status epilepticus

Status epilepticus
Daniel H. Jacobs MD
August 5, 2006

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www.onlineneurology.blogspot.com



Outline
I. Definition
II Types
III Differential Diagnosis and Diagnosis
IV Treatment
V Pitfalls and Prognosis

Definition-- SE Status epilepticus (America's Working Group on Status Epilepticus) --" more than thirty minutes of continuous seizures or two or more consecutive seizures without full recovery of consciousness in between"

Types
Generalized Status epilepticus
Absence Status epilepticus
Complex Partial Status Epilepticus
Partial status epilepticus continua
Myoclonic status epilepticus

Prognosis
Depends on the type of SE, age of the patient, duration of the SE, and etiology, iatrogenic complications and previous health of the patient. Mortality ranges from 3-52 % mortality reflecting that very different conditions are represented under the rubric SE. Some authors believe the true rate is 20-30 percent.

Greater Richmond Metropolitan Status Epilepticus Project analyzed 1000 cases of SE lasting median 92 minutes. There was a bimodal onset with children and the elderly overrepresented.

Children less than 16 (including infants) have a mortality of only three percent. The mortality related to febrile seizures is nearly zero, that related to other causes has only a slightly higher mortality, and that mortality that exists is related to horrible underlying diagnoses, not to SE itself. The rate of cognitive abnormalities after SE is 15-20 percent, some of which is related to the underlying diagnosis rather than the seizures. Children did have a higher rate than adults of recurrent SE.

Older people have a higher mortality who are ill, and this cohort undoubtedly includes many patients who have agonal SE after cardiac arrest and before death. Patients more than 65 having SE due to anoxia have a 92 % mortality, with similar patients of all ages having a 71 % mortality. In older adults, SE can precipitate myocardial infarction (MI), elevated cardiac enzymes and/or EKG changes in up to ten percent of patients, at any age.

Relatively high survival is associated with SE in patients with known epilepsy who experience SE due to subtherapeutic levels of antiepileptic drugs (AED's).

Duration of SE is the primary modifiable determinant of outcome. Prognosis worsens exponentially as SE lengthens to three hours, after which only small increments in mortality are seen. Earlier presentation, diagnosis and appropriate treatment can shorten duration and improve mortality.

Nonconvulsive or "subtle" SE has several types (see below) including complex partial SE, absence SE, or patients demonstrating periodic epileptiform discharges (PED's) on their EEG's. Nonconvulsive SE has a mortality of 64 % which is higher than convulsive SE, with certain subtypes representing favorable exceptions. Some epileptologists favor treating every discharge on the EEG after generalized SE, requiring obtaining EEG monitoring, in order to reduce mortality.

Unfavorable symptoms include autonomic incompetence, such as failure to achieve tachycardia and hypertension after SE, which worsens prognosis. Cardiac arrythmias may be latent and underlying, due to cocaine or other drugs, of to sympathetic discharge ("voodoo death") associated pathologically with myofibrillar necrosis rather than CAD. The choice of drug used is not related to mortality, although some drugs can produce respiratory depressions (barbiturates and benzodiazepines).

