▪ 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.