1. The Management of Seizures and SE in the Emergency Department

2. Associate Professor & Research Development Director Department of Emergency Medicine, University of Illinois at Chicago Chicago, IL (edsloan@uic.edu) Edward Sloan, MD, MPH, FACEP

3. Edward Sloan, MD, MPH Global Objectives  Learn more about seizures  Increase awareness of Rx options  Enhance our ED management  Improve patient care & outcomes  Maximize staff & patient satisfaction  Be prepared for the EM board exam

4. Edward Sloan, MD, MPH Session Objectives  Provide seizure and SE overview  Summarize what Rx options exist  Discuss specific sub-groups  Outline ED Rx strategies

5. Edward Sloan, MD, MPH Sz Epidemiology:  Epilepsy seen in 1/150 people  For each epilepsy pt, 1 ED visit every 4 years  1-2% of all ED visits  Significant costs

6. Edward Sloan, MD, MPH Seizure Mechanism:  Sz = abnormal neuronal discharge with recruitment of otherwise normal neurons  Loss of GABA inhibition

7. Edward Sloan, MD, MPH Pathophysiology:  Glutamate toxic mediator  Necrosis occurs even if systemic problems are treated (HTN, fever, rhabdomyolysis, resp acidosis, hypoxia)

8. Edward Sloan, MD, MPH Pathophysiology:  Early compensation for increased CNS metabolic needs  Decompensation at 40-60 minutes, associated with tissue necrosis

9. Edward Sloan, MD, MPH Seizure Classification:  Generalized: both cerebral hemispheres  Partial: one cerebral hemisphere

10. Edward Sloan, MD, MPH Generalized Seizures :  Convulsive: tonic-clonic  Non-convulsive: absence

11. Edward Sloan, MD, MPH Generalized Seizures :  Primary generalized: starts as tonic-clonic seizure  Secondarily generalized: tonic-clonic seizure occurs as a consequence of a non- convulsive seizure

12. Edward Sloan, MD, MPH Partial Seizures :  Simple partial: no impaired consciousness  Complex partial: impaired consciousness

13. Edward Sloan, MD, MPH Specific Seizure Types :  Absence: Petit mal  Partial: Jacksonian, focal motor  Complex partial: temporal lobe, psychomotor

14. Edward Sloan, MD, MPH Status Epilepticus:  Sz > 5- 10 minutes = SE  Two sz without a lucid interval = SE (Assumes ongoing sz during coma)

15. Edward Sloan, MD, MPH SE Epidemiology:  Risk of SE greatest at extremes of age: pediatric and geriatric populations  SE: occurs in setting of acute insult, chronic epilepsy, or new onset seizure  150,000 cases per year

16. Edward Sloan, MD, MPH SE Classification:  GCSE: Generalized convulsive SE, with tonic- clonic motor activity  Non-GCSE

17. Edward Sloan, MD, MPH Two Non-GCSE Types:  Non-convulsive SE  Absence SE  Complex-partial SE  Subtle SE  Late generalized convulsive SE  Coma, persistent ictal discharge  Very grave prognosis

18. Edward Sloan, MD, MPH AMS in Seizures:  Mental status should improve by 20-40 minutes  If pt comatose, then subtle SE is possible: EEG  Up to 20% of pts with coma still are in SE

19. Edward Sloan, MD, MPH Ongoing SE Effects:  Over 40-60 min, loss of metabolic compensation  With ongoing SE, systemic BP & CBF drop

20. Edward Sloan, MD, MPH SE Mortality:  SE mortality > 30% when sz longer than 60 minutes  Underlying sz etiology contributes to mortality

21. Edward Sloan, MD, MPH Subtle SE:  Mortality exceeds 50%  Often after hypoxic insult  Coma  Limited motor activity  Stop the sz, EEG confirm

22. Edward Sloan, MD, MPH General ED Management:  ABCs  Glucose, narcan, thiamine  Rapid sequential use of AEDs  Directed evaluation

23. Edward Sloan, MD, MPH Lab Evaluation:  Key lab abnormality: hypoglycemia, in up to 2%  Directed labs, including anti-epileptic drug levels

24. Edward Sloan, MD, MPH Lumbar Puncture:  Fever and CSF pleocytosis can occur in SE without meningitis  Use clinical criteria to determine LP need  AMS, immunocompromise, meningismus

25. Edward Sloan, MD, MPH Neuroimaging with CT:  CT useful with focal sz, change in sz type or frequency, co-morbidity  Req’d in new-onset sz  Non-contrast unless mass lesion suspected

