Phenytoin prophylaxis in severe pre-eclampsia and eclampsia.
OBJECTIVE
To determine plasma phenytoin levels and seizure outcome in women given phenytoin for seizure prophylaxis in severe pre-eclampsia and eclampsia.


METHODS
Prospective observational study comparing two phenytoin loading regimens.


METHODS
Two UK teaching hospitals.


METHODS
Sixty-seven consecutive women with severe pre-eclampsia and five with eclampsia.


METHODS
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.


METHODS
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.
Robson
S C
SC
RPMS Institute of Obstetrics & Gynaecology, Queen Charlotte's and Chelsea Hospital, London.
Redfern
N
N
Seviour
J
J
Campbell
M
M
Walkinshaw
S
S
Rodeck
C
C
de Swiet
M
M
D000328:Adult; D004305:Dose-Response Relationship, Drug; D004461:Eclampsia / Q000097:blood / Q000517:prevention & control*; D005260:Female; D006801:Humans; D010672:Phenytoin / Q000009:adverse effects / Q000097:blood / Q000627:therapeutic use*; D011225:Pre-Eclampsia / Q000097:blood / Q000517:prevention & control; D011247:Pregnancy; D011446:Prospective Studies; D012640:Seizures / Q000517:prevention & control
D010672:Phenytoin