The ED Treatment of Seizure and SE Patients: What the 2004 ACEP Seizure Clinical Policy Doesn’t...

The ED Treatment of The ED Treatment of Seizure and SE Patients:Seizure and SE Patients:

What the 2004 ACEP What the 2004 ACEP Seizure Clinical Policy Seizure Clinical Policy

Doesn’t Tell YouDoesn’t Tell You

1 Edward P. Sloan, MD, MPH, FACEP


Professor &

Research Development Director

Department of Emergency Medicine, University of Illinois at Chicago

Chicago, IL

([email protected])

Edward Sloan, MD, MPH, FACEPEdward Sloan, MD, MPH, FACEP

Attending PhysicianAttending PhysicianEmergency MedicineEmergency Medicine

University of Illinois HospitalOur Lady of the Resurrection Hospital

Chicago, IL



Global ObjectivesGlobal Objectives

• Learn more about seizures

• Increase awareness of Rx options

• Enhance our ED management

• Improve patient care & outcomes

• Maximize staff & patient satisfaction


Session ObjectivesSession 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


Clinical HistoryClinical History24 yo femaleEMS to EDGeneralized seizure at home CFD: IV diazepam, resolvedHx seizure since childhoodOn DepakoteNo recent BHTNo recent illness


ED PresentationED PresentationPost-ictal in EDNon-focal neurological examNo evidence of trauma or toxicityAppropriate, verbal, answers questionsHas recurrent generalized seizureProlonged duration (>5 min)

Is this patient an outlier?What is his optimal management?

What the 2004 ACEP What the 2004 ACEP Seizure Clinical PolicySeizure Clinical Policy

Doesn’t Tell UsDoesn’t Tell Us



Important Sz/SE InfoImportant 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?


Important Sz/SE InfoImportant 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 & Epidemiology & PathophysiologyPathophysiology



Seizure EpidemiologySeizure 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


Seizure MechanismSeizure Mechanism

• Sz = abnormal neuronal discharge with recruitment of otherwise normal neurons

• Loss of GABA inhibition


Status EpilepticusStatus Epilepticus• Seizure > 5- 10 minutes

• Two seizures without a lucid interval

• Assumes ongoing seizure activity during time of diminished responsiveness


SE PathophysiologySE Pathophysiology• Early compensation meets

increased CNS metabolic needs (SBP, CBF ↑↑)

• Failure at 40-60 minutes, (SBP, CBF ↓↓)

• CNS tissue necrosis, adverse sequelae


SE PathophysiologySE Pathophysiology• Glutamate toxic mediator• CNS necrosis even if

systemic complications fully mitigated

• HTN, fever, rhabdomyolysis, hypercarbia, hypoxia, infection


AMS in Seizures/SEAMS 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


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


Status EpilepticusStatus Epilepticus

Systemic SE Effects:Systemic SE Effects:

• Hypertension (early)

• Hypotension (later)

• 49% Temp > 100.5 F°

• Lactic acidosis (pH < 7.00)

• Hypercarbia (increased pCO2)


Status Epilepticus

Ongoing SE Effects:

• Over 40-60 min, loss of metabolic compensation

• With ongoing SE, systemic BP & CBF drop


Status Epilepticus

SE Mortality:

• SE mortality > 30% when sz longer than 60 minutes

• Underlying sz etiology contributes to mortality


New-Onset: Sz RecurrenceNew-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 Seizure and SE Patient ClassificationClassification



Seizure ClassificationSeizure Classification

• Generalized: both cerebral hemispheres

• Partial: one cerebral hemisphere (localized)


Generalized SeizuresGeneralized Seizures

• Convulsive: tonic-clonic

• Non-convulsive: absence


Generalized SeizuresGeneralized Seizures

• Primary generalized:

starts as tonic-clonic sz

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


Partial SeizuresPartial Seizures

• Simple partial:

no impaired consciousness

• Complex partial:

impaired consciousness


Specific Seizure TypesSpecific Seizure Types• Absence: Petit mal

• Partial:

Jacksonian, focal motor

• Complex partial:

temporal lobe, psychomotor


SE ClassificationSE Classification

• GCSE:

Generalized convulsive SE

Tonic-clonic motor activity

• Non-GCSE


Two Non-GCSE TypesTwo Non-GCSE Types

• Non-convulsive SE:- Absence SE- Complex-partial SE

• Subtle SE:- Late generalized convulsive SE- Coma, persistent ictal discharge- Very grave prognosis


