Perioperative Ketamine and Esketamine for Postoperative Mood Symptoms After Orthopaedic Surgery: A Systematic Review of Randomized Controlled Trials.

OBJECTIVES: Perioperative anxiety and depression are common following major orthopaedic surgery and may adversely affect postoperative recovery. Ketamine and esketamine have rapid psychotropic effects; however, their effectiveness in reducing postoperative mood symptoms in orthopaedic patients remains uncertain. We systematically reviewed randomized evidence on the effects of these agents on postoperative anxiety, depression, and adverse events. METHODS: PubMed, Embase, and the Cochrane Library were searched for randomized controlled trials enrolling adults undergoing major orthopaedic procedures. Eligible studies compared ketamine or esketamine administered preoperatively, intraoperatively, or postoperatively with placebo or no ketamine-class agent. The primary outcomes were postoperative anxiety and depression assessed using validated scales. Secondary outcomes included drug-related adverse events. RESULTS: Nine randomized controlled trials were included, with follow-up durations ranging from 24 hours to 12 months. Five trials assessed postoperative anxiety using validated scales; four reported significantly lower anxiety scores with ketamine or esketamine at early postoperative time points, whereas one trial using a single preoperative dose of ketamine found no significant anxiolytic effect. Overall, perioperative ketamine or esketamine may be associated with lower early postoperative anxiety and depressive symptom scores in selected orthopaedic populations. Regarding safety, ketamine or esketamine did not appear to increase the incidence of common adverse events. CONCLUSION: Perioperative ketamine or esketamine appears to reduce early postoperative anxiety and depressive symptoms in orthopaedic patients without increasing postoperative nausea, vomiting, or dizziness. Further standardized trials are needed before firm conclusions can be drawn. LEVEL OF EVIDENCE: II.