eMedicine Specialties > Emergency Medicine > Neurology
Status Epilepticus: Treatment & Medication
Updated: Aug 24, 2009
- Overview
- Differential Diagnoses & Workup
- Treatment & Medication
- Follow-up
Treatment
Prehospital Care
- Supportive care, including ABCs, must be addressed in the prehospital setting.
- Historic clues may be evident to EMS providers.
- If the seizure fails to stop within 4-5 minutes or if the patient is continuing to seize at the time of EMS arrival, prompt administration of anticonvulsants may be necessary.
- Because of the refrigeration requirements and the infrequent use of most anticonvulsants, diazepam (Valium) is often the only anticonvulsant available in the prehospital setting. Diazepam may be administered intravenously (IV) or per rectum (PR).
Emergency Department Care
- Recognition of status epilepticus may be easy or difficult. The patient with sequential, generalized major motor convulsions is obvious; the patient with nonconvulsive or subtle status is a diagnostic dilemma.
- Psychogenic nonepileptic seizures may be, at times, indistinguishable from GCSE. A brief period of observation for atypical features, as described above (see Physical), may lead to the conclusion that the patient has nonepileptic seizures and does not need anticonvulsant therapy.
- Regardless of the clinical manifestations of generalized status epilepticus, aggressive supportive care and prompt termination of electrical seizure activity are the goals.
- Care is individualized to the patient; for example, nasopharyngeal airway placement is sufficient for some patients, particularly if the seizures are stopped and the patient is awakening. For other patients, endotracheal intubation is necessary.
- In neuromuscular paralysis, rapid sequence induction is necessary at times.
- Use short-acting paralytics to ensure that ongoing seizure activity is not masked.
- Use EEG monitoring if long-acting paralytics are used and if a question exists about seizure cessation.
- Initiate rapid glucose determination and correction.
- Establish intravenous access, ideally in a large vein. Intravenous administration is the preferred route for anticonvulsant administration because it allows therapeutic tissue levels to be attained more rapidly. Begin cardiac and other hemodynamic monitoring.
- Begin administration of anticonvulsant medication if seizure activity does not terminate within 4-5 minutes. If EMS history has already defined status epilepticus, treatment should begin immediately.
Consultations
- Neurologists, ideally those with special expertise in epilepsy, are the consultants of choice for status epilepticus.
- Other medical conditions or referral patterns may involve pediatricians, internists, or neurosurgeons.
Medication
"Seizures beget seizures" is a generally accepted clinical axiom. The argument follows that earlier treatment is more effective than later treatment in halting status epilepticus. Current consensus is that a benzodiazepine, notably lorazepam (Ativan), is the initial class of drug for the treatment of status epilepticus. A phenytoin, phenytoin sodium or fosphenytoin (Cerebyx), generally is agreed upon as the next drug to be administered.
Failure to respond to optimal benzodiazepine and phenytoin loading operationally defines refractory status epilepticus. No data clearly support a best third-line drug, controlled trials are lacking, and recommendations vary greatly. The list of third-line drugs includes phenobarbital, midazolam, propofol, pentobarbital, valproate, levetiracetam, lidocaine, and others. A clinical practice trend seems to be for use of propofol as a third-line agent, often initiated during induction for endotracheal intubation. Consultation with intensivists, neurologists, and other physicians is recommended. A general principle is to maximize benzodiazepine and phenytoin dosages before adding an additional agent. Many of these drugs are classified as category D in pregnancy. However, these drugs may be used in life-threatening situations, such as GCSE.
Benzodiazepines
These agents are used commonly as the first drug for treatment of GCSE. Lorazepam, when available, is thought to be the most effective and has a longer seizure half-life than diazepam.
Lorazepam (Ativan)
Sedative hypnotic with short onset of effects and relatively long half-life. By increasing action of GABA, a major inhibitory neurotransmitter in the brain, may depress all levels of CNS, including limbic and reticular formation. Important to monitor patient's BP after administering dose. Adjust as necessary.
