Lugli Licia, Garetti Elisabetta, Goffredo Bianca Maria, Candia Francesco, Crestani Sara, Spada Caterina, Guidotti Isotta, Bedetti Luca, Miselli Francesca, Della Casa Elisa Muttini, Roversi Maria Federica, Simeoli Raffaele, Cairoli Sara, Merazzi Daniele, Lago Paola, Iughetti Lorenzo, Berardi Alberto
Neonatal Intensive Care Unit, Women's and Children's Health Department, University Hospital of Modena, 41100 Modena, Italy.
Division of Metabolic Diseases and Drug Biology, Bambino Gesù Children's Hospital, Scientific Institute for hospitalization and care (IRCCS), 00100 Rome, Italy.
Biomedicines. 2023 Aug 27;11(9):2395. doi: 10.3390/biomedicines11092395.
Therapeutic hypothermia (TH) is the standard of care for newborns with moderate to severe hypoxic-ischemic encephalopathy (HIE). Discomfort and pain during treatment are common and may affect the therapeutic efficacy of TH. Opioid sedation and analgesia (SA) are generally used in clinical practice, and fentanyl is one of the most frequently administered drugs. However, although fentanyl's pharmacokinetics (PKs) may be altered by hypothermic treatment, the PK behavior of this opioid drug in cooled newborns with HIE has been poorly investigated. The aim of this phase 1 study protocol (Trial ID: FentanylTH; EUDRACT number: 2020-000836-23) is to evaluate the fentanyl time-concentration profiles of full-term newborns with HIE who have been treated with TH. Newborns undergoing TH receive a standard fentanyl regimen (2 mcg/Kg of fentanyl as a loading dose, followed by a continuous infusion-1 mcg/kg/h-during the 72 h of TH and subsequent rewarming). Fentanyl plasma concentrations before bolus administration, at the end of the loading dose, and 24-48-72-96 h after infusion are measured. The median, maximum, and minimum plasma concentrations, together with drug clearance, are determined. This study will explore the fentanyl time-concentration profiles of cooled, full-term newborns with HIE, thereby helping to optimize the fentanyl SA dosing regimen during TH.
治疗性低温（TH）是中重度缺氧缺血性脑病（HIE）新生儿的标准治疗方法。治疗期间的不适和疼痛很常见，可能会影响TH的治疗效果。阿片类药物镇静和镇痛（SA）在临床实践中普遍使用，芬太尼是最常用的药物之一。然而，尽管低温治疗可能会改变芬太尼的药代动力学（PKs），但这种阿片类药物在接受低温治疗的HIE新生儿中的PK行为尚未得到充分研究。这项1期研究方案（试验编号：FentanylTH；欧盟临床试验注册号：2020-000836-23）的目的是评估接受TH治疗的足月HIE新生儿的芬太尼时间-浓度曲线。接受TH治疗的新生儿接受标准芬太尼方案（2 mcg/Kg芬太尼作为负荷剂量，随后在TH的72小时及随后复温期间持续输注-1 mcg/kg/h）。测量推注给药前、负荷剂量结束时以及输注后24-48-72-96小时的芬太尼血浆浓度。确定血浆浓度的中位数、最大值和最小值以及药物清除率。本研究将探索接受低温治疗的足月HIE新生儿的芬太尼时间-浓度曲线，从而有助于优化TH期间芬太尼SA给药方案。
