A seizure is an episode of neurologic dysfunction resulting in change in motor activity or sensory perception caused by abnormal firing of neurons. Seizures can be generalized, with abnormal activity in both hemispheres of the brain and a change in mental status, or partial, involving only certain parts of the brain.

Simple partial seizures cause no change in mental status, while complex partial seizures do result in some degree of altered consciousness. Status epilepticus is defined as 5 minutes of continuous seizing or two or more episodes of seizures without a return to baseline between episodes.¹

Seizures are a common presentation in the emergency department and account for 1%-2% of all emergency department visits. Epilepsy affects more than 3 million people in the United States, with more than 200,000 new cases of seizure each year.² The most commonly affected are those at the extremes of age (younger than 2 years and older than 65 years old). Of the affected patients, approximately 100,000 will be in status epilepticus.

The work-up necessary for a complaint of seizure is dependent on several factors. When evaluating a patient with the complaint of seizures, the emergency physician should consider a few questions to guide management:

• Is the patient presenting with a true seizure, or is there a seizure mimic?
• Are there any underlying causes of the seizure, or is it secondary to a seizure disorder?
• Is this a first-time seizure, or does the patient have an established seizure history?
• Is the patient in status epilepticus?

This article will review the current evaluation, management, and disposition of patients presenting to the emergency department with seizures.

History and Physical Exam

Patients presenting with seizures often have a history of seizure disorder. Other key history to obtain includes compliance with medications, alcohol or barbiturate use, illicit substance abuse, recent fall or trauma, pregnancy, intracranial pathology, or travel outside of the United States. EMS is frequently a source of history for these patients as well, as the patient’s mental status may make it difficult to obtain history directly from the patient.

Seizures are known to produce many transient physiologic changes, such as apnea and subsequent hypoxia, fever, or hyperglycemia. The patient may also become hypertensive. The physical exam should be focused and attempt to identify these changes when possible. If the patient is actively seizing, the physician should know the type of seizure, presence of posturing, eye deviation, or other signs of focal deficits.

To distinguish a true seizure from a seizure mimic, note the following characteristics:

• Suggestive of seizure: Slow return of baseline mental status, available witnesses able to confirm shaking activity, bowel/bladder incontinence.
• Suggestive of syncope: Rapid return to baseline mental status, EKG with evidence of dysrhythmia or long QT syndrome.

Lab Tests

In general, studies have shown a low yield (only abnormal in approximately 15% of patients) for extensive laboratory testing unless indicated in history or physical exam.³ Leukocytosis and lactic acidosis may be present, but are transient and usually caused by the seizure itself.

ACEP’s clinical policy recommends that emergency physicians obtain serum glucose, sodium level, and pregnancy test in women of childbearing age.⁴

Patients currently on antiepileptic medications can also have the blood levels assessed when available.

Any patient with a history of malignancy should also have serum calcium levels assessed. Lumbar puncture should be considered for patients with immunocompromised states, severe headache, fever, suspicion for AIDS, or status epilepticus.

Of note, prolactin is occasionally used in the diagnosis of seizure.

In one meta-analysis, a prolactin level greater than 3 times normal when taken within 1 hour of the event had a positive likelihood ratio (LR) of 4.6 for generalized tonic-clonic seizure versus nonconvulsive syncope and LR of 8.9 for generalized tonic-clonic seizure versus pseudoseizure.⁵ However, because of the limitations of the study, lack of power, and sensitivity of just 71% (95% confidence interval 49%-87%), it is considered only moderately effective as a screening tool.

Imaging Studies

In the past, the timing for CT scan of the head for first-time seizure was controversial. However, because of the availability of CT scanners in the United States, there is almost no reason not to perform the head CT scan on initial presentation.

Head CT scans should also be done for any patient presenting with first-time partial seizure, trauma, immunocompromised state, history of malignancy, anticoagulation, suspicion for AIDS, persistent fever, new pattern or type of seizure, or new focal findings on neurologic exam.

Magnetic resonance imaging (MRI) is the diagnostic imaging test of choice. This is usually not available from the emergency department and done on an outpatient or inpatient basis.

Electroencephalogram (EEG) has a very high yield to predict seizure recurrence and is part of the full neurologic work-up. In the emergency department, it may be needed to ensure that an intubated (and pharmacologically paralyzed or heavily sedated) patient in status epilepticus is not still seizing subclinically.

Management

Treatment and disposition is largely dependent on the history and can be tailored to the individual patient. For all patients, ABC’s are the first step in treatment. Adequate oxygenation should be ensured and supportive care measures taken.

First-Time Seizure

Patients with first-time seizure usually present with a history of recent seizure activity that has resolved by the time they arrive at the emergency department.

Seizures are usually self-limited in this scenario and no further emergency department treatment is needed.

