J. Stephen Huff, MD

1. What the ACEP Seizure Clinical Policy Doesn’t Tell Us about Adult Seizure and Status Epilepticus Patients…A view from the real clinical world….

2. J. Stephen Huff, MD Associate ProfessorEmergency Medicine and NeurologyDepartment of Emergency MedicineUniversity of Virginia Health SystemCharlottesville, Virginia, United States

3. Objectives • Review Clinical Policy on Seizures… • Discuss policy development • Show limitations of policy development • Demonstrate practical use of policy

4. Process • Present brief case • Review ACEP Clinical Policy • Show policy application and limitations

5. Ann Emerg Med 2004;43:605 Clinical policy: Critical issues in the evaluation and management of adult patients presenting to the emergency department with seizures Not a comprehensive manual No substitute for clinician’s judgment

6. A word about policy development… • Key questions from membership • Subcommittee formation • Literature search • Review and grade literature • Strength of evidence recommendations • Peer and expert review

7. Level of Recommendations • Level A recommendations • High degree of clinical certainty • Strength of evidence Class I or multiple II • Level B recommendations • Reflect moderate clinical certainty • Class II studies or other • Level C recommendations • Preliminary or inconclusive evidence • Panel consensus

8. Clinical History 1 A 21 year-old college student presents to the ED after a witnessed generalized first seizure at a party. His examination is normal at this time. Past medical history is unremarkable. His history and that of his roommates indicate that there was nothing unusual about the evening. Are additional tests necessary?

9. New-Onset Seizure: Lab • What laboratory tests are indicated in the otherwise healthy adult patient with a new-onset seizure who has returned to baseline normal neurologic status?

10. New-Onset Seizure: Lab • Level A recommendations - None

11. New-Onset Seizure: Lab • Level B recommendations • 1. Determine a serum glucose and sodium level on patients with first-time seizure with no comorbidities who have returned to their baseline. • 2. Obtain a pregnancy test if a woman is of child-bearing age. • 3. Perform a lumbar puncture, after a head computed tomography (CT) scan, either in the ED or after admission, on patients who are immunocompromised.

12. New-Onset Seizure: Lab • The policy suggests that a serum glucose and sodium determinations are appropriate in this patient. Would you do anything differently with regard to laboratory testing?

13. Case 1 - Conclusion • The patient and friends had been experimenting with cocaine • Toxicologic analysis confirmed the presence of cocaine metabolites • The cocaine is the likely precipitant of his seizure. This patient should not be given a diagnosis of idiopathic epilepsy nor does he need anti-epileptic medications administered.

14. New-Onset Seizure: Lab • Commentary- Evidence-based recommendations suggest that laboratory work is of limited utility • In practice routine testing is prevalent • An approach directed by history and physical will have higher yield than an undirected approach

15. Clinical History 2 A 30 year-old graduate student comes to the ED with a friend following a generalized convulsion. He is healthy and takes no medications. He had been evaluated and released from the ED after a bicycle accident one week before and had attended classes this week in spite of an unusual headache. His examination is normal at this time. Past medical history is unremarkable. Should imaging be done in the ED?

16. New-Onset Seizure: CT • Which new-onset seizure patients who have returned to a normal baseline require a head CT scan in the ED?

17. New-Onset Seizure: CT • Level A recommendations - None

18. New-Onset Seizure: CT • Level B recommendations • When feasible, perform neuroimaging of the brain in the ED on patients with a first-time seizure. • Deferred outpatient neuroimaging may be used when reliable follow-up is available.

19. New-Onset Seizure: CT • The policy suggests that imaging may be deferred in this patient. Would you do anything different?

20. Picture

21. Case 2 • Imaging showed a large frontal epidural hematoma without midline shift. This illustrates the insensitivity at times of the bedside neurologic examination. The history of recent trauma should trigger the decision to pursue neuroimaging.

22. New-Onset Seizure: CT • Commentary-the history of trauma was the driving force in this case • In US practice, if logistically possible, patients will likely be imaged in the ED • The policy attempts to allow the clinician options if there is difficulty in getting prompt CT, or if elective MRI imaging might be promptly obtained • As technology evolves policy will change

23. Clinical History 3 A visiting clerical worker has a seizure while doing an audit at a local business. He is awake, alert, and examination is normal. There is no seizure history or significant medical history. He blames the event on late hours and poor sleeping quarters. Laboratory evaluation and initial imaging are performed and are unremarkable. What would you do?

24. New-Onset Seizure: Admission • Which new-onset seizure patients who have returned to normal baseline need to be admitted to the hospital and/or started on an antiepileptic drug?

