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Acute Management of Seizure Disorders in Children

Acute Management of Seizure Disorders in Children. What is a seizure?. Seizure : paroxysmal event characterized by a change in behavior of the patient; it is caused by abnormal and excessive activity of a group of cortical neurons. Epilepsy : occurrence of two or more unprovoked seizures.

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Acute Management of Seizure Disorders in Children

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  1. Acute Management of Seizure Disorders in Children

  2. What is a seizure? • Seizure: paroxysmal event characterized by a change in behavior of the patient; it is caused by abnormal and excessive activity of a group of cortical neurons. • Epilepsy: occurrence of two or more unprovoked seizures

  3. Etiology of Seizures • Acute Symptomatic • Remote Symtomatic • Idiopathic

  4. Classification of seizures

  5. Epilepsy Syndromes • Triad of seizure type or types, age and EEG findings • Different medications for different syndromes!! • Very different prognoses for different syndromes

  6. Was it a seizure?Nonepileptic events • Syncope- vasovagal, cardiogenic • Sandifer syndrome • Breath holding spell • Migraine • Tics • Psychogenic • Sleep myoclonus • Paroxysmal dystonia

  7. Management of Seizures in the ED • The first unprovoked seizure • Status Epilepticus • Convulsive • Nonconvulsive • Febrile Seizures • Neonatal Seizures • Managing the known epilepsy patient

  8. Managing a First Unprovoked Seizure in ChildhoodHistory • Describe seizure very carefully • Length of seizure- do not take parents estimate of time lapsed at face value! • What was child doing when the seizure occurred? • What did seizure look like at its onset? During the seizure? • What happened after the seizure? • What does the child remember? • Possible precipitants of seizure • Head trauma? Possible ingestion? New medication or supplement?Fever? Dehydration? Rash? Change in mental status? Recent travel? • Ask about other seizure types! • Absence: does your child eve stop an stare and not respond • Myoclonus • Review of systems • Headaches, double vision, weakness, numbness, vomiting, etc • General ROS • PMH • Developmental History

  9. Managing a First Unprovoked Seizure in ChildhoodPhysical • General exam • Including: vital signs, signs of head trauma, signs of meningitis and sepsis, rash, etc • Directed general exam • Head circumference • Dysmorphic features • Neurocutaneous stigmata • Extremity abnormality • Organomegaly • Neurologic Exam • Mental status, including assessment of developmental level • Cranial Nerves • M otor • Reflexes • Tone • Gait • Cerebellar

  10. Managing a First Unprovoked Seizure in ChildhoodLaboratory EvaluationHertz D et al: Practice Parameter: Evaluating a first nonfebrile seizure in children. Neurology 2000; 55:616. • The below recommendations are for the child who has retrrned to baseline • “There is sufficient Class I evidence… to provide a recommendation…that an EEG be obtained in all children in whoma nonfebrile seizure has been diagnosed, to predict the riskof recurrence and to classify the seizure type and epilepsysyndrome. “ • “The decision to perform other studies, including LP,laboratory tests, and neuroimaging, for the purpose of determiningthe cause of the seizure and detecting potentially treatableabnormalities, will depend on the age of the patient and thespecific clinical circumstances. Children of different agesmay require different management strategies”

  11. Managing a First Unprovoked Seizure in ChildhoodLaboratory Evaluation • Blood • CBC, CMP • Urine • Utox- consider • Urinalysis • Neuroimaging • CT • If focal onset seizure, Todd’s paralysis, focal exam, possibility of trauma • If onset of seizure not witnessed • If follow up not assured • MRI • May be done as outpatient if felt to be warranted • EEG • outpatient

  12. Treatment of the child with a first unprovoked seizureHirtz d et al: Practice parameter: Treatment of the child with a first unprovoked seizureNeurology 2003;60:166. • “Treatment with AED is not indicated for the prevention of thedevelopment of epilepsy (Level B).” • “Treatment with AED maybe considered in circumstances wherethe benefits of reducingthe risk of a second seizure outweighthe risks of pharmacologicand psychosocial side effects (LevelB).” • In general, first unprovoked seizures are not treated with long term anticonvulsants

  13. Risk factors for seizure recurrence after first unprovoked seizure • Todd’s paralysis • Seizure in sleep • Developmental Delay • Neurologic abnormality • Abnormal neuroimaging • Abnormal EEG • Positive family history for epilepsy

