Seizure Assessment in the Emergency Department 

Updated: Jul 05, 2022
Author: Bobak Zonnoor , MD, MMM; Chief Editor: Andrew K Chang, MD, MS 

Overview

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. The term “ictus” describes the period in which the seizure occurs, and the term “postictal” 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 consists of abnormal neuronal firing that is limited to 1 hemisphere or area of the brain and that manifests itself as seizure activity on 1 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. Previously, the patient with 30 minutes of continuous seizure activity or a series of seizures without a return to full consciousness was defined as being in status epilepticus (SE). Newer definitions suggest that SE is defined by duration of 5 continuous minutes of generalized seizure activity or 2 or more separate seizure episodes without return to baseline.[1]  The International League Against Epilepsy established another definition of SE, with two operational dimensions, t1 and t2. Time point t1 is when the seizure is considered to be abnormally prolonged and treatment should begin, and time point t2 is when seizure activity may lead to long-term harm and increasingly aggressive interventions should be initiated.[2] These two times points are generally accepted to be 5 minutes and 30 minutes, as irreversible neuronal injury may result after 20–30 minutes of continuous seizing. Refractory status epilepticus (RSE) is a seizure that does not respond to appropriate doses of a benzodiazepine and a second-line antiepileptic drug (AED).

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, or autonomic function.

This sudden biochemical imbalance between excitatory neurotransmitters and the N-methyl D aspartate (NMDA) receptor and inhibitory forces (eg, gamma-aminobutyric acid [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.[3] During a generalized seizure, there can be a period of transient apnea and subsequent hypoxia. In a physiologic 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.[4] Hyperglycemia and lactic acidosis occur within minutes of a convulsive episode and usually resolve within 1 hour.[5] 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 (SE), 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.[6]

 

Etiology

For patients with known seizure disorder, the most likely cause is subtherapeutic levels of antiepileptic medications, which usually occur for 1 of the following reasons:

  • 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 list of possible causes is longer and includes the following:

  • Central nervous system (CNS) pathologies (stroke, neoplasm, trauma, hypoxia, vascular abnormality)

  • Metabolic abnormalities (hypoglycemia/hyperglycemia, hyponatremia/hypernatremia, hypercalcemia, hepatic encephalopathy)

  • Toxicologic etiologies (alcohol withdrawal, cocaine, isoniazid, theophylline)

  • Infectious 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 a history of travel and in immigrants.

    • Multiple case reports have shown seizure to be a rare manifestation in patients diagnosed with COVID-19. Seizures have been documented in patients with no prior history of epilepsy. It is unclear if the seizures are due to the virus itself; or the electrolyte derangements, organ failure, and hypoxia often associated with SARS-CoV-2.[7, 8]

 

Epidemiology

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.[9] Overall, approximately 50,000–150,000 cases will reach status epilepticus (SE). It has been estimated that there are approximately one million yearly visits to emergency departments due to seizures, accounting for about 1% of all ED visits in the United States.[10]

Incidence is highest in those younger than 2 years and in those older than 65 years. Males are slightly more likely to develop epilepsy than females.

History of head trauma, history of stroke, and family history of epilepsy are all independent risk factors for first seizures in adults.[11] After the first seizure, overall recurrence risk in adults is 30-40% (greatest in the first 6 months). This risk drops to less than 10% in 2 years.[11]

 

Presentation

Patient history

A history of epilepsy is often noted (if the patient is unconscious, family, friends, or prehospital personnel can be questioned). Other history findings may include the following:

  • Recent noncompliance with medications

  • History of central nervous system (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 examination

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.

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 is important. As noted (see Overview), any seizure with loss of consciousness is considered a complex seizure .

Focal deficits on neurologic examination 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 postictal period.

Special concerns

Special concerns in patients with seizures in the ED include the following:

  • Eclampsia

  • Trauma

  • Intracranial hemorrhage (ICH)

  • Alcohol withdrawal or medication withdrawal

  • Drug-induced seizures

Seizures in pregnancy are a complication of severe, untreated preeclampsia. In fact, eclampsia can occur up to 4 weeks after delivery.[12] Seizing pregnant patients should be treated just as nonpregnant patients are 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.[13]

In addition, patients with postpartum eclampsia, especially those with late postpartum eclampsia, have a higher incidence of cerebral venous thrombosis, intracranial hemorrhage, and acute ischemic stroke than do eclamptic patients diagnosed prepartum. Although most women with typical eclampsia do not need brain imaging, postpartum eclamptic patients and those with focal neurological deficits, persistent visual disturbances, and symptoms refractory to magnesium and antihypertensive treatment should undergo thorough diagnostic testing, preferably including MRI.[14]

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 is not significantly affected by early use of antiepileptic medications.[15, 16]

Stroke related to ICH may predispose the patient to seizures. Deep, small intraparenchymal bleeds are thought to be low risk unless they involve the temporal regions. Larger bleeds that cause mass effects pose a higher risk of seizures. Common practice is to consider a prophylactic loading dose of an antiepileptic medication (typically levetiracetam).

