52 years (range 22-72), mean APACHE II was 23.9 (range 11-42), 17 (56.7%) patients were male and 17 (56.7%) had hematological malignancies. Upon presentation, 10(33.4%) patients had 1 organ failure, 12(40%) had 2 organ failure, 3(9.9%) had 3 organ failure, and 2(6.7%) had 4 organ failure. Twenty-four (80%) patients had one positive culture upon presentation, while 4 (13.3%) had two positive cultures and 1 (3.3%) had three positive cultures. The majority of the positive cultures were in the blood (n=12; 32%), transbronchial aspirate/sputum (n=12; 32%%) and wound (n=5; 24.3%). All reported Acinetobacter baumannii were carbapenem-resistant. Most common types of infection were nosocomial pneumonia (n=24; 80%), permanent central line infections (n=7; 23.3%) and temporary central line infections (n=6; 20%). The ICU length of stay was 10 days (range 0-28) and ICU mortality was reported in 21 patients (70%). Conclusions: Severe sepsis and septic shock due to carbapenem-resistant acinetobacter baumanni in cancer patients is associated with high mortality. Measures are needed to reduce the incidence of central line infections in this patient population.

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Introduction: Advances in therapeutics have resulted in prolonged life expectancy of patients with cancer. These patients especially ones with metastatic disease have diminished physiological reserve and remain at high risk of sepsis secondary to immunosuppression from both the chemotherapeutic agents used as well as the underlying malignancy. Outcomes of severe sepsis have not been systematically studied in this population. Hypothesis: Patients with metastatic disease and severe sepsis have higher mortality rate and have different discharge destinations in comparison to similar counterparts without metastatic disease. Methods: Using the Nationwide Inpatient Sample (NIS) from 2007 to 2009, patients older than 18 years, discharged with severe sepsis were identified using ICD-9-CM codes as described in literature. The discharge destinations were identified using the NIS variable DISPUB92. Studied outcomes were mortality, length of hospital stay and discharge disposition. We also examined rates of invasive mechanical ventilation, blood transfusion, use of central venous catheters and new dialysis. Results: There were total of 2,544,941 estimated adult discharges with severe sepsis from 2007 to 2009. Of these, 437,093 (17.2%) had a diagnosis of cancer and of these, 33.6% had metastatic disease. The all-cause in-hospital mortality in patients with metastatic disease was significantly higher at 42.2% (p<0.001) when compared with 29.4% in cancer patients and 24.9% in those without cancer. The median hospital length of stay was 11 days (interquartile range [IQR] 5-22 days) while in those without cancer was 9 days (IQR 5-17 days). The utilization of invasive mechanical ventilation, central venous catheters and new dialysis were significantly lower in this group. Of the survivors, 25.4% were discharged to a hospice facility as compared to 6.2% of patients without cancer. Transfer to skilled nursing facility, intermediate care, long term acute care and rehabilitation centers were significantly lower for persons with metastatic disease. Conclusions: Patients with severe sepsis and metastatic disease have significantly higher in-hospital mortality and higher rate of discharge to hospice facilities.

Central Venous Oxygen Saturation Under Non-Protocolized Resuscitation Is Not Related to Survival in Severe Sepsis or Septic Shock

Protocolized hemodynamic resuscitation in severe sepsis or septic shock is not universally applied in all emergency departments and general hospital wards around the world. It is unknown whether ScvO2 levels are associated with the clinical outcome of severe sepsis or septic shock under nonprotocolized resuscitation. In this prospective study, we enrolled 124 noncirrhotic patients who were admitted to intensive care units for severe sepsis or septic shock. The average Acute Physiology and Chronic Health Evaluation II score was 25.3 (SD, 7.6). According to ScvO2 levels after initial resuscitation before intensive care unit admission, patients were divided into high (ScvO2 ≥ 70%, n = 63) and low (ScvO2 < 70%, n = 61) ScvO2 groups. Compared with high ScvO2 groups, low ScvO2 groups showed no significant differences in 28-day mortality (25.4% vs. 24.6%; P = 0.943) or hospital mortality (30.2% vs. 31.1%; P = 0.794). Multivariate logistic regression models showed that low mean arterial pressure (hazard ratio, 0.967; 95% confidence interval, 0.940-0.994; P = 0.019) and high central venous pressure (hazard ratio, 1.150; 95% confidence interval, 1.057-1.251; P = 0.001) after initial resuscitation were associated with higher 28-day mortality. On the contrary, ScvO2 levels after resuscitation were not related to 28-day or hospital mortality. In conclusion, our results showed that mean arterial pressure and central venous pressure were still the most important hemodynamic variables in initial hemodynamic resuscitation. Low postresuscitation ScvO2 was not associated with a worse outcome. It is possible that ScvO2 less than 70% might not necessarily be associated with tissue hypoxia, and critical ScvO2 levels require to be determined by further studies.

