PharmD May 28 2014 UW Medicine Status Epilepticus Definition Status Epilepticus SE 5 minutes of more of continuous clinical andor electrographic seizure activity OR Recurrent seizure activity without recovery between seizures ID: 248737
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Slide1
Ives Hot, PharmDMay 28, 2014UW Medicine
Status
EpilepticusSlide2
DefinitionStatus Epilepticus
(SE)
5 minutes of more of continuous clinical and/or electrographic seizure activity
-OR-
Recurrent seizure activity without recovery between seizures Slide3
Epidemiology Estimated 100,000 to 200,000 episodes of SE in the United States annually
Mortality: 17-26%
Additional 10-23% of patients have disabling neurological deficits Slide4
CategorizationConvulsive
Associated with rhythmic jerking of extremities
Findings: tonic-
clonic
movements, mental status impairment, focal neurological deficits
Non-convulsive
Seen on electroencephalogram (EEG) without clinical findings
Refractory (RSE)
Patients who DO NOT respond to standard treatment
Received adequate doses of initial benzodiazepine
Second acceptable antiepileptic drug (AED)Slide5
Etiology Acute: Metabolic disturbances
Sepsis
CNS infection: meningitis, encephalitis, abscess
Stroke
Head trauma
Pharmacologic
Hypertensive encephalopathy
Autoimmune encephalitis Slide6
Etiology Chronic: Pre-existing epilepsy
Breakthrough seizure
Discontinuation/non-adherence to AED
Chronic ethanol abuse
CNS tumors
Remote CNS pathology ( stroke, abscess, TBI, cortical
dysplasia
)Slide7
Diagnostic Work-upAll Patients
Finger-stick glucose
Vital Signs
Head computed tomography
Lab:
CBC
, BMP, Ca, Mg, AED levels
Continuous EEG monitoring
Consider
Brain MRI
Lumbar puncture
Toxicology panel
Other lab testsSlide8
Prognosis
Convulsive
Non-convulsive
RSE
Mortality
-Discharge:
9-21%
-30-day: 19-27%
-Discharge: 18-52%
-30-day: 65%
-Discharge: 23-61%
Morbidity
-Severe neurological
sequealae
: 11-16%
-Return to functional baseline 39% at
3 months
Factors associated with poor outcome
-Underlying etiology
-De novo
-Duration
-Focal
neurological signs present at onset
-Impaired consciousness
-Age
-Underlying etiology
-Severe mental status impairment
-Duration
-Underlying etiology
-Age
-Duration
-High APACHE-2
scale scores Slide9
Treatment Goals
Emergently stop both clinical and electrographic seizure activity
Definitive control of SE should occur within 60 minutes Slide10
TreatmentAirway protectionEstablish and support baseline vital signs
Establish medication route (Peripheral IV access), in order to:
Stop seizure
Establish
euvolemia
Reverse thiamine deficiency/treat hypoglycemia
Other: labs, EEG, diagnostic testing, neurologic exam
Determine patient’s historySlide11
Drugs That Can Lower Seizure Threshold
Antibiotics
Imipenem
,
penicillins
,
cephalosporins
,
metronidazole
,
isoniazid
Antihistamines
Antipsychotics
Antidepressants
Bupropion
Tricyclics
Baclofen
Fentanyl
Ketamine
Lidocaine
Lithium
Meperidine
Propoxyphene
TheophyllineSlide12
Emergent Initial Therapy Agent of choice = Benzodiazepines
IV:
lorazepam
(Class I, Level A)
IM:
midazolam
(Class I, Level A)
PR: diazepam (Class
IIa
, Level A)
MOA:
increase frequency of
chloride
channel opening in
CNS GABA(A) receptors—decreasing neuronal
excitability
-VERSUS-
MOA of Phenobarbital: enhances GABA (A) chloride currents by increasing duration of chloride channel opening
First-line medications control SE in 80% of patients when initiated within 30 minutes, but in only 40% if started after 2 hours of onset Slide13Slide14
Intranasal Midazolam
Administration
Use of atomizer
Use 5mg/mL
injectable
solution
Higher concentration
injectable
solution to minimize volume
Maximum dose is 1
mL
per
nare
Adverse effects
Burning/irritation Slide15
Urgent Control Therapy Required following benzodiazepine administration in all patients who present with SE
UNLESS known cause of SE is identified and corrected
Goal 1: Rapid attainment of therapeutic levels of an AED and continued dosing for maintenance
Goal 2: To stop SE, if the patient failed emergent control Slide16Slide17
Fosphenytoin versus Phenytoin
MOA: stabilizes neuronal membranes and decreases seizure activity by increasing efflux or decreasing influx of Na ions across cell membranes in the motor cortex during generation of nerve impulses
Dosing difference
Fosphenytoin
is converted to
phenytoin
on a 1:1 molar basis
Molecular weight
fosphenytoin
> Molecular weight of
phenytoin
Greater weight of
fosphenytoin
must be givenSlide18
Questions? Slide19
References Brophy GM, Bell R,
Claassen
J, et al. Guidelines for the evaluation and management of status
epilepticus
.
Neurocrit
Care.
2012;17(1):3-23.
Arif
H, Hirsch LJ. Treatment of status
epilepticus
.
Semin
Neurology
. 2008;28(3):342-354.
Stecker
MM. Status
epilepticus
in adults.
UpToDate
Web site. http://www.uptodate.com/. Accessed May 23, 2014.
UpToDate
Web site. http://
www.uptodate.com
/. Accessed May 24, 2014.