Edward P. Sloan, MD, MPH, FACEP

1. The ED Treatment of Seizure and SE Patients:What the 2004 ACEP Seizure Clinical Policy Doesn’t Tell You Edward P. Sloan, MD, MPH, FACEP 1

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

3. Attending PhysicianEmergency MedicineUniversity of Illinois HospitalOur Lady of the Resurrection HospitalChicago, IL Edward P. Sloan, MD, MPH, FACEP 3

5. Global Objectives • Learn more about seizures • Increase awareness of Rx options • Enhance our ED management • Improve patient care & outcomes • Maximize staff & patient satisfaction

6. Session Objectives • Discuss what the policy doesn’t tell us • Provide seizure and SE concepts • Examine epidemiology, diagnosis, ED Rx • Generate a common perspective • Highlight areas for improvement • Outline opportunities • Develop a plan

7. Clinical History • 24 yo female • EMS to ED • Generalized seizure at home • CFD: IV diazepam, resolved • Hx seizure since childhood • On Depakote • No recent BHT • No recent illness

8. ED Presentation • Post-ictal in ED • Non-focal neurological exam • No evidence of trauma or toxicity • Appropriate, verbal, answers questions • Has recurrent generalized seizure • Prolonged duration (>5 min) • Is this patient an outlier? • What is his optimal management?

9. What the 2004 ACEP Seizure Clinical PolicyDoesn’t Tell Us Edward P. Sloan, MD, MPH, FACEP 9

10. Important Sz/SE Info • What is the pathology that we treat? • How do we simply classify Sz/SE? • What is an acceptable SE protocol? • What is the time frame for Rx?

11. Important Sz/SE Info • What therapies can be used? • What therapies should be used? • Based on what evidence and consensus should these decisions be made? • Why? In which patients?

12. Epidemiology & Pathophysiology Edward P. Sloan, MD, MPH, FACEP 12

13. Seizure Epidemiology • Epilepsy in 1/150 people • For each epilepsy pt, 1 ED visit every 4 years • 1-2% of all ED visits • Toxic/metabolic, febrile, non-compliance, trauma

14. Seizure Mechanism • Sz = abnormal neuronal discharge with recruitment of otherwise normal neurons • Loss of GABA inhibition

15. Status Epilepticus • Seizure > 5- 10 minutes • Two seizures without a lucid interval • Assumes ongoing seizure activity during time of diminished responsiveness

16. SE Pathophysiology • Early compensation meets increased CNS metabolic needs (SBP, CBF ↑↑) • Failure at 40-60 minutes, (SBP, CBF ↓↓) • CNS tissue necrosis, adverse sequelae

17. SE Pathophysiology • Glutamate toxic mediator • CNS necrosis even if systemic complications fully mitigated • HTN, fever, rhabdomyolysis, hypercarbia, hypoxia, infection

18. AMS in Seizures/SE • Mental status should improve by 20-40 minutes • If pt remains comatose, consider subtle SE & EEG • Up to 20% of comatose pts in are in subtle SE

19. Status EpilepticusSE Epidemiology: • Risk of SE: greatest at age extremes (pediatric and geriatric populations) • SE: occurs in setting of new onset sz, acute insult, or chronic epilepsy • 150,000 cases per year

20. Status EpilepticusSystemic SE Effects: • Hypertension (early) • Hypotension (later) • 49% Temp > 100.5 F° • Lactic acidosis (pH < 7.00) • Hypercarbia (increased pCO2)

21. Status EpilepticusOngoing SE Effects: • Over 40-60 min, loss of metabolic compensation • With ongoing SE, systemic BP & CBF drop

22. Status EpilepticusSE Mortality: • SE mortality > 30% when sz longer than 60 minutes • Underlying sz etiology contributes to mortality

23. New-Onset: Sz Recurrence • 51% seizure recurrence risk • 75% of recurrent seizures occur within 2 years of first sz • Within 24 hours of ED visit: a small % will seize (1%) • Partial sz, CNS abn inc risk

