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