Status Epilepticus in Adults

Background

• Status epilepticus is abnormally prolonged seizure activity which can lead to the alteration of neuronal networks, neuronal injury, and neuronal death, depending on the type and duration of the seizure.
• Subtypes of status epilepticus:
  • Convulsive status epilepticus is generally defined by ≥ 5 minutes of sustained seizure activity with prominent (and usually bilateral) motor symptoms.
  • Nonconvulsive status epilepticus is generally defined by ≥ 10-15 minutes of sustained seizure activity without prominent motor symptoms, but which may include generalized absence status, focal symptoms, and/or impaired consciousness.
  • Subtypes include myoclonic status epilepticus, epilepsia partialis continua, and others.
• Refractory status epilepticus occurs when clinical or electrographic seizures continue despite treatment with first- and second-line antiseizure medications.
• Status epilepticus may be caused by a wide range of structural, infectious, toxic-metabolic, or autoimmune disorders, but can also have an unknown or cryptogenic etiology.
• More than 15% of patients with epilepsy experience at least 1 episode of status epilepticus.

Evaluation

• Do not delay therapy to obtain an electroencephalogram (EEG) in clinically apparent status epilepticus. However, continuous EEG is typically necessary to diagnose nonconvulsive status epilepticus.
• Diagnostic workup should be completed as soon as possible and occur simultaneously with treatment.
• Diagnose convulsive status epilepticus in patients with ≥ 5 minutes of sustained seizure activity with prominent motor symptoms and impairment of consciousness.
• Diagnosis of nonconvulsive status epilepticus:
  • Suspect nonconvulsive status epilepticus in patients with:
    • coma and cessation of motor symptoms following convulsive status epilepticus ("subtle" status epilepticus)
    • clinical presentations generally lasting ≥ 10-15 minutes, including:
      • impaired consciousness of varying severity (from mild amnesia to stupor) (suggestive of absence status epilepticus)
      • behavioral changes, sensory symptoms (including gustatory, olfactory, visual, and tactile symptoms), and aphasia (focal nonconvulsive status epilepticus without impaired consciousness)
      • prolonged auras, progressing to include behavioral alterations, confusion, and oral or manual automatisms (focal nonconvulsive status epilepticus with impaired consciousness)
  • Use continuous EEG to confirm diagnosis of nonconvulsive status epilepticus.
• Initiate continuous EEG monitoring within 1 hour of status epilepticus onset (Strong recommendation).
• Perform blood testing including fingerstick and blood glucose testing, complete blood count, basic metabolic panel, calcium and magnesium, and antiseizure medication levels.
• Consider other testing based on clinical suspicion of underlying etiology, including:
  • other blood testing (comprehensive toxicology panel, liver function testing, serial troponins, arterial blood gas, coagulation studies, and/or screening for inborn errors of metabolism)
  • neuroimaging for suspected stroke, tumor, abscess, or other intracranial structural disorders
  • lumbar puncture if suspicion of central nervous system (CSF) infection
• Diagnose refractory status epilepticus in patients with clinical or electrographic seizures which continue despite treatment with first- and second-line antiseizure medications.

