Status epilepticus (SE) is a medical and neurologic emergency. Given the significant risk of mortality, and the possibility of successful therapeutic intervention, it is essential for all physicians to be able to efficiently identify and treat patients in SE.

The definition of SE is based on the clinical manifestation, a prolonged seizure or a series of seizures during which the patient has incomplete recovery of consciousness, and duration. The duration parameter is controversial and has created a flux in our definition of SE. In their 1981 definition of SE, the International League Against Epilepsy describes the time elements as "sufficient length" and "frequently enough" [1]. For definition and management purposes, both of these quantifiers are ambiguous.

Elegant animal studies in the 1970s and 1980s revealed significant damage to the brain after 30 minutes of seizure activity, even with control of blood pressure, respiration, and body temperature [2,3,4]. These studies lent credence to the choice of 30 minutes as a specific time point to define SE. Although seizures can spontaneously remit after 10 to 29 minutes [5], in studies of the natural course of generalized tonic-clonic seizures, it has been well documented that, in humans, most seizures will terminate spontaneously within a few minutes [6]. For this reason, it has been proposed that an operational definition of SE should involve timing much shorter than 30 minutes [7].

The operational definition of SE proposed by Lowenstein, Bleck, and Macdonald is a continuous, generalized, convulsive seizure lasting greater than five minutes (in an adult or child older than five years), or two or more seizures during which the patient does not return to baseline consciousness [7]. Recent treatment studies including the Veterans Administration Cooperative Trial on Treatment of SE and the Pre-Hospital Treatment of SE study have used times of ten and five minutes respectively [8,9]. For treatment purposes, it is more practical to conceptualize SE using these narrower time windows. Shinnar et al. analyzed the duration of new-onset seizure activity in 407 children, and concluded that seizures lasting longer than five to ten minutes were unlikely to stop spontaneously, and should be treated [10].

The classification systems used for SE are discrepant throughout the literature. Many schemes have been generated that rely on both clinical and electrographic findings. It is important to note that virtually all seizure types may become prolonged, thereby fulfilling the definition of SE [11]. In an effort to provide a simple overview, a clinical approach will be favored here.

Prolonged convulsions with impaired consciousness constitutes generalized convulsive SE (GCSE). Although a patient with convulsions is easily recognized, some patients who have been in GCSE may progress to have minimal or no apparent motor activity but still show seizures on an electroencephalograph (EEG) [12]. The clinician must be aware of this situation, because aggressive treatment for this group is just as important as it is for the obviously convulsing patient [13].

The patient with nonconvulsive SE (NCSE) can exhibit a wide variety of clinical manifestation including coma, confusion, somnolence, altered affect, fugue states, aphasia, abnormal autonomic/vegetative symptoms, delusions, hallucinations, and paranoia [14]. The NCSE can be divided into either generalized (absence), focal (complex partial), or other. The 'epileptic twilight state', during which there is intact arousal with impairment of attention, can represent the clinical overlap between generalized and focal NCSE [12]; the distinction often rests in the electrographic findings. Nonconvulsive SE should be considered in the differential diagnosis of coma, as in a recent study at the Medical College of Virginia, in which 8% of the patients in coma were in NCSE [15].

Prolonged focal seizures, such as isolated hand jerking, associated with intact consciousness, comprises simple partial SE. Some authors conceptualize this entity as a separate category, while others include it as a subtype of NCSE [16].

The causes of SE are varied. Table 1 shows the etiologies of SE in an urban hospital-based population [16]. Although the data on causes of status, reported by DeLorenzo (Table 2), show some correspondence, there are discrepancies such as the higher proportion of cerebrovascular disease, anoxia, and hypoxia [17]. These data sets include only the adult population. In children, up to 51% are secondary to infectious etiologies [16].

As a result of sympathetic overdrive, the body responds to GCSE with both systemic and cerebral effects, whereas, to NCSE, systemic effects are more limited. Systemic effects of GCSE are summarized in Table 3. In the initial phase of GCSE, blood pressure, glucose, and lactate increase, and pH decreases. After this initial phase, at approximately 30 minutes, a second phase begins. During this second phase, blood pressure and glucose normalize (sometimes decreasing even further), lactate normalizes, and respiratory compromise and hyperthermia ensue [22].

In both animal models and humans, GCSE has been shown to result in damage to the brain [3,22,23]. The reasons for this damage have not been completely elucidated; however, several contributing factors are believed to exist. Some of the systemic manifestations described in Table 3 can play a contributory role. Meldrum et al. showed that hyperthermia causes damage to the hippocampus and cortex [24]. Additionally, it has also been shown that reduction of temperature results in shorter duration of SE and less damage [25]. Initially during SE, there is increased cerebral blood flow to meet the elevated demands; however, as the cerebral blood flow falls, there is a mismatch between blood supply and the utilization of oxygen and glucose, resulting in a lower energy state and metabolic–substrate mismatch [22]. It is important to note that in experiments where systemic factors are controlled, there is still damage to the brain [2,24].

An area of expanding research is excitotoxic-induced cell injury, an important cause of damage to neurons [26]. The damage to neurons is based on a complex interplay of multiple factors. Significant to this process is the inhibition of γ-aminobutyric acid (a principle inhibitory neurotransmitter), and the excessive action of glutamate (an excitatory neurotransmit-ter). Additionally, apoptosis is likely to play a role in cell death during SE. Given the probability of cerebral injury, it is imperative for the clinician to recognize and treat SE expeditiously.

Refractory SE is defined as ongoing seizures despite the use of two first-line agents, usually a benzodiazepine plus either phenytoin or phenobarbital. Definitive therapy often requires doses of medications that cause respiratory suppression and hypotension, so patients should be intubated and transferred to an intensive care unit if this has not already been done. Treiman et al. showed that respiratory suppression requiring mechanical ventilation occurred in 18.9%, and pressor support was needed in 32.6% of patients treated for SE [8]. Patients at this stage of SE require EEG monitoring, since the physical exam is clouded by the use of paralytics for intubation and the potential for electromechanical dissociation.

The traditional goal of therapy has a burst suppression pattern on EEG for 12–24 hours before attempting to taper medications. There are no convincing prospective data to suggest that a burst suppression pattern is required to control or to prevent recurrent seizures [35], thus we recommend seizure suppression as a goal, regardless of the EEG background.

As the issue of SE is often faced by practitioners of critical care, it is imperative that SE be recognized and treated as a medical emergency. Given the complex pathophysiology, being able to abort SE will contribute to a decrease in the systemic effects and neurologic injury. First line treatment with benzodiazepines, followed by the other agents discussed above, provide the maximal potential for successful management of SE.

None declared.

ASE = acute status epilepticus; EEG = electroencephalograph; GCSE = generalized convulsive status epilepticus; NCSE = nonconvulsive status epilepticus; SE = status epilepticus.