Efficacy and safety of N-methyl-d-aspartate receptor antagonists for preventing acute postoperative pain: A systematic review and network meta-analysis of randomized controlled trials
Authors' conclusion
Esketamine and high-dose dextromethorphan achieved clinically meaningful reductions in VAS pain scores at 24 h postoperatively.
Study context
- Population
- Surgical patients receiving N-methyl-d-aspartate (NMDA) receptor antagonists to prevent acute postoperative pain
- Participants
- 3,055 patients · 47 randomized controlled trials (RCTs)
- Comparison
- NMDA receptor antagonists for preventing acute postoperative pain
- Outcome
- Pain score
- Follow-up
- 24 h postoperatively
Methodological detailsBayesian network meta-analysis (GeMTC, BUGSnet), Certainty of evidence for most outcomes low to very low
- Bayesian network meta-analysis (GeMTC, BUGSnet)
- Certainty of evidence for most outcomes low to very low
Pooled result
As reported in the abstract
24-h postoperative pain score · 24 h
MD (95% CrI)
Esketamine
−1.39(−2.57 to −0.37)
High-dose dextromethorphan
−1.17(−1.81 to −0.53)
Medium-dose ketamine
−0.93(−1.74 to −0.08)
Further pooled results
24-h postoperative morphine consumption
| MD (95% CrI) | ||
|---|---|---|
| Medium-dose dextromethorphanOptimal | −10.50 (−19.66 to −1.45) | |
| −20−10010Difference (linear scale) |
Time to first postoperative analgesic request
| MD (95% CrI) | ||
|---|---|---|
| High-dose dextromethorphan | 206.41 (24.39–394.30) | |
| −2000200400Difference (linear scale) |
Rescue analgesic requirements
| OR (95% CrI) | ||
|---|---|---|
| Magnesium sulphate | 6.91 (1.64–24.97) | |
| 0.050.21520Odds ratio (log scale) |
- 24-h postoperative morphine consumption: 95% CrI
- Time to first postoperative analgesic request: 95% CrI
- Rescue analgesic requirements: only intervention that significantly reduced rescue analgesic requirements
- Rescue analgesic requirements: 95% CrI
Safety
Incidence of postoperative nausea and vomiting (PONV)
| OR (95% CrI) | ||
|---|---|---|
| Medium-dose dextromethorphanSignificantly reduced the incidence of PONV | 15.32 (1.48–334.61) | |
| Ketamine via PCEASignificantly reduced the incidence of PONV | 5.88 (1.31–30.88) | |
| 0.050.21520Odds ratio (log scale) |
- Incidence of PONV: 95% CrI
Original publication
Efficacy and safety of N-methyl-d-aspartate receptor antagonists for preventing acute postoperative pain: A systematic review and network meta-analysis of randomized controlled trials. J Clin Anesth. Published 11 May 2026. doi:10.
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