Multifaceted interventions to decrease mortality in patients with severe sepsis/septic shock-a quality improvement project.
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ABSTRACT:
SUBMITTER: Siontis B
PROVIDER: S-EPMC4614979 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Morbidity and mortality from sepsis remains unacceptably high. Large variability in clinical practice, plus the increasing awareness that certain processes of care associated with improved critical care outcomes, has led to the development of clinical practice guidelines in a variety of areas related to infection and sepsis. The Surviving Sepsis Guidelines for Management of Severe Sepsis and Septic Shock were first published in 2004, revised in 2008, and recently revised again and published in 2013. The first part of this manuscript is a summary of the 2013 guidelines with some editorial comment. The second part of the manuscript characterizes hospital based sepsis performance improvement programs and highlights the sepsis bundles from the Surviving Sepsis Campaign as a key component of such a program.
| S-EPMC3916373 | biostudies-literature
Project description:ObjectivesTo assess the prevalence of immunocompromised diagnoses among children with severe sepsis and septic shock, and to determine the association between immunocompromised diagnoses and clinical outcomes after adjustment for demographics and illness severity.DesignRetrospective multicenter cohort study.SettingEighty-three centers in the Virtual Pediatric Systems database.PatientsChildren with severe sepsis or septic shock admitted to a participating PICU between January 1, 2012, and December 31, 2016.InterventionsNone.Measurements and main resultsAcross 83 centers, we identified 10,768 PICU admissions with an International Classification of Diseases, 9th Revision, Clinical Modification code for severe sepsis or septic shock; 3,021 of these patients (28%) had an immunocompromised diagnosis. To evaluate variation across centers and determine factors associated with PICU mortality, we used mixed-effect logistic regression models. Among patients without hematopoietic cell transplant, congenital immunodeficiency (adjusted odds ratio, 1.90; 95% CI, 1.24-2.92), multiple prior malignancies (adjusted odds ratio, 1.86; 95% CI, 1.15-2.99), and hemophagocytic lymphohistiocytosis (adjusted odds ratio, 3.09; 95% CI, 1.91-4.98) were associated with an increased odds of PICU mortality. Among patients with prior hematopoietic cell transplant, liquid malignancy (adjusted odds ratio, 3.15; 95% CI, 2.09-4.74), congenital immunodeficiency (adjusted odds ratio, 6.94; 95% CI, 3.84-12.53), multiple prior malignancies (adjusted odds ratio, 3.54; 95% CI, 1.80-6.95), and hemophagocytic lymphohistiocytosis (adjusted odds ratio, 2.79; 95% CI, 1.36-5.71) were associated with an increased odds of PICU mortality. PICU mortality varied significantly by center, and a higher mean number of sepsis patients per month in a center was associated with lower PICU mortality (adjusted odds ratio, 0.94; 95% CI, 0.90-0.98). PICU resource utilization varied by immunocompromised diagnosis and history of hematopoietic cell transplant, and among survivors immunocompromised patients have shorter median PICU length of stay compared with patients without immunocompromised diagnoses (p < 0.001).ConclusionsImmunocompromised diagnoses are present in 28% of children with severe sepsis or septic shock. Multiple prior malignancies, hemophagocytic lymphohistiocytosis, congenital immunodeficiency, and hematopoietic cell transplant are independently associated with an increased odds of PICU mortality in children with severe sepsis or septic shock. Significant variation exists in PICU mortality among centers despite adjustment for immunocompromised diagnoses, known risk factors for sepsis-related mortality, and center-level sepsis volume.
