Ketamine in perioperative analgesia for knee surgeries: Review of evidence from randomized controlled trials

Dmitri Souzdalnitski MD, PhD , Glenn R. Rech RPh , Aleksandr Naydinskiy BSc , Daria Suzdalnitskaya , Roman V. Isakov , Maged Guirguis MD
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引用次数: 2

Abstract

Successful perioperative analgesia for knee surgeries results in improved patient satisfaction and promotes successful rehabilitation. However, effective perioperative pain control is commonly a challenging task for knee surgeries. Such surgical procedures as total knee replacement or knee arthroscopy may be accompanied by severe postoperative pain. As opioids and nonsteroidal anti-inflammatory drugs are commonly used, the side effects of these types of medicines are quite common as well, especially in patients with chronic pain, as they are commonly dissatisfied with regular analgesia. Patients with chronic pain tend to have lower tolerance to pain, and be dependent and tolerant to opioids. These patients typically require higher doses of analgesics, which further negatively affect patients’ safety and the overall perioperative experience. Multimodal perioperative analgesia helps to spare opioids and promote successful rehabilitation. Ketamine is a noncompetitive N-Methyl-d-aspartate (NMDA) receptor antagonist that has been used for multimodal perioperative analgesia as an adjunct to opioids and nonsteroidal anti-inflammatory drugs. Despite the significant number of papers evaluating the role of ketamine in perioperative analgesia, the feasibility of ketamine for perioperative pain control in knee surgeries remains a subject of debate. There are only a limited number of high-quality studies on the topic. We used a systematic approach to evaluate randomized controlled trials with perioperative ketamine used for knee surgeries. The majority of the studies confirmed that the utilization of ketamine in perioperative analgesia was associated with lower pain scores, reduced opioid use, improved knee joint mobility, and an increase in patient tolerance for physical therapy and rehabilitation. The techniques for ketamine administration and dosing varied significantly, which may explain the inconsistencies between the reports. In addition, some of the studies, even those of high quality, used nitrous oxide in both the study and control groups. Nitrous oxide has NMDA receptor antagonist properties, as does ketamine. None of the studies reported whether patients were taking methadone, dextromethorphan, memantine, or magnesium sulfate, which are NMDA receptor antagonists too. The concomitant use of NMDA receptor antagonists, other than ketamine, may have interfered with the realization of analgesic effects of ketamine. Although it is largely accepted that NMDA receptor antagonism at the spinal level explains most of the analgesic effects of ketamine, it also interacts at other multiple receptors centrally, including, cholinergic receptors, nicotinic and muscarinic, adrenergic, central NMDA, and non-NMDA glutamate receptors. These influences may potentially explain why patients treated with other NMDA receptor antagonists had improved with ketamine as well. Ketamine also interacts with opioid receptors at supraspinal sites, where it produces supraspinal antinociception. Some of the studies did not report whether the participants were opioid naïve or opioid dependent. That might be an important determinant of the analgesic effect because opioid dependent patients are shown to benefit from the ketamine significantly. None of the examined randomized controlled trials assessed the effects of ketamine on opioid dependent patients. The variability between the outcomes of ketamine utilization for perioperative analgesia for knee surgeries might be, at least partially, explained by these findings.

氯胺酮在膝关节手术围手术期镇痛中的应用:随机对照试验证据综述
成功的围手术期镇痛可提高患者满意度并促进成功的康复。然而,有效的围手术期疼痛控制通常是膝关节手术的一个具有挑战性的任务。诸如全膝关节置换术或膝关节镜检查等外科手术可能伴有严重的术后疼痛。由于阿片类药物和非甾体类抗炎药是常用的,这类药物的副作用也很常见,特别是对于慢性疼痛患者,因为他们通常不满意常规镇痛。慢性疼痛患者往往对疼痛的耐受性较低,对阿片类药物有依赖性和耐受性。这些患者通常需要更高剂量的镇痛药,这进一步对患者的安全性和整体围手术期体验产生负面影响。多模式围手术期镇痛有助于节省阿片类药物,促进成功康复。氯胺酮是一种非竞争性n -甲基-d-天冬氨酸(NMDA)受体拮抗剂,作为阿片类药物和非甾体抗炎药的辅助药物,已被用于多模式围手术期镇痛。尽管有大量的论文评价氯胺酮在围手术期镇痛中的作用,但氯胺酮在膝关节手术围手术期疼痛控制中的可行性仍然是一个有争议的话题。关于这一主题的高质量研究数量有限。我们采用了一种系统的方法来评估围手术期氯胺酮用于膝关节手术的随机对照试验。大多数研究证实,氯胺酮在围手术期镇痛中的使用与较低的疼痛评分、减少阿片类药物的使用、改善膝关节活动能力以及增加患者对物理治疗和康复的耐受性有关。氯胺酮的施用技术和剂量差异很大,这可能解释了报告之间的不一致。此外,一些研究,甚至是高质量的研究,在研究组和对照组中都使用了一氧化二氮。氧化亚氮和氯胺酮一样具有NMDA受体拮抗剂的特性。没有研究报告患者是否服用美沙酮、右美沙芬、美金刚或硫酸镁,这些也是NMDA受体拮抗剂。同时使用NMDA受体拮抗剂,而不是氯胺酮,可能会干扰氯胺酮镇痛作用的实现。虽然人们普遍认为氯胺酮在脊髓水平上的NMDA受体拮抗作用解释了氯胺酮的大部分镇痛作用,但它也与其他多个中枢受体相互作用,包括胆碱能受体、烟碱和毒蕈碱受体、肾上腺素能受体、中枢NMDA受体和非NMDA谷氨酸受体。这些影响可能潜在地解释了为什么使用其他NMDA受体拮抗剂治疗的患者使用氯胺酮也有改善。氯胺酮也与椎骨上的阿片受体相互作用,产生椎骨上抗感觉。一些研究没有报告参与者是否阿片类药物naïve或阿片类药物依赖。这可能是镇痛效果的一个重要决定因素,因为阿片类药物依赖患者从氯胺酮中明显受益。没有一项随机对照试验评估氯胺酮对阿片类药物依赖患者的影响。氯胺酮应用于膝关节手术围手术期镇痛的结果差异,至少部分可以用这些发现来解释。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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