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 pCO2 near 3.5 kPa. Rectal temperature was kept at about 35 degrees C. Thiopental was infused with a rate of 2-4 mg X h-1 X 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 X h-1 X kg-1 (group A) and 0.32 liters X h-1 X kg-1 (group B). The volume of distribution at steady-state was 5.41 liters X kg-1 (group A) and 8.26 liters X kg-1 (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.