Impact of perioperative ketamine on enhanced recovery after abdominal surgery

Citation:

Raymond BL, Allen BFS, Freundlich RE, McEvoy MD, Parrish CG, Ruble SR, et al. IMpact of PerioperAtive KeTamine on Enhanced Recovery After abdominal Surgery (IMPAKT ERAS): a pragmatic randomised single-cluster trial. Br J Anaesth. 2025;135(6):1770–1778. doi:10.1016/j.bja.2025.08.001.

Study at a glance

- Design and setting: Pragmatic, double-blind, placebo-controlled single-centre cluster RCT by week (Vanderbilt, USA) in adults ≥18 yr undergoing elective major abdominal ERAS surgery (colorectal, surgical oncology, complex ventral hernia; N=1,522 analysed ITT).

- Interventions: Ketamine arm received 0.5 mg kg−1 i.v. bolus at induction, then 5 μg kg−1 min−1 intraoperatively and 2.5 μg kg−1 min−1 for 48 h postoperatively; placebo arm received volume- and rate-matched saline. Both arms followed an intensive multimodal ERAS analgesic pathway (regional block, lidocaine, NSAIDs, gabapentin, opioids as needed).

- Primary outcome (hospital length of stay): Median LOS 5 days in both arms (ketamine IQR 4–8; placebo 3–7). Cluster- and covariate-adjusted OR for longer stay with ketamine 1.21 (95% CI 1.00–1.47) – no reduction in LOS, possible small increase; moderate-certainty evidence.

- Key secondary (opioids and recovery): Total in-hospital opioid use was similar (median 82.5 vs 90 MME; adjusted OR 0.85, 95% CI 0.71–1.01). Fewer patients on ketamine met early discharge milestones by 48 h (12.5% vs 17.3%; adjusted OR 0.68, 95% CI 0.50–0.93), suggesting no functional recovery benefit.

- Safety: Ketamine increased adverse effects and early infusion discontinuation (any early stop for side-effects 32.3% vs 13.3%; OR ≈2). Debilitating hallucinations (2.7% vs 0.9%; OR 2.69) and debilitating dizziness (8.3% vs 1.5%; adjusted OR 6.05) were more frequent; ICU transfer was also higher with ketamine (5.7% vs 2.9%; adjusted OR 2.03, 95% CI 1.14–3.63). Thirty-day readmissions were similar.

- Certainty and take-home: Well-conducted, double-blind cluster RCT with objective EHR outcomes and low attrition; overall RoB 2 judgement “some concerns” (selective reporting of some exploratory outcomes) but generally robust. Moderate-certainty evidence that adding a 48 h ketamine infusion to high-intensity ERAS multimodal analgesia does not improve LOS or opioid use and increases neuropsychiatric and other adverse effects.