Adding a Second Multimodal Analgesic: Effects on 24‑hr Opioid Use and Early Pain

A systematic review and meta-analysis of randomized trials in adults undergoing non-cardiac surgery evaluated whether adding a second multimodal analgesic component (a two-component regimen), compared with a single component, influenced acute postoperative outcomes. The authors reported pooled results for 24-hour postoperative opioid consumption (in oral morphine equivalents) and pain scores at 4 hours postoperatively. For key outcomes, the report presented pooled effect estimates alongside statistical heterogeneity (I²). The findings were framed as average effects with substantial between-trial variability rather than a single uniform effect across settings.

For opioid consumption, the systematic review and meta-analysis compared regimens that included standard care plus two multimodal components versus standard care plus one component. In the pooled analysis of 17 trials contributing 24 comparisons, adding a second component was associated with a mean reduction in 24-hour opioid consumption of 5.2 mg oral morphine equivalents (95% CI, −7.7 to −2.7; p<0.01). The authors reported very high statistical heterogeneity for this estimate (I²=99%). They concluded that adding a second multimodal analgesic component may modestly improve acute postoperative pain control and may reduce opioid consumption.

Early pain outcomes followed a similar pattern. Across 19 trials (29 comparisons), the authors reported a pooled reduction in pain scores at 4 hours postoperatively of −0.5 points on a numeric rating scale (95% CI, −0.8 to −0.2), with high heterogeneity (I²=94%). The authors noted that heterogeneity remained very high and that subgroup analyses did not identify a clearly superior added multimodal component when comparing different adjunct options. Overall, the pooled reporting was consistent with small average improvements in early pain measures alongside substantial between-study inconsistency in effect sizes.

Adverse-event reporting was summarized descriptively, with rates described as generally comparable between two-component and one-component regimens across included trials. Within that overall pattern, the review noted some reductions in postoperative nausea and vomiting in analyses where those events were reported. The authors also noted evidence gaps beyond the immediate postoperative window, with limited data on long-term outcomes and quality of recovery. The review’s scope centered on short-term opioid and early pain outcomes, with comparatively limited longer-term and detailed safety information in the pooled trial record as reported.

Key Takeaways:

• Adding a second multimodal analgesic component was associated with lower 24-hour postoperative opioid consumption and was described as modestly improving acute postoperative pain control.
• Early postoperative pain scores were reported as modestly lower on average, with high heterogeneity across trials.
• Subgroup analyses did not identify a single superior added component; adverse events were generally similar overall, with some reported reductions in postoperative nausea and vomiting, and longer-term outcomes were sparsely reported.