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Epidemiology and Societal Costs. 6.5/1000 Prevalence; 2.5 million in the US147,000 Newly diagnosed pts./year28% of pts. with epilepsy visit ED annually82,000 Hospitalizations/year$3.6 Billion, annual cost. Status Epilepticus: Epidemiology. 50,000-150,000 Cases annually50 Cases/100,000 populationInfants and elderly are a greater risk20% of pts with epilepsy develop SE by age 5Etiology: 1/3 acute insult, 1/3 chronic,1/3 new onset.
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1. Seizure Disorders Abraham Berger, MD, F.A.C.E.P.
Department of Emergency Medicine
Beth Israel Medical Center, N.Y.
2. Epidemiology and Societal Costs 6.5/1000 Prevalence; 2.5 million in the US
147,000 Newly diagnosed pts./year
28% of pts. with epilepsy visit ED annually
82,000 Hospitalizations/year
$3.6 Billion, annual cost
3. Status Epilepticus: Epidemiology 50,000-150,000 Cases annually
50 Cases/100,000 population
Infants and elderly are a greater risk
20% of pts with epilepsy develop SE by age 5
Etiology: 1/3 acute insult, 1/3 chronic,1/3 new onset
4. Emergency Department Seizures Epidemiology of acute Seizures in 200 Pts.
Krumholtz;Epilepsia;1989:30;175
Epilepsy Patients 46%
New Onset 35%
Febrile 15%
Secondary Seizures 4%
5. Seizure Outcomes Injury/Death 15%
Head contusions/Lacerations (Common)
Mortality
1.2% of all seizures
3% to 26% in Status Epilepticus
10X higher in adults (Vs..... Children)
Highest with hypoxic or ischemic insult
6. Status Epilepticus: Duration & Mortality Status Epilepticus > 60 Min:
10-fold greater 30-day mortality(32% Vs..... 2.7%)
Worse outcome associated with:
Longer duration SE
SE refractory to first-line therapy
7. Seizure Mechanisms Abnormal discharge by unstable neurons
Propagation by recruitment of normal neurons
Failure of normal inhibitory neurotransmitters GABA
Enhancement of excitatory neurotransmitters glutamate, aspartate, acetylcholine
Interference with normal metabolic processes
Glucose, 02 metabolism
Na+, Ca++, K+, Cl- ion shifts
8. Acute Symptomatic SeizuresPrecipitating Causes Review of 696 Pts: Annegers. Epilepsia 1995;36:327
9. Status Epilepticus: Etiology Lowenstien and Aldredge:
Neurology 1993;43:483
Studied 154 Patients, found SE
Non Compliance 25%
ETOH 25%
Other Etiologies divided equally:
Tox,CNS ID/CA,Trauma,Stroke,Metabolic,
Cardiac arrest,Refractory, Unknown
10. New-Onset SeizuresRecurrence RisksTardy Am J Emerg Med 1995;13:1 51% recurrence risk after 1st unprovoked SZ
75% recurrence rate within 2 yrs of a 1st SZ
20% will seize again within 24H
Predictors of recurrent risk
SZ Etiology (Partial and remote > risk)
EEG Findings
SE does not increase recurrence risk in Idiopathic SZs
11. ClassificationMosewich Mayo Clin Proc 1996;71;405 Partial
Simple Partial
Complex Partial
Generalized
Primary
Secondary
Duration
Self - limited
Status Epilepticus
12. SE: Definition Historical Definitions
2 seizures within 30 min w/o lucid interval
1 seizure greater than 30 min duration
Recent definitions
2 seizures over ant interval w/o lucidity
1 seizure of greater than 10 min duration
Treiman. Epilepsia 1993;34(Suppl 1)
13. Refractory SE Lack of response to first line drugs
Benzodiazepines
Phenytoin
Phenobarbital
2000-6000 cases yearly in USA
6%-9% of all SE cases
Bleck. Neurology Chronicle 1992;2:1
14. Cerebral Changes in SE CNS injury independent of systemic effects
Neuronal injury due to repetitive firing and excessive metabolic needs
CNS injury will occur even if systemic disturbances are treated (fever, HTN,motor activity)
Early in SE, BP and CBF inc.
