Evaluation for Blood Concentration and Efficacy/Safety of Continuous Administration of Thiamylal in Children

Abstract

Background: Thiamylal exerts excellent sedative effects. However, it is not routinely used because of its serious adverse effects. This study aimed to clarify the target blood concentration range and infusion rate of thiamylal in children by measuring its blood concentration and evaluating its relationship with efficacy and adverse effects. Methods: This study was approved by the Ethics Committee of Japanese Red Cross Kumamoto Hospital. The authors included 10 children aged between 1 and 7 years who had received continuous intravenous (IV) infusion of thiamylal for the management of refractory status epilepticus, excluding those who met the exclusion criteria. After a 2 mg/kg bolus injection of thiamylal, continuous IV infusion was initiated at a rate of 2–3 mg/kg/h. Thiamylal concentration in the blood was measured using high-performance liquid chromatography. The State Behavioral Scale and the frequency of bolus injections were used to evaluate efficacy. Blood pressure and heart rate were measured to evaluate adverse effects. Statistical analyses of the time to awakening and the factors affecting it were also conducted. Results: The State Behavioral Scale score during thiamylal administration was −2 or lower in all cases, suggesting that the depth of sedation was sufficient. The frequency of bolus injections decreased in a blood concentration-dependent manner, suggesting that the frequency tended to decrease, especially at thiamylal blood concentrations of 20 mcg/mL or higher. An increase of the infusion rate to 3 mg/kg/h was recommended, because the blood concentration may not reach 20 mcg/mL at an infusion rate of 2 mg/kg/h. There was also a case in which a rapid increase in blood concentration accompanied by a decrease in blood pressure and heart rate was observed when the infusion rate was increased to 4 mg/kg/h. Furthermore, the time to awakening after the end of administration correlated with the highest blood concentration during administration; therefore, delayed awakening was noted when using a high dose of thiamylal. Conclusions: The target blood concentration of thiamylal in children should be 20–30 mcg/mL, and the infusion rate should be based on 3 mg/kg/h.