Adult
4 mg IV slowly at 2 mg/min; if seizure continues or recurs after 10-15 min, administer an additional 4 mg IV slowly at 2 mg/min
Pediatric
Infants and children: 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
Adolescents: 0.07 mg/kg IV slowly over 2-5 min; repeat in 10-15 min prn; not to exceed 4 mg/dose
Alcohol, phenothiazines, barbiturates, and MAOIs increase CNS toxicity
Documented hypersensitivity; preexisting CNS hypotension; depression; narrow-angle glaucoma
Pregnancy
D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus
Precautions
Caution in renal or hepatic impairment, myasthenia gravis, organic brain syndrome, or Parkinson disease
Diazepam (Diastat, Valium)
Depresses all levels of CNS (eg, limbic and reticular formation), possibly by increasing activity of GABA. Individualize dosage and increase cautiously to avoid adverse effects.
Adult
5-10 mg IV q10-20min; repeat in 2-4 h prn; not to exceed 30 mg/8 h
Pediatric
0.05-0.3 mg/kg/dose IV over 2-3 min q15-30min; repeat in 2-4 h prn; not to exceed 10 mg
Phenothiazines, barbiturates, alcohols, and MAOIs increase toxicity
Documented hypersensitivity; narrow-angle glaucoma
Pregnancy
D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus
Precautions
Caution with other CNS depressants, low albumin levels, or hepatic disease (may increase toxicity)
Midazolam (Versed)
Used as alternative in termination of refractory status epilepticus. Because midazolam is water soluble, takes approximately 3 times longer than diazepam to peak EEG effects. Thus, clinician must wait 2-3 min to fully evaluate sedative effects before initiating procedure or repeating dose.
Adult
Loading dose: 0.2 mg/kg IV
Continuous infusion: 0.1-0.4 mg/kg/h
10-15 mg IM (when other access impossible)
Intubation and pressor support are necessary
Pediatric
Loading dose: 0.15 mg/kg IV
Maintenance dose: 1 mcg/kg/min; titrate dose upward q5min until clinical seizure activity controlled
Theophylline may antagonize sedative effects; narcotics and erythromycin may accentuate sedative effects because of decreased clearance
Documented hypersensitivity; preexisting hypotension; narrow-angle glaucoma; sensitivity to propylene glycol (diluent)
Pregnancy
D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus
Precautions
Caution in congestive heart failure, pulmonary disease, renal impairment, and hepatic failure
Anticonvulsants
These agents are used to terminate clinical and electrical seizure activity as rapidly as possible and to prevent seizure recurrence.
Phenytoin (Dilantin)
May act in motor cortex, where it may inhibit spread of seizure activity. Activity of brainstem centers responsible for tonic phase of grand mal seizures also may be inhibited. Dose should be individualized. Administer larger dose before retiring if dose cannot be divided equally.
Adult
Loading dose: 18-20 mg/kg IV; hypotension may necessitate slowing administration rate; rate not to exceed 50 mg/min (hypotension and arrhythmias can otherwise occur); if status epilepticus persists, may increase to total of 30 mg/kg
Pediatric
Administer as in adults
Amiodarone, benzodiazepines, chloramphenicol, cimetidine, fluconazole, isoniazid, metronidazole, miconazole, phenylbutazone, succinimides, sulfonamides, omeprazole, phenacemide, disulfiram, ethanol (acute ingestion), trimethoprim, and valproic acid may increase toxicity
Barbiturates, diazoxide, ethanol (chronic ingestion), rifampin, antacids, charcoal, carbamazepine, theophylline, and sucralfate may decrease effects
May decrease effects of acetaminophen, corticosteroids, dicumarol, disopyramide, doxycycline, estrogens, haloperidol, amiodarone, carbamazepine, cardiac glycosides, quinidine, theophylline, methadone, metyrapone, mexiletine, oral contraceptives, and valproic acid
Documented hypersensitivity; sinoatrial block; second- and third-degree AV block; sinus bradycardia; Adams-Stokes syndrome
Pregnancy
D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus
Precautions
Perform blood counts and urinalysis when therapy is begun and at monthly intervals for several months thereafter to monitor for blood dyscrasias; discontinue use if skin rash appears, and do not resume use if rash is exfoliative, bullous or purpuric; rapid IV infusion may result in death from cardiac arrest, marked by QRS widening; caution in acute intermittent porphyria and diabetes (may elevate blood glucose level); discontinue use if hepatic dysfunction occurs
Fosphenytoin (Cerebyx)
Diphosphate ester salt of phenytoin, which acts as water-soluble prodrug of phenytoin. Following administration, plasma esterases convert fosphenytoin to phosphate, formaldehyde, and phenytoin. Phenytoin, in turn, stabilizes neuronal membranes and decreases seizure activity. To avoid need to perform molecular weight-based adjustments when converting between fosphenytoin and phenytoin sodium doses, dose is expressed as phenytoin sodium equivalents (PE). Although can be administered IV/IM, IV is route of choice and should be used in emergency situations.
