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Status epilepticus

Introduction

  • medical emergency requiring prompt intervention to prevent the development of irreversible brain damage
  • recurrent epileptic seizures without full recovery of consciousness before the next seizure begins or more-or-less continuous clinical and/or electrical seizure activity lasting for more than 30 min whether or not consciousness is impaired.

Types

1. Repeated generalized tonic and/or clonic convulsive seizures where the patient does not fully recover neurological function between attacks

2. Non-convulsive status: prolonged "twilight" state

3. Continuous focal epileptic activity without alteration of consciousness.

Pathophysiology

  • pathophysiological effects of seizures on the brain are thought to result from both direct excitotoxic neuronal injury and secondary injury due to systemic complications such as hypotension and hypoxia
  • postulated that seizures result in excessive pre-synpatic release of glutamate. This activates post-synaptic glutamate receptors resulting in calcium influx into cells via receptor gated calcium channels and release of intracellular calcium stores. The increase in intracellular calcium ions activates calcium dependent enzymes that are responsible for irreversible neuronal injury.

Aetiology

  • may occur de novo, or, less commonly, in a previously diagnosed epileptic. Most common causes in a patient presenting for the first time:
  • Cerebral tumour, primary or secondary
  • Stroke of all varieties
  • Intracranial infection, ie meningitis, meningoencephalitis, or cerebral abscess
  • Hypoxic encephalopathy (eg post cardiac arrest)
  • Drug abuse and overdose, eg tricyclic antidepressants, theophylline, cocaine or other stimulants
  • Electrolyte disturbances, including:
  • hyponatraemia

  • hypocalcaemia

  • hypomagnesaemia

  • Hypoglycaemia
  • Human immunodeficiency virus infection
  • (By exclusion) First presentation of primary epilepsy

  • most common causes of generalised convulsive status in a previously diagnosed epileptic are:

    1. Poor compliance with medication
    2. Change in antiepileptic drug dosage or type
    3. Alcohol withdrawal
    4. Pseudostatus

Generalised convulsive status epilepticus

  • most common and dangerous form
  • includes a wide range of presentations from repeated overt generalized seizures to very subtle focal twitches of a localised part of the body (eg rhythmic nystagmoid eye jerks, twitching of an eyelid). Although the latter may superficially appear to be a form of focal epilepsy, they can be clearly distinguished from focal epilepsy by the fact that the patient has profound impairment of conscious level and bilateral EEG changes.
  • if a patient with generalized tonic-clonic convulsions is inadequately treated the generalized convulsions may stop despite continued ictal EEG discharges.
  • most important differential diagnosis is pseudoseizures. The distinction may be extremely difficult and can only be made with complete certainty with the benefit of EEG monitoring. The clinical features listed in below are suggestive of pseudoseizures:
  • More common in females
  • History of psychosocial disturbance
  • Consciousness may be retained in the presence of bilateral jerking
  • Resistance to examination
  • Vocalisation
  • Pelvic thrusting
  • Gaze aversion
  • Normal pupillary response during convulsion
  • Normal tendon reflexes and plantar responses immediately after convulsion

NB. Although prolactin levels are often increased following a single true fit and thus can be used to distinguish a single fit from a pseudoseizure, levels are not usually raised in status epilepticus.

  • morbidity and mortality relates in part to the neuronal injury which may result from inadequate treatment, in part to the systemic complications  and in part to the aetiology.

Nonconvulsive status epilepticus

  • accounts for at least 1/4 cases of status epilepticus
  • incidence is probably underestimated due to failure to diagnose it
  • divided into absence status epilepticus and complex partial status epilepticus.

Absence status epilepticus

  • characterised by a prolonged confusional state associated with generalised 3 Hz spike and slow wave EEG activity
  • coma is almost never a feature
  • not a life-threatening condition, unlike generalised convulsive SE and although it is a relatively common form of SE, patients rarely require admission to ICU.
  • major significance in ICU practice lies in the importance of differentiating between absence SE and the unresponsive state associated with prolonged generalised convulsive SE.

Complex partial status epilepticus

  • diagnosis may be difficult due to its variable presentation and the need for EEG confirmation.
  • ictal activity may be continuous or may be cyclical with failure to regain consciousness between seizures.
  • characteristic manifestation of ictal activity is altered mentation with variable responsiveness and amnesia
  • patients may demonstrate automatism and complex motor activity, bizarre behaviour and lateralizing or localizing neurological deficits (eg aphasia or paresis).
  • duration usually several minutes to hours.
  • prompt diagnosis is important as early treatment appears to be important in preventing neurological morbidity.

