Ives Hot, PharmD May 28, 2014 UW Medicine Status
Epilepticus
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Definition Status Epilepticus (SE) 5 minutes of more of
continuous clinical and/or electrographic seizure activity -OR-
Recurrent seizure activity without recovery between seizures
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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
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Categorization Convulsive 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)
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) receptorsdecreasing 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
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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
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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
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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 given
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Questions?
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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.