eMedicine Specialties > Emergency Medicine > Neurology

Seizures

M Tyson Pillow, MD, Assistant Director of Medical Education, Ben Taub General Hospital Emergency Center; Assistant Professor, Baylor College of Medicine
David S Howes, MD, Residency Program Director, Professor of Medicine, Section of Emergency Medicine, University of Chicago/Pritzker School of Medicine; Shaneen U Doctor, MD, Research Assistant, Department of Emergency Medicine, University of Chicago

Updated: Jan 22, 2010

Introduction

Background

A seizure is an episode of neurologic dysfunction caused by abnormal neuronal activity that results in a sudden change in behavior, sensory perception, or motor activity. The clinical spectrum of seizures includes simple and complex focal or partial seizures and generalized seizures.

The term epilepsy refers to recurrent, unprovoked seizures from known or unknown causes. Ictus describes the period in which the seizure occurs, and post-ictal refers to the period after the seizure has ended but before the patient has returned to his or her baseline mental status. A focal or partial seizure describes abnormal neuronal firing that is limited to one hemisphere or area of the brain that manifests itself as seizure activity on one side of the body or one extremity. These seizures are classified as simple partial if there is no change in mental status or complex partial if there is some degree of impaired consciousness.

A generalized seizure consists of abnormal electrical activity involving both cerebral hemispheres that causes an alteration in mental status. Traditionally, the patient with 30 minutes of continuous seizure activity or a series of seizures without a return to full consciousness is defined as being in status epilepticus (SE). Newer definitions suggest that status epilepticus is defined by duration of 5 continuous minutes of generalized seizure activity or 2 or more separate seizure episodes without return to baseline.^{[1 ]}This article focuses on the emergency department (ED) evaluation, management, and disposition of adult patients presenting for evaluation of seizure.

Febrile seizures in children are a distinct entity and are discussed in a separate article.

Pathophysiology

A seizure results when abnormal neuronal firing manifests clinically by changes in motor control, sensory perception, behavior, and/or autonomic function. This sudden biochemical imbalance between excitatory neurotransmitters and the NMDA receptor and inhibitory forces (GABA) at the neuronal cell membrane results in repeated, abnormal electrical discharges that may stay within a certain area of the brain or they may propagate throughout the brain resulting in generalized seizures. For example, in the event that these neuronal discharges are confined to the visual cortex, the seizure manifests itself with visual phenomena.

Seizures also produce a number of physiologic changes. Many of these systemic responses are thought to be a result of the catecholamine surge that accompanies seizures.^{[2 ]}During a generalized seizure, there can be a period of transient apnea and subsequent hypoxia. In a physiological effort to maintain appropriate cerebral oxygenation, the patient may become hypertensive. Additionally, transient hyperthermia may occur in up to 40% of patients and is thought to result from vigorous muscle activity that occurs in a seizure.^{[3 ]} Hyperglycemia and lactic acidosis occur within minutes of a convulsive episode and usually resolve within 1 hour.^{[4 ]}Transient leukocytosis may also be seen but is not accompanied by bandemia (unless infection is present).

In the setting of prolonged convulsive seizure activity or status epilepticus, there is pronounced systemic decompensation including hypoxemia, hypercarbia, hypertension followed by hypotension, hyperthermia, depletion of cerebral glucose and oxygen, cardiac dysrhythmias, and rhabdomyolysis. These changes may even take place despite adequate oxygenation and ventilation. In extremis, pulmonary edema and disseminated intravascular coagulation (DIC) have also been reported.^{[5 ]}

Frequency

United States

• Epilepsy and seizures affect more than 3 million American of all ages.
• Approximately 200,000 new cases occur each year, of which 40-50% will recur be classified as epilepsy.^{[6 ]}
• Overall, approximately 50,000-150,000 cases will reach status epilepticus.

Mortality/Morbidity

• Up to 50% of patients with epilepsy will have recurrent seizures despite medical therapy.^{[7 ]}
• Up to 25% of patients with a first-time, generalized seizure will have a recurrence within 2 years.^{[8 ]}
• The overall mortality rate is about 20% for those who reach status epilepticus.
• The mortality rates are highest for those older than 75 years, reflecting an increased incidence of degenerative, neoplastic, and vascular pathologies.

Sex

• Males are slightly more likely to develop epilepsy than females.

