II. Epidemiology

  1. Prevalence: 152,000 cases per year in United States
  2. Age (Bimodal distribution)
    1. Adults: Highest Incidence after age 60 years
    2. Children: Highest Incidence under age 1 year

III. Definition

  1. Diagnostic criteria (2015)
    1. Single unremitting Seizure lasting >5 minutes OR
    2. Frequent clinical Seizures without inter-ictal return to baseline lasting longer than 5 minutes
    3. Trinka (2015) Epilepsia 56(10): 1515-23 [PubMed]
  2. Classical diagnostic criteria
    1. Continuous Seizure activity longer than 30 minutes or
    2. Two or more sequential Seizures
      1. No recovery of consciousness between Seizures

IV. Pathophysiology

  1. Excessive excitation (excess glutamate)
  2. Ineffective inhibition (inadequate GABA)

V. Causes

  1. Poor Medication Compliance with low anticonvulsant drug levels
  2. Alcohol Withdrawal
  3. Drug Overdose or Toxin Ingestion
  4. Intracranial Infection such as Meningitis or Encephalitis
  5. Cerebral Neoplasm
  6. Metabolic disorder
    1. Electrolyte disturbance (especially Sodium, calcium and phosphorus)
    2. Inborn Errors of Metabolism

VI. Differential Diagnosis

VII. Signs

  1. See definition above
  2. Witnessed persistent Seizure
  3. Consciousness not regained within 5 minutes of Seizure

VIII. Labs

  1. Bedside Glucose
  2. Serum Electrolytes (e.g. Basic Metabolic panel with additional labs)
    1. Serum Sodium
    2. Serum Calcium
    3. Serum Phosphorus
    4. Serum Magnesium
    5. Renal Function tests (Serum Creatinine and Blood Urea Nitrogen)
  3. Hepatic panel
  4. Antiepileptic drug levels
  5. Urine Tox Screen
  6. Complete Blood Count

X. Management: Initial

  1. See ABC Management
  2. Control airway
    1. Nasal Airway
    2. Consider intubation
  3. Obtain IV Access with Normal Saline to keep open
  4. Administer oxygen
  5. Monitor Vital Signs closely
    1. Especially Temperature
    2. Telemetry
    3. Electrocardiogram

XI. Management: Non-Seizure medications

  1. Treat Hypoglycemia if present (based on bedside Glucose - consider if Glucose <80 mg/dl)
    1. Neonate: 0.5 mg/kg (5 ml/kg) D10W
    2. Child: 0.5 mg/kg (2 ml/kg) D25W
    3. Adult: 50 ml IV of D50W
  2. Consider Thiamine in Alcoholism or nutritional deficiency
    1. Thiamine 100 mg IV or IM
  3. Infants under age 2 years (empiric for Autosomal RecessivePyridoxine dependent Seizures)
    1. Pyridoxine 100 mg IV
  4. Severe Hyponatremia (typically in infant <3 months mistakenly fed free water)
    1. Hypertonic Saline 5-10 cc/kg 3% saline over 10 minutes

