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

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

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

4. Edward P. Sloan, MD, MPH 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

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

6. Board Chairman and President FERNE Board Chairman and President FERNE Chicago, IL

7. 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.

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

9. Today’s Agenda Present a clinical casePresent a clinical case Review seizure and SE clinical dataReview seizure and SE clinical data Discuss ED managementDiscuss ED management Provide fosphenytoin dataProvide fosphenytoin data Consider fosphenytoin useConsider fosphenytoin use Examine the patient outcomeExamine the patient outcome Close with a bonus caseClose with a bonus case

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

11. 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

12. 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

13. 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

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

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

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

17. Edward P. Sloan, MD, MPH Seizures Seizure Classification: Generalized: both cerebral hemispheres Generalized: both cerebral hemispheres Partial: one cerebral hemisphere (localized) Partial: one cerebral hemisphere (localized)

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

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 Seizures Partial Seizures: Simple partial: no impaired consciousness Simple partial: no impaired consciousness Complex partial: impaired consciousness Complex partial: impaired consciousness

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

22. Edward P. Sloan, MD, MPH Seizures Recurrent Seizure Risk 51% recurrence risk 51% recurrence risk 75% of recurrent sz occur within 2 years of first sz 75% of recurrent sz occur within 2 years of first sz Only a small % of pts will seize within 24 h Only a small % of pts will seize within 24 h Partial sz, CNS abnormality Partial sz, CNS abnormality

23. 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)

24. Edward P. Sloan, MD, MPH Status Epilepticus SE Epidemiology: Risk of SE: greatest at age extremes (pediatric and geriatric populations) Risk of SE: greatest at age extremes (pediatric and geriatric populations) SE: occurs in setting of new onset sz, acute insult, or chronic epilepsy SE: occurs in setting of new onset sz, acute insult, or chronic epilepsy 150,000 cases per year 150,000 cases per year

25. 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

26. 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

27. Edward P. Sloan, MD, MPH Systemic Effects: Seizures/SE Systemic 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

28. Edward P. Sloan, MD, MPH Seizures/SE Pathophysiology: Glutamate toxic mediator Glutamate toxic mediator Necrosis occurs even if systemic problems are treated (HTN, fever, rhabdomyolysis, resp acidosis, hypoxia) Necrosis occurs even if systemic problems are treated (HTN, fever, rhabdomyolysis, resp acidosis, hypoxia)

29. Edward P. Sloan, MD, MPH Seizures/SE Pathophysiology: Early compensation for increased CNS metabolic needs Early compensation for increased CNS metabolic needs Decompensation at 40-60 minutes, associated with tissue necrosis Decompensation at 40-60 minutes, associated with tissue necrosis

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

31. Edward P. Sloan, MD, MPH Seizures/SE 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

32. 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

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

34. Edward P. Sloan, MD, MPH Status Epilepticus Refractory SE: No response to first-line drugs (Benzos, phenytoins) No response to first-line drugs (Benzos, phenytoins) Significant CNS disorders Significant CNS disorders 6-9% of all SE cases 6-9% of all SE cases 20-30% mortality 20-30% mortality

35. 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

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

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

38. Edward P. Sloan, MD, MPH ED Management CT Neuroimaging: Req’d in new-onset sz Req’d in new-onset sz Useful with focal sz, change in sz type or frequency, co- morbidity Useful with focal sz, change in sz type or frequency, co- morbidity Non-contrast unless mass lesion suspected Non-contrast unless mass lesion suspected

39. Edward P. Sloan, MD, MPH New Onset Sz in Pregnancy 32 year old Hispanic female 23 weeks pregnant G3P2 two live births, no complications New onset seizure at 530 am in bed Generalized tonic-clonic seizure Brief, self-limited, no Rx required EMS to the ED, no seizure recurrence

40. Edward P. Sloan, MD, MPH

41. Focal hemorrhage

42. Edward P. Sloan, MD, MPH New Onset Sz in Pregnancy –Tertiary center diagnosis: cavernoma –Started on an anti-epileptic drug –No immediate need for operative intervention –Will follow as pregnancy progresses

