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Status epilepticus

State of continuous seizure lasting longer than 30 minutes or repeating convulsions lasting longer than 30 minutes without recovering consciousness between them.

Status epilepticus is recognized at two points in time – for convulsive seizures the first time point is five minutes at which the patient should be clinically diagnosed and treated for status epilepticus, and the second time point at 30 minutes is when neural damage is likely to occur.

A medical emergency characterized by continuous seizures or a lack of full recovery between seizures.

Affects 65-150,000 persons in the U.S. each year.

Has a reported incidence between 10 and 41 cases per 100,000 population with the variation partly reflecting different diagnostic criteria.

It has a mortality of approximately 20%.

Estimated that 1.3-16% of all patients with epilepsy will develop status epileptics.

Occurs in approximately 6% of visits to the ED.

Commoner in childhood than adulthood.

In adults largest group are those with underlying seizure disorder in whom drug withdrawal or alcohol precipitate status epilepticus.

CNS injury, stroke, anoxic insults, tumors and meningitis can induce status epilepticus.

Mortality ranges from 6-30%.

Among patients with status epileptics that survive functional ability will decline in 25%.

About 10% of patients recovering from status epilepticus demonstrate residual neurologic abnormalities.

Among children neurologic complications rates occur in 29% among infants younger than 1 year, 11% among children ages 1 to 3 years, and 6% among children older than 3 years of age.

In children 30% develop a chronic seizure disorder.

Mortality rate for children approximately 3%.

Older age, female sex, increased seizure duration, and continuous seizures are predictors of mortality after status epileptics.

Earlier termination of prolonged epileptic seizures by prehospital management is associated with better patient outcomes.

Management divides the medical therapy for status epilepticus into three main stages: the first line treatment for early status epilepticus, is often administered before the patient reaches the hospital, is a benzodiazepine usually intravenous lorazepam with buccal midazolam.

Current guidelines recommend but benzodiazepines followed by either fosphenytoin or phenytoin.

The second line medication is the use of intravenous preparations: fosphenytoin, levetiracetam, or sodium valproate given by infusion, usually in a hospital.

No randomized trial has shown any agent or combination of agents are  more effective for the treatment of convulsive status epilepticus than a benzodiazepine followed by a phenytoin or its prodrug fosphenytoin.

The third treatment for refractory status epilepticus is managed in an ICU and utilizes one of three anesthetic agents: midazolam, propofol, or thiopental.

Early termination of status epilepticus decreases the risk of respiratory and cardiac complications, and is associated with a reduced risk of admission to an ICU and decrease mortality among children.

Evidence supports the use of benzodiazepines as the initial treatment for status epilepticus.

Up to 1/3 of patients with status epilepticus do not respond to benzodiazepines.

Three drugs are commonly used to treat benzodiazepine refractory status epilepticus: levetiracetam, fosphenytoin, and valproate.

For status epilepticus intravenous levetiracetam, fosphenytoin , and valproate provide seizure cessation in approximately 50% of patients at one hour.

Fosphenytoin and phenytoin are associated with a higher risk of allergic reaction then valproate or levetiracetam.
Intravenous phenytoin is associated with a small risk of hypotension  and cardiac arrhythmias, especially when administered rapidly. 
 
Valproate is the most teratogenic anti-seizure medication income and is associated with a lower IQ and higher rates of autism in offspring, and should be avoided whenever the possibility of pregnancy exists.
 
This  effect is less common with fosphenytoin.

Proportion of subjects whose seizures were terminated at the time of arrival in the ED is 59.1% for patients receiving intravenous lorazepam, 42.6% for patients receiving intravenous diazepam and 21.1% in a group receiving intravenous placebo (Prehospital Treatment of Status of Epilepticus).

In a double-blind, randomized, noninferiority trial comparing efficacy of intramuscular midazolam with that of intravenous lorazepam for children and adults in status epileptics treated by paramedics:intramuscular midozalam was as safe and effective as intravenous lorazepam for prehospital seizure cessation (Silbergleit R et al).

New-onset refractory status epilepticus (NORSE) occurs without active epilepsy or other pre-existing relevant neurological disorder and has no clear for acute for active structural, toxic, or metabolic cause.

NORSE has an unpredictable course and frequently resolves a severe life altering cognitive problems, refractory epilepsy, or death.

NORSE is caused by a number of processes including autoimmune disease, paraneoplastic, or infectious, but more than half are cryptogenic.

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