Status Epilepticus


Article Author:
Todd Wylie


Article Editor:
Najib Murr


Editors In Chief:
Susan Jeno
Sarah Fabiano


Managing Editors:
Orawan Chaigasame
Carrie Smith
Abdul Waheed
Frank Smeeks
Kristina Soman-Faulkner
Benjamin Eovaldi
Radia Jamil
Sobhan Daneshfar
Pritesh Sheth
Hassam Zulfiqar
Steve Bhimji
John Shell
Matthew Varacallo
Ahmad Malik
Mark Pellegrini
James Hughes
Beata Beatty
Hajira Basit
Phillip Hynes
Kavin Sugumar


Updated:
6/4/2019 1:17:14 PM

Introduction

Status epilepticus is a neurological emergency requiring immediate evaluation and management to prevent significant morbidity or mortality. Previously, status epilepticus was defined as a seizure with a duration equal to or greater than 30 minutes, or a series of seizures in which the patient does not regain normal mental status between seizures. The Neurocritical Care Society guidelines from 2012 revised the definition to a seizure with 5 minutes or more of continuous clinical and/or electrographic seizure activity, or recurrent seizure activity without recovery between seizures.[1][2][3][4]

Status epilepticus may be convulsive, non-convulsive, or refractory. Convulsive status epilepticus consists of generalized tonic-clonic movements and mental status impairment. Non-convulsive status epilepticus is defined as seizure activity identified on an electroencephalogram (EEG), with no accompanying tonic-clonic movements. Refractory status epilepticus refers to continuing seizures (convulsive or non-convulsive) despite administration of appropriate anti-epileptic drugs.

Status epilepticus is the most common pediatric neurological emergency.[5][6]

Etiology

There are multiple etiologies for status epilepticus. [7]Potential acute processes include:

  • Central nervous system (CNS) infections (meningitis, encephalitis, and intracranial abscess)
  • Metabolic abnormalities (hypoglycemia, hyponatremia, hypocalcemia, hepatic encephalopathy, and inborn errors of metabolism in children)
  • Cerebrovascular accidents
  • Head trauma (with or without intracranial bleed)
  • Drug toxicity
  • Drug withdrawal syndromes (e.g., alcohol, benzodiazepines, and barbiturates)
  • Hypoxia
  • Hypertensive emergency
  • Autoimmune disorders

Chronic processes that may result in status epilepticus include, pre-existing epilepsy with breakthrough seizures or non-use of anti-epileptic drugs, ethanol withdrawal, CNS tumors, and remote CNS pathology (e.g., traumatic brain injury, stroke).

Acute processes account for most cases of status epilepticus in adults. Febrile status epilepticus is the most common cause in pediatric patients. CNS infections and inborn errors of metabolism are also common etiologies in children. The majority of pediatric patients with the first presentation of status epilepticus have no previous history of seizures.

Epidemiology

The incidence of status epilepticus has a bimodal age distribution with peaks during infancy and in the elderly. The incidence rate ranges between approximately 7 to 40 cases per 100,000 persons/year. Status epilepticus seems to be more common in males. A significant proportion of both children (16% to 38%) and adults (42% to 50%) with status epilepticus have a history of epilepsy. The short-term mortality (within 30 days) of status epilepticus ranges from 7.6% to 22% across all age groups and is highest amongst the elderly.[8]

Pathophysiology

A seizure is a paroxysmal electrical discharge of the neurons in the brain resulting in a change of function or behavior. It is important to understand that a seizure is a CNS event and may present as convulsive or non-convulsive. There are both excitatory neurotransmitters (glutamate, aspartate, and acetylcholine) and inhibitory neurotransmitters (gamma-aminobutyric acid) and mechanisms (calcium ion-dependent potassium ion current, and magnesium blockade of N-methyl-d-aspartate (NMDA)) in the brain that play a role in the genesis and inhibition of isolated seizures. Excessive excitation and/or inadequate inhibition results in status epilepticus.

History and Physical

Status epilepticus is defined as a seizure with 5 minutes or more of continuous clinical and/or electrographic seizure activity, or recurrent seizure activity without recovery between seizures. The findings of convulsive status epilepticus include generalized tonic-clonic movements of the extremities and impaired mental status. Temporary focal neurological deficits (e.g., Todd’s paralysis) may be present in the post-ictal period. Non-convulsive status epilepticus presents with impaired mental status, and may or may not have subtle motor signs such as tonic eye deviation. In non-convulsive status epilepticus, seizure activity is seen on the EEG despite the absence or paucity of overt clinical signs.