  14. Status Epilepticus in Children

  15. Definition of Status Epilepticus • 30 minute duration of seizures (or two or more sequential seizures without full recovery of consciousness between seizures) • For practical purposes, start treatment earlier

  16. Complications of Status Epilepticus • Hypoxemia • Acidemia • Glucose alterations • Blood pressure disturbances • Increased intracranial pressure • Morbidity • Neurologic sequelae • Focal motor deficits • Mental retardation • Behavioral disorders • Chronic epilepsy • Acute and chronic MRI changes • Mortality • 3-4%

  17. Status Epilepticus • Common in children, particularly in children less than 2 years old • Particularly common in children with epilepsy (9-27% over time have at least one episode of status)

  18. Classification of Status Epilepticus • Focal • Simple focal • Complex focal • Generalized • Convulsive • Nonconvulsive • Psychogenic

  19. Etiology of Status Epilepticus • Acute symptomatic • Remote symptomatic • Progressive Encephalopathy • Febrile • Cryptogenic

  20. Etiology of Status Epilepticus

  21. Differential Diagnosis of Status Epilepticus • Movement Disorder • Drug induced dystonic reaction • Sandifers syndrome • Breathholding spell • Spasm • Secondary to increased ICP • Psychogenic seizure

  22. Evaluation and Treatment of Convulsive Status Epilepticus

  23. Management of Status Epilepticus in ChildrenInitial ApproachStatus Epilepticus Working Party, 2000 • Initial assessment • A, B, Cs • Rapid neurologic examination • Brief history • Give high flow oxygen • Measure rapid blood glucose • More to avoid glucose infusion than the uncommon hypoglycemic seizures • Confirm epileptic seizure • Not all events are epileptic!!!! • Laboratory Studies • Glucose, electrolytes, calcium, magnesium • ABG • CBC • Serum anticonvulsant drug levels (if indicated) • Toxicology screening

  24. Brief, directed history • Has the child ever had a seizure before? • History of trauma? Fever? Ingestion? • What medications (including nonprescription) does the child take? • Was the child his usual self prior to this event? • Any medical problems? • Any neurologic/developmental problems? • If child with known epilepsy • Has the child missed dosage of medication • If so, consider loading with that medication • Be aware of paradoxical side effects of ACDS • Phenytoin and carbamazepine toxicity may precipitate SE

  25. Rapid Neurologic Evaluation • Observation • What is the patient doing • What are the movements? Which extremities involved? • Stiff or floppy? • What are eyes doing? Head? • Is patient at all responsive? • To verbal stimuli • Noxious stimuli • Withdrawal approprate? • Cranial Nerves • Pupil reactivity, extraocular movements • Motor/Sensory: • What parts of body are moving? What parts withdraw to nailbed pressure

  26. Treatment of Convulsive Status Epilepticus in ChildrenStatus Epilepticus Working Party, 2000 After 10 minutes After 10 minutes After 10 minutes After 10 minutes After 20 minutes

  27. Management of SE in childrenWith no IV access • Diazepam 0.5 mg/kg PR • Diastat • IV diazepam, inserted per rectum through butterfly (needle cut off!) • Repeat dose if no response in 5 minutes • Midazolam 0.1-0.2 mg/kg intramuscularly • If seizures continue another 10 minutes: • Insert interosseous line

  28. Management of SE in Children with IV accessOverview • Lorazepam 0.1 mg/kg IV over 30-60 seconds • If seizures continue another 10 minutes, repeat lorazepam dosage • If seizure continues: • Fosphenytoin18 PE/kg over 7 minutes or • Phenytoin 18-20mg/kg over 20 minutes (general rule of thumb: for each 1mg/kg phenytoin or 1PE/kg fosphenytoin expect rise in level by approximately 1) • If already on phenytoin load with phenobarbital 20mg/kg over 10 minutes • If seizure continues another 20 minutes: • Phenobarbital 20 mg/kg IV (2 mg/kg/min) • May repeat 10mg/kg every thirty minutes • Confirm this is truly an epileptic seizure and continue to look for underlying treatable cause • Call for back up from anesthetist or intensive care specialist

  29. Step 1: Lorazepam • Lorazepam 0.1 mg/kg IV over 30-60 seconds • If seizures continue another 5-10 minutes, repeat lorazepam dosage • Lorazepam vs. Diazepam • Lorazepam • Equally or more effective than diazepam • Longer duration of action (6-12 hours vs. <1 hour) • Less respiratory depression than diazepam • Not available rectally • Diazepam • Highly effective in rapidly terminating seizures • However, redistribution into adipose tissue limits anticonvulsant effect to less than 20 minutes • Available in rectal gel, which can be given outside the ED

