背景:丙泊酚和硫喷妥钠是新生儿麻醉中常用的诱导剂。尽管这两种催眠药已经在标签外使用了很多年,关于这些药物的药理学知识在新生儿中很少。新生儿身体成分的显著变异性,器官功能,和成熟使药理学研究高度相关,尽管具有挑战性。因此,目前关于硫喷妥钠和丙泊酚在新生儿中的麻醉诱导剂量的数据有限。此外,关于诱导剂量的药效学存在知识空白。
目的:确定不同孕龄新生儿异丙酚和硫喷妥钠麻醉诱导的半数有效剂量,评价麻醉诱导剂量对新生儿全身和脑血流动力学的药效学。
方法:这是一个单中心,prospective,开放标签,介入,剂量发现研究,包括从出生到出生后28天接受手术或诊断程序的全身麻醉的新生儿患者。患者将根据其妊娠和产后年龄进行分层,并分配到两个试验组之一:丙泊酚麻醉诱导或硫喷妥钠麻醉诱导。我们将使用Dixon的上下方法来估计两种药物在不同孕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。
结论:麻醉诱导后全身和脑局部血流动力学的改变可能对新生儿有害,尤其是早产儿和危重新生儿,由于它们的器官系统不成熟,减少生理储备,大脑自动调节功能受损.灌注稳态被认为是麻醉相关神经认知结果的重要且可修改的决定因素之一。因此,迫切需要在新生儿中进行麻醉诱导剂的剂量发现和安全性药理学研究,并被欧洲医药署视为高度优先事项。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的麻醉,并可能改善该组患者的麻醉相关结局。本文受版权保护。保留所有权利。
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.
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.
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.
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.
EudraCT (EudraCT Identifier: 2019-001534-34), 05.07.2022.