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Meta-analysis of protocolized goal-directed hemodynamic optimization for the management of severe sepsis and septic shock in the Emergency Department.

ABSTRACT: To perform a meta-analysis identifying studies instituting protocolized hemodynamic optimization in the emergency department (ED) for patients with severe sepsis and septic shock.We modeled the structure of this analysis after the QUORUM and MOOSE published recommendations for scientific reviews. A computer search to identify articles was performed from 1980 to present. Studies included for analysis were adult controlled trials implementing protocolized hemodynamic optimization in the ED for patients with severe sepsis and septic shock. Primary outcome data was extracted and analyzed by 2 reviewers with the primary endpoint being short-term mortality reported either as 28-day or in-hospital mortality.We identified 1,323 articles with 65 retrieved for review. After application of inclusion and exclusion criteria 25 studies (15 manuscripts, 10 abstracts) were included for analysis (n=9597). The mortality rate for patients receiving protocolized hemodynamic optimization (n=6031) was 25.8% contrasted to 41.6% in control groups (n=3566, p<0.0001).Protocolized hemodynamic optimization in the ED for patients with severe sepsis and septic shock appears to reduce mortality.

SUBMITTER: Wira CR

PROVIDER: S-EPMC3952890 | biostudies-other | 2014 Feb

REPOSITORIES: biostudies-other

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Management of sepsis and septic shock in the emergency department.

Project description:Early management of sepsis and septic shock is crucial for patients' prognosis. As the Emergency Department (ED) is the place where the first medical contact for septic patients is likely to occur, emergency physicians play an essential role in the early phases of patient management, which consists of accurate initial diagnosis, resuscitation, and early antibiotic treatment. Since the issuing of the Surviving Sepsis Campaign guidelines in 2016, several studies have been published on different aspects of sepsis management, adding a substantial amount of new information on the pathophysiology and treatment of sepsis and septic shock. In light of this emerging evidence, the present narrative review provides a comprehensive account of the recent advances in septic patient management in the ED.

| S-EPMC8354945 | biostudies-literature

Harmonizing international trials of early goal-directed resuscitation for severe sepsis and septic shock: methodology of ProCESS, ARISE, and ProMISe.

Project description:PurposeTo describe and compare the design of three independent but collaborating multicenter trials of early goal-directed resuscitation for severe sepsis and septic shock.MethodsWe 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.ResultsAll 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.ConclusionsHarmonization of study design and methods between severe sepsis trials is feasible and may facilitate pooling of data on completion of the trials.

| S-EPMC3864363 | biostudies-literature

Critical care ultrasound goal-directed versus early goal-directed therapy in septic shock.

Project description: Not available

| S-EPMC8724081 | biostudies-literature

Sustained elevation of resistin, NGAL and IL-8 are associated with severe sepsis/septic shock in the emergency department.

Project description:To identify biomarkers which distinguish severe sepsis/septic shock from uncomplicated sepsis in the Emergency Department (ED).Patients with sepsis underwent serial blood sampling, including arrival in the ED and up to three subsequent time points over the first 24 hours. Messenger RNA (mRNA) levels of 13 genes representing arms of the innate immune response, organ dysfunction or shock were measured in peripheral blood leucocytes using quantitative PCR, and compared with healthy controls. Serum protein concentrations of targets differentially expressed between uncomplicated sepsis and severe sepsis/septic shock were then measured at each time point and compared between the two patient groups.Of 27 participants (median age 66 years, (IQR 35, 78)), 10 had uncomplicated sepsis and 17 had sepsis with organ failure (14 septic shock; 3 had other sepsis-related organ failures). At the time of first sample collection in the ED, gene expression of Interleukin (IL)-10 and Neutrophil Gelatinase Associated Lipocalin (NGAL) were significantly higher in severe sepsis than uncomplicated sepsis. Expression did not significantly change over time for any target gene. Serum concentrations of IL-6, IL-8, IL-10, NGAL and Resistin were significantly higher in severe sepsis than uncomplicated sepsis at the time of first sample collection in the ED, but only IL-8, NGAL and Resistin were consistently higher in severe sepsis compared to uncomplicated sepsis at all time points up to 24 h after presentation.These mediators, produced by both damaged tissues and circulating leukocytes, may have important roles in the development of severe sepsis. Further work will determine whether they have any value, in addition to clinical risk parameters, for the early identification of patients that will subsequently deteriorate and/or have a higher risk of death.

| S-EPMC4208806 | biostudies-literature

Cost-effectiveness of molecular diagnostic assays for the therapy of severe sepsis and septic shock in the emergency department.