Investigations

Initial investigations:

Glucose, urea & creatinine, sodium, potassium, calcium
Anti-epileptic drug levels
Complete blood count
Oximetry or arterial blood gases
Urinalysis

Further investigations after stabilization:

Liver function tests
Magnesium
Toxicology screen
CT scan
Lumbar puncture
EEG

  • not all of the investigations need be performed in every patient;
  • selection depends on both the patient's history and presentation. Most patients with SE should have a CT scan performed at some stage but patients with established epilepsy who have already had a CT scan do not usually require another scan.
  • CNS infection must be seriously considered in all patients, especially young children with a fever. Lumbar puncture is indicated in patients with fits not controlled with a benzodiazepine and phenytoin, or evidence of craniofacial infection (eg otitis, mastoiditis), or nuchal rigidity. It is contraindicated in those in whom an intracranial space occupying lesion is suspected. Although CT scanning prior to lumbar puncture is not considered, by some, to be mandatory, it should be bourne in mind that in adults CNS tumours are a more common cause of epilepsy than CNS infection and that lumbar puncture is never a life-saving procedure. It has been suggested that, even in suspected meningitis, lumbar puncture be delayed for 30 minutes after a fit because of the transient cerebral oedema that accompanies a fit. Although CSF leucocytosis occurs in 20% of patients with SE, patients with CSF leucocytosis should be treated for suspected meningitis until the diagnosis is excluded by microbiological culture or antibody assays.

Management

Generalised convulsive SE

  • accurate history, with particular emphasis on an eye-witness account of the onset and the nature of the seizures should be obtained and physical examination should be performed but neither should delay initial emergency management.
  • there is evidence that the longer SE goes untreated the harder it is to control with drugs and in animals the risk of brain damage is directly related to the duration of SE
  • management involves control of the seizures to prevent neuronal damage and other secondary complication, management of the complications and treatment of the underlying pathology

1. Resuscitation
- Assess airway, breathing and circulation
- Place in left lateral position
- Give oxygen by facemask
- Consider tracheal intubation especially if patient is cyanosed
- Insert IV cannula and draw blood for investigations

2. If hypoglycaemic or if blood glucose estimation not available give glucose. In adults give 100 mg thiamine first then 50 ml 50% glucose IV bolus; in children give glucose 25% 2ml/kg.

3. Diazepam IV 0.2 mg/kg at 5 mg/min OR lorazepam 0.1 mg/kg at 2 mg/min. If diazepam is given to stop the status phenytoin should be given next to prevent recurrence.

4. If status persists give 15-20 mg/kg of phenytoin IV at a rate < 50 mg/min in adults and 1 mg/kg/min in children. Monitor ECG and BP during infusion. If hypotension or arrhythmias develop slow the rate of infusion.

5. If status persists after 20 mg/kg of phenytoin, give additional doses of 5 mg/kg to a maximal dose of 30 mg/kg

6. If status still continues give 20 mg/kg of phenobarbitone at 100 mg/min IV but be prepared to intubate and ventilate the patient as the risk of apnoea is high.

7. If status is still not controlled give anaesthetic doses of thiopentone (3-5 mg/kg), intubate and ventilate the patient.

Absence SE

  • patients do not usually require admission to ICU
  • management will depend to some extent on the availability of resuscitation equipment
  • if resuscitation equipment is to hand, IV diazepam or lorazepam are suitable first-line drugs. IV acetazolamide is safer but less effective (250 mg in children and adults < 35 kg; otherwise 500mg).
  • once absence SE has been terminated a long acting oral anticonvulsant should be started (eg valproate, ethosuximide or clonazepam).

Complex partial SE

  • treatment should be instituted as soon as the diagnosis has been confirmed with an EEG.
  • management is essentially the same as for generalised convulsive SE.

Drugs

Benzodiazepines

  • most commonly used first-line drugs in the control of status epilepticus
  • used intravenously, achieve high brain levels rapidly, and will usually terminate an attack of seizures within minutes (33% at 3 minutes, 80% within 5 minutes).
  • most commonly used benzodiazepine for this purpose is diazepam. It terminates status more rapidly (1-3 minutes) than lorazepam but because of rapid redistribution brain concentrations fall rapidly and fits often recur if it is used alone to treat status
  • lorazepam has a slower onset of action but longer duration of action.
  • some evidence, in children, that midazolam may terminate status in cases where adequate doses of diazepam and phenytoin have failed, without causing severe respiratory depression.
  • diazepam and lorazepam can also be given rectally when intravenous administration is not possible. If a rectal preparation is not available a Foley catheter should be inserted into the rectum and the balloon inflated. Either drug can then be simply diluted with an equal amount of saline and flushed into the rectum. The balloon of the catheter prevents leakage of the drug out of the rectum. Doses of 0.2-0.7 mg/kg of diazepam given rectally controls SE in most patients within 1-10 min.
  • absorption after intramuscular injection is erratic and this route should not be used.

