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依托咪酯与不同剂量依托咪酯复合使用行上消化道内镜检查术患儿的 ED 和 ED₅₀:采用上下序贯分配法的前瞻性剂量探索研究。

ED and ED of propofol combined with different doses of esketamine for children undergoing upper gastrointestinal endoscopy: A prospective dose-finding study using up-and-down sequential allocation method.

机构信息

Department of Anaesthesiology, Shanghai Children's Medical Centre, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.

出版信息

J Clin Pharm Ther. 2022 Jul;47(7):1002-1009. doi: 10.1111/jcpt.13635. Epub 2022 Mar 7.

Abstract

WHAT IS KNOWN AND OBJECTIVE

Propofol and esketamine are routine anaesthetics used in sedation or general anaesthesia for paediatric procedures. Coadministration could reduce the dose of either propofol or esketamine required and lower the incidence of drug-related adverse events. We designed a four-arm randomized controlled trial in children undergoing diagnostic upper gastrointestinal endoscopy to investigate the dose of propofol with different doses of esketamine inducing appropriate depth of anaesthesia in 50% patients (median effective dose, ED ).

METHODS

After getting the approval of the research ethics committee and informed consent, 92 paediatric patients planning for upper gastrointestinal endoscopy were divided into four groups randomly: esketamine 0, 0.25, 0.5 and 1 mg/kg groups (n = 23/group). Propofol doses followed the Dixon and Massey up-and-down method with different starting and interval doses between groups. During the first attempt of endoscope insertion, if patients' reactions prevented the insertion, it would be considered as a failure. The awakening time, total propofol doses, as well as the perioperative and post-procedure adverse events were evaluated and recorded for each patient.

RESULTS AND DISCUSSION

The ED (median, 95% confidence interval) of propofol was significantly greater in esketamine 0 and 0.25 mg/kg groups in comparison with the esketamine 0.5 and 1 mg/kg groups (4.1 [3.3-4.9]; 3.1 [2.5-3.8] mg/kg vs. 1.8 [1.1-2.4]; 0.8 [0.2-1.3] mg/kg, respectively, p < .05). The total doses of propofol in esketamine 0.5 and 1 mg/kg groups were statistically lower than these in esketamine 0 and 0.25 mg/kg group (p < .01). The mean blood pressure was lower in the esketamine 0 mg/kg group than that in 1 mg/kg group after administration and during the procedure (p < .01). The esketamine 1 mg/kg group showed a higher incidence of vomiting and visual disturbances than the other three groups (p < .001).

WHAT IS NEW AND CONCLUSION

In children who accomplished diagnostic paediatric upper gastrointestinal endoscopy under deep sedation/anaesthesia, the total dosage of propofol needed was reduced significantly in esketamine 0.5 and 1 mg/kg groups with a corresponding reduce in propofol-related hemodynamic changes. However, a higher incidence of esketamine-related adverse effects was found in esketamine 1 mg/kg group.

摘要

已知和目的

丙泊酚和依托咪酯是儿科手术镇静或全身麻醉中常规使用的麻醉剂。联合使用可以减少丙泊酚或依托咪酯的剂量,并降低药物相关不良事件的发生率。我们设计了一项四臂随机对照试验,纳入 92 例计划行诊断性上消化道内镜检查的儿科患者,以研究不同剂量依托咪酯(50%患者诱导适当麻醉深度的中位有效剂量,ED)与丙泊酚联合应用时丙泊酚的剂量。

方法

在获得研究伦理委员会的批准和知情同意后,92 例计划行上消化道内镜检查的儿科患者随机分为四组:依托咪酯 0、0.25、0.5 和 1mg/kg 组(每组 23 例)。各组之间的起始剂量和间隔剂量均采用 Dixon 和 Massey 上下法。如果患者在第一次尝试插入内镜时出现反应,导致无法插入,则视为失败。评估并记录每位患者的苏醒时间、丙泊酚总剂量、围手术期和术后不良事件。

结果与讨论

与依托咪酯 0.5 和 1mg/kg 组相比,依托咪酯 0 和 0.25mg/kg 组丙泊酚的 ED(中位数,95%置信区间)显著更高(4.1[3.3-4.9];3.1[2.5-3.8]mg/kg 比 1.8[1.1-2.4];0.8[0.2-1.3]mg/kg,p<.05)。依托咪酯 0.5 和 1mg/kg 组丙泊酚总剂量明显低于依托咪酯 0 和 0.25mg/kg 组(p<.01)。依托咪酯 0mg/kg 组给药后和手术期间的平均血压低于 1mg/kg 组(p<.01)。依托咪酯 1mg/kg 组呕吐和视觉障碍的发生率高于其他三组(p<.001)。

新发现和结论

在接受深度镇静/麻醉下完成诊断性儿科上消化道内镜检查的儿童中,依托咪酯 0.5 和 1mg/kg 组丙泊酚的总用量显著减少,相应地减少了丙泊酚相关的血液动力学变化。然而,依托咪酯 1mg/kg 组发现了更高的依托咪酯相关不良反应发生率。

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