The First Clinical Medical College of Lanzhou University, Lanzhou, China.
The Reproductive Medicine Center, The First Hospital of Lanzhou University, Lanzhou, China.
J Clin Pharm Ther. 2022 Oct;47(10):1495-1505. doi: 10.1111/jcpt.13763. Epub 2022 Aug 27.
It is estimated that 60% of children undergoing anaesthesia develop severe preoperative anxiety. The anxiety is associated with adverse reactions. Sedatives such as dexmedetomidine, midazolam, clonidine, ketamine, and melatonin can be used as premedication against preoperative anxiety. However, no consensus has been reached on the choice of pre-anaesthetic sedatives in children before selective surgery. Therefore, the current network meta-analysis (NMA) was carried out to evaluate different sedatives in children aged between 1 and 7 before general anaesthesia for selective surgery.
Randomized clinical trials (RCTs) were retrieved from Pubmed, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), and Web of Science databases from inception to October 22, 2021. Primary outcomes showed satisfactory sedation at parent separation and also at induction or mask acceptance. Secondary outcomes were those related to added benefits and side effects. The present NMA was conducted using the R software. Results of the study were reported as Relative Risk (RR) or Mean Difference (MD) at a 95% credible intervals (CrIs).
A total of 48 trials were included in the present study. It was found that the effectiveness of dexmedetomidine, midazolam, clonidine, and ketamine were superior to that of placebo in satisfactory sedation at parent separation and induction or mask acceptance. There was no significant difference between melatonin and placebo in satisfactory sedation at induction or mask acceptance. Dexmedetomidine, ketamine, clonidine, and melatonin were superior to placebo in reducing emergence delirium (ED). In addition, midazolam prolonged the length of stay in the post anaesthesia care unit (PACU) as compared with placebo. Dexmedetomidine caused a significant reduction in systolic blood pressure (SBP) and heart rate (HR). Nevertheless, it was noted that the hemodynamic changes were roughly within safety limits.
It was evident that the studied drugs can provide effective sedation with exception of melatonin and placebo. However, it was found that midazolam, ketamine, and clonidine lead to several side effects. The findings of the present study supported that dexmedetomidine, especially intranasal administration, has potential in the optimal selection of the sedatives for premedication in children. This is because the drug has effective sedation, reduced incidence of ED, side effects, and onset time.
据估计，60%接受麻醉的儿童会出现严重的术前焦虑。这种焦虑与不良反应有关。地塞米松、咪达唑仑、可乐定、氯胺酮和褪黑素等镇静剂可用作预防术前焦虑的术前用药。然而，对于选择性手术前儿童的麻醉前镇静剂选择，尚未达成共识。因此，目前进行了网络荟萃分析（NMA），以评估儿童在全身麻醉前接受选择性手术时使用不同镇静剂的情况。
从 Pubmed、Embase、Cochrane 对照试验中心注册库（CENTRAL）和 Web of Science 数据库中检索到随机临床试验（RCT），检索时间从成立到 2021 年 10 月 22 日。主要结局显示父母分离时、诱导或面罩接受时的满意镇静效果。次要结局是与附加益处和副作用相关的结局。本 NMA 使用 R 软件进行。研究结果以 95%可信区间（CrIs）的相对风险（RR）或均数差（MD）报告。
本研究共纳入 48 项试验。结果发现，地塞米松、咪达唑仑、可乐定和氯胺酮的有效性优于安慰剂，在父母分离和诱导或面罩接受时可达到满意的镇静效果。褪黑素与安慰剂在诱导或面罩接受时的满意镇静效果无显著差异。地塞米松、氯胺酮、可乐定和褪黑素在减少苏醒性谵妄（ED）方面优于安慰剂。此外，与安慰剂相比，咪达唑仑延长了麻醉后护理单元（PACU）的停留时间。地塞米松可显著降低收缩压（SBP）和心率（HR）。然而，需要注意的是，血流动力学变化大致在安全范围内。
研究药物除褪黑素和安慰剂外，均可提供有效镇静作用。然而，发现咪达唑仑、氯胺酮和可乐定会引起多种副作用。本研究结果表明，地塞米松，特别是鼻内给药，在儿童术前用药的最佳选择方面具有潜力。这是因为该药物具有有效的镇静作用，降低 ED 的发生率，减少副作用和起效时间。
