Download - Status Epilepticus
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Status Epilepticus
by
Robert S. Fisher, M.D., Ph.D.
Department of Neurology
Stanford, California USA
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Definition of Status Epilepticus
A state of continuing seizures for greater than 30 minutes, or recurrent seizures for at least 30 minutes without intervening return of consciousness.
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TYPES OF STATUS
Simple partial motorComplex partialAbsenceMyoclonicTonic-clonic
Epilepsia partialis cont.
Non-convulsive
Tonic-clonic
*
*Petit mal, spike-wave, absence
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About 30,000per year
Rochester Richmond
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The longer you wait, the harder to treat
With delay of treatment, more diazepam is required to stop seizures in an experimental model of status.
Walton & Treiman Epilepsia 1995 S4:45
0
1
2
3
4
5
mg
Val
ium
1st sz
2nd sz
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EARLY TREATMENT IS KEY
0 5 10 15 20 25 30 3560
70
80
90
100
110
DAYS
% SURVIVING
DeLorenzo, 1992 Epilepsia S4:15
rapid treatment
delayed treatment
<1hr
>1hr
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Symptomatic
Idiopathic
140,00060,000
2,000,000
Epilepsy Status
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CONCEPT OF - Overt status- Subtle status
Encephalopathy
Mild twitching
Unresponsiveness
EEG general ictal
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CAUSES OF STATUS: ADULTS
0 5 10 15 20 25 30
Cerebrovascular
Med change
Anoxia
ETOH-drug
Metabolic
Unknown
Fever/infection
Trauma
Tumor
Congenital%
from DeLorenzo et al. Epilepsia 1992; 33 (Suppl. 4): S15-25
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COMPLICATIONS OF STATUS
HyperthermiaShockRhabdomyolysisArrhythmiasAspirationPhysical Injuries
PsychosocialBrain cell lossDeath in 5-30%Iatrogenic injury
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Walker MC, Howard RS, Smith SJ, Miller DH, Shorvon SD, Hirsch NP. Diagnosis and treatment of status epilepticus on a neurological intensive care unit. QJM 1996; 89: 913-20.
26 pts admitted to neuro-ICU as status epilepticus Only 14 (54%) were in status epilepticus Six were in drug-induced coma or were encephalopathic Six had pseudo-status epilepticus: 4 were intubated.
MISDIAGNOSIS
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Discrete seizures
Waxing ictal
Continuous ictal
Continuous ictal with flat
PLEDs on flat background
SEQUENCE OF EEG CHANGESIN STATUS EPILEPTICUS
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Discrete seizures
FP1-F7
F7-T3
T3-T5
T5-O1
FP2-F8
F8-T4
T4-T6
T6-O2
1 sec 100 µV
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Continuous ictal discharges
FP1-F7
F7-T3
T3-T5
T5-O1
FP2-F8
F8-T4
T4-T6
T6-O2
1 sec 200 µV
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Fp1-F7
F7-T3
T3-T5
T5-O1
Fp2-F8
F8-T4
T4-T6
T6-O2
Fp1-F3
F3-C3
C3-P3
P3-O1
Fp2-F4
F4-C4
C4-P4
P4-O21 sec100 µV
PLEDS
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0
10
20
30
40
50
60
70
80
%
Discrete Waxing Continuous Cont with flat PLEDs
STAGE OF EEG & RESPONSE TO THERAPY
Treiman et al. from VA study 1996
% recovery
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In 1685, King Charles II of England suffered from an illness
that caused him to have convulsions. The treatments he underwent included: "letting" of one pint of blood; an enema of antimony, sacred bitters, rock salt, marrow leaves, violets,
beetroot, chamomile flowers, fennel seeds, linseed, cinnamon, cardamon seeds, and aloe; and
having his head shaved and blistered. Needless to say, the
King died.
quoted in:http://www.epilepsynl.com/newsletters/NewsletterFall2004.pdf
Charles II of EnglandKing of Scots, King of England and King of Ireland
(and Ruler of the American Colony)Reign: 29 May 1660 – 6 February 1685
Born: 29 May 1630 Died: 6 February 1685
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A 42 year old male known alcoholabuser was brought to the ER stiffand trembling. He was thought tobe exhibiting DT's (1), and was there-fore given diazepam by NG tube.This precipitated emesis and associatedaspiration (2). Then all 4 extremitiesbegan to jerk rhythmically.
HOW NOT TO TREAT STATUS
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An iv was established, and routinebloods sent to the lab (3). Anticonvul-sants were withheld for 45 minutespending arrival of the medical record (4).Seizure activity was terminated with 10mg diazepam iv push, but tonic-clonicmovements recurred 15 minutes later(5). Phenytoin 300 mg was given intra-muscularly to no effect (6).
HOW NOT TO TREAT STATUS
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Phenobarbital 500 mg iv was given as athird drug, resulting in apnea and hypo-tension (7). The patient resided in anICU for 24 hours, whereupon he awoke,exhibited no further seizures, and wasdischarged that day (8)
HOW NOT TO TREAT STATUS
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1. Secure the correct diagnosis2. Stabilize patient first3. Treat the treatable4. Stop within 30 minutes5. Immediate + long-term control6. Proper routes and doses of meds7. Expect cardiorespiratory trouble8. Diagnosis and follow-up
PRINCIPLES FOR STATUS
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STABILIZE
Airway Breathing Circulation Oxygen Dextrose ?
