▪ Smits et al. 2016 study13
Neonates admitted to the University Hospitals Leuven were eligible for inclusion when a propofol i.v. bolus was administered for procedural sedation for (semi-)elective endotracheal intubation. Patients were included after parental written informed consent was obtained. Approval of the study protocol was granted by the ethical board of the University Hospitals Leuven, Belgium. Inclusion further requested the absence of sedatives or analgesics, except acetaminophen in the previous 24 hours and cardiovascular and hemodynamic stability (judged by the attending neonatologist). The propofol dose at start of the procedure, for each patient, was determined based on a dose-finding approach13. Additional up-titration of the dose was allowed based on clinical need. The initial and total propofol dose ranges used in the study were 0.5-2 mg kg-1 and 0.5-4.5 mg kg-1 respectively13. Blood samples for propofol quantification were collected at 3 h and/or 12 h after propofol administration. Samples (300-600 µL) were collected from an arterial line if present, or venous puncture. The total blood volume sampled in every neonate was limited to 1 mL kg-1. Propofol quantification occurred by a sensitive HPLC-fluorescence method developed and validated for small volumes. Intra- and inter-day accuracy and precision were below 15%, and a LLOQ of 0.0069 µg mL-1 was calculated. A detailed description of the bioanalysis protocol has been published by Qi et al.16.