Status Epilepticus in Children Toni Petrillo Pediatric Critical Care Children’s Healthcare of Atlanta

Status epilepticus2 Status epilepticus (SE) presents in a multitude of forms, dependent on etiology and patient age (myoclonic, tonic, subtle, tonic-clonic, absence, complex partial etc.) Generalized, tonic-clonic SE is the most common form of SE

Status epilepticus3 Definition Conventional definition: Single seizure > 30 minutes Series of seizures > 30 minutes without full recovery

Status epilepticus4 Definition “If appropriate therapy is delayed, SE can cause permanent neurologic sequelae or death …” thus “ … any child who presents actively convulsing should be assumed to have SE.” Haafiz A. Pediatr Emerg Care 1999;15(2):119-29

Status epilepticus5 The longer SE persists, the lower is the likelihood of spontaneous cessation the harder is it to control the higher is the risk of morbidity and mortality Treatment for most seizures needs to be instituted after > 5 minutes of seizure activity Bleck TP. Epilepsia 1999;40(1):S64-6

Status epilepticus6 Causes Fever Medication change Unknown Metabolic Congenital Anoxic Other (trauma, vascular, infection, tumor, drugs) 36% 20% 9% 8% 7% 5% 15% DeLorenzo RJ. Epilepsia 1992;33 Suppl 4:S15-25

Status epilepticus7 Drugs which can cause seizures Antibiotics Penicillins Isoniazid Metronidazole Anesthetics, narcotics Halothane, enflurane Cocaine, fentanyl Ketamine Psychopharmaceuticals Antihistamines Antidepressants Antipsychotics Phencyclidine Tricyclic antidepressants

Status epilepticus8 Mortality Adults Children 15 to 22% 3 to 15% Reviewed in: Fountain NB. Epilepsia 2000;41 Suppl 2:S23-30

Status epilepticus9 Prolonged seizures Duration of seizure Lifethreateningsystemicchanges Death Temporarysystemicchanges

Status epilepticus10 Respiratory Hypoxia and hypercarbia -  ventilation (chest rigidity from muscle spasm) - Hypermetabolism (  O 2 consumption,  CO 2 production) - Poor handling of secretions - Neurogenic pulmonary edema?

Status epilepticus11 Hypoxia Hypoxia/anoxia markedly increase (triple?) the risk of mortality in SE Seizures (without hypoxia) are much less dangerous than seizures and hypoxia Towne AR. Epilepsia 1994;35(1):27-34

Status epilepticus12 Neurogenic pulmonary edema Rare complication Likely occurs as consequence of marked increase of pulmonary vascular pressure Johnston SC. Postictal pulmonary edema requires pulmonary vascular pressure increases. Epilepsia 1996;37(5):428-32

Status epilepticus13 Acidosis Respiratory Lactic Impaired tissue oxygenation Increased energy expenditure

Status epilepticus14 Hemodynamics Sympathetic overdrive Massive catecholamine / autonomic discharge Hypertension Tachycardia High CVP Exhaustion Hypotension Hypoperfusion Exhaustion Hypotension Hypoperfusion 0 min 60 min

Status epilepticus15 Cerebral blood flow - Cerebral O 2 requirement Blood pressure Blood flow O 2 requirement Seizure duration Hyperdynamic phase CBF meets CMRO 2 Exhaustion phase CBF drops as hypotension sets in Autoregulation exhausted Neuronal damage ensues Hyperdynamic phase CBF meets CMRO 2 Exhaustion phase CBF drops as hypotension sets in Autoregulation exhausted Neuronal damage ensues

Status epilepticus16 Glucose Seizure duration 30 min SE SE + hypoxia Hyperdynamic phase Hyperglycemia Exhaustion phase Hypoglycemia develops Hypoglycemia appears earlier in presence of hypoxia Neuronal damage ensues Hyperdynamic phase Hyperglycemia Exhaustion phase Hypoglycemia develops Hypoglycemia appears earlier in presence of hypoxia Neuronal damage ensues

Status epilepticus17 Hyperpyrexia Hyperpyrexia may develop during protracted SE, and aggravate possible mismatch of cerebral metabolic requirement and substrate delivery Treat hyperpyrexia aggressively Antipyretics, external cooling Consider intubation, relaxation, ventilation

Status epilepticus18 Other alterations Blood leukocytosis (50% of children) Spinal fluid leukocytosis (15% of children)  K +  creatine kinase Myoglobinuria