Project description:ObjectivesSepsis presents a major burden to the emergency department (ED). Because empiric inappropriate antimicrobial therapy (IAAT) is associated with increased mortality, rapid molecular assays may decrease IAAT and improve outcomes. We evaluated the cost-effectiveness of molecular testing as an adjunct to blood cultures in patients with severe sepsis or septic shock evaluated in the ED.MethodsWe developed a decision analysis model with primary outcome the incremental cost-effectiveness ratio expressed in terms of deaths averted. Costs were dependent on the assay price and the patients' length of stay (LOS). Three base-case scenarios regarding the difference in LOS between patients receiving appropriate (AAT) and IAAT were described. Sensitivity analyses regarding the assay cost and sensitivity, and its ability to guide changes from IAAT to AAT were performed.ResultsUnder baseline assumptions, molecular testing was cost-saving when the LOS differed by 4 days between patients receiving IAAT and AAT (ICER -$7,302/death averted). Our results remained robust in sensitivity analyses for assay sensitivity≥52%, panel efficiency≥39%, and assay cost≤$270. In the extreme case that the LOS of patients receiving AAT and IAAT was the same, the ICER remained≤$20,000/death averted for every studied sensitivity (i.e. 0.5-0.95), panel efficiency≥34%, and assay cost≤$313. For 2 days difference in LOS, the bundle approach was dominant when the assay cost was≤$135 and the panel efficiency was≥77%.ConclusionsThe incorporation of molecular tests in the management of sepsis in the ED has the potential to improve outcomes and be cost-effective for a wide range of clinical scenarios.

| S-EPMC6534337 | biostudies-literature

Effect of early goal-directed therapy on mortality in patients with severe sepsis or septic shock: a meta-analysis of randomised controlled trials.

Project description:OBJECTIVE:To determine whether patients with severe sepsis or septic shock could benefit from a strict and early goal-directed therapy (EGDT) protocol recommended by Surviving Sepsis Campaign (SSC) Guidelines. METHODS:MEDLINE/PubMed, EMBASE/OVID and Cochrane Central Register of Controlled Trials (CENTRAL) were searched between March 1983 and March 2015. Eligible studies evaluated the outcomes of EGDT versus usual care or standard therapy in patients with severe sepsis or septic shock. The primary outcomes were mortality within 28 days, 60 days and 90 days. Included studies must report at least one metric of mortality. RESULTS:5 studies that enrolled 4303 patients with 2144 in the EGDT group and 2159 in the control group were included in this meta-analysis. Overall, there were slight decreases of mortality within 28 days, 60 days and 90 days in the random-effect model in patients with severe sepsis or septic shock receiving EGDT resuscitation. However, none of the differences reached statistical significance (RR=0.86; 95% CI 0.69 to 1.06; p=0.16; p for heterogeneity=0.008, I(2)=71%; RR=0.94; 95% CI 0.81 to 1.10; p=0.46; p for heterogeneity=0.16, I(2)=43%; RR=0.98; 95% CI 0.88 to 1.10; p=0.75; p for heterogeneity=0.87, I(2)=0%, respectively). CONCLUSIONS:The current meta-analysis pooled data from five RCTs and found no survival benefit of EGDT in patients with sepsis. However, the included trials are not sufficiently homogeneous and potential confounding factors in the negative trials (ProCESS, ARISE and ProMISe) might bias the results and diminish the treatment effect of EGDT. Further well-designed studies should eliminate all potential source of bias to determine if EGDT has a mortality benefit.

| S-EPMC4785309 | biostudies-literature

Early goal-directed and lactate-guided therapy in adult patients with severe sepsis and septic shock: a meta-analysis of randomized controlled trials.

Project description:BackgroundThe ProCESS, ARISE, and ProMISe trials have failed to show that early goal-directed therapy (EGDT) reduces mortality in patients with severe sepsis and septic shock. Although lactate-guided therapy (LGT) has been shown to result in significantly lower mortality, its use remains controversial. Therefore, we performed a meta-analysis to evaluate EGDT vs. LGT or usual care (UC) in adult patients with severe sepsis and septic shock.MethodsRelevant randomized controlled trials published from January 1, 2001 to March 30, 2017 were identified in PubMed, EMBASE, Web of Science, and the Cochrane Library. The primary outcome was mortality; secondary outcomes included red cell transfusions, dobutamine use, vasopressor infusion, and mechanical ventilation support within the first 6 h and Acute Physiology and Chronic Health Evaluation II (APACHE II) score.ResultsSixteen studies enrolling 5968 patients with 2956 in EGDT, 2547 in UC, and 465 in LGT were included in this meta-analysis. Compared with UC, EGDT was associated with a lower mortality (10 trials; RR 0.85, 95% CI 0.74-0.97, P = 0.01), and this difference was more pronounced in the subgroup of UC patients with mortality > 30%. In addition, EGDT patients received more red cell transfusions, dobutamine, and vasopressor infusions within the first 6 h. Compared with LGT, EGDT was associated with higher mortality (6 trials; RR 1.42, 95% CI 1.19-1.70, P = 0.0001) with no heterogeneity (P = 0.727, I2 = 0%).ConclusionEGDT seems to reduce mortality in adult patients with severe sepsis and septic shock, and the benefit may primarily be attributed to red cell transfusions, dobutamine administration, and vasopressor infusions within the first 6 h. However, LGT may result in a greater mortality benefit than EGDT.

