Status epilepticus

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Overview
Status epilepticus (SE) refers to a life threatening condition in which the brain is in a state of persistent seizure. Definitions vary, but traditionally it is defined as one continuous seizure or recurrent seizures without regaining consciousness between seizures for greater than 30 minutes. Many doctors, however, believe that 5 minutes is sufficient to damage neurons and that seizures are unlikely to self-terminate by that time.

In known epileptics, this condition is associated with poor compliance (adherence to medication regimen), alcohol withdrawal, and metabolic disturbances. As a primary presentation it normally indicates a tumour or abscess.

It can also be induced by nerve agents such as soman.

Variants
Status epilepticus can be divided into two categories&mdash;convulsive and nonconvulsive, the latter of which is underdiagnosed.

Convulsive
Epilepsia partialis continua is a variant involving hour, day, or even week-long jerking. It is a consequence of vascular disease, tumours, or encephalitis, and is drug-resistant.

Generalized myoclonus is commonly seen in comatose patients following CPR and is seen by some as an indication of catastrophic damage to the neocortex.

Nonconvulsive
Complex partial status epilepticus, or CPSE, and absence status epilepticus are rare forms of the condition which are marked by nonconvulsive seizures. In the case of CPSE, the seizure is confined to a small area of the brain, normally the temporal lobe. But the latter, absence status epilepticus, is marked by a generalised seizure affecting the whole brain, and an EEG is needed to differentiate between the two conditions. This results in episodes characterized by a long-lasting stupor, staring and unresponsiveness.

Benzodiazepines
Shortly after it was introduced in 1963, diazepam became the first choice for SE. Even though other benzodiazepines such as clonazepam were useful, diazepam was relied upon almost exclusively. This began to change in 1975 with a preliminary study on lorazepam conducted by Waltregny and Dargent, who found that its pharmacological effects were longer lasting than those of an equal dose of diazepam. This meant it did not have to be repeatedly injected like diazepam, the effects of which would wear off 5–15 minutes later in spite of its 30-hour half-life (due to extensive redistribution of diazepam outside the vascular compartment as diazepam is highly lipid soluble). It has also been found that patients who were first tried on diazepam were much more likely to require endotracheal tubing than patients who were first tried on phenobarbital, phenytoin, or lorazepam.

Today, the benzodiazepine of choice is lorazepam for initial treatment due to its long (2–8 hour) duration of action and rapid onset of action, thought to be due to its high affinity for GABA receptors and to its low lipid solubility which causes it to remain in the vascular compartment. If lorazepam is not available, then diazepam should be given. Sometimes, the failure of lorazepam alone is considered to be enough to classify a case of SE as refractory.

Phenytoin and fosphenytoin
Phenytoin was once another first-line therapy, although the prodrug fosphenytoin can be administered three times as fast and with far fewer injection site reactions. If these or any other hydantoin derivatives are used, then cardiac monitoring is a must if they are administered intravenously. Because the hydantoins take 15–30 minutes to work, a benzodiazepine or barbiturate is often co-administered. Because of diazepam's short duration of action, they were often administered together anyway.

Barbiturates
Before the benzodiazepines were invented, there were the barbiturates, which are still used today if benzodiazepines or the hydantoins are not an option. These are used to induce a barbituric coma. The barbiturate most commonly used for this is phenobarbital. Thiopental or pentobarbital may also be used for that purpose if the seizures have to be stopped immediately or if the patient has already been compromised by the underlying illness or toxic/metabolic-induced seizures; however, in those situations, thiopental is the agent of choice.

The failure of phenobarbital therapy does not preclude the success of a lengthy comatose state induced by a stronger barbiturate such as secobarbital. Such was the case for Ohori, Fujioka, and Ohta ca. 1998, when they induced a 10-month long coma (or "anesthesia" as they called it) in a 26-year-old woman suffering from refractory status epilepticus secondary to viral encephalitis and then tapered her off the secobarbital very slowly while using zonisamide at the same time.

General anesthetics
If this proves ineffective or if barbiturates cannot be used for some reason, then a general anesthetic such as propofol is tried; sometimes it is used second after the failure of lorazepam. This also means putting the patient on artificial respiration. Propofol has been shown to be effective in suppressing the jerks seen in myoclonus status epilepticus, but as of 2002, there have been no cases of anyone going into myoclonus status epilepticus, undergoing propofol treatment, and then not dying anyway.

Lidocaine
The use of lidocaine in status epilepticus was first reported in 1955 by Bernhard, Boem and Hojeberg. Since then, it has been used in cases refractory to phenobarbital, diazepam, and phenytoin, and has been studied as an alternative to barbiturates and general anesthetics. Lidocaine is a sodium channel blocker and has been used where sodium channel dysfunction was suspected. However, in some studies, it was either ineffective or even harmful for most patients. The last is not so surprising in light of the fact that lidocaine has been known to cause seizures in humans and laboratory animals at doses greater than 15 µg/mL or 2–3 mg/kg.