Ellen de Kort

109 Propofol for intubation in neonates 7 INTRODUCTION As awake intubation has multiple harmful effects, 1–7 the routine use of premedication before non-emergency intubation in neonates has become standard of care. 8–11 However, there is insufficient knowledge and lack of consensus about the most effective and safe strategy. Propofol is considered one of the acceptable options, despite being off- label for use in newborns, gaps in knowledge regarding optimal dosing and concerns about safety. 12 Because of its rapid onset and recovery, and its ease of use, propofol as a sedative for endotracheal intubation has been implemented into clinical practice in several neonatal intensive care units (NICUs). 13-17 Previous trials have shown conflicting results on sedative effect and concerning effects on blood pressure. 16-19 Used propofol starting doses range from 1.0 to 2.5 mg/kg, with cumulative doses ranging from 1.0 to 6.0 mg/kg for successful intubation. 15-19 Although gestational age (GA) and postnatal age (PNA) are important determinants of propofol pharmacokinetics, 20 fixed propofol starting doses are often used for the entire neonatal population regardless of GA and PNA. The Exploratory Propofol Dose-Finding Study in Neonates (NEOPROP) is the only available dose-finding study in newborns that recently determined the effective propofol dose in 50% of patients (EC 50 ) for three different GA groups. This study also showed a great decrease in mean arterial blood pressure and a 62% incidence of hypotension. 21 It is crucial to find propofol doses that are safe and effective in the entire newborn population. Therefore, we performed the NEOPROP-2 trial, which aimed to find age- specific propofol starting doses that provide effective sedation without side effects in neonates. METHODS Study design and setting Aprospectivemulticenter dose-finding studywas conducted at three level III NICUs in the Netherlands between July 2014 and January 2018. An interim analysis was planned after every 6 months of inclusion, by an independent data and safety monitoring committee. The parents of all included patients provided written informed consent. Participants Neonates were eligible if they had a PNA <28 days and required non-emergency endotracheal intubation. Exclusion criteria were major congenital anomalies or neurological disorders, upper airway anomalies, sedative or opioid administration in the