Age

• Incidence is highest in those younger than 2 years and in those older than 65 years.

Clinical

History

• A history of epilepsy is often noted (if the patient is unconscious, family, friends, or prehospital personnel can be questioned).
• Recent noncompliance with medications
• History of CNS pathology (stroke, neoplasms, recent surgery)
• History of systemic neoplasms, infections, metabolic disorders, or toxic ingestions
• Recent trauma or fall
• Alcohol abuse
• Recent travel or immigration to the United States
• Pregnancy
• Focal symptoms (partial seizure activity) that then progressed to a generalized seizure

Physical

• A generalized seizure is recognizable at the bedside when tonic-clonic activity is present.
• If the patient is actively seizing, attempt to observe motor activity, as posturing (decerebrate/decorticate) and eye deviation may provide clues to the epileptic focus.
• A partial seizure may present as isolated seizure activity with or without loss of consciousness. The workup for partial seizures is more extensive and requires neurologic consultation.
• Identifying a partial seizure that then generalizes to a full tonic-clonic seizure may be difficult, as this may be missed as the initial presentation of a generalized seizure.
• Vital signs 
  • In a generalized, tonic-clonic seizure, accurate vital signs are difficult to obtain.
  • Low-grade fever may be present initially, but prolonged fever may be an indication of infectious etiology.
• Mental status examination 
  • As mentioned above, any seizure with loss of consciousness is termed complex.
• Neurologic examination 
  • Focal deficits may be evidence of an old lesion, new pathology, or Todd’s paralysis (transient, <24 h paralysis that mimics stroke)
  • Hyperreflexia and extensor plantar responses are indicative of a recent seizure but should resolve during the post-ictal period.

Causes

• The differential diagnosis for seizure disorder consists of a myriad of conditions.
• For patients with known seizure disorder, the most likely cause is subtherapeutic levels of antiepileptic medications, including the following: 
  • Medical noncompliance
  • Systemic derangement that may disrupt absorption, distribution, and metabolism of medication (infection)
• In addition, multiple other factors, including stress, lack of sleep, and caffeine use, may contribute to seizures in patients with known seizure disorder, but these are diagnoses of exclusion.
• For patients presenting with new-onset seizure disorder, the differential is broad: 
  • CNS pathologies (stroke, neoplasm, trauma, hypoxia, vascular abnormality)
  • Metabolic abnormalities (hypoglycemia/hyperglycemia, hyponatremia/hypernatremia, hypercalcemia, hepatic encephalopathy)
  • Toxicologic etiologies (alcohol withdrawal, cocaine, isoniazid, theophylline)
  • Infection etiologies (meningitis, encephalitis, brain abscess) – Neurocysticercosis and malaria are very common causes of seizures in the developing world and should be considered in patients with history of travel or immigrants.

Differential Diagnoses

Workup

Laboratory Studies

• Clinical information should guide the specific workup of a patient. 
  • Studies have shown a low yield for extensive laboratory tests in the evaluation of a patient presenting with a first-time, single seizure.
  • In one study, laboratory tests such as blood counts, blood glucose level, and electrolyte panels were abnormal in up to 15% of individuals.^{[9 ]}However, most abnormalities were incidental or insignificant.
• An ACEP Clinical Policy recommends the following in adults with new-onset seizure:^{[10 ]} 
  • Serum glucose level
  • Serum sodium level
  • Pregnancy test in women of childbearing age
• For patients with a first-time, generalized tonic-clonic seizure, obtain a chem 7 (electrolyte panel) and urine or serum pregnancy test. Other tests can be ordered at the physician's discretion based on the history and symptoms.
• For patients with known seizure disorder who are currently taking medications, blood levels of antiepileptic medications should be obtained. Levels are often not available for newer agents.
• For patients with a history of malignancy, serum calcium levels should be obtained.
• Toxicologic testing 
  • No evidence suggests that such testing changes outcomes.^{[11 ]}
  • Toxicologic testing may be beneficial for help with future medical and psychiatric management.
• An arterial blood gas (ABG) measurement has limited clinical utility for the patient in status epilepticus because it will likely reveal metabolic acidosis but should rapidly correct after the patient stops seizing.

