status epilepticus 1
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The Practical Management of
Status Epilepticus
David Y. Gosal,
Neuro SpR,Manchester Neurosciences Centre
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Before I commence
The following is a synthesis of best available
published information, national and local practice
guidelines amongst Neurologists/Intensivists, andfinally personal practice.
All criticism welcome.
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How To Define Status?
1981, ILAE (International League againstEpilepsy)
a seizure that persists for a sufficient length of
timeor is repeated frequently enoughthat
recovery between attacks does not occur
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How To Define Status?
More recent publications
A condition in which epileptic activity persistsfor 30 min or more
Based on primate models of the estimated duration
necessary to cause neuronal injury.
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But
This is not practical operational definition.
Longer periods with uncontrolled seizure activity,
more likely to develop a RSE syndrome. More practical guidelines needed to draw that
arbitrary line in sand, beyond which substantial
risk of developing clinical SE exists.
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Operational Definition
Continuous seizures lasting at least 5 minutesor two or more discrete seizures between which
there is an incomplete recovery of
consciousness.
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Premonitory Stage (pre-status)
Build up of seizure activity Increasing frequency and / or severity of events.
Commonly 2mg-4mg lorazepam given.
A proportion of cases of early status can beterminated.
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Confident diagnosis GTC status not alwayspossible
Pseudoseizures
Minor motor features
Subtle SE (Electromechanical dissociation)
small amplitude twitching movements.
occasionally quiet.
CPSE
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Pseudoseizures
Genuine and factitious seizures commonly occur
in same individual.
80% patients with NEAD are on anticonvulsants.
1/3 patients present with status.
2/3 positive motor attacks.
If treated as per status are highly likely to end up
on anaesthetic agents.
Can appear focal onset, bite tongue, becomeincontinent.
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Pseudoseizures: clinical features
Difficult, share many common characteristics.
Tremor like asynchronous waxing and waning
asynchronous movement.
Thrashing limbs.
Pelvic thrusting.
Back arching.
Unresponsive , resists eye opening, versive eye
movement to confrontation, strong stimuli. Fever, tachycardia, leucocytosis, acidosis non-
specific and late.
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Could this be pseudoseizure activity?
On balance, where there exists doubt, so long aspossibility of functional attacks have been
considered but felt less likely (and documented as
such), prompt treatment is best.
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Basic investigation and general medical
management
ABC.
Usual bloods.
Serum drug levels: CBZ, Phenytoin, Valproate.
Store 20mls of blood, and urine for toxicology ifno obvious aetiological cause.
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Initial treatment (Early Status 10-30min)
One area where some good class I evidence exists.
Three RCTs.
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Pre-hospital treatment by
paramedics.
2mg lorazepam, or 5mg diazepam
Placebo
Repeated dose after 4min if still
actively seizing
Lorazepam terminated 59.1%
Diazepam 42.6%
Placebo 21%
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384 patients
0.1mg/kg lorazepam
15mg/kg phenobarbital
0.15mg/kg diazepam / 18mg/kg
phenytoin18mg/kg phenytoin
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Duration of status and response to initial
therapies
0
10
20
30
40
50
60
70
80
0.5
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Initial anti-epileptic drug treatment (0-60min)
Lorazepam is benzodiazepine of choice. Smaller volume of distribution
Longer therapeutic half-life. Anti-seizure effect 12hrs.
Relatively fast onset action
Previous rectal diazepam does not preclude its use
2mg aliquots upto a max dose of 8mg in total
Diazepam
More lipid soluble Shorter half-life. Anti-seizure effect 15-30min.
Repeated dosing
Faster onset
?Respiratory compromise
-- Consider lignocaine / valproate
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Initial anti-epileptic drug treatment (0-60min)
I personally follow on with second-line agent inany individual with early status, irregardless of
seizure termination with benzodiazepines.
Phenytoin / Phenobarbitone most logical choices.
No evidence currently to choose between agents in
terms of efficacy, although in general
phenobarbitone is quicker in onset.
