The ED Treatment of Seizure and SE Patients: What the 2004 ACEP Seizure Clinical Policy Doesnt Tell

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The ED Treatment of Seizure and SE
PatientsWhat the 2004 ACEP Seizure Clinical
Policy Doesnt Tell You
Edward P. Sloan, MD, MPH, FACEP
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Edward Sloan, MD, MPH, FACEP

• Professor
• Research Development Director
• Department of Emergency Medicine, University of
  Illinois at Chicago
• Chicago, IL
• (edsloan_at_uic.edu)

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Attending PhysicianEmergency
MedicineUniversity of Illinois HospitalOur
Lady of the Resurrection HospitalChicago, IL
Edward P. Sloan, MD, MPH, FACEP
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(No Transcript)
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Global Objectives

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

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Session Objectives

• Discuss what the policy doesnt 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

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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

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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 (gt5 min)
• Is this patient an outlier?
• What is his optimal management?

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What the 2004 ACEP Seizure Clinical
PolicyDoesnt Tell Us
Edward P. Sloan, MD, MPH, FACEP
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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?

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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?

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

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Seizure Mechanism

• Sz abnormal neuronal discharge with recruitment
  of otherwise normal neurons
• Loss of GABA inhibition

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Status Epilepticus

• Seizure gt 5- 10 minutes
• Two seizures without a lucid interval
• Assumes ongoing seizure activity during time of
  diminished responsiveness

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SE Pathophysiology

• Early compensation meets increased CNS metabolic
  needs (SBP, CBF ??)
• Failure at 40-60 minutes, (SBP, CBF ??)
• CNS tissue necrosis, adverse sequelae

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SE Pathophysiology

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

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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

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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

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Status EpilepticusSystemic SE Effects

• Hypertension (early)
• Hypotension (later)
• 49 Temp gt 100.5 F
• Lactic acidosis (pH lt 7.00)
• Hypercarbia (increased pCO2)

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Status EpilepticusOngoing SE Effects

• Over 40-60 min, loss of metabolic compensation
• With ongoing SE, systemic BP CBF drop

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Status EpilepticusSE Mortality

• SE mortality gt 30 when sz longer than 60 minutes
• Underlying sz etiology contributes to mortality

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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

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

• Generalized both cerebral hemispheres
• Partial one cerebral hemisphere (localized)

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Generalized Seizures

• Convulsive tonic-clonic
• Non-convulsive absence

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Generalized Seizures

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

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Partial Seizures

• Simple partial
• no impaired consciousness
• Complex partial
• impaired consciousness

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Specific Seizure Types

• Absence Petit mal
• Partial
• Jacksonian, focal motor
• Complex partial
• temporal lobe, psychomotor

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SE Classification

• GCSE
• Generalized convulsive SE
• Tonic-clonic motor activity
• Non-GCSE

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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

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Subtle SE

• Severe insult, ie hypoxic
• Comatose
• Limited motor activity
• Mortality exceeds 50
• Stop the seizure
• EEG confirmation

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Refractory SE

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

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

• Benzodiazepines
• Phenytoins
• Barbiturates
• Other agents
• valproate
• propofol
• lidocaine

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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

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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

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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

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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

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PharmacotherapyRectal Diazepam

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

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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

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PharmacotherapyOral Phenytoin

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

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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

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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

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PharmacotherapyIV Phenobarbital

• GABA-inhib, effective SE Rx
• Infuse up to 50 mg/min
• 20-30 mg/kg, 10 mg/kg doses
• Therapeutic gt 40 µg/mL
• Respiratory depression
• Hypotension

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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 gt 100 µg/mL

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PharmacotherapyLidocaine

• Third-line, stabilizes membrane Na /K pump
• Decreased neuron excitability, refractory GCSE
• 3 mg/kg

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PharmacotherapyIV Propofol Infusion

• Likely GABA mechanism
• Provides burst suppression
• 2 mg/kg loading dose
• Hypotension, acidosis, hypoventilation
• Rapid onset, easily reversed

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PharmacotherapyIV Midazolam Infusion

• GABA mechanism
• Equal to diazepam infusion
• Greater breakthru sz rates
• Less hypotension
• Vs. propofol, pentobarb

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PharmacotherapyIV Pentobarbital

• Likely GABA mechanism
• Provides burst suppression
• 5 mg/kg loading dose
• 25 mg/kg infusion rate
• ICU monitoring required

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PharmacotherapyED Treatment Protocol

• Have AEDs easily available
• Rapid sequential AED use
• Maximize infusion rate
• Maximize mg/kg dosing
• Benzos, phenytoins, phenobarbital, valproate

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PharmacotherapyNo IV Access

• PR diazepam
• IM midazolam
• IM fosphenytoin
• Buccal, intranasal midazolam
• No IM phenytoin/phenobarbital

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Seizure/SE Pharmacotherapy

• 2nd Generation AEDs
• Currently used as outpt Rx
• Soon available in ED
• What role in ED SE Rx?

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

• Limited use within hospitals
• No defined AEDs
• No optimal Rx time period
• Lack of uniformity
• Suboptimal patient outcome

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ED ManagementSE Rx Timeline

• 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

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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

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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)

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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

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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)

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New Onset Sz Neuroimaging

• 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

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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)

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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

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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)

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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.

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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)

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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.

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Sz/SE EEG Monitoring

• When should an EEG be performed in the ED?

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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.

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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

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The Treatment of Status EpilepticusPatients in
2005 A Look at the EFA Working Groups 1993
JAMA Guidelines
Edward P. Sloan, MD, MPH, FACEP
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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

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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!

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Questions?? www.ferne.orgferne_at_ferne.orgEdwar
d P. Sloan, MD, MPHedsloan_at_uic.edu312 413 7490
ferne_acep_2005_spring_sloan_szse_addinfo.ppt
3/3/2005 800 PM
Edward P. Sloan, MD, MPH, FACEP
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