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Critical Care Explorations Jan 2024To perform a systematic review and meta-analysis to assess the efficacy and safety of corticosteroids in patients with sepsis.
OBJECTIVES
To perform a systematic review and meta-analysis to assess the efficacy and safety of corticosteroids in patients with sepsis.
DATA SOURCES
We searched PubMed, Embase, and the Cochrane Library, up to January 10, 2023.
STUDY SELECTION
We included randomized controlled trials (RCTs) comparing corticosteroids with placebo or standard care with sepsis.
DATA EXTRACTION
The critical outcomes of interest included mortality, shock reversal, length of stay in the ICU, and adverse events.
DATA ANALYSIS
We performed both a pairwise and dose-response meta-analysis to evaluate the effect of different corticosteroid doses on outcomes. We used Grading of Recommendations Assessment, Development and Evaluation to assess certainty in pooled estimates.
DATA SYNTHESIS
We included 45 RCTs involving 9563 patients. Corticosteroids probably reduce short-term mortality (risk ratio [RR], 0.93; 95% CI, 0.88-0.99; moderate certainty) and increase shock reversal at 7 days (RR, 1.24; 95% CI, 1.11-1.38; high certainty). Corticosteroids may have no important effect on duration of ICU stay (mean difference, -0.6 fewer days; 95% CI, 1.48 fewer to 0.27 more; low certainty); however, probably increase the risk of hyperglycemia (RR, 1.13; 95% CI, 1.08-1.18; moderate certainty) and hypernatremia (RR, 1.64; 95% CI, 1.32-2.03; moderate certainty) and may increase the risk of neuromuscular weakness (RR, 1.21; 95% CI, 1.01-1.45; low certainty). The dose-response analysis showed a reduction in mortality with corticosteroids with optimal dosing of approximately 260 mg/d of hydrocortisone (RR, 0.90; 95% CI, 0.83-0.98) or equivalent.
CONCLUSIONS
We found that corticosteroids may reduce mortality and increase shock reversal but they may also increase the risk of hyperglycemia, hypernatremia, and neuromuscular weakness. The dose-response analysis indicates optimal dosing is around 260 mg/d of hydrocortisone or equivalent.
PubMed: 38250247
DOI: 10.1097/CCE.0000000000001000 -
Nutrients Jul 2023The optimal timing of enteral nutrition (EN) in sepsis patients is controversial among societal guidelines. We aimed to evaluate the evidence of early EN's impact on... (Review)
Review
The optimal timing of enteral nutrition (EN) in sepsis patients is controversial among societal guidelines. We aimed to evaluate the evidence of early EN's impact on critically ill sepsis patients' clinical outcomes. We searched the MEDLINE, Embase, CINAHL, Cochrane Library, ClinicalTrials.gov, and ICTRP databases on 10 March 2023. We included studies published after 2004 that compared early EN versus delayed EN in sepsis patients. We included randomized controlled trials (RCTs), non-RCTs, cohort studies, and case-control studies. Forest plots were used to summarize risk ratios (RRs), including mortality and mean difference (MD) of continuous variables such as intensive care unit (ICU) length of stay and ventilator-free days. We identified 11 eligible studies with sample sizes ranging from 31 to 2410. The RR of short-term mortality from three RCTs was insignificant, and the MD of ICU length of stay from two RCTs was -2.91 and -1.00 days (95% confidence interval [CI], -5.53 to -0.29 and -1.68 to -0.32). Although the RR of intestinal-related complications from one RCT was 3.82 (95% CI, 1.43 to 10.19), indicating a significantly higher risk for the early EN group than the control group, intestinal-related complications of EN reported in five studies were inconclusive. This systematic review did not find significant benefits of early EN on mortality in sepsis patients. Evidence, however, is weak due to inconsistent definitions, heterogeneity, risk of bias, and poor methodology in the existing studies.
Topics: Humans; Enteral Nutrition; Critical Illness; Intensive Care Units; Sepsis; Case-Control Studies; Length of Stay
PubMed: 37513620
DOI: 10.3390/nu15143201 -
Chest Oct 2023IV fluids are recommended for adults with sepsis. However, the optimal strategy for IV fluid management in sepsis is unknown, and clinical equipoise exists.
BACKGROUND
IV fluids are recommended for adults with sepsis. However, the optimal strategy for IV fluid management in sepsis is unknown, and clinical equipoise exists.
RESEARCH QUESTION
Do lower vs higher fluid volumes improve patient-important outcomes in adult patients with sepsis?
