Propofol for endotracheal intubation in neonates: a dose-finding trial

Abstract

ObjectiveTo find propofol doses providing effective sedation without side effects in neonates of different gestational ages (GA) and postnatal ages (PNA).Design and settingProspective multicentere dose-finding study in 3 neonatal intensive care units.PatientsNeonates with a PNA <28 days requiring non-emergency endotracheal intubation.InterventionsNeonates 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 measuresThe primary outcome was the optimal single propofol starting dose that provides effective sedation without side effects in each age group.ResultsAfter inclusion of 91 patients, the study was prematurely terminated because the primary outcome was only reached in 13% of patients. Dose-finding was 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 analyses showed that GA and PNA did not predict effective sedation or the occurrence of hypotension.ConclusionsEffective sedation without side effects is difficult to achieve with 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.

Propofol in neonates causes a dose‐dependent profound and protracted decrease in blood pressure

“…15,17 Finally, MBP below 30 mm Hg is used to define hypotension, because some studies found loss of cerebral autoregulation below this threshold. 16,18,19 In our study and in the study of Smits et al, 13,14 were not as haemodynamically stable as they were presumed to be.…”

“…Neonates from the previously published NEOPROP‐2 trial were considered for inclusion 14 . The NEOPROP‐2 trial was a prospective multicentre dose‐finding trial conducted at three level III Neonatal Intensive Care Units in the Netherlands.…”

“…Neonates from the previously published NEOPROP-2 trial were considered for inclusion. 14 The haemodynamic status and risk of haemodynamic insufficiency were judged by the attending physician. If the attending physician judged the patient to be haemodynamically stable enough to receive propofol, the patient could be included in the trial.…”

“…In our recently performed propofol dose‐finding trial (NEOPROP‐2), we showed that propofol starting doses of 1.0 and 1.5 mg/kg were less effective in providing effective sedation compared to a propofol starting dose of 2.0 mg/kg. However, independent of the starting dose, propofol carried an unpredictable high risk of hypotension 14 …”

“…However, independent of the starting dose, propofol carried an unpredictable high risk of hypotension. 14 The aim of the current study was to further analyse the effects of different propofol starting doses on blood pressure. With this indepth analysis of the effects of propofol on blood pressure, we aimed to provide guidelines for the use of propofol in clinical practice.…”