Abstract

To investigate the safety and side effects of prolonged treatment with high-dose phenobarbital in patients suffering from acute encephalitis with refractory, repetitive partial seizures (AERRPS), 5 AERRPS patients meeting the Sakuma’s criteria were recruited from July 2003 to September 2008. During the treatment with high-dose phenobarbital, the blood pressure, heart rate, cardiac rhythm, respiratory rate, blood gas, skin conditions, state of consciousness, pupil size, seizures and long-range electroencephalogram were monitored. After intravenous bolus injection of phenobarbital (200 mg) or intramuscular infection of phenobarbital for induction, and then phenobarbital was intravenously administrated at 1 to 1.5 mg/kg/h or intramuscularly given (200 mg) (or intravenous bolus injection) q 2 to 4 h to maintain plasma concentrations. The daily overall dose of phenobarbital was 1.2 to 2.4 g. The serum level of phenobarbital reached 100 μg/ml within 24 h and remained for 24 d to 100 d. Follow up was carried out for at least 6 months. During the treatment of high dose phenobarbital, these 5 patients were in coma and the scores of Glasgow coma scale were 3 to 5. The brainstem reflex was mostly preserved and the spontaneous breathing was absent. The side effects in the circulation system included arrhythmia and hypotension. Sinus tachycardia (n = 3) and ventricular/supraventricular tachycardia (n = 2) were controlled by amiodarone, and the blood pressure was decreased by 40 to 55/64 to 86 mmHg (n = 2) which resolved after dopamine treatment (5 to 10 μg/kg/min). Liver injury was evident and observed in all 5 patients. The serum levels of alanine aminotransferase, aspartate aminotransferase and γ glutamyl transferase was 57 to 385 IU/L, 38 to 365 IU/L and 54 to 542 IU/L, respectively. The maximal level of serum ammonia was 187 μg/dl. No yellow skin was observed, and the serum levels of direct and indirect bilirubin were normal. Skin reaction was mild and kidney function almost intact. When the serum level of phenobarbital was decreased to 50 μg/ml, the consciousness and spontaneous breathing recovered and side effects were nearly absent. It is indicated that severe side effects may occur during prolonged treatment with high-dose phenobarbital. When this strategy is necessary, assisted ventilation is recommended and side effects should be closely monitored.

Key words: Encephalitis, status epilepticus, phenobarbital, side effect. safety.