Since full antiepileptic effect of phenytoin, whether given as fosphenytoin or parenteral phenytoin, is not immediate, coadministration of an IV benzodiazepine usually necessary to control GCSE.
IM administration of this medication has been approved. However IV still route of choice for status epilepticus. Cardiac monitoring required when administered IV but not required for IM administration.
Adult
15-20 mg PE/kg IV/IM at rate of 100-150 mg PE/min; if status epilepticus persists, may increase to total of 30 mg/kg
Pediatric
Administer as in adults
Amiodarone, benzodiazepines, chloramphenicol, cimetidine, disulfiram, ethanol (acute ingestion), omeprazole, phenacemide, phenylbutazone, succinimides, fluconazole, isoniazid, metronidazole, miconazole, sulfonamides, trimethoprim, and valproic acid may increase toxicity
Barbiturates, carbamazepine, theophylline, diazoxide, ethanol (chronic ingestion), rifampin, antacids, charcoal, and sucralfate may decrease effects
May decrease effects of acetaminophen, corticosteroids, dicumarol, disopyramide, doxycycline, estrogens, haloperidol, amiodarone, carbamazepine, cardiac glycosides, methadone, metyrapone, mexiletine, oral contraceptives, quinidine, theophylline, and valproic acid
Documented hypersensitivity; sinoatrial block; second- and third-degree AV block; Adams-Stokes syndrome
Pregnancy
D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus
Precautions
Blood dyscrasias have occurred—perform blood counts and urinalysis when therapy is begun and at monthly intervals for several months thereafter; discontinue use if skin rash appears; do not resume if rash is exfoliative, bullous, or purpuric; death from cardiac arrest has occurred after too-rapid IV administration, preceded sometimes by marked QRS widening; administer cautiously to patients with acute intermittent porphyria; exercise caution when administering to diabetics (may raise blood glucose levels); discontinue drug if hepatic dysfunction occurs
Anesthetics
These agents stabilize the neuronal membrane so the neuron is less permeable to ions. This prevents the initiation and transmission of nerve impulses, thereby producing the local anesthetic effects. In status epilepticus, lidocaine is indicated during refractory status only and is supported only by anecdotal reports. The consensus seems to be moving toward propofol or midazolam infusions for refractory status epilepticus.
Propofol (Diprivan)
Phenolic compound unrelated to other types of anticonvulsants. Has general anesthetic properties when administered IV. Growing anecdotal reports of use in refractory status epilepticus.
Intubation and ventilation required. Hypotension may require treatment.
Adult
Loading dose: 2 mg/kg IV
Maintenance dose: 0.1-0.2 mg/kg/min (6-12 mg/kg/h) IV
Pediatric
Not established
Recommended dose: 2-2.8 mg/kg IV
Reduce dose when administered concomitantly with benzodiazepines, opiates, phenothiazines, ethanol, or narcotics; may potentiate neuromuscular blockade of vecuronium; theophylline may weaken effects, and dose increase may be needed
Documented hypersensitivity; patients not mechanically ventilated
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions
Do not administer with blood or blood products using same IV catheter; patients may develop apnea; may experience decrease in systemic vascular resistance, leading to hypotension
Barbiturates
This class of anticonvulsant may be useful when the condition fails to respond to phenytoin and benzodiazepines. This is the commonly used third-line drug, but midazolam, propofol, and others are increasingly used in preference to phenobarbital, although no rigorous evidence supports the use of one third-line drug over another.
