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LeenaKämppi

Treatment of a Prolonged Epileptic Seizure and Status Epilepticus

Essentials

  • A prolonged seizure with unconsciousness is a life-threatening emergency situation requiring immediate care.
  • An epileptic seizure lasting for more than 5 minutes should be treated as an imminent status epilepticus.
  • Mortality and the risk of disability increase when a seizure with unconsciousness has lasted for more than 30 minutes. The prognosis can be influenced by early treatment that is as effective as possible.
  • Status epilepticus (SE) requires follow-up in hospital and aetiological investigations (brain imaging studies, cerebrospinal fluid (CSF) samples, additional laboratory investigations), as well as treatment even after the acute situation has settled.
  • When a patient with known epilepsy has had a prolonged seizure it is usually warranted to consider intensification of the basic medication and other possible measures by a neurologist.
  • Find out about locally available guidance on epilepsy/seizure first aid and when to contact emergency medical services.

Status epilepticus (SE)

  • Epileptic seizures are due to abnormal bursts of electrical activity in the brain. Ordinary epileptic seizures stop spontaneously in 1-4 minutes without special intervention.
  • In status epilepticus (SE), the seizure continues for more than 5 minutes or seizures recur so frequently that the patient cannot recover between them.
  • In SE, the mechanisms normally stopping a seizure fail or abnormal mechanisms are triggered leading to constant bursts of electrical activity in the brain. Pharmacotherapy is needed to interrupt the seizure(s).
  • The prevalence of SE is 20-40/100 000/year. About 60% of patients with SE have a history of epilepsy.
  • Even with effective treatment, SE is associated with a 2-40% mortality. The prognosis depends on the patient's age, the cause, type and severity of the SE, and any delay in treatment.
  • SE is classified into several types based on seizure characteristics.
    • Generalized convulsive SE (unconsciousness and motor symptoms)
    • Generalized SE with minor symptoms (unconsciousness in the absence of clear motor symptoms)
    • Focal convulsive SE (motor symptoms, preserved or impaired consciousness)
    • Focal SE with minor symptoms (other than motor symptoms, such as aphasia, preserved or impaired consciousness)
    • SE appearing as absence (associated with generalized absence epilepsies)
    • Myoclonic SE (associated with hypoxic-ischaemic brain injury and generalized types of epilepsy)
  • Myoclonic SE associated with hypoxic-ischaemic brain injury and generalized types of SE (convulsive SE and SE with minor symptoms) have the worst prognosis of all types of SE.
  • Common causes of SE
    • Poorly controlled epilepsy or changes to medication
    • Treatment-resistant epilepsy and certain epileptic syndromes, such as the Dravet syndrome http://www.orpha.net/consor/cgi-bin/OC_Exp.php?Expert=33069
    • Acute causes, such as encephalitis, fresh cerebral events, tumours, severe hyponatraemia, hypoxic-ischaemic brain injury, substance withdrawal

