Ellen de Kort

ABSTRACT Objective: To find propofol doses providing effective sedation without side effects in neonates of different gestational ages (GA) and postnatal ages (PNA). Design and setting: Prospective multicenter dose-finding study in 3 neonatal intensive care units. Patients: Neonateswith a PNAless than 28days requiringnon-emergencyendotracheal intubation. Interventions: Neonates were stratified into 8 groups based on GA and PNA. The first 5 neonates in every group received a dose of 1.0 mg/kg propofol. Based on sedative effect and side effects, the dose was increased or decreased in the next 5 patients until the optimal dose was found. Main outcome measures: The primary outcome was the optimal single propofol starting dose that provides effective sedation without side effects in each age group. Results: After inclusion of 91 patients, the studywas prematurely terminated because the primary outcomewas only reached in 13% of patients. Dose-findingwas completed in 2 groups, but no optimal propofol dose was found. Effective sedation without side effects was achieved more often after a starting dose of 2.0 mg/kg (28%) than after 1.0 mg/kg (3%) and 1.5 mg/kg (9%). Propofol-induced hypotension occurred in 59% of patients. Logistic regression analysis showed that GA and PNAdid not predict effective sedation or the occurrence of hypotension. Conclusions: Effective sedationwithout side effects is difficult to achievewith propofol and the optimal dose in different age groups of neonates could not be determined. The sedative effect of propofol and the occurrence of hypotension are unpredictable and show large inter-individual variability in the neonatal population.