1. Edward P. Sloan, MD, MPH Optimizing Seizure and SE Patient Management in the Emergency Department

2. Edward P. Sloan, MD, MPH SIMEU / ACEP Emergency Medicine Congress

3. Edward P. Sloan, MD, MPH Turino, Italy November 9-11, 2006

4. Edward P. Sloan, MD, MPH Edward P. Sloan, MD, MPH Professor Department of Emergency Medicine University of Illinois College of Medicine Chicago, IL

5. Edward P. Sloan, MD, MPH Attending Physician Emergency Medicine University of Illinois Hospital Our Lady of the Resurrection Hospital Chicago, IL

6. Edward P. Sloan, MD, MPH

7. Disclosures NovoNordisk, King Pharmaceuticals, UCB Pharma Advisory BoardsNovoNordisk, King Pharmaceuticals, UCB Pharma Advisory Boards Eisai Speakers’ BureauEisai Speakers’ Bureau ACEP Clinical Policies CommitteeACEP Clinical Policies Committee ACEP Scientific Review CommitteeACEP Scientific Review Committee Executive Board, FERNEExecutive Board, FERNE FERNE support by Abbott, Eisai, Pfizer, UCBFERNE support by Abbott, Eisai, Pfizer, UCB

8. Edward P. Sloan, MD, MPH Board Chairman and President FERNE Board Chairman and President FERNE Chicago, IL

9. Edward P. Sloan, MD, MPH Overview Mission Statement Patients with neurological emergencies deserve quality emergency care. Patients with neurological emergencies deserve quality emergency care. Quality scientific research. Quality scientific research. Case-oriented, evidence-based medical education on optimal acute neurological care. Case-oriented, evidence-based medical education on optimal acute neurological care. Use of technology to break down space and time barriers. Use of technology to break down space and time barriers. Advocacy. Advocacy.

10. Edward P. Sloan, MD, MPH www.ferne.org

11. Gabriella Paglia, MD Department of Emergency Neurology Az. Ospedaliera S.Giovanni Battista di Torino Cap 10126 TORINO C.so Bramante, 88/90 Italy A Special Welcome To…

12. Edward P. Sloan, MD, MPH Today’s Agenda Present a clinical casePresent a clinical case Ask a few questionsAsk a few questions Consider the possibilitiesConsider the possibilities Discuss ED managementDiscuss ED management Examine the patient outcomeExamine the patient outcome

13. Edward P. Sloan, MD, MPH A Clinical Case

14. Edward P. Sloan, MD, MPH Patient EMS Data 50?? yo male John Doe50?? yo male John Doe Generalized tonic-clonic seizureGeneralized tonic-clonic seizure Chicago Fire DepartmentChicago Fire Department Diazepam 5 mg IM, 15 mg IVDiazepam 5 mg IM, 15 mg IV Seizure continuous for 15 minutes +Seizure continuous for 15 minutes + EMS to EDEMS to ED No change in statusNo change in status

15. Edward P. Sloan, MD, MPH Patient Clinical History Unknown medsUnknown meds Unknown medical historyUnknown medical history Hx Needs surgery next month ??Hx Needs surgery next month ?? EtOH ??EtOH ?? Does not appear to be homelessDoes not appear to be homeless Accucheck 119Accucheck 119

16. Edward P. Sloan, MD, MPH ED Presentation Facial and shoulder twitching RFacial and shoulder twitching R Pt with gurgling BSPt with gurgling BS Nasopharyngeal airwayNasopharyngeal airway No evidence of trauma or toxicityNo evidence of trauma or toxicity IV access in neckIV access in neck Seizure persists x minutesSeizure persists x minutes

17. Edward P. Sloan, MD, MPH Seizure Patient Questions Is this a seizure?Is this a seizure? Is this status epilepticus?Is this status epilepticus? What is the pathophysiology?What is the pathophysiology? What is the best management?What is the best management? What is the likely patient outcome?What is the likely patient outcome?

