Hyperbaric oxygen therapy in patients after cardiopulmonary resuscitation for out-of-hospital cardiac arrest: A randomized controlled trial (HOT-RESUS 1 study)

BackgroundHyperbaric oxygen therapy (HBOT) after out-of-hospital cardiac arrest (OHCA) remained untested in humans despite promising preclinical evidence. We thus evaluated feasibility, safety, and early biological signals of HBOT across distinct clinical cohorts and exposure subgroups. MethodsThis prospective single centre randomized controlled multi-cohort study enrolled (i) intensive care (ICU) patients as soon as possible after return of spontaneous circulation (ROSC) (maximum 24 hours), (ii) long-term OHCA survivors, and (iii) healthy volunteers. Within each cohort, participants were stratified into HBOT exposure groups (no, one, or five sessions). Assessments included serial laboratory biomarkers (endothelial, inflammatory, oxidative stress, neuronal, myocardial), vascular stiffness, neurocognitive testing, and psychological questionnaires. Changes from baseline were analysed using Wilcoxon and Kruskal-Wallis tests, alongside adjusted general linear models (GLM) with key clinical covariates. ResultsHBOT delivery was feasible and safe, with full follow-up achieved across all three cohorts. In ICU patients, inflammatory (TNF-, CRP), oxidative stress (MPO, TBARS, ROMO-1), and endothelial dysfunction markers (ET-1, ADMA) improved over time, while neuronal injury (NSE) showed partial attenuation; signals were most evident in the 1x and 5x HBOT exposure groups. Among long-term survivors, global and domain-specific cognition, arterial stiffness (pulse wave velocity), and psychological measures improved, with effects primarily observed in HBOT groups. Volunteers exhibited stable cognition but reproducible PWV reductions in HBOT groups, indicating a vascular effect beyond the post-cardiac arrest context. ConclusionIn this feasibility study, HBOT was successfully implemented across ICU patients, survivors, and healthy volunteers, with dose-stratified exposure subgroups. Converging biological signals indicate the potential of HBOT towards an attenuation of systemic inflammation and oxidative stress, recovery of endothelial and vascular function, and mitigation of neuronal and myocardial injury. These early findings provide a rationale for further evaluations of HBOT as a pleiotropic intervention targeting the endothelium-inflammation-injury axis after cardiac arrest.