Perioperative Ketamine and Esketamine for Enhanced Recovery After Surgery (ERAS): A Systematic Review

Enhanced recovery after surgery (ERAS) protocol optimizes perioperative care and accelerates recovery. Ketamine and esketamine are increasingly incorporated into ERAS strategies.

This systematic review critically examines the evidence of perioperative ketamine and esketamine use within ERAS, focusing on postoperative pain, opioid consumption, nausea and vomiting, cognitive function, depression, and sleep quality.

Randomized controlled trials, meta-analyses, systematic reviews, and relevant clinical guidelines were identified. Evidence for each outcome was graded using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) framework.

Perioperative ketamine or esketamine consistently reduces postoperative pain and opioid consumption, particularly within the first 24-48 h after surgery. Both agents were associated with reductions in early postoperative depressive symptoms, especially among patients with preexisting depression. Evidence regarding postoperative neurocognitive disorders, including delirium and cognitive dysfunction, remains insufficient. Moderate-certainty evidence supports esketamine-associated improvements in postoperative nausea and vomiting and early postoperative sleep quality, particularly within 72 h after surgery.

Perioperative ketamine and esketamine are valuable adjuncts to ERAS multimodal analgesia, with evidence also supporting their effects on depressive and sleep disorders. However, evidence is limited by high heterogeneity, small sample sizes, underpower, inconsistent or non-standardized outcome assessment tools, and short follow-up durations. Optimal dosing strategies remain undetermined.