25. New-Onset Seizure: Admission • Level A recommendations - None • Level B recommendations - None

26. New-Onset Seizure: Admission • Level C recommendations • Patients with a normal neurologic examination can be discharged from the ED with outpatient follow-up. • Patients with a normal neurologic examination, no comorbidities, and no known structural brain disease do not need to be started on an antiepileptic drug in the ED.

27. New-Onset Seizure: Admission • The policy suggests that this patient may be discharged for outpatient follow-up without starting on medications… • Do you agree?

28. New-Onset Seizure: Admission • Level C recommendations • Patients with a normal neurologic examination can be discharged from the ED with outpatient follow-up. • Patients with a normal neurologic examination, no comorbidities, and no known structural brain disease do not need to be started on an antiepileptic drug in the ED.

29. Case 3 • The early seizure recurrence risk is simply not known. If discharged, the patient must have a stable social situation. Staying alone in a hotel room is not sufficient. • Perhaps the best option is to admit the patient for observation and an expedited diagnostic work-up

30. New-Onset Seizure: Admission • Commentary-Policy attempts to recognize the varied approach to this patient type • “new-onset seizures do not need to be admitted”- with reservations • normal exam • structurally normal brain • safety

31. Case 4 • A patient with a known seizure disorder for many years and a history of good seizure control presents to the ED after a seizure. He admits that he has missed his only medication, phenytoin, for several days. A phenytoin level is very low.

32. Effective Dosing: Phenytoin • What are effective phenytoin or fosphenytoin dosing strategies for preventing seizure recurrence in patients who present to the ED after having had a seizure with a subtherapeutic serum phenytoin level?

33. Effective Dosing: Phenytoin • Level A recommendations • None specified • Level B recommendations • None specified

34. Effective Dosing: Phenytoin • Level C recommendations • Administer an intravenous or oral loading dose of phenytoin or intravenous or intramuscular fosphenytoin, and restart daily oral maintenance dosing.

35. Case 4 • What would you do? • IV phenytoin or fosphenytoin? • PO phenytoin loading strategy? How? • Resume medications?

36. Case 4 • The patient is given an oral loading of phenytoin at 18 mg/kg and started back on his seizure medication. He has some nausea following the medication

37. Effective Dosing: Phenytoin • Commentary- No data exist to rationally guide therapy • The risk of early seizure recurrence in this patient population is not known

38. Case 5 • A patient with a history of difficult-to-control seizures presents to the emergency department minimally responsive after a flurry of seizures. There have been at least three witnessed seizures while in route. Current medications include valporate and levetiracetam.

39. Case 5 • Airway control is thought to be adequate when supplemented with a nasopharyngeal airway • Lorazepam 4 mg is administered intravenously • Phenytoin loading is accomplished

40. Status Epilepticus: Refractory • What agent(s) should be administered to a patient in status epilepticus who continues to seize after having received a benzodiazepine and a phenytoin?

41. Status Epilepticus: Refractory • Level A recommendations • None specified • Level B recommendations • None specified

42. Status Epilepticus: Refractory • Level C recommendations • Administer 1 of the following agents intravenously • “high-dose phenytoin” • phenobarbital • valproic acid • midazolam infusion • pentobarbital infusion • propofol infusion.

43. Case 5 • The clinical policy intimates that many options are equally effective (or ineffective). • What would you do in this case? • What would you do? • Which drug? • How much?

44. Case 5 • Many opinions • No data exist to guide specific therapies • Reasonable to empirically administer valproate in this patient, particularly if levels are demonstrated to be low

45. Status Epilepticus: Refractory • Commentary- Many options possible without clear superiority of one regimen • Midazolam infusion • Propofol infusion

46. Case 6 • A patient with a known seizure disorder and static encephalopathy (cerebral palsy) has a seizure • Normally walks with assistive devices but is high-functioning intellectually • Lives with family and takes two medications for seizures, valproate and carbamazepine

47. Case 6 • He receives lorazepam 4 mg IV in route to the hospital • No further generalized convulsive activity is observed • Occasional twitching of the eyelids with jerking of the eyes to the left • Not awakening after 30 minutes

48. EEG in ED • When should EEG testing be performed in the ED?

49. EEG in ED • Level A recommendations • None specified • Level B recommendations • None specified

50. EEG in ED • Level C recommendations • Consider an emergent EEG in patients suspected of being in nonconvulsive status epilepticus or in subtle convulsive status epilepticus, patients who have received a long-acting paralytic, or patients who are in drug-induced coma.