Generalised convulsive (tonic-clonic) status epilepticus is defined as a generalised convulsion lasting 30 minutes or longer, or repeated tonic-clonic convulsions occurring over a 30-minute period without recovery of consciousness between each convulsion.¹

Epidemiology

Estimated incidence is between 10 and 60 cases per 100,000 person/years.² The incidence is higher in poorer populations. It recurs in about a third of patients.³

Risk factors

• History of epilepsy.
• Age under 5 years or elderly.
• Genetic predisposition.
• Mental handicap.
• Structural brain pathology.

Potential precipitants

• Drug withdrawal.
• Intercurrent illness.
• Metabolic disturbance, e.g. hypoglycaemia.
• Cerebrovascular event.
• Alcohol intoxication or withdrawal.

Presentation

This would be the same as any convulsion, but unremitting. The diagnosis of tonic-clonic status is usually clear, although it needs to be distinguished from pseudo-status epilepticus which is non-epileptic attacks with a psychological basis.

Non-convulsive status (e.g. absence status or continuous partial seizures with preservation of consciousness) may be more difficult. In non-comatose patients it may present as confusion, personality change or psychosis.

Management in adults

General protective measures

• Make the patient comfortable.
• Ensure the head is protected.
• Release constricting neck wear.
• Move if in a dangerous situation (e.g. at the top of stairs).
• Call an ambulance to arrange urgent transfer to hospital.
• Secure airway (insert a Guedel or nasopharyngeal airway) and resuscitate.
• Give oxygen if possible
• Assess cardiorespiratory function and monitor blood pressure
• Establish intravenous (IV) access
• Consider the possibility of non-epileptic status.

Emergency drug therapy

This depends on the stage; premonitory, established or refractory:

• In the premonitory phase, diazepam 10-20 mg given rectally.
• In the established phase, IV Diazemuls®, repeated once, 15 minutes later, if status continues. Rectal diazepam will stop recurrent seizures in 70% of patients.⁴ IV diazepam will end status in 60-80% of patients or midazolam 10 mg, given buccally, may be easier to administer.⁵
• If seizures continue: lorazepam (IV) should be used as first-line treatment in the established phase, at a dose of 0.1 mg/kg (usually a 4 mg bolus, repeated once after 10-20 minutes; rate not critical). This has been shown to have a better efficacy than diazepam or phenytoin for stopping seizures and reducing the risk of status continuing.⁶
• Long-term maintenance: anti-epilepsy drug therapy must be given in parallel with emergency treatment. The choice of drug depends on previous therapy, the type of epilepsy, and the clinical setting. Any pre-existing therapy should be continued at full dose, and any recent reductions reversed.
• For sustained control or if seizures continue:
  • Established status: phenytoin infusion at a dose of 15-18 mg/kg and rate of 50 mg/minute, and/or phenobarbital 10-15 mg/kg at a rate of 100 mg/minute.
  • Refractory status requires general anaesthesia. The refractory stage (general anaesthesia) is reached 60/90 minutes after the initial therapy. In some situations, general anaesthesia should be initiated earlier and, occasionally, should be delayed.

Emergency investigations

• Pulse oximetry.
• Blood for blood gases.
• Glucose level.
• Renal and liver function.
• Electrolytes.
• Calcium and magnesium.
• FBC.
• Blood clotting.
• Anti-epilepsy drug levels.
• 5 ml of serum and 50 ml of urine samples should be saved for future analysis, including toxicology, especially if the cause of the status epilepticus is uncertain.

Other therapy

In patients likely to have poor nutrition:²

• Administer glucose (50 ml of 50% solution) and/or IV thiamine (250 mg) as high potency; Pabrinex#174 if there is any suggestion of alcohol abuse.
• Treat acidosis if severe.

Further management

• Establish aetiology. This is a common neurological problem in the elderly, with an underlying aetiology of stroke. Status epilepticus is associated with a high mortality.
• Identify and treat medical complications:
  • CXR to evaluate possibility of aspiration.
  • Other investigations depend on the clinical circumstances and may include brain imaging, and lumbar puncture.
  • Status is associated with community-acquired bacterial meningitis and fits, in the acute phase of the illness, are predictors of poor outcome.⁷

Monitoring

• Regular neurological observations and measurements of pulse, blood pressure, temperature.
• ECG, biochemistry, blood gases, clotting, blood count, drug levels.
• Patients require the full range of ITU facilities and care should be shared between anaesthetist and neurologist.
• EEG monitoring is necessary for refractory status. Consider the possibility of non-epileptic status.
• In refractory status epilepticus, the primary endpoint is suppression of epileptic activity on the EEG, with a secondary endpoint of burst-suppression pattern (i.e. short intervals of up to 1 second between bursts of background rhythm).

