Introduction

Limited options are available for the parenteral treatment of seizures. These options include the barbiturates (phenobarbital, pentobarbital, and pentothal), the benzodiazepines (diazepam, lorazepam, and midazolam), and phenytoin or fosphenytoin. Until the 1970s, parenteral phenobarbital was the primary agent used for the acute treatment of seizures. Although very effective in status epilepticus (SE) and acute seizures, a loading dose produces considerable sedation and may affect the patient's neurologic status. Over the past 20 years, intravenous (IV) phenytoin (and, more recently, fosphenytoin) has been one of the mainstays in the treatment of recurrent seizures and SE because of its acute and long-term effectiveness and relative lack of sedation. The effectiveness of IV phenytoin was initially reported by Wallis et al. (43). In 1976, Wilder et al. reported on 10 patients who received 13mg/kg for generalized convulsive SE (49). In 9 of the 10 patients, SE was controlled within 30 minutes. The following year (1977), Cranford, Leppik, and colleagues reported that a plasma phenytoin level above 20µg/mL was maintained for 24 hours when an IV loading dose of 17mg/kg was administered (9). The standard approach has evolved to use of a loading dose of 20mg/kg to treat acute seizures and SE.

The benzodiazepines are very effective acutely, but tolerance develops, and efficacy is lost with extended dosing. The rate of intramuscular (IM) absorption between the benzodiazepines also varies. When comparing oral and IM routes, time to peak concentration is the same for diazepam, whereas lorazepam is absorbed twice as quickly via the IM route. Lorazepam is absorbed more rapidly after rectal administration than after administration by either the oral or the IM route. Thus, the method of administration is an important consideration in the treatment of acute seizures.