Alcohol withdrawal can occur anywhere from 6 to 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.[17]

Barbiturate or benzodiazepine withdrawal may cause seizure. With certain agents, symptoms may not develop for days or even weeks after cessation of use.

Tricyclic antidepressant (TCA) overdose and isoniazid (INH) therapy/overdose are 2 of the more common causes of drug-induced seizures. An electrocardiogram (ECG) will show a widened QRS and prominent R wave in lead aVR. A QRS duration of more than 100 milliseconds was linked to increased risk of seizures, which has been validated by multiple studies.[18, 19] Treatment of TCA overdose consists of bicarbonate infusion and supportive care. Pyridoxine is the treatment of choice for known isoniazid (INH) ingestion.

 

Differential Diagnosis

Delirium Tremens

Delirium, Dementia, and Amnesia

Eclampsia

Encephalitis

Epidural and Subdural Infections

Febrile Seizures

Heatstroke

Hyperventilation Syndrome

Hypoglycemia

Hyponatremia

Hypothyroidism and Myxedema Coma

Meningitis

Movement Disorders in Individuals with Developmental Disabilities

Hemorrhagic Stroke

Ischemic Stroke

Subarachnoid Hemorrhage

Syncope

Anticholinergic Toxicity

Antidepressant Toxicity

Antihistamine Toxicity

Carbon Monoxide Toxicity

Cardiac Arrhythmias

Cyclic Antidepressant Toxicity

Isoniazid Toxicity

Transient Global Amnesia

Transient Ischemic Attack

Withdrawal Syndromes

Other conditions to be considered include the following:

  • Carotid sinus hypersensitivity

  • Fugue states

  • Heat exhaustion

  • Hyperventilation

  • Malingering

  • Migraine narcolepsy/cataplexy

  • Night terrors

  • Panic attacks

  • Paroxysmal vertigo

  • Trauma

  • Psychogenic Nonepileptic Seizures  

 

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 1 study, laboratory tests such as blood counts, blood glucose level, and electrolyte panels were abnormal in as many as 15% of individuals[20] ; however, most abnormalities were incidental or insignificant. Routine laboratory testing is not necessary in patients with known epilepsy with uncomplicated breakthrough seizures, other than testing of serum anticonvulsant levels when appropriate and available.

An American College of Emergency Physicians Clinical Policy recommends the following in adults with new-onset seizure:[21]  serum glucose level, serum sodium level, and pregnancy test in women of childbearing age.

For patients with a first-time, generalized tonic-clonic seizure, an electrolyte panel and a urine or serum pregnancy test should be obtained. Other tests can be ordered at the physician’s discretion on the basis of 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.

No evidence suggests that toxicologic testing changes outcomes.[22] 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 (SE) because it will likely reveal metabolic acidosis but should rapidly correct after the patient stops seizing.

 

Computed Tomography

For patients with new-onset seizures or those in status epilepticus (SE), noncontrast computed tomography (CT) of the head in the emergency department (ED) is the imaging procedure of choice because of its ready availability and ability to identify potential catastrophic pathologies.

For the patient who presents for a first-time, generalized tonic-clonic seizure that has returned to baseline mental status, who has normal results on neurologic examination, and who has no comorbidities, CT may be completed as on outpatient basis, provided that 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), a head CT should be performed on an emergency basis. A study by Dunn et al[11] showed that 41% of adults have abnormal CT after first generalized seizure, but only 6-10% are abnormal if there are no focal deficits. Another study showed that overall, CT scans in the emergency department for adults presenting with seizure resulted in a change of acute management in 9–17% of patients.[23] Dunn et al also demonstrated that the yield from scanning increases with age.

Approximately 3–41% of patients with first-time seizures will have abnormal findings on head CT.[24] The timing of CT scanning is still somewhat controversial.

