High-Dose Thiopental Pharmacokinetics in Brain-Injured Children and Neonates

Abstract

High-dose thiopental was administered in 8 children with uncontrollable seizures or hypoxic encephalopathy (group A) and 7 full-term neonates with neonatal asphyxia (group B), All of them were submitted to artificial hyperventilation to maintain pCO(2) near 3.5 kPa. Rectal temperature was kept at about 35 °C. Thiopental was infused with a rate of 2-4 mg^-1-kg^-1, with treatment lasting 32-192 h for group A (mean 103 h), and 36-48 h for group B (mean 38.5 h). Plasma concentration-time data were analysed pharmacokinetically. Thiopental elimination half-life was 14.5 h (group A) and 20.9 h (group B). The clearance of thiopental was 0.27 liters × h^-1 -kg"1 (group A) and 0.32 liters × h^-1 × kg-1 (group B). The volume of distribution at steady-state was 5.41 liters-kg 1 (group A) and 8.26 liters-kg-' (group B). These results show that high-dose thiopental pharmacokinetics is not very different for full-term newborns, children and adults. Elimination half-life and volume of distribution are changed when compared to single-dose studies, while clearance is only slightly modified. The time for disappearance of thiopental from blood is also very long (2 to 5 days). These pharmacokinetic characteristics would be worthy of consideration in cases where there may be prolonged use of thiopental, considering the risk of accumulation and toxicity.

Early Postnatal Seizures in a Neonate with Wolf–Hirschhorn Syndrome

“…However, in 2003, another study on WHS showed that neonates aged between 1 day and <1 month had tonicclonic seizures and were treated with phenobarbital. 8 Thus, seizure onset in WHS can occur in the neonatal period; however, to our knowledge, this is the first case report on early postnatal seizures in a neonate with WHS.…”

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…”

Pharmacological sedation management in the paediatric intensive care unit

“…Like pentobarbital, thiopental is a suitable agent for patients with raised intracranial pressure. PK and PD studies have been rarely performed in children, and most of them date from the 1980s . Despite a reported double clearance compared to adults, doses do not need to be doubled .…”