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Current evidence of multimodal anesthesia on postoperative outcomes: A systematic review and Meta-analysis
Stefano M Arigoni1, Adina B Heitmann-Frei1, Marc S von Gernler2
1Department of Anaesthesiology and Pain Medicine, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland.
Background:
Multimodal anesthesia (MMA) is widely used to reduce opioid use and improve postoperative recovery. However, evidence for bundled MMA regimens-defined as opioids plus ≥2 adjunct analgesic modalities-has not been systematically synthesized across patient-centered outcomes.
Methods:
We performed a systematic review and meta-analysis of randomized controlled trials comparing MMA (opioids plus ≥2 adjuncts, including regional techniques and/or systemic agents such as dexmedetomidine, ketamine, intravenous lidocaine, clonidine, or magnesium) with opioid-based general anesthesia in adults undergoing elective surgery. MEDLINE, Embase, CINAHL, Web of Science, and the Cochrane Library were searched to 28 October 2025. Primary outcomes were postoperative pain, PONV, QoR-15, and pulmonary complications. Secondary outcomes included opioid consumption in Morphine Milligram Equivalent (MME) and PACU length of stay. Risk of bias was assessed with RoB 2 and certainty with GRADE. Registered in PROSPERO (CRD42024470056).
Results:
Twenty-one RCTs (n = 1828) were included. At 24 h, no clear effect of MMA on pain intensity was observed (10 trials, n = 785; MD -0.6, 95% CI -1.5 to 0.2; very low certainty). MMA reduced PONV incidence (4 trials, n = 352; RR 0.59, 95% CI 0.44 to 0.77; low certainty). For secondary outcomes, MMA reduced opioid consumption (10 trials, n = 915; MD -7.0 mg MME, 95% CI -12.8 to -1.3; moderate certainty), with the opioid-sparing effect persisting at 48 h (MD -14.0 mg MME) and study end (MD -16.0 mg). Data for QoR-15, PACU stay, and pulmonary complications were insufficient for pooling.
Conclusions:
MMA shows no clear effect on postoperative pain at 24 h but reduces PONV incidence and opioid consumption. Evidence certainty ranges from moderate to very low. Larger, standardized trials are needed to define optimal MMA regimens and patient selection.
Insights
Multimodal anesthesia (MMA) reduces postoperative nausea and vomiting (PONV) and opioid consumption but shows no clear effect on pain at 24 hours. Further research is needed for optimal MMA regimens.
Area of Science:
- Anesthesiology
- Surgical Recovery
- Pain Management
Background:
- Multimodal anesthesia (MMA) is utilized to decrease opioid requirements and enhance postoperative recovery.
- Bundled MMA regimens, defined as opioids plus two or more adjunct analgesic modalities, lack systematic synthesis for patient-centered outcomes.
Purpose of the Study:
- To systematically review and meta-analyze randomized controlled trials (RCTs) evaluating bundled multimodal anesthesia regimens versus traditional opioid-based anesthesia.
- To assess the impact of MMA on patient-centered outcomes including postoperative pain, nausea/vomiting, quality of recovery, and opioid consumption.
Main Methods:
- A systematic review and meta-analysis of 21 RCTs (n=1828) comparing MMA (opioids + ≥2 adjuncts) with opioid-based general anesthesia.
- Primary outcomes included postoperative pain, PONV, QoR-15, and pulmonary complications. Secondary outcomes were opioid consumption (MME) and PACU length of stay.
- Searches conducted across major databases (MEDLINE, Embase, etc.) up to October 2025; risk of bias and certainty of evidence assessed using RoB 2 and GRADE.
Main Results:
- MMA demonstrated a reduction in postoperative nausea and vomiting (PONV) incidence (RR 0.59, low certainty).
- A significant reduction in opioid consumption was observed with MMA (MD -7.0 mg MME at 24h, moderate certainty), with sustained effects.
- No clear effect of MMA on pain intensity at 24 hours was found (MD -0.6, very low certainty). Data for QoR-15, PACU stay, and pulmonary complications were insufficient for pooling.
Conclusions:
- Multimodal anesthesia (MMA) effectively reduces PONV incidence and opioid consumption but does not significantly impact postoperative pain at 24 hours.
- The certainty of evidence ranges from moderate to very low across outcomes.
- Larger, standardized trials are recommended to optimize MMA protocols and patient selection for improved surgical recovery.
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