18. Edward P. Sloan, MD, MPH Seizure/SE Clinical Data

19. Edward P. Sloan, MD, MPH Seizures Generalized Seizures: Primary generalized: starts as tonic-clonic sz Primary generalized: starts as tonic-clonic sz Secondarily generalized: tonic-clonic sz develops from a non-convulsive partial sz, ie aura (common) Secondarily generalized: tonic-clonic sz develops from a non-convulsive partial sz, ie aura (common)

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

21. Edward P. Sloan, MD, MPH Status Epilepticus SE Classification: GCSE: (Generalized convulsive SE) with tonic- clonic motor activity GCSE: (Generalized convulsive SE) with tonic- clonic motor activity Non-GCSE Non-GCSE

22. Edward P. Sloan, MD, MPH Status Epilepticus Two Non-GCSE Types: Non-convulsive SE Non-convulsive SE Absence SE Absence SE Complex-partial SE Complex-partial SE Subtle SE Subtle SE Late generalized convulsive SE Late generalized convulsive SE Coma, persistent ictal discharge Coma, persistent ictal discharge Very grave prognosis Very grave prognosis

23. Edward P. Sloan, MD, MPH Status Epilepticus Systemic SE Effects: Hypertension (early) Hypertension (early) Hypotension (later) Hypotension (later) 49% will have temp > 100.5 F° 49% will have temp > 100.5 F° Lactic acidosis Lactic acidosis Hypercarbia Hypercarbia

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

25. Edward P. Sloan, MD, MPH Status Epilepticus SE Mortality: SE mortality > 30% when sz longer than 60 minutes SE mortality > 30% when sz longer than 60 minutes Underlying sz etiology contributes to mortality Underlying sz etiology contributes to mortality

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

27. Edward P. Sloan, MD, MPH ED Management SE Rx Timeline: 0-30 min: ABCs, benzos 0-30 min: ABCs, benzos 30-60 min: Phenytoins 30-60 min: Phenytoins 60-90 min: Levetiracetam, phenobarbital, valproate 60-90 min: Levetiracetam, phenobarbital, valproate 90-120 min: Midazolam, propofol 90-120 min: Midazolam, propofol CT, EEG, ICU/OR CT, EEG, ICU/OR

28. Edward P. Sloan, MD, MPH ED Anti-epileptic Drug (AED) Use

29. Edward P. Sloan, MD, MPH Seizure Pharmacotherapy Benzodiazepines Phenytoins Barbiturates Other agents –levetiracetam –propofol –valproate

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

31. Edward P. Sloan, MD, MPH Pharmacotherapy Benzodiazepines: GABA inhibition Diazepam: short acting, limited AMS and protection (intubation more common) Lorazepam: prolonged AMS and protection Pediatric sz: IV lorazepam limits respiratory compromise

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

33. Edward P. Sloan, MD, MPH Pharmacotherapy Phenytoin: Stabilize memb Na + channels, regulate Ca + + channels For generalized sz, and SE Constant infusion over IVP Use pump to prevent comp Therapeutic at 10-20 µg/mL

34. Edward P. Sloan, MD, MPH Oral Phenytoin: Pharmacotherapy Oral Phenytoin: 18mg/kg oral load 64% reach 10mg/mL levels by 8 hrs (therapeutic) Delayed absorption due to large loading, or drug prep

35. Edward P. Sloan, MD, MPH Pharmacotherapy Fosphenytoin: Pro-drug, dose same as pht 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

36. Edward P. Sloan, MD, MPH Pharmacotherapy IV Levetiracetam: Second generation AED Oral and IV bioequivalent Adjunct therapy No therapeutic level defined 1500 to 3000 mg infusion Few adverse effects

