Ketamine/esketamine for preventing rebound pain after peripheral nerve block: a systematic review and meta-analysis of randomized controlled trials

Minerva Anestesiol. 2026 Mar 20. doi: 10.23736/S0375-9393.25.19528-X. Online ahead of print.

ABSTRACT

INTRODUCTION: Rebound pain after peripheral nerve block is a frequent problem that compromises recovery and patient satisfaction. Whether ketamine or esketamine can prevent this phenomenon remains uncertain.

EVIDENCE ACQUISITION: We performed a systematic review and meta-analysis of randomized controlled trials evaluating ketamine or esketamine, given intravenously or perineurally, compared with placebo or no intervention. The primary outcome was rebound pain; secondary outcomes included postoperative pain scores, opioid use, and adverse events.

EVIDENCE SYNTHESIS: Six trials including 884 patients were analyzed. Ketamine/esketamine reduced the incidence of rebound pain (RR 0.48; 95% CI, 0.38-0.60). Subgroup analyses showed consistent effects across intravenous and perineural routes, with stronger evidence for esketamine. Postoperative pain scores at 12, 24, and 48 hours were lower in the intervention group. No significant differences were found in opioid consumption or in adverse events such as nausea, dizziness, delirium, or nightmares.

CONCLUSIONS: Esketamine, administered intravenously or perineurally, appears to lower the risk of rebound pain and improve analgesia without increasing side effects. However, these conclusions are tempered by the limited number of studies and some clinical heterogeneity. Therefore, the current analysis serves more as a working hypothesis generating interest for future large, high-quality trials, which are needed to confirm these results and define optimal dosing strategies before clear clinical recommendations can be made.

PMID:41860056 | DOI:10.23736/S0375-9393.25.19528-X