Low-dose ketamine in painfull orthopaedic surgery: a systematic review and meta-analysis

Background: Ketamine is a phencyclidine intravenous anaesthetic that blocks N-methyl-D-aspartate receptors and HCN channels in the CNS. Lately it has gained acceptance in a low-dose form, with studies showing an analgesic benefit in orthopaedic surgery. Our goal was to critically appraise and synthesise current evidence regarding use of low-dose ketamine in major, painful orthopaedic surgeries. Methods: We conducted searches in Medline, Embase, Cochrane, and specialty journals for randomised controlled trials (RCTs) that compared low-dose ketamine to placebo. Primary outcomes included total opioid use, time to first opioid, and VAS pain scores. Meta-analyses were undertaken in RevMan software using a random effects model. We rated the quality of the evidence using the GRADE Working Group criteria. Results: We included 20 studies across four subgroups for meta-analysis. The overall quality of the evidence was moderate. Ketamine significantly decreased total opioid use and pain scores (VAS) at 24 and 48 h (Opioid: standardised mean difference [SMD] -0.82 [-1.24, -0.40], p=0.0001, and -0.65 [-1.03,-0.27], p=0.0008; VAS: SMD -0.53 [-0.91, -0.15], p=0.006 and -0.60 [-1.05, -0.16], p=0.008), and delayed the time to first opioid dose (SMD 0.64 [0.01, 1.27], p=0.05). Results for nausea and hallucinations were equivocal, whereas results for chronic pain were inconclusive. The most prominent effects were seen in total joint operations. Conclusion: Low-dose ketamine is an effective adjuvant that decreases pain and opioid requirements in painful orthopaedic procedures, especially in the first 24 h after procedure. Future research should focus on arthroscopic procedures and the incidence of chronic pain.