丙泊酚和硫喷妥钠用于新生儿静脉麻醉诱导：剂量测定试验的研究方案

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丙泊酚和硫喷妥钠用于新生儿静脉麻醉诱导：剂量测定试验的研究方案

贵州医科大学    麻醉与心脏电生理课题组

翻 译：马艳燕  编 辑：柏雪  审 校：曹莹

背景：丙泊酚和硫喷妥钠是新生儿麻醉中常用的诱导药。尽管这两种催眠药已经超说明书使用多年，但新生儿中关于这些药物的药理学知识很少。新生儿的身体成分、器官功能和成熟度的显著差异使得药理学研究具有高度相关性，尽管具有挑战性。因此，目前关于新生儿中硫喷妥钠和丙泊酚的麻醉诱导剂量的数据有限。此外，关于诱导剂量的药效学方面还存在知识空白。 

目的：确定丙泊酚和硫喷妥钠在不同胎龄和产后新生儿患者中的中位有效麻醉诱导剂量，并评估麻醉诱导剂量对新生儿全身和脑血流动力学的药效学影响。  

方法：这是一项单中心、前瞻性、开放标签、介入性、剂量测定研究，包括从出生到产后28天接受全身麻醉以进行手术或诊断的新生儿患者。患者将根据其胎龄和出生后年龄进行分层，并分配到两个试验组中（丙泊酚麻醉诱导组或硫喷妥钠麻醉诱导组）。我们将使用Dixon序贯法来估计两种药物在不同胎龄和产后新生儿中的中位有效麻醉诱导剂量。此外，我们将研究麻醉诱导剂量与全身和脑血流动力学变化之间的关系。  

讨论：麻醉诱导引起的全身和大脑局部血流动力学改变可能对新生儿有害，尤其是早产儿和危重新生儿，因为它们的器官系统不成熟、生理储备减少和大脑自动调节受损。灌注稳态被认为是麻醉相关神经认知结局的重要且可改变的决定因素之一。因此，迫切需要对新生儿麻醉诱导药进行剂量测定和安全性药理学研究，并被欧洲药品管理局列为高度优先事项。估计足够的诱导剂量以确保最佳的麻醉深度，同时避免全身和脑血流动力学紊乱，将有助于确保安全麻醉，并可能改善这组患者的麻醉相关结局。

原始文献来源  ：Vassileva Vesselinova I, Jensen KN, Hansen TG. Propofol and thiopental for intravenous induction in neonates: study protocol for a dose-finding trial. Acta Anaesthesiol Scand. 2023 Mar 15. doi: 10.1111/aas.14238.  

英文原文：

Propofol and thiopental for intravenous induction in neonates: study protocol

for a dose-finding trial

Background: Propofol and thiopental are commonly used induction agents in neonatal anesthesia. Even though both hypnotics have been used off-label for many years, pharmacological knowledge regarding these agents is scarce in neonates. The significant variability in neonates’ body composition, organ function, and maturation makes pharmacological studies highly relevant albeit challenging. As a result, there is currently limited data about the anesthetic induction dose of thiopental and propofol in neonates. In addition, a knowledge gap exists concerning the pharmacodynamics of induction doses.  

Objective: To determine the median effective anesthetic induction dose of propofol and thiopental in neonatal patients of different gestational and postnatal ages and evaluate the pharmacodynamics of the anesthesia induction doses on the neonatal systemic and cerebral hemodynamics. 

Methods: This is a single-center, prospective, open-label, interventional, dose-finding study, including neonatal patients from birth up to 28 postnatal days undergoing general anesthesia for surgical or diagnostic procedures. The patients will be stratified according to their gestational and postnatal age and allocated to one of the two trial arms: anesthesia induction with propofol or anesthesia induction with thiopental. We will use Dixon‘s up-and-down method to estimate the median effective anesthesia induction dose of both agents in neonates of different gestational and postnatal ages. In addition, we will study the relationship between anesthesia induction doses and changes in systemic and cerebral hemodynamics.   

Discussion: Alterations in the systemic and cerebral regional hemodynamics secondary to anesthesia induction may be harmful in neonates, especially premature and critically ill   newborns, due to their immature organ systems, reduced physiological reserves, and impaired cerebral autoregulation. Perfusion homeostasis is considered one of the significant and modifiable determinants of anesthesia-related neurocognitive outcomes. Therefore, dose-finding and safety pharmacological studies of the anesthetic induction agents in neonates are urgently needed and acknowledged as a high priority by the European Medicine   Agency. Estimating adequate induction doses to ensure optimal depth of anesthesia while avoiding systemic and cerebral hemodynamic disturbances will help ensure safe anesthesia and potentially improve anesthesia-related outcomes in this group of patients.  

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校对：Michel.米萱

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