Placental transfer and pharmacokinetics of thiopentone in newborn infants

Abstract

Background and Objectives Thiopentone, a short-acting barbiturate, has been introduced as premedication for intubation in newborn infants. The objectives of this study were to assess the pharmacokinetics of thiopentone in newborn infants, and to unravel whether placental transfer of the drug should be taken into account if administered to infants exposed to it during delivery.

Methods Plasma concentrations were assessed with high-pressure liquid chromatography in samples from delivering mothers (n=27) receiving a median dose of 5.5 mg/kg (range 3.8–7.7) thiopentone for Caesarean section in gestational week 37.6 (range 25.7–41.4) and from corresponding umbilical cord blood (n=28). In infants (n=30) born at 35.4 weeks gestation (range 27.9–42.0) undergoing surgery at a median postnatal age of 24.5 h (range 4–521), repeated blood levels were assessed after administering a dose of 3 mg/kg thiopentone on clinical indication before intubation (seven samples per infant from 5 min to 48 h after administration).

Results The umbilical/maternal concentration ratio was 0.7, the mean concentration of thiopentone was 55.7 µmol/l (SD±15.3) in mothers and 39.3 µmol/l (SD±12.5) in venous cord blood. In newborn infants undergoing surgery, the terminal half-life of thiopentone was 8 h (interquartile range (IQR) 2.5–10.8), and clearance 0.092 l/min per kg/postnatal age in days (IQR 0.02–0.1).

Conclusions Thiopentone might be used as premedication for short-lasting intubation after birth, for example, for surfactant administration. During the first 4 h after birth the dose needs to be adjusted for maternal dosage as well as for the weight of the infant.