26. Edward Sloan, MD, MPH Neuroimaging with MRI:  Useful with refractory sz  Complements plain CT  Can be done as outpt

27. Edward Sloan, MD, MPH EEG Monitoring:  EEG to rule out subtle SE  Prolonged coma, RSI, induced coma with propofol, pentobarbital  Obtain EEG in 120 minutes  Two-lead EEG in ED

28. Edward Sloan, MD, MPH AED loading:  Repeated seizures, high- risk population, significant SE risk  No need to determine level in ED after loading  Oral loading in low risk pts

29. Edward Sloan, MD, MPH Hospital Admission:  Repeated sz, high-risk pt, significant SE risk  Esp if no AED loading  New-onset seizure: admission is preferred (complete w/u, observe)

30. Edward Sloan, MD, MPH New-Onset Sz: Recurrent Sz  51% recurrence risk  75% of recurrent sz occur within 2 years of first sz  Only a small % of pts will seize within 24 h  Partial sz, CNS abn inc risk

31. Edward Sloan, MD, MPH ED Discharge:  Follow-up & EEG needed, esp if no AED prescribed  Driving documentation is critical. Know state law.

32. Edward Sloan, MD, MPH Pharmacotherapy of Seizures  Benzodiazepines  Phenytoins  Barbiturates  Other agents  valproate  propofol

33. Edward Sloan, MD, MPH General AED Concepts:  Most drugs are at least 80% effective in Rx seizures, SE  Have AEDs available in ED  Maximize infusion rate in SE  Use full mg/kg doses

34. Edward Sloan, MD, MPH Benzodiazepines:  GABA drug  Diazepam: short acting, limited AMS and protection  Lorazepam: prolonged AMS and protection  Pediatric sz: IV lorazepam limits respiratory compromise

35. Edward Sloan, MD, MPH Rectal Diazepam:  Diazepam rectal gel pre- packaged for rapid use  Dose 0.5 mg/kg, less respiratory depression seen than with IV use

36. Edward Sloan, MD, MPH Phenytoin:  Phenytoin: Na + channel Rx  Load at 18 mg/kg, 1.5 doses  Infuse at 50 mg/min max  Use pump to prevent comp  Level 10-20 µg/mL

37. Edward Sloan, MD, MPH Fosphenytoin:  Fos: pro-drug, dose same  Infuse at 150 mg/min in SE  Can be given IM up to 20cc  Level 10-20 µg/mL  Delayed level: 2h IV, 4 h IM

38. Edward Sloan, MD, MPH IV Phenobarbital:  GABA-like, effective sz Rx  Limited availability  Infuse up to 50 mg/min  20-30 mg/kg, 10 mg/kg doses  Level > 40 µg/mL

39. Edward Sloan, MD, MPH IV Valproate:  Likely GABA mechanism  Useful in peds, possibly SE  Rate up to 300 mg/min  25-30 mg/kg, 3-6 mg/kg/min  Level > 100 µg/mL

40. Edward Sloan, MD, MPH Refractory SE:  SE refractory to benzos, phts, phenobarb, valproate  Propofol, pentobarb: useful third line agents  Midazolam infusion also useful  Respiratory depression, BP  Must control airway, get EEG

41. Edward Sloan, MD, MPH IV Propofol:  Likely GABA mechanism  Provides burst suppression  2 mg/kg loading dose  Hypotension, resp depression, acidosis  Easily reversed

42. Edward Sloan, MD, MPH IV Pentobarbital:  Likely GABA mechanism  Provides burst suppression  5 mg/kg loading dose  25 mg/kg infusion rate  ICU monitoring required

43. Edward Sloan, MD, MPH ED Treatment Protocol:  Have AEDs easily available  Rapid sequential AED use  Maximize infusion rate  Maximize mg/kg dosing  Benzos, phenytoins, phenobarbital, valproate

44. Edward Sloan, MD, MPH No IV Access:  PR diazepam  IM midazolam  IM fosphenytoin  Buccal, intranasal midazolam  No IM phenytoin/phenobarbital

45. Edward Sloan, MD, MPH Special Populations  Drug and alcohol-related seizures  Acute CVA  Post-traumatic  Pregnancy  Pediatrics  Elderly  Psychogenic seizures

46. Edward Sloan, MD, MPH Drug-related Sz:  Stimulants, anti-depressants, theophylline and cocaine commonly can cause sz  Most sz treated with benzos  Phenytoin less useful

47. Edward Sloan, MD, MPH Drug-related Sz Rx:  INH: Blocks GABA production  Vit B6, pyridoxine  5 gr IVP x 6, match ingestion gr  Theophylline: eliminate with hemodialysis, hemoperfusion  Tricyclics, cocaine: benzos,?? utility of other drugs

