Status Epilepticus in Children

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

2. 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 epilepticus

3. Definition • Conventional definition: • Single seizure > 30 minutes • Series of seizures > 30 minutes without full recovery Status epilepticus

4. 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 epilepticus

5. 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 epilepticus

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

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

8. 15 to 22% 3 to 15% Mortality • Adults • Children Reviewed in: Fountain NB. Epilepsia 2000;41 Suppl 2:S23-30 Status epilepticus

9. Prolonged seizures Life threatening systemic changes Temporary systemic changes Death Duration of seizure Status epilepticus

10. Respiratory • Hypoxia and hypercarbia • ß ventilation (chest rigidity from muscle spasm) • Hypermetabolism (Ý O2 consumption, Ý CO2 production) • Poor handling of secretions • Neurogenic pulmonary edema? Status epilepticus

11. 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 epilepticus

12. 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 epilepticus

13. Acidosis • Respiratory • Lactic • Impaired tissue oxygenation • Increased energy expenditure Status epilepticus

14. Hemodynamics • Sympathetic overdrive • Massive catecholamine / autonomic discharge • Hypertension • Tachycardia • High CVP • Exhaustion • Hypotension • Hypoperfusion 0 min 60 min Status epilepticus

15. Cerebral blood flow - Cerebral O2 requirement • Hyperdynamicphase • CBF meets CMRO2 • Exhaustion phase • CBF drops as hypotension sets in • Autoregulation exhausted • Neuronal damage ensues O2 requirement Blood flow Blood pressure Seizure duration Status epilepticus

16. Glucose SE 30 min SE + hypoxia Seizure duration Glucose • Hyperdynamicphase • Hyperglycemia • Exhaustion phase • Hypoglycemia develops • Hypoglycemia appears earlier in presence of hypoxia • Neuronal damage ensues Status epilepticus

17. 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 epilepticus

18. Other alterations • Blood leukocytosis (50% of children) • Spinal fluid leukocytosis (15% of children) • Ý K+ • Ý creatine kinase • Myoglobinuria Status epilepticus

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

20. 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 O2, consider BVM ventilation • If using paralytic agent to intubate, assume that SE continues Status epilepticus

21. Initial investigations • Labs • Na, Ca, Mg, PO4 , glucose • CBC • Liver function tests, ammonia • Anticonvulsant level • Toxicology Status epilepticus

22. 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 epilepticus

23. 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 epilepticus

24. Treatment • Hyponatremia: • Give 5 cc/kg of 3% (hypertonic saline) • Hypocalcemia: • Give 20-25 mg/kg of Calcium Chloride Status epilepticus

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

26. Anticonvulsants • Rapid acting plus • Long acting Status epilepticus

27. 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 epilepticus

28. 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. Benzodiazepines Status epilepticus

29. Phenytoin 20 mg/kg i.v. over 20 min pH 12 Extravasation causes severe tissue injury Onset 10-30 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 Anticonvulsants - Long acting Status epilepticus

30. Anticonvulsants - Long acting • Phenobarbital • 20 mg/k g i.v. over 10 - 15 min • Onset 15-30 min • May cause hypotension, respiratory depression Status epilepticus

31. Initial choice of long acting anticonvulsants in SE Is patient an infant? Is patient already receiving phenytoin? No Yes At high risk for extravasation ? (small vein, difficult access etc.)? Phenobarbital No Yes Phenytoin Fosphenytoin Status epilepticus

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

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

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

35. Non - convulsive SE ? • Up to 20% of children with SE have non - convulsive SE after tonic - clonic SE Status epilepticus

36. Non - convulsive SE ? • If child does not begin to respond to painful stimuli within 20 - 30 minutes after tonic - clonic SE, suspect non - convulsive SE • Urgent EEG Status epilepticus

37. References • Haafiz A, Kissoon N. Status epilepticus: current concepts. Pediatr Emerg Care 1999;15(2):119-29. • 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; 1998. p. 625-35. Status epilepticus