Seizures and status epilepticus are frequent neurologic emergencies in the emergency department, accounting for 1% of all emergency department visits. The management of this time-sensitive and potentially life-threatening condition is challenging for both prehospital providers and emergency clinicians. The approach to seizing patients begins with differentiating seizure activity from mimics and follows with identifying potential secondary etiologies, such as alcohol-related seizures. The approach to the patient in status epilepticus and the patient with nonconvulsive status epilepticus constitutes a special clinical challenge. This review summarizes the best available evidence and recommendations regarding diagnosis and resuscitation of the seizing patient in the emergency setting.
A 19-year-old man with no serious medical history presents to the ED after reports of seizure-like activity. According to the patient’s mother, he was lying on the sofa when he became unresponsive and began having tonic-clonic activity in all extremities. The episode lasted 30 seconds, included urine incontinence, and was followed by a 20-minute period of confusion. He said there have been no previous episodes; however, the mother reports that he once had a febrile seizure as a child. The patient denies drug use and infectious symptoms. On arrival, the patient is awake and completely responsive, with a normal neurologic examination. You wonder if this patient needs neuroimaging and whether he should be admitted to the hospital for a workup…
You receive a notification from EMS that they are bringing in a 22-year-old man who was “found down" and has been having tonic-clonic seizures on and off, without return to baseline, for at least 30 minutes. EMS gives an ETA of 10 minutes. The paramedics have been unable to secure an IV line and they ask you if diazepam should be given IM or rectal…or should they give lorazepam IM or midazolam IM instead? On arrival to the ED, the patient is actively seizing. His blood glucose is 162 mg/dL. He is given a total of 10 mg of IM midazolam while an intraosseous line is established. While seizure activity slows, it does not completely abate, even after a fosphenytoin load of 1400 PE is given over 10 minutes. The nurse asks you, “Doctor, what’s next?”
An 80-year-old woman is brought to the ED after having a first-time, witnessed, generalized tonic-clonic seizure about an hour before. Paramedics report no medications given in the field. You quickly assess the patient, who appears confused, with reactive pupils, moving extremities, and no evidence of focal deficits. After the nurse confirms a normal blood sugar of 120 mg/dL, you immediately take the patient for a head CT, which shows evidence of old lacunar infarcts and atrophy, but no midline deviation, edema, or any other finding to explain her altered mental status. By the time the results of basic metabolic testing are back (with no abnormalities), it’s been over 2 hours since your patient has had any evidence of convulsive seizure activity, which seems a little long for a postictal period. You wonder if you are missing something…
Seizure can be defined as a sudden change in behavior, characterized by an alteration in sensory perception or motor activity. Seizures are caused by abnormal, excessive, and synchronous electrical firing in groups of neurons. Convulsion refers specifically to the motor manifestations of this abnormal electrical activity. The clinical spectrum of seizures is wide and includes focal or generalized motor activity, altered mental status, sensory or psychic experiences, and autonomic disturbances.
Seizures may be classified according to whether they are caused by an underlying process (provoked) or not (unprovoked). Acute central nervous system (CNS) insults, toxins, or acute metabolic derangements can trigger provoked seizures.
Epilepsy is a condition of recurrent unprovoked seizures. For example, a patient who suffers head trauma might have an acute seizure but would not be considered to have epilepsy unless there are recurrent unprovoked events as a result of the brain injury.
The term ictus refers to the period during which a seizure occurs. Postictal period refers to the interval immediately following the seizure but before the patient returns to baseline mental status. An aura is a focal seizure and is defined by the area of the brain where the seizure originates (eg, a patient with a temporal lobe focus may have a déjà vu experience before the focal event spreads into a generalized tonic-clonic seizure).
Seizures are also classified as partial or generalized (see Table 1). Partial seizure (also known as focal seizure) occurs due to abnormal neuronal firing within a limited and confined population of neurons in 1 brain hemisphere, whereas generalized seizure denotes an abnormal neuronal firing throughout both brain hemispheres. Partial seizures are further classified as simple when they do not involve a change in mental status and complex when there is some degree of impaired consciousness. Furthermore, generalized seizures can be classified according to the specific type of motor activity (ie, tonic, clonic, tonic-clonic, or myoclonic).
