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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.

OBJECTIVES:. We sought to identify and prioritize improvement strategies that Critical Care Medicine (CCM) programs could use to inform and advance gender equity among physicians in CCM. DESIGN:. This study involved three sequential phases: 1) scoping review that identified strategies to improve gender equity in all medical specialties; 2) modified consensus process with 48 CCM stakeholders to rate and rank identified strategies; and 3) in-person stakeholder meeting to refine strategies and discuss facilitators and barriers to their implementation. SETTING:. CCM. SUBJECTS:. CCM stakeholders (physicians, researchers, and decision-makers; mutually inclusive). INTERVENTIONS:. None. MEASUREMENTS AND MAIN RESULTS:. We identified 190 unique strategies from 416 articles. Strategies were grouped thematically into 20 categories across four overarching pillars of equity: access, participation, reimbursement, and culture. Participants prioritized 22 improvement strategies for implementation in CCM. The top-rated strategy from each pillar included: 1) nominate gender diverse candidates for faculty positions and prestigious opportunities (equitable access); 2) mandate training in unconscious bias and equitable treatment for committee (e.g., hiring, promotion) members (equitable participation); 3) ensure equitable starting salaries regardless of sex or gender (equitable reimbursement); and, 4) conduct 360° evaluations of leaders (including their direct work circle of supervisors, peers, and subordinates) through a diversity lens (equitable culture). Interprofessional collaboration, leadership, and local champions were identified as key enablers for implementation. CONCLUSIONS:. We identified stakeholder-prioritized strategies that can be used to inform and enhance gender equity among physicians in CCM under four overarching equity pillars: access, participation, reimbursement, and culture. Implementation approaches should include education, policy creation, and measurement, and reporting.

OBJECTIVES:. To create evidence-based consensus statements for restricted ICU visitation policies to support critically ill patients, families, and healthcare professionals during current and future pandemics. DESIGN:. Three rounds of a remote modified Delphi consensus process. SETTING:. Online survey and virtual polling from February 2, 2021, to April 8, 2021. SUBJECTS:. Stakeholders (patients, families, clinicians, researchers, allied health professionals, decision-makers) admitted to or working in Canadian ICUs during the coronavirus disease 2019 pandemic. MEASUREMENTS AND MAIN RESULTS:. During Round 1, key stakeholders used a 9-point Likert scale to rate experiences (1—not significant, 9—significant impact on patients, families, healthcare professionals, or patient- and family-centered care) and strategies (1—not essential, 9—essential recommendation for inclusion in the development of restricted visitation policies) and used a free-text box to capture experiences/strategies we may have missed. Consensus was achieved if the median score was 7–9 or 1–3. During Round 2, participants used a 9-point Likert scale to re-rate experiences/strategies that did not meet consensus during Round 1 (median score of 4–6) and rate new items identified in Round 1. During Rounds 2 and 3, participants ranked items that reached consensus by order of importance (relative to other related items and experiences) using a weighted ranking system (0–100 points). Participants prioritized 11 experiences (e.g., variability of family’s comfort with technology, healthcare professional moral distress) and developed 21 consensus statements (e.g., communicate policy changes to the hospital staff before the public, permit visitors at end-of-life regardless of coronavirus disease 2019 status, creating a clear definition for end-of-life) regarding restricted visitation policies. CONCLUSIONS:. We have formulated evidence-informed consensus statements regarding restricted visitation policies informed by diverse stakeholders, which could enhance patient- and family-centered care during a pandemic.

