eMedicine Specialties > Neurology > Neurological Emergencies

Status Epilepticus: Treatment & Medication

Author: Mark Spitz, MD, Professor, Department of Neurology, University of Colorado Health Sciences Center
Coauthor(s): Frank Lum, MD, Instructor, Department of Neurology, University of Colorado Health Sciences Center; Jose E Cavazos, MD, PhD, Assistant Professor, Departments of Medicine (Neurology), Pharmacology, and Physiology, University of Texas Health Science Center at San Antonio; Edward Maa, MD, Epilepsy Fellow, Department of Neurology, University of Colorado Health Science Center
Contributor Information and Disclosures

Updated: Mar 8, 2007

Treatment

Medical Care

Both generalized tonic-clonic style status epilepticus and subtle status epilepticus must be treated aggressively. Maintenance of vital signs, including respiratory function, is of major importance. Any indication of respiratory insufficiency should be addressed by intubation. Finally, systemic acidosis is not a major concern because it is usually transient, and medical treatment to normalize acidosis can lead to a rebound metabolic alkalosis when the status epilepticus stops. In addition, evidence suggests that acidosis has antiseizure effects.

SE must be treated rapidly. Therefore, the treating physician should not wait for a blood level to return from a laboratory test before given the patient a loading dose of phenytoin. The same protocol should be followed regardless of whether the patient is already taking phenytoin. Assume that the patient is noncompliant because this is the most common cause of SE in patients with known epilepsy. Even if the patient has been compliant and even the phenytoin levels were already in the therapeutic range (10-20 µg/mL), data suggest that 20-30 µg/mL is more effective than of 10-20 µg/mL in stopping seizures.

High doses can cause ataxia and sedation. Because the patient is likely to be hospitalized after the SE is controlled, these adverse effects are less important than they would be in a patient being treated on an outpatient basis. SE is a life-threatening situation, and the patient will be admitted to the hospital after treatment. Therefore, if treatment errs, it should err on the side of excessive medication. Temporary adverse effects are preferred to irreversible brain damage or death.

  • No reports of prospective, double-blind studies on the treatment of SE have been published recently. Therefore, the best initial drug treatment remains uncertain.
  • Treiman et al (1998) compared treatments for generalized convulsive SE, investigating the use of diazepam followed by phenytoin, lorazepam, phenobarbital, or phenytoin.
    • As an initial IV treatment for overt generalized convulsive SE, lorazepam was more effective than phenytoin alone.
    • Although lorazepam was no more effective than phenobarbital or diazepam plus phenytoin, it was easier to use.
    • Not studied was fosphenytoin, a newer drug than the others that is theoretically a significant improvement over phenytoin.
  • The duration, underlying etiology, EEG pattern, and clinical presentation at the start of treatment largely determine the response to treatment.
    • The more advanced the stage of SE, the less favorable the response to treatment.
    • In the recently completed VA Cooperative study, 56% of patients who were first seen with overt, generalized convulsive SE responded to initial treatment. Only 15% of the individuals with subtle, generalized convulsive SE responded to initial treatment (Treiman, 1998).

Surgical Care

Surgical treatment, which consists of ablating a structural abnormality, hemispherectomy, subpial resection, or vagal-nerve stimulator placement, is a last-resort maneuver that is rarely performed (D'Giano, 2001; Ma, 2001; Winston; 2001; Duane, 2004).

Consultations

  • Clinicians other than neurologists usually begin treatment for SE because most patients who present with SE have never had a seizure.
  • When first- and second-line pharmacologic therapies fail, an anesthesiologist may be needed to perform intubation and administer general anesthesia.
  • A neurologist should be obtained, especially if the patient's condition is not responding to initial therapy and if EEG is needed.

Medication

Most patients who are treated aggressively with a benzodiazepine, fosphenytoin, and/or phenobarbital experience complete cessation of their seizures. If SE does not stop, general anesthesia is indicated. No reports of prospective studies on the treatment of refractory SE have been published; however, investigators from retrospective reviews have described the use of pentobarbital, thiopental, midazolam infusion, propofol, levetiracetam, topiramate, valproate, and inhaled anesthetic agents.