During a convulsive event, metabolic acidosis, hypotension, hypoxia, hypoglycemia, hyperthermia, rhabdomyolysis, and pulmonary edema may develop. Clinical data indicate that permanent neuronal damage may occur after 30 minutes of epileptic activity, even with control of blood pressure, respiration, and body temperature.1,2 Thus, status epilepticus (SE) has traditionally been defined as unremitting seizure activity lasting at least 30 minutes or intermittent seizures without recovery of full consciousness. However, irreversible neuronal injury and pharmacoresistance may occur before this traditionally defined time parameter, and spontaneous cessation of epileptic activity is unlikely to occur after 5 minutes of ongoing activity.1-5 Consequently, it is now generally accepted that SE be defined as a seizure lasting for 5 minutes or more, or recurrent seizure activity without an interictal return to baseline.3,6-9
SE is categorized into 2 basic categories: (1) generalized convulsive status epilepticus (GCSE) and (2) nonconvulsive status epilepticus (NCSE). GCSE is a medical emergency, with mortality directly correlated with the duration of the event. It is typically characterized by seizures with tonic or tonic-clonic activity.2,10
A patient is considered to be in refractory status epilepticus (RSE) when the seizure does not terminate after treatment with a benzodiazepine and a second antiepileptic drug (AED). One retrospective cohort study of 74 patients in GCSE found that 30% of them progressed to RSE.11
NCSE presents clinically as an alteration in behavior that is associated with continuous epileptiform discharges on electroencephalogram (EEG). The altered mental status may range from a subtle change to coma, and may be associated with subtle motor signs such as twitching, blinking, eye deviation, persistent aphasia, or somatosensory findings.12 NCSE should also be considered in patients in coma of undetermined etiology. A prospective study of 236 patients in coma revealed that 8% actually carried the diagnosis of NCSE.13
Infections, benzodiazepine withdrawal, and electrolyte abnormalities have been associated with NCSE in patients with and without a pre-existing diagnosis of epilepsy.14,15 NCSE has been reported in all age groups, with incidence rates of between 2 and 20 cases per 100,000 individuals, and it can be the first manifestation of a seizure disorder.16,17 EEG makes the definitive diagnosis. However, because of the wide spectrum of clinical presentations, NCSE continues to represent a diagnostic challenge to even the most experienced clinicians. According to the presence or absence of consciousness impairment and the type of motor activity, NCSE can be classified into 4 subtypes (see Table 2). NCSE may persist after a convulsive event and should be suspected in a patient who appears to have a prolonged postictal period.
In addition to simple partial SE, distinct forms of NCSE include absence SE and complex partial SE, and subtle convulsive SE. Absence SE and complex partial SE may present with variable degrees of impaired consciousness and very subtle motor activity (such as isolated blinking). A particularly challenging type is subtle SE, which evolves from GCSE as muscles fatigue or neurons become exhausted; its prognosis is much worse than other types of NCSE.16 The diagnosis of subtle convulsive status is made in the presence of EEG changes and evidence of previous overt epileptic seizures or GCSE. A United States Department of Veterans Affairs (VA) Cooperative Study demonstrated a substantially worse outcome in subtle SE than in GCSE (with mortality rates of 65% and 27%, respectively).18
This issue of Emergency Medicine Practice provides an evidence-based review of the diagnosis and manage ment of adult patients presenting to the emergency department (ED) with seizure and SE, with a focus on the clinical situations most commonly encountered in daily practice.
An extensive review of the English-language literature was performed on the National Library of Medicine PubMed database using the following search terms: seizures, status epilepticus, epilepsy, emergency medical services, and emergency department. References that were pertinent to emergency management were reviewed and relevant information extracted. Among all reviewed publications, the ones with the highest level of evidence have been highlighted in the references section. Additionally, expert consensus statements have been selected and summarized in Table 3, although consensus is not always supported by high-level evidence.
Management of patients with a first-time unprovoked seizure in the ED is guided by practice consensus among individual experts and societies, as there is a paucity of randomized prospective studies. Most studies addressing the utility of laboratory testing and imaging for these patients are retrospective data analyses. Two areas of particularly limited evidence are the risk of seizure recurrence and determination of the need for outpatient observation and follow-up versus hospital admission.
