Efficacy and safety of ketamine in total hip arthroplasty: a systematic review.

Abstract

Total hip arthroplasty (THA) is a common procedure for end-stage hip disorders, yet optimal perioperative pain management remains challenging. Ketamine and its S-enantiomer, esketamine, have been proposed as adjuncts in multimodal analgesia due to their opioid-sparing effects and unique mechanisms. However, existing evidence on their efficacy and safety in THA patients is conflicting and has not been systematically reviewed. A systematic search of PubMed, Cochrane Library, EMBASE, and Web of Science was conducted from inception to February 2026. Studies were included if they involved THA patients receiving perioperative ketamine or esketamine and reported outcomes related to pain, opioid use, delirium, functional recovery, or adverse events. Quality was assessed using the Cochrane Risk of Bias 2 (RoB 2) tool for randomized controlled trials and the Newcastle-Ottawa Scale (NOS) for cohort studies. Thirteen studies (10 RCTs, 3 cohort studies) encompassing 693,978 patients were included. Although several studies reported reductions in postoperative pain scores and opioid consumption, as well as improvements in early functional recovery and emotional status, these findings were not universal, and heterogeneity across study protocols precludes definitive conclusions. Findings on postoperative delirium were conflicting: one large RCT reported a significant reduction, while a retrospective study suggested increased risk with ketamine use. No serious adverse events were reported; however, psychotomimetic effects such as hallucinations and nightmares were more common in some ketamine groups compared to controls. Perioperative ketamine may offer benefits in analgesia, opioid sparing, and functional recovery after THA, but its effects on delirium are inconsistent and may depend on dosing and patient characteristics. Individualized administration and cautious use in high-risk elderly patients may be considered, though further research is needed to clarify optimal protocols.