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 cmH2O increase in early TWA PEEP was associated with higher ICU mortality (adjusted odds ratio [OR], 1.14; 95% confidence interval [CI], 1.10-1.18) and in-hospital mortality (adjusted OR, 1.11; 95% CI, 1.07-1.15). Restricted cubic spline analyses suggested a generally increasing risk pattern without a clear threshold. Subgroup analyses showed no significant effect modification, and sensitivity analyses addressing exposure definition, timing, incomplete observation, and alternative covariate adjustment yielded consistent results. In the external validation cohort (n = 285), the association remained directionally consistent for ICU mortality (OR, 1.31; 95% CI, 1.08-1.59) and in-hospital mortality (OR, 1.29; 95% CI, 1.07-1.57). 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.