Phenytoin

  • can cause hypotension and cardiac arrythmias, especially in patients with pre-existing heart disease.
  • blood pressure and ECG should be monitored during infusion of phenytoin and the rate of infusion slowed if the patient develops hypotension, prolonged QT interval or cardiac arrhythmias. If SE stops before the complete dose is given the infusion rate should be slowed to decrease the chance of adverse effects.
  • not stable in dextrose solutions and is only stable in saline for 30 minutes.
  • absorption is unpredictable when given intramuscularly and therefore in an emergency situation this route should not be used. Intramuscular injection has the additional disadvantage that it may cause sterile abscesses.
  • if the plasma phenytoin concentration is known, the additional dose of phenytoin required in order to achieve a therapeutic plasma concentration can be calculated using the following formula:

      Loading dose (mg) = 0.65 weight (kg) x (Cdesired - Ccurrent)

      where C is the phenytoin concentration in mg/l (divide by 4 if in µmol/l)

  • phenytoin is highly albumin-bound and thus total phenytoin levels will be low in hypoalbuminaemic patients even if concentration of free (active) fraction is normal. Total phenytoin levels can be corrected for hypoalbuminaemia using the following in formula. However the correction is not always reliable and free phenytoin concentration should be measured if phenytoin toxicity is suspected despite corrected concentration that lies within the therapeutic range.

Fosphenytoin

  • water soluble disodium phosphate ester of phenytoin which can be given intramuscularly. 

Sodium valproate

  • now available in an intravenous form but there is to date no controlled data regarding its efficacy in the treatment of status epilepticus
  • case reports of valproate being used to treat SE successfully

Paraldehyde

  • may be of use in situations where intravenous access is limited or difficult (eg children).
  • give intramuscularly, followed by massage The dose is 5 ml every 30 min as necessary. Time to peak plasma level is 0.5-1 hr.
  • adverse effects include right heart failure, pulmonary oedema, pulmonary haemorrhage and hypotension. Damage to adjacent nerves and sterile muscle abscesses may occur following IM injection.

Neuromuscular blocking agents

  • indicated if uncontrolled fitting causes respiratory embarrassment or severe lactic acidosis. should only be used if continuous EEG monitoring is also used as the clinical expression of seizure activity is abolished

Intensive care monitoring

In status epilepticus refractory to treatment with phenytoin and phenobarbitone the following monitoring may be necessary:

  • Intra-arterial blood pressure
  • Capnography
  • Pulse oximetry
  • Central venous pressure
  • Pulmonary artery wedge pressur
  • EEG
  • Intracranial pressure

EEG monitoring

In prolonged SE or in patients paralysed with muscle relaxants, motor activity may not be present and in these cases continuous electroencephalography (EEG) is necessary. This can be performed using a full EEG or a cerebral function monitor.

Intracranial pressure monitoring

Continuous ICP monitoring is indicated in the presence of persisting, severe or progressive elevated intracranial pressure.

Outcome

The prognosis of patients with status epilepticus is related to the aetiology, the patient's age, the duration of SE, the occurence of systemic complications, especially anoxia, and the type of treatment. Estimated mortality ranges from 3% to 35%.

Status epilepticus in children

The majority of cases of SE occur in young children with 21% occurring in the first year of life and 64% in the first 5 years. More than 90% of cases are convulsive and the majority are generalised. The commonest causes of SE in children (< 16years old) in order of frequency:

  • Fever or infection
  • Medication change
  • Idiopathic
  • Metabolic
  • Congenital
  • Anoxia
  • CNS infection
  • Cerebrovascular disease
  • Drug related
  • Tumour

Overall mortality in recent paediatric series is 3-10% and neurological sequelae in children with idiopathic or febrile status epilepticus is rare. The favourable outcome may be due to advances in therapy and to the resistance of the immature brain to damage from seizures. The risk of subsequent seizures in a child who presents with idiopathic SE is no greater than a child who presents with a brief fit and the risk of another episode of SE is very low.

Further reading

Gomersall CD, Oh TE. Status epilepticus. In Oh TE (ed), Intensive Care Manual, 4th Ed., Butterworth Heinemann, Oxford, 1997, pp 381-5

 


© Charles Gomersall December 1999

 

©Charles Gomersall, April, 2014 unless otherwise stated. The author, editor and The Chinese University of Hong Kong take no responsibility for any adverse event resulting from the use of this webpage.
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