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
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.
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
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
- Hypoxic encephalopathy (eg post cardiac arrest)
- Drug abuse and overdose, eg tricyclic antidepressants, theophylline,
cocaine or other stimulants
- Electrolyte disturbances, including:
- 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
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
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
- More common in females
- History of psychosocial disturbance
- Consciousness may be retained in the presence of
- Resistance to examination
- 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
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
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
duration usually several minutes to hours.
prompt diagnosis is important as early treatment appears to be important in
preventing neurological morbidity.
Glucose, urea & creatinine, sodium, potassium, calcium
Anti-epileptic drug levels
Complete blood count
Oximetry or arterial blood gases
Further investigations after stabilization:
Liver function tests
- 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
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
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
- 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
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.
patients do not usually require admission to ICU
management will depend to some extent on the availability of resuscitation
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.
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
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.
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
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:
- 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.
water soluble disodium phosphate ester of phenytoin which can be given
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
may be of use in situations where intravenous access is limited or difficult
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
- Pulse oximetry
- Central venous pressure
- Pulmonary artery wedge pressur
- Intracranial pressure
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
Intracranial pressure monitoring
Continuous ICP monitoring is indicated in the presence of persisting, severe
or progressive elevated intracranial pressure.
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%
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
- CNS infection
- Cerebrovascular disease
- Drug related
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.
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