Effect of Inhalation of Hydrogen Gas on Postoperative Recovery After Hepatectomy: A Randomized, Double-Blind, Placebo-Controlled Trial

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Abstract
Hydrogen has antioxidant and anti-inflammatory properties that may attenuate perioperative stress responses. However, its clinical impact on postoperative recovery remains unclear. This randomized, double-blind, placebo-controlled trial evaluated whether perioperative hydrogen inhalation improves early recovery after hepatectomy. Sixty-eight patients undergoing elective hepatectomy were randomized (1:1) to receive 5% hydrogen gas or placebo air via nasal cannula from postoperative day (POD) 1 to POD7. The primary endpoint was the total Quality of Recovery-40 (QoR-40) score on POD3, analyzed at α = 0.2 with 80% confidence intervals in accordance with the pre-specified statistical analysis plan. Secondary and exploratory outcomes, analyzed at α = 0.05, included postoperative liver function, oxidative stress markers, and QoR-40 subdomain scores. Analyses were performed in the modified intention-to-treat population using the Mann–Whitney U test. Sixty-four patients (hydrogen, n = 31; placebo, n = 33) were analyzed. At POD3, the median QoR-40 score was 192.0 (184.0–198.0) vs. 163.0 (140.0–190.0) (p < 0.001), indicating significantly better early recovery in the hydrogen group. As supportive findings, prothrombin activity was higher with hydrogen (85.0% vs. 76.2%, p = 0.005), and QoR-40 subdomain analysis showed significantly higher emotions and physical independence scores, whereas comfort, pain, and patient support domains showed no difference. No other between-group differences were observed in biochemical parameters or urinary 8-OHdG levels. Perioperative hydrogen inhalation significantly improved early postoperative recovery after hepatectomy, primarily through psychophysical domains of well-being. These findings suggest that hydrogen may selectively enhance emotional stability and functional independence during the early recovery phase.
Funding Information
  • Helix Japan Co., Ltd.

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