Phenytoin more widely accepted and used thanphenobarbitone possibly because historically, oral
phenytoin was preferred to phenobarbitone as
maintenance therapy.
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Initial anti-epileptic drug treatment: Sodium
Valproate
If worried re arrhythmias, hypotension, sedation,
can use valproate.
Has been reported to be effective in GTCSE.
Efficacy rates 63% in one study.
Loading dose 25-45mg/kg. Rate 200-500mg/min.
Continuous infusion rate upto 6mg/min.
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384 patients
0.1mg/kg lorazepam
15mg/kg phenobarbital
0.15mg/kg diazepam / 18mg/kg
phenytoin
18mg/kg phenytoin
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Initial anti-epileptic drug treatment: Sodium
Valproate
If worried re arrhythmias, hypotension, sedation,
can use valproate.
Has been reported to be effective in GTCSE.
Efficacy rates 63% in one study.
Loading dose 25-45mg/kg. Rate 200-500mg/min.
Continuous infusion rate upto 6mg/min.
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Phenytoin
Common problem is that about 70% patients
admitted to ITU are given an inadequate loadingdose.
I normally give a dose of 15mg/kg at a rate of50mg/min in young, 20-30mg/min in elderly.
Risk bradycardia secondary to drug, andhypotension secondary to glycol additives.
A further 5mg/kg given almost immediatelyafterwards if no response to initial dose.
Can give upto 30mg/kg., before considerationanaesthesia.
Cardiac monitoring necessary..unnecessary delays.
15-20minutes at least to take effect.
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Phenytoin
If already on phenytoin, give 10mg/kg, andrequest urgent levels.
Must be aggressive with dosing, and even if
responds to initial dose, should aim for high
normal levels. Range 40-80 micromoles/litre.
Request serum phenytoin level 1/2hr to 1 hr after
loading dose, and keep giving iv aliquots, with
levels after each dose until desired range. In general for micromoles/l, for every 4
micromoles/l off desired target, give 1mg/kg.
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Phenytoin
Non-linear elimination kinetics because capable ofsaturating metabolising enzyme.
In general 20mg/kg usually saturates.
Predominately protein bound. In
hypoalbuminaemic states can be clinically toxic
with apparently normal total serum levels.
Adjusted Phenytoin = Measured total conc.
(0.2 x albumin) + 0.1
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Refractory Status (60min onwards)
No accepted definition.
30-50% patients fail initial benzo / phenytoin Rx. Expert consensus and all current guidelines
advise that by this stage patient should be
transferred to ITU for general anaesthesia.
Urgently suppress seizures (Time is brain)
Manage systemic adverse effects
Find possible aetiology
SE becomes more refractory with time
RSE Mortality 20%
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Compensated Decompensation
Mortality
30%
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Refractory Status (60min onwards)
No accepted definition.
30-50% patients fail initial benzo / phenytoin Rx. Expert consensus and all current guidelines
advise that by this stage patient should be
transferred to ITU for general anaesthesia.
Suppress seizures
Manage systemic adverse effects
Find possible aetiology
SE becomes more refractory with time
RSE Mortality 20%
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60% European Neurologists, epileptologists,intensivists use third anti-epileptic agent.
(43% US)
Some evidence to show that 50% refractorycases successfully treated.
?but at what cost.
But, in practice
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Anaesthetic agents
Choice of agent
What depth of anaesthesia
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Treatment of Refractory Status Epilepticus with Pentobarbital,
Propofol, or Midazolam: A Systematic review
Jan Claassen et al.,Epilepsia, 43(2);146-153, 2002
193 patients, 28 trials.
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Propofol in the treatment of refractory status epilepticusParviainen I et al., Intensive Care Med (2006) 32:1075
10 patients with refractory SE.
Terminated seizure activity in all initially.
Quality of burst suppression unsatisfactory.
Incremental doses of propofol needed.
Most needed noradrenaline.
Need continuous EEG monitoring.
