Introduction

Intravenous (IV) diazepam was first used for the treatment of status epilepticus (SE) in 1965 by Henry Gastaut (45). Since that time, benzodiazepines have remained the preferred agents for initial therapy for the clinical management of SE. Compared with other antiseizure agents, benzodiazepines are highly potent, easily administered, and have a rapid onset of clinical effect. However, drugs of this class also cause dose-related depression of respiratory drive, cardiovascular compromise, and a depression of consciousness (81).

The most commonly used benzodiazepines for the treatment of SE are clonazepam (outside the United States), diazepam, lorazepam, and midazolam. These agents, used as initial therapy for the treatment of SE, are the focus of this chapter. In the United States clonazepam in not available as an IV preparation, and only diazepam and lorazepam are approved by the Food and Drug Administration for the treatment of SE. Midazolam is primarily administered by alternative routes—intramuscular (IM), intranasal, buccal—when IV therapy is not feasible, or as a continuous infusion for SE refractory to standard therapy (e.g., bolus doses of benzodiazepines, phenytoin, and phenobarbital [40]). Intravenous therapy is always preferred as long as support measures are available to manage the potential complications of treatment. Nonetheless, midazolam and the other benzodiazepines have pharmacokinetic features that make them potentially useful for transmucosal and IM treatment. The use of benzodiazepines for the prehospital treatment of SE is also discussed.