Death in epilepsy may be related to factors other than SE. Depression and suicide may be increased ninefold or more in epileptics. Sudden unexplained death with epilepsy (SUDEP) may occur at any age and has a frequency as high as 1:250, with SUDEP 18 fold higher among men and higher among patients with early (adolescent) onset of epilepsy. Low AED levels are associated with SUDEP. Autopsies may be negative. The etiology may be related to sympathetic catecholamine discharges.
Status epilepticus is a neurologic emergency. The first item is medical stablization airway-breathing-circulation. Confused patients should be given thiamine, then glucose (50 grams_, thiamine (100 mg i-v), Narcan (0.4-2.0 mg i-v), and flumazenil (if indicated) 0.2 mg i-v. Labs should be sent, including electrolytes, CBC, diff, Ca, Mg, PO4, extra red top, AED levels, tox screen/ ETOH level.
Several drugs may be used for the acute treatment of SE, but the key is knowing in detail the pharmacokinetic proporties of the chosen drugs. Lorazepam is often given first line, and is considered the most rapidly effective. The dose is 0.5-1.0 mg/kg, Unlike diazepam, is not metabolized by the liver and has a longer half life. Typically, if lorazepam is used a longer acting drug needs to be added immediately. Cerebyx can be given i-v. Unlike i-v Dilantin, Cerebyx can be given rapidly, without cardiac monitoring, can be given i-m if no i-v access is obtained, and does not cause purple hand syndrome (safer and more effective), Dosing is identical to Dilantin. IT IS NOT ONE GRAM. The dosing is 20 mg/kg, about 1500 grams in an average sized patient, and underdosing can cause recurrent seizures. In patients with verified diagnosis of overt GCSE, response rates were as follows: lorazepam, 64.9%; phenobarbital, 58.2%; diazepam and phenytoin, 55.8%; and phenytoin alone, 43.6%. In statistical comparison of the pairs, only the difference between lorazepam and phenytoin alone was significant.
If the patient has a single seizure and is able to swallow pills, they may be orally loaded with Dilantin Kapseals, 100 mg tablets in the 20 mg/kg dosing schedule. Typically for a 80 kg man, 400 mg po q 3 hours times four doses is reasonable. A Dilantin level should be checked the following morning and a daily dose ordered. LIQUID DILANTIN GIVEN THROUGH DOBHOFFS NEVER ACHIEVES THERAPEUTIC LEVELS! (Give Kapseals or i-v Cerebyx).
Alternatives: Depacon (= i-v Depakote) 20 mg/kg i-v over five minutes, phenobarbital 10-20 mg/kg i-v with monitoring over an hour. In refractory SE (ie, that which does not respond to either regimen above), a commonly used protocol is intravenous pentobarbital. A loading dose of 5 mg/kg is followed by 0.5-3 mg/kg/h titrated to cessation of seizures or a burst-suppression pattern on EEG. In a recent study of patients with refractory SE, Krishnamurthy and Drislane concluded that the survival rate was better in patients whose EEG was more suppressed. Hypotension is a risk of pentobarbital infusion. In patients who cannot tolerate pentobarbital, alternatives include continuous infusion of benzodiazepines (eg, midazolam or propofol).
Pitfalls
1. Failure to perform EEG-- may miss nonconvulsive SE and the chance to treat. May miss pseudoseizures and overtreat patient.
2. Failure to perform lumbar puncture-- may miss meningitis
3. Failure to consider a diagnosis of herpes encephalitis-- must be treated early
4. Using above medications incorrectly
5. Failure to order EEG monitoring on admission if patient is not back to normal-- similar to 1-- may miss ongoing SE
6. Discharge from ER prior to patient returning to baseline cognitively-- may miss HSVE
7. Failure to consider differential diagnosis-- intoxication, locked in syndrome, psychogenic SE etc.
Complex partial status epilepticus
Favorable neurologic outcomes of CPSE have been reported regardless of whether medical treatment was successful. Few reports indicate serious sequelae complicating CPSE. Thus, the question of how aggressively to treat CPSE remains controversial. In general, pending a good, randomized trial, CPSE should be treated similarly to GCSE, except that treatment should stop before the use of general anesthesia (eg, pentobarbital coma).
In acute stages and for diagnosis, treatment with an intravenous benzodiazepine may be helpful. Often, out-of-hospital treatment with rectal or oral benzodiazepines aborts an episode. Williamson believes that, since most patients with CPSE have a history of epilepsy, concomitant AED therapy should be optimized.
Walker and Shorvon reported that, although most episodes of CPSE are self-terminating, recurrent episodes are encountered, and medical treatment is often disappointing. Patients who have medically refractory localization-related epilepsy should be evaluated for surgical therapy.
Absence status epilepticus
Walker and Shorvon reported that ASE responds rapidly to intravenous benzodiazepines. D'Agostino and coworkers believe that valproate is the medication of choice for ASE. Although effective, this treatment may result in complications such as sedation and respiratory depression. Kaplan summarized a case of a female with known absence epilepsy in which hospitalization was avoided by treating ASE with intravenous valproate. Snead et al stated that the more atypical the SE, the more difficult it is to control with benzodiazepines and other forms of therapy. Patients with primary generalized epilepsy should have optimized valproate or ethosuximide therapy to prevent recurrent episodes of ASE. Thomas et al reported that long-term anticonvulsant therapy might not be necessary in adults who are middle-aged or older at the onset of de novo ASE.

References:
Boggs JG, Towne AR, DeLorenzo RJ, Pellock JM. Status Epilepticus. In Gilchrist, James. Prognosis in Neurology, Butterworth-Heinemann, 1998.

Shinnar S, Pellock JM, Berg AT. An inception cohort of children with febrile status epilepticus: cohort characteristics and early outcome. Epilepsia 1995;36 (suppl 4):31.