A randomized, double-blinded, placebo-controlled trial of phenytoin for the prevention of early posttraumatic seizures in children with moderate to severe blunt head injury - 25/08/11

Doi : 10.1016/j.annemergmed.2003.09.016

Kelly D. Young, MD ^a,^b,^g, Pamela J. Okada, MD ^d, Peter E. Sokolove, MD ^e, Michael J. Palchak, MD ^e, Edward A. Panacek, MD ^e, Jill M. Baren, MD ^f, Kenneth R. Huff, MD ^b,^g, Duncan Q. McBride, MD ^c,^g, Stanley H. Inkelis, MD ^a,^b,^g, Roger J. Lewis, MD, PhD ^a,^g,^⁎
^a Department of Emergency Medicine, Harbor-University of California–Los Angeles Medical Center, Torrance, CA, USA
^b Department of Pediatrics, Harbor-University of California–Los Angeles Medical Center, Torrance, CA, USA
^c Department of Neurosurgery, Harbor-University of California–Los Angeles Medical Center, Torrance, CA, USA
^d Department of Pediatrics, University of Texas Southwestern, Children's Medical Center of Dallas, Dallas, TX, USA
^e Department of Emergency Medicine, University of California–Davis Medical Center, Sacramento, CA, USA
^f Department of Emergency Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA, USA
^g University of California–Los Angeles School of Medicine, Los Angeles, CA, USA

Address for correspondence: Roger J. Lewis, MD, PhD, Department of Emergency Medicine, Harbor-University of California–Los Angeles Medical Center, 1000 West Carson Street, Box 21, Torrance, CA 90509; 310-222-6741, fax 310-782-1763

Abstract

Study objective

We determine the efficacy of prophylactic phenytoin in preventing early posttraumatic seizures in children with moderate to severe blunt head injury.

Methods

Children younger than 16 years and experiencing moderate to severe blunt head injury were randomized to receive phenytoin or placebo within 60 minutes of presentation at 3 pediatric trauma centers. The primary endpoint was posttraumatic seizures within 48 hours; secondary endpoints were survival and neurologic outcome 30 days after injury. A Bayesian decision-theoretic clinical trial design was used to determine the probability of remaining posttraumatic seizure free for each treatment group.

Results

One hundred two patients were enrolled, with a median age of 6.1 years. Sixty-eight percent were boys. The 2 treatment groups were well matched. During the 48-hour observation period, 3 (7%) of 46 patients given phenytoin and 3 (5%) of 56 patients given placebo experienced a posttraumatic seizure. There were no significant differences between the treatment groups in survival or neurologic outcome after 30 days. According to these results, the probability that phenytoin has the originally hypothesized effect of reducing the rate of early posttraumatic seizures by 12.5% is 0.0053. The probability that phenytoin has any prophylactic efficacy is 0.383. The median effect size in this trial was −0.015 (seizure rate increased by 1.5% in the phenytoin group), 95% probability interval −0.127 to 0.091 (12.7% higher rate of posttraumatic seizures to a 9.1% lower rate of posttraumatic seizures with phenytoin).

Conclusion

The rate of early posttraumatic seizures in children may be much lower than previously reported. Phenytoin did not substantially reduce that rate.

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Plan

Introduction

Background

Importance

Goals of this investigation

Materials and methods

Theoretical model of the problem

Study design

Setting

Selection of the participants

Interventions

Data collection and processing

Outcome measures

Primary data analysis

Results

Characteristics of study subjects

Limitations

Discussion

In retrospect

Author contributions: RJL conceived the study, designed the trial, and obtained research funding. RJL, KDY, PJO, and PES supervised the conduct of the trial and data collection. MJP, JMB, and SHI assisted in recruiting patients and data collection at participating centers. DQM, KRH, and EAP provided consultation in trial design and implementation. RJL performed the statistical analysis. KDY, PES, and RJL drafted the manuscript, and all authors contributed to its revision. RJL takes responsibility for the paper as a whole.
Supported in part by an Emergency Medicine Foundation Career Development Award (Dr. Lewis), a grant from the Dean's Research Fund at University of California–Davis School of Medicine (Dr. Panacek), and donation of injectable phenytoin from Parke-Davis Pharmaceuticals.
Reprints not available from the authors.