| S-EPMC6264603 | biostudies-literature

Usefulness of ischemia-modified albumin in the diagnosis of sepsis/septic shock in the emergency department.

Project description:ObjectiveNo studies have evaluated the diagnostic value of ischemia-modified albumin (IMA) for the early detection of sepsis/septic shock in patients presenting to the emergency department (ED). We aimed to assess the usefulness of IMA in diagnosing sepsis/septic shock in the ED.MethodsThis retrospective, observational study analyzed IMA, lactate, high sensitivity C-reactive protein, and procalcitonin levels measured within 1 hour of ED arrival. Patients with suspected infection meeting at least two systemic inflammatory response syndrome criteria were included and classified into the infection, sepsis, and septic shock groups using Sepsis-3 definitions. Areas under the receiver operating characteristic curves (AUCs) with 95% confidence intervals (CIs) and multivariate logistic regression were used to determine diagnostic performance.ResultsThis study included 300 adult patients. The AUC (95% CI) of IMA levels (cut-off ≥85.5 U/mL vs. ≥87.5 U/mL) was higher for the diagnosis of sepsis than for that of septic shock (0.729 [0.667-0.791] vs. 0.681 [0.613-0.824]) and was higher than the AUC of procalcitonin levels (cut-off ≥1.58 ng/mL, 0.678 [0.613-0.742]) for the diagnosis of sepsis. When IMA and lactate levels were combined, the AUCs were 0.815 (0.762-0.867) and 0.806 (0.754-0.858) for the diagnosis of sepsis and septic shock, respectively. IMA levels independently predicted sepsis (odds ratio, 1.05; 95% CI, 1.00-1.09; P=0.029) and septic shock (odds ratio, 1.07; 95% CI, 1.02-1.11; P=0.002).ConclusionOur findings indicate that IMA levels are a useful biomarker for diagnosing sepsis/septic shock early, and their combination with lactate levels can enhance the predictive power for early diagnosis of sepsis/septic shock in the ED.

| S-EPMC7550814 | biostudies-literature

The C-Reactive Protein/Albumin Ratio as an Independent Predictor of Mortality in Patients with Severe Sepsis or Septic Shock Treated with Early Goal-Directed Therapy.

Project description:BackgroundSepsis, including severe sepsis and septic shock, is a major cause of morbidity and mortality. Albumin and C-reactive protein (CRP) are considered as good diagnostic markers for sepsis. Thus, initial CRP and albumin levels were combined to ascertain their value as an independent predictor of 180-day mortality in patients with severe sepsis and septic shock.Materials and methodsWe conducted a retrospective cohort study involving 670 patients (>18 years old) who were admitted to the emergency department and who had received a standardized resuscitation algorithm (early goal-directed therapy) for severe sepsis and septic shock, from November 2007 to February 2013, at a tertiary hospital in Seoul, Korea. The outcome measured was 180-day all-cause mortality. A multivariate Cox proportional hazard model was used to identify the independent risk factors for mortality. A receiver operating characteristic (ROC) curve analysis was conducted to compare the predictive accuracy of the CRP/albumin ratio at admission.ResultsThe 180-day mortality was 28.35% (190/670). Based on the multivariate Cox proportional hazard analysis, age, the CRP/albumin ratio at admission (adjusted HR 1.06, 95% CI 1.03-1.10, p<0.001), lactate level at admission (adjusted HR 1.10, 95% CI 1.05-1.14, p<0.001), and the Sequential Organ Failure Assessment (SOFA) score at admission (adjusted HR 1.12, 95% CI 1.07-1.18, p<0.001) were independent predictors of 180-day mortality. The area under the curve of CRP alone and the CRP/albumin ratio at admission for 180-day mortality were 0.5620 (P<0.001) and 0.6211 (P<0.001), respectively.ConclusionThe CRP/albumin ratio was an independent predictor of mortality in patients with severe sepsis or septic shock.

| S-EPMC4497596 | biostudies-literature

Severe sepsis and septic shock: management and performance improvement.

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

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