The patient should receive sodium level and glucose level tests, a pregnancy test (as applicable), and a head CT scan.

Patients who present with a generalized seizure with no other worrisome history can be discharged home with close follow-up. Even with a normal EEG and normal CT scan, 1- and 4-year recurrence rates are 14% and 24%, respectively.⁶ However, antiepileptic medications do not affect this recurrence rate, so these agents are not routinely started after the first-time seizure.

Several states (California, Delaware, Nevada, New Jersey, Oregon, and Pennsylvania) have mandatory reporting laws.

Known Seizure Disorder

In patients with a known seizure disorder, a head CT scan should be considered for patients with new focal deficits, significant trauma, persistent fever, new pattern of seizure, or suspicion of AIDS, infections, or anticoagulation. Blood levels of pertinent medications should be obtained.

If antiepileptic medication blood levels are found to be low, a loading dose is given in the emergency department. Levels of phenytoin, carbamazapine, phenobarbital, and valproic acid are readily available in the emergency department.

Phenytoin is classically given as 1 g in the emergency department, with half of the medication being given orally and half intravenously, but this may be subtherapeutic in obese patients or patients with difficult-to-control seizures. Oral administration alone is cheaper than the IV route and can achieve therapeutic levels when given in appropriate doses (19 mg/kg in men and 23 mg/kg in women) divided every 2-4 hours at 400-600 mg per dose to minimize GI and neurologic side effects.^7,8

Fosphenytoin is the preferred drug if given intravenously (to avoid the complications of the propylene glycol diluent of phenytoin) and can be given at a dose of 15-20 phosphenytoin equivalents (PE)/kg.

Valproic acid or phenobarbitol can be given as a parenteral loading dose of 20 mg/kg, but this is not recommended for phenobarbital in the awake, alert, nonseizing patient because of the heavy sedative effects of phenobarbital.

Carbamazepine is not recommended to be loaded orally because of the high rates of adverse events.⁹

Levetiracetam is one of the newest antiepileptic medications. Levels cannot be readily checked in the emergency department, but because of its wide therapeutic index, it is generally considered safe to give in the ED without knowing the patient’s compliance. (See box for dosing.)

Overall, even with therapeutic levels, up to 50% of patients with epilepsy will have recurrent seizures despite medical therapy.⁴

Pregnancy

Eclampsia is defined as a new onset of grand mal seizure activity (and possible coma) during pregnancy or post partum (up to 4 weeks after delivery). Magnesium sulfate should be administered to prevent subsequent seizures. It is given intravenously as a loading dose of 4-6 g over 20 minutes with a maintenance dose of 1-2 g/h as continuous IV infusion. For patients who continue to have seizure activity while receiving magnesium, seizures can be treated with benzodiazepines.

Intracranial Hemorrhage

Hemorrhagic stroke (or intracranial bleeding from trauma) may predispose a patient to seizures. Larger bleeds causing mass effect are at higher risk, while deep, small intraparenchymal bleeds that do not involve the temporal regions are considered low risk. Common practice is to give a prophylactic loading dose of phenytoin or fosphenytoin.

Trauma

Four percent of epilepsy is caused by trauma. The risk of post-traumatic seizures is directly related to the severity of injury, but is not affected by early use of antiepileptic medication.^10,11

Alcohol Withdrawal

Seizures caused by alcohol withdrawal classically occur 6-48 hours after cessation of drinking and can occur at any blood alcohol level.

Large doses of benzodiazepines, and occasionally phenobarbital as a second-line agent, may be necessary to prevent or control seizures. Interestingly, one study found a benefit to giving benzodiazepines to alcoholic patients who presented to the emergency department with a complaint of seizures even if they were not actively seizing.¹²

Toxin-Induced Seizures

In general, the underlying principle is to maximize benzodiazepines, then consider phenobarbital over phenytoin as a second-line agent. Specific treatments include:

• Isoniazid – pyridoxine
• Tricyclic antidepressants – alkalinize the urine, hemodialysis
• Buproprion – hemodialysis
• Lithium – hemodialysis
• Aspirin – alkalinize the urine, hemodialysis

For those patients who present to the emergency department actively seizing, address the ABCs by administering supplemental oxygen and observing for cyanosis, establish IV access, remove tight clothing, determine blood glucose level, and initiate drug therapy to help control the seizure activity. Benzodiazepines are given acutely, but most seizures are isolated and self-limiting.

Status Epilepticus

The newer definition of status epilepticus came about from data that seizure activity is largely bimodal, lasting less than 5 minutes or approximately 30 minutes.¹³ In animal models, irreversible neuronal damage starts as early as 20 minutes to 1 hour of continuous seizures. The goal is to control the seizure before neuronal injury occurs, theoretically between 20 and 60 minutes.