XII. Management: Protocol

  1. Precautions
    1. Following Benzodiazepines
      1. No evidence in 2014 to suggest one antiepileptic is better than another (e.g. Keppra, Valproic Acid)
    2. (2014) Ann Emerg Med 63(4): 437-47 [PubMed]
  2. First: Benzodiazepines (choose one)
    1. Precaution
      1. Do not underdose (give full dose to have best chance to terminate Seizure)
      2. IV Lorazepam and IV Diazepam have equivalent efficacy in Status Epilepticus
      3. Midazolam IM, intranasal or buccal may be more effective than Diazepam IV or rectal
      4. Neonatal Seizure
        1. Call pharmacy at presentation to have phenobarbital available in case Benzodiazepines fail
    2. Lorazepam (Ativan)
      1. Initial: 0.1 mg/kg IV (<2 mg/minute) up to 4 mg maximum
      2. May repeat once in 5-10 minutes
      3. Avoid more than 2 doses in children due to risk of respiratory depression
      4. Phamacokinetics: Onset in 2-3 minutes with duration of action 12-24 hours
    3. Diazepam (Valium)
      1. IV or IM: 0.2 to 0.3 mg/kg IV up to 10 mg/dose maximum (may repeat once in 5 minutes)
      2. Rectal: 0.2 to 0.5 mg/kg per Rectum up to maximum of 20 mg
        1. Instill via lubricated Feeding Tube inserted 4-5 cm into the Rectum OR
        2. Via tuberculin syringe (without needle) intra-rectally
        3. Hold buttocks closed after instilling medication
      3. Pharmacokinetics: Onset in 1-3 minutes with duration of action 5-15 minutes
        1. Must be immediately followed with longer acting anticonvulsant (e.g. Fosphenytoin) due to short duration
      4. Efficacy
        1. Diazepam is as effective as Lorazepam in Status Epilepticus
          1. Chamberlain (2014) JAMA 311(16): 1652-60
        2. Diazepam IM dosing is as effective as IV dosing
          1. Silbergleit (2012) N Engl J Med 366:591-600 [PubMed]
    4. Midazolam (Versed)
      1. Alternative agent when longer acting Benzodiazepines not available or without IV Access (e.g. Ambulance)
        1. Lorazepam and Diazepam are preferred if available
      2. IV: 0.15 mg/kg (then infused IV at 1 mcg/kg/min and titrated every 5 min as needed) up to 10 mg
      3. IM: 0.2 mg/kg of the IV formulation
        1. Weight 13-40 kg: 5 mg IM
        2. Weight >40 kg: 10 mg IM
      4. Rectal: 0.25 to 0.5 mg/kg
        1. May be delivered via tuberculin syringe (without needle) intra-rectally
      5. Intranasal: 0.2 mg/kg of the IV formulation (best delivered via atomizer)
      6. Buccal mucosa: 0.5 mg/kg of the IV formulation
  3. Next (if refractory after 5 minutes): Choose one
    1. If Neonatal Seizure skip to phenobarbital below (due to higher efficacy in this age group)
    2. Pharmacokinetics: Both agents have onset within 10-30 minutes with a duration of action of 12-24 hours
    3. Fosphenytoin (Cerebyx)
      1. Dose: 20 mg/kg IV or IM (at 3 mg/kg/min up to 150 mg/min) up to 1000 mg maximum
      2. Preferred over Phenytoin
        1. Fosphenytoin can be infused with dextrose
        2. Fosphenytoin has lower risk of arrhythmia (due to no Ethylene Glycol in base)
        3. Fosphenytoin may be given IM or delivered a faster IV rate (not tissue toxic)
          1. However onset of activity is similar to that with Phenytoin
          2. Fosphenytoin is converted to active Phenytoin form
    4. Phenytoin (Dilantin) - Fosphenytoin is preferred instead (see above)
      1. Dose: 20 mg/kg IV (at 1 mg/kg/min up to 50 mg/min) up to to 1000 mg maximum
      2. May repeat once with Phenytoin 5-10 mg/kg IV
      3. Maintenance with Phenytoin 50 mg/min
    5. Levetiracetam (Keppra)
      1. Dosing recommended in Status Epilepticus is higher
        1. Dose: 60 mg/kg IV (up to 4500 mg/dose) for single dose
      2. Typical dosing
        1. Load: 20-30 mg/kg IV at 5 mg/kg/min (may give additional second 20 mg/kg IV dose)
        2. Maximum: 3 grams (or 80 mg/kg/day)
      3. IV formulation is not FDA approved in children
      4. Limited data in Status Epilepticus
    6. Valproic Acid (Depakote)
      1. Dosing recommended in Status Epilepticus is higher
        1. Dose: 40 mg/kg IV (up to 3000 mg/dose)
      2. Typical dosing
        1. Load: 20 mg/kg IV over 1 to 5 minutes
        2. Maintain: 5 mg/kg/hour
      3. Less Sedation, respiratory depression, and cardiovascular effects than any of the other agents
      4. Risk of hepatotoxicity
      5. Risk of hyperammonemia (avoid in age under 2 years, especially if inborn error of metabolism)
  4. Next (if refractory after 30 minutes)
    1. Phenobarbital (less commonly used in 2014 - used if second line options not available)
      1. Dose: 20 mg/kg IV
        1. May repeat once with Phenobarbital 5-10 mg/kg IV
        2. Maximal infusion rate: 0.5 to 1 mg/kg/minute up to 50 mg/min
      2. Pharmacokinetics: Onset within 10-20 minutes and duration of 1-3 days
      3. Be prepared to ventilate patient
  5. Next (if refractory after 60 minutes)
    1. Preparation
      1. Requires full life support (coma state)
        1. Intubate and ventilate
        2. Rapid Sequence Intubation
          1. Consider Pentobarbital, Benzodiazepines, Ketamine or Propofol for induction agent
      2. Foley Catheter
      3. Electroencephalogram (EEG)
        1. Dosages below titrated based on EEG
        2. Infusion slowed every 4-6 hours to check EEG status
      4. Follow Temperature closely
        1. Treat hyperthermia with rectal Acetaminophen 15 mg/kg up to 650-1000 mg every 6 hours
      5. Pressor support
        1. Often required for next set of medictions
    2. Choose one medication
      1. Pentobarbital (Nembutal)
        1. Load: 5 mg/kg IV (up to 15 mg/kg, coma dose)
        2. Maintain: 0.5 to 1 mg/kg/hour (up to 5 mg/kg/hour)
        3. Anticipate myocardial depression with secondary reduced Cardiac Output and Hypotension
      2. Midazolam (Versed)
        1. Load: 0.2 mg/kg IV
        2. Maintain: 1 mcg/kg/min
        3. Titrate: Increase by 1 mcg/kg/min every 15 minutes until burst suppression (up to 0.75 to 10 mg/hour)
        4. Anticipate respiratory depression
      3. Propofol (Diprivan)
        1. Load: 1 to 2 mg/kg IV
        2. Maintain: 2-10 mg/kg/hour if Propofol loading dose aborted the Seizure
        3. Anticipate apnea and Hypotension with rapid infusion
      4. Ketamine
        1. Antagonizes NMDA receptors
        2. Dose: 1.5 to 2 mg/kg
        3. If Ketamine aborts Seizure, then start Propofol maintenance at dose as above
        4. Case reports of neurotoxicity in adults

