Several factors influence treatment in neonates: (1) variations in the metabolic half-lives of drugs, (2) associated etiologic conditions (e.g., hypoxia prolongs the half-life of many drugs and may affect the renal or gastrointestinal clearance rate), and (3) greater difficulty in identifying the end point of seizure control in neonates.

Effective seizure control is obtained by rapidly achieving therapeutic blood levels of the anticonvulsant chosen. Newborns have different rates of metabolism and excretion of anticonvulsants from older infants and children. In infants younger than 7 days of age, the half-life of phenobarbital, the drug of first choice, is 100 h and, after 28 days of continuous therapy, the half-life of the drug is reduced to 60 to 70 h.

In the presence of hypoxia with tissue acidosis and associated renal and hepatic dysfunction, anticonvulsant half-lives may be increased, with therapeutic and toxic levels achieved more readily, and requiring lower dose and less frequent administration of AEDs.

Blood levels of phenobarbital of 16 to 40 pg/mL are necessary to achieve seizure control in the majority of cases. Levels of 40 to 80 pg/mL have been maintained in resistant cases with inconsistent benefit. Dosages of phenobarbital of 3 to 4 mg/kg/day maintain mid to high therapeutic levels and prevent toxicity.

Phenytoin is the second drug of choice in treating neonatal seizures. Fosphenytoin is well tolerated in neonates and can be used for induction and maintenance therapy without the problems associated with phenytoin administration. Loading doses of fosphenytoin are 15 to 20 mg PE/kg at 3 mg PE/kg/min with IV maintenance of 4 to 8 mg PE/kg/day. When converting to oral dosage of phenytoin, 8 to 12 mg/kg/day is typically required. Free phenytoin levels up to 2.2 pg/mL may be necessary for adequate seizure control.

Pyridoxine (vitamin B6) 100 mg/day is empirically used when no reasonable cause for seizures has been identified and the seizures remain uncontrolled. Seizure reduction rather than EEG improvement is the best indication of B 6 response, Biotin 10 mg/day is the long-term replacement therapy for biotinidase deficiency.

In status epilepticus of neonates, diazepam or lorazepam must be used with caution, since its half-life may be prolonged, and respiratory depression superimposed on an immature and possibly compromised respiratory apparatus should be anticipated. Diazepam may exaggerate hyperbilirubinemia by uncoupling the bilirubin-albumin complex and should be used with caution in jaundiced babies.

Treatment principles in the management of neonatal seizures are as follows:

1. Identify and correct treatable causes (hypocalcemia, hypoglycemia, and electrolyte imbalance).

2. Identify and treat associated problems such as sepsis, hyperbilirubinemia, and acidosis.

3. Initiate anticonvulsant therapy with appropriate loading doses, and carefully observe blood levels to adjust the maintenance dosage ( Table 121-6).

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