43. Edward P. Sloan, MD, MPH ED Management MRI Neuroimaging: Useful with refractory sz Useful with refractory sz Complements plain CT Complements plain CT Can be done as outpatient Can be done as outpatient

44. Edward P. Sloan, MD, MPH ED Management EEG Monitoring: Use to rule out subtle SE Use to rule out subtle SE Two-lead EEG in ED, within 120 minutes Two-lead EEG in ED, within 120 minutes In RSI, prolonged coma, propofol or pentobarbital induced coma In RSI, prolonged coma, propofol or pentobarbital induced coma

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

46. 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

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

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

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

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

51. Edward P. Sloan, MD, MPH Pharmacotherapy Clinical Setting: Three seizure settingsThree seizure settings Self-limited seizure, load req’dSelf-limited seizure, load req’d Flurry of seizures, at-risk for SEFlurry of seizures, at-risk for SE Status epilepticusStatus epilepticus Provides framework for discussionProvides framework for discussion

52. 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

53. 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

54. 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

55. 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

56. 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

57. 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

58. Adverse Events Following IV CEREBYX ® or IV Phenytoin Cerebyx ® (fosphenytoin sodium injection) [package insert]. Morris Plains, NJ: Warner- Lambert; 2002. Refer to full Prescribing Information for the full adverse events incidence. Pruritis unique to fospht

59. Edward P. Sloan, MD, MPH Pharmacotherapy Fosphenytoin: Cost-effective in 6 settings –Rapid infusion in “at-risk pts” –Rapid infusion in SE –High-risk IV access –No IV access (IM) –No cardiac monitoring (IM) –Poor patient compliance

60. Edward P. Sloan, MD, MPH Fosphenytoin Rapid Infusion in “At-risk” Pts: Infuse at 100-150 mg/min Infuse at 100-150 mg/min Load in 10-20 minutes Load in 10-20 minutes Therapeutic after diazepam Therapeutic after diazepam Limits lorazepam use Limits lorazepam use Lowers monitoring need Lowers monitoring need

61. Edward P. Sloan, MD, MPH Fosphenytoin Rapid Infusion in SE: Infuse at 150 mg/min in SE Infuse at 150 mg/min in SE One gram infusion in 7 min One gram infusion in 7 min Full 20 mg/kg load in 10 min Full 20 mg/kg load in 10 min 30 mg/kg load in 15 min 30 mg/kg load in 15 min Fos resuscitation, next AED Fos resuscitation, next AED

62. CEREBYX ® and IV Phenytoin: Comparable Pharmacokinetic Profiles Time After Start of Infusion (min) Mean Plasma-Free Phenytoin Concentration (  g/mL) Cerebyx ® (fosphenytoin sodium injection) [package insert]. Morris Plains, NJ: Warner- Lambert; 2002. Always consult full Prescribing Information in package insert. N = 12 Similar time to therapeutic free phenytoin level

63. 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

64. Edward P. Sloan, MD, MPH Fosphenytoin High-risk IV Access Murphy’s Law Murphy’s Law Extravasations will occur Extravasations will occur Long-term complications go undetected by ED physicians Long-term complications go undetected by ED physicians Consider your preferences Consider your preferences

65. Edward P. Sloan, MD, MPH Fosphenytoin No IV Access IVDA in lock-up, prevent SEIVDA in lock-up, prevent SE Must achieve adequate levelMust achieve adequate level Avoid ED problemsAvoid ED problems ED nurse time, agitationED nurse time, agitation Adverse exposure riskAdverse exposure risk Prolonged ED throughput timeProlonged ED throughput time

66. Edward P. Sloan, MD, MPH Fosphenytoin No IV Access Out of hospital settingOut of hospital setting Protocol in EMS settingProtocol in EMS setting Long transports in rural EMSLong transports in rural EMS Specialty care providersSpecialty care providers Nursing homesNursing homes Private MD officesPrivate MD offices