  30. Step 2: Load Fosphenytoin (or Phenytoin)

  31. Phenytoin Can be diluted in NS only! Maximum concentration of 10mg per ml Infusion rate < 1 mg/kg/min (Therefore 18 mg/kg is infused over no less than 18 minutes) Risk of hypotension and cardiac arrythmia Monitor heartrate BP and EKG Extravasation reaction, purple glove syndrome Fosphenytoin Pro drug: converted into phenytoin Can be diluted in commonly used diluents Can infuse 3 times more rapidly than phenytoin (ie, over 7-8 minutes) Decreased risk hypertension and arrhythmia Decreased risk extravasation reactions (pH of 8) Dosed in phenytoin equivalents (PE) which can be confusing. Phenytoin vs. Fosphenytoin

  32. Step 2: Fosphenytoin (or phenytoin) • Fosphenytoin18-20 PE/kg over 7 minutes or Phenytoin 18-20mg/kg over 20 minutes • If already on phenytoin, load with phenobarbital 20mg/kg over 10 minutes • General rule of thumb: for each 1 mg/kg phenytoin (or 1PE/kg fosphenytoin) expect level to rise by 1)

  33. Step 3: Phenobarbital • If seizure continues another 20 minutes: • Phenobarbital 20 mg/kg IV (2 mg/kg/min) • May repeat 10mg/kg every thirty minutes • Confirm this is truly an epileptic seizure and continue to look for underlying treatable cause

  34. Phenobarbital • Long acting anticonvulsant; very long half life (90 hours) • Respiratory depression and sedation potentiated by benzodiazepine

  35. Steps 4 and 5 • If seizures continue: • Call for backup from anesthetist or intensive care specialist • Rapid sequence induction of anesthesia • Use only short acting neuromuscular paralytics (or can mask signs of seizure) • Isoflurane and desflurane • Please note: this is rarely done in the US

  36. Refractory SE • Definition: continued seizures after 2 or 3 antiepileptic drugs have failed • Will usually need EEG monitoring at this point; typically titrate to burst suppression; intubation and intravascular monitoring in ICU setting

  37. Refractory SE • Inhalational anesthetics • Midazolam • Pentobarbital • Propofol • Valproic acid • Keppra • IV pyridoxine

  38. Midazolam • Short half life • IV, IM, intranasal, PO, buccal or rectal • Can be given as continuous IV infusion for refractory SE • Midazolam infusion • 0.1-0.3 mg/kg IV followed by 1mcg/kg/min IV infusion. • Increase every 15 minutes as necessary • Maximum 8-10 mcg/kg/min

  39. Pentobarbital • Short acting; used for refractory SE • Significant side effects: respiratory depression, hypotension, myocardial depression, reduced cardiac output, pulmonary edema, ileus • Intubation and intravascular monitoring required • 5-10 mg/kg intravenously/IO loading dose followed by 0.5-3 mg/kg/h • Thiopental • Used for refractory SE • Active metabolites which can accumulate • Possibly higher adverse reactions than pentobarbital

  40. Propofol • Intravenous anesthetic • Small number of studies show effectiveness • Risk of hypotension, apnea, metabolic acidosis and bradycardia • Contraindicated in child on ketogenic diet • 1-2 mg/kg load, followed by 2-10 mg/kg/hr infusion

  41. Valproic acid • Not yet approved for initial treatment of SE • Appears effective and safe • Dosage • 20-40 mg/kg IV (diluted 1:1 with normal saline or 5% dextrose in water) over 5-10 minutes; may repeat in 10-15 minutes • Follow with IV infusion of 5 mg/kg/hr

  42. Keppra • 1500 to 4000mg IV • A few small studies have showed promise

  43. Summary: Refractory SE • Inhalational anesthetics • Pentobarbital • Short acting; Significant side effects: respiratory depression, hypotension, myocardial depression, reduced cardiac output, pulmonary edema, ileus; Intubation and intravascualr monitoring usually required • Thiopental • Active metabolites which can accumulate; Possibly higher adverse reactions than pentobarbital • Propofol • Intravenous anesthetic; Risk of hypotension, apnea and bradycardia • Contraindicated in child on ketogenic diet • Midazolam • Short half life; IV, IM, intranasal, PO, buccal or rectal • 0.1-0.3 mg/kg IV followed by 1mcg/kg/min IV infusion; increase every 15 minutes as necessary; maximum 8-10 mcg/kg/min • Valproic acid • 20-40 mg/kg IV (diluted 1:1with normal saline or 5% dextrose in water) over 5-10 minutes; may repeat in 10-15 minutes. Follow with IV infusion of 5 mg/kg/hr • Keppra • Consider IV pyridoxine