Imaging Studies

• Computed tomography 
  • For patients with new-onset seizures or those in status epilepticus, noncontrast head CT in the ED is the imaging procedure of choice because of availability and ability to identify potential catastrophic pathologies. 
    • For the patient who presents for first-time, generalized tonic-clonic seizure that has returned to baseline mental status with a normal neurologic examination and who has no comorbidities, CT may be completed as on outpatient basis provided follow-up is ensured. However, because of the availability and speed of CT scanning in the ED, routine CT scanning for first-time seizure is strongly recommended.
    • For any partial seizure or suspected intracranial process (trauma, history of malignancy, immunocompromise, or anticoagulation, new focal neurologic examination, age >40 y), then a head CT should be performed emergently.
    • Approximately 3-41% of patients with first-time seizures will have abnormal head CT findings.^{[12 ]}Timing of the CT is still somewhat controversial.
    • In patients with a known seizure disorder, consider a head CT if any of the following are present: new focal deficits, trauma, persistent fever, new character or pattern to the seizures, suspicion for AIDS, infection, or anticoagulation.
• Magnetic resonance imaging: MRI may be a better diagnostic test because of higher yield and ability to identify smaller lesions, but availability from the ED may be a limiting factor. In addition, MRI is time-consuming and may interfere with adequate patient monitoring.

Other Tests

• Electrocardiography (ECG) should be considered in certain patients. Seizure activity can be precipitated by cerebral hypoperfusion from an arrhythmia. The ECG may identify the following:
  • Prolonged QTc
  • Widened QRS
  • Prominent R in aVR
  • Heart block
• Electroencephalography
  • Electroencephalography (EEG) is not routinely available in the ED.
  • EEG should be part of the full neurodiagnostic workup, as it has substantial yield and ability to predict risk of seizure recurrence.
  • In the ED, EEG should be considered if available and if the patient is paralyzed, is intubated, or is in refractory status epilepticus to ensure that seizure activity is controlled.

Procedures

• Lumbar puncture: Lumbar puncture should be considered for patients with immunocompromise, persistent fever, severe headache, or persistently altered mental status.

Treatment

Prehospital Care

• Care is mostly supportive, as most seizures are short duration, especially pediatric simple febrile seizures.
• ABCs, including oxygenation and airway assessment, temperature assessment, blood glucose assessment, and spinal precautions, should be performed as needed.
• Intravenous access should be obtained for almost all patients (may be deferred in those with simple febrile seizures).
• EMS protocols should include benzodiazepines (either IV, IM, or rectal) for prolonged seizures or status epilepticus. 

Emergency Department Care

Care should be individualized for the patient presenting with seizure.

• Sometimes, the most difficult part of the ED evaluation is differentiating whether the patient has had a seizure. Clues to the diagnosis include a clear history of tonic-clonic movements, urinary or bowel incontinence, post-episode confusion, and tongue biting.
• Attempt to obtain history from EMS providers, family, friends, or observers who may have been present during the episode.
• For those who present with a witnessed seizure who have stopped seizing, supportive care is adequate. 
  • If antiepileptic medication levels are found to be low, then a loading dose given in the ED and discharge home is appropriate as long as there are no other concerning features to the presentation.
  • Phenytoin is an extremely common antiepileptic medication and is classically given as "one gram" in the ED, sometimes with the medication being delivered as half oral and half parenteral. Oral absorption of the drug can be erratic, but, when given in the appropriate doses (15-20 mg/kg PO either as a single dose or divided into 400-600 mg per dose every 2 h), it can achieve therapeutic serum levels.^{[13,14 ]}
  • Both valproic acid and phenobarbital can also be given parenterally as a loading dose at 20 mg/kg.^{[15 ]}
  • Carbamazepine has proven to be effective for oral loading, but it is associated with a high rate of adverse effects. Therefore, oral loading is not recommended at this time.^{[16 ]}
  • Newer antiepileptic drugs, such as lamotrigine and levetiracetam, have varying drug profiles and are still being studied. Doses of these medications should be given in consultation with a neurologist.

• Airway management
  • Administer oxygen.
  • For patients who are in status epilepticus or cyanotic, endotracheal intubation using rapid sequence intubation (RSI) should be strongly considered.
    • If using RSI, short-acting paralytics should be used to ensure that ongoing seizure activity is not masked.
    • Consider EEG monitoring in the ED if the patient has been paralyzed because there is no other method to determine if seizure activity is still present.
• Establish large-bore intravenous access.
• Initiate rapid glucose determination and treat appropriately.
• Consider antibiotics with or without antiviral agents, depending on the clinical situation.
• The goal of treatment is to control the seizure before neuronal injury occurs (theoretically between 20 min to 1 h).
• CNS infections and anoxic injury are the leading causes of mortality associated with status epilepticus.