Phenobarbital (Luminal, Barbita)
Exhibits anticonvulsant activity in anesthetic doses. In status epilepticus, important to achieve therapeutic levels as quickly as possible. IV dose may require approximately 15 min to attain peak levels in brain.
If IM route chosen, administer into large muscle such as gluteus maximus or vastus lateralis or other areas where risk of encountering nerve trunk or major artery is low. Permanent neurologic deficit may result from injection into or near peripheral nerves. Restrict IV use to conditions in which other routes not possible, either because patient is unconscious or because prompt action required. If used to terminate GCSE, administer up to 15-20 mg/kg. Ventilation and intubation may be necessary. Hypotension may require treatment.
A trend is to recommend agents other than phenobarbital (propofol, midazolam, other barbiturates) for refractory status epilepticus.
Adult
15-20 mg/kg IV; maximum infusion rate of 100 mg/min
Pediatric
15-20 mg/kg over 10-15 min IV in single or divided dose
Some patients may require 5 mg/kg/dose IV q15-30min until seizure controlled or 40 mg/kg administered
May decrease effects of chloramphenicol, digitoxin, corticosteroids, carbamazepine, theophylline, verapamil, metronidazole, and anticoagulants (patients stabilized on anticoagulants may require dosage adjustments if added to or withdrawn from their regimen); alcohol may produce additive CNS effects and death; chloramphenicol, valproic acid, and MAOIs may increase toxicity; rifampin may decrease effects; induction of microsomal enzymes may decrease effects of oral contraceptives in women (must use additional contraceptive methods to prevent unwanted pregnancy; menstrual irregularities may also occur)
Documented hypersensitivity; severe respiratory disease; marked impairment of liver function; nephritis
Pregnancy
D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus
Precautions
In prolonged therapy, evaluate hematopoietic, renal, hepatic, and other organ systems; caution in fever, hyperthyroidism, diabetes mellitus, and severe anemia since adverse reactions can occur; caution in myasthenia gravis and myxedema
Pentobarbital (Nembutal)
Short-acting barbiturate with sedative, hypnotic, and anticonvulsant properties. Can produce mood alteration at all levels of CNS. Use only in refractory status when other agents have failed. Patients need intubation and respiratory support.
Adult
Loading dose: 12 mg/kg IV
Maintenance dose: 5 mg/kg/h IV infusion; titrate to EEG inactivity
Pediatric
Administer as in adults
Alcohol may produce additive CNS effects and death; chloramphenicol may inhibit metabolism; may enhance chloramphenicol metabolism; MAOIs may enhance sedative effects; valproic acid appears to decrease metabolism, increasing toxicity; can decrease effects of anticoagulants (patients may require dosage adjustments if barbiturates added to or withdrawn from regimen); decreased contraceptive effect may occur because of induction of microsomal enzymes (alternate form of birth control suggested); may decrease corticosteroid and digitoxin effects through induction of hepatic microsomal enzymes, which increase metabolism; decreases theophylline levels and may decrease effects; may decrease verapamil bioavailability
Documented hypersensitivity; liver failure
Pregnancy
D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus
Precautions
Patient may become tolerant to hypnotic effects; caution in hypovolemic shock, respiratory dysfunction, renal dysfunction, congestive heart failure, previous addiction to sedative hypnotics
More on Status Epilepticus |
| Overview: Status Epilepticus |
| Differential Diagnoses & Workup: Status Epilepticus |
 Treatment & Medication: Status Epilepticus |
| Follow-up: Status Epilepticus |
| References |
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References
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Further Reading
Keywords
status epilepticus, generalized convulsive status epilepticus, GCSE, seizure, subtle status epilepticus, nonconvulsive status epilepticus, epilepsy, seizure disorder, tonic-clonic activity, persistent tonic seizure, idiopathic seizure disorder, stroke, hypoxic injury, tumor, subarachnoid hemorrhage, trauma, toxicologic effects, electrolyte abnormality, hyponatremia, hypernatremia, hypercalcemia, hepatic encephalopathy, meningitis, brain abscess, encephalitis, metabolic acidosis, isoniazid toxicity, anticonvulsant irregularity