Late in SE, BP and CBF dec.
Aminoff. Am J Med 1980;69:657
Wijdcks. Mayo Clin Proc 1994;69:1044
15. Systemic Changes in SE BP: early Inc followed by hypotension
Fever: 50% have t > 100.5 F
Lactic acidosis: 30% pH <7.00
Hypercarbia: 84% will have inc paco2
Leukocytosis w/o bands
CSF pleocytosis: 2-18% have >5 PMNs
Aminoff. Am J Med 1980;69:657
Wijdcks. Mayo Clin Proc 1994;69:1044
16. Post Ictal Physical Findings Focal findings
anisocoria
plantar response
hyperreflexia
evidence of trauma (tongue lacerations)
Altered Mental Status
improvement should occur within 20-30 min
17. Laboratory TestingTurnbull. Ann Emerg Med 1990;19:373 Metabolic tests
2.5% of Szs due to chemical derangement
Drug levels
Tox and ETOH levels (when indicated)
Finger stick
Pulse Oximetry
HCG
EKG
18. Lumbar Puncture Indications
Immunocomprimised
Meningeal signs
Persistent AMS
Fever alone not an indication
ACEP Ann Emerg Med 1993;22:987
19. Neuroimaging-Emergent Rec.ACEP Guidelines; Ann Emerg Med 1996;27:114
Recent Trauma
Cancer
Anticoagulation
AIDS
New focal deficit
Persistent AMS
Fever
Persistent Headache
20. Neuroimaging-Options ACEP Guidelines; Ann Emerg Med 1996;27:114
Consider Imaging
First time seizure patients
Older than 40 Y
Partial onset seizure
Prior history of Sz
New pattern or type
prolonged postictal
Worsening mental status
21. CT Scan Abnormal CT; most likely
Abnormal neuro exam post recovery
Malignancy history
Abnormal CT; less likely
ETOH related Szs (w/o trauma)
Initial CT should be non-contrast
22. MRIBronen. AJR 1992;159:1165
Intractable epilepsy
25% positive CT
50% positive MRI
After a negative non-contrast CT in ED
? appropriate in ED due to off site location
23. Emergent EEG Indications
Prolonged (>30 min) AMS
SE requiring Neuromuscular paralysis
SE requiring Barbiturate coma or general anesthesia
Privitera. Emerg Med Clin N Am;1994;12:1089
24. Pharmacological RX Benzodiazepines
Phenytoin
Fosphenytoin
Phenobarbital
Propofol
Valproic Acid
Lidocaine
25. Benzodiazepines GABA inhibition of repetitive firing
80% Control of SE in 47 studies
Lorazepam Vs..... diazepam
adult SE - comparable efficacy
pediatric seizures
Lorazepam may be more effective
intubation more common with diazepam
Chiulli. J Emerg Med 1991;9:13/Treiman. Neurology 1990;40(suppl2)32
26. Phenytoin Stabilizes membrane Na+ channels
Regulates Ca++
Effective in gen..... SZs and SE
18 mg/kg loading dose results in Rx levels up to 24h (10mcg/ml)
Constant infusion preferred to slow IVP use
27. Phenytoin Advantages
Extensive experience
Low risk of respiratory depression
Little effect on consciousness
Jordan. Neurosurg Clin n Am 1994;5:671
Limitations
Toxic diluents (high pH)
Cardiac and soft tissue complications
Hypotension
Rate/infusion related
Cardiac monitoring
Used as post-resuscitation drug in acute szs
28. Phenytoin: PO 18 mg/kg oral load
65% achieve level of 10mcg/ml by 8 h
Delay in achieving Rx level did not result inc. Sz recurrence within 8 h
Osborn, H. Ann Emerg Med 1987;16:407
29. Fosphenytoin H2O sol. pro drug
Complete conversion in vivo to phenytoin
Rx levels within 2.7 min (IV)
Conversion comparable in all demographic groups and all disease states No toxic diluents
pH 8.7
Less infusion site complications
Available IM dose
Dosing in equivalents
1gm FP=1gm Phenytoin
Wilder Arch Neurol 1996;53:784
30. Phenobarbital Crosses BBB slowly
Long 1/2 life (21-42 h)
Enhances GABA inhibition
Infuse @ 100 mg/min up to 10 mg/kg
Monitor for:
Resp. depression
Hypotension
3rd line Rx for refractory gen.... conv. SE
Stops SZ motor activity and suppresses EEG burst patterns
Intubation, Vent support, HD and EEG monit. req..
