Perioperative Hydrogen Inhalation and Postoperative Pain After Endoscopic Discectomy: A Pilot Non-Randomized Clinical Study with Exploratory Murine Data

Background/Objectives: Postoperative pain after endoscopic discectomy may reflect acute surgical nociception superimposed on pre-existing radicular symptoms. Molecular hydrogen (H2) has antioxidant and anti-inflammatory properties, but clinical evidence for perioperative analgesia is limited. We evaluated the association between perioperative H2 inhalation and postoperative pain and analgesic requirements. Methods: This open-label, non-randomized pilot study enrolled 37 patients in two consecutive periods (H2, n = 25; control, n = 12). Because original outcome records for 12 H2-period participants could no longer be retrieved at the time of manuscript preparation, the complete-case clinical analysis included 25 source-verifiable participants (H2, n = 13; control, n = 12). H2 was delivered via nasal cannula as a 66.7% H2/33.3% O2 source gas at 2 L/min (estimated inspired H2 approximately 4%). Pain was evaluated with a numerical rating scale (NRS) preoperatively, at post-anesthesia care unit (PACU) arrival, at 1, 6, 12, and 24 h, and at 1 month. Longitudinal scores were analyzed using generalized estimating equations with Holm-adjusted comparisons. A parallel exploratory murine chronic constriction injury (CCI) experiment (n = 6/group) assessed mechanical allodynia over 14 days of daily H2 inhalation. Results: The group-by-time interaction was significant (Wald χ2(6) = 56.68, p < 0.001). After Holm adjustment, pain scores were lower with H2 at PACU arrival (difference, −3.21; adjusted p = 0.002), 1 h (−2.42; adjusted p = 0.004), and 1 month (−3.45; adjusted p < 0.001). Intraoperative fentanyl use and rescue analgesic use were also lower in the H2 group; no adverse events were documented in the analyzed cohort. In the murine CCI experiment, H2-treated mice showed higher ipsilateral paw withdrawal thresholds than air-exposed controls. Conclusions: Perioperative H2 inhalation was associated with lower pain scores at selected time points and reduced analgesic requirements. These preliminary findings require confirmation in randomized trials. Trial registration: ClinicalTrials.gov NCT05476575.