Associations of positive end-expiratory pressure (PEEP) with extubation failure and clinical outcomes in invasively ventilated patients with acute brain injury: A secondary analysis of the ENIO study

Background: Invasive mechanical ventilation (IMV) is crucial for managing acute brain injury (ABI) patients, yet the effects of positive end-expiratory pressure (PEEP) on outcomes are not well understood. This study aimed to evaluate the relationship between PEEP levels and risk of extubation failure as well as intensive care unit (ICU) mortality in ABI patients. Methods: This post-hoc analysis of the ENIO study included 1512 ABI patients from the ENIO cohort, excluding those without available data on PEEP at day 1 and who never received an extubation trial. PEEP levels were recorded at days 1, 3, 7, and on the day of extubation. Logistic regression assessed the association between PEEP and extubation failure, while Cox proportional hazards regression analyzed ICU mortality. Results: Among 1154 included patients, extubation failure occurred in 21.2 % and ICU mortality was 3.7 %. Higher median PEEP at days 1, 3, and 7 was independently associated with increased odds ratio (OR) of extubation failure (OR = 1.13; 95 %CI = 1.01-1.26; p = 0.0294). At the time of extubation, higher PEEP was also significantly associated with extubation failure (OR = 1.13; 95 %CI = 1.02-1.25; p = 0.0218) and ICU mortality (Hazard Ratio, HR = 1.38; 95 %CI = 1.12-1.69; p = 0.0026). However, at sensitivity analyses adjusted for acute respiratory distress syndrome (ARDS), PEEP was no longer significantly associated with outcomes, while ARDS itself was an independent predictor of extubation failure. Conclusions: Extubating ABI patients at higher PEEP levels was associated with an increased risk of extubation failure and ICU mortality. However, this association likely reflects underlying respiratory pathology or disease severity. Our findings suggest that PEEP level may serve as a surrogate marker for extubation readiness, rather than a modifiable risk factor, and highlight the need for individualized assessment prior to extubation.