The 30 minute definition It is a prolonged seizure that last more than 30 minutes, or Recurrent seizures during which the patient does not regain consciousness within a 30 min period. The theory is that neuronal damage may begin after 30 minutes

According to the presence or absence of motor activity:  Convulsive status epilepticus  Nonconvulsive status epilepticus According to the cause  Symptomatic, when there is a definite cause  Remote symptomatic with acute precipitant.  Idiopathic with unknown cause.

Convulsions that are associated with rhythmic jerking of extremities.  Generalized tonic clonic  Focal seizures  Myoclonic seizures  Absence seizures

Defined as seizure activity seen on electroencephalogram (EEG) without clinical findings associated with GCSE. This patient presents with:  Tonic eye deviation that often occurs in the setting of acute brain injury).  Prolonged post-ictal state  Complex partial seizures without recovery of consciousness

Patients who continue to experience either clinical or electrographic seizures after receiving adequate doses of an initial benzodiazepine followed by a second acceptable antiepileptic drug (AED) will be considered refractory.

 Super-refractory SE: SE that continues 24 hours or more after the onset of anesthesia, including those cases in which the SE recurs on reduction or withdrawal of anesthesia.

 Febrile convulsion is the most common cause in children 52%  Epilepsy:  First presentation  Difficult seizure control  Subtheraputic anticonvulant levels  Cerebrovascular disease  Metabolic abnormalities  Idiopathic  Hypoxia  CNS infections  Trauma  Poisoning

Basic lab investigations  CBC  Blood gases  Blood: Magnesium, electrolytes, calcium, glucose, and creatinine

Advanced lab investigations  Metabolic investigations: ammonia  Toxicology screening  Anti-convulsants level  ESR, RF, antineutrophil cytoplasmic antibodies ANCA, serum complement.  Lumbar puncture

Brain imaging  CT  MRI  MR angiography to diagnose CNS vascultitis  EEG  PET CT to diagnose epileptogenic zone

Cortical hyperperfusion frontal right during NCSE. Bottom left: EEG shows right frontal spike-and-wave activity.

Mortality Convulsive status epilepticus Mortality ranges from 3 to 11 % Mortality in the first year is 17.8% and 24% in the first six months. NCSE : mortality is higher in those diagnosed after 24 hours reaching 75% RSE : the mortality rate is high in symptomatic SE 20%

Convulsive SE  Severe neurological or cognitive sequelae: 11–16 %. RSE  A new deficit occurrs in 36  Motor and visual deficits may be seen at 1 year after SE.  Morbidity and mortality is highest in those with symptomatic SE or a progressive encephalopathy

 The exact mechanism is still unknown  Theoretically it is either failure of phyisologic neuronal inhibition or an excess of excitation.  Clinically demonstrated by poor response of prolonged seizures to the GABA agonists benzodiazepines and barbiturates, a phenomenon called time-dependant pharmaco-resistance

 Cardiovascular compromise and hypotension  Hyperpyrexia  Rhabdomyolysis that may lead to renal failure  Raised intracranial pressure  Risk of hospital acquired infection  Cardiac arrhythmias are also common with higher mortality in these patients

 Lactic acidosis  Stress cardiomyopathy  Neurogenic pulmonary edema  Fractures

Initially  Assessment  Management of airway, breathing, and circulation:  Secure the airways  Administer O2  Obtain IV access

 Maintain air way  Intubate if necessary  Supplement oxygen  Continuous cardiovascular monitoring  Find vascular access

 All protocols take a staged approach to treatment.  Typically, in Stage 1 (early status Epilepticus),therapy is with benzodiazepines.  If seizures continue despite this therapy, the patient is said to be in Stage 2 (established status Epilepticus) and therapy is with intravenous anti-epileptic drugs such as phenytoin, Phenobarbital or valproate.

