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

2 Professor & Research Development Director Department of Emergency Medicine, University of Illinois at Chicago Chicago, IL Edward Sloan, MD, MPH, FACEP

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

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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 Edward P. Sloan, MD, MPH, FACEP 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 Edward P. Sloan, MD, MPH, FACEP 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 Edward P. Sloan, MD, MPH, FACEP 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?

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

10 Edward P. Sloan, MD, MPH, FACEP 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 Edward P. Sloan, MD, MPH, FACEP 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?

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

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

15 Edward P. Sloan, MD, MPH, FACEP Status Epilepticus Seizure > minutes Two seizures without a lucid interval Assumes ongoing seizure activity during time of diminished responsiveness

16 Edward P. Sloan, MD, MPH, FACEP SE Pathophysiology Early compensation meets increased CNS metabolic needs (SBP, CBF ↑↑) Failure at minutes, (SBP, CBF ↓↓) CNS tissue necrosis, adverse sequelae

17 Edward P. Sloan, MD, MPH, FACEP SE Pathophysiology Glutamate toxic mediator CNS necrosis even if systemic complications fully mitigated HTN, fever, rhabdomyolysis, hypercarbia, hypoxia, infection

18 Edward P. Sloan, MD, MPH, FACEP AMS in Seizures/SE Mental status should improve by minutes If pt remains comatose, consider subtle SE & EEG Up to 20% of comatose pts in are in subtle SE

19 Edward P. Sloan, MD, MPH, FACEP Status Epilepticus SE 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 Edward P. Sloan, MD, MPH, FACEP Status Epilepticus Systemic SE Effects: Hypertension (early) Hypotension (later) 49% Temp > F° Lactic acidosis (pH < 7.00) Hypercarbia (increased pCO2)

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

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

23 Edward P. Sloan, MD, MPH, FACEP 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

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

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

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

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

28 Edward P. Sloan, MD, MPH, FACEP Partial Seizures Simple partial: no impaired consciousness Complex partial: impaired consciousness

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

30 Edward P. Sloan, MD, MPH, FACEP SE Classification GCSE: Generalized convulsive SE Tonic-clonic motor activity Non-GCSE

31 Edward P. Sloan, MD, MPH, FACEP 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 Edward P. Sloan, MD, MPH, FACEP Subtle SE Severe insult, ie hypoxic Comatose Limited motor activity Mortality exceeds 50% Stop the seizure EEG confirmation

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

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

35 Edward P. Sloan, MD, MPH, FACEP Seizure/SE Pharmacotherapy Benzodiazepines Phenytoins Barbiturates Other agents -valproate -propofol -lidocaine

36 Edward P. Sloan, MD, MPH, FACEP ED SE Treatment 0-30 min: ABCs, benzos min: Phenytoins min: Phenobarb/valproate min: Propofol/midazolam min: CT, EEG, ICU/OR

37 Edward P. Sloan, MD, MPH, FACEP 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 Edward P. Sloan, MD, MPH, FACEP ED Management 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

39 Edward P. Sloan, MD, MPH, FACEP 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

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

41 Edward P. Sloan, MD, MPH, FACEP 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 µg/mL

42 Edward P. Sloan, MD, MPH, FACEP 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

43 Edward P. Sloan, MD, MPH, FACEP Pharmacotherapy Fosphenytoin: Pro-drug, dose same as pht Infuse at 150 mg/min in SE Can be given IM up to 20cc Level µg/mL Delayed level: 2h IV, 4 h IM

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

46 Edward P. Sloan, MD, MPH, FACEP Pharmacotherapy IV Valproate: Likely GABA mechanism Useful in peds, possibly SE Rate up to 300 mg/min mg/kg, 3-6 mg/kg/min Therapeutic > 100 µg/mL

47 Edward P. Sloan, MD, MPH, FACEP Lidocaine: Pharmacotherapy Lidocaine: Third-line, stabilizes membrane Na + /K + pump Decreased neuron excitability, refractory GCSE 3 mg/kg

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

49 Edward P. Sloan, MD, MPH, FACEP Pharmacotherapy IV Midazolam Infusion: GABA mechanism Equal to diazepam infusion Greater breakthru sz rates Less hypotension -Vs. propofol, pentobarb

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

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

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

53 Edward P. Sloan, MD, MPH, FACEP Seizure/SE Pharmacotherapy 2nd Generation AEDs Currently used as outpt Rx Soon available in ED What role in ED SE Rx?

