Intranasal application of xenon reduces opioid requirement and postoperative pain in patients undergoing major abdominal surgery: A randomized controlled trial

Background: Both central sensitization after peripheral tissue injury and the development of opioid tolerance involve activation of N-methyl-d-aspartate (NMDA) receptors. At subanesthetic doses the NMDA receptor antagonist xenon suppresses pain-evoked sensitization of pain-processing areas in the central nervous system. Although numerous studies describe the effect of NMDA receptor antagonists on postoperative pain, clinical studies elucidating their intraoperative analgesic potency when applied in a low dosage are still largely missing. Methods: To analyze the analgesic effect of low-dose xenon using new application Methods, the authors tested nasally applied xenon as an add-on treatment for analgesia in 40 patients undergoing abdominal hysterectomy. Within a randomized double-blind placebo-controlled study design, intraoperative and postoperative requirement of opioids as well as postoperative subjective experiences of pain were measured as primary outcome variables. Results: Intranasal application of xenon significantly reduced intraoperative opioid requirement (mean difference [MD] -2.0 μg/min; 95% CI [CI₉₅]-0.53 to -3.51, Bonferroni correction adjusted P value [p_corr]= 0.028) without relevant side effects and significantly reduced postoperative pain (MD -1.34 points on an 11-point rating scale; CI₉₅ -0.60 to -2.09, p _corr = 0.002). However, postoperative morphine consumption (MD -8.8 μg/min; CI₉₅ 1.2 to -18.8, p_corr = 0.24) was not significantly reduced in this study. Conclusions: Low-dose xenon significantly reduces intraoperative analgesic use and postoperative pain perception. Because NMDA receptor antagonists suppress central sensitization, prevent the development of opioid tolerance, and reduce postoperative pain, the intraoperative usage of NMDA receptor antagonists such as xenon is suggested to improve effectiveness of pain management within a concept of multimodal analgesia.