OBJECTIVE:. To summarize the evidence comparing various balanced crystalloid solutions. DATA SOURCES:. We searched MEDLINE, EMBASE, PUBMED, and CENTRAL databases. STUDY SELECTION:. We included randomized controlled trials that directly compared the IV administration of one balanced crystalloid solution with another. DATA EXTRACTION AND ANALYSIS:. We examined metabolic and patient-important outcomes and conducted meta-analysis using random effects model. For comparisons or outcomes with insufficient data to allow for pooling, we describe results narratively. We assessed risk of bias for individual trials using the Cochrane risk of bias tool and certainty of evidence using Grading of Recommendations, Assessment, Development and Evaluations methodology. DATA SYNTHESIS:. We included 24 randomized controlled trials comparing Plasmalyte, Ringer’s Lactate, Ringerfundin, Hartmann’s solution, Ringer’s Bicarbonate, Sterofundin, Kabilyte, Normosol, and novel balanced solutions. Of the included studies, 16 were performed in the perioperative setting, six in the ICU, one in the emergency department, and one in healthy volunteers. Administration of Plasmalyte resulted in a lower postinfusion serum chloride concentration (mean difference, 0.83 mmol/L lower; 95% CI, 0.03–1.64 mmol/L lower, low certainty), higher postinfusion base excess (mean difference, 0.65 mmol/L higher, 95% CI, 0.25–1.05 mmol/L higher, low certainty), and lower postinfusion serum lactate levels (mean difference, 0.46 mmol/L lower; 95% CI, 0.05–0.87 mmol/L lower, low certainty) compared with administration of any other balanced crystalloid. There were no important differences in postinfusion serum pH or potassium when comparing Plasmalyte with other balanced crystalloids. Data addressing other comparisons or examining the impact of different balanced crystalloids on patient-important outcomes were sparsely reported and too heterogeneous to allow for pooling. CONCLUSIONS:. Administration of Plasmalyte results in lower serum concentrations of chloride and lactate, and higher base excess than other balanced crystalloids. The certainty of evidence is low and requires further study in large randomized controlled trials to inform the choice of balanced crystalloid in patients requiring volume replacement.

Objectives:. Sepsis is responsible for a substantial proportion of global childhood morbidity and mortality. However, evidence demonstrates major inaccuracies in the use of the term “sepsis” in clinical practice, coding, and research. Current and previous definitions of sepsis have been developed using expert consensus but the specific criteria used to identify children with sepsis have not been rigorously evaluated. Therefore, as part of the Society of Critical Care Medicine’s Pediatric Sepsis Definition Taskforce, we will conduct a systematic review to synthesize evidence on individual factors, clinical criteria, or illness severity scores that may be used to identify children with infection who have or are at high risk of developing sepsis-associated organ dysfunction and separately those factors, criteria, and scores that may be used to identify children with sepsis who are at high risk of progressing to multiple organ dysfunction or death. Data Sources:. We will identify eligible studies by searching the following databases: MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials. Study Selection:. We will include all randomized trials and cohort studies published between January 1, 2004, and March 16, 2020. Data Extraction:. Data extraction will include information related to study characteristics, population characteristics, clinical criteria, and outcomes. Data Synthesis:. We will calculate sensitivity and specificity of each criterion for predicting sepsis and conduct a meta-analysis if the data allow. We will also provide pooled estimates of overall hospital mortality. Conclusions:. The potential risk factors, clinical criteria, and illness severity scores from this review which identify patients with infection who are at high risk of developing sepsis-associated organ dysfunction and/or progressing to multiple organ dysfunction or death will be used to inform the next steps of the Pediatric Sepsis Definition Taskforce.

Objectives:. To determine if a set of time-varying biological indicators can be used to: 1) predict the sepsis mortality risk over time and 2) generate mortality risk profiles. Design:. Prospective observational study. Setting:. Nine Canadian ICUs. Subjects:. Three-hundred fifty-six septic patients. Interventions:. None. Measurements and Main Results:. Clinical data and plasma levels of biomarkers were collected longitudinally. We used a complementary log-log model to account for the daily mortality risk of each patient until death in ICU/hospital, discharge, or 28 days after admission. The model, which is a versatile version of the Cox model for gaining longitudinal insights, created a composite indicator (the daily hazard of dying) from the “day 1” and “change” variables of six time-varying biological indicators (cell-free DNA, protein C, platelet count, creatinine, Glasgow Coma Scale score, and lactate) and a set of contextual variables (age, presence of chronic lung disease or previous brain injury, and duration of stay), achieving a high predictive power (conventional area under the curve, 0.90; 95% CI, 0.86–0.94). Including change variables avoided misleading inferences about the effects of day 1 variables, signifying the importance of the longitudinal approach. We then generated mortality risk profiles that highlight the relative contributions among the time-varying biological indicators to overall mortality risk. The tool was validated in 28 nonseptic patients from the same ICUs who became septic later and was subject to 10-fold cross-validation, achieving similarly high area under the curve. Conclusions:. Using a novel version of the Cox model, we created a prognostic tool for septic patients that yields not only a predicted probability of dying but also a mortality risk profile that reveals how six time-varying biological indicators differentially and longitudinally account for the patient’s overall daily mortality risk.