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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).

OBJECTIVES:. We planned to synthesize evidence examining the potential efficacy and safety of performing physical rehabilitation and/or mobilization (PR&M) in adult patients receiving extracorporeal life support (ECLS). DATA SOURCES:. We included any study that compared PR&M to no PR&M or among different PR&M strategies in adult patients receiving any ECLS for any indication and any cannulation. We searched seven electronic databases with no language limitations. STUDY SELECTION AND DATA EXTRACTION:. Two reviewers, independently and in duplicate, screened all citations for eligibility. We used the Cochrane Risk of Bias 2 and Cochrane Risk Of Bias In Non-randomized Studies of Interventions tools to assess individual study risk of bias. Although we had planned for meta-analysis, this was not possible due to insufficient data, so we used narrative and tabular data summaries for presenting results. We assessed the overall certainty of the evidence for each outcome using the Grading of Recommendations Assessment, Development, and Evaluation framework. DATA SYNTHESIS:. We included 17 studies that enrolled 996 patients. Most studies examined venovenous extracorporeal membrane oxygenation (ECMO) and/or venoarterial ECMO as a bridge to recovery in the ICU. We found an uncertain effect of high-intensity/active PR&M on mortality, duration of mechanical ventilation, ICU length of stay, hospital length of stay, or quality of life compared with low-intensity/passive PR&M in patients receiving ECLS (very low certainty due to very serious imprecision). There was similarly an uncertain effect on safety events including clinically important bleeding, spontaneous intracerebral hemorrhage, limb ischemia, accidental decannulation, or ECLS circuit dysfunction (very low certainty due to very serious risk of bias and imprecision). CONCLUSIONS:. Based on the currently available summary of evidence, there is an uncertain effect of high-intensity/active PR&M on patient important outcomes or safety in patients receiving ECLS. Despite indirect data from other populations suggesting potential benefit of high-intensity PR&M in the ICU; further high-quality randomized trials evaluating the benefits and risks of physical therapy and/or mobilization in this population are needed.

OBJECTIVES:. To perform a systematic review and meta-analysis to evaluate the association of various measures of glycemic variability, including time-domain and complexity-domain, with short-term mortality in patients with critical illness. DATA SOURCES:. We searched Embase Classic +, MEDLINE, and the Cochrane Database of Systematic Reviews from inception to November 3, 2023. STUDY SELECTION:. We included English language studies that assessed metrics of glycemic variation or complexity and short-term mortality in patients admitted to the ICU. DATA EXTRACTION:. Two authors performed independent data abstraction and risk-of-bias assessments. We used a random-effects model to pool binary and continuous data and summarized estimates of effect using odds ratios and mean difference. We used the Quality in Prognosis Studies tool to assess risk of bias and the Grading of Recommendations, Assessment, Development and Evaluations to assess certainty of pooled estimates. DATA SYNTHESIS:. We included 41 studies (n = 162,259). We demonstrate that increased sd, coefficient of variance, glycemic lability index, and decreased time in range are probably associated with increased mortality in critically ill patients (moderate certainty) and that increased mean absolute glucose, mean amplitude of glycemic excursion, and detrended fluctuation analysis may be associated with increased mortality (low certainty). CONCLUSIONS:. We found a consistent association between increased measures of glycemic variability and higher short-term mortality in patient with critical illness. Further research should focus on standardized measurements of glycemic variation and complexity, along with their utility as therapeutic targets and prognostic markers.

OBJECTIVES:. To compare the relative efficacy of pharmacologic interventions in the prevention of delirium in ICU trauma patients. DATA SOURCES:. We searched Medical Literature Analysis and Retrieval System Online, Embase, and Cochrane Registry of Clinical Trials from database inception until June 7, 2022. We included randomized controlled trials comparing pharmacologic interventions in critically ill trauma patients. STUDY SELECTION:. Two reviewers independently screened studies for eligibility, extracted data, and assessed risk of bias. DATA EXTRACTION:. Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines for network analysis were followed. Random-effects models were fit using a Bayesian approach to network meta-analysis. Between-group comparisons were estimated using hazard ratios (HRs) for dichotomous outcomes and mean differences for continuous outcomes, each with 95% credible intervals. Treatment rankings were estimated for each outcome in the form of surface under the cumulative ranking curve values. DATA SYNTHESIS:. A total 3,541 citations were screened; six randomized clinical trials (n = 382 patients) were included. Compared with combined propofol-dexmedetomidine, there may be no difference in delirium prevalence with dexmedetomidine (HR 1.44, 95% CI 0.39–6.94), propofol (HR 2.38, 95% CI 0.68–11.36), nor haloperidol (HR 3.38, 95% CI 0.65–21.79); compared with dexmedetomidine alone, there may be no effect with propofol (HR 1.66, 95% CI 0.79–3.69) nor haloperidol (HR 2.30, 95% CI 0.88–6.61). CONCLUSIONS:. The results of this network meta-analysis suggest that there is no difference found between pharmacologic interventions on delirium occurrence, length of ICU stay, length of hospital stay, or mortality, in trauma ICU patients.