Pharmacokinetics of Thiopental in the Asphyxiated Neonate

Abstract

The pharmacokinetic properties of thiopental were studied in 10 asphyxiated neonates (mean ± SE; birth weight, 3,244 ± 212 g; gestational age, 40 ± 1 weeks) as part of a randomized, controlled trial which tested the ability of barbiturate therapy to decrease central nervous system damage secondary to perinatal asphyxia. Therapy was begun at a mean age of 2.3 h in all and was initially given as a loading dose of 15 mg/kg over 30 min followed by a constant infusion. The mean steady-state thiopental concentration was 13.4 ± 3.7 μg/ml (mean ± SD) and the average time to reach steady state was 7 ± 5 h. Mean elimination half-life, plasma clearance and volume of distribution for thiopental were 39 h (range 26-70), 66 ml/(h × kg) (range 31-172), and 3.6 liters/kg (range 1.1-6.7), respectively. Arterial blood pressure support was required in 8 of 10 patients. While it appears feasible to give thiopental to the asphyxiated neonate at the reported infusion rates, the risk-benefit ratio is increased by the frequent associated hypotension and need for pharmacologic blood pressure support.

Maturational pharmacokinetics of single intravenous bolus of propofol

“…Propofol is a highly lipophylic compound and therefore exhibits rapid distribution from blood into subcutaneous fat and the central nervous system – where it exerts its pharmacodynamic effects – with subsequent redistribution. Propofol has these distributive properties in common with other drugs such as thiopental (1–5,8,17,18). It is therefore useful to compare the present observations on maturational aspects of propofol disposition with pharmacokinetic observations on thiopental (Table 3).…”

“…Median propofol clearance in neonates was 442 (range 97–2185) ml·min −1 ·70 kg −1 or approximately 25% of adult clearance with a fast maturation to clearance at an adult level in toddlers (1–3 years) (10,11). Median thiopental clearance (ml·min −1 ·70 kg −1 ) in asphyxiated neonates was 10–15% of adult clearance (ml·70 kg −1 ·min −1 ) while clearance was already at adult levels in young children (5 months–13 years) (17,18). It is not unlikely that the associated asphyxia further contributed to the relatively more pronounced reduction in thiopental clearance in neonates (17).…”

“…Median thiopental clearance (ml·min −1 ·70 kg −1 ) in asphyxiated neonates was 10–15% of adult clearance (ml·70 kg −1 ·min −1 ) while clearance was already at adult levels in young children (5 months–13 years) (17,18). It is not unlikely that the associated asphyxia further contributed to the relatively more pronounced reduction in thiopental clearance in neonates (17).…”

Thiopental Efficacy in Phenobarbital-Resistant Neonatal Seizures

“…The low total administered thiopental dose and the different schedule compared to previous reports concerning thiopental utilization in neonates [15,16] and children [17] (10-15 mg/kg loading dose followed by a maintain ing infusion of 0.75-5 mg/g/h) avoid the major side effects (severe hypotension and quicker and shorter lasting, so that, if necespharmacodynamic tolerance) related to this sary, it can be administered again (as de scribed here for 1 newborn) with less risk of…”

Placental transfer and pharmacokinetics of thiopentone in newborn infants

“…In a study published in 1988 on thiopentone administrated over 24 h as neuroprotective treatment to 10 asphyxiated newborn infants, the half-life and clearance varied considerably from 26 to 70 h and from 31 to 172 ml/h per kilogram, respectively 41. Asphyxia should thus also be taken into account when administering thiopentone soon after birth.…”