Cerebral perfusion pressure trajectories and cumulative exposure metrics predict in-hospital mortality in acute brain injury

Objective Fixed cerebral perfusion pressure (CPP) targets may not fully capture dynamic changes in acute brain injury (ABI). We aimed to identify CPP trajectory phenotypes, evaluate cumulative CPP metrics, and examine their associations with in-hospital mortality in ICU patients with ABI. Methods This multicenter retrospective cohort study included 1,466 adults with ABI from three ICU databases (MIMIC-IV, eICU, and NSICU). CPP trajectory phenotypes were identified using latent class growth modeling. Cumulative CPP metrics were derived using threshold-specific methods at 50, 60, and 70 mmHg and a mixed-effects approach. Associations with in-hospital mortality were assessed using multivariable Cox regression and survival analyses. The incremental prognostic value of CPP trajectory was evaluated as a secondary exploratory analysis. Results Four CPP trajectory phenotypes were identified: Stable Normal, Gradual Recovery, Labile Improvement, and Rapid Decline. Compared with Stable Normal, mortality risk increased progressively in Gradual Recovery (HR 1.720, 95% CI 1.252–2.362), Labile Improvement (HR 2.081, 95% CI 1.508–2.873), and Rapid Decline (HR 5.313, 95% CI 3.547–7.958; all P < 0.001). Higher cumulative CPP metrics derived from threshold-specific and mixed-effects approaches were consistently associated with lower in-hospital mortality (all P < 0.001). Survival analyses showed clear separation across phenotypes, with Stable Normal showing the highest survival probability and Rapid Decline the lowest. Adding CPP trajectory to a baseline model modestly improved discrimination and reclassification (AUC 0.759 to 0.773, P = 0.011; IDI 0.025; continuous NRI 0.157; both P < 0.001). Conclusions Distinct CPP trajectory phenotypes and cumulative CPP metrics were associated with in-hospital mortality in ICU patients with ABI. CPP trajectory also provided modest incremental prognostic information and warrants prospective validation.