Document Detail


A prospective randomized trial of perioperative seizure prophylaxis in patients with intraparenchymal brain tumors.
MedLine Citation:
PMID:  23394340     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
OBJECT: Seizures are a potentially devastating complication of resection of brain tumors. Consequently, many neurosurgeons administer prophylactic antiepileptic drugs (AEDs) in the perioperative period. However, it is currently unclear whether perioperative AEDs should be routinely administered to patients with brain tumors who have never had a seizure. Therefore, the authors conducted a prospective, randomized trial examining the use of phenytoin for postoperative seizure prophylaxis in patients undergoing resection for supratentorial brain metastases or gliomas.
METHODS: Patients with brain tumors (metastases or gliomas) who did not have seizures and who were undergoing craniotomy for tumor resection were randomized to receive either phenytoin for 7 days after tumor resection (prophylaxis group) or no seizure prophylaxis (observation group). Phenytoin levels were monitored daily. Primary outcomes were seizures and adverse events. Using an estimated seizure incidence of 30% in the observation arm and 10% in the prophylaxis arm, a Type I error of 0.05 and a Type II error of 0.20, a target accrual of 142 patients (71 per arm) was planned.
RESULTS: The trial was closed before completion of accrual because Bayesian predictive probability analyses performed by an independent data monitoring committee indicated a probability of 0.003 that at the end of the study prophylaxis would prove superior to observation and a probability of 0.997 that there would be insufficient evidence at the end of the trial to choose either arm as superior. At the time of trial closure, 123 patients (77 metastases and 46 gliomas) were randomized, with 62 receiving 7-day phenytoin (prophylaxis group) and 61 receiving no prophylaxis (observation group). The incidence of all seizures was 18% in the observation group and 24% in the prophylaxis group (p = 0.51). Importantly, the incidence of early seizures (< 30 days after surgery) was 8% in the observation group compared with 10% in the prophylaxis group (p = 1.0). Likewise, the incidence of clinically significant early seizures was 3% in the observation group and 2% in the prophylaxis group (p = 0.62). The prophylaxis group experienced significantly more adverse events (18% vs 0%, p < 0.01). Therapeutic phenytoin levels were maintained in 80% of patients.
CONCLUSIONS: The incidence of seizures after surgery for brain tumors is low (8% [95% CI 3%-18%]) even without prophylactic AEDs, and the incidence of clinically significant seizures is even lower (3%). In contrast, routine phenytoin administration is associated with significant drug-related morbidity. Although the lower-than-anticipated incidence of seizures in the control group significantly limited the power of the study, the low baseline rate of perioperative seizures in patients with brain tumors raises concerns about the routine use of prophylactic phenytoin in this patient population.
Authors:
Adam S Wu; Victoria T Trinh; Dima Suki; Susan Graham; Arthur Forman; Jeffrey S Weinberg; Ian E McCutcheon; Sujit S Prabhu; Amy B Heimberger; Raymond Sawaya; Xuemei Wang; Wei Qiao; Kenneth R Hess; Frederick F Lang
Publication Detail:
Type:  Journal Article; Randomized Controlled Trial; Research Support, Non-U.S. Gov't     Date:  2013-02-08
Journal Detail:
Title:  Journal of neurosurgery     Volume:  118     ISSN:  1933-0693     ISO Abbreviation:  J. Neurosurg.     Publication Date:  2013 Apr 
Date Detail:
Created Date:  2013-04-02     Completed Date:  2013-07-01     Revised Date:  2014-08-04    
Medline Journal Info:
Nlm Unique ID:  0253357     Medline TA:  J Neurosurg     Country:  United States    
Other Details:
Languages:  eng     Pagination:  873-83     Citation Subset:  AIM; IM    
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MeSH Terms
Descriptor/Qualifier:
Adolescent
Adult
Aged
Aged, 80 and over
Anticonvulsants / therapeutic use*
Bayes Theorem
Brain Neoplasms / surgery*
Craniotomy
Female
Glioma / surgery
Humans
Incidence
Kaplan-Meier Estimate
Male
Middle Aged
Perioperative Care*
Phenytoin / therapeutic use*
Prospective Studies
Seizures / epidemiology*,  prevention & control*
Supratentorial Neoplasms / surgery
Treatment Outcome
Young Adult
Grant Support
ID/Acronym/Agency:
P30 CA016672/CA/NCI NIH HHS
Chemical
Reg. No./Substance:
0/Anticonvulsants; 6158TKW0C5/Phenytoin
Comments/Corrections

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