Status epilepticus

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Status epilepticus
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Status epilepticus
Classification and external resources
eMedicineemerg/554 article/908394

Status epilepticus (SE) is a life-threatening condition in which the brain is in a state of persistent seizure. Definitions vary, but currently it is defined as one continuous, unremitting seizure lasting longer than five minutes,[1] or recurrent seizures without regaining consciousness between seizures for greater than five minutes. Previous definitions used a 30-minute time limit.[2] Treatment is, however, generally started after the seizure has lasted five minutes. It is always considered a medical emergency. There is some evidence that five minutes is sufficient to damage neurons and that seizures are unlikely to self-terminate by that time.

First aid guidelines for seizures state that, as a rule, an ambulance should be called for seizures lasting longer than five minutes (or sooner if this is the patient's first seizure episode and no precipitating factors are known, or if SE happens to a person with epilepsy whose seizures were previously absent or well controlled for a considerable time period). The mortality rate of status epilepticus is estimated at 20%.[2] However, with optimal neurological care, adherence to the medication regimen, and a good prognosis (no other underlying uncontrolled brain or other organic disease), the patient—even people who have been diagnosed with epilepsy—in otherwise good health can survive with minimal or no brain damage, and can decrease their risk of death and even avoid future seizures.[3]

Signs and symptoms[edit]

Status epilepticus can be divided into two categories—convulsive and nonconvulsive, the latter of which is underdiagnosed.[citation needed]


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.[4]


Complex partial status epilepticus (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.


Only 25% of people who experience seizures or status epilepticus have epilepsy.[3] Causes include:


Diazepam that can be inserted rectally is often prescribed to caregivers of people with epilepsy. This enables treatment of multiple seizures prior to being able to seek medical care.


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 its pharmacological effects were longer lasting than those of an equal dose of diazepam.[6] This meant it did not have to be repeatedly injected like diazepam,[7] the effects of which would wear off five to 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,[8] or lorazepam.[9]

Today, the benzodiazepine of choice in North America for initial treatment is lorazepam due to its relatively long (2–8 hr) duration of action when injected, and its rapid onset of action, which is 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, or intravenous access is not possible, then diazepam should be given.[10] In several countries outside North America, intravenous clonazepam is regarded as the drug of first choice. For instance, the Acute Boekje, a guideline for the assessment and treatment of medical emergencies used nationwide in the Netherlands, recommends clonazepam as the first-line treatment of convulsive status epilepticus.[11] Cited advantages of clonazepam include a longer duration of action than diazepam and a lower propensity for the development of acute tolerance than lorazepam.[12] The use of clonazepam for this indication has not caught on in North America, as it is not available as an intravenous formulation there.[12]

Particularly in children, another increasingly popular treatment choice is buccal and intranasal midazolam, which can be given into the side of the mouth or the nose, respectively.[13] Sometimes, the failure of lorazepam alone is considered to be enough to classify a case of SE as refractory.

Phenytoin and fosphenytoin[edit]

Phenytoin was once another first-line therapy,[14] 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 coadministered. Because of diazepam's short duration of action, they were often administered together anyway.

Carbamazepine and valproate[edit]

Valproate is available to be given intravenously, and may be used for status epilepticus. Carbamazepine is not available in an intravenous formulation, and does not play a role in status epilepticus.[14]


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, circa 1998, when they induced a ten-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.[15]

General anesthetics[edit]

If this proves ineffective or if barbiturates cannot be used for some reason, then a general anesthetic such as propofol[16] is tried; sometimes it is used second after the failure of lorazepam.[17] This also means putting the patient on artificial ventilation. 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.[18]


The use of lidocaine in status epilepticus was first reported in 1955 by Bernhard, Boem, and Hojeberg.[19] 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.[20][21] Lidocaine is a sodium channel blocker and has been used where sodium channel dysfunction was suspected.[22] However, in some studies, it was either ineffective or even harmful for most patients.[23] 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[24] or 2–3 mg/kg.[25]


Ketamine, an NMDA antagonist drug, can be used as a last resort for drug-resistant status epilepticus.[26]


About one in five people who have the disease, a total of 42,000 annually in the United States, will die within 30 days of having an initial SE seizure. The great majority of these people have an underlying brain condition causing their status seizure such as brain tumor, brain infection, brain trauma or stroke. However, people with diagnosed epilepsy who have a status seizure also have an increased risk of death if their condition is not stabilized quickly, their medication and sleep regimen adapted and adhered to, and stress and other stimulant (seizure trigger) levels controlled.


In the United States, about 40 cases of SE occur annually per 100,000 people.[27] This includes about 10-20% of all first seizures.


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