XIII. Prognosis

  1. Mortality
    1. Overall: 22%
    2. Children: 3%
    3. Adults: 26%
    4. Elderly: 38%
    5. DeLorenzo (1996) Neurology 46:1026-35 [PubMed]
  2. Morbidity
    1. High Incidence of neurologic sequelae

XIV. Complications

  1. Anoxic brain injury
  2. Death
  3. Rhabdomyolysis (after 30-60 minutes of Seizure)

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Ontology: Status Epilepticus (C0038220)

Definition (NCI) A life-threatening situation in which the brain is in a continuous state of seizure.
Definition (MSH) A prolonged seizure or seizures repeated frequently enough to prevent recovery between episodes occurring over a period of 20-30 minutes. The most common subtype is generalized tonic-clonic status epilepticus, a potentially fatal condition associated with neuronal injury and respiratory and metabolic dysfunction. Nonconvulsive forms include petit mal status and complex partial status, which may manifest as behavioral disturbances. Simple partial status epilepticus consists of persistent motor, sensory, or autonomic seizures that do not impair cognition (see also EPILEPSIA PARTIALIS CONTINUA). Subclinical status epilepticus generally refers to seizures occurring in an unresponsive or comatose individual in the absence of overt signs of seizure activity. (From N Engl J Med 1998 Apr 2;338(14):970-6; Neurologia 1997 Dec;12 Suppl 6:25-30)
Concepts Disease or Syndrome (T047)
MSH D013226
ICD10 G41 , G41.9
SnomedCT 194499008, 193019007, 155039002, 192998006, 13973009, 230456007
English STATUS EPILEPTICUS, Status epilepticus, unspec, Status epilepticus, unspecified, [X]Status epilepticus, unspec, [X]Status epilepticus, unspecified, Generalized Status Epilepticus, Status Epilepticus, Generalized, Status Epilepticus [Disease/Finding], status epilepticus, epilepticus status, [X]Status epilepticus, unspecified (disorder), Status epilepticus, Status epilepticus (disorder), epilepsy; status, epilepticus; status, status; epilepticus, status; epileptic, Status epilepticus NOS, Status Epilepticus
German STATUS EPILEPTICUS, Status epilepticus, nicht naeher bezeichnet, Status epilepticus
Italian Stato epilettico, Stato epilettico generalizzato, Status epilepticus
Swedish Status epilepticus
Japanese テンカンジュウセキジョウタイ, 癲癇重積状態, 癲癇重積症, てんかん発作重積, 発作重積状態, 小発作状態, てんかん重積, てんかん重積状態, 小発作重積状態
Czech status epilepticus, Status epilepticus
Finnish Epileptinen sarjakohtaus
Russian PETIT MAL, STATUS, EPILEPTICHESKII STATUS, PETIT MAL, СТАТУС, ЭПИЛЕПТИЧЕСКИЙ СТАТУС
Portuguese ESTADO DE MAL EPILEPTICO, Estado Epilético Parcial Simples, Estado Epilético não Convulsivo, Estado Epilético Convulsivo Generalizado, Estado Epilético Parcial Complexo, Estado de mal epiléptico, Estado Epiléptico
Spanish ESTADO EPILEPTICO O STATUS EPILEP, [X]estado epiléptico, no especificado (trastorno), [X]estado epiléptico, no especificado, Estatus epiléptico, estado epiléptico, estado epiléptico (trastorno), Estado Epiléptico
French ETAT DE MAL EPILEPTIQUE, Etat de mal épileptique, État de mal épileptique
Korean 상세불명의 간질 지속상태, 간질 지속상태
Polish Stan padaczkowy
Hungarian Status epileptikus
Norwegian Status epilepticus, Generalisert status epilepticus
Dutch epilepsie; status, epilepticus; status, status; epilepsie, status; epilepticus, Status epilepticus, niet gespecificeerd, status epilepticus, Status epilepticus, Complexe partiële status epilepticus