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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)

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Etiology Acute: Metabolic disturbances Sepsis CNS infection: meningitis, encephalitis, abscess Stroke Head trauma Pharmacologic Hypertensive encephalopathy Autoimmune encephalitis

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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)

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Diagnostic Work-up All 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 tests

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Prognosis ConvulsiveNon-convulsiveRSE 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

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Treatment Goals Emergently stop both clinical and electrographic seizure activity Definitive control of SE should occur within 60 minutes

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Treatment Airway protection Establish 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 patients history

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Drugs That Can Lower Seizure Threshold Antibiotics Imipenem, penicillins, cephalosporins, metronidazole, isoniazid Antihistamines Antipsychotics Antidepressants Bupropion Tricyclics Baclofen Fentanyl Ketamine Lidocaine Lithium Meperidine Propoxyphene Theophylline

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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.