In patients with a known seizure disorder, consider head CT if any of the following are present: new focal deficits, trauma, persistent fever, new character or pattern to the seizures, suspicion of AIDS, infection, or anticoagulation. In general, however, the evidence is inadequate to support or refute the usefulness of emergency CT in persons with chronic seizures.[23]

 

Magnetic Resonance Imaging

Magnetic resonance imaging (MRI) may be a better diagnostic test because of higher yield and ability to identify smaller lesions, but its availability in the ED may be a limiting factor. In addition, MRI is time-consuming and may interfere with adequate patient monitoring.

 

Other Studies

Electrocardiography (ECG) should be considered in certain patients. Seizure activity can be precipitated by cerebral hypoperfusion from an arrhythmia. ECG may identify the following:

  • Prolonged QTc

  • Widened QRS

  • Prominent R in aVR

  • Heart block

Electroencephalography (EEG) is not routinely available in the emergency department (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 (SE) to ensure that seizure activity is controlled.

In one study, EEG performed within 24 hours after a first seizure detected epileptiform abnormalities in 51% of patients compared with only 34% of those who had a later EEG.[25]  A prospective study of 164 patients with cessation of clinical convulsive status epilepticus who subsequently had continuous EEG monitoring noted that 48% of the subjects still had evidence of seizures on EEG.[26] Secondary analysis of data gathered from participants of the Established Status Epilepticus Treatment Trial (ESETT) found that among those with clinical treatment success and EEG performed within 24 hours, nearly 40% had electrographic seizues with no clinical evidence of active seizures.[27] These results suggest that EEG monitoring, if available, is likely beneficial for patients with termination of convulsive SE in the emergency department.

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

 

Treatment and Management

"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 (SE).[28, 29]

In caring for the seizure patient in the emergency department (ED), 3 basic pitfalls must be avoided. The first is 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. Electroencephalography (EEG) is the diagnostic modality of choice for identifying these patients.

The second is failure to control seizure activity aggressively. Neurologic dysfunction is theorized to occur after 20–30 minutes of continuous seizure activity, even despite adequate oxygenation and ventilation. Therefore, there should be a low threshold for aggressive treatment of any seizure activity that lasts over 5 minutes.

As neurologic dysfunction can happen after 20–30 minutes of continuous seizing and SE becomes more difficult to end as the duration of seizure increases, new ideas are being explored to expedite care. Introducing a SE alert, similar to a code stroke, reduced the time of administration of a second-line AED from 58 minutes to 22 minutes.[30]

The third is failure to consider the underlying etiology. Although medication noncompliance and subtherapeutic medication levels are among the most common causes of seizure presentations to the ED, patients should also be screened for underlying infectious or metabolic causes of seizure 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.

Prehospital care of the seizure patient is mostly supportive; most seizures are of short duration, especially pediatric simple febrile seizures. The ABCs (A irway, B reathing, C irculation) should be evaluated as necessary, including oxygenation and airway assessment, temperature assessment, blood glucose assessment, and spinal precautions.

Intravenous (IV) access should be obtained for almost all patients (it may be deferred in those with simple febrile seizures). Emergency medical service (EMS) protocols should include benzodiazepines (IV, intramuscular [IM], or rectal) for prolonged seizures or SE.

ED care should be individualized. Sometimes, the most difficult part of the ED evaluation is determining whether the patient has had a seizure. Clues to the diagnosis include a clear history of tonic-clonic movements, urinary or bowel incontinence, postepisode confusion, and tongue biting. However, one study showed that myoclonic jerking was found in 90% of individuals in which syncope was induced.[11] Attempt to obtain history from EMS providers, family, friends, or observers who may have been present during the episode.

Medications

Current consensus is that benzodiazepines are the preferred drug class for the initial treatment of SE. Lorazepam, when available, is thought to be the most effective of the benzodiazepines and has a longer seizure half-life than diazepam. Lorazepam is the favored agent when intravenous access is obtained, while midazolam is preferred for intramuscular injections and can be given nasally or bucally.[31]

No difference in efficacy was observed between caregiver-administered intranasal midazolam and rectal diazepam for terminating sustained seizures (ie, >5 minutes) in children at home.[32] Caregiver’s satisfaction was higher with the inhaled midazolam (easier to administer) and the median time from medication administration to seizure cessation was 1.3 minutes less for inhaled midazolam compared with rectal diazepam.