Evaluation

The diagnosis of convulsive status epilepticus is made clinically but requires emergent neuroimaging and laboratory studies to identify a potential etiology. A head computed tomography (CT) scan is appropriate in most situations and most easily obtained. Magnetic resonance imaging (MRI) of the brain is more sensitive for identifying malformations in pediatric patients, but may be difficult to obtain and may require sedation. Laboratory studies should include bedside blood glucose level, serum electrolytes (sodium, potassium, calcium, and magnesium), BUN, creatinine, serum bicarbonate, a complete blood count, and a lumbar puncture with cerebrospinal fluid (CSF) evaluation. If the patient has a known seizure disorder, anti-epileptic drug levels should be obtained. Suspicion of toxic ingestion mandates toxicology studies (e.g., urine toxicology screen, serum levels of specific toxins such as theophylline or lithium). Other studies may be considered based on the presentation (liver function tests, inborn errors of metabolism, and coagulation studies). A pregnancy test should be obtained in all women of child-bearing years. An EEG should be obtained. Non-convulsive status epilepticus requires all of the previously mentioned imaging and laboratory studies for identification of an underlying etiology, but also requires EEG monitoring for diagnosis.[9][10][11]

Treatment / Management

Status epilepticus must be addressed quickly and in an organized manner, with simultaneous assessment/management of the airway, breathing, and circulation, while also administering antiepileptic drug (AED) treatment. The primary goal of management is to definitively abort seizure activity as rapidly as possible while supporting the patient’s cardiovascular and respiratory status.[11][12]

  • Position the head to maintain an open airway (rapid sequence intubation may be necessary at any point during management if oxygenation or ventilation is impaired).
  • Provide supplemental oxygen.
  • Initiate monitoring of the heart rate, respiratory rate, blood pressure, and oxygen saturation.
  • Obtain vascular access.
  • Check a bedside blood glucose and treat hypoglycemia if present (if thiamine deficiency a possibility, administer thiamine before dextrose).
  • Benzodiazepines are the antiepileptic drug of choice for emergent control treatment. A repeat dose may be administered if seizures do not resolve following the first dose. Intravenous administration is preferred, but benzodiazepines can be administered via the intramuscular, rectal, nasal, or buccal route if vascular access is not available.
  • If benzodiazepines do not abort the seizures, other antiepileptic drug choices include fosphenytoin, phenobarbital, levetiracetam, and valproic acid (concern for hepatotoxicity with valproic acid use in children younger than two years).
  • Urgent control therapy with an antiepileptic drug (fosphenytoin, phenobarbital, levetiracetam, or valproic acid) following seizure control is required in all patients.
  • Refractory status epilepticus should be treated with a continuous infusion of an antiepileptic drug. Choices include an intravenous (IV) infusion of midazolam, pentobarbital, thiopental, or propofol (propofol infusion should not be used in children due to the risk of propofol infusion syndrome).
  • Magnesium sulfate is indicated for pregnant women with eclampsia.
  • A neurologist should be consulted early in the treatment stage right after the administration of first-line therapy.

All patients with status epilepticus require hospital admission, preferably to the intensive care unit.

Pearls and Other Issues

There are known risks of congenital disabilities due to exposure to some antiepileptic drugs (phenytoin, valproate sodium, and phenobarbital) during the first trimester of pregnancy. In the setting of status epilepticus, fetal well-being is dependent on immediate, successful management of seizure activity in the mother. Lorazepam is recommended for emergency control treatment if status epilepticus occurs during the first trimester. Levetiracetam should be considered for urgent control therapy in this setting as evidence suggests a lower risk of associated congenital disabilities in comparison to some other antiepileptic drugs (phenytoin, valproate sodium, and phenobarbital). If eclampsia is suspected, intravenous magnesium sulfate is the antiepileptic drug of choice. Delivery of the fetus is the definitive treatment of eclampsia.

Enhancing Healthcare Team Outcomes

Status epilepticus is best managed by a multidisciplinary team that includes neurology nurses. To improve outcomes, clinicians should avoid unnecessary imaging studies or laboratory work up when the patient is having a seizure. Status epilepticus must be addressed quickly and in an organized manner, with simultaneous assessment/management of the airway, breathing, and circulation, while also administering antiepileptic drug (AED) treatment. The primary goal of management is to definitively abort seizure activity as rapidly as possible while supporting the patient’s cardiovascular and respiratory status.

Once the patient is stable, investigations can begin.


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Status Epilepticus - Questions

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What is the first-line drug of choice to terminate status epilepticus?



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A patient is brought to the emergency department in status epilepticus. What drug should be administered initially?



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What medication should not be used to treat status epilepticus?



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A 23-year-old has three successive, witnessed, grand mal seizures and has not recovered consciousness. The patient is obtunded, withdraws to pain only, and does not open her eyes spontaneously. Which of the following should not be included in the initial management of this patient?