Initial therapies:

• Benzodiazepines - Considered first-line therapy
  • Intravenous options include lorazepam, diazepam, and midazolam.
  • If intravenous access cannot be obtained, then IM lorazepam or midazolam, or rectal diazepam can be considered.
  • Intravenous lorazepam was found to be superior to intravenous diazepam in both seizure cessation and preventing recurrent seizures.^{[17 ]}
  • A common regimen is 0.1 mg/kg of lorazepam (Ativan) IV given at 2 mg/min or 0.2 mg/kg diazepam IV given at 5-10 mg/min.
  • Very large doses of benzodiazepines may be needed. Note: There is no specific upper limit to benzodiazepine dose when used for acute seizure control. As with all sedatives, monitor the patient for respiratory or cardiovascular depression.
• Phenytoin - Usually considered the second-line agent for patients who continue to seize despite aggressive benzodiazepine therapy
  • The recommended dose is 20 mg/kg IV and can be augmented with another 10 mg/kg IV if the patient is still seizing.
  • Care should be taken with the administration of parenteral phenytoin because the propylene glycol diluent may cause hypotension, cardiac arrhythmias, and death if given too quickly.^{[18,19 ]}
  • Fosphenytoin is a phenytoin precursor that is considered to be safer than phenytoin by some authors as it does not contain a propylene glycol diluent.^{[20 ]}Other authors have disputed a safety advantage for fosphenytoin, and it is much more expensive than phenytoin.^{[21 ]}Fosphenytoin may be administered intramuscularly, and this is an advantage for patients without intravenous access.
• Valproic acid – Effective in treating all forms of seizure
  • Recommended dose of valproic acid is 15-20 mg/kg.
  • Valproic acid has an excellent safety profile.^{[22 ]}
  • It is contraindicated in hepatic dysfunction because of the extremely rare occurrence of fatal idiosyncratic hepatotoxicity.^{[23,24 ]}
• Phenobarbital – Similar efficacy to lorazepam
  • Recommended dose of phenobarbital is 20 mg/kg, but, like phenytoin, it can be given up to 30 mg/kg for severe refractory seizures.
  • Phenobarbital may cause hypotension and respiratory depression.

Continuous infusions:

• If 2 or more of the initial drug therapies fail to control the seizures, then the next line of treatment includes continuous infusions of antiepileptic medications. The major side effects are hypotension and respiratory depression, and the patient should be intubated (if not already completed up to this point) and preparation made to support the patient's cardiovascular status.
  • Pentobarbital
    • Pentobarbital is shorter acting than phenobarbital, but it is more sedating.
    • Pentobarbital should be administered in a bolus at 5-15 mg/kg, then continuous infusion of 0.5-10 mg/kg/h as tolerated.
  • Midazolam: Midazolam is administered as a 0.2 mg/kg bolus, then continuous infusion of 0.05-2 mg/kg/h.
  • Propofol
    • Limited data are available, but propofol appears to be very effective at terminating seizures.
    • Propofol is administered in a bolus at 2-5 mg/kg, then continuous infusion of 20-100 mcg/kg/min.
    • It is limited by infusion syndrome of hypotension, metabolic acidosis, and hyperlipidemia seen with prolonged infusions.^{[25 ]}
• There is very little evidence to guide use of these medications.
• Midazolam is slightly less effective at stopping seizures versus propofol or pentobarbital, but treatment with midazolam has a lower frequency of occurrence of hypotension.^{[23 ]}

Consultations

Many patients with seizure may be managed without consultation. Consultation should be considered in the following circumstances:

• Status epilepticus: Consider consulting a neurologist or an intensivist.
• Breakthrough seizure in a compliant patient with therapeutic levels: Consider consulting the physician who is chronically managing the patient's seizure disorder. Medication changes may be needed and ideally should be coordinated with a physician providing ongoing care.

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. 

Phenytoin or fosphenytoin (Cerebyx) is the next drug to be administered when a second drug is needed.

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 barbiturates, propofol, valproate, levetiracetam, and lidocaine. 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 generalized convulsive status epilepticus (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.

