Mozhdehi panah.MD Neurologist

 Definition  Etiology  Treatment  Complication

 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.

 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

 Ongoing convulsive or nonconvulsive seizures following administration of an initial benzodiazepine and a nonbenzodiazepine AED, given in appropriate dose.  Incidence : 30%

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

 Incidence : 7-41 per 100,000 <1above 60  Bimodal age distribution : peak incidence rate in <1 and above 60 years.

 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

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

 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

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

 Acute symptomtic  Remote symptomatic  AED nonadherence

 Acute symptomtic  Remote symptomatic  AED nonadherence  Withdrawal syndrome

 Alcohol  Barbiturate  Benzodiazepines

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

 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

 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

 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

 Initial assessment and suport  Initial pharmacologic therapy  Alternative second line therapies  Out of hospital/prehospital 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).

1-Benzodiazepines 2-Non-Benzodiazepine AED

 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

 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.

 High lipid solubility  Rapidly cross BBB  Rapid onset of its effect : seconds  Initial termination of seizure : %  Durartion of anticonvulsants effect : <20 min  Recurence of seizure : 50% in 2 hr  Rate of injection : 5 mg/min

 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

 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

 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.

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

 Fosphenytoin or phenytoin  Valproate  Phenobarbital

 First line (Grade 2C)  Preferred formulation of phenytoin  Water-soluble  Loading dose: mg/kg  Lower risk of irritation at injection site  Rate of infusion : mg/min  However, the delay in hepatic conversion of fosphenytoin to active phenytoin makes the latency of clinical effect approximately the same as phenytoin

 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

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

 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

Preferred to phenytoin in primary CGSE Loading dose: 20mg/kg FDA approved only for slow infusion rate :20mg/ min Rate of seizure control ; 50-90%

 Loading dose:20mg/kg  Infusion rate: 30-50mg/min  Intuabation is often required to provide secure airway  Side efects :sedation, respiration arrest  Half life : hr

 Loading dose : mg  Seizure control rate : 68%

 Loading dose : mg, IV  Side effect: third degree AV block, angioedema

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

 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.

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

 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)

 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.

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

 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

 If seizure continue within 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.

 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.

 Side effects: hypotension, respirstory depression, propofol infusion syndrome

 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.

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

 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.

 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

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