Impact of sex on outcomes in critically ill patients with subarachnoid hemorrhage: a secondary analysis of a French prospective cohort study

BACKGROUND: Aneurysmal subarachnoid hemorrhage (aSAH) remains a severe condition with high morbidity and mortality. Evidence on sex-related differences in outcomes and complication profiles is inconsistent. We assessed the association between sex and 90-day functional outcome and ICU complications in aSAH patients requiring intensive care. METHODS: We performed a retrospective secondary analysis of the ATLANREA cohort (NCT02426255), a prospective multicenter ICU registry in western France. Adult patients (≥ 18 years) admitted with aSAH between January 1, 2013, and December 31, 2022, requiring orotracheal intubation within 24 h and for ≥ 24 h, were included. The primary outcome was favourable neurological status at day 90 (Glasgow Outcome Scale-Extended [GOS-E] > 4). A prespecified baseline multivariable logistic model included sex, age, WFNS grade, collapsed Fisher grade and mydriasis. Age subgroup analyses (≤ 42, 43-50, > 50 years) were prespecified as exploratory and complemented by a formal sex × age interaction test. RESULTS: Among 865 patients, 540 (62.4%) were women. Women were older than men (58 [IQR 49-66] vs. 54 [45-63] years; p < 0.001), while WFNS and Fisher grades were similar by sex. Ninety-day GOS-E was available for 682/869 patients (78.8%). Favourable outcome rates were similar in women and men (42.2% vs. 41.4%; p = 0.90). In the baseline complete-case model, sex was not significantly associated with favourable outcome (male OR 0.745, 95% CI 0.517-1.067; p = 0.11), whereas age, higher WFNS grades and mydriasis were independently associated with worse outcome. Sensitivity analyses (best-/worst-case imputation and multiple imputation) suggested a modest sex effect under some assumptions. Ordinal modelling of 8-level GOS-E yielded consistent findings (male OR 0.767, 95% CI 0.568-1.035; p = 0.083). There was no evidence of sex × age interaction (p = 0.585). Vasospasm was more frequent in women (48.9% vs. 41.6%; p = 0.048), whereas men had more secondary pulmonary infections (34.4% vs. 18.9%; p = 0.008). CONCLUSIONS: Although sex was not an independent predictor of 90-day neurological outcome in this multicenter cohort of intubated ICU patients with severe aSAH, women were older and had slightly higher vasospasm rates but fewer systemic complications, particularly infections. These findings support incorporating sex and age into future prognostic work and underscore the importance of systemic complications in recovery after severe aSAH. TRIAL REGISTRATION: ATLANREA cohort, www. CLINICALTRIALS: gov, NCT02426255.