Dosing

Adult

0.1 mg/kg IV slowly at 2 mg/min; there is no set maximum dose of benzodiazepines, but consider switching to another agent after 10 mg total dose

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

Interactions

Alcohol, phenothiazines, barbiturates, and MAOIs increase CNS toxicity

Contraindications

Documented hypersensitivity; preexisting CNS hypotension; depression; narrow-angle glaucoma

Precautions

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.

Dosing

Adult

0.2 mg/kg given 5-10 mg IV q10-20min; consider another agent after administering 30 mg total dose

Pediatric

0.05-0.2 mg/kg/dose IV over 2-3 min q15-30min; repeat in 2-4 h prn; not to exceed 10 mg

Interactions

Phenothiazines, barbiturates, alcohols, and MAOIs increase toxicity

Contraindications

Documented hypersensitivity; narrow-angle glaucoma

Precautions

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.

Dosing

Adult

0.1 mg/kg IV slowly at 2 mg/min; there is no set maximum dose of benzodiazepines, but consider switching to another agent after 10 mg total dose
Loading dose (before continuous infusion): 0.2 mg/kg IV
Continuous infusion: 0.05-2 mg/kg/h IV
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

Interactions

Theophylline may antagonize sedative effects; narcotics and erythromycin may accentuate sedative effects because of decreased clearance

Contraindications

Documented hypersensitivity; preexisting hypotension; narrow-angle glaucoma; sensitivity to propylene glycol (diluent)

Precautions

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 may also be inhibited. Dose should be individualized. Administer larger dose before retiring if dose cannot be divided equally.

Dosing

Adult

Loading dose: 18-20 mg/kg PO/IV; hypotension may necessitate slowing parenteral 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

Interactions

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

Contraindications

Documented hypersensitivity; sinoatrial block; second- and third-degree AV block; sinus bradycardia; Adams-Stokes syndrome

Precautions

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, 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.

Dosing

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

Interactions

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

Contraindications

Documented hypersensitivity; sinoatrial block; second- and third-degree AV block; Adams-Stokes syndrome

Precautions

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; caution in acute intermittent porphyria and diabetes (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.

Dosing

Adult

Loading dose: 2-5 mg/kg IV
Maintenance dose: 0.02-0.1 mg/kg/min IV

Pediatric

Not established
Recommended dose: 2-2.8 mg/kg IV

Interactions

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

Contraindications

Documented hypersensitivity; patients not mechanically ventilated

Precautions

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.

Dosing

Adult

15-20 mg/kg IV; maximum infusion rate of 100 mg/min; may give additional dose to max of 30 mg/kg

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 30 mg/kg administered

Interactions

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)

Contraindications

Documented hypersensitivity; severe respiratory disease; marked impairment of liver function; nephritis

Precautions

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.

Dosing

Adult

Loading dose: 5-15 mg/kg IV
Maintenance dose: 0.5-10 mg/kg/h IV infusion; titrate to EEG inactivity

Pediatric

Administer as in adults

Interactions

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

Contraindications

Documented hypersensitivity; liver failure

Precautions

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, or previous addiction to sedative-hypnotics

Follow-up

Further Inpatient Care

Disposition is based on the patient's severity and underlying cause of seizures. Most patients will be admitted to a telemetry floor for close monitoring, further workup, and treatment of their underlying condition. Any patient with status epilepticus, severe alcohol withdrawal, or underlying conditions (eg, diabetic ketoacidosis) requiring intensive monitoring and care is best served in an ICU setting.

Further Outpatient Care

For first-time, generalized tonic-clonic seizures with no concerning features and a normal emergency department workup, the patient can be discharged home once good follow-up is arranged on an urgent basis with the patient's primary care physician or a neurologist.

Patients who were found to have subtherapeutic levels of medications can be given loading doses orally or parenterally as indicated and follow up with their primary physician or neurologist on an urgent basis.

Inpatient & Outpatient Medications

Inpatient medications are given based on the patient's underlying diagnosis, severity, and preexisting medications in consultation with a neurologist.
 
Outpatient medications may include phenytoin, valproic acid, gabapentin, levetiracetam, carbamazepine, phenobarbital, or other medications. Any changes to medication regimen should be completed in consultation with the patient's neurologist or primary physician.

Transfer

In patients with severe, refractory seizures, patients with complicated diagnoses, or any patient who exceeds the resources of the hospital (eg, inability to get EEG monitoring in the ED for a paralyzed seizing patient), then strong consideration should be made to transferring the patient to a higher level of care.

