Post on 22-Dec-2015
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
2 Edward P. Sloan, MD, MPH, FACEP
Professor &
Research Development Director
Department of Emergency Medicine, University of Illinois at Chicago
Chicago, IL
(edsloan@uic.edu)
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
3 Edward P. Sloan, MD, MPH, FACEP
4 Edward P. Sloan, MD, MPH, FACEP
5 Edward P. Sloan, MD, MPH, FACEP
Global ObjectivesGlobal 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 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
7 Edward P. Sloan, MD, MPH, FACEP
Clinical HistoryClinical History24 yo femaleEMS to EDGeneralized seizure at home CFD: IV diazepam, resolvedHx seizure since childhoodOn DepakoteNo recent BHTNo recent illness
8 Edward P. Sloan, MD, MPH, FACEP
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
9 Edward P. Sloan, MD, MPH, FACEP
10 Edward P. Sloan, MD, MPH, FACEP
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?
11 Edward P. Sloan, MD, MPH, FACEP
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
12 Edward P. Sloan, MD, MPH, FACEP
13 Edward P. Sloan, MD, MPH, FACEP
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
14 Edward P. Sloan, MD, MPH, FACEP
Seizure MechanismSeizure Mechanism
• Sz = abnormal neuronal discharge with recruitment of otherwise normal neurons
• Loss of GABA inhibition
15 Edward P. Sloan, MD, MPH, FACEP
Status EpilepticusStatus Epilepticus• Seizure > 5- 10 minutes
• Two seizures without a lucid interval
• Assumes ongoing seizure activity during time of diminished responsiveness
16 Edward P. Sloan, MD, MPH, FACEP
SE PathophysiologySE Pathophysiology• Early compensation meets
increased CNS metabolic needs (SBP, CBF ↑↑)
• Failure at 40-60 minutes, (SBP, CBF ↓↓)
• CNS tissue necrosis, adverse sequelae
17 Edward P. Sloan, MD, MPH, FACEP
SE PathophysiologySE 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/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
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 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)
21 Edward P. Sloan, MD, MPH, FACEP
Status Epilepticus
Ongoing SE Effects:
• Over 40-60 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 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
24 Edward P. Sloan, MD, MPH, FACEP
25 Edward P. Sloan, MD, MPH, FACEP
Seizure ClassificationSeizure Classification
• Generalized: both cerebral hemispheres
• Partial: one cerebral hemisphere (localized)
26 Edward P. Sloan, MD, MPH, FACEP
Generalized SeizuresGeneralized Seizures
• Convulsive: tonic-clonic
• Non-convulsive: absence
27 Edward P. Sloan, MD, MPH, FACEP
Generalized SeizuresGeneralized 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 SeizuresPartial Seizures
• Simple partial:
no impaired consciousness
• Complex partial:
impaired consciousness
29 Edward P. Sloan, MD, MPH, FACEP
Specific Seizure TypesSpecific Seizure Types• Absence: Petit mal
• Partial:
Jacksonian, focal motor
• Complex partial:
temporal lobe, psychomotor
30 Edward P. Sloan, MD, MPH, FACEP
SE ClassificationSE Classification
• GCSE:
Generalized convulsive SE
Tonic-clonic motor activity
• Non-GCSE
31 Edward P. Sloan, MD, MPH, FACEP
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
32 Edward P. Sloan, MD, MPH, FACEP
Subtle SESubtle 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 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
34 Edward P. Sloan, MD, MPH, FACEP
35 Edward P. Sloan, MD, MPH, FACEP
Seizure/SE PharmacotherapySeizure/SE Pharmacotherapy
• Benzodiazepines• Phenytoins• Barbiturates• Other agents
- valproate- propofol- lidocaine
36 Edward P. Sloan, MD, MPH, FACEP
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
37 Edward P. Sloan, MD, MPH, FACEP
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
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 10-20 µg/mL
42 Edward P. Sloan, MD, MPH, FACEP
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
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 10-20 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• 20-30 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
• 25-30 mg/kg, 3-6 mg/kg/min
• Therapeutic > 100 µg/mL
47 Edward P. Sloan, MD, MPH, FACEP
Pharmacotherapy
Lidocaine: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 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
54 Edward P. Sloan, MD, MPH, FACEP
55 Edward P. Sloan, MD, MPH, FACEP
SE ProtocolsSE 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
• 30-45 min: Phenytoins
• 45-75 min: Phenobarb/valproate
• 75-90 min: Propofol/midazolam
• 90-150 min: CT, EEG, ICU/OR
57 Edward P. Sloan, MD, MPH, FACEP
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
58 Edward P. Sloan, MD, MPH, FACEP
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)
59 Edward P. Sloan, MD, MPH, FACEP
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
60 Edward P. Sloan, MD, MPH, FACEP
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)
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: NeuroimagingNew Onset Sz: Neuroimaging
62 Edward P. Sloan, MD, MPH, FACEP
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)
63 Edward P. Sloan, MD, MPH, FACEP
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
64 Edward P. Sloan, MD, MPH, FACEP
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)
65 Edward P. Sloan, MD, MPH, FACEP
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.
66 Edward P. Sloan, MD, MPH, FACEP
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)
67 Edward P. Sloan, MD, MPH, FACEP
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.
68 Edward P. Sloan, MD, MPH, FACEP
Sz/SE: EEG MonitoringSz/SE: EEG Monitoring
When should an EEG be performed in the ED?
69 Edward P. Sloan, MD, MPH, FACEP
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.
70 Edward P. Sloan, MD, MPH, FACEP
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
71 Edward P. Sloan, MD, MPH, FACEP
72 Edward P. Sloan, MD, MPH, FACEP
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
73 Edward P. Sloan, MD, MPH, FACEP
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??
www.ferne.orgwww.ferne.orgferne@ferne.orgferne@ferne.org
Edward P. Sloan, MD, MPHEdward P. Sloan, MD, MPHedsloan@uic.edu
312 413 7490312 413 7490
ferne_acep_2005_spring_sloan_szse_addinfo.ppt 3/3/2005 8:00 PM
74 Edward P. Sloan, MD, MPH, FACEP