Status Epilepticus 1

5/24/2018 Status Epilepticus 1

1/51

The Practical Management of

Status Epilepticus

David Y. Gosal,

Neuro SpR,Manchester Neurosciences Centre


2/51

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.


3/51

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


4/51

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.


5/51

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.


6/51

Operational Definition

Continuous seizures lasting at least 5 minutesor two or more discrete seizures between which

there is an incomplete recovery of

consciousness.


7/51Compensated Decompensation


8/51


9/51

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.


10/51

Confident diagnosis GTC status not alwayspossible

Pseudoseizures

Minor motor features

Subtle SE (Electromechanical dissociation)

small amplitude twitching movements.

occasionally quiet.

CPSE


11/51

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.


12/51

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.


13/51

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.


14/51

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.


15/51

Initial treatment (Early Status 10-30min)

One area where some good class I evidence exists.

Three RCTs.


16/51

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%


17/51

384 patients

0.1mg/kg lorazepam

15mg/kg phenobarbital

0.15mg/kg diazepam / 18mg/kg

phenytoin18mg/kg phenytoin


18/51

Duration of status and response to initial

therapies

0

10

20

30

40

50

60

70

80

0.5


19/51

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


20/51

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.


21/51

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.


22/51

384 patients

0.1mg/kg lorazepam

15mg/kg phenobarbital

0.15mg/kg diazepam / 18mg/kg

phenytoin

18mg/kg phenytoin


23/51

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.


24/51

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.


25/51

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.


26/51

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


27/51

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%


28/51

Compensated Decompensation

Mortality

30%


29/51

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%


30/51

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


31/51

Anaesthetic agents

Choice of agent

What depth of anaesthesia


32/51

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.


33/51

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.


34/51

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.


35/51

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


36/51

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.


37/51

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.


38/51

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.


39/51

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


40/51

Other forms of status

Non-convulsive status epilepticus (NCSE). Myoclonic status.

Focal motor status


41/51

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


42/51


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.


43/51


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


44/51

Myoclonic status

Usually seen with the primary epilepsysyndromes.

Can be a sign of impending tonic-clonic status.

IV benzodiazepine

IV valproate


45/51

Focal motor status

Epilepsia partialis continua (EPC).


46/51

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.


47/51


48/51


49/51


50/51


51/51

Documents

Status Epilepticus 1