Deterrence/Prevention

To date, no data support that any intervention other than medications effectively prevents seizures or status epilepticus. Therefore, medication compliance should always be emphasized to every patient.

Complications

Seizure complications are generally uncommon when medications are taken as indicated. Complications include drug side effects, tongue biting, and other minor trauma from falls during seizures. As an inpatient, fall precautions should be followed to ensure that patients do not inadvertently injure themselves.

Prognosis

Prognosis depends on both the underlying etiology of seizures and effectively terminating seizures before irreversible neurologic damage has occurred. A portion of patients with seizures will continue to have seizures despite optimal medical therapy.

Patient Education

Patients can be counseled to be prepared for seizure activity and avoid things that would put them at risk for complications. By law, patients are not able to drive unless they have been seizure free on medications for 1 year in most states. Any recreational activity that puts them at increased risk of injury if a seizure were to occur should be performed with at least one other person who is knowledgeable of the patient's condition and able to intervene if necessary. Patients can also carry rectal diazepam for treatment of breakthrough seizures. Many seizures are preceded by an aura, and patients can be educated to recognize their aura to prepare for a seizure.

Miscellaneous

Medicolegal Pitfalls

A few pitfalls may predispose the physician to ligation when taking care of the seizure patient:

• Failure to recognize seizure activity: Nonconvulsive seizure is a rare presentation of altered mental status (AMS) but should always be on the differential of the comatose patient. EEG is the diagnostic modality of choice to identify these patients.
• Failure to aggressively control seizure activity: Neurologic dysfunction is theorized to occur after 20 minutes of continuous seizure activity, even despite adequate oxygenation and ventilation. Therefore, there should be a low threshold to aggressively treat any seizure activity that lasts over 5 minutes.
• Failure to consider underlying etiology: Although medication noncompliance or subtherapeutic medication levels are among the most common causes of seizure presentations to the ED, patients should be screened for underlying infectious or metabolic causes of the seizures when indicated. In patients with therapeutic medication levels, fever, AMS, or other indication, laboratory and imaging studies should be considered, though breakthrough seizures often occur even in compliant patients with therapeutic drug levels.

Special Concerns

• Eclampsia: Seizures in pregnancy are a complication of severe, untreated preeclampsia. In fact, eclampsia can occur up to 4 weeks after delivery.^{[26 ]}Seizing pregnant patients should be treated just as the nonpregnant patient because the risk of complications from the seizure outweighs the risk of toxicity from the antiepileptics. Fortunately, eclamptic seizures are usually short in duration. Magnesium sulfate is the treatment of choice for eclamptic seizures because it is the most effective medication for prevention of recurrent seizures.^{[27 ]}
• Trauma: Seizures after trauma can be due to a variety of injuries and intracranial pathology must be ruled out. The risk of posttraumatic seizures with an obvious underlying injury is directly related to the severity of the injury but not significantly affected by early use of antiepileptic medications.^{[28,29 ]}
• Intracranial hemorrhage: Hemorrhagic stroke may predispose the patient to seizures. Deep, small intraparenchymal bleeds are thought to be low risk unless they involve the temporal regions. Larger bleeds causing mass effects are at higher risk for causing seizures. Common practice is to consider a prophylactic loading dose of an antiepileptic medication (commonly phenytoin or fosphenytoin).
• Alcohol withdrawal: This can occur anywhere from 6-48 hours after cessation of drinking and can occur at any blood alcohol level. Benzodiazepines are the mainstay of therapy, and large doses may be necessary to control the withdrawal and prevent or control seizures.^{[30 ]}
• Medication withdrawal: Barbiturate or benzodiazepine withdrawal may cause seizure. With certain agents, symptoms may not develop for days or even weeks after cessation of use.
• Drug-induced seizures: Tricyclic antidepressant (TCA) overdose and isoniazid (INH) therapy/overdose are two of the more common toxic causes of seizures. An ECG will show a widened QRS and prominent R wave in lead aVR. Treatment of TCA overdose consists of bicarbonate infusion and supportive care. Pyridoxine is the treatment of choice of known INH ingestion.

References

1. Lowenstein DH, Bleck T, Macdonald RL. It's time to revise the definition of status epilepticus. Epilepsia. Jan 1999;40(1):120-2. [Medline].