  44. Diagnostic Assessment Searching for causes of acute symptomatic seizures • Metabolic • Hypoglycemia • Hypocalcemia • Hyponatremia • Inborn Error of Metabolism • Febrile • Trauma • Infectious • Meningitis • Sepsis • Stroke • Ischemic • Hemorrhagic • Tumor • Brain Malformation • Hypertensive • Etc.

  45. Diagnostic assessmentRiveillo et al: Practice Parameter: Diagnostic assessment of the child with status epilepticus (an evidence-based review) Neurology 2006;67:1542-1550 • Basic bloods: CBC, electrolytes, calcium, glucose are assumed will be obtained • Blood cultures • Insufficient data to support or refute whether blood cultures should be done on a routine basis on whom there is no clinical suspicion of infection • Corollary: if there is clinical suspicion of infection, obtain one • LP • Insufficient data to support or refute whether CSF cultures should be done on a routine basis on whom there is no clinical suspicion of CNS infection • Corollary: if there is clinical suspicion of CNS infection, obtain LP. • If mental status remains clouded after seizure is stopped and the clinical suspicion is low for meningitis, can wait for 1-2 hours to see if patient returns to baseline. If patient has not returned to baseline at that point, will need to do LP • In an infant, definitely LP • Measuring AED levels • AED levels should be considered when a child with epilepsy on AED prophylaxis develops SE • Translation: send the levels

  46. Diagnostic assessmentRiveillo et al: Practice Parameter: Diagnostic assessment of the child with status epilepticus (an evidence-based review) Neurology 2006;67:1542-1550 • Toxicology testing • Toxicology testing may be considered in children with SE, when no apparent etiology is immediately identified • Metabolic and genetic testing • Studies for inborn errors of metabolism should be considered when the initial evaluation reveals no etiology, especially if there is a preceding history suggestive of a metabolic disorder such as: • Unexplained neonatal encephalopathy • Neurologic deterioration during an acute illness • Unexplained developmental delay • Unexplained acidosis or coma (bear in mind status itself caused acidosis) • Unusual odors in urine • Need to eat frequently to prevent lethargy • Insufficient date to support or refute whether genetic testing should be done routinely in children with SE • Initial metabolic tests to consider if indicated as above • Amino acids • Urine organic acids • Ammonia • ABG • VLCFA • Lactic acid/pyruvate

  47. Diagnostic assessmentRiveillo et al: Practice Parameter: Diagnostic assessment of the child with status epilepticus (an evidence-based review) Neurology 2006;67:1542-1550 • EEG • An EEG may be considered in a child presenting with new onset SE as it may determine whether there are focal or generalized abnormalities that may influence diagnostic and treatment decisions • An EEG may be considered in a child presenting with SE if the diagnosis of pseudostatus epilepticus is suspected • Translation: Get an EEG • Neuroimaging • Neuroimaging may be considered for the evaluation of the child with SE if there are clinical indications or if the etiology is unknown (if etiology is known, eg has a history of epilepsy, usually do not need neuroimaging acutely) • If neuroimaging is done, it should only be done after the child is appropriately stabilized and the seizure activity stopped • In acute period, CT scan (rather than MRI) is safer as patient can be closely monitored. However, MRI provides superior detail

  48. Diagnostic Assessment • CBC, electrolytes, calcium, glucose • LP indicated if there is clinical suspicion of CNS infection. • in a young infant, have low threshold for LP • If patient has not returned to baseline mental status after a period of time (I usually use 4-6 hour cut off), then will need LP • Measure AED levels, if appropriate • Consider toxicology testing • Consider urgent imaging (CT scan) • Get an EEG (non emergent) • Consider MRI • Metabolic and genetic testing • Consider studies for inborn errors of metabolism if the initial evaluation reveals no etiology • Possibilities • Amino acids • Urine organic acids • Ammonia • ABG • VLCFA • Lactic acid/pyruvate

  49. Disposition • Patient gets admitted for observation for 24 hours • Or, longer, depending on underlying cause

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