Treatment of SE

  • Treatment goals
    • Securing vital functions
    • Stopping clinical seizure symptoms and bursts of electrical activity in the brain as soon as possible
    • Preventing the case from becoming treatment-resistant by starting treatment quickly with sufficient doses
    • Preventing the recurrence of seizure symptoms
    • Preventing and treating systemic complications (such as infections, thromboembolism)
    • Investigating and treating aetiological factors
    • Minimizing mortality and residual symptoms affecting functional capacity
  • Treatment is staged according to the time that has elapsed.
    • 0-5 min: ordinary epileptic seizure → first-aid treatment
      • Securing vital functions (ABC: Airway, Breathing, Circulation)
      • Securing breathing by assistance or by placing the patient in the lateral position
      • Preventing further injuries
    • 5-20 min: early status epilepticus → first-stage treatment
      • Giving supplemental oxygen through a mask, and establishing intravenous access (Ringer or NaCl 0.9%)
      • Measurement of blood glucose and treatment of hypoglycaemia
      • Thiamine 250 mg i.v. before correction of hypoglycaemia
      • ECG monitoring and pulse oximetry
      • Pharmacotherapy with benzodiazepines
        • No venous access (relatives / first response unit)
        • Intravenous access (advanced level or physician unit / hospital)
          • Midazolam 2.5 mg i.v. up to 7.5 mg
          • Lorazepam 2-4 mg i.v. up to 8 mg
          • Diazepam 10 mg i.v. up to 30 mg
          • Dose repeated every 5 minutes, as necessary
      • 20-40 min: status epilepticus → second-stage treatment
        • Proceed to second-stage pharmacotherapy if first-stage treatment is not sufficient to stop the seizure. Use i.v. antiepileptic loading.
        • There are several alternative intravenous antiepileptic drugs. As clinical trials have not been able to show any drug to be superior to others, all available drugs can be used in practice. When choosing the drug, it is essential to consider the patient's total medication, any contraindications, risks, drug interactions or similar mechanisms of action.
        • In emergency care, a physician unit may have started loading with levetiracetam before hospital admission. In some cases, patients may be transferred under propofol sedation without giving antiepileptic loading doses. All this should be considered when planning further treatment in the hospital.
        • Second-stage drug options
        • Proceeding to third-stage treatment should not be delayed by giving several second-stage drugs and waiting for a response. However, focal SE and situations where the patient is not considered to benefit from intensive care form exceptions where it may be justified to give several second-stage drugs.
      • >40 min: treatment-resistant, or refractory, SE → third-stage treatment
        • SE is classified as treatment-resistant if the seizure cannot be stopped despite appropriately administered first- and second-stage medication. If so, proceed to third-stage treatment by administering general anaesthesia in an intensive care / surveillance unit.
      • Third-stage drug options
      • The aim of the treatment is to stop clinical seizure symptoms and suppress bursts seen in EEG for 12-24 hours. Continuous EEG monitoring should be started.
      • The cause of the SE should be assessed at this stage, at the latest, and treatment consistent with the aetiology started.
    • Further treatment should be chosen individually. The patient will need hospital treatment even if a prolonged seizure is resolved by first-stage treatment, already. Finding out the causes of the SE, intensifying the basic medication, and recovery will take time. For further treatment, it is important to assess and implement measures to prevent recurrent SE.

Examination of a patient with SE

  • Clinical status
    • Is the seizure symptom unilateral, focal?; level of consciousness
    • Focal symptoms, meningism, signs of trauma
  • Laboratory tests
    • ECG
    • Basic blood count with platelet count, Na, K, CRP, CK, glucose, ionised calcium, creatinine, ALT
    • GT, CDT/PEth, urine drug screen, intoxication samples, as considered necessary
    • Antiepileptic drug concentrations as considered necessary; serum valproate, serum carbamazepine, free serum phenytoin, for example, may be available during on-call hours (find out about locally available on-call tests). Measuring other antiepileptic drug concentrations may also be useful in order to assess treatment compliance.
  • Imaging
    • Cranial CT is the primary emergency imaging method.
    • Cranial MRI as considered necessary
    • Jugular/cerebral CT angiography as a differential diagnostic examination if extensor rigidity due to basilar thrombosis is suspected.
  • CSF as necessary to exclude CNS infection
  • EEG should be utilized in the diagnosis and monitoring of treatment response in patients with SE.
    • Diagnosis: unclear sequelae of a bout of unconsciousness, drug effect, SE, other cause?
    • Differential diagnosis: epileptic symptom, functional symptom or cerebrovascular disorder?
    • Monitoring of treatment response: assessment of the end of SE/burst, assessment of the degree of burst suppression

First-aid medication in patients with epilepsy

  • Few adults with epilepsy need first-aid medication administered by another person in addition to their continuous medication, because most seizures stop spontaneously within 4 minutes.
  • Buccal midazolam or rectal diazepam can be prescribed for a patient with epilepsy and a risk or history of prolonged epileptic seizure to be used as first-aid medication. Both drugs require the provision of guidance for a family member or regular assistant.

    References

    • Trinka E, Cock H, Hesdorffer D et al. A definition and classification of status epilepticus--Report of the ILAE Task Force on Classification of Status Epilepticus. Epilepsia 2015;56(10):1515-23. [PubMed]
    • Glauser T, Shinnar S, Gloss D et al. Evidence-Based Guideline: Treatment of Convulsive Status Epilepticus in Children and Adults: Report of the Guideline Committee of the American Epilepsy Society. Epilepsy Curr 2016;16(1):48-61. [PubMed]
    • Kapur J, Elm J, Chamberlain JM et al. Randomized Trial of Three Anticonvulsant Medications for Status Epilepticus. N Engl J Med 2019;381(22):2103-2113. [PubMed]