 If seizures continue despite this treatment for up to 1 h, the patient is said to be in Stage 3 ( refractory status Epilepticus) and GA is indicated.  If seizure continue despite GA for >24h the patient is said to be in Super Refractory SE.

support ABC and give oxygen establish IV access rapid glucose check and consider critical lab Na, Ca Mg proceed with AED 5 minute s Diazepam orMidazolam IV 0.3mg/kg intranasal: 0.2 mg/kg pr 0.5MG/KGbuccal : 0.5mg/kg IV max < 5 years 5mg/doseMax 5mg/nostril > 5 years 10 mg/dosebuccal max 10 mg 5 minute s phenytoin IV 20mg/kg in NS only over 5-10 minutes max 1000 mg 5 minutes phenobarbital IV 20 mg.kg in NS or D5W over 20 minutes or IV push over minutes max 1000 mg 10minutes RSE intubate if needed arrange for admission to ICU

Midazolam continuous infusion IV 0.15 mg/kg bolus then 2mic/kg/min infusion Increase as need 2 mic/kg/min q5 min Bolus 0.15 mg/kg with each increase Max infusion 25mic/kg/min Midazolam continuous infusion IV 0.15 mg/kg bolus then 2mic/kg/min infusion Increase as need 2 mic/kg/min q5 min Bolus 0.15 mg/kg with each increase Max infusion 25mic/kg/min If no seizures within for 48 hrs Taper midazolam Decrease by 1 mic/kg/min q 15 min If seizures persist Thiopental continuous infusion via CVL 2- 4 mg/kg bolus then 2-4 mg/kg/hr Increase as needed by 1 mg/kg/hr every 30 minutes Bolus 2 mg/kg with each increase Max infusion 6 mg/kg/hr Discontinue midazolam and phenobarbitone If seizure recur, reinstate midazolam for another 48 hr If no seizures for 48 hrs Taper thiopenatal Decrease rate by 25% q3 hrs Reinstitute phenobarbitone while tapering if seizures persist If seizures recur Individualized therapy

Treat the underlying condition; meningitis, or increased intracranial pressure Start AED to abort the electrical activity Benzodiazepine is the first line therapy Routes of administration IV, IM, buccal, nasal, and rectal Lorazepam preferred IV Midazolam preferred IM, can be given buccal and nasal Diazepam preferred rectal

 Urgent control therapy is required after short acting benzodiazepine  For patients who respond to emergent initial therapy and have complete resolution of SE, the goal is rapid attainment of therapeutic levels of an AED and continued dosing for maintenance therapy.  For patients who fail emergent initial therapy, the goal of urgent control therapy is to stop SE.

The preferred top tier agents that are generally used for urgent control of SE are  IV fosphenytoin/phenytoin  valproate sodium  phenobarbital  Levetiracetam  continuous infusion midazolam

Treatment of RSE is extremely difficult Continuous infusion of  benzodiazepines  Propofol  Phenobarbitone  General anasthetics  Surgical treatment

Midazolam infusion 2-24Mic/kg/min Advantages  Rapid onset of action  Short half life  Lower incidence of cardiovascular depression Disadvantage  Tachyphylaxis High dose diazepam is also an alternative

Advantage  Rapid onset of action  Short half life Disadvantage  Rapid tapering can precipitate seizures  Respiratory depression  Prolonged usage produce “ propofol infusion syndrome” (metabolic acidosis, rhabdomyolysis, bradyrhythmias, lipemia, death”

 Intravenous valproic acid  Caution with hepatic patients Disadvatage  Hyperammonemia in predisposed child  Thrombocytopenia  Fatal hepatotoxicity

 Ketamine is NMDA antagonist that has anticonvulsants and neuroprotective properties  Lidocaine is another option although not commonly uses

 Pyridoxine (vitamin B6) is a cofactor for both glutamic acid decarboxylase and GABA transaminase  Pyridoxine dependency is a rare disorder it presents in neonatal or infantile period but may present as lates as age 2.5 years.