Status Epilepticus

Ives Hot, PharmD

May 28, 2014

UW Medicine

Status Epilepticus

Definition

Status Epilepticus (SE)

5 minutes of more of continuous clinical and/or electrographic seizure activity

-OR-

Recurrent seizure activity without recovery between seizures

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)

Etiology

Acute:

Metabolic disturbances

Sepsis

CNS infection: meningitis, encephalitis, abscess

Stroke

Head trauma

Pharmacologic

Hypertensive encephalopathy

Autoimmune encephalitis

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)

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

Prognosis

ConvulsiveNon-convulsiveRSEMortality-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

Treatment Goals

Emergently stop both clinical and electrographic seizure activity

Definitive control of SE should occur within 60 minutes

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

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

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

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

Questions?

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.