Abstract 111: Combination Therapy of Hydrogen Inhalation and Hypothermic Temperature Control Improves Neurological Outcomes After Out-of-Hospital Cardiac Arrest

Abstract

Background: In a randomized trial, we demonstrated that hydrogen (H 2 ) inhalation improves outcomes after cardiac arrest (CA). All patients underwent target temperature management (TTM), but the selection of a target temperature between 32 and 36 °C varied per institutional protocol. Hypothesis: The combination of hypothermic TTM and H 2 improves neurological outcomes after CA. Aims: This study aimed to investigate the interaction of H 2 and hypothermic TTM on neurological outcomes after CA. Methods: This post-hoc analysis of a randomized controlled trial (HYBRID II Trial; jRCTs031180352) included comatose patients after cardiogenic out-of-hospital CA (OHCA). They received either 2% H 2 mixed oxygen (H 2 group) or oxygen alone (control group) for 18 hours under hypothermic TTM (<35°C) or normothermic TTM (35-36°C). A target temperature was reached quickly, maintained for 24 hours, and rewarmed over 48 hours. A good neurological outcome was defined as a Cerebral Performance Category (CPC) of 1 or 2 at 90 days. The neurological outcomes were compared between the H 2 and control groups under hypothermic or normothermic TTM. Results: The analysis included 72 patients with outcome data (39 and 33 patients in the H 2 and control group, respectively). Hypothermic TTM was implemented in 25 (64%) and 24 (73%) patients in the H 2 and control group, respectively (P=0.46). Under hypothermic TTM, 17 (68%) and 9 (38%) patients achieved CPC 1 or 2 in the H 2 and control group, respectively (relative risk 1.81 [95%CI: 1.05-3.66]). In contrast, under normothermic TTM, CPC of 1 or 2 was achieved in 5 (36%) and 4 (44%) patients (P>0.99) in the H 2 and control group, respectively. A multivariable logistic regression analysis indicated that the interaction between H 2 and hypothermic TTM was independently associated with CPC 1 or 2 at 90 days (adjusted odds ratio 3.71 [95%CI: 1.14-12.1]) after adjusting for confounding factors including age, sex, witness status, bystander CPR implementation, shockable rhythm, CA duration, and time from the return of spontaneous circulation to gas inhalation. Conclusions: H 2 in combination with hypothermic TTM improved neurologicaloutcomes after cardiogenic OHCA. However, the favorable effects of inhaled H 2 were not observed under normothermic TTM.