The Seizing Patient

Abdul Aziz Al SibaniR 1

Objective

• To know the causes and classification of seizure

• How to approach a seizing patient • Management of seizing pt • Case scenarios• Seizure caused by toxins • Seizure in pregnancy• Febrile aizure

Introduction

• A seizure is the clinical manifestation of excessive, abnormal cortical neuronal activity.

• Primary vs secondary (reactive)• Generalized vs partial

Reactive seizures in adults

• Seizures caused by metabolic derangement• Seizures caused by infectious diseases • Seizures caused by drugs and toxins • Seizures caused by trauma• Seizures associated with malignancy or vasculitis • Seizures caused by strokes, AVM and migraines• Seizures caused by degenerative disease of the

CNS • Gestational seizure

Status epilepticus • Serial seizure activity without interictal

recovery or prolonged, continuous seizure activity.

• Overall 30 day mortality for patients with generalized status epilepticus was 19-27%

• The most common cause of status epilepticus is discontinuation of AEM.

ETIOLOGY OF STATUS EPILEPTICUS: COMMON CAUSATIVE DISORDERS

• Metabolic Disturbances Hepatic encephalopathy

Hypocalcemia Hypoglycemia or hyperglycemia Hyponatremia Uremia

• Infectious Processes CNS abscess Encephalitis Meningitis

• Intoxication Bupropion Camphor Clozapine Cyclosporine Flumazenil Fluoroquinolones Imipenem Isoniazid Lead Lidocaine Lithium Metronidazole Theophylline Tricyclic antidepressants

• Withdrawal Syndromes Alcohol

Antiepileptic drugs Baclofen Barbiturates Benzodiazepams

• CNS Lesions Acute hydrocephalus Anoxic or hypoxic insult Arteriovenous malformations Brain metastases Cerebrovascular accident Chronic epilepsy Eclampsia Head trauma Intracerebral hemorrhage Neoplasm Neurosurgery Posterior reversible leukoencephalopathy Remote structural injury

The Seizing Patient

• Case I: • First time seizure presenting to ER, seizure

resolved by time off arrival

• Was this truly a seizure?

seizure

1. Abrupt onset2. Brief duration3. Altered mental status4. Purposeless activity5. Unprovoked 6. Post-ictal state

• Syncope classically masquerades as seizure and may include body movements

1) Clues that episode may have been syncope: Brief episode of unconscousness followed by rapid return of mental staus

2) Clues that episode may have been seizure:Bowel/bladder incontinence, presence of post-ictal confusional period

• Perform thorough history and physical looking for clues to conditions that may lead to seizures:

• Review history for use of drugs• Review history for neurological symptoms suggesting

focal disease:• Ask about any changes in mental status, motor or sensory

function• Perform physical exam:• Examine head and tongue for signs of trauma• Examine for focal neuro deficits may point to speficic

brain lesion as etiology of seizures:• Focal motor or sensory deficits, ocular movement

abnormalities, gait instability, pronator drift

• Lab testing:• Blood sugar, PT, urea and electrolytes• ECG• CT brain • EEG

• Should Anti-Epileptics be started from the Emergency Department?

Case II

• Patient with known H/O seizure presenting to ER

• Seizure resolved by time off arrival • Drug level: 1. If anti-epileptic dug can be measured and is at

subtherapeutic levels2. If anti-epileptic drug can be measured and is at

therapeutic levels3. If anti-epileptic drug cannot be measured

Case III

• Paramedics call with status epilepticus notification • 54 yrs old male found seizing at home, tonic clonic

type pattern • Negative PMHx and family Hx• RBS 100• BP 180/100, HR 110/min, RR 20• Paramedics have attempted multiple IV, all

attempts failed • Paramedics call for orders; what is your response?

Case III

• Status epilepticus: Pre-Hospital: • no IV access:• IM midazolam 0.2mg/kg to 10mg max• Buccal midazolam 0.2mg/kg to 10mg max• Rectal diazepam 0.5 mg/kg to 20 mg max

• Status epilepticus: Pre-Hospital: • IV access obtained :• Lorazepam IV 0.1mg /kg to 4mg max• Diazepam IV 0.2mg /kg to 10 mg max

Case III, cont,

• Paramedics have given lorazepam 2mg IV • Pt started seizing again as paramedics pull into

ED• What is next action:1. RSI2. Fosphenytoin 3. Lorazepam 2-4 mg iv 4. Diazepam 5-10 mg iv

Rapid assessment and stabilization

• A B C D • Lorazepam • Paediatric dose: 0.1mg/kg bolus • Adults: 2-4mg bolus • May repeat twice prn

Midazolam

• Highly lipophilic drug:• May be given intramuscularly or across

mucous membranes with high resultant peak serum levels

• Fast onset of action• Heat stable and easily stored for EMS use

Diazepam

• Highly lipophilic drug• Available as gel with good efficacy when given

via rectal route• Heat stable and easily stored for EMS use• Will control seizures when given intravenously• May be less optimal than lorazepam

Lorazepam

• Less lipophilic properties-not optimal when given via intramuscular route

• Longer redistribution half life over diazepam as less lipophilic

• Heat labile and should be refrigerated for long term storage• If given in adequate doses, will terminate seizures in 90%

patients• Allow 5 minutes to assess for drug efficacy• Once 8-12 mg of lorazepam given and patient still seizing:• Defines refractory status epilepticus and time to move to

new drug

Case III, cont,

• Pt continues to seize despite administration of 12 mg lorazepam

• What is next?

