Emergency Management of Seizures Sarah A. Murphy, MD Pediatric Critical Care Fellow, MGH

1. Emergency Management of SeizuresSarah A. Murphy, MDPediatric Critical Care Fellow, MGH

2. This presentation will review emergency management of seizure/convulsions • We will begin with a review of the approach to a child who presents with: • lethargy • unconsciousness OR • convulsions/seizures

3. Assess for Coma or Convulsions: AVPU • Is the child: • Alert? • Responding to Voice? • Responding to Pain? • Unconscious? • A child who is not alert but responding to voice is lethargic • A child who does not respond to pain is unconscious

4. Unconscious or Convulsion: • Manage Airway • Give diazepam or paraldehyde if convulsing • Position unconscious child • Give IV glucose:

8. Obtain History: • Fever? • Head Injury? • Drug or Toxin exposure? • Birth asphyxia or injury if newborn?

9. Examination: • AVPU score • General: • Pallor • Jaundice • Edema • Petechial Rash • Head and Neck: • Stiff neck • Signs of trauma • Pupilary reactions • Fontanelle • Posture

10. Laboratory Investigations: • Blood glucose • Blood smear for malaria • Blood pressure • Urine microscopy • Electrolytes

11. Differential Diagnosis of Lethargy, Unconscious, or Convulsions: • Meningitis: irritable, stiff neck or bulging fontanelle, petechial rash • Cerebral Malaria: jaundice, anemia, pallor, convulsions, hypoglycemia • Febrile convulsions: history of same, seziure associated with fever, age 6 mos to 5 years, normal blood smear • Hypolycemia: responds to treatment with glucose, check for malaria • Head injury: signs of trauma

12. Differential Diagnosis of Lethargy, Unconscious, or Convulsions: • Poisoning: suggested by history • Shock: unlikely to cause seizures, poor capillary refill, rapid weak pulse • Glomerulonephritis with encephalopathy: raised BP, edema, decreased urine, blood in urine • DKA: high blood sugar, polydipsia and polyuria, deep breathing

13. Differential Diagnosis of lethargy, unconsciousness or convulsions IN NEONATE • Birth Asphyxia:difficult delivery, onset in 1st three days of life • Intracranial hemorrhage:low-birth weight or pre-term infant with onset in 1st three days of life • Hemolytic disease of newborn/ kernicterus:jaundice, pallor, bacterial infection, onset in 1st three days of life

14. Differential Diagnosis of lethargy, unconsciousness or convulsions IN NEONATE • Neonatal tetanus: onset from 3-14days of life, irritability, difficulty breast-feeding, trismus, spasms, seizures • Meningitis: high-pitched cry, tense fontanelle, apneic episodes • Sepsis: fever or hypothermia, shock, seriously ill

15. Emergency Management of Seizures?

16. Clinical Diagnosis of Seizure • Altered Mental Status • Hypotonia • Emesis • Eye deviation • Tonic-clonic movements • Incontinence

17. Pathophysiology of Seizures • Cellular Mechanisms responsible for Status Epilepticus • Natural progression of Status Epilepticus • Systemic complications of Status Epilepticus • Neuropathology • CNS mechanisms for neuronal damage/death

18. Cellular Mechanisms • A group of neurons in the CNS become depolarized with abnormal synchrony and fire action potentials repetitively, interfering with normal brain function • This abnormal paroxysmal activity is intermittent and usually self-limited, lasting seconds to a few minutes

19. Cellular Mechanisms • Cellular explanation likely multifactorial: • Increased release of excitatory Neurotransmitters (Glutamate) • Decreased release of inhibitory neurotransmitters (GABA) • Increased/decreased neurotransmitter sensitivity • Changes affecting ionic and voltage-gated channels at neuronal synapses  membrane instability

20. Natural History of SE • As the duration of SE progresses, there is a distinct evolution with predictable effects in the human body • Systemic changes occur in phases • Phase I (<30 mins) • Phase II (30-60 mins) – severe systemic distress • Phase III (>60 mins) – Refractory SE