2. Huff JS. Status Epilepticus. eMedicine from WebMD. Updated August 24, 2009. Available at http://emedicine.medscape.com/article/793708-overview.

3. Wachtel TJ, Steele GH, Day JA. Natural history of fever following seizure. Arch Intern Med. Jun 1987;147(6):1153-5. [Medline].

4. Orringer CE, Eustace JC, Wunsch CD, Gardner LB. Natural history of lactic acidosis after grand-mal seizures. A model for the study of an anion-gap acidosis not associated with hyperkalemia. N Engl J Med. Oct 13 1977;297(15):796-9. [Medline].

5. Jagoda A, Riggio S. Refractory status epilepticus in adults. Ann Emerg Med. Aug 1993;22(8):1337-48. [Medline].

6. Hauser WA, Hesdorffer DC. Epilepsy: Frequency, Causes, and Consequences. New York: Demos Publications; 1990.

7. Semah F, Picot MC, Adam C, Broglin D, Arzimanoglou A, Bazin B. Is the underlying cause of epilepsy a major prognostic factor for recurrence?. Neurology. Nov 1998;51(5):1256-62. [Medline].

8. French JA, Pedley TA. Clinical practice. Initial management of epilepsy. N Engl J Med. Jul 10 2008;359(2):166-76. [Medline].

9. Krumholz A, Wiebe S, Gronseth G, et al. Practice Parameter: evaluating an apparent unprovoked first seizure in adults (an evidence-based review): report of the Quality Standards Subcommittee of the American Academy of Neurology and the American Epilepsy Society. Neurology. Nov 20 2007;69(21):1996-2007. [Medline].

10. American College of Emergency Physicians. Clinical policy: Critical issues in the evaluation and management of adult patients presenting to the emergency department with seizures. Ann Emerg Med. May 2004;43(5):605-25. [Medline].

11. Olson KR, Kearney TE, Dyer JE, Benowitz NL, Blanc PD. Seizures associated with poisoning and drug overdose. Am J Emerg Med. May 1994;12(3):392-5. [Medline].

12. Tardy B, Lafond P, Convers P, et al. Adult first generalized seizure: etiology, biological tests, EEG, CT scan, in an ED. Am J Emerg Med. Jan 1995;13(1):1-5. [Medline].

13. Ratanakorn D, Kaojarern S, Phuapradit P, Mokkhavesa C. Single oral loading dose of phenytoin: a pharmacokinetics study. J Neurol Sci. Mar 20 1997;147(1):89-92. [Medline].

14. Van Der Meyden CH, Kruger AJ, Muller FO, Rabie W, Schall R. Acute oral loading of carbamazepine-CR and phenytoin in a double-blind randomized study of patients at risk of seizures. Epilepsia. Jan-Feb 1994;35(1):189-94. [Medline].

15. Venkataraman V, Wheless JW. Safety of rapid intravenous infusion of valproate loading doses in epilepsy patients. Epilepsy Res. Jun 1999;35(2):147-53. [Medline].

16. Purcell TB, McPheeters RA, Feil M, Chavez R. Rapid oral loading of carbamazepine in the emergency department. Ann Emerg Med. Aug 2007;50(2):121-6. [Medline].

17. Prasad K, Al-Roomi K, Krishnan PR, Sequeira R. Anticonvulsant therapy for status epilepticus. Cochrane Database Syst Rev. Oct 19 2005;CD003723. [Medline].

18. Gellerman GL, Martinez C. Fatal ventricular fibrillation following intravenous sodium diphenylhydantoin therapy. JAMA. Apr 24 1967;200(4):337-8. [Medline].

19. Zoneraich S, Zoneraich O, Siegel J. Sudden death following intravenous sodium diphenylhydantoin. Am Heart J. Mar 1976;91(3):375-7. [Medline].

20. Wilder BJ. Use of parenteral antiepileptic drugs and the role for fosphenytoin. Neurology. Jun 1996;46(6 Suppl 1):S1-2. [Medline].

21. Lin T. Fosphenytoin. Cleveland Clinic Center for Continuing Education. Available at http://www.clevelandclinicmeded.com/medicalpubs/pharmacy/novdec2004/fosphenytoin.htm. Accessed August 7, 2009.

