Perioperative Hydrogen Inhalation and Postoperative Pain After Endoscopic Discectomy: A Pilot Non-Randomized Clinical Study with Exploratory Murine Data
Sung CH, Ko WC, Kung CC, Hung CF. · Medicina (Kaunas). 2026;62(9):1785. Published 16 September 2026.
Study at a glance
A small nonrandomized study found lower pain scores at some time points after hydrogen–oxygen inhalation during spine surgery. Only 25 of 37 enrolled patients could be analyzed: records for 12 hydrogen patients were unavailable. The groups were treated in different periods and patients were not blinded. Differences were significant immediately after surgery, at one hour and at one month, but not at every assessment. These results cannot establish that hydrogen caused the differences. Mouse and blood-cell experiments were exploratory.
Human
Adults aged 20–75 undergoing endoscopic discectomy for chronic sciatica.
Open nasal cannula during the operation only, alongside standard anesthetic/sedation care. · Source: 66.7% H₂ / 33.3% O₂. Inspired H₂ approximately 4% was estimated after air entrainment, not measured.
During the operation only; exact session duration not verified. Pain assessed in PACU, at 1, 6, 12 and 24 hours, and at one month.
Pain, PACU: hydrogen: 2.04 ± 1.76; comparator: 5.25 ± 2.86; between group: Difference −3.21; 95% CI −5.02 to −1.41; Holm-adjusted p = 0.002. Pain, 1 hour: between group: Difference −2.42; 95% CI −3.85 to −0.98; Holm-adjusted p = 0.004. Pain, 6 / 12 / 24 hours: between group: Holm-adjusted p = 0.071 / 0.081 / 0.350; not significant. Pain, one month: between group: Difference −3.45; 95% CI −4.80 to −2.10; Holm-adjusted p < 0.001. Intraoperative fentanyl: hydrogen: 265.38 ± 99.24 micrograms; comparator: 347.92 ± 93.82 micrograms; between group: Difference −82.54 micrograms; 95% CI −162.61 to −2.47; p = 0.044. Rescue analgesia: hydrogen: 5/13; comparator: 10/12; between group: p = 0.041.
Nonrandomized sequential cohorts, no sham or blinding, and original outcomes missing for 12 of 25 hydrogen-period patients. Small samples and time-period or co-treatment confounding prevent causal conclusions. Inspired and environmental H₂ concentration were not measured. The registered one-week outcome was unavailable; the one-month contrast partly reflects increased pain in controls. Mouse and blood-cell findings do not validate a human mechanism. Pain P values were Holm adjusted; displayed confidence intervals were not multiplicity adjusted.
What kind of evidence is this?
Human
Pilot open-label, nonrandomized clinical study with sequential treatment periods; separate exploratory mouse and human blood-cell experiments in the same publication.
Musculoskeletal and pain research
Inhaled H₂
Information not yet classified
Some editorial classification fields are still pending. The source-reported outcomes and result are shown below; Hydrogenology does not infer a positive or negative signal from prose automatically.
Methods
Adults aged 20–75 undergoing endoscopic discectomy for chronic sciatica.
37 enrolled: 25 in the hydrogen period and 12 controls. Only 25 source-verifiable patients were analyzed (13 hydrogen, 12 control); original outcome records for 12 of 25 hydrogen-period participants were unavailable. No imputation.
During the operation only; exact session duration not verified. Pain assessed in PACU, at 1, 6, 12 and 24 hours, and at one month.
Open nasal cannula during the operation only, alongside standard anesthetic/sedation care.
Hydrogen and oxygen source-gas mixture; source composition is distinct from inspired concentration.
Source: 66.7% H₂ / 33.3% O₂. Inspired H₂ approximately 4% was estimated after air entrainment, not measured.
Reported total source-gas flow 2 L/min. The approximately 1.33 L/min H₂ component follows from the mixture proportion; it is not a measured inhaled dose.
33.3% O₂ in the source mixture; controls received standard oxygen/air without a sham device.
Standard oxygen/air without hydrogen; no sham gas device.
Outcomes and reported result
Postoperative 0–10 numerical pain-rating score over time.
Pain, PACU: hydrogen: 2.04 ± 1.76; comparator: 5.25 ± 2.86; between group: Difference −3.21; 95% CI −5.02 to −1.41; Holm-adjusted p = 0.002. Pain, 1 hour: between group: Difference −2.42; 95% CI −3.85 to −0.98; Holm-adjusted p = 0.004. Pain, 6 / 12 / 24 hours: between group: Holm-adjusted p = 0.071 / 0.081 / 0.350; not significant. Pain, one month: between group: Difference −3.45; 95% CI −4.80 to −2.10; Holm-adjusted p < 0.001. Intraoperative fentanyl: hydrogen: 265.38 ± 99.24 micrograms; comparator: 347.92 ± 93.82 micrograms; between group: Difference −82.54 micrograms; 95% CI −162.61 to −2.47; p = 0.044. Rescue analgesia: hydrogen: 5/13; comparator: 10/12; between group: p = 0.041.
The available main full text was reviewed for methods, results, limitations and declarations. Remaining source-specific uncertainties are stated in this record.
No adverse events documented in the 25 verifiable clinical records; substantial missing source records and small sample prevent a reliable general safety conclusion.
Male C57BL/6 mice with sciatic-nerve chronic-constriction injury, n = 6/group, received H₂/O₂ 1.5 hours/day for 14 days versus air. It was a preventive/protective exposure, not proof of reversal of established pain. Control gas was not oxygen matched. Human PBMC pre/post analysis used 13 hydrogen patients without a parallel control. The mouse and blood-cell findings do not establish a mechanism or clinical benefit in humans.
A reported association, difference or mechanism is not automatically a clinical benefit.
Limitations and applicability
Nonrandomized sequential cohorts, no sham or blinding, and original outcomes missing for 12 of 25 hydrogen-period patients. Small samples and time-period or co-treatment confounding prevent causal conclusions. Inspired and environmental H₂ concentration were not measured. The registered one-week outcome was unavailable; the one-month contrast partly reflects increased pain in controls. Mouse and blood-cell findings do not validate a human mechanism. Pain P values were Holm adjusted; displayed confidence intervals were not multiplicity adjusted.
Adults aged 20–75 undergoing endoscopic discectomy for chronic sciatica. Findings apply only to the studied design and exposure; no treatment or device recommendation.
Cathay General Hospital 111-CGH-FJU-03 and Fu Jen Catholic University Hospital PL-202108018-V.
No conflicts of interest declared.
No single-study GRADE certainty rating is assigned. Read how records and evidence assessments are prepared.
Sources and record status
PMID: 42796391 · DOI: 10.3390/medicina62091785
Complete article in PubMed Central, including tables.
AI-assisted editorial review of the available main full text, 29 October 2026. The source version and access limitations are stated in this record. No independent clinical or statistical assessment has been performed.
Methods 2.1–2.9 Results 3.1–3.3; Tables 1–2 Discussion 4 and Conclusions 5 Ethics, registration, funding and conflict declarations
AI-assisted editorial review of the available main full text, 29 October 2026. Complete article in PubMed Central, including tables.
ClinicalTrials.gov registration NCT05476575 was first submitted on 27 October 2021; recruitment began on 28 October 2021. The record was first publicly posted on 27 July 2022, after the final recruitment period. The article describes registration as prospective because submission preceded recruitment. The registry describes a nonrandomized, unmasked study with actual enrollment of 37.
29 October 2026
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