37. Edward P. Sloan, MD, MPH Pharmacotherapy IV Phenobarbital: GABA-inhib, effective SE Rx Infuse up to 50 mg/min 20-30 mg/kg, 10 mg/kg doses Therapeutic > 40 µg/mL Respiratory depression Hypotension

38. Edward P. Sloan, MD, MPH Pharmacotherapy 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 Therapeutic > 100 µg/mL

39. Edward P. Sloan, MD, MPH Pharmacotherapy IV Midazolam Infusion: GABA mechanism Equal to diazepam infusion Greater breakthru sz rates Less hypotension –vs. propofol, pentobarb

40. Edward P. Sloan, MD, MPH Pharmacotherapy IV Propofol Infusion: Likely GABA mechanism Provides burst suppression 2 mg/kg loading dose Hypotension, acidosis, hypoventilation Rapid onset, easily reversed

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

42. Edward P. Sloan, MD, MPH Pharmacotherapy ED Treatment Protocol: Have AEDs easily available Rapid sequential AED use Maximize infusion rate Maximize mg/kg dosing Benzos, phenytoins, other bolus AEDs, continuous AEDs

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

44. Edward P. Sloan, MD, MPH ED Patient Outcome

45. Edward P. Sloan, MD, MPH ED Patient Management Lorazepam 2 mg IVP x 5 over 10 minutesLorazepam 2 mg IVP x 5 over 10 minutes Persistent facial and R shoulder activityPersistent facial and R shoulder activity AMS: generalized seizure continuesAMS: generalized seizure continues Fosphenytoin 1 gram PE over 10 minFosphenytoin 1 gram PE over 10 min Seizure ended, pt remained obtundedSeizure ended, pt remained obtunded Intubation immediately followedIntubation immediately followed Lidocaine, sux, rocuroniumLidocaine, sux, rocuronium

46. Edward P. Sloan, MD, MPH ED Diagnostic Evaluation Non-contrast CT: Prior strokes, atrophyNon-contrast CT: Prior strokes, atrophy Metabolic tests normalMetabolic tests normal Toxicology screening negativeToxicology screening negative Phenytoin level cancelledPhenytoin level cancelled Diagnoses:Diagnoses: AMSAMS Status EpilepticusStatus Epilepticus Respiratory FailureRespiratory Failure

47. Edward P. Sloan, MD, MPH Family Arrives, Pt History Pt with history refractory seizures Pt with history refractory seizures Hx carotid artery occlusion R Hx carotid artery occlusion R Due for carotid endarterectomy Due for carotid endarterectomy Phenobarbital & dilantin, compliant Phenobarbital & dilantin, compliant Prior history of SE treated at UIC Prior history of SE treated at UIC No medic alert bracelet No medic alert bracelet No recent illness, trauma, EtOH No recent illness, trauma, EtOH

48. Edward P. Sloan, MD, MPH Patient Outcome EEG in ED, within 150 minutes EEG in ED, within 150 minutes Neuro consultation, no subtle SE Neuro consultation, no subtle SE Admit to Neuro ICU Admit to Neuro ICU Repeated paralytic dosing Repeated paralytic dosing Final disposition for carotid Rx Final disposition for carotid Rx

49. Edward P. Sloan, MD, MPHConclusions ED seizure patient Rx needs to address both the immediate seizure and the long-term epilepsy management In general, ED seizure patient Rx focuses on parenteral AED use Must understand principles that govern ED AED use and priorities of those that provide long-term epilepsy Rx

50. Edward P. Sloan, MD, MPHRecommendations Be able to identify the seizure type and optimal patient therapies based on etiology, demographics, and risk/benefit Establish seizure and SE protocol Stop the acute seizure & prevent SE Wisely prescribe so that follow-up epilepsy management can be optimized

51. Edward P. Sloan, MD, MPH Questions? www.FERNE.org edsloan@uic.edu 312 413 7490 ferne_simeu_2006_sloan_seizure_111006_final 10/17/2015 6:28 PM (11/10 646 am)