Analgesic effect of premixed nitrous oxide in postoperative rehabilitation for ankle fractures: a randomized controlled trial

Clinical Snapshot

Key Findings

• P Value: p < 0.001 for both time points

• Effect Size: T1: median difference -3.0 points; T2: median difference -2.0 points

• Primary Outcome: Pain scores significantly lower in nitrous oxide group at both time points

• Nnt Or Sensitivity: NNT not calculable from available data, but effect sizes suggest low NNT for clinically meaningful pain reduction

• Confidence Interval: T1: 95% CI -3.4 to -2.6; T2: 95% CI -2.8 to -1.2

Clinical Application

High feasibility - nitrous oxide delivery systems are standard in most hospitals and can be easily implemented in rehabilitation settings Nitrous oxide is TGA-approved and widely available in Australian hospitals. Could complement existing PBS-subsidized oral analgesics and align with RACGP pain management guidelines emphasizing multimodal approaches Adults undergoing postoperative rehabilitation for ankle fractures with moderate to severe pain (≥4/10)

Abstract

INTRODUCTION: The global incidence of ankle fractures is on the rise, effective postoperative rehabilitation is a crucial aspect of surgical management. However, the occurrence of severe pain during the rehabilitation continues to pose a substantial clinical challenge. METHODS: The study utilizes a dual-arm, single-center, double-blind, randomized controlled trial design. A total of 100 participants were enrolled. Participants included patients experiencing acute pain (self-reported pain score ≥4) who underwent postoperative rehabilitation for ankle fractures. Participants undergoing rehabilitation training were randomized to receive either 65% nitrous oxide or 100% oxygen. The primary outcome measured was the pain score, while secondary outcomes encompassed anxiety scores, physiological indices, side effects, patient and therapist satisfaction, acceptance, and residual pain. RESULTS: Pain scores were found to be significantly lower in the nitrous oxide group than in the oxygen group (T1: median difference -3.0, [95% CI -3.4 to -2.6]; p < 0.001; T2: median difference -2.0, [95% CI -2.8 to -1.2]; p < 0.001). Compared with the oxygen group, both therapists (p < 0.001) and participants (p < 0.001) in the nitrous oxide group reported significantly higher satisfaction levels. Acceptance rate showed significant intergroup differences (p < 0.001). No severe adverse effects were observed in either group. Anxiety scores between the two groups did not show a significant difference (p = 0.31, η2 = 0.027). CONCLUSION: The safety and analgesic profile of nitrous oxide renders it a suitable option for pain management in postoperative ankle fractures rehabilitation, thus providing a safe and easily manageable alternative to the current available strategies. CLINICAL TRIAL REGISTRATION: We have registered at https://www.chictr.org.cn and the registration number is: ChiCTR2400089379. In comparison with oxygen gas, nitrous oxide has been demonstrated to reduce pain during rehabilitation training following ankle fracture surgery, offering a practical and effective alternative to oral analgesics.The use of nitrous oxide in postoperative rehabilitation training for ankle fractures is relatively safe, with few and mild adverse reactions.Patients and rehabilitation therapists reported high satisfaction with nitrous oxide intervention, and residual pain was significantly reduced.

References

1. 1.Qiu, X., Wang, F., Wang, Y., Dou, J., Cao, W., Zhang, L., Sun, C., Wang, W., & Tang, L. (2026). Analgesic effect of premixed nitrous oxide in postoperative rehabilitation for ankle fractures: a randomized controlled trial. Annals of Medicine. https://doi.org/10.1080/07853890.2026.2685317