| S-EPMC7311286 | biostudies-literature
Project description:BackgroundSerum procalcitonin (PCT) evaluation has been proposed for early diagnosis and accurate staging and to guide decisions regarding patients with sepsis, severe sepsis and septic shock, with possible reduction in mortality.ObjectivesTo assess the effectiveness and safety of serum PCT evaluation for reducing mortality and duration of antimicrobial therapy in adults with sepsis, severe sepsis or septic shock.Search methodsWe searched the Central Register of Controlled Trials (CENTRAL; 2015, Issue 7); MEDLINE (1950 to July 2015); Embase (Ovid SP, 1980 to July 2015); Latin American Caribbean Health Sciences Literature (LILACS via BIREME, 1982 to July 2015); and the Cumulative Index to Nursing and Allied Health Literature (CINAHL; EBSCO host, 1982 to July 2015), and trial registers (ISRCTN registry, ClinicalTrials.gov and CenterWatch, to July 2015). We reran the search in October 2016. We added three studies of interest to a list of 'Studies awaiting classification' and will incorporate these into formal review findings during the review update.Selection criteriaWe included only randomized controlled trials (RCTs) testing PCT-guided decisions in at least one of the comparison arms for adults (≥ 18 years old) with sepsis, severe sepsis or septic shock, according to international definitions and irrespective of the setting.Data collection and analysisTwo review authors extracted study data and assessed the methodological quality of included studies. We conducted meta-analysis with random-effects models for the following primary outcomes: mortality and time spent receiving antimicrobial therapy in hospital and in the intensive care unit (ICU), as well as time spent on mechanical ventilation and change in antimicrobial regimen from a broad to a narrower spectrum.Main resultsWe included 10 trials with 1215 participants. Low-quality evidence showed no significant differences in mortality at longest follow-up (risk ratio (RR) 0.81, 95% confidence interval (CI) 0.65 to 1.01; I2 = 10%; 10 trials; N = 1156), at 28 days (RR 0.89, 95% CI 0.61 to 1.31; I2 = 0%; four trials; N = 316), at ICU discharge (RR 1.03, 95% CI 0.50 to 2.11; I2 = 49%; three trials; N = 506) and at hospital discharge (RR 0.98, 95% CI 0.75 to 1.27; I2 = 0%; seven trials; N = 805; moderate-quality evidence). However, mean time receiving antimicrobial therapy in the intervention groups was -1.28 days (95% CI to -1.95 to -0.61; I2 = 86%; four trials; N = 313; very low-quality evidence). No primary study has analysed the change in antimicrobial regimen from a broad to a narrower spectrum.Authors' conclusionsUp-to-date evidence of very low to moderate quality, with insufficient sample power per outcome, does not clearly support the use of procalcitonin-guided antimicrobial therapy to minimize mortality, mechanical ventilation, clinical severity, reinfection or duration of antimicrobial therapy of patients with septic conditions.
| S-EPMC6353122 | biostudies-literature
Project description:Early prognostic prediction of sepsis is essential in adjusting therapeutic protocols to prevent deterioration and reduce mortality. We compared the predictive value of the serum concentration of the soluble triggering receptor expressed on myeloid cells 1 (sTREM-1) for 28-day mortality and for the development of severe sepsis or septic shock on the third day with the levels of interleukin (IL)-6, C-reactive protein (CRP) and procalcitonin (PCT). The study was conducted on 85 patients with sepsis. sTREM-1, CRP, PCT and IL-6 concentrations were measured upon study inclusion (day 0) and on days 1, 2, 3 and 5. APACHE II, SAPS II and SOFA scores were analyzed. The sTREM-1 levels (pg/ml) were higher in non-survivors than in survivors at admission (773 vs. 391, p < 0.001) and on days 1, 2, 3 and 5. In predicting the development of severe sepsis, the highest AUCs were found for PCT (0.744, 95% CI 0.638-0.85) and sTREM-1 (0.664, 95% CI 0.55-0.778); and in septic shock prediction, for PCT (0.766, 95% CI 0.665-0.867) and IL-6 (0.707, 95% CI 0.595-0.819). sTREM-1 positively correlated with APACHE II, SAPS II and SOFA scores. At inclusion, significant AUC for predicting 28-day mortality was 0.772 for the sTREM-1 (95% CI 0.672-0.871), 0.858 for APACHE II (95% CI 0.768-0.948), 0.847 for SAPS II (95% CI 0.733-0.96), 0.806 for SOFA score (95% CI 0.698-0.915). sTREM-1 can early predict the 28-day sepsis mortality, although its effectiveness is lower in comparison with clinical severity scores.
