A study conducted across 15 emergency medical facilities in Japan has shown that hydrogen gas (H2) inhalation increased the possibility of neurologically intact survival among patients who remain comatose following the return of spontaneous circulation from out-of-hospital cardiac arrest (OHCA). The multicenter, double-blind, randomized controlled trial was conducted as part of the activities of the Keio University Center for Molecular Hydrogen Medicine and was led by Professor Masaru Suzuki of the Tokyo Dental College (Specially Appointed Professor at Keio University Global Research Institute) and assistant professors Koichiro Honma (Emergency Medicine) and Motoaki Sano (Cardiology) of the Keio University School of Medicine, among others.
When a victim suffers sudden cardiogenic cardiac arrest, immediate cardiopulmonary resuscitation is crucial in restoring their circulation and saving their life. In those who initially restore spontaneous circulation after OHCA, the significant subsequent morbidity and mortality are primarily due to the cerebral and cardiac dysfunction that accompanies prolonged whole-body ischemia. This state, called post-cardiac arrest syndrome, comprises anoxic brain injury, post-cardiac arrest myocardial dysfunction, systemic ischemia/reperfusion response, and persistent precipitating pathology. With the brain's heightened susceptibility to global ischemia, the majority of cardiac arrest patients who are successfully resuscitated have impaired consciousness, and some remain in a vegetative state. No effective therapy that diminishes the ischemia/reperfusion injury has been developed yet besides targeted temperature management, which is recommended by international guidelines.
This research group previously reported that inhalation of H2 after cardiac arrest reduces mortality and brain injury in a rodent model. However, there has been no evidence in human clinical settings. To determine whether the H2 inhalation therapy improved neurologically intact patients who remain comatose following the return of spontaneous circulation from OHCA, the group conducted a multicenter, double-blind, randomized controlled trial, the most reliable trial method at emergency medical facilities in Japan.
As the study was terminated prematurely because the COVID-19 pandemic led to a drastic increase in the demand for ventilators and a chronic staff shortage that hampered patient enrollment, the increase in participants with good neurological outcomes following post-OHCA H2 inhalation in a selected population of patients was not statistically significant.
However, the secondary outcomes suggest that H2 inhalation may increase 90-day survival from 61% to 85%. Further, 90-day survival with no neurological deficits increased from 21% to 46%. H2 has been recognized as safe for the human body, and no side effects attributable to H2 were observed in this clinical trial. This treatment is expected to save the lives of many patients when implemented in clinical settings.
The results of this study were published in eClinicalMedicine
on March 17, 2023 (JST).