23_common_epilepticus

Generalized, Tonic-Clonic Status Epilepticus in Children : 

Generalized, Tonic-Clonic Status Epilepticus in Children Heinrich Werner, MD Pediatric Critical Care University of Kentucky Children’s Hospital

Objectives : 

Objectives The participant will increase her/his ability to define status epilepticus using a practical, mechanistic approach ability to list probable causes for status epilepticus in children understanding of the pathophysiologic events knowledge of treatment strategies for pediatric status epilepticus

Slide 3: 

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 (GCSE) is the most common form of SE The following presentation refers to generalized, tonic-clonic SE

Definition : 

Definition Conventional “textbook” definition of status epilepticus: Single seizure > 30 minutes Series of seizures > 30 minutes without full recovery

Why 30 minutes ? : 

Why 30 minutes ? Animal experiments in the 1970s and 1980s had shown that ... … neuronal injury could be demonstrated after 30 min of seizure activity, even while maintaining respiration and circulation Nevander G. Ann Neurol 1985;18(3):281-90.

More practical: Mechanistic definition : 

More practical: Mechanistic definition GCSE is a condition which most likely will not terminate rapidly and / or spontaneously GCSE is a condition which requires prompt intervention Lowenstein DH. Epilepsia 1999

Slide 7: 

The longer SE persists, the lower is the likelihood of spontaneous cessation the harder it is to control the higher is the risk of morbidity and mortality Bleck TP. Epilepsia 1999;40(1):S64-6 The Status Epilepticus Working Party. Arch Dis Child 2000;83(5):415-9.

Typical seizure duration : 

Typical seizure duration Children > 5 years: Typical, generalized tonic-clonic seizure lasts < 5 minutes Young children and infants: Paucity of data. Suggested time frame for typical tonic-clonic seizure : < 10-15 minutes Reviewed in: Lowenstein DH. It's time to revise the definition of status epilepticus. Epilepsia 1999;40(1):120-2.

Revised Definition : 

Revised Definition Generalized, convulsive status epilepticus in older children (> 5 years) refers to > 5 minutes of continuous seizure or >2 discrete seizures with incomplete recovery of consciousness Patients with generalized seizure activity at arrival in the ER are treated promptly regardless of prior duration Lowenstein DH, Bleck T, Macdonald RL. It's time to revise the definition of status epilepticus. Epilepsia 1999;40(1):120-2.

Causes : 

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

Drugs which can cause seizures : 

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

Mortality : 

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

Mortality : 

Mortality The primary determinant of mortality and morbidity of SE in children is its etiology The greatest mortality and highest rate of neurological deficits occurs when SE is caused by an acute neurological condition (infection, trauma, stroke) Mitchell WG. J Child Neurol 2002;17 Suppl 1:S36-43.

Prolonged seizures : 

Prolonged seizures Duration of seizure Life threatening systemic changes Death Temporary systemic changes

Respiratory : 

Respiratory Hypoxia and hypercarbia Ventilation (chest rigidity from muscle spasm) Hypermetabolism ( O2 consumption, CO2 production) Poor handling of secretions Neurogenic pulmonary edema?

Hypoxia : 

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

Neurogenic Pulmonary Edema : 

Neurogenic Pulmonary Edema Rare complication of SE in children Likely occurs as consequence of marked increase of pulmonary vascular pressure during SE Johnston SC. Postictal pulmonary edema requires pulmonary vascular pressure increases. Epilepsia 1996;37(5):428-32

Acidosis : 

Acidosis Respiratory Lactic Impaired tissue oxygenation Increased energy expenditure

Hemodynamics : 

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

Cerebral blood flow - Cerebral O2 requirement : 

Cerebral blood flow - Cerebral O2 requirement Blood pressure Blood flow O2 requirement Seizure duration Hyperdynamic Exhaustion Lothman E. Neurology 1990;40(5 Suppl 2):13-23. Hyperdynamic phase CBF meets CMRO2 Exhaustion phase CBF drops as hypotension sets in Autoregulation exhausted Neuronal damage ensues

Glucose : 

Glucose Lothman E. Neurology 1990;40(5 Suppl 2):13-23. Hyperdynamic phase Hyperglycemia Exhaustion phase Hypoglycemia develops Hypoglycemia appears earlier in presence of hypoxia Neuronal damage ensues