STUDY DESIGN AND METHODS
We updated a systematic review with meta-analysis and trial sequential analysis of randomized clinical trials assessing lower vs higher IV fluid volumes in adult patients with sepsis. The coprimary outcomes were all-cause mortality, serious adverse events, and health-related quality of life. We followed the recommendations from the Cochrane Handbook and used the Grading of Recommendations Assessment, Development and Evaluation approach. Primary conclusions were based on trials with low risk of bias if available.
RESULTS
We included 13 trials (N = 4,006) with four trials (n = 3,385) added to this update. The meta-analysis of all-cause mortality in eight trials with low risk of bias showed a relative risk of 0.99 (97% CI, 0.89-1.10; moderate certainty evidence). Six trials with predefined definitions of serious adverse events showed a relative risk of 0.95 (97% CI, 0.83-1.07; low certainty evidence). Health-related quality of life was not reported.
INTERPRETATION
Among adult patients with sepsis, lower IV fluid volumes probably result in little to no difference in all-cause mortality compared with higher IV fluid volumes, but the interpretation is limited by imprecision in the estimate, which does not exclude potential benefit or harm. Similarly, the evidence suggests lower IV fluid volumes result in little to no difference in serious adverse events. No trials reported on health-related quality of life.
TRIAL REGISTRATION
PROSPERO; No.: CRD42022312572; URL: https://www.crd.york.ac.uk/prospero/.
PubMed: 37142091
DOI: 10.1016/j.chest.2023.04.036 -
Critical Care Medicine Dec 2023This study aimed to conduct a comprehensive and updated systematic review with network meta-analysis (NMA) to assess the outcome benefits of various blood purification... (Meta-Analysis)
Meta-Analysis
OBJECTIVES
This study aimed to conduct a comprehensive and updated systematic review with network meta-analysis (NMA) to assess the outcome benefits of various blood purification modalities for adult patients with severe infection or sepsis.
DATA SOURCES
We conducted a search of PubMed, MEDLINE, clinical trial registries, Cochrane Library, and Embase databases with no language restrictions.
STUDY SELECTION
Only randomized controlled trials (RCTs) were selected.
DATA EXTRACTION
The primary outcome was overall mortality. The secondary outcomes were the length of mechanical ventilation (MV) days and ICU stay, incidence of acute kidney injury (AKI), and kidney replacement therapy requirement.
DATA SYNTHESIS
We included a total of 60 RCTs with 4,595 participants, comparing 16 blood purification modalities with 17 interventions. Polymyxin-B hemoperfusion (relative risk [RR]: 0.70; 95% CI, 0.57-0.86) and plasma exchange (RR: 0.61; 95% CI, 0.42-0.91) were associated with low mortality (very low and low certainty of evidence, respectively). Because of the presence of high clinical heterogeneity and intransitivity, the potential benefit of polymyxin-B hemoperfusion remained inconclusive. The analysis of secondary outcomes was limited by the scarcity of available studies. HA330 with high-volume continuous venovenous hemofiltration (CVVH), HA330, and standard-volume CVVH were associated with shorter ICU stay. HA330 with high-volume CVVH, HA330, and standard-volume CVVH were beneficial in reducing MV days. None of the interventions showed a significant reduction in the incidence of AKI or the need for kidney replacement therapy.
CONCLUSIONS
Our NMA suggests that plasma exchange and polymyxin-B hemoperfusion may provide potential benefits for adult patients with severe infection or sepsis/septic shock when compared with standard care alone, but most comparisons were based on low or very low certainty evidence. The therapeutic effect of polymyxin-B hemoperfusion remains uncertain. Further RCTs are required to identify the specific patient population that may benefit from extracorporeal blood purification.
