Department of Anesthesiology and Intensive Care, Odense University Hospital, Odense, Denmark.
Department of Anesthesiology and Intensive Care, Akershus University Hospital, Lørenskog, Norway, and Oslo University, Oslo, Norway.
Acta Anaesthesiol Scand. 2023 Jul;67(6):820-828. doi: 10.1111/aas.14238. Epub 2023 Jun 2.
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.
异丙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被超适应证使用多年，但新生儿的药理学知识却很匮乏。新生儿的身体成分、器官功能和成熟度存在显著差异，这使得药理学研究变得非常重要，但也极具挑战性。因此，目前关于新生儿硫喷妥钠和异丙酚麻醉诱导剂量的数据非常有限。此外，关于诱导剂量的药效学也存在知识空白。
确定不同胎龄和出生后年龄的新生儿患者中异丙酚和硫喷妥钠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。
这是一项单中心、前瞻性、开放标签、干预性、剂量探索研究，纳入了出生后至 28 天内接受全身麻醉以进行手术或诊断程序的新生儿患者。这些患者将根据胎龄和出生后年龄进行分层，并分配到两个试验组之一：异丙酚麻醉诱导或硫喷妥钠麻醉诱导。我们将使用 Dixon 的上下法来估计不同胎龄和出生后年龄的新生儿中这两种药物的中位有效麻醉诱导剂量。此外，我们还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。
麻醉诱导引起的全身和脑区域性血流动力学改变可能对新生儿有害，尤其是对早产儿和危重新生儿，因为他们的器官系统不成熟、生理储备减少和脑自动调节受损。灌注平衡被认为是麻醉相关神经认知结局的重要且可调节的决定因素之一。因此，欧洲药品管理局迫切需要对新生儿的麻醉诱导药物进行剂量探索和安全性药理学研究，并将其作为优先事项之一。估计适当的诱导剂量以确保最佳麻醉深度，同时避免全身和脑血流动力学紊乱，将有助于确保该组患者的安全麻醉，并可能改善麻醉相关结局。
EudraCT（EudraCT 标识符：2019-001534-34），2022 年 7 月 5 日。
