Centre for Evidence-Based Medicine, Nuffield Department of Primary Care Health Sciences, University of Oxford, Oxford, UK; Southern New Hampshire Medical Center, Nashua, NH, USA.
Dartmouth-Hitchcock Medical Center, Lebanon, NH, USA.
Br J Anaesth. 2019 Sep;123(3):325-334. doi: 10.1016/j.bja.2019.05.043. Epub 2019 Jul 18.
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.
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.
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.
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.
氯胺酮是一种苯环己哌啶静脉麻醉剂，可阻断中枢神经系统中的 N-甲基-D-天冬氨酸受体和 HCN 通道。最近，它以低剂量形式被接受，并在骨科手术中显示出镇痛益处。我们的目标是批判性地评估和综合目前关于在主要疼痛性骨科手术中使用低剂量氯胺酮的证据。
我们在 Medline、Embase、Cochrane 和专业期刊中进行了随机对照试验（RCT）的搜索，比较了低剂量氯胺酮与安慰剂。主要结局包括总阿片类药物用量、首次使用阿片类药物的时间和 VAS 疼痛评分。使用 RevMan 软件进行了荟萃分析，采用随机效应模型。我们使用 GRADE 工作组标准来评估证据质量。
我们纳入了 20 项研究，分为四个亚组进行荟萃分析。总体证据质量为中等。氯胺酮显著降低了 24 小时和 48 小时时的总阿片类药物用量和疼痛评分（VAS）（阿片类药物：标准化均数差 [SMD] -0.82 [-1.24，-0.40]，p=0.0001 和 -0.65 [-1.03，-0.27]，p=0.0008；VAS：SMD -0.53 [-0.91，-0.15]，p=0.006 和 -0.60 [-1.05，-0.16]，p=0.008），并延迟了首次使用阿片类药物的时间（SMD 0.64 [0.01，1.27]，p=0.05）。恶心和幻觉的结果不确定，而慢性疼痛的结果不确定。在全关节手术中观察到最显著的效果。
低剂量氯胺酮是一种有效的辅助药物，可减轻疼痛和阿片类药物需求在疼痛性骨科手术中，尤其是在手术后的前 24 小时内。未来的研究应集中在关节镜手术和慢性疼痛的发生率上。
