Early time-weighted average PEEP and mortality in sepsis-associated myocardial injury requiring invasive mechanical ventilation: a retrospective cohort study with external validation.

Background: Sepsis-associated myocardial injury (SAMI) defines a cardiovascularly vulnerable population in whom ventilatory strategies may affect hemodynamic stability. Accordingly, we investigated whether higher early time-weighted average (TWA) positive end-expiratory pressure (PEEP) is associated with mortality in patients with SAMI. Methods: This retrospective study used Medical Information Mart for Intensive Care IV (MIMIC-IV) and an external cohort to examine adult intensive care unit (ICU) patients with SAMI who received invasive mechanical ventilation (IMV) within 24 h of ICU admission. Associations with ICU and in-hospital mortality were estimated using generalized propensity score (GPS) weighting in covariate-adjusted logistic regression models. Nonlinearity was evaluated using restricted cubic splines. Effect modification was examined in prespecified subgroups, and robustness was assessed through sensitivity analyses. Results: The derivation cohort included 3,421 patients, with ICU and in-hospital mortality rates of 29% and 37%, respectively. In the primary GPS-weighted covariate-adjusted model, each 1 cmH Conclusions: Among patients with SAMI receiving invasive mechanical ventilation, higher early TWA PEEP was consistently associated with increased ICU and in-hospital mortality in both derivation and external validation cohorts.