48. Edward Sloan, MD, MPH EtOH-related Seizures:  Occur 12 hrs p last drink  Lorazepam optimal Rx for sz  Lorazepam in DTs and sz prevention  Phenytoin ?? sz flurries, SE

49. Edward Sloan, MD, MPH Seizures in Acute CVA:  Seizures can occur in stroke  Consider prophylaxis with elderly, large hemorrhage, anterior CVA location

50. Edward Sloan, MD, MPH Post-traumatic Seizures:  High-risk populations exist  Early prophylaxis stops early sz, not late sz onset  Phenytoins, valproate

51. Edward Sloan, MD, MPH Seizures in Pregnancy:  Seizures related to changing AED levels and eclampsia  Benzos may be useful initially  Magnesium 4-6 g load, 1-2 g/hr  Respiratory depression, BP

52. Edward Sloan, MD, MPH Pediatric Seizures:  Peds sz, SE in kids 0-3 yrs  Common ED problem  80% are febrile sz  CNS abnormalities: afebrile sz  Cocaine, hyponatremia, meningitis  Outcome good, CNS plastic

53. Edward Sloan, MD, MPH Febrile Seizures:  6 months to 5 years  Up to 50% repeat febrile sz  Increased risk if age < 1 yr  No increased epilepsy risk  Complex: focal, > 15 min duration, flurry of sz

54. Edward Sloan, MD, MPH Febrile Seizure ED Rx:  Limited need for LP  Sz as sole manifestation of meningitis not seen  HIB: meningitis rare  Treat bacteremia (WBC > 15k)  CBC, blood cx, ceftriaxone

55. Edward Sloan, MD, MPH Other Pediatric Sz Types  Neonatal seizures  Benign childhood epilepsy (Rolandic)  Infantile spasms (West syndrome)  Lennox-Gastaut syndrome  Atonic seizures  Juvenile myoclonic epilepsy (JME)

56. Edward Sloan, MD, MPH Juvenile Myoclonic Epilepsy:  Common in teens, young adults  Etiology of generalized TC seizures  History of staring spells, AM clumsiness, myoclonus  Sleep deprivation, EtOH precipitants  Valproate may be best acute Rx

57. Edward Sloan, MD, MPH Seizures in the Elderly:  AMS: non-convulsive SE  Drug-drug interactions  CVD, tumor, toxicities  Caution for hypotension, cardiac dysrhythmias, IV AED extravasation

58. Edward Sloan, MD, MPH Psychogenic Sz:  Functional sz, not neurogenic  Conversion disorder, not faking it  Seen in 20% of epilepsy pts  Neurogenic sz in up to 60% of psychogenic sz pts: treat first!  Characteristic mvmts noted

59. Edward Sloan, MD, MPH EMS Seizure Rx:  Sz cause recurrent EMS need  ALS care for CNS findings, unstable, high risk  Low risk fractures (BB/collar)  IV, PR diazepam  IM midazolam

60. Edward Sloan, MD, MPH Research in Sz, SE:  Treiman D: VA Coop study  Alldredge B: PHTSE  Huff S: ED Sz epidemiology  EFA Working Group (JAMA)  Hampers L: Febrile sz ED Rx

61. Edward Sloan, MD, MPH EFA Guidelines:  Protocol: ABCs, know drugs, adequate doses  Benzodiazepines, phenytoins, phenobarb/valproate  Midazolam, propofol, pentobarb  Specify general timelines

62. Edward Sloan, MD, MPH SE Rx Timeline:  0-30 min: ABCs, benzos  30-45 min: Phenytoins  45-75 min: Phenobarb/valproate  75+ min: Refractory SE Rx  90-150 min: CT, EEG, ICU/OR

63. Edward Sloan, MD, MPH ACEP CPC Questions  Clinical Policy Committee  Written guidelines  Clinically relevant questions  Role of oral loading  Subtle SE, EEG use  Post-benzo AED therapy in SE  New onset seizure ED Rx

64. Edward Sloan, MD, MPH Sz, SE Conclusions  Sz, SE: medical emergencies  Early Rx is critical  Many Rx options exist  Maximize ED Rx  Have a plan  Have meds readily available  Use EEG when indicated

65. Edward Sloan, MD, MPH Slide Content  Slides on FERNE website  EM physicians, neuro emergencies  www.FERNE.org  Look for button on main page  2001 ICEP Seizure Lecture

66. Edward Sloan, MD, MPH FERNE Sz Symposium  Tuesday October 16, 2001  4:00 to 6:00 pm  U of Chicago Gleacher Center  Clinical Issues in ED Seizure Rx  Register online at www.FERNE.org