Patient-Centered Intrathecal Morphine Dose-Response in Major Abdominal Surgeries when Augmented by Innovative 5-drug Antiemetic Prophylaxis

Brian A. Williams ^1,2* Daniel E Hall ^1,2 Chelsee Dalessandro ² Kelly E Garbelotti ² John M Ludden ²

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

For abdominal surgery involving cephalad surgical trespass (sleeve gastrectomy, pancreatectomy), existing intrathecal morphine recommendations of <=150 μg may not achieve meaningful analgesia, leading to probable side effects from intravenous opioids during/after surgery. Our specific aims are to present (i) an intrathecal morphine dosing guideline to improve upon existing guideline doses (≤150 µg), and (ii) an analgesic duration predictor derived from the proposed versus existing dosing guideline.We used a mixed method multi-hypothetical framework to demonstrate that 5-drug antiemetic prophylaxis before spinal morphine may allow for ≥250 μg doses, which with further refinement may confer meaningful analgesia, downstream opioid sparing, and prevention of nausea/vomiting. A retrospective, case-matched quality improvement initiative was implemented, after which we used multiple regression to (i) calculate successful spinal morphine dosing, and (ii) predict analgesic duration in our Veteran patient population.As opposed to currently-recommended <=150 μg, 250 μg was the dosing start-point for spinal morphine, with available adjustments for gender, height, and age. The 250 μg dose (and incremental adjustments) was associated with 16 hr baseline duration, while <200 μg was associated with only 8 hr baseline duration; these latter durations (i.e., ≤8 hr) were adversely influenced by factors that did not affect the ≥250 μg duration.We achieved meaningful prophylaxis against nausea/vomiting with the 5 "keyword" drugs (all 5 drugs used in 94% of our patients with the ≥250 μg morphine dose). This seems to facilitate adherence to oral/enteral non-opioid analgesics after surgery, possibly contributing to analgesic duration. Conversely, avoidance of usual intraoperative (fentanyl, remifentanil, hydromorphone) and postoperative (hydromorphone, oxycodone, hydrocodone) opioids may have prolonged perceived analgesic duration (and avoided nausea) by not creating opioidinduced hyperalgesia and/or tolerance. We presume that morphine ≥250 μg had sufficient "cephalad reach" for varying procedures, as well as for endoscopic cased converted to open. This interaction may prevent reflexive intraoperative administration of usual intravenous opioids. Five-drug antiemetic prophylaxis may allow for improved analgesic outcomes and systemic opioid reductions, via patient-based parameters of a spinal morphine dose startpoint of at least 250 μg, as opposed to currently-recommended doses of <=150 μg.