Evaluation of the role of sex as a prognostic factor in critically ill adults with sepsis: a systematic review and meta-analysis

Abstract

Background: Incidence and sepsis-related mortality are failing, but sepsis continues to be a leading cause of admission and death in intensive care units (ICUs). Although the preceding evidence suggests sex-related risk differences for developing sepsis, the influence of sex on mortality outcomes remains unclear as previous studies showed discordant results. This systematic review assesed the independent effect of sex for mortality among critically ill patients with sepsis.Methods: Electronic databases were searched up to 17th July 2020 for studies that examined independent associations between sex and mortality outcomes in critically ill adults with sepsis while controlling for covariates. Primary meta-analyses were performed by pooling adjusted estimates for a pre-specified core set of adjustment factors. The primary outcomes included all-cause hospital mortality and 28-day all-cause hospital mortality. The secondary outcomes included 7-day all-cause hospital mortality, 1-year all-cause mortality, and all-cause ICU mortality.Results: Among the 14304 records identified, 12 studies (71850 participants) were included. Meta-analysis showed inconclusive results on sex-based differences in hospital mortality (OR 0.95, 95% CI 0.55 to 1.64; very low-certainty evidence) and ICU mortality (OR 1.19, 95% CI 0.79 to 1.78; very low-certainty evidence). Meta-analysis found higher 28-day hospital mortality in the female group (OR 1.18, 95% CI 1.05 to 1.32; very low-certainty evidence). No studies reported on 7-day hospital mortality. A single study provided adjusted estimates on 1-year mortality reporting lower risk in the female group (OR 0.83 95% CI 0.68 to 0.98; low-certainty of evidence). The main reasons for assessing the certainty of evidence as very low were inconsistency and imprecision while downgrading to low-certainty was risk of bias and imprecision.Conclusions: The prognostic independent effect of sex on hospital mortality, 28-day hospital mortality, and ICU mortality for critically ill adults with sepsis is uncertain. Female sex may be associated with decreased 1-year mortality. No included studies reported on 7-day all-cause hospital mortality.

Sex differences in long-term survival after intensive care unit treatment for sepsis: A cohort study

“…Three systematic reviews of sex differences in mortality of sepsis patients treated in the ICU have reported an absence of well-designed studies and significant heterogeneity [4][5][6]. In studies where sex differences in sepsis mortality are observed, differences between men and women's innate and adaptive immune response are cited [7], with greater protection in women attributed to the immune enhancing effects of estrogen, and male disadvantage related to the immunosuppressive properties of male androgens, particularly testosterone.…”