Anticonvulsant agents

A useful algorithm for the treatment of SE is as follows (see Image 1):

  • Start an IV line, administer a 50-mL bolus of 50% dextrose IV, then start the anticonvulsant.
  • Administer diazepam or lorazepam 0.15 mg/kg IV over 5 minutes, followed by fosphenytoin 15-20 mg phenytoin equivalents (PE)/kg at a rate not to exceed 150 mg/min.
  • Intubate if necessary, and control hyperthermia.
  • If seizures continue after 20 minutes, give additional fosphenytoin 10 mg PE/kg.
  • If seizures continue after 20 minutes, give additional fosphenytoin 10 mg PE/kg.
  • If seizures continue, administer general anesthesia.


Diazepam (Valium)

Extremely lipid-soluble agent that quickly enters brain in first pass and often stops seizures in 1-2 min. Rapidly distributes to other stores of body fat. Serum concentration decreases to 20% of maximum concentration (Cmax) 20 min after IV infusion.

Adult

0.1 mg/kg IV q5min, repeat prn; not to exceed 30 mg in 8 h

Pediatric

0.1 mg/kg IV q5min, repeat prn; not to exceed 30 mg in 8 h

None reported as contraindicated for this indication

Pregnancy

B - Usually safe but benefits must outweigh the risks.

Precautions

None reported for this indication


Lorazepam (Ativan)

Less fat-soluble benzodiazepine than diazepam and therefore takes 5-10 min to stop seizures, and has smaller volume of distribution. Serum concentrations 50% of Cmax at 20 min.

Adult

0.1 mg/kg IV slowly over 2-5 min; repeat in 10-15 min prn; not to exceed 8 mg dose

Pediatric

0.1 mg/kg IV slowly over 2-5 min; repeat prn in 10-15 min at 0.05 mg/kg; not to exceed 4 mg/dose

None reported as contraindicated for this indication

Pregnancy

D - Unsafe in pregnancy

Precautions

None reported for this indication


Phenytoin (Dilantin)

Mainstay in treatment of SE. Must be administered slowly and therefore takes longer to enter brain than benzodiazepines. Has advantage of being long-term anticonvulsant and can be administered PO after acute illness. Not water soluble, and must be solubilized in propylene glycol carrier with pH 12 to prepare IV form; therefore, cannot be given >50 mg/min without risk of significant hypotension and cardiac arrhythmias. Also major risk of potential irritation at IV site and vascular compromise of infused limb. Therefore, use in SE should be avoided if possible.

Adult

15-20 mg/kg IV, not to exceed 50 mg/min; intubate if necessary and control hyperthermia; if seizures continue after 20 min, give additional 10 mg/kg; target levels after correction of hypoalbuminemia should be 20-30 mcg/mL in SE

Pediatric

Administer as in adults

None reported as contraindicated for this indication

Pregnancy

C - Safety for use during pregnancy has not been established.

Precautions

Risk of hypotension and cardiac arrhythmias (perform cardiac monitoring during infusion); infusion rate should be <50 mg/min


Fosphenytoin (Cerebyx)

Phosphorylated phenytoin prodrug. Highly water-soluble and therefore easier to administer than phenytoin. Enzymatically converted to phenytoin after mean 8 min and therefore can be administered more rapidly than standard phenytoin.

Adult

20 mg/kg PE IV; if seizures do not end give additional 10 mg PE/kg; target levels after correction of hypoalbuminemia should be 20-30 PE/ml for SE

Pediatric

20 mg/kg PE IV; if seizures do not end, give additional 10 mg PE/kg

None reported as contraindicated for this indication

Pregnancy

B - Usually safe but benefits must outweigh the risks.

