الرحیم الرحمن الله بسم

Status EpilepticusMozhdehi panah.MD

Neurologist

Definition Etiology Treatment Complication

Status Epilepticus

ILAE define 20 years ago as a single seizure of >30 minute duration or a series of epileptic seizures during which function is not regained between ictal event in a 30 minute period.

Definition

Status should be interrupted urgently due to decrease mortality ,cardiorespiratory morbidity or refractory status.

>5 minutes of continious seizures or 2 or more seizures between which there is

incomplete recovery of consciousness

Operational definition

Ongoing convulsive or nonconvulsive seizures following administration of an initial benzodiazepine and a nonbenzodiazepine AED , given in appropriate dose.

Incidence : 30%

Refractoty status epilepticus

Generalized Convulsive Status Epilepticus (GCSE)

Focal motor status epilepticus Myoclonic status epilepticus Tonic status epilepticus Non Convulsive Status Epilepticus (NCSE)

Classification

Incidence : 7-41 per 100,000

Bimodal age distribution : peak incidence rate in <1 and above 60 years .

Epidemiology

Acute symptomtic Remote symptomaticAED nonadherenceWithdrawal syndromeMetabolic abnormality or sepsisUse of drugs that lower seizure tresholdAutoimmune or paraneoplastic encephalitisNew onset refractory status

Etiology

Stroke,head traume, SAH, cerebral hypoxia Infection (encephalitis ,meningitis, abscess) Brain tumor

Acute symptomtic Remote symptomaticAED nonadherenceWithdrawal syndromeMetabolic abnormality or sepsisUse of drugs that lower seizure tresholdAutoimmune or paraneoplastic encephalitisNew onset refractory status

Etiology

Prior head injury or neurosurgery, perinatal cerebral ischemia, AVM,benign brain tumor

Acute symptomtic Remote symptomatic AED nonadherence

Etiology

Acute symptomtic Remote symptomatic AED nonadherence Withdrawal syndrome

Etiology

Alcohol Barbiturate Benzodiazepines

Acute symptomtic Remote symptomatic AED nonadherence Withdrawal syndrome Metabolic abnormality or sepsis

Etiology

Hypoglycemia Hepatic encephalopathy Uremia Hyponatremia Hyperglycemia Hypocalcemia hypomagnesemia

Acute symptomtic Remote symptomatic AED nonadherence Withdrawal syndrome Metabolic abnormality or sepsis Use of drugs that lower seizure treshold

Etiology

Theophylline Imipenem High dose of penicillin G Quinolone Metronidazole INH Tricyclic antidepressant Bupropion Lithium Clozapine Flumazenil Cyclosporine Lidocaine

Acute symptomtic Remote symptomatic AED nonadherence Withdrawal syndrome Metabolic abnormality or sepsis Use of drugs that lower seizure treshold Autoimmune or paraneoplastic encephalitis

Etiology

Acute symptomtic Remote symptomatic AED nonadherence Withdrawal syndrome Metabolic abnormality or sepsis Use of drugs that lower seizure treshold Autoimmune or paraneoplastic encephalitis New onset refractory status

Etiology

Treatment

Initial assessment and suport Initial pharmacologic therapy Alternative second line therapies Out of hospital/prehospital treatment

Treatment

Assessment of cardiorespiratory function Oral airway Intravenous line Blood is drawn for glucose, BUN,

electrolytes, and a metabolic and drug screen.

Normal saline infusion Glucose (with thiamine if malnutrition and

alcoholism are potential factors).

Initial assessment and suport

1-Benzodiazepines2-Non-Benzodiazepine AED

Initial pharmacologic therapy

Benzodiazepines

Lorazepam 0.1 mg/kg , upto 4mg per dose Diazepam 0.15 mg/kg ,up to 10 mg per

dose Midazolam 5-10 mg IM Clobazam

Benzodiazepines

First-line (Grade 1A) Time of from its injection to its maximum

effect : 2 min Effective duration of action against seizure :

4-6 hours Rate of injection : 2 mg/min This should be repeated after 1 min if

seizure continue.

Lorazepam

High lipid solubility Rapidly cross BBB Rapid onset of its effect : 10-20 seconds Initial termination of seizure : 50-80 % Durartion of anticonvulsants effect : <20

min Recurence of seizure : 50% in 2 hr Rate of injection : 5 mg/min

Diazepam

Rectal gel of diazepam is also available Provide rapidly delivery , when IV access is

dificult , or for at home use for patients who have frequent repetitive or prolonged seizures

Diazepam

Rapid onset in termination of seizure activity : less than 1 minute

Short half life in CNS Administration route: IM , buccal , intranasal Very effective when IV access is not

available : pre-hospital treatment

Midazolam

Onset of effect between diazepam and lorazepam

Duration of effect is more prolonged than diazepam

IV injection Can be used in refractory status as adjuant

therapy when given entrally by NG tube.