Comparison of clinical outcomes between intermittent and continuous monitoring of central venous oxygen saturation (ScvO2) in patients with severe sepsis and septic shock: a pilot study

BackgroundThe Surviving Sepsis Campaign (SSC) to improve patient outcomes in severe sepsis and septic shock contains recommendations for protocolised resuscitation including early goal-directed therapy (EGDT) resuscitation. In EGDT, central venous...

Hospitalizations, costs, and outcomes of severe sepsis in the United States 2003 to 2007

Hospitalizations, costs, and outcomes of severe sepsis in the United States 2003 to 2007

Toll-like receptor 9 activation in neutrophils impairs chemotaxis and reduces sepsis outcome*

To investigate the role of toll-like receptor 9 on sepsis-induced failure of neutrophil recruitment to the site of infection. Prospective experimental study. University research laboratory. Model of polymicrobial sepsis induced by cecal ligation and puncture in wild-type and toll-like receptor 9-deficient mice. Toll-like receptor 9-deficient mice with cecal ligation and puncture-induced severe sepsis did not demonstrate failure of neutrophil migration and consequently had a low systemic inflammatory response and a high survival rate. Upon investigating the mechanism by which toll-like receptor 9 deficiency prevents the failure of neutrophil migration, it was found that neutrophils derived from toll-like receptor 9--deficient mice with cecal ligation and puncture-induced severe sepsis expressed high levels of chemokine C-X-C motif receptor 2 (CXCR2) and had reduced induction of G-protein-coupled receptor kinase 2. These findings suggest that the poor outcome of severe sepsis is associated with toll-like receptor 9 activation in neutrophils, which triggers G-protein-coupled receptor kinase 2 expression and CXCR2 downregulation. These events account for the reduction of neutrophil migration to the site of infection, with consequent spreading of the infection, onset of the systemic inflammatory response, and a decrease in survival.

Editorial: How nurses can support the Surviving Sepsis Campaign

Editorial: How nurses can support the Surviving Sepsis Campaign

Hospitalizations, costs, and outcomes of severe sepsis in the United States 2003 to 2007

To assess trends in number of hospitalizations, outcomes, and costs of severe sepsis in the United States. Temporal trends study using the Nationwide Inpatient Sample. Adult patients with severe sepsis (defined as a diagnosis of sepsis and organ dysfunction) diagnosed between 2003 and 2007. We determined the weighted frequency of patients hospitalized with severe sepsis. We calculated age- and sex-adjusted population-based mortality rates for severe sepsis per 100,000 population and also used logistic regression to adjust in-hospital mortality rates for patient characteristics. We calculated inflation-adjusted costs using hospital-specific cost-to-charge ratios. We identified a rapid steady increase in the number of cases of severe sepsis, from 415,280 in 2003 to 711,736 in 2007 (a 71% increase). The total hospital costs for all patients with severe sepsis increased from $15.4 billion in 2003 to $24.3 billion in 2007 (57% increase). The proportion of patients with severe sepsis and only a single organ dysfunction decreased from 51% in 2003 to 45% in 2007 (p < .001), whereas the proportion of patients with three or four or more organ dysfunctions increased 1.19-fold and 1.51-fold, respectively (p < .001). During the same time period, we observed 2% decrease per year in hospital mortality for patients with severe sepsis (p < .001), as well as a slight decrease in the length of stay (9.9 days to 9.2 days; p < .001) and a significant decrease in the geometric mean cost per case of severe sepsis ($20,210 per case in 2003 and $19,330 in 2007; p = .025). The increase in the number of hospitalizations for severe sepsis coupled with declining in-hospital mortality and declining geometric mean cost per case may reflect improvements in care or increases in discharges to skilled nursing facilities; however, these findings more likely represent changes in documentation and hospital coding practices that could bias efforts to conduct national surveillance.