The previously mentioned ESETT study was a multicenter, randomized, blinded trial comparing levetiracetam, fosphenytoin, and valproate for 384 patients with status epilepticus refractory to treatment with benzodiazepines. ESETT demonstrated that the three agents had the same efficacy, achieving the primary endpoint of cessation of status epilepticus and improvement in level of consciousness at 60 minutes in almost 50% of patients.[33] Removing the possibly subjective component of improvement in level of consciousness, there was approximately 60% cessation of SE at 60 minutes with all three AEDs.[33] As a result of this landmark trial, levetiracetam is the preferred second-line AED as it demonstrated the same effectiveness at terminating SE while being the safest and easiest to administer. Although not statistically significant, fosphenyotin was associated with more hypotension and intubations.

No data clearly support a best third-line drug, controlled trials are lacking, and recommendations vary greatly. The list of third-line drugs includes infusions of midazolam, propofol, barbiturates, and ketamine. A general principle is to maximize benzodiazepine and second-line AED 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 SE (GCSE).

Barbiturates may be useful when the condition fails to respond to phenytoin and benzodiazepines. Phenobarbital is the commonly used third-line drug, but midazolam, propofol, and others are increasingly used in preference to this agent, though no rigorous evidence supports the use of one third-line drug over another. The consensus seems to be moving toward propofol or midazolam infusions for refractory SE.

Ketamine has been demonstrated to be a relatively effective and safe drug for treatment of both refractory and super-refractory status epilepticus.[34, 35] There is an absence of guidance on the therapeutic dosage of ketamine for refractory SE, one study found that doses up to 10 mg/kg/h were not associated witih increased complications or mortality than lower doses.[34]  One recommeded dosing regimen for ketamine, is a 0.5–3 mg/kg loading dose, followed by an infusion at 0.3–4 mg/kg/hr.[36] The decision to start ketamine and the dosage should be discussed with a neurologist prior to initiation. There is still controversy in relation to when ketamine should be started, either along with standard general anesthetics in refractory SE or when standard agents have failed in super-refractory SE.[36]

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. For inpatient treatment, fall precautions should be followed to ensure that patients do not inadvertently injure themselves.

Management of patients who have stopped seizing

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, it is appropriate to give a loading dose in the ED and discharge the patient home, as long as there are no other concerning features to the presentation.

The loading dose of levetiracetam is 1500 mg oral load or 1000–1500 mg IV. Fosphenytoin can be administered at 18 PE/kg parenterally (max rate of 150 PE/min).

Phenytoin is a common antiepileptic medication and is classically given as “1 g” in the ED; it is sometimes delivered half orally (PO) and half parenterally. Oral absorption of phenytoin can be erratic, but when the agent is 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.[37, 38]

Valproic acid can be given parenterally as a 20 mg/kg loading dose.[39]

Initial considerations for patients with ongoing seizure

If the patient’s seizure activity has not abated at ED presentation, the ABCs should be addressed as follows.

Administer oxygen. For patients who are in SE or are cyanotic, endotracheal intubation using rapid sequence intubation (RSI) should be strongly considered. If RSI is employed, short-acting paralytics should be given 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 IV 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). Central nervous system (CNS) infections and anoxic injury are the leading causes of mortality associated with SE.

Management of patients with active seizure

ED management of active seizures begins with administration of benzodiazepines, which is considered first-line therapy. IV options include lorazepam, diazepam, and midazolam. If IV access cannot be obtained, then IM lorazepam or midazolam, or rectal diazepam can be considered. IV lorazepam was found to be superior to IV diazepam in both seizure cessation and preventing recurrent seizures.[40]

A common regimen is 0.1 mg/kg of lorazepam IV given at 2 mg/min or 0.2 mg/kg of diazepam IV given at 5–10 mg/min. Very large doses of benzodiazepines may be needed. 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.

Levetiracetam is considered the second-line agent for patients who continue to seize despite aggressive benzodiazepine therapy. A loading dose of levetiracetam is 60 mg/kg IV, with a maximum of 4500 mg, infused over 5–15 minutes.[33]

Intravenous valproate has a loading dose of 40 mg/kg (max of 3000 mg) infused at a rate of 10 mg/kg/minute.[41] Valproic acid has an excellent safety profile.[42]  It is contraindicated in hepatic dysfunction because of the extremely rare occurrence of fatal idiosyncratic hepatotoxicity.[43, 44]

A third AED, fosphenytoin, the preferred formulation of phenytoin for rapid dosing, can be given at 20 mg PE/kg with a maximum of 1500 mg PE/dose.[41]  Fosphenytoin may be administered IM, and this is an advantage for patients without IV access.

