Table 5_Estimated preventive dose of racemic ketamine for shivering and pruritus prophylaxis in cesarean delivery: a Monte Carlo simulation guided network meta-analysis.docx

BackgroundThe use of ketamine and esketamine in cesarean delivery is limited by their dose-dependent adverse effects. This study aimed to precisely quantify the dose-response relationships for the prevention of shivering and pruritus and to determine the associated risk of neuropsychiatric side effects, thereby defining its therapeutic window.
MethodsA systematic review and network meta-analysis were conducted. We searched databases for randomized controlled trials (RCTs) evaluating a single intravenous bolus of ketamine or esketamine during cesarean delivery under neuraxial anesthesia. Study quality was assessed using the Cochrane RoB 2 tool. We integrated traditional and network meta-analysis with logistic regression, Monte Carlo simulation, and polynomial regression to establish continuous dose-response models and calculate key dose parameters (ED50, ED95).
Results25 studies(3,842 participants) were included. The ED50 for preventing pruritus and shivering were 0.122 mg/kg (95% CI, 0.087–0.164) and 0.329 mg/kg (95% CI, 0.260–0.412), respectively. However, at doses of 0.273 mg/kg (ED50) and 0.761 mg/kg (ED95), 50% and 95% of parturients, respectively, experienced subjective side effects.
ConclusionThe benefits of low-dose ketamine (≈0.12 mg/kg) for pruritus prophylaxis clearly outweigh its risks. In contrast, the dose required for shivering prevention (≈0.33 mg/kg) falls within the range where side effects become common, resulting in a narrow therapeutic window. This study provides critical dose-finding evidence for individualized, goal-directed use of ketamine in cesarean delivery.
Systematic Review Registrationhttps://www.crd.york.ac.uk/PROSPERO/view/CRD420251073122, identifier CRD420251073122.

**背景** 氯胺酮（ketamine）与艾司氯胺酮（esketamine）在剖宫产术中的应用受限于其剂量依赖性不良反应。本研究旨在精准量化二者用于预防寒战与瘙痒的量效关系，并明确其神经精神系统相关不良反应风险，进而明确其治疗窗。

**方法** 本研究采用系统评价与网状meta分析方法。我们检索了数据库中关于椎管内麻醉下剖宫产术中单次静脉推注氯胺酮或艾司氯胺酮的随机对照试验（RCTs）。采用Cochrane偏倚风险2工具（Cochrane RoB 2）对研究质量进行评价。本研究整合传统meta分析与网状meta分析，结合逻辑回归、蒙特卡洛模拟及多项式回归构建连续量效模型，并计算关键剂量参数（半数有效剂量ED50、95%有效剂量ED95）。

**结果** 本研究共纳入25项研究，涉及3842名受试者。用于预防瘙痒与寒战的半数有效剂量ED50分别为0.122 mg/kg（95%置信区间：0.087~0.164）与0.329 mg/kg（95%置信区间：0.260~0.412）。而当剂量达到0.273 mg/kg（ED50）与0.761 mg/kg（ED95）时，分别有50%与95%的产妇出现主观不良反应。

**结论** 低剂量氯胺酮（约0.12 mg/kg）用于瘙痒预防时，其获益显著大于风险。与之相反，预防寒战所需剂量（约0.33 mg/kg）处于不良反应高发的剂量范围，导致其治疗窗较窄。本研究为剖宫产术中氯胺酮的个体化目标导向应用提供了关键的剂量探索证据。

**系统评价注册** 本系统评价已在PROSPERO平台注册，注册号为CRD420251073122，注册链接：https://www.crd.york.ac.uk/PROSPERO/view/CRD420251073122。