Optimal multimodal analgesia combinations to reduce pain and opioid use following non-cardiac surgery: an instrumental variable analysis.

Graham LA, Illarmo S, Wren SM, Mudumbai SC, Odden MC. Optimal multimodal analgesia combinations to reduce pain and opioid use following non-cardiac surgery: an instrumental variable analysis. Regional Anesthesia and Pain Medicine. 2025 Jul 17 DOI: 10.1136/rapm-2025-106720.

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Abstract:

BACKGROUND: Multimodal analgesia (MMA) is a perioperative pain management strategy that targets various pain pathways, resulting in reduced postoperative pain and opioid use. Unfortunately, the optimal combinations of pain medications to use with perioperative MMA remain uncertain. Our goal was to estimate the treatment effect of MMA on postoperative pain and opioid use and identify optimal non-opioid medication combinations to enhance MMA benefits. METHODS: The study population includes all patients undergoing elective non-cardiac surgery with general anesthesia between 1 January 2017 and 31 December 2022 at six geographically similar Veterans Health Administration hospitals. An instrumental variable (IV) analysis was conducted using the anesthesiologist as the instrument to emulate randomization to receiving specific pain medication combinations. Outcomes were self-reported pain and opioid use after surgery. RESULTS: Of the 23 238 procedures included in the study, 46.1% received MMA. MMA was more common in younger patients, females and those with a lower probability of mortality. With IV analysis, inpatients with MMA required 6.8 fewer oral morphine equivalents (OMEs, 95% CI -10.2, to -3.4) in the postoperative period, and outpatients with MMA reported postoperative pain scores that were, on average, 1.0 unit lower than patients who did not receive MMA (95% CI -1.6 to -0.4). Combinations of non-steroidal anti-inflammatory drugs (NSAIDs) plus dexamethasone or regional anesthesia resulted in the greatest reductions in postoperative opioid use (mean reduction -29.5 OMEs, 95% CI -36.9 to -19.5 and mean reduction -28.4 OMEs, 95% CI -40.1 to -16.8, respectively). CONCLUSION: Our findings further support existing evidence on the effectiveness of MMA in reducing postoperative pain and opioid use following non-cardiac surgery. Importantly, our study highlights that dexamethasone and NSAIDs, not acetaminophen, which is almost universally used in MMA regimens, resulted in the greatest reduction of postoperative pain and postoperative opioid use. This has significant implications for the continued use of NSAIDs and dexamethasone in MMA protocols and underscores the need for future studies exploring the independent effect of intravenous acetaminophen on postoperative pain.