If using rapid-sequence intubation, short-acting paralytics are preferred to prevent masking of ongoing seizure activity.

Antibiotics with or without antivirals should also be considered and adequate oxygenation confirmed because central nervous system infections and anoxic injury are major concerns in patients in status epilepticus.

Benzodiazepines are the first line of treatment and the mainstay of seizure management. Intravascular (including both intravenous and intraosseous routes) options include lorazepam, midazolam, and diazepam.

If IV/IO access cannot be obtained, intramuscular lorazepam or midazolam or rectal diazepam can be used. IV lorazepam has been found to be superior to intravascular diazepam.¹⁴

Lorazepam’s efficacy as compared to midazolam is unclear, but midazolam is possibly superior.15 Perhaps the most common regimen is 2 mg of lorazepam repeated every minute as needed to a maximum of 10 mg.

Phenytoin or fosphenytoin is considered second-line treatment. For status epilepticus, the recommended dose is 20 mg/kg, and another 10 mg/kg bolus can be considered (for a total of 30 mg/kg).⁴ Fosphenytoin is considered safer because of the lack of the propylene glycol diluent and can be given at a faster rate.¹⁶

Failure to respond to benzodiazepine and phenytoin defines refractory status epilepticus. Approximately 9%-30% of status epilepticus becomes refractory and mortality jumps to 50%.¹⁵

Third-line agents to consider at this point include valproic acid, phenobarbital, and levetiracetam. Valproic acid has an excellent safety profile and is recommended at a dose of 20 mg/kg, although doses as high as 45 mg/kg can be used.17 It is contraindicated in patients with hepatic disease or disfunction because of the extremely rare occurrence of fatal idiosyncratic hepatotoxicity.^18,19

Phenobarbital dosing is similar to phenytoin in that it is given at 20 mg/kg, but can be given up to 30 mg/kg for refractory seizures. It is highly sedating and usually causes significant respiratory depression and hypotension requiring intervention.

Levetiracetam is a newer antiepileptic drug currently used for the treatment of seizures that is showing potential for the treatment of status epilepticus. Several case series demonstrated the potential benefit of levetiracetam in patients with status epilepticus.^15,20,21 The mechanism of action is not completely understood, but the benefits of the drug include its wide therapeutic index, ease of administration, lack of interaction with other antiepileptic drugs, and low incidence of side effects (primarily central nervous system effects, sleepiness, and vomiting).

Levetiracetam is available in intravenous formulation and can be given at 100-300 mg/min. Loading doses have not been established, but usually range from 1.5 to 2 g in adults, with a daily maintenance dose of 2 g per day. No adjustment is needed for patients with hepatic dysfunction. The drug is renally excreted, but can still be used safely in patients with renal insufficiency, including end-stage renal disease, by adjusting the dosing schedule.

At this point, levetiracetam can be considered an adjunct to current status epilepticus management. It may have a role as a third-line alternative (after benzodiazepines and phenytoin/fosphenytoin) to help obviate the need for stronger sedative drugs and avoid causing respiratory depression and hypotension.

If these measures have failed to control seizure activity, continuous infusions of pentobarbital, midazolam, or propofol should be used. There is little evidence to guide the use of these medications. It is the authors’ opinion that the dosing of the continuous infusions should be titrated up to the maximum tolerable dose (even with some mild hypotension) until the possibility of subclinical nonconvulsive status epilepticus has been evaluated by EEG. The major side effects are hypotension and respiratory depression, so the patient should be intubated and measures taken to support cardiovascular status (fluids and occasionally vasoactive medications).

Midazolam can be bolused at 0.2-0.3 mg/kg, then infused at 0.05-2 mg/kg/hr. Of the continuous infusions, midazolam was associated with the least amount of hypotension but higher rates of breakthrough seizures.¹⁸

Propofol is bolused at 2-5 mg/kg, then infused at 20-100 mcg/kg/min. It appears to be equally efficacious as midazolam, with fewer breakthrough seizures but more hypotension.

Propofol use is limited by infusion syndrome consisting of hypotension, metabolic acidosis, and hyperlipidemia seen with prolonged infusions.²²

Pentobarbital is bolused at 5-15 mg/kg, then infused at 0.5-10 mg/kg/hr. Compared with midazolam and propofol, it has the highest rates of seizure control and the fewest breakthrough seizures, but almost double the rate of significant hypotension.

Summary

Seizures are a common complaint seen in the emergency department. There are many important steps that the physician can take to optimize care for these “routine” patients. In addition, the emergency physician must always be aware of possible complicating factors including pregnancy, toxidromes, and status epilepticus. Levetiracetam is a new medication that is showing potential as another option for treatment in even the most severe patients and should be considered as an addition to the standard therapy.

References

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