Topics: Adult; Humans; Shock, Septic; Network Meta-Analysis; Randomized Controlled Trials as Topic; Sepsis; Polymyxin B; Acute Kidney Injury
PubMed: 37470680
DOI: 10.1097/CCM.0000000000005991 -
Emerging Microbes & Infections Dec 2023Extended-spectrum beta-lactamase-producing Enterobacteriaceae (ESBL-PE) bacteremia can have poor clinical outcomes. Thus, determining the predictors of mortality from... (Meta-Analysis)
Meta-Analysis Review
Extended-spectrum beta-lactamase-producing Enterobacteriaceae (ESBL-PE) bacteremia can have poor clinical outcomes. Thus, determining the predictors of mortality from ESBL-PE bacteremia is very important. The present systematic review and meta-analysis aimed to evaluate studies to determine predictors associated with ESBL-PE bacteremia mortality. We searched PubMed and Cochrane Library databases for all relevant publications from January 2000 to August 2022. The outcome measure was mortality rate. In this systematic review of 22 observational studies, 4607 patients with ESBL-PE bacteremia were evaluated, of whom 976 (21.2%) died. The meta-analysis showed that prior antimicrobial therapy (RR, 2.89; 95% CI, 1.22-6.85), neutropenia (RR, 5.58; 95% CI, 2.03-15.35), nosocomial infection (RR, 2.46; 95% CI, 1.22-4.95), rapidly fatal underlying disease (RR, 4.21; 95% CI, 2.19-8.08), respiratory tract infection (RR, 2.12; 95% CI, 1.33-3.36), Pitt bacteremia score (PBS) (per1) (RR, 1.35; 95% CI, 1.18-1.53), PBS ≥ 4 (RR, 4.02; 95% CI, 2.77-5.85), severe sepsis (RR, 11.74; 95% CI, 4.68-29.43), and severe sepsis or septic shock (RR, 4.19; 95% CI, 2.83-6.18) were found to be mortality predictors. Moreover, urinary tract infection (RR, 0.15; 95% CI, 0.04-0.57) and appropriate empirical therapy (RR, 0.39; 95% CI, 0.18-0.82) were found to be a protective factor against mortality. Patients with ESBL-PE bacteremia who have the aforementioned require prudent management for improved outcomes. This research will lead to better management and improvement of clinical outcomes of patients with bacteremia caused by ESBL-PE.
Topics: Humans; Enterobacteriaceae Infections; Enterobacteriaceae; Bacteremia; Sepsis; beta-Lactamases; Anti-Bacterial Agents; Retrospective Studies; Treatment Outcome
PubMed: 37219067
DOI: 10.1080/22221751.2023.2217951 -
Frontiers in Nutrition 2023An increasing number of studies indicate that vitamin C (VC) reduces the mortality of adult septic patients, while some articles suggest otherwise. We performed this...
BACKGROUND
An increasing number of studies indicate that vitamin C (VC) reduces the mortality of adult septic patients, while some articles suggest otherwise. We performed this systematic review and meta-analysis to resolve the discrepancies in reported results concerning the efficacy of VC in septic patients.
METHODS
We comprehensively searched MEDLINE, EMBASE, and the Cochrane Central Register of Controlled trials for randomized controlled trials (RCTs) evaluating the efficacy of intravenous VC (IVVC) on adult septic patients published from inception to November 28, 2022. The quality of outcomes for eligible studies was assessed using the Recommendations Assessment, Development, and Evaluation methodology. The results were analyzed using the pooled mean difference (MD) or risk ratio (RR) and 95% confidence intervals (CIs).
RESULTS
Twenty-two studies (3,570 adult septic patients) were included. IVVC treatment did not improve 28-day mortality compared to the control group (RR, 0.92; 95% CI, 0.81-1.04; = 26%; evidence risk, moderate). IVVC monotherapy decreased mortality (RR, 0.69; 95% CI, 0.52-0.93; = 57%), whereas combination therapy did not affect mortality (RR, 1.03; 95% CI, 0.90-1.17; =0%). IVVC had a trend to decrease the mortality of septic patients (RR, 0.83; 95% CI, 0.69-1.00; = 33%) but did not affect septic shock patients (RR, 1.01; 95% CI, 0.85-1.21; = 18%). IVVC reduced the duration of vasopressor use (MD, -8.45; 95% CI, -15.43 to -1.47; evidence risk, very low) but did not influence the incidence of AKI, ICU length of stay, duration of mechanical ventilation.
CONCLUSIONS
IVVC treatment did not improve the 28-day mortality in septic patients. Subgroup analysis indicated that VC had a trend to decrease the 28-day mortality in patients with sepsis but not septic shock. IVVC monotherapy, rather than combination therapy, decreased the 28-day mortality in septic patients. The findings imply that Hydrocortisone, Ascorbic acid, Thiamine (HAT) combination therapy is not superior to IVVC monotherapy for septic patients. These findings warrant further confirmation in future studies, which should also investigate the mechanisms underlying the enhanced efficacy of IVVC monotherapy in septic patients.
SYSTEMATIC REVIEW REGISTRATION
https://inplasy.com/.
