Sex as a prognostic factor for mortality in critically ill adults with sepsis: a systematic review and meta-analysis

OBJECTIVE: To assess the role of sex as an independent prognostic factor for mortality in patients with sepsis admitted to intensive care units (ICUs). DESIGN: Systematic review and meta-analysis. DATA SOURCES: MEDLINE, Embase, Web of Science, ClinicalTrials.gov and the WHO Clinical Trials Registry from inception to 17 July 2020. STUDY SELECTION: Studies evaluating independent associations between sex and mortality in critically ill adults with sepsis controlling for at least one of five core covariate domains prespecified following a literature search and consensus among experts. DATA EXTRACTION AND SYNTHESIS: Two authors independently extracted and assessed the risk of bias using Quality In Prognosis Studies tool. Meta-analysis was performed by pooling adjusted estimates. The Grades of Recommendations, Assessment, Development and Evaluation approach was used to rate the certainty of evidence. RESULTS: From 14 304 records, 13 studies (80 520 participants) were included. Meta-analysis did not find sex-based differences in all-cause hospital mortality (OR 1.02, 95% CI 0.79 to 1.32; very low-certainty evidence) and all-cause ICU mortality (OR 1.19, 95% CI 0.79 to 1.78; very low-certainty evidence). However, females presented higher 28-day all-cause mortality (OR 1.18, 95% CI 1.05 to 1.32; very low-certainty evidence) and lower 1-year all-cause mortality (OR 0.83, 95% CI 0.68 to 0.98; low-certainty evidence). There was a moderate risk of bias in the domain adjustment for other prognostic factors in six studies, and the certainty of evidence was further affected by inconsistency and imprecision. CONCLUSION: The prognostic independent effect of sex on all-cause hospital mortality, 28-day all-cause mortality and all-cause ICU mortality for critically ill adults with sepsis was uncertain. Female sex may be associated with decreased 1-year all-cause mortality. PROSPERO REGISTRATION NUMBER: CRD42019145054.