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High-dose thiopental pharmacokinetics in brain-injured children and neonates
Insights
High-dose thiopental pharmacokinetics in children and neonates show prolonged elimination half-lives and large volumes of distribution. These findings highlight the potential for thiopental accumulation and toxicity during extended treatment periods.
Area of Science:
- Pharmacology
- Pediatric Critical Care
Background:
- High-dose thiopental is used for refractory seizures and hypoxic encephalopathy in children and neonates.
- Understanding thiopental pharmacokinetics is crucial for optimizing its use and minimizing toxicity in vulnerable populations.
Purpose of the Study:
- To analyze the pharmacokinetic profile of high-dose thiopental in children and neonates.
- To compare thiopental pharmacokinetics between children with various conditions and neonates with asphyxia.
Main Methods:
- Pharmacokinetic analysis of plasma concentration-time data from 8 children and 7 neonates receiving high-dose thiopental infusions.
- Artificial hyperventilation and controlled rectal temperature were maintained during treatment.
Main Results:
- Thiopental elimination half-life was 14.5 h in children and 20.9 h in neonates.
- Clearance was 0.27 L/h/kg in children and 0.32 L/h/kg in neonates.
- Volume of distribution at steady-state was 5.41 L/kg in children and 8.26 L/kg in neonates, with elimination half-life and volume of distribution differing from single-dose studies.
Conclusions:
- High-dose thiopental pharmacokinetics in neonates and children are similar to adults.
- Prolonged elimination half-life and large volume of distribution necessitate careful consideration of accumulation and toxicity risks with extended thiopental use.
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.