PubMed: 37599680
DOI: 10.3389/fnut.2023.1211194 -
Cureus Oct 2023The optimal fluid management strategy for patients with sepsis remains a topic of debate. This meta-analysis aims to evaluate the impact of restrictive versus liberal... (Review)
Review
The optimal fluid management strategy for patients with sepsis remains a topic of debate. This meta-analysis aims to evaluate the impact of restrictive versus liberal fluid regimens on mortality, adverse events, and other clinical outcomes in patients with sepsis. We systematically reviewed 11 randomized controlled trials published between 2008 and 2023, comprising a total of 4,121 participants. The studies assessed 90-day mortality, 30-day mortality, adverse events, hospital length of stay, ICU admission rate, mechanical ventilation, ventilator-free days, ICU-free days, and vasopressor-free days. Quality assessments indicated minimal bias across the studies. The meta-analysis showed no statistically significant difference in 90-day mortality between restrictive and liberal fluid regimens (OR, 0.93; 95% CI, 0.80 to 1.70; P=0.30). Similar results were observed for 30-day mortality (OR, 0.73; 95% CI, 0.30 to 1.80; P=0.50). Adverse events were comparable between the two groups (OR, 0.81; 95% CI, 0.55 to 1.19; P=0.28). Furthermore, there were no significant differences in hospital length of stay (OR, 0.47; 95% CI, -0.85 to 1.80; P=0.48) or ICU admission rate (OR, 1.09; 95% CI, 0.66 to 1.77; P=0.75) between the restrictive and liberal fluid regimens. Regarding mechanical ventilation and ventilator-free days, no significant distinctions were observed (OR, 0.87; 95% CI, 0.65 to 1.17; P=0.48; OR, 0.99; 95% CI, -0.17 to 2.15; P=0.09, respectively). ICU-free days and vasopressor-free days also showed no significant differences between the two groups (OR, 0.97; 95% CI, -0.28 to 2.21; P=0.13; OR, -0.38; 95% CI, -1.14 to 0.37; P=0.32, respectively). This comprehensive meta-analysis of clinical trials suggests that restrictive and liberal fluid management strategies have comparable outcomes in patients with sepsis, including mortality, adverse events, and various clinical parameters. However, most studies favored restrictive fluid regimen over liberal approach regarding the number of vasopressor-free days, need for mechanical ventilation, adverse events, 30-day mortality, and 90-day mortality in sepsis patients.
PubMed: 37899903
DOI: 10.7759/cureus.47783 -
Critical Care Explorations Jul 2024Although clinicians may use methylene blue (MB) in refractory septic shock, the effect of MB on patient-important outcomes remains uncertain. We conducted a systematic... (Meta-Analysis)
Meta-Analysis
OBJECTIVES
Although clinicians may use methylene blue (MB) in refractory septic shock, the effect of MB on patient-important outcomes remains uncertain. We conducted a systematic review and meta-analysis to investigate the benefits and harms of MB administration in patients with septic shock.
DATA SOURCES
We searched six databases (including PubMed, Embase, and Medline) from inception to January 10, 2024.
STUDY SELECTION
We included randomized clinical trials (RCTs) of critically ill adults comparing MB with placebo or usual care without MB administration.
DATA EXTRACTION
Two reviewers performed screening, full-text review, and data extraction. We pooled data using a random-effects model, assessed the risk of bias using the modified Cochrane tool, and used Grading of Recommendations Assessment, Development, and Evaluation to rate certainty of effect estimates.
DATA SYNTHESIS
We included six RCTs (302 patients). Compared with placebo or no MB administration, MB may reduce short-term mortality (RR [risk ratio] 0.66 [95% CI, 0.47-0.94], low certainty) and hospital length of stay (mean difference [MD] -2.1 d [95% CI, -1.4 to -2.8], low certainty). MB may also reduce duration of vasopressors (MD -31.1 hr [95% CI, -16.5 to -45.6], low certainty), and increase mean arterial pressure at 6 hours (MD 10.2 mm Hg [95% CI, 6.1-14.2], low certainty) compared with no MB administration. The effect of MB on serum methemoglobin concentration was uncertain (MD 0.9% [95% CI, -0.2% to 2.0%], very low certainty). We did not find any differences in adverse events.
CONCLUSIONS
Among critically ill adults with septic shock, based on low-certainty evidence, MB may reduce short-term mortality, duration of vasopressors, and hospital length of stay, with no evidence of increased adverse events. Rigorous randomized trials evaluating the efficacy of MB in septic shock are needed.
REGISTRATION
Center for Open Science (https://osf.io/hpy4j).