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Breathing Pulse Blood Pressure EKG EEG
MONITOR
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Ten Centers, 530 evaluable patients
Four iv regimens for initial Rx GTC status PHT 18 mg/kg DZP 0.15 mg/kg, then PHT 18 mg/kg PBB 15 mg/kg LOR 0.1 mg/kg
Endpoint: seizure-free from 20-60 minutes Clinical
EEG
VA COOP STATUS STUDY
Treiman et al. from VA study 1996
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0
10
20
30
40
50
60
70
%
LOR PBB DZP+PHT PHT
CONTROL BY DRUG
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You stop the visible seizures,but the patient doesn’t wake upfor an hour.
What should you do?
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20% had EEG statuscontinuing after behavioralseizures had stopped.
80%
20%
Treiman et al. from VA study 1996
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Rate of recurrence39 day outcomeAdverse events
No differences amongfour treatment group for :
Treiman et al. from VA study 1996
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Outcome Overt Subtle
Improved, discharged 53% 9%Still in hospital 21% 25%Died 27% 65%
Treiman et al. 1996 VA Coop
But – is usual outcome really this poor?
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100 consecutive ICU NCSE patients. 18 (18%) died: 14/52 (27%) in acute medical group 1/31 (3%) in the epilepsy group 3/17 (18%) in the cryptogenic group
Mental status impairment was severe in 33 Complications occurred in 39
Shneker BF, Fountain NB. Assessment of acute morbidity and mortality in nonconvulsive status epilepticus. Neurology 2003;61:1066-1073.
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lorazepam (Ativan) phenytoin (Dilantin) phenobarbital
pentobarbitalpropofol (Diprivan)midazolam (Versed)
isofluoraneetomidatelidocaineparaldehydemagnesiumfurosemide
cooling ???
DRUG THERAPY
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PENTOBARBITAL
CVP line or Swan Load: 5-15 mg/kg in 250 cc NS over 1 hr Orders for neosynephrine or pressors Continuous EEG monitoring Maintain 1-20 mg/kg per minute Aim for about 70-90% EEG suppression Taper after a few days over half a day
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FP1-F7F7-T3T3-T5T5-O1FP2-F8F8-T4T4-T6T6-O2FP1-F3F3-C3C3-P3P3-O1FP2-F4F4-C4C4-P4P4-O2
1 sec 100 µV
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PROPOFOL: USE IN STATUS
Quicker wake-up
Maybe less respiratory depression
Bolus of 2 mg/kg
Continuous infusion 1-10 mg/kg/hr (17-170 ug/kg/m)
EEG monitoring with titration to burst-suppression
Supportive care for comatose patients
Be aware of expense
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PROPOFOL: ADVERSE EFFECTS
Respiratory depression with induction > 2.5 mg/kg
Hypotension in about 15%
Bradycardia in about 5%
< 0.2% of 25,981 pts needed hemodynamic support
Increases serum triglycerides
Lipid, egg, glycerol solvent may get infected
Propofol infusion syndrome (rare)
Sometimes paradoxical induction of seizures
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6 y/o Boy with Shunt Failure
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Elderly Man Post-Anoxia
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36 y/o man with 10 Tonic-Clonic Seizures Today
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Prior EEG: Half-Speed
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Triphasics vs. Nonconvulsive Status
• Difficult EEG distinction, perhaps impossible• Both show periodic frontal 3-phase sharp potentials• Triphasics can have an after-going slow wave• Both wax and wane• Both can have an anterior-posterior gradient• Triphasics tend to decline with sleep (but variably)• Waxing-waning awareness in both• Involves BDZ receptors in both• What is metabolic encephalopathy anyway?
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6 y/o Girl with Status Epilepticus
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Elderly Woman with Renal Failure
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1 sec
100 µV
FP1-F7F7-T3T3-T5T5-O1FP2-F8F8-T4T4-T6T6-O2FP1-F3F3-C3C3-P3P3-O1FP2-F4F4-C4C4-P4P4-O2
Triphasic waves
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SPECIAL CIRCUMSTANCES
Need IV medication phenytoin
fosphenytoin phenobarbital
diazepam, lorazepam, midazolam Depacon (valproic acid)
paraldehyde (if obtainable) levetiracetam (Keppra) lacosamide (Vimpat)
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SPECIAL CIRCUMSTANCES
Need to avoid sedation
Most except
phenobarbital
benzodiazepines
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SPECIAL CIRCUMSTANCES
Need to avoid WBC depression
Most OK, Except
carbamazepine
oxcarbazepine
valproic acid
felbamate
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SPECIAL CIRCUMSTANCES
Need to avoid low sodium
Most OK, Except carbamazepine
oxcarbazepine
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COMMON MISTAKES
1. Fail to recognize status
2. Fail to deliver emergency support
3. Not treating reversible causesHypoglycemiaHypocalcemiaHypoxiaToxic ingestionHyperthermiaOther reversible causes
4. Too slow with meds
5. Partial polypharmacy
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CONCLUSIONS
1. Status is common and lethal
2. Early/effective treatment makes a difference
3. Subtle status can be missed
4. First support the patient & treat the treatable
5. Lorazepam is the favored therapy
6. Several other drugs can be used later: e.g., propofol or pentobarbital coma
7. With best therapy, mortality remains high