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

Edward P. Sloan, MD, MPH

Optimizing Seizure Optimizing Seizure and SE Patient and SE Patient

Management in the Management in the Emergency Emergency DepartmentDepartment


SIMEU / ACEP SIMEU / ACEP Emergency MedicineEmergency Medicine

CongressCongress


Turino, Italy Turino, Italy November 9-11, 2006November 9-11, 2006



Professor

Department of Emergency MedicineUniversity of Illinois College of Medicine

Chicago, IL


Attending PhysicianEmergency Medicine

University of Illinois HospitalOur Lady of the Resurrection Hospital

Chicago, IL



DisclosuresDisclosures• NovoNordisk, King Pharmaceuticals, UCB NovoNordisk, King Pharmaceuticals, UCB

Pharma Advisory BoardsPharma 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


Board Chairman and PresidentBoard Chairman and President

FERNEFERNE

Chicago, IL


OverviewOverview

Mission StatementMission Statement• Patients with neurological Patients with neurological

emergencies deserve quality emergencies deserve quality emergency care.emergency care.

• Quality scientific research. Quality scientific research. • Case-oriented, evidence-based medical Case-oriented, evidence-based medical

education on optimal acute neurological education on optimal acute neurological care.care.

• Use of technology to break down space Use of technology to break down space and time barriers.and time barriers.

• Advocacy.Advocacy.


www.ferne.orgwww.ferne.org


Gabriella Paglia, MD

Department of Emergency NeurologyAz. Ospedaliera S.Giovanni Battista

di TorinoCap 10126 TORINOC.so Bramante, 88/90Italy

A Special Welcome To…A Special Welcome To…


Today’s AgendaToday’s Agenda• Present a clinical casePresent a clinical case• Ask a few questionsAsk a few questions• Consider the possibilitiesConsider the possibilities• Discuss ED managementDiscuss ED management• Examine the patient outcomeExamine the patient outcome


A Clinical CaseA Clinical Case


Patient EMS DataPatient EMS Data• 50?? yo male John Doe50?? yo male John Doe• Generalized tonic-clonic seizure Generalized tonic-clonic seizure • Chicago Fire Department Chicago Fire Department • Diazepam 5 mg IM, 15 mg IV Diazepam 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


Patient Clinical HistoryPatient 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


ED PresentationED Presentation• Facial and shoulder twitching RFacial and shoulder twitching R• Pt with gurgling BS Pt 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


Seizure Patient QuestionsSeizure Patient Questions

• Is this a seizure?Is this a seizure?• Is this status epilepticus?Is this status epilepticus?• What is the pathophysiology?What is the pathophysiology?• What is the best management?What is the best management?• What is the likely patient outcome?What is the likely patient outcome?


Seizure/SE Seizure/SE Clinical DataClinical Data


Seizures

Generalized Seizures:• Primary generalized:Primary generalized: starts as starts as

tonic-clonic sztonic-clonic sz• Secondarily generalized:Secondarily generalized:

tonic-clonic sz develops from tonic-clonic sz develops from a non-convulsive partial sz, ie a non-convulsive partial sz, ie aura (common)aura (common)


Status Epilepticus:

• Sz > 5- 10 minutesSz > 5- 10 minutes

• Two sz without a lucid Two sz without a lucid interval (Assumes interval (Assumes ongoing sz during coma)ongoing sz during coma)


Status Epilepticus

SE Classification:

• GCSE:GCSE: (Generalized (Generalized convulsive SE) with tonic-convulsive SE) with tonic-clonic motor activityclonic motor activity

• Non-GCSENon-GCSE


Status Epilepticus

Two Non-GCSE Types:• Non-convulsive SENon-convulsive SE

• Absence SEAbsence SE• Complex-partial SEComplex-partial SE

• Subtle SESubtle SE• Late generalized convulsive SELate generalized convulsive SE• Coma, persistent ictal Coma, persistent ictal

dischargedischarge• Very grave prognosisVery grave prognosis


Status EpilepticusStatus Epilepticus

Systemic SE Effects:Systemic SE 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


