S-氯胺酮能减轻术后疼痛吗？

术中静脉注射S-氯胺酮对腰椎融合术后非阿片类药物治疗患者的镇痛作用是暂时的，非剂量依赖的：一项随机、双盲、安慰剂对照临床试验

&&&& 背 景 &&&&

脊柱手术往往伴有严重的疼痛。阿片类药物是术后疼痛管理的基石，但其诸多副作用限制了其临床应用。一些研究表明静脉注射氯胺酮辅助治疗可以减少背部手术后的阿片类药物用量和疼痛。然而，氯胺酮在这一适应症中的确切作用尚待阐明。我们比较了2种不同剂量的S-氯胺酮和安慰剂对成人、非阿片类药物治疗的腰椎融合术后患者术后镇痛药用量、疼痛和不良事件的影响。

&&&& 方 法 &&&&

198例接受腰椎融合术的无阿片患者被纳入这项双盲试验，并随机分为3个研究组：C组（安慰剂）切皮前静脉注射生理盐水（0.9%氯化钠[NaCl]）负荷量，随后持续静脉输注0.9%NaCl。K2组和K10组切皮前静脉注射S-氯胺酮（0.5mg/kg），K2组随后术中持续静脉输注S-氯胺酮（0.12mg/kg/h），K10组随后术中持续静脉输注S-氯胺酮（0.6mg/kg/h）。

麻醉方案：术前口服10mg安定，常规监测心电图、有创动脉压、脉搏氧饱和度，胃长宁（0.2mg)、异丙酚(2-3mg/kg）、芬太尼(1.5-5μg/kg)和罗库溴铵（0.6-1mg/kg），随后行全凭静脉麻醉(异丙酚6-15mg/kg/h和瑞芬太尼0.05-2μg/kg/min输注)。在手术结束时，患者接受静脉输注对乙酰氨基酚(10mg/mL，100mL)和芬太尼(50μg)。

术后镇痛是通过静脉病人自控镇痛（IV-PCA）装置输注羟考酮来实现。负荷量0.05mg/kg，锁定时间为10min，最大次数5/h。

主要终点是术后48小时累积羟考酮消耗量。

次要终点包括术后2年内的术后疼痛，时间点为PACU 中的1、2和3小时，病房中的 4、6、8、18、24、32、42和48小时，术后3个月和24个月；不良事件（术后恶心呕吐、中枢神经系统副作用）以及术后即刻的镇静和意识障碍程度，时间点为入PACU即刻、拔管后2小时，评估量表为MMSE。

&&&& 结 果 &&&&

患者的一般资料如表一。

试验路径如图一。

48小时羟考酮累积消耗量的中位数[四分位间距（IQR）]K2组为154.5[120]mg，K10组为160[109]mg，C组为178.5[176]mg。K2组和C组之间的估计差异为−24mg（97.5%置信区间[CI]：−73.8至31.5；P=0.170），K10组和C组之间的估计差异为−18.5mgC（97.5%可信区间[CI]：78.5-29.5；P=0.458）。两组间无显著性差异。

两个氯胺酮治疗组的术后疼痛评分在术后第4个小时显著降低，但在随后2年研究期内没有显著差异。

氯胺酮剂量越高，镇静作用越强。

然而，研究组之间不良事件发生率的差异不显著。

&&&& 结 论 &&&&

未接受阿片类药物治疗的成人研究人群中，术中静脉输注0.12或0.6mg/kg/h S-氯胺酮在减少腰椎融合术后48小时羟考酮用量方面均不优于安慰剂。未来的研究应评估氯胺酮在特定的、能受益于阿片类药物用量减少的人群中应用的可行性。

原文摘要

AnalgesicEffect of Intraoperative Intravenous S-Ketamine in Opioid-Naïve Patients AfterMajor Lumbar Fusion Surgery Is Temporary and Not Dose-Dependent: A Randomized,Double-Blind, Placebo-Controlled Clinical Trial

BACKGROUND:Severe pain often accompanies major spine surgery. Opioids are the cornerstone ofpostoperative pain management but their use can be limited by numerous sideeffects. Several studies claim that adjuvant treatment with intravenous (IV)ketamine reduces opioid consumption and pain after back surgery. However, theexact role of ketamine for this indication is yet to be elucidated. We compared2 different doses of S-ketamine with placebo on postoperative analgesic consumption,pain, and adverse events in adult, opioid-naïve patients after lumbar fusionsurgery.

METHODS:One hundred ninety-eight opioid-naïve patients undergoing lumbar spinal fusionsurgery were recruited to this double-blind trial and randomly assigned into 3study groups: Group C (placebo) received a preincisional IV bolus of saline(sodium chloride [NaCl] 0.9%) followed by an intraoperative IV infusion of NaCl0.9%. Both groups K2 and K10 received a preincisional IV bolus of S-ketamine(0.5 mg/kg); in group K2, this was followed by an intraoperative IV infusion ofS-ketamine (0.12 mg/kg/h), while in group K10, it was followed by anintraoperative IV infusion of S-ketamine (0.6 mg/kg/h). Postoperative analgesiawas achieved by an IV patient-controlled analgesia (IV PCA) device deliveringoxycodone. The primary end point was cumulative oxycodone consumption at 48 hoursafter surgery. The secondary end points included postoperative pain up to 2years after surgery, adverse events, and level of sedation and confusion in theimmediate postoperative period.

RESULTS:The median [interquartile range (IQR)] cumulative oxycodone consumption at 48 hourswas 154.5 [120] mg for group K2, 160 [109] mg for group K10, and 178.5 [176] mgfor group C. The estimated difference was −24 mg between group K2 and group C(97.5% confidence interval [CI], −73.8 to 31.5; P = .170) and −18.5 mg betweengroup K10 and C (97.5% CI, 78.5–29.5; P = .458). There were no significantdifferences between groups. Postoperative pain scores were significantly lowerin both ketamine treatment groups at the fourth postoperative hour but notlater during the 2-year study period. The higher ketamine dose was associatedwith more sedation. Otherwise, differences in the occurrence of adverse eventsbetween study groups were nonsignificant.

CONCLUSIONS:Neither a 0.12 nor a 0.6 mg/kg/h infusion of intraoperative IV S-ketamine was superiorto the placebo in reducing oxycodone consumption at 48 hours after lumbarfusion surgery in an opioid-naïve adult study population. Future studies shouldassess ketamine’s feasibility in specific study populations who most benefitfrom reduced opioid consumption.

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