Phenytoin was previously considered the second-line agent for seizures refractory to benzodiazepines. 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.[45, 46]

Phenobarbital is similar to lorazepam with respect to efficacy. The recommended dose is 20 mg/kg, but phenobarbital can be given in doses as high as 30 mg/kg for severe refractory seizures. Phenobarbital may cause hypotension and respiratory depression.

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. The patient should be intubated (if this has not already been done), and preparations should be made to support the patient’s cardiovascular status.

Pentobarbital has a shorter duration of action than phenobarbital does but a greater sedating effect. Pentobarbital should be administered in a bolus at 5 mg/kg, that can be repeated if seizure activity continues. The initial boluses are followed by continuous infusion of 0.5–5 mg/kg/h as tolerated.

Midazolam is administered as a 0.2 mg/kg boluses given at a rate of 2 mg/min, followed by continuous infusion of 0.05–2 mg/kg/h. Midazolam is slightly less effective at stopping seizures than either propofol or pentobarbital, but treatment with midazolam has a lower frequency of occurrence of hypotension.[43]

Propofol appears to be very effective at terminating seizures, but only limited data are available. Propofol is administered in boluses at 1–2 mg/kg up to a maximum of 10 mg/kg, followed by continuous infusion of 20–100 µg/kg/min. It is limited by the syndrome of hypotension, metabolic acidosis, and hyperlipidemia seen with prolonged infusions.[47]

Currently, there are no randomized controlled trials available to guide the treatment of refractory status epilepticus.[48] New avenues that have been investigated include hypothermia, transcranial stimulation, and deep brain stimulation.

Consultations

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

  • SE - Consider consulting a neurologist or an intensivist.

  • Breakthrough seizure in a compliant patient with therapeutic levels - Consider consulting the physician responsible for long-term management of the patient’s seizure disorder. Medication changes may be needed and ideally should be coordinated with a physician providing ongoing care.

Further inpatient care

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

Further outpatient care

For those with first-time generalized tonic-clonic seizures with no concerning features (eg, failure to return to baseline), a normal ED workup, and not at risk for repeat seizure (eg, alcoholics), 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.[11]

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

In/outpatient medications

Inpatient medications are given on the basis of 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 the medication regimen should be completed in consultation with the patient’s neurologist or primary physician. Little evidence suggests the need to start medications out of the ED. In fact, one study showed that antiepileptic drugs started immediately after first unprovoked generalized tonic-clonic seizures or started after seizure recurrence do not affect survival over the succeeding 20 years.[49]

Transfer

If a patient is experiencing severe, refractory seizures, has a complicated diagnosis, or has requirements that exceed the resources of the hospital (eg, a paralyzed seizing patient who requires EEG monitoring that is unavailable in the ED), strong consideration should be given to transferring the patient to a higher level of care.

Deterrence/prevention

To date, there have been no data to indicate that any intervention other than medications effectively prevents seizures or SE. Therefore, medication compliance should always be emphasized to every patient.

 

Prognosis

Prognosis depends both on the underlying etiology of seizures and on whether seizures can be effectively terminated before irreversible neurologic damage has occurred. The overall mortality rate is about 20% for those who reach status epilepticus (SE). The mortality rates are highest for those older than 75 years, reflecting an increased incidence of degenerative, neoplastic, and vascular pathologies.

As many as 50% of patients with epilepsy will have recurrent seizures despite medical therapy.[50] As many as 25% of patients with a first-time generalized seizure will have a recurrence within 2 years.[51]

 

Patient Education

Patients can be counseled to be prepared for seizure activity and to 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 1 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. Treatment action plans provide instructions to patients with chronic conditions and facilitate managment of acute exacerbations or reoccurences. Acute seizure action plans (ASAP) can guide patients and their caregivers on medication administration and actions to take before the arrival of EMS or a visit to the emergency department.[52] Seizure action plans should be developed with a patient's primary care provider or neurologist, but a generalized plan can be provided to patients upon discharge from the ED as they wait for followup appointments.[52]

These plans can clarify when rescue medication should be administered, when it is appropriate to wait to see a physician as an outpatient, or when to call 911 or visit an emergency department. This intervention can reinforce appropriate actions, decrease apprehension, decrease ED visits and costs for the patient, and decrease the time to adminstration of benzodiazepines in areas lacking quick access to emergency services.