Time-dependent effects of positive end-expiratory pressure on hemodynamics, respiratory mechanics and clinical outcomes in patients receiving veno-arterial extracorporeal membrane oxygenation

Over 50% of patients receiving veno-arterial extracorporeal membrane oxygenation (VA-ECMO) die, mostly due to inadequate cardiac recovery. Moderate-to-high positive end-expiratory pressure (PEEP) may positively influence cardiac recovery and survival by optimizing biventricular loading conditions through improved heart-lung interaction. Participants in the multicenter observational cohort study (PRECISE-ECLS) were eligible if they received VA-ECMO support for more than 24 h in one of the six participating Dutch ICUs (2016–2024) and had longitudinal PEEP data for the first 48 h. Hemodynamic and respiratory parameters were assessed over 5 days, stratified by PEEP group. Associations between cumulative PEEP exposure and outcomes, including 30-day VA-ECMO weaning failure as primary endpoint and mortality, were assessed using time-dependent joint models integrating longitudinal PEEP trajectories with time-to-event analyses. 409 VA-ECMO-supported patients (mean age 59 years, 70% male) were categorized into a low (≤ 8 cmH₂O; n = 191), intermediate (8.1–13.9 cmH₂O; n = 169), and high (≥ 14 cmH₂O; n = 49) PEEP group. PEEP levels were comparable before versus after VA-ECMO initiation (median difference 0 cmH₂O; IQR − 1 to 2). Compared with low PEEP, higher PEEP levels were applied to sicker patients and were not accompanied by clear adverse temporal trends in the hemodynamic or respiratory variables examined. Higher cumulative PEEP exposure was not significantly associated with the hazard of 30-day VA-ECMO weaning failure (HR 0.97, 95% CI 0.92–1.01) and mortality (HR 0.96, 95% CI 0.90–1.02). PEEP levels remained largely unchanged after VA-ECMO initiation. Higher PEEP was preferentially applied to patients with greater illness severity, and no consistent adverse temporal trends were observed in the measured hemodynamic or respiratory variables. Among patients surviving beyond the first 24 h, cumulative PEEP exposure was not significantly associated with 30-day risks of VA-ECMO weaning failure and mortality. ClinicalTrials.gov; NCT05444764; first posted on July 6th, 2022. PEEP levels before and after VA-ECMO initiation were largely comparable, despite major changes in cardiopulmonary physiology. Higher PEEP was preferentially applied to patients with greater illness severity, and no consistent adverse trends were observed in the measured hemodynamic or respiratory variables. Among patients surviving beyond the first 24 hours, cumulative PEEP exposure was not significantly associated with 30-day VA-ECMO weaning failure or mortality.