Phenytoin prophylaxis in severe pre-eclampsia and eclampsia

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Abstract
Objective To determine plasma phenytoin levels and seizure outcome in women given phenytoin for seizure prophylaxis in severe pre‐eclampsia and eclampsia. Design Prospective observational study comparing two phenytoin loading regimens. Setting Two UK teaching hospitals. Subjects Sixty‐seven consecutive women with severe pre‐eclampsia and five with eclampsia. Interventions The first 29 women were given a 15 mg/kg intravenous loading dose of phenytoin. The next 43 received 17.5 mg/kg. All were given 500 mg phenytoin 12 h after completion of the loading dose and then 250 mg every 12 h for four doses. Main outcome measures Total plasma phenytoin levels at 30 min, 6 h and 12 h after loading dose, 6 h after first maintenance dose and on days 2 and 3 of maintenance therapy; eclamptic seizures after starting phenytoin. Results Mean plasma phenytoin levels were higher at 30 min and 6 h after the 17.5 mg/kg loading dose. Nine of 29 (31%) phenytoin levels 30 min after the loading dose were above the therapeutic range in the 15 mg/kg group compared with 26/38 (68%) in the 17.5 mg/kg group (P<0.01). Six of 27 (22%) phenytoin levels 12 h after the loading dose were subtherapeutic in the 15 mg/kg group compared with 2/38 (5%) in the 17.5 mg/kg group (P<0.05). Three women, two in the 17.5 mg/kg group, developed seizures after starting phenytoin. All three had plasma levels within the therapeutic range. Conclusions Compared with a loading dose of 17.5 mg/kg, loading with 15 mg/kg phenytoin was associated with a lower incidence of high plasma levels at 30 min but a higher incidence of subtherapeutic levels at 12 h. Seizures occur in 2 to 3% of pre‐eclamptics despite apparently therapeutic phenytoin levels.

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