Effect of hydrogen gas inhalation on patient QOL after hepatectomy: protocol for a randomized controlled trial

INTRODUCTION: Molecular hydrogen had been considered inactive in vivo but is an antioxidant that selectively reduces highly toxic reactive oxygen species (ROS). Animal studies have reported that hydrogen gas inhalation helped alleviate cerebral and cardiac ischemia-reperfusion injuries. In humans, hydrogen inhalation therapy is presently approved as a treatment under Advanced Medical Care B in Japan (jRCTs031180352: limited to adult patients who suffered out-of-hospital cardiac arrest and are in a continuous coma) and its effectiveness is being examined in a clinical trial. The Japanese government has introduced the “Advanced Medical Care System” to promote the development of drugs and devices under governmental regulations. Advanced Medical Care B is a system designed for unapproved or off-label drugs or medical technologies used in a clinical trial setting. Hepatectomy is generally performed with repeated hepatic blood-flow occlusion and then reperfusion (ischemia and reperfusion). No report, however, has been made on ROS inhibition by hydrogen inhalation therapy or its effectiveness in post-hepatectomy patients. Hydrogen gas inhalation in the early stages after hepatectomy is anticipated to inhibit liver dysfunction by inhibiting ROS. METHODS AND ANALYSIS: This study is a randomized, controlled, double-blind superiority trial, which will be conducted as a “specified clinical trial” in accordance with the Clinical Trials Act in Japan. Trial registration was prospectively completed before the first participant was enrolled. The subjects will be patients who will undergo hepatectomy and will be allocated randomly into group A with hydrogen gas inhalation or group B with air inhalation after hepatectomy. The study will examine if hydrogen gas inhalation improves QOL of post-hepatectomy patients. The primary endpoint is patient QOL (score of a 40-item quality of recovery questionnaire, QoR40) on postoperative day 3 and the secondary endpoints are QoR40s besides that on postoperative day 3, grade of postoperative complications (Clavien-Dindo score), level of pain (Numerical Rating Scale (NRS)), amount of dietary intake, liver function, inflammation level, 8-hydroxydeoxyguanosine (urinary 8-OHdG) level, and number of pedometer-assessed steps. ETHICS AND DISSEMINATION: The study protocol has been approved by the Niigata University Central Review Board of Clinical Research. The findings of this study will be widely disseminated through peer-reviewed publications and conference presentations. TRIAL REGISTRATION: jRCTs 03220332. Registered on 21 January 2021