Chronic Pain and the Opioid Epidemic: Are We Ignoring the Potential Benefits of Nitrous Oxide?

To the Editor The November 2017 issue of Anesthesia & Analgesia featured many articles on the opioid crisis. Within these articles, the intraoperative choice of anesthetic agents was minimally mentioned in the editorial by Yaster et al1 with no specific recommendations and Kumar et al2 who focused on regional anesthesia and nonanesthetic adjuvants. Neither article considered the potential of nitrous oxide to reduce perioperative opioid usage and chronic postsurgical pain. Achieving these goals has the potential to help combat the postsurgical opioid epidemic. The majority of heroin users got their start from medically prescribed opioids.3 First, the Evaluation of Nitrous Oxide in the Gas Mixture for Anesthesia-II study has shown reduced chronic pain in specific patient populations (Asians and patients with variants in the methylenetetrahydrofolate reductase gene).4 Reducing chronic pain would be expected to reduce opioid use in most patients. In the absence of specific or physical contraindications or a prolonged anesthetic, this should be an indication to use nitrous oxide in these populations, particularly in surgeries associated with chronic postsurgical pain. Any technique that is opioid sparing should decrease the likelihood of becoming addicted. Nitrous oxide (70%) has analgesic efficacy equivalent to 0.17 µg/kg/min of remifentanil.5 The use of nitrous oxide would be expected to reduce or eliminate the intraoperative opioid requirement. Tolerance and opioid-induced hyperalgesia (OIH) result from opioid use. It is possible that if one can reduce the amount of opioid given, one may be less likely to get into the vicious cycle of increasing opioid use due to tolerance or OIH. Clinical studies have reported increased postoperative pain despite increased postoperative opioid use in patients who received high doses of intraoperative opioids.6–10 Higher doses of opioids seemed to increase the extent of wound hyperalgesia, and this was associated with an increased risk of chronic pain at 3, 6, and 9 months.11 Nitrous oxide has been shown to reduce OIH.12 Tolerance can develop during a surgical procedure. Additional research is warranted to demonstrate that the analgesia of nitrous oxide can reduce the development of tolerance by reducing intraoperative opioid use. Many practitioners have been dissuaded from using nitrous oxide because of the concern of major cardiovascular morbidity and mortality and an increased risk of surgical site infections. In combination with another retrospective study of 49,016 patients where nitrous oxide use was associated with decreased 30-day mortality and decreased in-hospital mortality/morbidity and a Cochrane review, the results of the Evaluation of Nitrous Oxide in the Gas Mixture for Anesthesia-II have essentially eliminated these concerns.13–17 The other major reason for not using nitrous oxide has been the concern for postoperative nausea and vomiting. If a patient has been administered an antiemetic, there is a small nonsignificant increased risk of severe postoperative nausea and vomiting.18 It appears that the major patient outcome objections to the use of nitrous oxide have been effectively refuted. In summary, evidence suggests that the use of nitrous oxide reduces long-term chronic pain and OIH in some patients. It is possible that nitrous oxide use can reduce the development of tolerance. Intraoperative opioid use may be reduced because of the analgesia provided by nitrous oxide. Those who have decided not to use nitrous oxide should reconsider that decision. Using nitrous oxide will not solve the entire opioid problem, but it has the potential to help. While this letter is not a complete pro/con discussion, I argue that in the absence of a specific medical or physical contraindication to nitrous oxide or a prolonged anesthetic, one should be using nitrous oxide whenever possible. Further investigation of the potential of nitrous oxide to mitigate postsurgical opioid overuse and its disastrous consequences is warranted. Jonathan V. Roth, MDDepartment of AnesthesiologyAlbert Einstein Medical CenterPhiladelphia, Pennsylvania[email protected]