Seizure and SE Protocols and the ACEP Policy 54 Edward P. Sloan, MD, MPH, FACEP

55 Edward P. Sloan, MD, MPH, FACEP SE Protocols Limited use within hospitals No defined AEDs No optimal Rx time period Lack of uniformity Suboptimal patient outcome

56 Edward P. Sloan, MD, MPH, FACEP ED Management SE Rx Timeline: 0-30 min: ABCs, benzos min: Phenytoins min: Phenobarb/valproate min: Propofol/midazolam min: CT, EEG, ICU/OR

57 Edward P. Sloan, MD, MPH, FACEP ACEP Clinical Policy What % pts continue to seize? How to Rx new onset sz pts? Optimal phenytoin loading? What Rx if benzodiazepines fail? When is an EEG indicated? Annals of Emer Med, May 2004

58 Edward P. Sloan, MD, MPH, FACEP New Onset Sz: Laboratory 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 is abnormal test that changes management)

59 Edward P. Sloan, MD, MPH, FACEP New Onset Sz: Laboratory Testing Level A recommendations: None 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

60 Edward P. Sloan, MD, MPH, FACEP 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)

61 Edward P. Sloan, MD, MPH, FACEP Level A recommendations: None 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

62 Edward P. Sloan, MD, MPH, FACEP New Onset Sz: Disposition/AED Loading 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)

63 Edward P. Sloan, MD, MPH, FACEP New Onset Sz: Disposition/AED Loading Level A recommendations: None Level B recommendations: None 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

64 Edward P. Sloan, MD, MPH, FACEP 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)

65 Edward P. Sloan, MD, MPH, FACEP Sz/SE: Phenytoin Loading -Level A recommendations. None -Level B recommendations. None -Level C recommendations: Administer an intravenous or oral loading dose of phenytoin or intravenous or intramuscular fosphenytoin, and restart daily oral maintenance dosing.

66 Edward P. Sloan, MD, MPH, FACEP 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)

67 Edward P. Sloan, MD, MPH, FACEP Sz/SE SE Therapeutics Level A recommendations. None Level B recommendations. None Level C recommendations: -Administer one of the following agents intravenously: “high-dose phenytoin,” phenobarbital, valproic acid, midazolam infusion, pentobarbital infusion, or propofol infusion.

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

69 Edward P. Sloan, MD, MPH, FACEP Sz/SE: EEG Monitoring Level A recommendations. None Level B recommendations. None Level C recommendations: -Consider an emergent EEG in patients suspected of being in non-convulsive status epilepticus or in subtle convulsive status epilepticus, patients who have received a long-acting paralytic, or patients who are in a drug-induced coma.

70 Edward P. Sloan, MD, MPH, FACEP ACEP Clinical Policy Evidence based clinical policies are useful tools in clinical decision making Clinical policies do not create a “standard of care” but do provide a foundation for clinical practice at a national level The current literature on acute seizure management does not support the creation of any “level A” recommendations -Only 2 of the 6 clinical questions have sufficient evidence to support “level B” recommendations -4 of the 6 recommendations are “level C”

The Treatment of Status Epilepticus Patients in 2005: A Look at the EFA Working Group’s 1993 JAMA Guidelines 71 Edward P. Sloan, MD, MPH, FACEP

72 Edward P. Sloan, MD, MPH, FACEP EFA Guideline: Key Learning Points SE is an important ED problem New therapeutic options exist 2004 ACEP clinical policy useful AAN EFA update will improve care Fundamental approach will not change -Have a plan, quickly utilize multiple drugs -Fully dose on a mg/kg basis -Aggressively utilize resources

73 Edward P. Sloan, MD, MPH, FACEP Key Learning Points The ACEP seizure policy is useful Important questions remain Issues exist because of limited info Which therapy for which patient? How to maximize patient outcomes and clinical practice? Continue to learn!

Questions?? Edward P. Sloan, MD, MPH Questions?? Edward P. Sloan, MD, MPH ferne_acep_2005_spring_sloan_szse_addinfo.ppt 3/3/2005 8:00 PM 74 Edward P. Sloan, MD, MPH, FACEP