Hyperpyrexia : 

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

Other alterations : 

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

Slide 24: 

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

Treatment : 

Treatment Arterial blood gas? All children in SE develop acidosis. It often resolves rapidly with termination of SE Intubate? It may be difficult to intubate a child with active seizures Stop or slow seizures first, give O2, consider BVM ventilation If using paralytic agent to intubate, assume that SE continues

Initial investigations : 

Initial investigations Labs Na, Ca, Mg, PO4 , glucose CBC Liver function tests, ammonia Anticonvulsant drug level Toxicology

Initial investigations : 

Initial investigations Lumbar puncture Always defer LP in unstable patients, but never delay antibiotic/antiviral treatment if indicated CT scan Indicated for focal seizures or focal deficit or focal EEG, history of trauma or bleeding disorder Treatment of convulsive status epilepticus. Recommendations of the Epilepsy Foundation of America's Working Group on Status Epilepticus. JAMA 1993;270(7):854-9.

Treatment : 

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)

Treatment : 

Treatment The longer you wait to administer anticonvulsants, the more anticonvulsants you will need to stop SE Most common mistake is ineffective dose

Anticonvulsants : 

Anticonvulsants Rapid acting plus Long acting

Anticonvulsants - Rapid acting : 

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

Benzodiazepines : 

Benzodiazepines Diazepam High lipid solubility Thus very rapid onset Redistributes rapidly Thus rapid loss of anticonvulsant effect Adverse effects are persistent: Hypotension Respiratory 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.

Benzodiazepine - Rectal : 

Benzodiazepine - Rectal Rectal diazepam 0.3 to 0.5 mg/kg rectal gel, typically reaches anticonvulsant levels within 5-10 minutes Intravenous solution given rectally is equally effective (and much cheaper) Seigler RS. J Emerg Med1990;8(2):155-9. Cost : 5 mg Diastat rectal gel $ 78.00 5 mg diazepam intravenous solution $ 1.40

Benzodiazepine - Intramuscular : 

Benzodiazepine - Intramuscular Intramuscular midazolam 0.2 mg/kg i.m. Aqueous solution is rapidly absorbed, anticonvulsant effect begins after 2 minutes Intramuscular lorazepam Can be given, but lacks water solubility, thus later onset than midazolam Chamberlain JM. Pediatr Emerg Care 1997;13(2):92-4. Towne AR. J Emerg Med 1999;17(2):323-8.

Anticonvulsants - Long acting : 

Anticonvulsants - Long acting 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

If in doubt, measure free phenytoin! : 

If in doubt, measure free phenytoin! Phenytoin is largely protein bound (> 90%, varies with serum protein concentration) Free phenytoin = active phenytoin (anticonvulsant and toxic effects) Toxicity more likely with hypoalbuminemia (usually if < 2 g/dL) Therapeutic levels Total phenytoin: 10 - 20 mcg/ml Free phenytoin: 0.8 - 1.6 mcg/ml

Anticonvulsants - Long acting : 

Anticonvulsants - Long acting Phenobarbital 20 mg/kg i.v. over 10 - 15 min Onset 15-30 min May cause hypotension, respiratory depression

Initial choice of long acting anticonvulsants in SE : 

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

If SE persists : 

If SE persists Propofol infusion 5-10 mg/kg/hr after bolus 2 mg/kg 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 Paraldehyde: no longer allowed for human use Isoflurane

Non - convulsive status epilepticus : 

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

Non - convulsive SE ? : 

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

Non - convulsive SE ? : 

Non - convulsive SE ? Up to 20% of children with SE have non - convulsive SE after tonic - clonic SE Particularly common in infants < 2 months Mitchell WG. J Child Neurol 2002;17 Suppl 1:S36-43.

Non - convulsive SE ? : 

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

Case Scenario (1a) : 

Case Scenario (1a) A 2 y.o. boy arrives in your ER via ambulance, with active seizures. Parents had called 911, crew found pt having generalized, tonic-clonic seizure No drugs given yet What are your priorities?