Management

• Emergency management should be completed prior to, or upon arrival to, emergency department or intensive care setting.
  • Monitor oxygenation, blood pressure, and heart rate.
    • Maintain airway patency with head positioning and provide oxygen via nasal cannula or mask.
    • Consider intubation if further respiratory assistance is required.
    • Provide vasopressor support if systolic blood pressure < 90 mm Hg or mean arterial pressure < 70 mm Hg.
  • Initiate electrocardiography (ECG) monitoring.
  • Collect finger stick blood glucose. If blood glucose < 60 mg/dL, give thiamine 100 mg IV followed by D50W (50% dextrose) 50 mL IV.
  • Establish IV access in large veins.
  • Perform laboratory testing for blood glucose, complete blood count, basic metabolic panel, calcium and magnesium, and antiseizure medication levels.
• Use continuous EEG to monitor treatment effects in all patients with status epilepticus (Strong recommendation).
• The goal of pharmacologic treatment is the immediate cessation of all seizures and the prevention of seizure recurrence.
  • Emergent initial therapy:
    • Short-acting benzodiazepines are the preferred first-line antiseizure medication in all patients (Strong recommendation).
    • IV administration is preferred (use intramuscular, rectal, nasal, or buccal routes if IV is not feasible).
    • The preferred initial therapy options include:
      • lorazepam 0.1 mg/kg IV (maximum 4 mg/dose); may be repeated in 5-10 minutes (Strong recommendation)
      • midazolam 0.2 mg/kg intramuscularly (maximum 10 mg/dose) (Strong recommendation); ease of administration and storage may make midazolam especially preferable for prehospital administration (alternative dosing is 0.2 mg/kg intranasally or 0.5 mg/kg buccally)
      • diazepam 0.2 mg/kg rectally (Strong recommendation) (alternative dosing is 0.15 mg/kg IV push at a rate not exceeding 5 mg/minute [maximum 10 mg/dose]; may be repeated in 5 minutes)
    • Additional medications to correct known or suspected nutrient deficiencies which may cause status epilepticus include thiamine 100 mg and 50% glucose IV in adults with hypoglycemia.
  • Urgent control therapy with second-line, longer-acting antiseizure medications should follow the initial therapy in most patients.
    • The goal is to maintain control after seizure cessation, or to achieve seizure cessation in patients unresponsive to emergent initial therapy.
    • In patients already on medication for known epilepsy, consider IV bolus dose of regular antiseizure medication before starting new agent.
    • Specific options include:
      • fosphenytoin 20 mg phenytoin equivalents/kg IV bolus at a rate not exceeding 150 mg phenytoin equivalents/minute (maximum 1,500 mg phenytoin equivalents/dose); may give an additional 5 mg/kg 10 minutes after loading dose (Weak recommendation)
      • levetiracetam 60 mg/kg IV (maximum 4,500 mg) single dose (Weak recommendation)
      • valproate sodium 20-40 mg/kg IV bolus (maximum 3,000 mg/dose) at rate of 3-6 mg/kg/minute; may give an additional 20 mg/kg 10 minutes after loading dose (Weak recommendation)
      • midazolam 0.2 mg/kg IV bolus at rate of 2 mg/minute, followed by a continuous infusion at 0.05-2 mg/kg/hour (0.83-33 mcg/kg/minute) (Weak recommendation)
      • phenobarbital 20 mg/kg IV bolus at rate of 50-100 mg/minute; may give additional 5-10 mg/kg 10 minutes following loading dose (Weak recommendation)
      • phenytoin 20 mg/kg IV bolus at a rate not exceeding 1 mg/kg/minute (maximum 50 mg/minute); may give an additional 5-10 mg/kg 10 minutes after loading dose (Weak recommendation)
  • For refractory status epilepticus (in which patients do not respond to standard treatment), a continuous infusion of an antiseizure medication should be started and titrated until there is cessation of electrographic seizures or burst suppression (Strong recommendation).
    • Medication options for continuous IV infusion therapy for refractory status epilepticus (based on limited evidence) include:
      • midazolam 0.2 mg/kg loading dose, followed by 0.1-2 mg/kg/hour (1.7-33 mcg/kg/minute) maintenance infusion
      • propofol 1-2 mg/kg loading dose, followed by 2-12 mg/kg/hour (33-200 mcg/kg/minute) maintenance infusion
      • pentobarbital 5-15 mg/kg loading dose, followed by 0.5-5 mg/kg/hour (8.3-83 mcg/kg/minute) maintenance infusion
      • ketamine 1.5-4.5 mg/kg loading dose, followed by 2-7.5 mg/kg/hour (33-125 mcg/kg/minute) maintenance infusion
      • thiopental 4 mg/kg loading dose, followed by 0.3-0.4 mg/kg/minute maintenance infusion (not available in the United States)
    • Continuous infusions may require assisted ventilation and cardiovascular monitoring.
    • After 24-48 hours of seizure cessation (while monitored on EEG) and initiation of a maintenance antiseizure medication, continuous infusion can be slowly withdrawn (Weak recommendation).
    • Additional treatment options for refractory status epilepticus not responsive to continuous IV infusion therapy (super-refractory status epilepticus) include:
      • inhaled anesthetics including isoflurane or desflurane
      • nasogastric administration of oral antiseizure medications such as perampanel, pregabalin, or topiramate
      • resective surgery (if noneloquent brain region can be identified as definitive seizure focus)
      • repetitive transcranial magnetic stimulation (rTMS), vagal nerve stimulation, or deep brain stimulation
      • electroconvulsive therapy
      • other adjunctive therapies such as immunomodulatory therapy (if immunologic disease is suspected cause), ketogenic diet, and therapeutic hypothermia