Table 2 | Etiologic factors of generalized convulsive status epilepticus Subtherapeutic antiepileptic drug levels Cerebral trauma Infection, central nervous system or general Cerebrovascular accident Metabolic disturbance (e.g. electrolyte imbalance) Drug overdose Hypoxia History of epilepsy Tumor Alcohol abuse healthy population. The overall mortality in SE has been reported to be approximately 30% (estimates range from 2 to 61%), whereas NCSE-associated mortality appears to be higher, approximately 50% (estimates range from 33 to 57%) (Rüeegg & Dichter 2003). There are about 102 000–152 000 new cases of SE in the USA per year and around 22 000–42 000 deaths annually associated with the condition (DeLorenzo et al. 1995). At approximately 22%, this mortality rate is within the overall SE mortality range reported by Rüeegg and Dichter (2003). Data from other countries also show that SE is common. For example, the minimum estimated incidence is approximately 20 per 100 000 in Switzerland and Germany (Rosenow et al. 2002), while in India, SE accounted for 11% of neurologic admissions to intensive care units (Swaminathan et al. 1998). It is interesting to note that in studies in the USA, the incidence of SE in the black population is three times higher than in Caucasians (reviewed in Rosenow et al. 2002). In addition, the incidence is higher in males and is age-related, with the highest incidence in children and the elderly. As the relative proportion of the aging population is increasing globally, it is expected that there will be a corresponding increase in the incidence of SE (Rosenow et al. 2002). About a third of all instances of SE occur in patients with a history of epilepsy or febrile seizures, one-third in patients whose first sign of epilepsy is an episode of SE, and the remaining third result from encephalopathic insult to the brain (Treiman 1999). Other causes of SE include trauma, hypoxia, stroke, infection, and drug withdrawal (Table 2). Patients with a first episode of SE are at considerable risk for both future episodes and the development of chronic epilepsy (Lowenstein & Alldredge 1998). Although outcome is usually worse in patients with SE of long duration and those with physiologic disturbances, it is the etiology of SE (Table 2) that has the greatest influence on outcome. Mortality is highest in elderly patients or when SE is secondary to an acute event (e.g. acute stroke, central nervous system infection, head trauma, metabolic disturbances, drug toxicity, and hypoxia). In contrast, SE secondary to previous strokes, withdrawal from alcohol or anticonvulsant drugs, tumours, or epilepsy has a more favorable prognosis (Manno 2003). To date, one study has looked at a long-term outcome, 10-year mortality after a first episode of SE that received medical attention (Logroscino et al. 2002). In this study 40% of patients who survived the first 30 days after an incident episode of SE Core Evidence 2005;1(1) Fosphenytoin | clinical impact review died within the next 10 years: three times the mortality rate compared with the general population over the same time period. This study indicated that significant risk factors for long-term mortality (prolonged SE duration, myoclonic SE, and advanced age) replicated those factors that influence short-term mortality (Towne et al. 1994). Recently, the inpatient costs associated with SE in the USA alone have been estimated to range from $US3.8–7 billion per year (Sirven & Waterhouse 2003). Current therapy options for status epilepticus Because of the emergency nature of the condition, the aim of SE treatment is the prompt termination of seizure activity and subsequent prevention of seizure recurrence. Once the patient is diagnosed with SE, rapid administration of drug therapy is necessary to both reduce the potential for neurologic morbidity and increase the probability of response to therapy; SE of long duration is less responsive to drug therapy compared with SE of shorter duration (Lowenstein & Alldredge 1998). Initial drug treatment of SE usually involves a parenterally administered benzodiazepine (lorazepam or diazepam) or a hydantoin (Lowenstein & Alldredge 1998; Holmes & Riviello 1999; Manno 2003). Most cases of SE respond to these initial treatment options. However, SE that does not respond to these therapies is considered to be refractory. Agents used in this situation include phenobarbital or pentobarbital, propofol, and midazolam. Current treatments for SE are shown in Table 3. There have been a number of attempts to identify optimal treatment regimens for SE. Treatment protocols shorten the time needed to control seizures. Typically they include the sequential administration of benzodiazepines, phenytoin, and phenobarbital, and finally pentobarbital-induced coma for patients with refractory seizures (Manno 2003). However, it has been suggested that actual drug choice may be less important than the development of a protocol itself (Shorvon 2001), but this reflects the importance of achieving a rapid response. The ideal drug for the treatment of SE should be easy to administer, achieve immediate and long-lasting antiseizure activity, and also be free from serious respiratory depression, cardiovascular and sedative effects, and local irritation at the injection site. However, all the currently available therapies used to treat SE fail this ideal in some respect. Adverse events with the benzodiazepines include respiratory suppression, hypotension, and sedation. Similarly, although the hydantoins lack sedative effects they have also been associated with hypotension. In addition, local venous irritation, pain, and phlebitis can also occur with intravenous phenytoin. Phenobarbital, which is sedative, is often used following failure to control SE with a benzodiazepine or hydantoin; however, it too is associated with systemic hypotension. Finally, propofol, another option if previous therapy has failed, may lead to instances of severe metabolic acidosis particularly in children with metabolic enzymatic defects (Manno 2003). Despite the potential adverse events associated with these agents, they still have a place in the therapeutic management of SE. Even with the development of medication protocols, treatment may still vary among physicians. A recent survey of neurologists (mainly 67