Determinants of intensive care unit-acquired acute brain injury in acute respiratory distress syndrome: a retrospective cohort study of ventilator settings and patient factors.

BACKGROUND: Acute respiratory distress syndrome (ARDS) is associated with neurological complications, but whether mechanical ventilation parameters or patient factors predominantly contribute to intensive care unit (ICU)-acquired acute brain injury (ABI) remains unclear. We aimed to determine whether ICU-acquired ABI in ARDS is independently associated with positive end-expiratory pressure (PEEP) and driving pressure delivered early after intubation or, instead, with patient-level factors. METHODS: We conducted an exploratory, single-center retrospective cohort study of mechanically ventilated ARDS patients (January 2019 to June 2023). ICU-acquired ABI was defined as a new acute intracranial lesion on computed tomography (CT) or magnetic resonance imaging (MRI) obtained more than 72 hours after ICU admission. In a pre-specified analysis, PEEP and driving pressure measured in the first 24 hours after intubation were tested for independent association with ABI using Firth penalized logistic regression with multiple imputation, adjusting for pre-specified confounders [age, sex, arterial partial pressure of oxygen (PaO2)/fraction of inspired oxygen (FiO2) ratio, vasopressor use, and extracorporeal membrane oxygenation (ECMO)], with platelet count and C-reactive protein (CRP) analyzed as separate host-factor exposures. Robustness, subtype, exposure-window, and analyses accounting for the selective use of neuroimaging were performed. RESULTS: Among 2,844 patients (median age, 66 years; 62% male), 54 (1.9%) developed ICU-acquired ABI. Neither PEEP [adjusted odds ratio (OR) =1.02; 95% confidence interval (CI): 0.91 to 1.14] nor driving pressure (adjusted OR =1.01; 95% CI: 0.96 to 1.06) was independently associated with ABI, and this null result held across the pre-specified adjustment sets, both ischemic and hemorrhagic subtypes, the imaged subcohort, and inverse-probability weighting. Thrombocytopenia (platelet <100×103/µL) was independently associated with ABI (adjusted OR =3.22; 95% CI: 1.77 to 5.88), with CRP associated only with ischemic lesions. ABI was associated with a longer ICU stay (adjusted β =16.4 days) and higher in-hospital mortality (adjusted OR =2.92). CONCLUSIONS: In ARDS, neither PEEP nor driving pressure was independently associated with ICU-acquired ABI once exposures were time-aligned, whereas thrombocytopenia was. At the airway pressures used in contemporary practice, brain injury appeared to be related more to the patient's hematologic vulnerability than to ventilator settings, and these findings do not support restricting lung-protective ventilation out of concern for neurological harm. This exploratory analysis, with 54 events, cannot exclude smaller effects and requires prospective confirmation.