Topics: Methylene Blue; Humans; Shock, Septic; Randomized Controlled Trials as Topic; Length of Stay; Critical Illness
PubMed: 38904978
DOI: 10.1097/CCE.0000000000001110 -
Diagnostic and Prognostic Research Aug 2023Numerous biomarkers have been proposed for diagnosis, therapeutic, and prognosis in sepsis. Previous evaluations of the value of biomarkers for predicting mortality due... (Review)
Review
Basal procalcitonin, C-reactive protein, interleukin-6, and presepsin for prediction of mortality in critically ill septic patients: a systematic review and meta-analysis.
BACKGROUND
Numerous biomarkers have been proposed for diagnosis, therapeutic, and prognosis in sepsis. Previous evaluations of the value of biomarkers for predicting mortality due to this life-threatening condition fail to address the complexity of this condition and the risk of bias associated with prognostic studies. We evaluate the predictive performance of four of these biomarkers in the prognosis of mortality through a methodologically sound evaluation.
METHODS
We conducted a systematic review a systematic review and meta-analysis to determine, in critically ill adults with sepsis, whether procalcitonin (PCT), C-reactive protein (CRP), interleukin-6 (IL-6), and presepsin (sCD14) are independent prognostic factors for mortality. We searched MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials up to March 2023. Only Phase-2 confirmatory prognostic factor studies among critically ill septic adults were included. Random effects meta-analyses pooled the prognostic association estimates.
RESULTS
We included 60 studies (15,681 patients) with 99 biomarker assessments. Quality of the statistical analysis and reporting domains using the QUIPS tool showed high risk of bias in > 60% assessments. The biomarker measurement as a continuous variable in models adjusted by key covariates (age and severity score) for predicting mortality at 28-30 days showed a null or near to null association for basal PCT (pooled OR = 0.99, 95% CI = 0.99-1.003), CRP (OR = 1.01, 95% CI = 0.87 to 1.17), and IL-6 (OR = 1.02, 95% CI = 1.01-1.03) and sCD14 (pooled HR = 1.003, 95% CI = 1.000 to 1.006). Additional meta-analyses accounting for other prognostic covariates had similarly null findings.
CONCLUSION
Baseline, isolated measurement of PCT, CRP, IL-6, and sCD14 has not been shown to help predict mortality in critically ill patients with sepsis. The role of these biomarkers should be evaluated in new studies where the patient selection would be standardized and the measurement of biomarker results.
TRIAL REGISTRATION
PROSPERO (CRD42019128790).
PubMed: 37537680
DOI: 10.1186/s41512-023-00152-2 -
Frontiers in Medicine 2024Methylene blue is an interesting approach in reducing fluid overload and vasoactive drug administration in vasodilatory shock. The inhibition of guanylate cyclase...
BACKGROUND
Methylene blue is an interesting approach in reducing fluid overload and vasoactive drug administration in vasodilatory shock. The inhibition of guanylate cyclase induced by methylene blue infusion reduces nitric oxide production and improves vasoconstriction. This systematic review and meta-analysis aimed to assess the effects of methylene blue administration compared to placebo on the hemodynamic status and clinical outcomes in patients with sepsis and septic shock.
METHODS
The authors specifically included randomized controlled trials that compared the use of methylene blue with placebo in adult patients with sepsis and septic shock. The outcomes were length of intensive care unit stay, hemodynamic parameters [vasopressor use], and days on mechanical ventilation. We also evaluated the abnormal levels of methemoglobinemia. This systematic review and meta-analysis were recorded in PROSPERO with the ID CRD42023423470.
RESULTS
During the initial search, a total of 1,014 records were identified, out of which 393 were duplicates. Fourteen citations were selected for detailed reading, and three were selected for inclusion. The studies enrolled 141 patients, with 70 of them in the methylene blue group and 71 of them in the control group. Methylene blue treatment was associated with a lower length of intensive care unit stay (MD -1.58; 95%CI -2.97, -0.20; = 25%; = 0.03), decreased days on mechanical ventilation (MD -0.72; 95%CI -1.26, -0.17; = 0%; = 0.010), and a shorter time to vasopressor discontinuation (MD -31.49; 95%CI -46.02, -16.96; = 0%; < 0.0001). No association was found with methemoglobinemia.
CONCLUSION
Administering methylene blue to patients with sepsis and septic shock leads to reduced time to vasopressor discontinuation, length of intensive care unit stay, and days on mechanical ventilation.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42023423470, CRD42023423470.
PubMed: 38698779
DOI: 10.3389/fmed.2024.1366062