22. Systemic Complications of SE(Rogers, ch.22) 10C 20C /nl nl 900% 200% 300% 300%

23. Neuropathology Autopsy findings include: • Hippocampal necrosis • Widespread cerebellar necrosis • Degeneration of Purkinje cells • Necrosis and neuronal loss in the cerebral cortex. Cause of neuropathologic changes: • Perhaps due to systemic physiologic alteration (hypotension, hypoxia, hyperpyrexia, acidosis) • Perhaps intrinsic CNS mechanisms related to electrical activity

24. Neurologic Damage • In animal models, irreversible neurologic damage in 90-120 mins • With prolonged tonic-clonic activity: hypoxia, hypoglycemia, hyperkalemia, hyperkalemia, increased ICP • Even with control of BP, oxygenation, ventilation, glucose and fever, neuronal cell death occurs

25. Hypothesized CNS mechanisms of neuronal damage/death • Excessive presynaptic release of excitatory transmitter  intracellular postsynaptic changes  dendritic swelling and cell death. • Inhibitory-excitatory interaction: over-excitation combined with decrease of GABA-mediated inhibition. • Possible unmasking of excitatory glutamate receptor channel-mediated events

26. Initial Emergency Management of Seizures • Stabilize the patient • Address underlying causes of seizure • Treat seizures • Choices of anti-epileptic drugs

27. Stabilize the patient Maintain Cardiovascular and Respiratory Function: • airway protection • maintain ventilation, oxygenation • support circulation • establish vascular access

28. Stabilize the patient • Position the patient to avoid aspiration, suffocation, physical injury • Elevate HOB • Turn patient on side after seizure event to prevent aspiration • Suction available for vomitus, secretions • Bars, rails and close monitoring to prevent physical harm

29. Stabilize the patient Assess A, B, C, D’s ……

30. Stabilize the patient • Airway protection • 100% oxygen on all patients • attempt to open airway with jaw thrust if needed • oral or nasopharyngeal airway if easily placed • suctioning of emesis/secretions • ETT if necessary (RSI)*

31. Stabilize the patient • Breathing • support by using muscle relaxation if necessary

32. Stabilize the patient • Circulation • verify good BP • secure PIV • NS 20cc/kg

33. Stabilize the patient • Dextrose • Check blood sugar • If suspecting low bood sugar, give 25% dextrose in water, 2-4ml/kg • 10 mL/kg D10 in neonates

34. RSI for Status Epilepticus AIRWAY • Airway obstruction • Loss of cough/gag • Hypoventilation • Hypoxemia • Risk of aspiration Preoxygenate w/ 100% O2 (avoid PPV) Atropine 0.02mg/kg (0.1mg min-1mg max) Cricoid pressure • Sedative • Thiopental 3-5mg/kg or • Versed 0.05-0.1mg/kg or • Propofol 1-3mg/kg Paralytic -Succinylcholine 1-2mg/kg or -Vecuronium 0.1-0.3mg/kg

35. Address underlying causes • Elicit quick history • Trauma • Antecedent illness • Fever • Ingestion • Skipped meds • Obtain critical labs • Chem 7, Ca, Phos, CBC, tox screen, AED levels

36. Address underlying causes • Correct and then prevent metabolic derangements: • Hydration • Electrolytes • Glucose • Lactate

37. Common Causes of Seizures • Fever • Hypoglycemia • Hypoxia • Poisoning • Head Trauma • Meningitis • Idiopathic

39. Treat Seizures 1. Evaluate and treat underlying cause 2. Stop clinical/electrical seizure activity (using Anti-Epileptic Drugs)

40. The longer the seizure, the more difficult to control so…ACT FAST!

41. Lowenstein and Alldredge: • Seizures stopped by 1st line therapy in 80% of patients if started in the 1st 30 mins • But 1st line drugs stopped seizures in only 40% of patients if started > 2hrs after seizure

42. Implementing Drug Therapy “It’s not the particular choice of drug but rather the timing, route, and vigor of therapy that are major determinants of duration of status epilepticus and subsequent morbidity.” Rogers et al. “When treating status epilepticus, the therapeutic endpoint is not the production of a particular drug concentration but rather a clinical and/or electrical endpoint.” Rogers et al.

