Table 3_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：氯胺酮与艾司氯胺酮在剖宫产术中的应用受其剂量依赖性不良反应的限制。本研究旨在精准量化其预防寒战与瘙痒的量效关系，并明确与之相关的神经精神不良反应风险，进而明确其治疗窗口。
方法：本研究开展了系统评价与网络meta分析（network meta-analysis）。我们检索了数据库中关于神经轴阻滞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（randomized controlled trials, RCTs）。采用Cochrane RoB 2工具评估研究质量。我们结合传统meta分析与网络meta分析，联合logistic回归、蒙特卡洛模拟（Monte Carlo simulation）与多项式回归构建连续量效模型，并计算关键剂量参数（ED50、ED95）。
结果：本研究共纳入25项研究，涉及3842名受试者。预防瘙痒与寒战的ED50分别为0.122 mg/kg（95%置信区间[CI]：0.087~0.164）与0.329 mg/kg（95%[CI]：0.260~0.412）。然而，当剂量分别达到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（≈0.12 mg/kg）用于瘙痒预防的获益显著大于其风险。与之相反，预防寒战所需的剂量（≈0.33 mg/kg）处于不良反应高发的剂量范围，导致其治疗窗口较窄。本研究为剖宫产术中氯胺酮的个体化、目标导向性应用提供了关键的剂量探索证据。
系统评价注册信息：https://www.crd.york.ac.uk/PROSPERO/view/CRD420251073122，注册号：CRD420251073122。