67. Pain Scores at Injection Site Following IM Administration of CEREBYX ® or Saline Adapted with permission from Pryor FM et al. Epilepsia. 2001;42:245-250. Always consult full Prescribing Information in package insert. Subjects (%) 1-Hour Follow-up Immediately Post-Injection (10 mg PE/kg) IM fos pain similar to IM saline

68. IM CEREBYX ® Administered at a Single and Multiple Sites (N = 3) (N = 4) (N = 11) (N = 3) (N = 11)(N = 12) (N = 3) (N = 13) 100 Ramsay RE et al. Epilepsy Res. 1997;28:181-187. Always consult full Prescribing Information in package insert. 14 pts, 15+cc IM injection

69. Edward P. Sloan, MD, MPH Fosphenytoin No Cardiac Monitoring ED overcrowdingED overcrowding High acuity, stretched resourcesHigh acuity, stretched resources Utilize IM loadingUtilize IM loading No need for monitoringNo need for monitoring Less risk of hypotensionLess risk of hypotension No unplanned rapid infusionNo unplanned rapid infusion More disposition optionsMore disposition options

70. Edward P. Sloan, MD, MPH Fosphenytoin Poor Patient Compliance Pt refuses to stay for infusionPt refuses to stay for infusion About to enter high risk settingAbout to enter high risk setting Utilize IM loadingUtilize IM loading Rapidly therapeuticRapidly therapeutic Half load IM, half POHalf load IM, half PO Reduced SE riskReduced SE risk Rapid dispo, not AMARapid dispo, not AMA

71. Edward P. Sloan, MD, MPH Fosphenytoin Use in Elderly Patients Caution with hypotension when rapidly infused Caution with hypotension when rapidly infused CVA neuroprotection study CVA neuroprotection study Related to phenytoin moiety Related to phenytoin moiety Rate related, slow infusion Rate related, slow infusion

72. Edward P. Sloan, MD, MPH Fosphenytoin Use in Pediatric Patients Used in infants and children Used in infants and children Reasonable to use in all ages Reasonable to use in all ages Safety not an issue Safety not an issue IM and IV use both possible IM and IV use both possible Neonate indication and use: in consultation with peds neurology Neonate indication and use: in consultation with peds neurology

73. 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

74. 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

75. 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 Per mg/kg load, level up 5 µg/mL

76. Edward P. Sloan, MD, MPH IV Lidocaine: Pharmacotherapy IV Lidocaine: Third-line, stabilizes membrane Na + /K + pump Decreased neuron excitability, refractory GCSE 3 mg/kg Not effective relative to others

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

78. 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

79. 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

80. 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

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

82. Edward P. Sloan, MD, MPH ACEP Seizure/SE Clinical Policy

83. Edward P. Sloan, MD, MPH Evidence Based Guidelines Define the clinical question –Focused questions best –Outcome measure must be determined Grade the strength of evidence Incorporate practice patterns, available expertise, resources and risk/benefit

84. Edward P. Sloan, MD, MPH ACEP Clinical Policies Identify questions of clinical importance to ED practitioners Analyze the quality of data available related to disease state Differentiate anecdotal experience from practice supported by evidence

85. Edward P. Sloan, MD, MPH Evidence Strength Strength (Class) of evidence –I: Randomized, double blind interventional studies for therapeutic effectiveness; prospective cohort for diagnostic testing or prognosis –II: Retrospective cohorts, case control studies, cross-sectional studies –III: Observational reports; consensus reports Evidence strength downgraded if flawed methodologically

86. Edward P. Sloan, MD, MPH Recommendation Strength Strength of recommendations: – A (Standard): High degree of certainty based on Class I studies – B (Guideline): Moderate clinical certainty based on Class II studies – C (Option): Inconclusive certainty based on Class III evidence, consensus

87. Edward P. Sloan, MD, MPH

88. New Onset Sz: Lab Testing What lab tests are indicated in the otherwise healthy adult patient with a new onset seizure who has returned to a baseline normal neurological status? (Outcome measure: abnormal lab that changes management)