| S-EPMC6061141 | biostudies-literature
Project description:BackgroundThere is ample literature available on the association between both time to antibiotics and appropriateness of antibiotics and clinical outcomes from sepsis. In fact, the current state of debate surrounds the balance to be struck between prompt empirical therapy and care in the choice of appropriate antibiotics (both in terms of the susceptibility of infecting organism and minimizing resistance arising from use of broad-spectrum agents). The objective of this study is to determine sepsis bundle compliance and the appropriateness of antimicrobial therapy in patients with severe sepsis and septic shock and its impact on outcomes.MaterialThis study was conducted in the ICU of a tertiary care, private hospital in São Paulo, Brazil. A retrospective cohort study was conducted from July 2005 to December 2012 in patients with severe sepsis and septic shock.ResultsA total of 1,279 patients were identified with severe sepsis and septic shock, of which 358 (32.1%) had bloodstream infection (BSI). The inpatient mortality rate was 29%. In evaluation of the sepsis bundle, over time there was a progressive increase in serum arterial lactate collection, obtaining blood cultures prior to antibiotic administration, administration of broad-spectrum antibiotics within 1 hour, and administration of appropriate antimicrobials, with statistically significant differences in the later years of the study. We also observed a significant decrease in mortality. In patients with bloodstream infection, after adjustment for other covariates the administration of appropriate antimicrobial therapy was associated with a decrease in mortality in patients with severe sepsis and septic shock (p = 0.023).ConclusionsThe administration of appropriate antimicrobial therapy was independently associated with a decline in mortality in patients with severe sepsis and septic shock due to bloodstream infection. As protocol adherence increased over time, the crude mortality rate decreased, which reinforces the need to implement institutional guidelines and monitor appropriate antimicrobial therapy compliance.
| S-EPMC4222820 | biostudies-literature
Project description:BackgroundAging-related changes in platelet and monocyte interactions may contribute to adverse outcomes in sepsis but remain relatively unexamined. We hypothesized that differential platelet-monocyte aggregate (PMA) formation in older septic patients alters inflammatory responses and mortality.MethodsWe prospectively studied 113 septic adults admitted to the intensive care unit with severe sepsis or septic shock. Patients were dichotomized a priori into one of two groups: older (age ? 65 years, n = 28) and younger (age < 65 years, n = 85). PMA levels were measured in whole blood via flow cytometry within 24 hours of admission. Plasma levels of IL-6 and IL-8, proinflammatory cytokines produced by monocytes upon PMA formation, were determined by commercial assays. Patients were followed for the primary outcome of 28-day, all-cause mortality.ResultsElevated PMA levels were associated with an increased risk of mortality in older septic patients (hazard ratio for mortality 5.64, 95% confidence interval 0.64-49.61). This association remained after adjusting for potential confounding variables in multivariate regression. Receiver operating curve analyses demonstrated that PMA levels greater than or equal to 8.43% best predicted 28-day mortality in older septic patients (area under the receiver operating curve 0.82). Plasma IL-6 and IL-8 levels were also significantly higher in older nonsurvivors. In younger patients, neither PMA levels nor plasma monokines were significantly associated with mortality.ConclusionsIncreased PMA formation, and associated proinflammatory monokine synthesis, predicts mortality in older septic patients. Although larger studies are needed, our findings suggest that heightened PMA formation in older septic patients may contribute to injurious inflammatory responses and an increased risk of mortality.
| S-EPMC4366600 | biostudies-literature
Project description:For more than two decades, sepsis was defined as a microbial infection that produces fever (or hypothermia), tachycardia, tachypnoea and blood leukocyte changes. Sepsis is now increasingly being considered a dysregulated systemic inflammatory and immune response to microbial invasion that produces organ injury for which mortality rates are declining to 15-25%. Septic shock remains defined as sepsis with hyperlactataemia and concurrent hypotension requiring vasopressor therapy, with in-hospital mortality rates approaching 30-50%. With earlier recognition and more compliance to best practices, sepsis has become less of an immediate life-threatening disorder and more of a long-term chronic critical illness, often associated with prolonged inflammation, immune suppression, organ injury and lean tissue wasting. Furthermore, patients who survive sepsis have continuing risk of mortality after discharge, as well as long-term cognitive and functional deficits. Earlier recognition and improved implementation of best practices have reduced in-hospital mortality, but results from the use of immunomodulatory agents to date have been disappointing. Similarly, no biomarker can definitely diagnose sepsis or predict its clinical outcome. Because of its complexity, improvements in sepsis outcomes are likely to continue to be slow and incremental.
