Placental transfer and pharmacokinetics of thiopentone in newborn infants

Abstract

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.

Rapid Sequence Induction is Superior to Morphine for Intubation of Preterm Infants: A Randomized Controlled Trial

“…7 We have studied postnatal pharmacokinetics and pharmacodynamics of thiopental, and found it suitable even for extremely preterm infants. 25,34 Recently propofol, a short-acting sedative, has been suggested for newborns, since it provided good intubation conditions without muscle relaxants in a RCT. 28 However, in preterm infants, significant cerebral and systemic hypotensive effects may occur.…”

Thiopentone elimination in newborn infants: exploring Michaelis-Menten kinetics

“…This current analysis differs from the earlier analysis 19 in that size was standardized using allometric models a priori in order to investigate the other covariates of PNA, PMA and sex. A great many physiological‐, structural‐ and time‐related variables scale predictably within and between species with weight exponents of 0.75, 1 and 0.25, respectively.…”

“…The Regional Ethics Committee in Southern Sweden approved the research. Time–concentration data for this first‐order and Michaelis–Menten elimination study were obtained from patients included in two previous reports 18,19 . Data from 30 neonates [27.9–42 weeks post‐menstrual age (PMA), 1.5–3.9 kg] given thiopentone at a median age of 24.5 h after birth [post‐natal age (PNA)] for induction of anaesthesia 19 were combined with those from a further seven neonates (26–45 weeks PMA, 0.6–3.5 kg) reported in an investigation of a neonate given an accidental overdose 18 .…”

“…Time–concentration data for this first‐order and Michaelis–Menten elimination study were obtained from patients included in two previous reports 18,19 . Data from 30 neonates [27.9–42 weeks post‐menstrual age (PMA), 1.5–3.9 kg] given thiopentone at a median age of 24.5 h after birth [post‐natal age (PNA)] for induction of anaesthesia 19 were combined with those from a further seven neonates (26–45 weeks PMA, 0.6–3.5 kg) reported in an investigation of a neonate given an accidental overdose 18 . The larger data set included approximately six blood samples per neonate taken at 5, 10, 20 min, 6, 12 and 24 h while that for the additional seven neonates comprised 23 irregularly timed samples over 12 h. The overdose index neonate rendered four samples at 20 min, 6, 12 and 68 h. Full details are available from the original publications 18,19 …”

“…A recent case report of a thiopentone overdose administered to a neonate showed elimination over a 72‐h period that did not demonstrate the typical exponential decay associated with first‐order elimination 18 . Time–concentration profiles for this index patient and others reported after single‐dose administration were examined using both first‐order and Michaelis–Menten elimination 18,19 . We aimed to use the extended data set to investigate if elimination could be satisfactorily described using Michaelis–Menten elimination, if clearance or maximum rate of metabolism ( V max ) increased with age and if pharmacokinetic differences between adult and neonate might elucidate observed sedation effects from thiopentone.…”