▪ Allegaert et al., 2007 study8
Patients underwent elective chest tube removal, (semi-)elective chest tube placement or endotracheal intubation. Approval of the study protocol was granted by the local ethical board of the University Hospital Gasthuisberg, Leuven, Belgium. Patients were included after parental written informed consent was obtained. Inclusion criteria were the availability of the arterial line for sequential blood sampling and cardiovascular and respiratory stability (judged by the attending neonatologist). GA, PNA, PMA, body weight (BW), length and serum creatinine were registered upon inclusion. Propofol was administered for sedation prior to the medical procedure. Propofol (3 mg kg-1) was administered once as an i.v. bolus infused over 10 seconds. In addition, patients received either continuous fentanyl or tramadol or intermittent acetaminopheni.v. infusions 14. Analgesic therapy was titrated based on systematic evaluation of pain during the neonatal stay and was not standardized14. Arterial blood samples were collected 1, 5, 15, 30, 60, 90, 120, 240, 480, 720 and 1440 min after propofol administration. The total arterial blood volume sampled per individual neonate was limited to 1.8 mL kg-1. The bioanalytical method was performed on whole blood using high-performance liquid chromatography (HPLC) with a fluorescence detector. Linearity was found for standard curves of propofol in whole blood in the range of 0.02–20 µg mL-1. Intra- and inter-day coefficients of variation were lower than 15%. The lower limit of quantification (LLOQ), determined as the lowest concentration with a coefficient of variation lower than 20%, was 0.02 µg mL-1. A detailed description of the bioanalysis was published by Allegaert et al8.
Sepúlveda et al, 2011 study12
Infants were admitted for cleft lip and cleft palate surgery. Approval of the study protocol was granted by the institutional ethics committee of the School of Medicine, Clínica Alemana, Santiago, Chile. Infants were included after parental written informed consent was obtained. Inclusion criteria were American Society of Anesthesiologists (ASA) I or II status, absence of respiratory, renal, hepatic or endocrine dysfunction and no familial or personal history of allergic reaction to propofol or any of its formulation constituents. Age, BW and length were registered upon inclusion. GA was imputed to 38 weeks for this study only, due to absence of this covariate. Propofol was administered for the indication of generalized anesthesia. An i.v. bolus dose of propofol 2.5 mg kg-1 was administered with subsequenti.v. continuous infusion of propofol 8 mg kg-1h-1 maintained throughout the surgery. Anesthesia was induced using sevoflurane 6% in oxygen. Sevoflurane administration was terminated after securing the airway with a tracheal tube to allow for mechanical ventilation. Children received remifentanil infusion at an initial rate of 0.2 μg kg-1 min-1. Remifentanil infusion rate was adjusted during surgery to maintain immobility and hemodynamic stability. Arterial blood samples were collected 1, 2, 3, 5, 10, 20 and 60 min after i.v. bolus injection, at the moment of discontinuation of the propofol infusion (end of the surgery) and at 1, 3, 5, 30, 60, 120 min thereafter. Arterial blood samples of 2 mL were collected. The bioanalysis method was performed on blood plasma using HPLC with a fluorescence detector using a method described by Seno et al.15. Linearity was found for standard curves of plasma propofol in the range of 0.1–10 µg mL-1. Intra- and inter-day coefficients of variation were lower than 10%. The LLOQ was 0.1 µg mL-1.