Treating status epilepticus in children

There is an incidence of 20-50/100,000 children per year. Fits are most commonly associated with febrile illnesses.The management of a child who presents with a tonic-clonic convulsion lasting more than 5 minutes should be the same as the child who is in established status.

• General measures are the same as outlined above for adults:
  • A, B, C resuscitation. Give O₂. Check blood glucose.
  • A quick treatment response will produce the most effective outcome. There is increased morbidity and mortality associated with status lasting more than 60 minutes.⁸
• If immediate IV access : IV lorazepam 0.1 mg/kg, given over 30-60 seconds.
• If no IV access: diazepam 0.5 mg/kg, given rectally, or buccal midazolam may be easier.
• If seizure is continuing at 5 minutes:
  • If IV access: load with phenytoin 18 mg/kg IV over 20 minutes or, if already on phenytoin, give phenobarbital 20 mg/kg IV over 10 minutes.
  • If no IV access: give paraldehyde 0.4 ml/kg rectally (given with same volume of olive oil or normal saline).
• Wait 5 minutes and if still fitting:
  • IV access definitely required. Try the interosseous route as an alternative.
  • Call the on-call anaesthetist or intensive care medic.
  • Rapid sequence induction of anaesthesia using thiopental 4 mg/kg IV.

Non-convulsive status epilepticus in adults and children

This is less common than tonic-clonic status epilepticus. Treatment for non-convulsive status epilepticus is less urgent than for convulsive status epilepticus. Treatment should be considered as follows:

• Maintenance or reinstatement of usual oral anti-epileptic therapy.
• Use of IV benzodiazepines under EEG control, particularly if the diagnosis is not established.
• Referral for specialist advice and/or EEG monitoring.

Prognosis

Aetiology and conscious level predict outcome.⁹

• If the patient presents for the first time with status epilepticus, the chance of a structural brain lesion is greater than 50%.
• Mortality and the risk of permanent brain damage are increased with duration of the attack (especially if over 1 hour). Mortality rates can be as high as 5-10% in adults and 3% in children.

Prevention

Good seizure control in pre-existing epilepsy.

Document references

1. Epilepsy, Clinical Knowledge Summaries (June 2009)
2. Walker M; Status epilepticus: an evidence based guide. BMJ. 2005 Sep 24;331(7518):673-7.
3. Hesdorffer DC, Logroscino G, Cascino GD, et al; Recurrence of afebrile status epilepticus in a population-based study in Rochester, Minnesota. Neurology. 2007 Jul 3;69(1):73-8. [abstract]
4. Dreifuss FE, Rosman NP, Cloyd JC, et al; A comparison of rectal diazepam gel and placebo for acute repetitive seizures. N Engl J Med. 1998 Jun 25;338(26):1869-75. [abstract]
5. Treiman DM, Meyers PD, Walton NY, et al; A comparison of four treatments for generalized convulsive status epilepticus. Veterans Affairs Status Epilepticus Cooperative Study Group. N Engl J Med. 1998 Sep 17;339(12):792-8. [abstract]
6. Prasad K, Al-Roomi K, Krishnan PR, et al; Anticonvulsant therapy for status epilepticus. Cochrane Database Syst Rev. 2005 Oct 19;(4):CD003723. [abstract]
7. Wang KW, Chang WN, Chang HW, et al; The significance of seizures and other predictive factors during the acute illness for the long-term outcome after bacterial meningitis. Seizure. 2005 Dec;14(8):586-92. Epub 2005 Oct 25. [abstract]
8. Eriksson K, Kalviainen R; Pharmacologic management of convulsive status epilepticus in childhood. Expert Rev Neurother. 2005 Nov;5(6):777-83. [abstract]
9. Kaplan PW; The clinical features, diagnosis, and prognosis of nonconvulsive status epilepticus. Neurologist. 2005 Nov;11(6):348-61. [abstract]

Internet and further reading

• British Epilepsy Association
• EFNS guideline on the management of status epilepticus, European Federation of Neurological Societies (2006)
• Chang RS, Tse AC, Mak W, et al; From drugs to delirium. Lancet. 2008 May 17;371(9625):1722.
• Scott RC, Kirkham FJ; Clinical update: childhood convulsive status epilepticus. Lancet. 2007 Sep 1;370(9589):724-6.

Acknowledgements