Stepwise weaning, risk of emergent seizure activity.Reduction 5% infusion rate/hr over 24hours.
Weaning time from ventilator 50% quicker than
thiopentone.
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Similar to propofol, effectively terminated seizures.
Easier to attain and keep burst suppression.
Doses needed higher than generally recommended.
Recovery from anaesthesia prolonged
---most had co-morbid conditions.
Most ended up with RTI.
Theoretical advantage of being neuroprotective by dose-
dependently reducing cerebral metabolic rate and 02
comsumption.
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127 patients with status epilepticus.
47 patients with RSE of various aetiologies.
2/3 burst suppression.
Incidence of potentially serious / fatal aetiologies
same in both groups.
Outcome was independent of the specific coma-
inducing agents used and the extent of EEG burstsuppression, suggesting that the underlying cause
represents the main determinant.
Mortality 23% RSE, 8% SE
Baseline 31% RSE, 50% SE
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Conclusions in RSE Evidence for treatment poor and based on retrospective
studies. More important to initiate anaesthesia with undue delay,
rather than argue over pros and cons of any particulartreatment.
Continuous monitoring until electrographic seizures
abolished, and at least daily monitoring is required in allcases of RSE is a minimum.
Is burst suppression really necessary? Prospective trial
How long anaesthesia should be administered is unclear,
and probably depends on underlying aetiology. Barbituates have someadvantages over other agents, but at
expense of respiratory complications and prolonged ITUstay.
Prognosis ultimately depends on aetiology.
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What if nothing works?
Repeated failed attempts at withdrawal anaesthesia. Even with known epilepsy, should have MRI and CSF as a
minimum.
Serum amticonvulsant levels.
Alternative anti-epileptics iv valproate worth a go
Leviteracetam
Topiramate
Anoxic / metabolic brain damage..Post-anoxic myoclonus? Longer and deeper anaesthesia.
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Prognosis
Mortality and morbidity severely influenced byunderlying aetiology. Cannot give reliable figures
for condition itself.
Mortality 20%
Morbidity; high risk recurrent seizures, cognitive
deficits, and future episodes
Many aetiological causes, useful to divide into
acute and chronic processes.
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Acute processes
Stroke
Metabolic disturbances
CNS infection
TraumaDrug Toxicity
Hypoxia
Difficult to manage
Higher mortality
Chronic processes
Pre-existing epilepsy
Ethanol abuse
Old CVA
Relatively long-standingtumours
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Other forms of status
Non-convulsive status epilepticus (NCSE). Myoclonic status.
Focal motor status
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Non-convulsive status epilepticus
Absense Status Rare
Primary generalised epilepsy
Learning disabled
Profound stupor
Occur after tonic-clonic seizure / GTCSstatus
Eyelid / facial myoclonia
Little evidence that it is harmful in itself Iv valproate, or iv benzodiazepines
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Non-convulsive status epilepticus
Complex partial status epilepticus Much more prevalent
Elderly
Vastly under-diagnosed
Confusedprofound stupor Focal motor phenomenon
Fluctuating symptoms
Level of consciousness can be occasionally
significantly impairediv phenytoin, andoccasionally will need anaesthesia
Quite refractory to treatment.
Unsure how aggressively to treat..individualistic.
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Non-convulsive status epilepticus
Husain et al, 2003, JNNP,74,189-91 Altered consciouness / mental state
Remote risk factor seizure eg previous stroke
Ocular movement abnormality
100% predictive value
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Myoclonic status
Usually seen with the primary epilepsysyndromes.
Can be a sign of impending tonic-clonic status.
IV benzodiazepine
IV valproate
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Focal motor status
Epilepsia partialis continua (EPC).
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Conclusions
Serious medical condition with high mortalityrate.
Relative dearth of evidence on how to treatcondition.
Despite this, good practical guidelines exist. Pick your drugs, know them well, and use enough.
Ask for specialist help early.
Prognosis depends on aetiology, delay in initiationof appropriate treatment, and usual co-morbidfactors.
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