Association of early lactate with 365-day all-cause mortality in critically ill patients with acute ischemic stroke: A retrospective cohort study using MIMIC-IV.

Lactate may integrate tissue hypoperfusion, adrenergic stress, impaired hepatic clearance, and metabolic responses to cerebral ischemia. Although not stroke-specific, early elevation may identify critically ill patients with concurrent neurological injury and extracerebral organ dysfunction. We evaluated the association between early lactate and all-cause mortality in critically ill patients with a hospitalization-level acute ischemic stroke (AIS) diagnosis. This retrospective cohort study used Medical Information Mart for Intensive Care IV version 3.1 (2008-2022). Adults with an AIS code in any diagnosis position were screened. The earliest lactate recorded during the index intensive care unit stay was used. The primary outcome was 365-day all-cause mortality. Adjusted Cox regression assessed time-to-event associations, and logistic regression evaluated fixed-horizon outcomes. Models were adjusted for demographics, comorbidity burden, neurological and global illness severity, organ dysfunction, hemodynamic and laboratory variables, and liver disease. Patients with and without lactate measurements were compared; calibration, restricted cubic splines, Kaplan-Meier curves, subgroup, decision curve, and sensitivity analyses were also performed. Among 2001 eligible patients, 859 had an early lactate measurement and 1142 did not; measured patients had greater illness severity and more frequent invasive ventilation. During 365 days, 286 patients (33.3%) died. Each 1 mmol/L lactate increase was associated with higher mortality (adjusted hazard ratio [HR], 1.14; 95% confidence interval [CI], 1.07-1.22; P < .001). Versus Q1, adjusted HRs were 1.74 (95% CI, 1.22-2.50) for Q3 and 2.00 (95% CI, 1.37-2.92) for Q4. Adding lactate increased the 5-fold cross-validated area under the curve from 0.744 to 0.755 and reduced the Brier score from 0.187 to 0.182, with calibration slopes of 0.87 and 0.86. Early lactate was associated with short- and long-term all-cause mortality in critically ill patients with a hospitalization-level AIS diagnosis. Selection into lactate testing was substantial, the incremental predictive gain was small, and external validation is required. Lactate should be interpreted as a complementary marker of systemic and neurological stress rather than a stand-alone predictor.