RESUMEN
The specific timing of maintenance phenytoin therapy in children has not been addressed. Prevention of a subtherapeutic phenytoin level is important for seizure control. We devised a protocol using an 18 mg/kg loading dose of phenytoin with serial levels (obtained after 2,6,12 hours) and analyzed the results in 20 consecutive patients. A therapeutic level (greater than 10 micrograms/ml) was present in all patients at 2 hours, in 16 of 20 at 6 hours, and in 10 of 20 at 12 hours. The patients were divided into 2 groups by the 12-hour levels: group I: therapeutic level; and group II: subtherapeutic level. The mean 2-hour level in group I was 22.7 micrograms/ml versus 15.6 micrograms/ml in group II (P less than 0.001). The mean decline in plasma concentration in individual patients was 0.7 micrograms/ml/hr in group I versus 1.02 micrograms/ml/hr in group II (P less than 0.05). We now use the 2-hour level to decide the timing of maintenance phenytoin therapy and have devised an equation to estimate the duration of the therapeutic range. Phenytoin can be administered at 12 hours when the 2-hour level is satisfactory or earlier when the 2-hour level indicates that a subtherapeutic level will occur.
Asunto(s)
Fenitoína/administración & dosificación , Convulsiones/tratamiento farmacológico , Estado Epiléptico/tratamiento farmacológico , Adolescente , Niño , Preescolar , Esquema de Medicación , Humanos , Lactante , Infusiones Intravenosas , Fenitoína/sangre , Fenitoína/uso terapéuticoRESUMEN
Primidone can be used for seizures refractory to standard antiepileptic drugs. We administered primidone, 25 mg/kg/day in 3 divided doses, to 10 patients and obtained serum levels of primidone, phenobarbital, and phenylethylmalonic acid at 1, 2, 4, 6, and 8 hours on day 1, alternate days until discharge, and after 6 weeks. Other antiepileptic drugs were discontinued in 8 of 10 patients with refractory seizures. Mean primidone levels were 10.6 +/- 4.4 micrograms/ml by day 3 and remained stable until discharge. Phenylethylmalonic acid was detected by 6 hours and increased to 11.1 +/- 4.0 micrograms/ml by day 7. Phenobarbital levels in 3 of 10 patients not previously treated with phenobarbital ranged from 0.6-3.4 micrograms/ml by day 5. The mean initial phenobarbital level was 30.1 +/- 10.5 micrograms/ml and had decreased to less than 15 micrograms/ml by day 7. Seizure control occurred within 5 days in 8 of 10 patients and was achieved by day 3 in 6 of 8 patients, coinciding with primidone levels greater than 10 micrograms/ml. No toxic effects of primidone were observed. All levels decreased during subsequent examinations suggesting auto-induction of metabolic systems. Our data indicate that seizure control is best correlated with primidone and phenylethylmalonic acid levels and unrelated to phenobarbital levels in this age group.
Asunto(s)
Enfermedades del Recién Nacido/tratamiento farmacológico , Primidona/uso terapéutico , Convulsiones/tratamiento farmacológico , Relación Dosis-Respuesta a Droga , Humanos , Recién Nacido , Fenobarbital , Primidona/efectos adversosRESUMEN
The hypercarbia stimulation test is a valuable technique to document the absence of brainstem responsiveness to elevated levels of carbon dioxide (PCO2); however, its application has been limited by concern that hypoxemia may induce cardiovascular instability. We investigated hemodynamic and oxygen (PO2) changes in 19 patients: group 1 (17 patients) had no spontaneous ventilations at PCO2 values ranging from 37-129 torr; group 2 (2 patients) had spontaneous ventilations at less than 38 torr. Group 1 was separated into 2 subgroups: A (10 patients) with PO2 greater than 153 torr and B (7 patients) with PO2 less than 80 torr. Hemodynamic changes (less than 10% variation in baseline pulse and blood pressure) occurred in 9 of 10 patients in group 1A and all patients in Group 1B. Mean differences in pulse and blood pressure changes between these groups were not significant; therefore, pulse and blood pressure changes are not predictive of hypoxemia and hypercarbia is not necessary to induce spontaneous ventilation in patients with intact medullary function.