| S-EPMC5538252 | biostudies-other
Project description:BackgroundSevere sepsis is a potentially deadly illness and always requires intensive care. Do-not-resuscitate (DNR) orders remain a debated issue in critical care and limited data exist about its impact on care of septic patients, particularly in East Asia. We sought to assess outcome of severe sepsis patients with regard to DNR status in Taiwan.MethodsA retrospective cohort study was conducted in intensive care units (ICUs) between 2008 and 2010. All severe sepsis patients were included for analysis. Primary outcome was association between DNR orders and ICU mortality. Volume of interventions was used as proxy indicator to indicate aggressiveness of care.ResultsSixty-seven (9.4%) of 712 patients had DNR orders on ICU admission, and these patients were older and had higher disease severity compared with patients without DNR orders. Notably, DNR patients experienced high ICU mortality (90%). Multivariate analysis revealed that the presence of DNR orders was independently associated with ICU mortality (odds ratio: 6.13; 95% confidence interval: 2.66-14.10). In propensity score-matched cohort, ICU mortality rate (91%) in the DNR group was statistically higher than that (62%) in the non-DNR group (p <0.001). Regarding ICU interventions, arterial and central venous catheterization were more commonly used in DNR patients than in non-DNR patients.ConclusionsFrom the Asian perspective, septic patients placed on DNR orders on ICU admission had exceptionally high mortality. In contrast to Western reports, DNR patients received more ICU interventions, reflecting more aggressive approach to dealing with this patient population. The findings in some ways reflect differences between East and West cultures and suggest that DNR status is an important confounder in ICU studies involving severely septic patients.
| S-EPMC4944975 | biostudies-literature
Project description:OBJECTIVE:We aim to synthesise up-to-date randomised trials to investigate the effects of levosimendan on mortality and clinical outcomes in severe sepsis and septic shock. METHODS:A collection of databases including PubMed, EMBASE, Cochrane Central Register and Web of Science were searched updated to August 2017. Randomised trials were included when they pertain to the use of levosimendan in severe sepsis or septic shock compared with any category of inotropes, or as an adjunct to standard therapy with mortality reported. The primary outcome was mortality, and the secondary outcomes were clinical performances including serum lactate, cardiac function, vasopressor requirement and fluid infusion. RESULTS:A total of 10 studies with 1036 patients were included in this meta-analysis. The results revealed that levosimendan could not reduce mortality significantly in severe sepsis and septic shock (OR 0.89, 95% CI 0.69 to 1.16, P=0.39). Levosimendan use could reduce serum lactate more effectively, and enhance cardiac contractibility with increased cardiac index and left ventricular ejection fraction. However, its use could also increase fluid infusion but not reduce norepinephrine dose. No significant benefit in mortality could be observed of levosimendan versus dobutamine use, or in patients with proven cardiac dysfunction. CONCLUSIONS:Current evidence is not sufficient to support levosimendan as superior to dobutamine or as an optimal adjunct in severe sepsis and septic shock. More large-scale randomised trials are necessary to validate levosimendan use in sepsis.
| S-EPMC5884355 | biostudies-literature
Project description:The role of recombinant activated protein C (aPC) during sepsis is still controversial. It showed anti-inflammatory effect and improved the microvascular perfusion in experimental models of septic shock. The present study was aimed at testing the hypothesis that recombinant aPC therapy improves the microcirculation during severe sepsis.Prospective observational study on patients admitted in a 12-beds intensive care unit of a university hospital from July 2010 to December 2011, with severe sepsis and at least two sepsis-induced organ failures occurring within 48 hours from the onset of sepsis, who received an infusion of aPC (24 mcg/kg/h for 96 hours) (aPC group). Patients with contraindications to aPC administration were also monitored (no-aPC group).At baseline (before starting aPC infusion, T0), after 24 hours (T1a), 48 hours (T1b), 72 hours (T1c) and 6 hours after the end of aPC infusion (T2), general clinical and hemodynamic parameters were collected and the sublingual microcirculation was evaluated with sidestream dark-field imaging. Total vessel density (TVD), perfused vessel density (PVD), De Backer score, microvascular flow index (MFIs), the proportion of perfused vessels (PPV) and the flow heterogeneity index (HI) were calculated for small vessels. The perfused boundary region (PBR) was measured as an index of glycocalyx damage. Variables were compared between time points and groups using non parametric or parametric statistical tests, as appropriate.In the 13 aPC patients mean arterial pressure (MAP), base excess, lactate, PaO2/FiO2 and the Sequential Organ Failure Assessment (SOFA) score significantly improved over time, while CI and ITBVI did not change. MFIs, TVD, PVD, PPV significantly increased over time and the HI decreased (p?<?0.05 in all cases), while the PBR did not change. No-aPC patients (n?=?9) did not show any change in the microcirculation over time. A positive correlation was found between MFIs and MAP. TVD, PVD and De Backer score negatively correlated with norepinephrine dose, and the SOFA score negatively correlated with MFIs, TVD and PVD.aPC significantly improves the microcirculation in patients with severe sepsis/septic shock.NCT01806428.
| S-EPMC3848895 | biostudies-literature