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剖宫产腰麻-硬膜外联合麻醉期间输注去甲肾上腺素和去氧肾上腺素预防低血压的相对效价测定:一项随机上下序贯分配研究

Determination of the Relative Potency of Norepinephrine and Phenylephrine Given as Infusions for Preventing Hypotension During Combined Spinal-Epidural Anesthesia for Cesarean Delivery: A Randomized Up-And-Down Sequential Allocation Study.

作者信息

Qian Jing, Zhao Yan-Ping, Deng Jia-Li, Wang Li-Zhong, Xiao Fei, Shen Bei, Yao Han-Qing

机构信息

Department of Anesthesia, Jiaxing Women and Children's Hospital of Wenzhou Medical University, Jiaxing, China.

Jiaxing University Affiliated Women and Children Hospital, Jiaxing, China.

出版信息

Front Pharmacol. 2022 Jul 14;13:942005. doi: 10.3389/fphar.2022.942005. eCollection 2022.

Abstract

The relative potency of norepinephrine and phenylephrine given as boluses to treat hypotension during spinal anesthesia for cesarean delivery has been reported but few data are available for infusions. This study aimed to determine the relative potency of norepinephrine and phenylephrine when given by infusion for preventing hypotension during combined spinal-epidural anesthesia for cesarean delivery. This was a prospective, randomized, double-blind, up-and-down sequential allocation study. Patients were randomly allocated to receive a prophylactic infusion of norepinephrine or phenylephrine started immediately after induction of anesthesia. The first patients received either norepinephrine 0.1 μg/kg/min or phenylephrine 0.5 μg/kg/min. An effective infusion rate was defined when no hypotension occurred before delivery. For each subsequent patient, the norepinephrine infusion rate was decreased or increased by 0.01 μg/kg/min or the phenylephrine infusion rate was decreased or increased by 0.05 μg/kg/min according to whether the infusion was effective or ineffective respectively in the previous patient. Values for the infusion rate that was effective in preventing hypotension in 50% of patients (ED50) for norepinephrine and phenylephrine were estimated using up-and-down sequential analysis and relative potency was estimated. Probit regression was used as a backup and sensitivity analysis. The ED50 values for norepinephrine and phenylephrine calculated by the up-and-down method were 0.061 (95% CI 0.054-0.068) μg/kg/min and 0.368 (95% CI 0.343-0.393) μg/kg/min respectively. The estimated relative potency ratio for ED50 for norepinephrine to phenylephrine was 6.03:1 (95% CI 5.26:1 to 6.98:1). Under the conditions of this study, norepinephrine given by infusion was about 6 times more potent than phenylephrine. This information is useful for clinical practice and further comparative studies of norepinephrine versus phenylephrine. http://www.chictr.org.cn/showproj.aspx, identifier [ChiCTR2200056237].

摘要

剖宫产脊髓麻醉期间,静脉推注去甲肾上腺素和去氧肾上腺素治疗低血压的相对效价已有报道,但关于静脉输注的数据较少。本研究旨在确定剖宫产腰麻-硬膜外联合麻醉期间静脉输注去甲肾上腺素和去氧肾上腺素预防低血压的相对效价。这是一项前瞻性、随机、双盲、序贯分配研究。患者在麻醉诱导后立即随机分配接受去甲肾上腺素或去氧肾上腺素预防性输注。首例患者接受去甲肾上腺素0.1μg/kg/min或去氧肾上腺素0.5μg/kg/min输注。若分娩前未发生低血压,则定义为有效输注速率。对于随后的每位患者,则根据前一位患者输注是否有效,分别将去甲肾上腺素输注速率降低或增加0.01μg/kg/min,或将去氧肾上腺素输注速率降低或增加0.05μg/kg/min。采用序贯分析估计去甲肾上腺素和去氧肾上腺素在50%患者中预防低血压有效的输注速率值(ED50),并估计相对效价。采用概率回归作为备用和敏感性分析。通过序贯法计算的去甲肾上腺素和去氧肾上腺素的ED50值分别为0.061(95%CI 0.054-0.068)μg/kg/min和0.368(95%CI 0.343-0.393)μg/kg/min。去甲肾上腺素与去氧肾上腺素ED50的估计相对效价比为6.03:1(95%CI 5.26:1至6.98:1)。在本研究条件下,静脉输注的去甲肾上腺素效价约为去氧肾上腺素的6倍。该信息对临床实践以及去甲肾上腺素与去氧肾上腺素的进一步比较研究具有参考价值。http://www.chictr.org.cn/showproj.aspx,标识符[ChiCTR2200056237]

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/30f8/9330490/176c89c28cc9/fphar-13-942005-g001.jpg

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