Nitrous oxide analgesia for rehabilitation after anterior cruciate ligament reconstruction: A randomized controlled trial

Ziyang Wang; Lingjun Zhou; Fei Wang; Xiaochen Jiang; Weifeng Wang; Xueling Qiu; Yihui Xing; Chongjian Fu; Ping Zhong; Lu Tang

doi:10.1016/j.rehab.2024.101897

Nitrous oxide analgesia for rehabilitation after anterior cruciate ligament reconstruction: A randomized controlled trial

Ann Phys Rehabil Med. 2025 Jan 10;68(2):101897. doi: 10.1016/j.rehab.2024.101897. Online ahead of print.

Authors

Ziyang Wang¹, Lingjun Zhou², Fei Wang³, Xiaochen Jiang¹, Weifeng Wang¹, Xueling Qiu⁴, Yihui Xing⁵, Chongjian Fu⁶, Ping Zhong⁷, Lu Tang⁸

Affiliations

¹ Department of Stomatology, The 960th Hospital of People's Liberation Army of China (PLA), Jinan, Shandong, 250031, China; School of Nursing, Shandong Second Medical University, Weifang, Shandong, 261053, China.
² School of Nursing, Naval Military Medical University, Shanghai, 571623, China.
³ Department of Anesthesiology, The 960th Hospital of People's Liberation Army of China (PLA), Jinan, Shandong, 250031, China.
⁴ Department of Stomatology, The 960th Hospital of People's Liberation Army of China (PLA), Jinan, Shandong, 250031, China; School of Nursing, Shandong First Medical University, Taian, 271016, China.
⁵ Department of Outpatient Comprehensive Management, Qingdao Stomatological Hospital, Qingdao, 266001, China.
⁶ Department of Stomatology, The 960th Hospital of People's Liberation Army of China (PLA), Jinan, Shandong, 250031, China.
⁷ Department of rehabilitation medicine, The 960th Hospital of People' s Liberation Army of China (PLA), Jinan, 250031, China.
⁸ Department of Stomatology, The 960th Hospital of People's Liberation Army of China (PLA), Jinan, Shandong, 250031, China. Electronic address: tanglu_office@163.com.

PMID: 39798171
DOI: 10.1016/j.rehab.2024.101897

Abstract

Background: Although there is increasing emphasis on rehabilitation training after ligament reconstruction, little is known about the pain induced by the procedure itself. Procedural success may be limited by pain and anxiety. Nitrous oxide is widely used to alleviate procedural pain. However, few studies have been conducted to show the efficacy and safety of nitrous oxide for rehabilitation training.

Objectives: To explore the short-term efficacy and safety of nitrous oxide for acute pain elicited by rehabilitation training.

Methods: A double-blinded randomized placebo-controlled trial was conducted in the department of rehabilitation medicine. People willing to participate in the trial and sign informed consent, ≥18 years old, who had acute pain (self-reported pain score ≥4) caused by rehabilitation training after anterior cruciate ligament reconstruction were recruited. Participants undergoing rehabilitation training were randomized to receive either 65 % nitrous oxide or 100 % oxygen. The primary outcome was the pain score. Secondary outcomes were sedation score, range of motion, vital signs, physician and participant satisfaction, acceptance, and side effects.

Results: 120 people were enrolled; 60 received nitrous oxide and 60 received oxygen. The nitrous oxide group had a significantly lower pain score than the placebo group (P < 0.001, median difference -3, 95 % CI -4 to -2, effect size η² = 0.369) and sedation scores (P < 0.001, median difference 1, 95 % CI 1 to 1, η² = 0.263) during the procedure. Both physician (P < 0.001) and participant (P < 0.001) satisfaction were significantly higher in the intervention group than the placebo group. Acceptance (willingness to use the same gas next time) differed between groups (P < 0.001). No serious side effects occurred.

Conclusion: This study provides evidence supporting the efficacy and safety of self-administered nitrous oxide to reduce procedural pain during rehabilitation training after anterior cruciate ligament reconstruction.

Keywords: Anesthesia; Anterior cruciate ligament reconstruction; Nitrous oxide; Rehabilitation.