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DOSE-FINDING STUDY AND PHARMACODYNAMIC ASSESSMENT OF PROPOFOL FOR (SEMI-)ELECTIVE INTUBATION IN NEONATES
  1. Anne Smits1,
  2. Liesbeth Thewissen1,
  3. Alexander Caicedo2,
  4. Johan Nicolaï3,
  5. Pieter Annaert3,
  6. Gunnar Naulaers1,
  7. Karel Allegaert1
  1. 1Neonatal Intensive Care Unit, University Hospitals Leuven, Belgium
  2. 2Department of Electrical Engineering (ESAT), STADIUS Center for Dynamical Systems, Signal Processing and Data Analytics, KU Leuven, Belgium
  3. 3Drug Delivery and Disposition, Department of Pharmaceutical and Pharmacological Sciences, KU Leuven, Belgium

Abstract

Introduction The optimal propofol dose and its safety for procedural sedation in neonates is controversial. The aim of this study was to perform a prospective propofol dose-finding study with pharmacodynamic (PD) assessment during (semi-)elective intubation in neonates.

Methods Patients were stratified in 4 groups by postmenstrual and postnatal age. The first patient in each group received 1 mg/kg intravenous propofol bolus. Dosing for the next patient was determined using the up-and-down method. Propofol ED50 doses [effective dose for successful intubation (as well as extubation in INSURE -intubation, surfactant, extubation-cases) in 50% of patients] were calculated, with simultaneous assessment of clinical scores, continuous vital sign monitoring and propofol blood concentrations (3 and 12h after dosing).

Results Thirty-five neonates (weight 540–3290 g) were included. Using initial and total propofol dose ranges of 0.5–2 and 0.5–4.5 mg/kg respectively, median propofol ED50 range for preterm neonates <10 days was 0.480–1.287 mg/kg. Clinical recovery was not attained at the end of the scoring period (21 minutes). A median decrease in mean arterial blood pressure (MABP) between −29.41% and −39.09% from baseline, and a short-lasting decrease in peripheral (SaO2) and regional cerebral (rScO2) oxygen saturation was documented. Variability in MABP, SaO2 and rScO2 was not explained by weight, age or propofol concentrations.

Conclusions Low propofol doses sufficiently sedate neonates for intubation, but clinical recovery takes time and is accompanied by permissive hypotension. Propofol ED50 doses are provided and need integration in a prospective validation approach. Finally, feasibility of continuous monitoring for neonatal pharmacodynamic research was demonstrated.

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