Murphy Glenn S, Avram Michael J, Greenberg Steven B, Benson Jessica, Bilimoria Sara, Maher Colleen E, Teister Kevin, Szokol Joseph W
Anesthesiology. 2021 May 1;134(5):697-708. doi: 10.1097/ALN.0000000000003743.
Despite application of multimodal pain management strategies, patients undergoing spinal fusion surgery frequently report severe postoperative pain. Methadone and ketamine, which are N-methyl-d-aspartate receptor antagonists, have been documented to facilitate postoperative pain control. This study therefore tested the primary hypothesis that patients recovering from spinal fusion surgery who are given ketamine and methadone use less hydromorphone on the first postoperative day than those give methadone alone.
In this randomized, double-blind, placebo-controlled trial, 130 spinal surgery patients were randomized to receive either methadone at 0.2 mg/kg (ideal body weight) intraoperatively and a 5% dextrose in water infusion for 48 h postoperatively (methadone group) or 0.2 mg/kg methadone intraoperatively and a ketamine infusion (0.3 mg · kg-1 · h-1 infusion [no bolus] intraoperatively and then 0.1 mg · kg-1 · h-1 for next 48 h [both medications dosed at ideal body weight]; methadone/ketamine group). Anesthetic care was standardized in all patients. Intravenous hydromorphone use on postoperative day 1 was the primary outcome. Pain scores, intravenous and oral opioid requirements, and patient satisfaction with pain management were assessed for the first 3 postoperative days.
Median (interquartile range) intravenous hydromorphone requirements were lower in the methadone/ketamine group on postoperative day 1 (2.0 [1.0 to 3.0] vs. 4.6 [3.2 to 6.6] mg in the methadone group, median difference [95% CI] 2.5 [1.8 to 3.3] mg; P < 0.0001) and postoperative day 2. In addition, fewer oral opioid tablets were needed in the methadone/ketamine group on postoperative day 1 (2 [0 to 3] vs. 4 [0 to 8] in the methadone group; P = 0.001) and postoperative day 3. Pain scores at rest, with coughing, and with movement were lower in the methadone/ketamine group at 23 of the 24 assessment times. Patient-reported satisfaction scores were high in both study groups.
Postoperative analgesia was enhanced by the combination of methadone and ketamine, which act on both N-methyl-d-aspartate and μ-opioid receptors. The combination could be considered in patients having spine surgery.
尽管应用了多模式疼痛管理策略，但接受脊柱融合手术的患者术后仍经常报告严重疼痛。美沙酮和氯胺酮作为N-甲基-D-天冬氨酸受体拮抗剂，已被证明有助于术后疼痛控制。因此，本研究检验了主要假设：脊柱融合手术后恢复的患者，给予氯胺酮和美沙酮者在术后第一天使用的氢吗啡酮比仅给予美沙酮者少。
在这项随机、双盲、安慰剂对照试验中，130例脊柱手术患者被随机分为两组，一组术中接受0.2mg/kg（理想体重）的美沙酮，术后48小时接受5%葡萄糖水溶液输注（美沙酮组）；另一组术中接受0.2mg/kg美沙酮，并输注氯胺酮（术中0.3mg·kg-1·h-1输注[无负荷剂量]，随后48小时为0.1mg·kg-1·h-1[两种药物均按理想体重给药]；美沙酮/氯胺酮组）。所有患者的麻醉护理均标准化。术后第1天静脉使用氢吗啡酮是主要观察指标。在术后前3天评估疼痛评分、静脉和口服阿片类药物需求量以及患者对疼痛管理的满意度。
美沙酮/氯胺酮组术后第1天静脉注射氢吗啡酮的中位数（四分位间距）较低（美沙酮组为2.0[1.0至3.0]mg，而美沙酮组为4.6[3.2至6.6]mg，中位数差异[95%CI]为2.5[1.8至3.3]mg；P<0.0001），术后第2天也是如此。此外，美沙酮/氯胺酮组术后第1天（美沙酮组为2[0至3]片，而美沙酮组为4[0至8]片；P=0.001）和术后第3天所需的口服阿片类药片较少。在24次评估中的23次，美沙酮/氯胺酮组静息、咳嗽和活动时的疼痛评分较低。两个研究组患者报告的满意度评分都很高。
美沙酮和氯胺酮联合使用可增强术后镇痛效果，二者作用于N-甲基-D-天冬氨酸和μ阿片受体。脊柱手术患者可考虑使用该联合用药方案。
