Upgrading Intrathecal Morphine for Postoperative Pain Mitigation in Abdominal Surgery: An Exploratory Multiple Regression Analysis of Observational Data addressing co-administered spinal Magnesium Sulfate, en route to both enhanced systemic Opioid Sparing and Opioid Avoidance

Brian A. Williams^1,2*Ridhi Choragudi¹Christopher A. Schumacher¹Kelly Garbelotti²Catalin S. Ezaru^1,2Monique Y. Boudreaux-Kelly²Luca La Colla^1,3John M. Ludden²

• ¹University of Pittsburgh, Pittsburgh, United States
• ²VA Pittsburgh Healthcare System, Veterans Health Administration, United States Department of Veterans Affairs, Pittsburgh, Pennsylvania, United States
• ³UPMC Presbyterian, Pittsburgh, Pennsylvania, United States

For major abdominal surgery, we explored "usual" opioid-avoiding effects of spinal magnesium 25 mg added to intrathecal morphine (250+ µg in women, 300+ µg in men; ITM+Mg + ). We evaluated associated benefits of several integrated care "bundles": 5-drug antiemetic prophylaxis, multiple-day postoperative antiemetic boosters (perphenazine and aprepitant), boosters for non-opioid transitional analgesia, and strategically-avoided usual opioids intraoperatively (fentanyl, hydromorphone, etc.). We also explored antiemetic outcomes, and pruritus, on postoperative days 0-2. We hypothesized these bundles would independently and interactively influence associated outcomes.We used a mixed-method framework to demonstrate whether these bundles, integrated with ITM+Mg + , were all associated with one or more milestones en route to improving described outcomes (prevented postoperative nausea/vomiting [PONV], avoided postoperative opioids, etc.). We did so via retrospective, case-matched quality improvement methodology for a singlehospital population of ITM-receiving Veterans, applying multiple regression to determine (i) PONV prevention success on days 0-1 separately from day 2, (ii) success of avoiding usual opioids (by withholding discretionary fentanyl/hydromorphone intraoperatively en route to avoiding the need for patient-requested hydromorphone/oxycodone postoperatively), and (iii) predictors/signals of itching, including related to the ITM-upgrade to ITM+Mg + .ITM+Mg + , at the described doses, supported by 5-antiemetic prophylaxis and three-drug nonopioid transitional analgesics, was associated with significant opioid-avoiding improvements. Postoperative avoidance of usual opioids was associated with both ITM+Mg + use and intraoperative and immediate postoperative avoidance of "usual opioids" (fentanyl, hydromorphone, etc.). PONV on days 0-1 (versus day 2) appears to have differing predictor patterns, warranting both 5-MMAEPPx preoperatively, and future antiemetic upgrade from 2drug booster prophylaxis (perphenazine/aprepitant) to also include palonosetron every 40 hours. ITM historical control major abdominal surgery cases before ITM+Mg + had a 14% "usual opioid avoidance rate" (35/246), which showed significant associated improvements with ITM+Mg + use, usual opioid avoidance, and integration with the other described care bundles (34/60, 57%, P<0.001).Multiple "bundles" appear to address both sustained antiemetic success and "usual opioid avoidance." ITM-related pruritus requires further study regarding prophylaxis and treatment, in order to allow ITM+Mg + to achieve its full enhanced recovery potential, when trying to avoid postoperative exposure to usual opioids.