Status epilepticus19 Oxygen, oral airway. Avoid hypoxia! Consider bag-valve mask ventilation. Consider intubation IV/IO access. Treat hypotension, but NOT hypertension A A B B C C

Status epilepticus20 Treatment Arterial blood gas? All children in SE have acidosis. It often resolves rapidly with termination of SE Intubate? It may be difficult to intubate the actively seizing child Stop or slow seizures first, give O 2, consider BVM ventilation If using paralytic agent to intubate, assume that SE continues

Status epilepticus21 Initial investigations Labs Na, Ca, Mg, PO 4, glucose CBC Liver function tests, ammonia Anticonvulsant level Toxicology

Status epilepticus22 Initial investigations Lumbar puncture Always defer LP in unstable patient, but never delay antibiotic/antiviral rx if indicated CT scan Indicated for focal seizures or deficit, history of trauma or bleeding d/o

Status epilepticus23 Treatment Give glucose (2-4 ml/kg D25%, infants 5 ml/kg D10%), unless normo- or hyperglycemic Hyperglycemia has no negative effect in SE (as long as significant hyperosmolality is being avoided)

Status epilepticus24 Treatment Hyponatremia: Give 5 cc/kg of 3% (hypertonic saline) Hypocalcemia: Give mg/kg of Calcium Chloride

Status epilepticus25 Treatment The longer you wait with anticonvulsant, the more anticonvulsant you will need to stop SE Most common mistake is ineffective dose

Status epilepticus26 Anticonvulsants Rapid acting plus Long acting

Status epilepticus27 Anticonvulsants - Rapid acting Benzodiazepines Lorazepam 0.1 mg/kg i.v. over 1-2 minutes Diazepam 0.2 mg/kg i.v. over 1-2 minutes If SE persists, repeat every 5-10 minutes

Status epilepticus28 Benzodiazepines Diazepam High lipid solubility Thus very rapid onset Redistributes rapidly Thus rapid loss of anticonvulsant effect Adverse effects are persistent: Hypotension Respir depression Lorazepam Low lipid solubility Action delayed 2 minutes Anticonvulsant effect 6-12 hrs Less respiratory depression than diazepam Midazolam May be given i.m.

Status epilepticus29 Anticonvulsants - Long acting Phenytoin 20 mg/kg i.v. over 20 min pH 12 Extravasation causes severe tissue injury Onset min May cause hypotension, dysrhythmia Cheap Fosphenytoin 20 mg PE/kg i.v. over 5-7 min PE = phenytoin equivalent pH 8.6 Extravasation well tolerated Onset 5-10 min May cause hypotension Expensive

Status epilepticus30 Anticonvulsants - Long acting Phenobarbital 20 mg/k g i.v. over min Onset min May cause hypotension, respiratory depression

Status epilepticus31 Initial choice of long acting anticonvulsants in SE Is patient an infant? Is patient already receiving phenytoin? Is patient an infant? Is patient already receiving phenytoin? YesNo At high risk for extravasation ? (small vein, difficult access etc.)? Phenobarbital YesNo PhenytoinFosphenytoin

Status epilepticus32 If SE persists Midazolam infusion mcg/kg/min after bolus 0.15 mg/kg Pentobarbital infusion 1-3 mg/kg/hr after bolus 10 mg/kg

Status epilepticus33 Non - convulsive status epilepticus How do you tell that patient’s seizures have stopped?

Status epilepticus34 Non - convulsive SE ? Neurologic signs after termination of SE are common: Pupillary changes Abnormal tone Babinski Posturing Clonus May be asymmetrical

Status epilepticus35 Non - convulsive SE ? Up to 20% of children with SE have non - convulsive SE after tonic - clonic SE

Status epilepticus36 Non - convulsive SE ? If child does not begin to respond to painful stimuli within minutes after tonic - clonic SE, suspect non - convulsive SE Urgent EEG

Status epilepticus37 References Haafiz A, Kissoon N. Status epilepticus: current concepts. Pediatr Emerg Care 1999;15(2): Bleck TP. Management approaches to prolonged seizures and status epilepticus. Epilepsia 1999;40(1):S64-6. Orlowski JP, Rothner DA. Diagnosis and treatment of status epilepticus. In: Fuhrman BP, Zimmerman JJ, editors. Pediatric Critical Care. St. Louis: Mosby; p