Definitions for the strength of the recommendations (Level A, B, C, U) and classification of evidence (Class I-IV) are provided at the end of the "Major Recommendations" field.
Practice Recommendations
For adult patients with severe traumatic brain injury (TBI) (typically with prolonged loss of consciousness or amnesia, intracranial hematoma or brain contusion on computed tomography [CT] scan, and/or depressed skull fracture):
- Prophylactic treatment with phenytoin, beginning with an intravenous (IV) loading dose, should be initiated as soon as possible after injury to decrease the risk of post-traumatic seizures occurring within the first 7 days (Level A).
- Prophylactic treatment with phenytoin, carbamazepine, or valproate should not routinely be used beyond the first 7 days after injury to decrease the risk of post-traumatic seizures occurring beyond that time (Level B).
These recommendations are generally consistent with those from other national specialty organizations, as well as with the findings on post-traumatic seizures from a recent meta-analysis (as of 2001) of antiepileptic drug (AED) prophylactic effect in a variety of epileptogenic conditions.
Definitions:
Strength of Recommendations
Level A: Established as effective, ineffective, or harmful for the given condition in the specified population. Usually, an "A" recommendation requires that the pooled result from two or more distinct class I studies demonstrates a consistent, significant, and important effect.
Level B: Probably effective, ineffective, or harmful for the given condition in the specified population. Usually, a "B" recommendation requires that a single class I study demonstrates a significant and important effect or the pooled result from two or more distinct class II studies demonstrates a consistent, significant, and important effect.
Level C: Possibly effective, ineffective, or harmful for the given condition in the specified population. Usually, a "C" recommendation requires that a single class II study demonstrates a significant and important effect or the pooled result of two or more distinct class III studies demonstrates a consistent, significant, and important effect.
Level U: Data are inadequate or conflicting. Given current knowledge, treatment is unproven and an evidence-based recommendation cannot be made.
Classification of Evidence
Class I: Evidence provided by a randomized, controlled clinical trial (RCT) with masked outcome assessment in a representative population. The following are required: a) primary outcomes are clearly defined; b) exclusion and inclusion criteria are clearly stated; c) there is adequate accounting of dropouts and crossovers with numbers sufficiently low to have minimal potential for bias; and d) relevant baseline characteristics are substantially equivalent among treatment groups. For the purposes of this parameter, a loss-to-follow-up rate of <10% was required to meet criterion c.
Class II: Evidence provided by a prospective matched group cohort study in a representative population with masked outcome assessment that meets a through d above or an RCT that lacks one criterion a through d.
Class III: All other controlled trials (including well-defined natural history controls or patients serving as their own controls) in a representative population where outcome assessment is independent of patient treatment.
Class IV: Evidence from studies not assessing outcomes independent of treatment, uncontrolled studies, case series, case reports, or expert opinion.