Nielsen Rikke Vibeke, Fomsgaard Jonna Storm, Siegel Hanna, Martusevicius Robertas, Nikolajsen Lone, Dahl Jørgen Berg, Mathiesen Ole
Department of Neuroanesthesiology, Rigshospitalet-Glostrup, Copenhagen University Hospital, Glostrup, Denmark.
Department of Anesthesiology, Nykoebing Falster Hospital, Nykoebing Falster, Denmark, Copenhagen University Hospital.
Pain. 2017 Mar;158(3):463-470. doi: 10.1097/j.pain.0000000000000782.
Perioperative handling of surgical patients with opioid dependency represents an important clinical problem. Animal studies suggest that ketamine attenuates central sensitization and hyperalgesia and thereby reduces postoperative opioid tolerance. We hypothesized that intraoperative ketamine would reduce immediate postoperative opioid consumption compared with placebo in chronic pain patients with opioid dependency undergoing lumbar spinal fusion surgery. Primary outcome was morphine consumption 0 to 24 hours postoperatively. Secondary outcomes were acute pain at rest and during mobilization 2 to 24 hours postoperatively (visual analogue scale), adverse events, and persistent pain 6 months postoperatively. One hundred fifty patients were randomly assigned to intraoperative S-ketamine bolus 0.5 mg/kg and infusion 0.25 mg·kg·h or placebo. Postoperatively, patients received their usual opioids, paracetamol and IV patient-controlled analgesia with morphine. In the final analyses, 147 patients were included. Patient-controlled analgesia IV morphine consumption 0 to 24 hours postoperatively was significantly reduced in the ketamine group compared with the placebo group: 79 (47) vs 121 (53) mg IV, mean difference 42 mg (95% confidence interval -59 to -25), P < 0.001. Sedation was significantly reduced in the ketamine group 6 and 24 hours postoperatively. There were no significant differences regarding acute pain, nausea, vomiting, hallucinations, or nightmares. Back pain at 6 months postoperatively compared with preoperative pain was significantly more improved in the ketamine group compared with the placebo group, P = 0.005. In conclusion, intraoperative ketamine significantly reduced morphine consumption 0 to 24 hours after lumbar fusion surgery in opioid-dependent patients. The trend regarding less persistent pain 6 months postoperatively needs further investigation.
对有阿片类药物依赖的外科手术患者进行围手术期处理是一个重要的临床问题。动物研究表明,氯胺酮可减轻中枢敏化和痛觉过敏,从而降低术后阿片类药物耐受性。我们假设,对于接受腰椎融合手术的有阿片类药物依赖的慢性疼痛患者,术中使用氯胺酮与使用安慰剂相比,将减少术后即刻阿片类药物的用量。主要结局指标是术后0至24小时吗啡用量。次要结局指标包括术后2至24小时静息和活动时的急性疼痛(视觉模拟评分)、不良事件以及术后6个月的持续性疼痛。150例患者被随机分配至术中静脉注射S-氯胺酮负荷剂量0.5 mg/kg并持续输注0.25 mg·kg·h或安慰剂组。术后,患者接受其常用的阿片类药物、对乙酰氨基酚以及静脉自控吗啡镇痛。在最终分析中,纳入了147例患者。与安慰剂组相比,氯胺酮组术后0至24小时静脉自控吗啡用量显著减少:分别为79(47)mg和121(53)mg静脉用量,平均差值42 mg(95%置信区间-59至-25),P<0.001。氯胺酮组术后6小时和24小时镇静作用显著减轻。在急性疼痛、恶心、呕吐、幻觉或噩梦方面无显著差异。与术前疼痛相比,氯胺酮组术后6个月背痛的改善程度显著优于安慰剂组,P = 0.005。总之,术中氯胺酮显著减少了阿片类药物依赖患者腰椎融合术后0至24小时的吗啡用量。术后6个月持续性疼痛较轻的趋势需要进一步研究。