22. Marik PE, Varon J. The management of status epilepticus. Chest. Aug 2004;126(2):582-91. [Medline].

23. Claassen J, Hirsch LJ, Emerson RG, Mayer SA. Treatment of refractory status epilepticus with pentobarbital, propofol, or midazolam: a systematic review. Epilepsia. Feb 2002;43(2):146-53. [Medline].

24. Powell-Jackson PR, Tredger JM, Williams R. Hepatotoxicity to sodium valproate: a review. Gut. Jun 1984;25(6):673-81. [Medline].

25. Cannon ML, Glazier SS, Bauman LA. Metabolic acidosis, rhabdomyolysis, and cardiovascular collapse after prolonged propofol infusion. J Neurosurg. Dec 2001;95(6):1053-6. [Medline].

26. Lubarsky SL, Barton JR, Friedman SA, Nasreddine S, Ramadan MK, Sibai BM. Late postpartum eclampsia revisited. Obstet Gynecol. Apr 1994;83(4):502-5. [Medline].

27. Which anticonvulsant for women with eclampsia? Evidence from the Collaborative Eclampsia Trial. Lancet. Jun 10 1995;345(8963):1455-63. [Medline].

28. Annegers JF, Hauser WA, Coan SP, Rocca WA. A population-based study of seizures after traumatic brain injuries. N Engl J Med. Jan 1 1998;338(1):20-4. [Medline].

29. Temkin NR, Haglund MM, Winn HR. Causes, prevention, and treatment of post-traumatic epilepsy. New Horiz. Aug 1995;3(3):518-22. [Medline].

30. D'Onofrio G, Rathlev NK, Ulrich AS, Fish SS, Freedland ES. Lorazepam for the prevention of recurrent seizures related to alcohol. N Engl J Med. Mar 25 1999;340(12):915-9. [Medline].

31. Epilepsy Foundation of America's Working Group on Status Epilepticus. Treatment of convulsive status epilepticus. Recommendations of the Epilepsy Foundation of America's Working Group on Status Epilepticus. JAMA. Aug 18 1993;270(7):854-9. [Medline].

32. Shearer P, Park D. Seizures and Status Epilepticus: Diagnosis and Management in the Emergency Department. Emergency Medicine Practice. August 2006;8(8).

33. Unger AH, Sklaroff HJ. Fatalities following intravenous use of sodium diphenylhydantoin for cardiac arrhythmias. Report of two cases. JAMA. Apr 24 1967;200(4):335-6. [Medline].

Keywords

seizures, seizure symptoms, seizure causes, seizure diagnosis, seizure treatment, seizures in the ED, status epilepticus, seizure, epilepsy, focal seizure, partial seizure, ictus, postictal

Contributor Information and Disclosures

Author

M Tyson Pillow, MD, Assistant Director of Medical Education, Ben Taub General Hospital Emergency Center; Assistant Professor, Baylor College of Medicine
M Tyson Pillow, MD is a member of the following medical societies: Air Medical Physician Association, American College of Emergency Physicians, American Medical Association, American Medical Student Association/Foundation, Emergency Medicine Residents Association, Society for Academic Emergency Medicine, and Student National Medical Association
Disclosure: Nothing to disclose.

Coauthor(s)

David S Howes, MD, Residency Program Director, Professor of Medicine, Section of Emergency Medicine, University of Chicago/Pritzker School of Medicine
David S Howes, MD is a member of the following medical societies: American College of Emergency Physicians, American College of Physicians-American Society of Internal Medicine, and Society for Academic Emergency Medicine
Disclosure: Nothing to disclose.

Shaneen U Doctor, MD, Research Assistant, Department of Emergency Medicine, University of Chicago
Disclosure: Nothing to disclose.

Medical Editor

Richard S Krause, MD, Senior Faculty, Department of Emergency Medicine, State University of New York at Buffalo School of Medicine
Richard S Krause, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Emergency Medicine, American College of Emergency Physicians, and Society for Academic Emergency Medicine
Disclosure: Nothing to disclose.

Pharmacy Editor

Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: eMedicine Salary Employment

Chief Editor

Rick Kulkarni, MD, Assistant Professor of Surgery, Section of Emergency Medicine, Yale-New Haven Hospital
Rick Kulkarni, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Emergency Medicine, American College of Emergency Physicians, American Medical Association, American Medical Informatics Association, Phi Beta Kappa, and Society for Academic Emergency Medicine
Disclosure: WebMD Salary Employment

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