Circulating cell-free DNA levels measured by a novel simple fluorescent assay are predictive for outcome of severe sepsis

Circulating cell-free DNA (CFD) was found to be a predictor of outcome in severe sepsis and septic shock [1]. The standard CFD assays are work-intensive and not practical for routine clinical laboratory use. We have recently developed a new simple, fast and reliable assay for CFD measurement. The aim was to evaluate the association between admission levels of CFD and severe sepsis outcome in patients hospitalized in intensive care utilizing the new assay.

Outcomes in severe sepsis and patients with septic shock do not matter! PIRO is a score to treat severe septic and septic shock patients not to measure outcomes

Outcomes in severe sepsis and patients with septic shock do not matter! PIRO is a score to treat severe septic and septic shock patients not to measure outcomes

IL-17A rs1974226 GG genotype is associated with increased susceptibility to Gram-positive infection and mortality of severe sepsis

IL-17A plays a key role in host defense against microbial infection including Gram-positive bacteria. Genetic factors contribute to the host defense. Whether genetic variation of IL-17A is associated with altered clinical outcome of severe sepsis is unknown.

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.

Nationwide Trends of Severe Sepsis in the 21st Century (2000–2007)

Severe sepsis is common and often fatal. The expanding armamentarium of evidence-based therapies has improved the outcomes of persons with this disease. However, the existing national estimates of the frequency and outcomes of severe sepsis were made before many of the recent therapeutic advances. Therefore, it is important to study the outcomes of this disease in an aging US population with rising comorbidities. We used the Healthcare Costs and Utilization Project's Nationwide Inpatient Sample (NIS) to estimate the frequency and outcomes of severe sepsis hospitalizations between 2000 and 2007. We identified hospitalizations for severe sepsis using International Classification of Diseases, Ninth Revision, Clinical Modification codes indicating the presence of sepsis and organ system failure. Using weights from NIS, we estimated the number of hospitalizations for severe sepsis in each year. We combined these with census data to determine the number of severe sepsis hospitalizations per 100,000 persons. We used discharge status to identify in-hospital mortality and compared mortality rates in 2000 with those in 2007 after adjusting for demographics, number of organ systems failing, and presence of comorbid conditions. The number of severe sepsis hospitalizations per 100,000 persons increased from 143 in 2000 to 343 in 2007. The mean number of organ system failures during admission increased from 1.6 to 1.9 (P < .001). The mean length of hospital stay decreased from 17.3 to 14.9 days. The mortality rate decreased from 39% to 27%. However, more admissions ended with discharge to a long-term care facility in 2007 than in 2000 (35% vs 27%, P < .001). An increasing number of admissions for severe sepsis combined with declining mortality rates contribute to more individuals surviving to hospital discharge. Importantly, this leads to more survivors being discharged to skilled nursing facilities and home with in-home care. Increased attention to this phenomenon is warranted.

Improving severe sepsis outcomes, managing cholesterol in patients with diabetes, and pediatric adverse events

Improving severe sepsis outcomes “An empiric antimicrobial guide specific for severe sepsis was associated with a reduced length of stay, a significantly earlier time to first dose antibiotic, and significantly lower total and variable hospital costs,” reported Hutchison et al.1 Information was abstracted from charts of 119 patients treated at a large medical center. The control group consisted of 67 patients treated before implementation of the medication guide, and the intervention group included 52 patients treated after implementation. The guide provided recommendations of first and second antibiotic choice based on the origin (e.g., health care iatrogenesis, communityacquired or a patient with neutropenia) and the location of the severe sepsis (e.g., lung, skin, gastrointestinal). Postimplementation, the time to first antibiotic administration (9.8 ± 8.8 vs. 14.7 ± 11.5 hours) and the overall length of stay (1.77 ± 1.13 vs. 14.90 ± 45.07 days) were significantly shorter. Significant cost savings were realized in the total (30%) and variable costs ($2,831) of the patient stay. Implications. The two most important factors in successful sepsis treatment are time to treatment and antibiotic choice. Evidence-based recommendations contained on a single page were cost effective and improved care by getting the correct antibiotic to the patient more quickly.

