Treatment of Epilepsy in Treatment of Epilepsy in ERER

Submitted to Submitted to AskTheNeurologist.Com

in 2007in 2007

Author Anon.Author Anon.

The first seizureThe first seizure

• Is it really first event?Is it really first event?

• If established that it is, in fact first, If established that it is, in fact first, unprovoked event decision to treat unprovoked event decision to treat depends on depends on

- risk factors for recurrence- risk factors for recurrence- risks of drug treatment- risks of drug treatment- patient preference- patient preference

Seizure recurrenceSeizure recurrence

• Over 50% of patients who will have Over 50% of patients who will have recurrence following first seizure will do so recurrence following first seizure will do so within 6 monthswithin 6 months

• Recurrence rate varies from 36 – 77%Recurrence rate varies from 36 – 77%

• If careful history taken to ensure seizure is If careful history taken to ensure seizure is definitely “ first ever” then recurrence rate definitely “ first ever” then recurrence rate drops to 35%drops to 35%

• Recurrence rate following second seizure Recurrence rate following second seizure is 80-90%is 80-90%

Risk factors for seizure Risk factors for seizure recurrencerecurrence

• History of prior neurological injury or lesionHistory of prior neurological injury or lesion

• History of epilepsy in a siblingHistory of epilepsy in a sibling

• Transient neurological deficit ( Todd’s )Transient neurological deficit ( Todd’s )

• EEG with generalised epileptiform dischargesEEG with generalised epileptiform discharges

Treatment of status Treatment of status epilepticusepilepticus

• Acute emergency managementAcute emergency management

- Prevents injury- Prevents injury

• Rational drug administrationRational drug administration- Limits morbidity due to systemic - Limits morbidity due to systemic

changes or changes or seizure-induced seizure-induced neuronal damageneuronal damage

DefinitionsDefinitions

ILE:ILE:“ “ seizure that persists for a seizure that persists for a sufficient sufficient length of time or is length of time or is repeated frequently repeated frequently enough enough that recovery between attacksthat recovery between attacksdoes not occur”does not occur”

Most literature specifies time period of Most literature specifies time period of 20-30 minutes as estimate of time 20-30 minutes as estimate of time necessary to cause injury to CNSnecessary to cause injury to CNS

Operational definitionOperational definition

“ “ Continuous seizures lasting at least 5 Continuous seizures lasting at least 5 minutes or 2 or more discrete minutes or 2 or more discrete seizures between which there is seizures between which there is incomplete recovery of incomplete recovery of consciousness”consciousness”

Predictors of outcomePredictors of outcome

• AgeAge• CauseCause - Metabolic- Metabolic

- Infection- Infection- CVA- CVA- Trauma- Trauma

• Known epileptic patients have best prognosis

OutcomesOutcomes

• Overall mortality is 20%Overall mortality is 20%• Patients whose first ever seizure is status Patients whose first ever seizure is status

epilepticus have substantial risk of future epilepticus have substantial risk of future episodes and the developmennt of chronic episodes and the developmennt of chronic epilepsyepilepsy

• Predominant factor affecting outcome is Predominant factor affecting outcome is causecause

• Myoclonic status epilepticus after hypoxia Myoclonic status epilepticus after hypoxia carries especially grave prognosiscarries especially grave prognosis

• Duration of status epilepticus is correlated Duration of status epilepticus is correlated with neurological morbidity and lack of with neurological morbidity and lack of responsiveness to drug treatmentresponsiveness to drug treatment

Assessment and supportive Assessment and supportive measuresmeasures• ABCABC - protect airway- protect airway

- 100 % O2100 % O2- BP controlBP control

• Monitoring - ECG- BP- ABG’s- Biochemistry- Body temperature

GlucoseGlucose

• Hypoglycemia should be excludedHypoglycemia should be excluded

• Usually treat empirically with 50ml of Usually treat empirically with 50ml of 50% glucose50% glucose

• Should always precede glucose Should always precede glucose administration with 100mg thiamine IVadministration with 100mg thiamine IV

Blood pressureBlood pressure

• Hypertension usually occurs early in Hypertension usually occurs early in coursecourse

• Subsequently BP labile and often dropsSubsequently BP labile and often drops

• Fluids and vasopressors may be requiredFluids and vasopressors may be required

• Aim for high/normal rangeAim for high/normal range

Body temperatureBody temperature

• May often be result of seizures May often be result of seizures themselves rather than co-existing themselves rather than co-existing infectioninfection

• Should be treated with passive Should be treated with passive coolingcooling

Systemic treatmentSystemic treatment

• Avoid over-hydration ( cerebral Avoid over-hydration ( cerebral oedema )oedema )