89. Edward P. Sloan, MD, MPH New Onset Sz: Lab Testing Level B recommendations: –Determine a serum glucose and sodium on patients with a first time seizure with no co-morbidities who have returned to their baseline –Obtain a pregnancy test in women of child bearing age –Perform a LP after a head CT either in the ED or after admission on patients who are immuno- compromised

90. Edward P. Sloan, MD, MPH New Onset Sz: Neuroimaging Which new onset seizure patients who have returned to a normal baseline require neuroimaging in the ED? (Outcome measure: abnormal CT)

91. Edward P. Sloan, MD, MPH Level B recommendations: –When feasible, perform a head CT of the brain in the ED on patients with a first time seizure –Deferred outpatient neuroimaging may be utilized when reliable follow-up is available New Onset Sz: Neuroimaging

92. Edward P. Sloan, MD, MPH New Onset Sz: Dispo/AED Use Which new onset seizure patients who have returned to normal baseline need to be admitted to the hospital and / or started on an AED? (Outcome measure: short term morbidity or mortality)

93. Edward P. Sloan, MD, MPH New Onset Sz: Dispo/AED Use Level C recommendations: –Patients with a normal neurological examination can be discharged from the ED with outpatient follow-up –Patients with a normal neurological examination and no co-morbidities and no know structural brain disease do not need to be started on an anti- epileptic drug in the ED

94. Edward P. Sloan, MD, MPH Sz/SE: Phenytoin Loading What are effective phenytoin dosing strategies for preventing seizure recurrence in patients who present to the ED with a sub-therapeutic serum phenytoin level? (Outcome measure: short term seizure recurrence)

95. Edward P. Sloan, MD, MPH Sz/SE: Phenytoin Loading –Level C recommendation: −Administer an intravenous or oral loading dose of phenytoin or intravenous or intramuscular fosphenytoin, and restart daily oral maintenance dosing.

96. Edward P. Sloan, MD, MPH Sz/SE SE Therapeutics What agent(s) should be administered to a patient in status who continues to seize despite a loading dose of a benzodiazepine and a phenytoin? (Outcome measure: cessation of motor activity)

97. Edward P. Sloan, MD, MPH Sz/SE SE Therapeutics Level C recommendation: –Administer one of the following agents intravenously: “high- dose phenytoin,” phenobarbital, valproic acid, midazolam infusion, pentobarbital infusion, or propofol infusion.

98. Edward P. Sloan, MD, MPH Sz/SE: EEG Monitoring When should an EEG be performed in the ED?

99. Edward P. Sloan, MD, MPH Sz/SE: EEG Monitoring Level C recommendation: –Consider an emergent EEG for patients suspected of being in non- convulsive SE or in subtle convulsive SE, for patients who have received a long-acting paralytic, or for patients who are in a drug-induced coma.

100. Edward P. Sloan, MD, MPH ACEP Summary Evidence based clinical policies are useful tools in clinical decision making Policy does not create a “standard of care” Provides a foundation for clinical practice at a national level The current literature does not support the creation of any “level A” recommendations –2 of the 6 clinical questions have sufficient evidence to support “level B” recommendations –4 of the 6 recs are “level C”

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

102. 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

103. 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

104. 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

105. 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

106. Edward P. Sloan, MD, MPHConclusions Effective ED seizure patient Rx is critical to good long-term outcome Parenteral ED AED use can be easily implemented for effectiveness Must understand principles that govern ED AED use and priorities of those that provide long-term epilepsy Rx Those principles are fortunately simple and straightforward

107. 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 Understand fully the optimal use of all parenteral and 2 nd generation AEDs Stop the acute seizure & prevent SE Wisely prescribe so that follow-up epilepsy management can be optimized

108. Edward P. Sloan, MD, MPH Questions? www.FERNE.org edsloan@uic.edu 312 413 7490 ferne_2007_stcatherine_sloan_seizures_final 5/2/2015 1:30 AM