43. Implementing Drug Therapy • Anticipate consequences of therapy • Respiratory depression • Hypotension

44. Anticonvulsants: Based on availability • First-line • Diazepam, or Lorazepam • Paraldehyde • Second-line • Phenytoin or • Phenobarbitol • Third-line • Thiopental • Midazolam • Isoflurane • Propofol

47. Diazepam (Valium) • Can be administered IV/PR • Avoid repeated doses  accumulation of drug and metabolites • Pharmacokinetics : • Highly lipid-soluble  easily passes across blood brain barrier, and large volume of distribution • Rapid distribution into brain (10 sec) • CSF concentrations reach ½ maximum value in 3 minutes • Then, with redistribution, rapid drop in serum concentration • Pharmacodynamics: • Depresses all levels of the CNS, including the limbic and reticular formation by binding to the benzodiazepine site on the gamma-aminobutyric acid (GABA) receptor complex and modulating GABA, which is a major inhibitory neurotransmitter in the brain • Onset of action ~2 mins • Duration of action ~15 mins • Low toxicity: sedation, hypotension, respiratory depression, laryngospasm, CV collapse, arrest • Use: seizure activity compromising vital functions • IV diazepam + LD phenytoin

48. Paraldehyde • Can be given: • IM: The usual intramuscular dose of paraldehyde for status epilepticus is 0.15 to 0.3 ml/kg. Can give additional dose (0.05 ml/kg). The dose may be repeated in 2 to 6 hours and no more than 5 milliliters should be administered in one site (AMA Department of Drugs, 1986). • IV:1)  The usual dose 0.1 to 0.15 ml/kg. The intravenous solution should be well-diluted in normal saline. Higher doses 0.3ml/kg increase the incidence of adverse effects 2)  Administration of intravenous paraldehyde is not recommended • PR: The usual rectal dose is 4-8 ml diluted with an equal or double amount of oil or isotonic sodium chloride. The paraldehyde should be diluted 2:1 in olive or cottonseed oil or mixed in 200 ml of NS. Rectal absorption is slow and peak plasma levels will not occur for 2 to 4 hours (Coniglio & Garnett, 1989).

49. Paraldehyde Pharmacokinetics : • Metabolism by LIVER, 70% to 80%, with the rate of elimination slowed by hepatic insufficiency (Gilman et al, 1985) Pharmacodynamics: Onset: intramuscular: 2 to 3 minutes, oral: 10 to 15 minutes Peak Response: intramuscular: 5 to 15 minutes Use: Paraldehyde is a rapidly acting hypnotic, with sleep normally ensuing in 10 to 15 minutes. It has no analgesic properties and may produce excitement or delirium in the presence of pain. Paraldehyde is effective for all types of convulsions and delirium at high doses. Respiratory depression and hypotension also occur in high doses, but little effect on respiration and blood pressure occur at therapeutic doses (Gilman et al, 1985).

50. Lorazepam (Ativan) • Given over 2 minutes • may repeat Q10 mins x 2 • Beware of tachyphylaxis with successive doses • Pharmacokinetics • Lipid-solubility and volume of distribution half that of diazepam • Half-life twice that of diazepam • Longer onset of action (2 mins)   • Pharmacodynamics • Depresses all levels of the CNS, including the limbic and reticular formation, by binding to the benzodiazepine site on the gamma-aminobutyric acid (GABA) receptor complex and modulating GABA, which is a major inhibitory neurotransmitter in the brain • Onset of action • Oral: Within 60 minutes  I.M.: 30-60 minutes  I.V.: 15-30 minutes • Duration of action 4-6 hrs • Half-life significantly prolonged in newborns (40hrs vs 10) • Low toxicity: sedation, hypotension, respiratory depression, badycardia, CV collapse, arrest • Use: First-line therapy for SE