Non-Opioid Analgesics in Adults After Major Surgery : A Comprehensive Systematic Review

Abstract

Background: Postoperative pain management remains heavily reliant on opioids, despite risks of addiction, respiratory depression, and ileus. Non-opioid analgesics offer potential alternatives, but their comparative efficacy across major surgeries is unclear. Methods: This comprehensive systematic review synthesized data from 80 randomized controlled trials, etc evaluating non-opioid analgesics in adults after major surgery. Interventions included NSAIDs, acetaminophen, IV lidocaine, dexamethasone, gabapentinoids, nefopam, regional techniques (epidural, TAP, QLB, paravertebral, EOIP blocks), multimodal protocols, and suzetrigine. Outcomes included pain intensity (VAS/NRS), opioid consumption (morphine equivalents), adverse effects, and recovery metrics. Results: NSAIDs (IV/IM) consistently reduced pain and opioid use across cesarean, orthopedic, and abdominal surgeries (p<0.001), with etoricoxib reducing morphine by 31-34% (p<0.001) and IV ibuprofen reducing 24h morphine from 39.1mg to 29.8mg (p<0.001). Acetaminophen IV outperformed oral in spine surgery (66% lower morphine equivalents, p=0.001). IV lidocaine significantly accelerated gastrointestinal recovery (flatus reduced by ~6h, bowel movement by ~8h) and reduced opioid consumption by 35% (p<0.001). Dexamethasone reduced pain and opioids (MD -6.66mg morphine equivalents, p<0.001) and enhanced TAP block duration (PONV RR 0.40). Regional techniques: quadratus lumborum block reduced 24h morphine by ~24mg (p<0.01); erector spinae plane block achieved MCID for pain; paravertebral block matched epidural analgesia with fewer adverse events (p=0.02). Multimodal triple therapy (paracetamol+NSAID+adjunct) reduced morphine by 26mg vs. single agents (p<0.001). Opioid-free anesthesia reduced PONV by 40% (RR 0.60) with comparable pain control. Suzetrigine (NaV1.8 inhibitor) showed efficacy equivalent to opioid combinations but without opioid-related AEs (nausea RR 0.72). Discussion: Non-opioid analgesics provide significant, clinically meaningful reductions in pain and opioid consumption when used as multimodal combinations. Regional techniques are superior for acute nociceptive pain but require systemic NSAIDs for visceral components. IV lidocaine’s primary benefit is gastrointestinal recovery, not late pain relief. Dexamethasone offers dual antiemetic-analgesic benefits. Triple therapy is superior to double or single agents. Conclusion: Multimodal non-opioid analgesia is highly effective and opioid-sparing after major surgery. Routine adoption of NSAIDs, acetaminophen, dexamethasone, and targeted regional blocks within enhanced recovery protocols is strongly recommended. Cardiac surgery requires further NSAID safety trials. Suzetrigine is a promising novel agent for acute pain.