L.A. Graham1,2, S.S. Illarmo1, M.C. Odden5,6, S.C. Mudumbai3,7,8, S.M. Wren2,4 1VA Palo Alto Healthcare Systems, Health Economics Resource Center, Palo Alto, CA, USA 2Stanford University, Stanford-Surgery Policy Improvement Research And Education Center (S-SPIRE), Department Of Surgery, Stanford, CA, USA 3VA Palo Alto Healthcare Systems, Center For Innovation To Implementation, Palo Alto, CA, USA 4VA Palo Alto Healthcare Systems, Department Of General Surgery, Palo Alto, CA, USA 5VA Palo Alto Healthcare Systems, Geriatric Research, Education, And Clinical Center (GRECC), Palo Alto, CA, USA 6Stanford University, Epidemiology And Population Health, Stanford, CA, USA 7VA Palo Alto Healthcare Systems, Anesthesiology, Perioperative, And Pain Medicine, Palo Alto, CA, USA 8Stanford University, Anesthesiology, Palo Alto, CA, USA
Introduction:
Multimodal analgesia (MMA) is a perioperative pain management strategy that utilizes multiple types of pain medications to target different pain pathways, leading to a reduction in postoperative pain and opioid use. It is recognized as an optimal approach for pain management and is increasingly used across the United States. MMA involves a combination of various types of medications and delivery routes, which include neuraxial anesthesia and peripheral nerve blockades, along with intravenous acetaminophen, non-steroidal anti-inflammatory drugs (NSAIDs), and N-methyl-D-aspartate (NMDA) receptor-blocking agents. Optimal medication combinations for MMA are still unknown. Our objective was to leverage a quasi-experimental study design to identify MMA combinations that result in the greatest reductions in postoperative opioid use.
Methods:
Retrospective cohort study of inpatients who underwent an elective noncardiac surgical procedure with general anesthesia at six geographically similar hospitals between January 1, 2017 and December 31, 2022. The exposure, MMA, was defined as 2 or more nonopioid pain medications plus an opioid administered within 6 hours before surgery through the end of the operation. The outcome was opioid use in the 24 hours following surgery or post-anesthesia unit discharge. Opioids were standardized using oral morphine equivalents (OMEs). An instrumental variable (IV) analysis was conducted using the anesthesiologist as the instrument and interaction terms to estimate the joint effect of each potential two-medication combination.
Results:
8,836 procedures were included in the study (92.1% male, average 66.7 years of age), and 55.5% received MMA. MMA was more common in younger patients, females, and those with a lower comorbidity burden. Overall, 41.0% of patients received regional anesthesia, 39.1% received intravenous acetaminophen, 32.0% received more than 8 milligrams of dexamethasone, 28.1% received ketamine, and 10.3% received an NSAID. In IV analyses, NSAIDs resulted in the greatest significant reduction in postoperative opioid use [21.3 OMEs, 95% confidence interval (CI) 15.1, 27.5], followed by ketamine (5.1 OMEs, 95%CI 1.7, 8.6) and dexamethasone (4.6 OMEs, 95%CI 2.7, 6.6). After adjusting for other medications, intravenous acetaminophen was not associated with postoperative opioid use (p=0.52). Combinations of NSAIDs plus dexamethasone or regional anesthesia resulted in the greatest significant reductions in postoperative opioid use (mean reduction 29.5 OMEs, 95%CI 19.5, 36.9, and mean reduction 28.4 OMEs, 95%CI 16.8, 40.1, respectively).
Conclusion:
NSAIDs, dexamethasone, and ketamine resulted in the greatest reduction of 24-hour postoperative opioid use, not intraoperative intravenous acetaminophen. Our findings support the continued use of NSAIDs and dexamethasone in MMA protocols and highlight the need for future studies exploring the independent effect of intravenous acetaminophen on postoperative pain.