24. Seizure and SE Patient Classification Edward P. Sloan, MD, MPH, FACEP 24

25. Seizure Classification • Generalized: both cerebral hemispheres • Partial: one cerebral hemisphere (localized)

26. Generalized Seizures • Convulsive: tonic-clonic • Non-convulsive: absence

27. Generalized Seizures • Primary generalized: starts as tonic-clonic sz • Secondarily generalized: tonic-clonic sz from a non-convulsive partial sz, ie aura (common)

28. Partial Seizures • Simple partial: no impaired consciousness • Complex partial: impaired consciousness

29. Specific Seizure Types • Absence: Petit mal • Partial: Jacksonian, focal motor • Complex partial: temporal lobe, psychomotor

30. SE Classification • GCSE: Generalized convulsive SE Tonic-clonic motor activity • Non-GCSE

31. 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

32. Subtle SE • Severe insult, ie hypoxic • Comatose • Limited motor activity • Mortality exceeds 50% • Stop the seizure • EEG confirmation

33. Refractory SE • No response to first-line drugs (Benzos, phenytoins) • Severe CNS pathology • 6-9% of all SE cases • Overlap with subtle SE Dx??

34. Seizure and SE Patient Management Edward P. Sloan, MD, MPH, FACEP 34

35. Seizure/SE Pharmacotherapy • Benzodiazepines • Phenytoins • Barbiturates • Other agents • valproate • propofol • lidocaine

36. ED SE Treatment • 0-30 min: ABCs, benzos • 30-45 min: Phenytoins • 45-75 min: Phenobarb/valproate • 75-90 min: Propofol/midazolam • 90-150 min: CT, EEG, ICU/OR

37. ED AED Use: Concepts • Most drugs are at least 80% effective in Rx seizures, SE • Utilize a protocol • Have AEDs available in ED • Maximize infusion rate in SE • Provide full mg/kg doses

38. ED ManagementAED loading: • Repeated seizures, high-risk population, significant SE risk • No need to determine level in ED after loading • Oral loading in low risk pts

39. PharmacotherapyBenzodiazepines: • GABA inhibition • Diazepam: short acting, limited AMS and protection (intubation more common) • Lorazepam: prolonged AMS and protection • Pediatric sz: IV lorazepam limits respiratory compromise

40. PharmacotherapyRectal Diazepam: • Diazepam rectal gel pre-packaged for rapid use • Dose 0.5 mg/kg, less respiratory depression seen than with IV use

41. PharmacotherapyPhenytoin: • 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

42. PharmacotherapyOral Phenytoin: • 18mg/kg oral load • 64% reach 10mg/mL levels by 8 hrs (therapeutic) • Delayed absorption due to large loading, or drug prep

43. PharmacotherapyFosphenytoin: • 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

44. PharmacotherapyFosphenytoin: • Cost-effective in 5 settings • Rapid infusion in SE • High-risk IV access • No IV access (IM) • No cardiac monitoring (IM) • Poor patient compliance

45. PharmacotherapyIV 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

46. PharmacotherapyIV 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

47. PharmacotherapyLidocaine: • Third-line, stabilizes membrane Na + /K + pump • Decreased neuron excitability, refractory GCSE • 3 mg/kg

48. PharmacotherapyIV Propofol Infusion: • Likely GABA mechanism • Provides burst suppression • 2 mg/kg loading dose • Hypotension, acidosis, hypoventilation • Rapid onset, easily reversed

49. PharmacotherapyIV Midazolam Infusion: • GABA mechanism • Equal to diazepam infusion • Greater breakthru sz rates • Less hypotension • Vs. propofol, pentobarb

50. PharmacotherapyIV Pentobarbital: • Likely GABA mechanism • Provides burst suppression • 5 mg/kg loading dose • 25 mg/kg infusion rate • ICU monitoring required