Status Epilepticus

Ongoing SE Effects:

• Over 40-60 min, loss of Over 40-60 min, loss of metabolic compensationmetabolic compensation

• With ongoing SE, systemic With ongoing SE, systemic BP & CBF dropBP & CBF drop


Status Epilepticus

SE Mortality:• SE mortality > 30% when sz SE mortality > 30% when sz

longer than 60 minuteslonger than 60 minutes

• Underlying sz etiology Underlying sz etiology contributes to mortalitycontributes to mortality


General ED Management:

• ABCsABCs• Glucose, narcan, thiamineGlucose, narcan, thiamine• Rapid sequential use of Rapid sequential use of

AEDsAEDs• Directed evaluationDirected evaluation


ED Management

SE Rx Timeline:• 0-30 min: ABCs, benzos0-30 min: ABCs, benzos• 30-60 min: Phenytoins30-60 min: Phenytoins• 60-90 min: Levetiracetam, 60-90 min: Levetiracetam,

phenobarbital, valproate phenobarbital, valproate • 90-120 min: Midazolam, propofol 90-120 min: Midazolam, propofol

CT, EEG, ICU/ORCT, EEG, ICU/OR


ED Anti-epileptic ED Anti-epileptic Drug (AED) UseDrug (AED) Use


Seizure Pharmacotherapy• Benzodiazepines• Phenytoins• Barbiturates• Other agents

–levetiracetam–propofol –valproate


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


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

IV Levetiracetam:• Second generation AED

• Oral and IV bioequivalent

• Adjunct therapy

• No therapeutic level defined

• 1500 to 3000 mg infusion

• Few adverse effects


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

IV Midazolam Infusion:• GABA mechanism

• Equal to diazepam infusion

• Greater breakthru sz rates

• Less hypotension

–vs. propofol, pentobarb


Pharmacotherapy

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

hypoventilation• Rapid onset, easily reversed


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, other

bolus AEDs, continuous AEDs


Pharmacotherapy

No IV Access:• PR diazepam

• IM midazolam

• IM fosphenytoin

• Buccal, intranasal midazolam

• No IM phenytoin/phenobarbital


ED Patient OutcomeED Patient Outcome


ED Patient ManagementED 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• 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


ED Diagnostic EvaluationED 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


Family Arrives, Pt HistoryFamily Arrives, Pt History• Pt with history refractory seizuresPt with history refractory seizures

• Hx carotid artery occlusion RHx carotid artery occlusion R

• Due for carotid endarterectomyDue for carotid endarterectomy

• Phenobarbital & dilantin, compliant Phenobarbital & dilantin, compliant

• Prior history of SE treated at UICPrior history of SE treated at UIC

• No medic alert bracelet No medic alert bracelet

• No recent illness, trauma, EtOHNo recent illness, trauma, EtOH


Patient OutcomePatient Outcome• EEG in ED, within 150 minutesEEG in ED, within 150 minutes

• Neuro consultation, no subtle SENeuro consultation, no subtle SE

• Admit to Neuro ICU Admit to Neuro ICU

• Repeated paralytic dosing Repeated paralytic dosing

• Final disposition for carotid RxFinal disposition for carotid Rx


ConclusionsConclusions• ED seizure patient Rx needs to address

both the immediate seizure and the long-term epilepsy management

• In general, ED seizure patient Rx focuses on parenteral AED use

• Must understand principles that govern ED AED use and priorities of those that provide long-term epilepsy Rx


RecommendationsRecommendations

• Be able to identify the seizure type and optimal patient therapies based on etiology, demographics, and risk/benefit

• Establish seizure and SE protocol• Stop the acute seizure & prevent SE• Wisely prescribe so that follow-up

epilepsy management can be optimized


Questions?Questions?

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