Shaner. Neurology 1988;38:202
Jagoda. Ann Emerg Med 1993;22:1337
31. Propofol Anesthetic agent; GABA Mechanism
Provides burst suppression
Loading dose: 2 mg/kg
Requires cont.. infusion
EEG monitoring required
32. Lidocaine Membrane stabilization effect @ Na+ /K+ pump
Reduces neuronal excitability
Possible role in refractory SE
3rd line agent
Load at 1.5 mg to 3 mg/kg
Walker. Acad Emerg Med 1997;4:918
33. Primary Causes of Drug Induced Seizures Antidepressants 28%
Stimulants 28%
Other 26%
Antihistamines 8%
INH 5%
Theophylline 5%
Olson. Am J Emerg Med 1993;11:565/ SF Poison Control Data
34. Cocaine Consider multiple etiologies (inhale,body stuffing)
Indirect CNS causes:
Ischemia, hemorrhage, vasculitis
DX work up low yield in pts with brief Sz who return to nl cns status
RX: Benzos
AVOID Beta-Blockers
Holland. Ann Emerg Med 1992;21:772
35. Isoniazid (INH) Inhibits pyridoxine kinase
enzyme that forms pyridoxal phosphate
cofactor in GABA formation
Rx: pyridoxine 1 g for 1 g of INH
unknown overdoses:5g IVP, repeat q 5hX6
36. Theophylline Szs common in chronic ingestions
Rx with benzo and barbiturates
Phenytoin probably not effective
Enhance elimination
multiple doses of activated charcoal
hemodialysis or hemoperfusion
37. Cyclic Antidepressants Sz (40%) and coma (60%) common in TCA deaths
Szs more likely when QRS > 100 msec
Rx: Benzos
consider pentobarbital or Propofol in ref. SE
phenytoin,NaHCO3
Callahan. Ann Emerg Med 1985;14:1
38. ETOH Withdrawal SZs 60% occur within 24 h of last drink
Peak incidence by 12 h of last drink
60% recurrence
44% of Sz due to ETOH
Prolonged post ictal state-gen.. good outcome
Alderedge. Epilepsia 1993;34:1033
39. Diagnosis & Treatment Baseline chemistries
CT for head trauma, or focal findings
IV D5NS, thiamine,K,Mg,Benzo.
Avoid progression of disease to DTs
Alderedge. Epilepsia 1993;34:1033
40. Pregnancy and Seizures Changes in SZ frequency and medication levels may occur
SE rare; mortality inc with SE
Fetal monitoring necessary
Evaluate for eclampsia
Jagoda. Ann Emerg Med 1991;20:80
41. Magnesium Sulfate Prevention of Eclampsia
Smooth muscle relaxant
Superior to phenytoin for prophylaxis
Lower risk of recurrence Vs..... diazepam and phenytoin
Lucas. 1995;333:201
42. SZs in the Elderly Increased risk for drug-drug and or drug-disease state interactions
inc drug utilization
inc freq.. Co-morbid dis.
Non-convulsive SE may present as new onset AMS
Greatest Sz frequency and incidence at ages <1&>60 Common Etiologies
CVA 60%
Tumors 10-15%
Metabolic or drug/etoh toxicity 10%
Kugler. Neurology 1996;46:(suppl.A)176
43. Conclusion Szs and SE are medical emergencies
Optimal outcome depends on early interventions
appropriate drugs
Dosing based on mg/kg requirements
Aggressive Rx needed
Develop plan (mgmt,met studies, imaging)