Department of Anesthesia, Women's Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, China.
Department of Anesthesiology and Critical Care Medicine, Peking University First Hospital, Beijing, China.
JAMA Netw Open. 2023 Apr 3;6(4):e239321. doi: 10.1001/jamanetworkopen.2023.9321.
Epidural anesthesia is a primary choice for cesarean delivery, but supplemental analgesics are often required to relieve pain during uterine traction.
To investigate the sedative and analgesic effects of intravenous esketamine administered before childbirth via cesarean delivery with the patient under epidural anesthesia.
DESIGN, SETTING, AND PARTICIPANTS: This multicenter, double-blind randomized clinical trial assessed 903 women 18 years or older who had full-term single pregnancy and were scheduled for elective cesarean delivery with epidural anesthesia in 5 medical centers in China from September 18, 2021, to September 20, 2022.
Patients were randomized to receive intravenous injection of 0.25 mg/kg of esketamine or placebo before incision.
The coprimary outcomes included scores on the numeric rating scale of pain (an 11-point scale, with 0 indicating no pain and 10 indicating the worst pain; a difference of ≥1.65 points was clinically meaningful) and Ramsay Sedation Scale (a 6-point scale, with 1 indicating restlessness and 6 indicating deep sleep without response; a difference of ≥2 points was clinically meaningful) immediately after fetal delivery. Secondary outcomes included neonatal Apgar score assessed at 1 and 5 minutes after birth.
A total of 600 women (mean [SD] age, 30.7 [4.3] years) were enrolled and randomized; all were included in the intention-to-treat analysis. Immediately after fetal delivery, the score on the numeric rating scale of pain was lower with esketamine (median [IQR], 0 [0-1]) than with placebo (median [IQR], 0 [0-2]; median difference, 0; 95% CI, 0-0; P = .001), but the difference was not clinically important. The Ramsay Sedation Scale scores were higher (sedation deeper) with esketamine (median [IQR], 4 [3-4]) than with placebo (median [IQR], 2 [2-2]; median difference, 2; 95% CI, 2-2; P < .001). The neonatal Apgar scores did not differ between the 2 groups at 1 minute (median difference, 0; 95% CI, 0-0; P = .98) and at 5 minutes (median difference, 0; 95% CI, 0-0; P = .27). Transient neurologic or mental symptoms were more common in patients given esketamine (97.7% [293 of 300]) than in those given placebo (4.7% [14 of 300]; P < .001).
For women undergoing cesarean delivery under epidural anesthesia, a subanesthetic dose of esketamine administered before incision produced transient analgesia and sedation but did not induce significant neonatal depression. Mental symptoms and nystagmus were common but transient. Indications and the optimal dose of esketamine in this patient population need further clarification, but study should be limited to those who require supplemental analgesia.
ClinicalTrials.gov Identifier: NCT04548973.
硬膜外麻醉是剖宫产的首选，但在子宫牵引时通常需要辅助镇痛剂来缓解疼痛。
研究在硬膜外麻醉下剖宫产分娩前静脉注射艾司氯胺酮对产妇的镇静和镇痛作用。
设计、地点和参与者：这是一项多中心、双盲随机临床试验，评估了 2021 年 9 月 18 日至 2022 年 9 月 20 日在中国 5 家医疗中心接受择期剖宫产且接受硬膜外麻醉的 903 名 18 岁及以上、足月单胎妊娠的女性。
患者随机接受 0.25mg/kg 艾司氯胺酮或安慰剂静脉注射。
主要复合结局包括分娩后即刻的疼痛数字评分量表（疼痛程度为 11 分制，0 表示无痛，10 表示最痛；差值≥1.65 分具有临床意义）和 Ramsay 镇静评分（镇静程度为 6 分制，1 表示烦躁不安，6 表示深度睡眠无反应；差值≥2 分具有临床意义）。次要结局包括新生儿出生后 1 分钟和 5 分钟的 Apgar 评分。
共有 600 名（平均[标准差]年龄 30.7[4.3]岁）女性被纳入并随机分组；所有患者均纳入意向治疗分析。分娩后即刻，艾司氯胺酮（中位数[IQR]，0[0-1]）组的疼痛数字评分量表评分低于安慰剂（中位数[IQR]，0[0-2]；中位数差值，0；95%CI，0-0；P=.001），但差异无临床意义。艾司氯胺酮（中位数[IQR]，4[3-4]）组的 Ramsay 镇静评分高于安慰剂（中位数[IQR]，2[2-2]；中位数差值，2；95%CI，2-2；P<.001）。两组新生儿在 1 分钟（中位数差值，0；95%CI，0-0；P=.98）和 5 分钟（中位数差值，0；95%CI，0-0；P=.27）的 Apgar 评分无差异。给予艾司氯胺酮的患者（97.7%[293/300]）比给予安慰剂的患者（4.7%[14/300]）更常出现短暂的神经或精神症状（P<.001）。
对于接受硬膜外麻醉剖宫产的女性，在切开前给予亚麻醉剂量的艾司氯胺酮可产生短暂的镇痛和镇静作用，但不会引起明显的新生儿抑制。精神症状和眼球震颤常见但短暂。该患者人群中艾司氯胺酮的适应证和最佳剂量仍需进一步明确，但研究应仅限于需要辅助镇痛的患者。
ClinicalTrials.gov 标识符：NCT04548973。
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