Introduction

Phenobarbital is commonly considered to be a third-choice drug for status epilepticus (SE), to be used if benzodiazepines and phenytoin fail (7). There are few data to support this notion, however, and the only two controlled studies comparing phenobarbital to other treatments (24, 28) yielded evidence that phenobarbital is as good as currently available alternatives in terms of efficacy and adverse effects profile. Therefore, there remains some uncertainty about its proper role. Other barbiturates used for the treatment of SE are primarily employed as anesthetic agents for refractory status. They are discussed in chapter 37.

Barbituric acid, the parent compound of barbiturates, was synthesized in 1863 by von Baeyer, a student of Kekule. The name supposedly derives from St. Barbara, the patron saint of artillery officers, with whom von Baeyer celebrated his discovery, and from urea (10). The first sedative barbiturate barbital was introduced in 1903. Although Hauptmann reported the use of phenobarbital as an antiepileptic agent in 1912, its adoption as the primary agent against SE was slow.

In Wechsler's standard textbook of neurology, which went through seven editions between 1927 and 1952, rectal chloral hydrate or chloroform anesthesia were the recommended treatments, along with high colonic saline irrigations, through the 1930s. In 1935, intravenous sodium amytal was listed as an alternative (31), and in 1943, sodium phenobarbital was also listed (32).

Phenobarbital then remained the drug of choice for SE until the 1960s, when diazepam became more popular. It was supplanted after 1980 by the combination of diazepam and phenytoin. As late as 1978, 25% of American neurologists selected phenobarbital as their first choice (9). Phenobarbital has been the favored initial agent by many for neonatal SE (1), though lorazepam followed by phenobarbital for neonatal SE has been suggested more recently (22).