What question did this study set out to answer?

This review aims to evaluate the efficacy and safety of ketamine and its enantiomer, esketamine, in patients undergoing total hip arthroplasty.

June 4, 2026Open Access

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

Key Points

This review aims to evaluate the efficacy and safety of ketamine and its enantiomer, esketamine, in patients undergoing total hip arthroplasty.
Conducted a systematic search across PubMed, Cochrane Library, EMBASE, and Web of Science up to February 2026.
Included studies involved THA patients using ketamine or esketamine, reporting on outcomes related to pain, opioid use, and adverse events.
Quality assessed using the Cochrane Risk of Bias 2 tool for RCTs and the Newcastle–Ottawa Scale for cohort studies.
Thirteen studies were reviewed, including 10 RCTs and 3 cohort studies with a total of 693,978 patients.
Some studies reported reduced postoperative pain scores and opioid consumption but varied in findings, indicating no universal effects.
Conflicting results on postoperative delirium; some studies showed benefit while others indicated increased risk, especially in vulnerable populations.

Abstract

Abstract Background 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. Methods 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. Results 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. Conclusions 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.

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