1. Ives Hot, PharmD May 28, 2014 UW Medicine
Status Epilepticus
Ives Hot, PharmD
May 28, 2014
UW Medicine

2. Definition Status Epilepticus (SE)
5 minutes of more of continuous clinical and/or electrographic seizure activity
-OR-
Recurrent seizure activity without recovery between seizures

3. 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
Add uptodate stats

4. Categorization Convulsive Non-convulsive Refractory (RSE)
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)

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

6. Etiology Chronic: Pre-existing epilepsy Chronic ethanol abuse
Breakthrough seizure
Discontinuation/non-adherence to AED
Chronic ethanol abuse
CNS tumors
Remote CNS pathology ( stroke, abscess, TBI, cortical dysplasia)

7. Diagnostic Work-up All Patients Consider 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

8. 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
-Severe mental status impairment
-High APACHE-2 scale scores

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

10. 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 patient’s history
1 and 2

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

12. 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
1 and 2
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

14. Intranasal Midazolam Administration Adverse effects 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

15. 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

17. 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

18. Questions?

19. 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):
Stecker MM. Status epilepticus in adults. UpToDate Web site. Accessed May 23, 2014.
UpToDate Web site. Accessed May 24, 2014.