Precautions

Risk of hypotension and cardiac arrhythmias (perform cardiac monitoring during infusion); infusion rate should be <150 mg/min


Phenobarbital (Luminal, Barbita)

Best studied barbiturate in treatment of SE. Can be administered 20 mg/min IV. If patient has received benzodiazepine, potential for respiratory suppression significantly increased.

Adult

20 mg/kg IV q20min until seizures controlled or total 1-2 g administered

Pediatric

20 mg/kg IV over 10-15 min in single or divided dose until seizure controlled or 40 mg/kg administered

Combination with benzodiazepines causes significant respiratory depression; strongly consider elective intubation before combination given

Pregnancy

B - Usually safe but benefits must outweigh the risks.

Precautions

None reported for this indication

More on Status Epilepticus

Overview: Status Epilepticus
Differential Diagnoses & Workup: Status Epilepticus
Treatment & Medication: Status Epilepticus
Follow-up: Status Epilepticus
Multimedia: Status Epilepticus
References
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Further Reading

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Keywords

SE, absence status epilepticus, complex partial status epilepticus, generalized convulsive status epilepticus, nonconvulsive status epilepticus, simple partial status epilepticus, subtle status epilepticus, Treiman's classification, nonepileptic seizures, NES

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Contributor Information and Disclosures

Author

Mark Spitz, MD, Professor, Department of Neurology, University of Colorado Health Sciences Center
Mark Spitz, MD is a member of the following medical societies: American Academy of Neurology, American Clinical Neurophysiology Society, and American Epilepsy Society
Disclosure: abbott Consulting fee Independent contractor

Coauthor(s)

Frank Lum, MD, Instructor, Department of Neurology, University of Colorado Health Sciences Center
Disclosure: Nothing to disclose.

Jose E Cavazos, MD, PhD, Assistant Professor, Departments of Medicine (Neurology), Pharmacology, and Physiology, University of Texas Health Science Center at San Antonio
Jose E Cavazos, MD, PhD is a member of the following medical societies: American Academy of Neurology, American Clinical Neurophysiology Society, American Epilepsy Society, and Society for Neuroscience
Disclosure: Glaxo-SmithKline Honoraria Speaking and teaching; Ortho-McNeil Neurologics Honoraria Speaking and teaching; UCB Pharma Honoraria Speaking and teaching

Edward Maa, MD, Epilepsy Fellow, Department of Neurology, University of Colorado Health Science Center
Disclosure: Nothing to disclose.

Medical Editor

Joseph F Hulihan, MD, Vice President, Medical Affairs, Ortho-McNeil Janssen Scientific Affairs, LLC
Joseph F Hulihan, MD is a member of the following medical societies: American Academy of Neurology, American Clinical Neurophysiology Society, American Epilepsy Society, American Headache Society, and American Medical Association
Disclosure: Johnson & Johnson Salary Employment; Johnson & Johnson Stock Employment

Pharmacy Editor

Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: Nothing to disclose.

Managing Editor

Norberto Alvarez, MD, Assistant Professor, Department of Neurology, Harvard Medical School; Consulting Staff, Department of Neurology, Boston Children's Hospital
Norberto Alvarez, MD is a member of the following medical societies: American Academy of Neurology, American Epilepsy Society, and Child Neurology Society
Disclosure: Nothing to disclose.

CME Editor

Selim R Benbadis, MD, Professor, Director of Comprehensive Epilepsy Program, Departments of Neurology and Neurosurgery, University of South Florida School of Medicine, Tampa General Hospital
Selim R Benbadis, MD is a member of the following medical societies: American Academy of Neurology, American Academy of Sleep Medicine, American Clinical Neurophysiology Society, American Epilepsy Society, and American Medical Association
Disclosure: Nothing to disclose.

Chief Editor

Nicholas Y Lorenzo, MD, Chief Editor, eMedicine Neurology; Consulting Staff, Neurology Specialists and Consultants
Nicholas Y Lorenzo, MD is a member of the following medical societies: Alpha Omega Alpha and American Academy of Neurology
Disclosure: Nothing to disclose.

 
 
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