Clobazam

Lorazepam IV : 4mg Midazolam IM : 5-10 mg

Prehospital tretment

Non-Benzodiazepine AED

Fosphenytoin or phenytoin Valproate Phenobarbital

Non-Benzodiazepine AED

First line (Grade 2C) Preferred formulation of phenytoin Water-soluble Loading dose: 20-30 mg/kg Lower risk of irritation at injection site Rate of infusion :100-150 mg/min However, the delay in hepatic conversion of

fosphenytoin to active phenytoin makes the latency of clinical effect approximately the same as phenytoin

Fosphenytoin

Can be given intramuscularly in cases where venous access is difficult ,however less predictable effect and longer time to onset of seizure activity

Less cardiovascular effect compare to phenytoin

Fosphenytoin

loading dose : 20 mg/kg Intravenous Rate of injection: less than 50 mg/min If seizures continue, an additional 5 mg/kg is

indicated More rapid administration risks hypotension

and heart block Must be given through a freely running line

with normal saline (it precipitates in other fluids)

Should not be injected intramuscularly.

Phenytoin

Phenytoin (but not phosphenytoin) and any of the benzodiazepines are incompatible and will precipitate if infused through the same intravenous line

Phenytoin

In an epileptic patient known to be taking anticonvulsants chronically but in whom the serum level of drug is unknown, it is probably best to administer the

full-recommended dose of phenytoin

Phenytoin

Preferred to phenytoin in primary CGSELoading dose: 20mg/kgFDA approved only for slow infusion

rate :20mg/ minRate of seizure control ; 50-90%

Valproate

Loading dose:20mg/kg Infusion rate: 30-50mg/min Intuabation is often required to provide

secure airway Side efects :sedation , respiration arrest Half life : 87-100 hr

Phenobarbital

Loading dose : 2000-4000 mg Seizure control rate : 68%

Levetiracetam

Loading dose : 200-400 mg , IV Side effect: third degree AV block, angioedema

Lacosamide

Ongoing convulsive or nonconvulsive seizures following administration of an initial benzodiazepine and a nonbenzodiazepine AED , given in appropriate dose

Refractoty status epilepticus

The optimal treatment of RSE is more contoversial.

It is critical to provide adequate ventilatory and hemodynamic support

Patients should be intubated and monitored by continious electroencephalogram.

Refractoty status epilepticus

Primary drugs used for RSE: -Midazolam -Propofol -Pentobarbital

Refractoty status epilepticus

Main points in selection of drugs: -Urgency of seizure control -Pharmakokinetic of various drugs -Drugs already used and failed -Potential complication of treatment (hypotension & risk of prolonged MV)

Refractoty status epilepticus

Pentobarbital is more popular ,because more seizure control rate , but has more sedation and more ventilatory need

Pentobarbital and propofol have greater risk of hemodynamic instability.

Refractoty status epilepticus

Midazolam & propofol have advantages for patients at risk for ventilatory dependence with prolonged therapy(severe pulmonary disease ,severe debilitation, or malignancy)

Refractoty status epilepticus

Water soluble, rapidly acting banzodiazepine

loading dose : 0.2 mg/kg Infusion rate : 2mg/min Additional dose should be given every 5

min,until seizure stop (max dose : 2 mg/kg) Followed by an continious infusion of 0.1 to

0.4 mg/kg/h(can be titrated upwardly upto 5mg/kg/hour) with control of blood pressure

Midazolam

If seizure continue within 45-60 minute, propofol or pentobarbital should be started

Side effects: hypotension(less common than pentobarbital) ,tachyphylaxis ,withdrawal seizure ,

Relapse of seizure is more common when higher doses is used.

Midazolam

Highly lipophilic phenol , GABA-A agonist

loading dose : 1-2 mg/kg( in 5 min) and then repeated until seizure stop

Continious infusion as an intravenous drip of 2 to 8 mg/kg/h may be required but should not be maintained more than 48 hr.

Propofol

Side effects: hypotension, respirstory depression , propofol infusion syndrome

Propofol

Propofol infusion syndrome : rhabdomyolysis, severe matabolic

acidosis ,and cardiac and renal failure

More common in prolonged use (48 hr) and in infusion rates of greater than 5mg/kg/hr.

ABG, CPK, lactic acid, TG, amylase should be checked.

Propofol

If seizure controlled with propofol , the effective infusion rate should be maintained for 24 hr , and then tapered 5% per hr.

Propofol

Loading dose:5mg/kg over 10 min. Max infusion rate :50mg/min If seizure persist: additional 5mg/ kg dose Continious infusion rate: 1 mg/ kg/hr Side effects: hypotension, prolonged

sedation If seizure controlled , infusion must be

continued for 24 hr before discontinuation of drug.

Pentobarbital

Petit mal status should be managed by intravenous lorazepam, valproic acid, or both, followed by ethosuximide.

Nonconvulsive status is treated along the

lines of grand mal status, usually stopping short of using anesthetic agents.

Myoclonic status is treated with benzodiazepines and valproate .

Physical examination Imaging LP EEG

Postictal assessment

Rising temperature Acidosis Hypotension Renal failure from myoglobinuria Epileptic encephalopathy Aspiration pneumonia Neurogenic pulmonary edema Respiratory failure

Complication of status epilepticus