Guidelines pertaining to the appropriate choice of AED in SE patients treated in the ED are limited by the lack of subject randomization and outcome reporting of AED levels rather than patient-oriented outcomes (ie, seizure cessation or recurrence). There is not enough good-quality evidence to make definitive recommendations as to the utility of ED-based EEG in patients who appear to have stopped seizing, although a growing body of literature supports early consideration of nonconvulsive or subtle SE when patients do not return to baseline as expected. Evidence outlining recommended treatment modality and agents of choice for patients with RSE is based mainly on small case series, retrospective studies, and survey data from critical care neurologists and epileptologists.
1. “The patient was no longer shaking, so I assumed he was no longer seizing.”
While a tonic-clonic seizure will be more clinically evident, patients presenting with partial seizures involving the nonmotor areas of the brain may be more difficult to recognize.
2. “The patient was seizing – I never thought she was hypoglycemic.”
Missing hypoglycemia on the evaluation of a seizing or postictal patient is a pitfall that should never occur. Check blood glucose together with vital signs in all patients who are seizing or who appear to be postictal.
3. “I never expected the patient to be so hyponatremic.”
Patients with seizure disorders can seize for many reasons, and a systematic evaluation is always required in order to catch underlying infectious or metabolic causes of seizure. This is particularly true in patients with multiple comorbidities (such as renal failure).
4. “I assumed the patient knew that he shouldn’t drive.”
All patients who have had a seizure should be explicitly advised not to drive or engage in activity that puts them at risk. Discharge all seizure patients with directed safety instructions regarding driving and operating machinery. Given the unpredictable nature of seizures, even a brief seizure can result in death or severe injuries to the patient or others. Patients with recent seizures should be advised not to drive until their seizures are controlled and, ideally, not until they follow up with their neurologist, AED levels are rechecked, and therapy is optimized.
5. “I forgot to ask about other medications.”
Always inquire about new medications in patients on AEDs. Most AEDs are metabolized in the liver, so taking them in conjunction with other hepatically metabolized medications may reduce the AED serum level to a nontherapeutic range. Many commonly used drugs (including antibiotics, antipsychotics, and antidepressants) can lower the seizure threshold and explain a breakthrough seizure that occurs despite compliance with therapy. Risk
6. “The patient was in a coma – I never suspected he could actually be seizing.”
Never forget that NCSE can present as coma and maintain a low threshold for obtaining a bedside EEG.
7. “I assumed the patient seized because her AED blood level was low.”
AED serum levels are a guide to therapy but not an absolute. Many patients are well controlled at low serum levels but have breakthrough seizures due to physical or mental stressors such as sleep deprivation. In these cases, treatment consists not of increasing the AED dose but eliminating the stressor.
8. “I thought the best way to address the hypoxia was to focus on treating the seizure.”
Oxygenation and perfusion are fundamental to successful management of the patient in SE. Hypoxia and hypotension are the 2 most consistent predictors of increased morbidity and mortality in all types of emergencies involving the brain. Particularly in patients with prolonged seizures, standard emergency medicine interventions (such as securing the airway and ensuring oxygenation) should not be delayed.
9. “I thought the seizure would stop on its own.”
Time is brain, and failing to aggressively control seizure activity increases morbidity. While most seizures cease without intervention, some patients need medications. Have a benzodiazepine dose readily available in case it is needed; intramuscular midazolam is an excellent option when intravenous access is not available.
10. “I was too busy treating the patient to talk to EMS.”
EMS personnel often have key information needed to care for a patient. Many patients are either postictal or under the effect of benzodiazepine treatment when they arrive to the ED, so they are not able to fully cooperate during the evaluation. It is always important to get as much information as possible from the EMS crew, including type of convulsion, medication, and doses that were given in the field.
Evidence-based medicine requires a critical appraisal of the literature based upon study methodology and number of subjects. Not all references are equally robust. The findings of a large, prospective, randomized, and blinded trial should carry more weight than a case report.
To help the reader judge the strength of each reference, pertinent information about the study, such as the type of study and the number of patients in the study, will be included in bold type following the reference, where available.
Felipe Teran, MD., Katrina Harper-Kirksey, MD., Andy Jagoda, MD, FACEP
January 1, 2015