Outcomes in severe sepsis and patients with septic shock: Pathogen species and infection sites are not associated with mortality: Erratum

Outcomes in severe sepsis and patients with septic shock: Pathogen species and infection sites are not associated with mortality: Erratum

The Outcome of Polymicrobial Sepsis Is Independent of T and B CellS

The contribution of the adaptive and innate immune systems to the pathogenesis and outcome of sepsis remains a fundamental yet controversial question. Here, we use mice lacking the recombination activating gene 1 (Rag-1) to study the role of T and B cells in sepsis after cecal ligation and puncture (CLP). Spleens of Rag-1 mice were atrophic and completely devoid of CD3 T cells and CD19 B cells. Wild-type mice and Rag-1 mice (both on a C57BL/6J background) underwent CLP or sham surgery. Both wild-type and Rag-1 mice developed clinical signs of sepsis within the first day after CLP. This included severe hypothermia as measured by a decrease in body surface temperature and organ dysfunction as detected by plasma increases in blood urea nitrogen and lactate dehydrogenase levels. Survival curves of wild-type and Rag-1 mice after CLP were superimposable, with 35% survival in the wild-type group and 27% survival in the Rag-1 group, respectively (not significant, P = 0.875). Using multiplex bead-based assays, the mediator concentrations for 23 cytokines and chemokines were measured in plasma of wild-type and Rag-1 mice 8 h after CLP or sham surgery. Compared with sham surgery mice, the highest mediator levels were observed for granulocyte colony-stimulating factor, keratinocyte chemoattractant, IL-6, monocyte chemotactic protein 1, and IL-10. Levels for most mediators were unaffected by the absence of T and B lymphocytes. Only the concentrations of IL-6 and IL-17 were found to be significantly lower in Rag-1 mice compared with wild-type mice. In conclusion, the absence of T and B cells in the CLP model used does not appear to affect the acute outcome of severe sepsis.

Clinical and Demographic Factors Associated with Antipyretic Use in Gram-Negative Severe Sepsis and Septic Shock

Antipyretic therapy is commonly prescribed for patients with infection, but studies of its impact on clinical outcomes have yielded mixed results. No data exist to characterize the use of antipyretic medications in patients with severe sepsis or septic shock. To identify clinical and demographic factors associated with antipyretic medication administration in severe sepsis and septic shock. This single-center, retrospective, cohort study assessed febrile patients (temperature ≥ 38.3 °C) with gram-negative severe sepsis or septic shock at an 1111-bed academic medical center between January 2002 and February 2008. Patients were excluded if they had liver disease, acute brain injury, or allergy to acetaminophen. Generalized estimating equations were used to estimate the effect of clinical factors on treatment of patients with antipyretic medications. Although 76% of patients in this febrile cohort (n = 241) were prescribed an antipyretic agent, only 42% received antipyretic therapy; 95% of the doses were acetaminophen. Variables associated with antipyretic treatment were maximum body temperature (OR 2.11, 95% CI 1.53 to 2.89), time after sepsis diagnosis (OR 0.88, 95% CI 0.82 to 0.95), surgery during hospitalization (OR 0.49, 95% CI 0.31 to 0.80), death within 36 hours (OR 0.35, 95% CI 0.15 to 0.85), and mechanical ventilation (OR 0.58, 95% CI 0.34 to 0.98). Severity of illness factors, demographic factors, and patient treatment location did not predict who would receive antipyretic therapy. Most febrile episodes in patients with gram-negative severe sepsis or septic shock were not treated with antipyretic medications. Further studies are needed to demonstrate the effect of antipyretics on clinically relevant outcomes in severe sepsis and septic shock.