Subtle SESubtle SE

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


Refractory SERefractory 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 Seizure and SE Patient Management Management



Seizure/SE PharmacotherapySeizure/SE Pharmacotherapy

• Benzodiazepines• Phenytoins• Barbiturates• Other agents

- valproate- propofol- lidocaine


ED SE TreatmentED 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


ED AED Use: ConceptsED 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


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


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


Pharmacotherapy

Rectal Diazepam:

• Diazepam rectal gel pre-packaged for rapid use

• Dose 0.5 mg/kg, less respiratory depression seen than with IV use


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


Pharmacotherapy

Oral Phenytoin:Oral Phenytoin:

• 18mg/kg oral load

• 64% reach 10mg/mL levels by 8 hrs (therapeutic)

• Delayed absorption due to large loading, or drug prep


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


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


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


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


Pharmacotherapy

Lidocaine:Lidocaine:

• Third-line, stabilizes membrane Na + /K + pump

• Decreased neuron excitability, refractory GCSE

• 3 mg/kg


Pharmacotherapy

IV Propofol Infusion:• Likely GABA mechanism• Provides burst suppression• 2 mg/kg loading dose• Hypotension, acidosis,

hypoventilation• Rapid onset, easily reversed


Pharmacotherapy

IV Midazolam Infusion:

• GABA mechanism

• Equal to diazepam infusion

• Greater breakthru sz rates

• Less hypotension - Vs. propofol, pentobarb


Pharmacotherapy

IV Pentobarbital:

• Likely GABA mechanism

• Provides burst suppression

• 5 mg/kg loading dose

• 25 mg/kg infusion rate

• ICU monitoring required


Pharmacotherapy

ED Treatment Protocol:

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

phenobarbital, valproate


Pharmacotherapy

No IV Access:

• PR diazepam

• IM midazolam

• IM fosphenytoin

• Buccal, intranasal midazolam

• No IM phenytoin/phenobarbital


Seizure/SE PharmacotherapySeizure/SE Pharmacotherapy

• 2nd Generation AEDs

• Currently used as outpt Rx

• Soon available in ED

• What role in ED SE Rx?

Seizure and SE Protocols Seizure and SE Protocols and the ACEP Policyand the ACEP Policy



SE ProtocolsSE Protocols

• Limited use within hospitals

• No defined AEDs

• No optimal Rx time period

• Lack of uniformity

• Suboptimal patient outcome


ED Management

SE 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


ACEP Clinical PolicyACEP 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


New Onset Sz: Laboratory TestingNew 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)


New Onset Sz: Laboratory TestingNew 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


New Onset Sz: NeuroimagingNew Onset Sz: Neuroimaging

Which new onset seizure patients who have returned to

a normal baseline require neuroimaging

in the ED?

(outcome measure: abnormal CT)


• 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: NeuroimagingNew Onset Sz: Neuroimaging


New Onset Sz: Disposition/AED LoadingNew 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)


New Onset Sz: Disposition/AED LoadingNew 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


Sz/SE: Phenytoin LoadingSz/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)


Sz/SE: Phenytoin LoadingSz/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.


Sz/SE SE TherapeuticsSz/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)


Sz/SE SE TherapeuticsSz/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.


Sz/SE: EEG MonitoringSz/SE: EEG Monitoring

When should an EEG be performed in the ED?


Sz/SE: EEG MonitoringSz/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.


ACEP Clinical PolicyACEP 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 EpilepticusThe Treatment of Status EpilepticusPatients in 2005: Patients in 2005:

A Look at the EFA Working Group’s A Look at the EFA Working Group’s 1993 JAMA Guidelines1993 JAMA Guidelines



EFA Guideline: EFA Guideline: Key Learning PointsKey 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


Key Learning PointsKey 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??Questions??

[email protected]@ferne.org

Edward P. Sloan, MD, MPHEdward P. Sloan, MD, [email protected]

312 413 7490312 413 7490

ferne_acep_2005_spring_sloan_szse_addinfo.ppt 3/3/2005 8:00 PM


http://www.ferne.org/

The ED Treatment of Seizure and SE Patients: What the 2004 ACEP Seizure Clinical Policy Doesn’t...

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