Authors: Wilson, Jenna M. et al.
Anesthesiology, July 14, 2025. DOI: 10.1097/ALN.0000000000005649
This prospective, randomized, double-blind trial examined whether intraoperative ketamine administration reduces postoperative pain after breast surgery and whether patient-specific pain sensitivity influences its effectiveness. Ketamine, an NMDA receptor antagonist, inhibits central sensitization—a key driver of persistent postoperative pain—but clinical results have been inconsistent, possibly due to individual variability in pain processing.
A total of 225 patients undergoing breast surgery were randomized to receive either intravenous ketamine or saline placebo. Before surgery, participants completed comprehensive pain and psychosocial assessments, and a subset underwent quantitative sensory testing to evaluate temporal summation of pain, a marker of central sensitization tendency. Postoperative pain severity and functional impact were assessed two weeks after surgery, and analyses adjusted for demographic and perioperative variables.
Overall, ketamine did not significantly reduce postoperative pain compared with placebo. Pain scores and pain interference outcomes were similar across treatment groups at the two-week follow-up. However, exploratory moderation analysis revealed that among patients with higher baseline temporal summation—indicating increased central sensitization—ketamine was associated with lower pain severity and less functional impact. This suggests that baseline pain processing profiles may determine which patients benefit from NMDA receptor–targeted interventions.
These findings indicate that ketamine’s analgesic effects are not universal but may be clinically relevant for a biologically defined subset of patients predisposed to heightened central pain amplification.
What You Should Know:
Intraoperative ketamine does not generally reduce postoperative pain after breast surgery but may offer meaningful benefit for patients showing high preoperative pain sensitivity and central sensitization. Future trials should incorporate mechanistic patient profiling to tailor perioperative analgesic strategies more precisely.
Thank you to Anesthesiology for publishing this insightful study advancing personalized approaches to perioperative pain management.