【罂粟摘要】艾司氯胺酮用于小儿胃肠内窥镜检查的有效性和安全性

艾司氯胺酮在小儿胃肠内镜检查中的作用尚不清楚。本研究旨在评价艾司氯胺酮用于小儿胃肠内镜检查的有效性和安全性。

在8个常见数据库中检索截至2023年10月的艾司氯胺酮用于小儿胃肠内镜检查的临床试验。临床试验被纳入系统评价和试验序贯分析（Trial Sequential Analysis, TSA）。对于效果大小的度量，使用了风险比（Risk Ratio, RR）和加权均数差（Weighted Mean Difference, WMD），分别使用二分类变量（如事件发生与否）和连续变量（如某种测量值）。当异质性检验显示I² < 50%时，采用固定效应模型进行meta分析和TSA；否则，采用随机效应模型进行分析。

在疗效情况方面，荟萃分析显示，与安慰剂或空白相比，艾司氯胺酮显著缩短了2.34 min的恢复时间(WMD−2.34；95%可信区间(CI) - 3.65, - 1.02；p = 0.0005)，丙泊酚用量减少0.70 mg/kg (WMD−0.70；95% ci - 0.98 ~ - 0.43；p＜0.00001)，平均心率增加4.77次/min (WMD 4.77；95% ci 2.67 ~ 6.87；p＜0.00001)和平均动脉压增加3.10 mmHg (WMD 3.10；95% ci 1.52 ~ 4.67；P = 0.0001)，而诱导时间和平均血氧差异无统计学意义。TSA提供了这些益处的确凿证据。在安全性方面，荟萃分析显示艾氯胺酮显著减少了59%的不自主运动(RR 0.41；95% ci 0.22 ~ 0.76；p = 0.005)和51%的窒息(RR 0.49；95% ci 0.26 ~ 0.92；p = 0.03)，同时显著增加98%的头晕(RR 1.98；95% ci 1.11, 3.56；P = 0.02)，总不良事件、呼吸抑制和呕吐发生率差异无统计学意义。TSA证实了不自主运动和头晕的确凿证据。分析显示，低剂量艾司氯胺酮≤0.3 mg/kg可显著缩短苏醒时间、减少丙泊酚用量和不自主运动，显著提高平均心率，且不增加头晕的发生。Begg 's检验（p = 0.327）和Egger 's检验（p = 0.413）显示低剂量艾司氯胺酮无显著的发表偏倚（无统计学意义），但漏斗图提示低剂量艾司氯胺酮存在潜在的发表偏倚（存在统计学意义）。 

艾司氯胺酮是儿童胃肠道内镜检查的有效辅助麻醉剂。然而，一般剂量的艾司氯胺酮可能会增加头晕的风险，低剂量艾司氯胺酮（≤0.3 mg/kg）可以避免头晕的风险。

原始文献来源： Yu Y,Deng J,Tong K, et al. Efficacy and safety of esketamine for pediatric gastrointestinal endoscopy: a meta-analysis and trial sequential analysis. Front Pharmacol. 2024;15:1379101. doi:10.3389/fphar.2024.1379101

Efficacy and safety of esketaminefor pediatric gastrointestinalendoscopy: a meta-analysis andtrial sequential analysis

Objective:The role of esketamine in pediatric gastrointestinal endoscopy is still unclear. This study aims to evaluate the efficacy and safety of esketamine for pediatric gastrointestinal endoscopy.

Methods:Clinical trials of esketamine for pediatric gastrointestinal endoscopy were searched in eight common databases, up to October 2023. These clinical trials were included in the meta-analysis and trial sequential analysis (TSA). The risk ratio (RR) and weighted mean difference (WMD) were used as the effect sizes for dichotomous variables and continuity variables, respectively. When the heterogeneity test showed I² < 50%,, the fixed effects model was used for the meta-analysis and TSA; Otherwise, the random effects model was used for them.

Results:In terms of efficacy endpoints, the meta-analysis showed that compared with placebo or blank, esketamine significantly decreased recovery time by 2.34 min (WMD −2.34; 95% Confidence interval [CI] −3.65, −1.02; p = 0.0005) and propofol consumption by 0.70 mg/kg (WMD −0.70; 95% CI −0.98, −0.43; p < 0.00001), and increased mean heart rate by 4.77 beats/min (WMD 4.77; 95% CI 2.67, 6.87; p < 0.00001) and mean arterial pressure by 3.10 mmHg (WMD 3.10; 95% CI 1.52, 4.67; p = 0.0001), while induction time and mean blood oxygen remained comparable. TSA indicated conclusive evidence for these benefits. In terms of safety endpoints, the meta-analysis revealed that esketamine significantly reduced involuntary movements by 59% (RR 0.41; 95% CI 0.22, 0.76; p = 0.005) and choking by 51% (RR 0.49; 95% CI 0.26, 0.92; p = 0.03), while significantly increasing dizziness by 98% (RR 1.98; 95% CI 1.11, 3.56; p = 0.02) and there were no significant differences in total adverse events, respiratory depression, and vomiting. TSA demonstrated conclusive evidence for involuntary movements and dizziness. Low-dose analysis showed that esketamine at ≤0.3 mg/kg significantly reduced recovery time, propofol consumption and involuntary movements, and significantly increasing mean heart rate, with no increase in dizziness. The Begg’s test (p = 0.327) and the Egger’s test (p = 0.413) indicated no significant publication bias, yet the funnel plot suggested potential publication bias.

Conclusion:Esketamine is an effective adjuvant anesthesia for children undergoing gastrointestinal endoscopy. However, the general dose of esketamine may increase the risk of dizziness, which can be avoided by administering a low dose (≤0.3 mg/kg).