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Optimal treatment with electroencephalographic (EEG) monitoring is needed for which of the following patients?



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Which statement regarding the treatment of status epilepticus is least accurate?



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A patient has four successive, witnessed generalized tonic-clonic seizures and is still unconscious. In the emergency department, the patient is lethargic and only withdraws to pain. His eyes do not open spontaneously. Which is not part of the initial management?



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The Treiman classification is used to evaluate status epilepticus (SE). Which one includes electrical activity with fragmentary or absent motor movement?



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A patient is in status epilepticus with grand mal seizures. He was initially given IV lorazepam, then fosphenytoin with the appropriate loading dose, and then IV phenobarbital. Which of the following is an appropriate next medication?



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What is the term for generalized tonic-clonic seizures with no recovery of consciousness?



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Which of the following medications is not used for the treatment of status epilepticus?



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What is the most common cause of status epilepticus in a child with epilepsy?



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Which of the following can occur in a patient with uncontrolled frequent generalized seizures?



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Which is the best initial treatment of status epilepticus?



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You are called to evaluate a 17-year-old male with a known history of seizures. When you arrive, the patient is actively seizing. The patient received IV lorazepam 20 minutes ago. Which is an appropriate second therapy option?



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A patient arrives via ambulance in status epilepticus. The spouse related to the paramedics that the client missed several doses of her phenytoin the past few days while on an alcohol drinking binge. She is postictal, incontinent of urine, and has secretions in her oral cavity mixed with blood and emesis. What are immediate interventions for this client? Select all that apply.



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Status Epilepticus - References

References

Xu MY, Poststroke seizure: optimising its management. Stroke and vascular neurology. 2019 Mar;     [PubMed]
Horváth L,Fekete I,Molnár M,Válóczy R,Márton S,Fekete K, The Outcome of Status Epilepticus and Long-Term Follow-Up. Frontiers in neurology. 2019;     [PubMed]
Peng P,Peng J,Yin F,Deng X,Chen C,He F,Wang X,Guang S,Mao L, Ketogenic Diet as a Treatment for Super-Refractory Status Epilepticus in Febrile Infection-Related Epilepsy Syndrome. Frontiers in neurology. 2019;     [PubMed]
Ramos AB,Cruz RA,Villemarette-Pittman NR,Olejniczak PW,Mader EC Jr, Dexamethasone as Abortive Treatment for Refractory Seizures or Status Epilepticus in the Inpatient Setting. Journal of investigative medicine high impact case reports. 2019 Jan-Dec;     [PubMed]
Won SY,Dubinski D,Sautter L,Hattingen E,Seifert V,Rosenow F,Freiman T,Strzelczyk A,Konczalla J, Seizure and status epilepticus in chronic subdural hematoma. Acta neurologica Scandinavica. 2019 May 18;     [PubMed]
Matricardi S,Canafoglia L,Ardissone A,Moroni I,Ragona F,Ghezzi D,Lamantea E,Nardocci N,Franceschetti S,Granata T, Epileptic phenotypes in children with early onset mitochondrial diseases. Acta neurologica Scandinavica. 2019 May 18;     [PubMed]
Langenbruch L,Krämer J,Güler S,Möddel G,Geßner S,Melzer N,Elger CE,Wiendl H,Budde T,Meuth SG,Kovac S, Seizures and epilepsy in multiple sclerosis: epidemiology and prognosis in a large tertiary referral center. Journal of neurology. 2019 May 8;     [PubMed]
Jobst BC,Ben-Menachem E,Chapman KE,Fu A,Goldman A,Hirsch LJ,Jehi LE,Kossoff EH,Plueger M,Rho JM,Schevon CA,Shinnar S,Sperling MR,Simeone TA,Wagner JL,Lado F, Highlights From the Annual Meeting of the American Epilepsy Society 2018. Epilepsy currents. 2019 May 3;     [PubMed]
Huertas González N,Barros González A,Hernando Requejo V,Díaz Díaz J, Focal status epilepticus: a review of pharmacological treatment. Neurologia (Barcelona, Spain). 2019 May 7;     [PubMed]
Sánchez Fernández I,Gaínza-Lein M,Lamb N,Loddenkemper T, Meta-analysis and cost-effectiveness of second-line antiepileptic drugs for status epilepticus. Neurology. 2019 May 14;     [PubMed]
Müllges W, [Diagnosis and treatment of status epilepticus in the intensive care unit]. Medizinische Klinik, Intensivmedizin und Notfallmedizin. 2019 May 3;     [PubMed]
Uppal P,Cardamone M,Webber C,Briggs N,Lawson JA, Management of status epilepticus in children prior to medical retrieval: Deviations from the guidelines. Journal of paediatrics and child health. 2019 Mar 28;     [PubMed]

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