Add-on phenytoin fails to prevent early seizures after surgery for supratentorial brain tumors: a randomized controlled study.
OBJECTIVE
To determine the potential effectiveness of phenytoin (PHT) in preventing early postoperative seizures in patients undergoing craniotomy for supratentorial brain tumors.


METHODS
Two hundred patients requiring elective craniotomy for supratentorial brain tumors were randomized to two groups of equal size, with a prospective, open-label, controlled design. One group received PHT (18 mg/kg as an intravenous intraoperative load, followed by additional daily doses aimed at maintaining serum PHT concentrations within the 10- to 20-aeg/ml range) for 7 consecutive days. In the other group, PHT was not administered. More than 90% of patients in both groups continued to take preexisting anticonvulsant medication (AEDs) with carbamazepine or phenobarbital throughout the study. The primary efficacy end point was the number of patients remaining free from seizures during the 7-day period after the operation.


RESULTS
Of 100 patients allocated to PHT, 13 experienced seizures during the 7-day observation period, compared with 11 of 100 patients in the placebo group (p > 0.05). Most seizures occurred in the first day after surgery in both groups. There were no differences between groups in the proportion of patients experiencing more than one seizure, but there was a trend for generalized seizures to be more common in PHT-treated patients than in controls (11 vs. five patients, respectively). Status epilepticus occurred in one patient in the PHT group and in two patients in the control group. Of the 13 PHT-treated seizure patients, 11 had serum PHT concentrations within the target range, and only two had concentrations below range on the days their seizures occurred.


CONCLUSIONS
PHT, given at dosages producing serum concentrations within the target range, failed to prevent early postoperative seizures in patients treated with concomitant AEDs. Prophylactic administration of PHT cannot be recommended in these patients.
De Santis
Antonio
A
Institute of Neurosurgery, Policlinico IRCCS, University of Milan, Italy.
Villani
Roberto
R
Sinisi
Marco
M
Stocchetti
Nino
N
Perucca
Emilio
E
D000293:Adolescent; D000328:Adult; D000368:Aged; D000927:Anticonvulsants / Q000008:administration & dosage / Q000009:adverse effects / Q000097:blood / Q000627:therapeutic use*; D002220:Carbamazepine / Q000627:therapeutic use; D002528:Cerebellar Neoplasms / Q000188:drug therapy* / Q000601:surgery*; D003399:Craniotomy / Q000009:adverse effects; D005260:Female; D006801:Humans; D015994:Incidence; D007430:Intraoperative Care; D008297:Male; D008875:Middle Aged; D010634:Phenobarbital / Q000627:therapeutic use; D010672:Phenytoin / Q000008:administration & dosage / Q000009:adverse effects / Q000097:blood / Q000627:therapeutic use*; D011182:Postoperative Care; D012307:Risk Factors; D012640:Seizures / Q000097:blood / Q000453:epidemiology / Q000209:etiology / Q000517:prevention & control*
D000927:Anticonvulsants; D002220:Carbamazepine; D010672:Phenytoin; D010634:Phenobarbital