Case Scenario (1b) : 

Case Scenario (1b) A,B,C. Stopping seizure. With supplemental O2, saturation signal comes and goes, but reads 100% when plethysmographic tracing looks acceptable. Lips are pink. Child is moving air with proper head positioning and jaw thrust HR 145/min, BP 130/85 Several unsuccessful i.v. attempts, still trying after 5 minutes. Continued seizure activity What next?

Case Scenario (1c) : 

Case Scenario (1c) Use alternate route for initial dose of benzodiazepine A few minutes after midazolam 7.5 mg im, seizures stop, but then start again. There was time enough for one of your best nurses to insert a 24g iv catheter into the pt’s hand. Vital signs unchanged Everybody looks to you for new orders

Case Scenario (1d) : 

Case Scenario (1d) After two doses of lorazepam and initiation of 20 mg/kg fosphenytoin, the child stops convulsing He currently is unresponsive, RR 12/min, O2Sat 100% in oxygen, HR 115/min, BP 105/60 ABG drawn earlier (sent by RN, you had not asked for it): pH 7.02 pCO2 76 pO2 95 BE - 8 What will you do ? Intubate (mental state, pCO2)? Give bicarb? Repeat ABG?

Case Scenario (1e) : 

Case Scenario (1e) Combined metabolic/respiratory acidosis to be expected during SE. Does not dictate intubation, does not require HCO3 As long as pt is oxygenating well, can wait for post-ictal state to resolve, without further ABG If pt remains completely unresponsive 30 minutes after cessation of GCSE, suspect non-convulsive SE

Case Scenario (2a) : 

Case Scenario (2a) 3 month old infant with a 4 day history of vomiting and diarrhea. Parents tried to maintain hydration using diluted formula , soda and now rice water Lethargic all day, then started convulsing Active, generalized tonic-clonic seizure on arrival in ER Your initial actions? Possible cause?

Case Scenario (2b) : 

Case Scenario (2b) Meningo-encephalitis? Sepsis? Electrolyte disturbance? After you start high flow oxygen via a partial rebreather mask, suction the airway and position the head in mild hyperextension with jaw thrust, O2 saturation reads around 60%, and the child looks blue. He is still seizing . You see no chest rise and hear no air entry. What is your plan of action?

Case Scenario (2c) : 

Case Scenario (2c) Saturation improves to about 85% with BVM ventilation, the pt looks less blue but not pink. Fairly violent seizure activity continues. Per your order, the first dose of lorazepam is going into the IV, but pt continues to seize and is cyanotic You give rocuronium 1 mg/kg rapidly iv, and expertly intubate the child. He is now being ventilated, pink and not seizing any more Good job! Anything else to be done? What information are you eagerly waiting for?

Case Scenario (2d) : 

Case Scenario (2d) Have to assume ongoing electrical seizures. What is the sodium? Blood sugar is 180 mg/dL, Na is 118 mEq/L Neuromuscular blockade is beginning to wear off, there is still seizure activity What now?

Case Scenario (2e) : 

Case Scenario (2e) After 20 mg/kg phenobarbital, and halfway into an infusion of 3% NaCl, seizure activity slows, and then stops You consider a CT, plan an LP, start antibiotics You have a high index of suspicion for ongoing electrical seizures (non-convulsive SE) in this infant

Suggested Reading : 

Suggested Reading 1. Fountain NB. Status epilepticus: risk factors and complications. Epilepsia 2000;41 Suppl 2:S23-30. 2. Treatment of convulsive status epilepticus. Recommendations of the Epilepsy Foundation of America's Working Group on Status Epilepticus. JAMA 1993;270(7):854-9. 3. Bassin S, Smith TL, Bleck TP. Clinical review: status epilepticus. Crit Care 2002;6(2):137-42. 4. Bleck TP. Management approaches to prolonged seizures and status epilepticus. Epilepsia 1999;40(1):S64-6. 5. DeLorenzo RJ, Towne AR, Pellock JM, et al. Status epilepticus in children, adults, and the elderly. Epilepsia 1992;33 Suppl 4:S15-25. 6. Haafiz A, Kissoon N. Status epilepticus: current concepts. Pediatr Emerg Care 1999;15(2):119-29. 7. Lowenstein DH, Bleck T, Macdonald RL. It's time to revise the definition of status epilepticus. Epilepsia 1999;40(1):120-2. 8. 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.