• Blood tests ( including Ca, Mg)Blood tests ( including Ca, Mg)

• Monitor oxygenationMonitor oxygenation

• Monitor rectal temperatureMonitor rectal temperature

11stst line drug treatments line drug treatments

• Benzodiazepines Benzodiazepines

- Diazepam vs Lorazepam- Diazepam vs Lorazepam

• Phenytoin vs FosphenytoinPhenytoin vs Fosphenytoin

• PhenobarbitalPhenobarbital

BenzodiazepinesBenzodiazepines

DiazepamDiazepam LorazepamLorazepam

More lipid solubleMore lipid soluble Less lipid solubleLess lipid soluble

More rapid More rapid penetration into brainpenetration into brain

Less rapid penetration Less rapid penetration into brain into brain

Rapid redistribution Rapid redistribution into body fat into body fat

Longer duration of Longer duration of action action

Necessitates use of a Necessitates use of a second long-acting second long-acting

drugdrug

Can be used aloneCan be used alone

LorazepamLorazepam

“ “ Despite their equivalence as initial Despite their equivalence as initial therapies, lorazepam has a longer therapies, lorazepam has a longer duration of antiseizure effect ( 12-24 duration of antiseizure effect ( 12-24 hours ) than diazepam ( 15-30 hours ) than diazepam ( 15-30 minutes)…..lorazepam preferable to minutes)…..lorazepam preferable to diazepam for the treatment of status diazepam for the treatment of status epilepticus”epilepticus”

FosphenytoinFosphenytoin• Water-soluble prodrug form of phenytoinWater-soluble prodrug form of phenytoin

• Does not contain propylene glycol Does not contain propylene glycol

( which is main limiting factor for rate of ( which is main limiting factor for rate of treatment as contributes to treatment as contributes to cardiovascular cardiovascular side effects)side effects)

• Less irritantLess irritant

• Can be given at a maximum rate of 150 Can be given at a maximum rate of 150 phenytoin equivalents / minute phenytoin equivalents / minute

• Phenytoin itself may only be Phenytoin itself may only be administered at a maximum rate of administered at a maximum rate of 50mg/min50mg/min

Maximal brain Maximal brain concentrations of phenytoinconcentrations of phenytoin

• Attainable in 20-25 minutes when Attainable in 20-25 minutes when phenytoin infused at maximal ratephenytoin infused at maximal rate

• Attainable within 10 minutes when Attainable within 10 minutes when Fosphenytoin infused at maximal Fosphenytoin infused at maximal ratesrates

PhenobarbitalPhenobarbital

• “ “ Highly effective”Highly effective”

• Recommend 20mg/kg at rate of 50 – Recommend 20mg/kg at rate of 50 – 75 mg/min75 mg/min

• Risk of apnea….especially if patient Risk of apnea….especially if patient has received BZD’shas received BZD’s

IV Valproic acidIV Valproic acid

• Effective in some forms of status Effective in some forms of status epilepticusepilepticus

• At time of publication insufficient At time of publication insufficient experience availableexperience available

Refractory status epilepticusRefractory status epilepticus

• Failure to control seizures with Failure to control seizures with BZD’s, phenytoin and phenobarbitalBZD’s, phenytoin and phenobarbital

• Requires administration of iv Requires administration of iv anaesthetic agentanaesthetic agent - Barbiturates- Barbiturates

- Midazolam- Midazolam- Propofol- Propofol

• EEG performed at 12hrs and EEG performed at 12hrs and thereafter every 24 hoursthereafter every 24 hours

MidazolamMidazolam Propofol Propofol PentobarbitalPentobarbital

Tachyphylaxis Tachyphylaxis necessitates necessitates dose variationdose variation

Doses Doses adjusted on adjusted on basis of EEG basis of EEG responsesresponses

PotentPotent

Assessment Assessment clinical and clinical and on basis of on basis of EEGEEG

Associated with Associated with profound systemic side profound systemic side effectseffects

Myocardial depressionMyocardial depression

VasodilatationVasodilatation

Decreased venous Decreased venous returnreturn

Decreased cardiac Decreased cardiac perfusionperfusion

Recommend saline and Recommend saline and dopamine infusiondopamine infusion

Recommendations Recommendations regarding Barbituratesregarding Barbiturates

• Severe hypotension requiring pressor Severe hypotension requiring pressor therapy limits safety of barbituratestherapy limits safety of barbiturates

• Preferable to reserve anaesthesia Preferable to reserve anaesthesia with barbiturates for patients in with barbiturates for patients in whom midazolam or propofol failswhom midazolam or propofol fails

Submitted to Submitted to

AskTheNeurologist.ComAskTheNeurologist.Com

in 2007in 2007

Author Anon.Author Anon.