• Phenytoin IV• Phosphenytoin

Second line approach

Phenytoin IV• works by stabilizing sodium channels• 20-30 mg/kg bolus • Max rate 1mg/kg/min or 50 mg/min• Disadvantages: Local tissue irritation/destruction if line infiltratesCannot be given IMmay cause metabolic acidosis / hypotensionCardiac arrhythmias may occur in rare cases-monitor on

telemetry

Phosphenytoin• Disodium phosphate ester of pheytoin• Measured in phosphenytoin units (PE)• Freely soluble in aqueous solutions• Less tissue damage if accidentally extravasates• Can be given intramuscularly• 20-30 PE/kg bolus• Max rate 3PE/kg/min or 150 PE/min• Disadvantages: May rarely cause hypotension and arrhythmias Drug hypersensitivity syndrome: Cross reactivity between phenytoin/phosphenytoin,

phenobarbital, carbamezipine and primidone resulting in rash, fever, lympadenopathy and occasional liver/renal damage

Case III, cont,

• Pt still seizing with tonic clonic movement• Pulse oximetry 96%• What medications would you order now?

Third line approach

• Many experts/pathways are now placing IV valproate and levetiracetam before use of phenobarbital.

Third line approach

Valproate IV• Classic anti-epileptic drug that also stabilizes

sodium channels• IV form now available and has been found

effective in refractory status epilepticus• 20 mg/kg bolus • Max rate 5mg/kg/min or 300mg/min• Can cause hepatotoxicity

Levetiracetam

• Newer anti-epileptic drug that has multiple sites of action:

• Blocks calcium dependent neurotransmitter release and modulates GABA receptors

• IV Formulation is now approved in adults• Pediatric use not FDA approved• 20 mg/kg bolus • Max rate 5mg/kg/min or 300mg/min

Phenobarbital

• Multiple effects include GABA mediated neuronal depression• Still considered first line therapy in treating seizures in

neonates• Advantages include rescue therapy in refractory status

epilepticus unresponsive to other medications• 20mg bolus • Max rate 1-2mg /kg /min or 50-100 mg/min• Prepare for intubation• Phenobarbital can cause high rate of hypotension• IV fluids should be given simultaneously• Pressors may also be needed to maintain blood pressure

Propofol:

• Used as constant infusion• Initiate with 1-2 mg/kg bolus• Continue infusion with 1 mg/kg/hour• Associated with high rate of hypotension:Give intravenous fluidsPressors may be needed

Midazolam

• Used as constant infusion• Initiate with 0.2 mg/kg bolus to max of 10 mg• Continue infusion with 0.2 mg/kg/hour

Special scenarios

1) Sympathomimetics:• Classic is cocaine• Maximize benzodiazepines dosages• Phenobarbital indicated instead of phenytoin for

second line therapy2) Alcohol Withdrawal Seizures:• Maximize benzodiazepine dose• Phenobarbital indicated instead of phenytoin for

second line therapy

3) Other specific drugs that may cause seizures:• Generally initiate therapy with benzodiazepine• Phenobarbital generally indicated as second

line agent over pheytoin

Case IV

• 28-yrs old female present to ED with h/o seizure

• PMHX – NSVD 3 weeks ago• Has second seizure in ED • What is your order?

Pregnancy

• Seizures may be sign of eclampsia after 20 weeks gestation

• May occur post-partum in segment of affected patients

• Load with 4-6 grams magnesium sulfate• Continue infusion with 1-2 grams per hour

Febrile seizure in children

• Seizure occurring in the presence of fever without CNS infection or other cause

• Occurs in 2 to 5% of all children between the age of 6 months and 5 years

• Simple vs complex

Uncomplicated seizure:• Duration of less than 15 minutes

in child 6 months to 5 years• Usually tonic-clonic, without

focality• Related more to rate of rise in

temperature, rather than absolute temperature

• Usual care-no specific seizure workup

• Perform infection workup as indicated

Complicated seizure:• Duration greater than 15

minutes• Focality to seizure

presentation• Occurring in children before

age 6 months and after 5 years

• May require specific seizure workup (CT, LP)

Conclusion

• Seizure is a common disease in routine Emergency Medicine practice

• Newer second generation medications increasingly used

• Serum levels cannot be rapidly obtained in Emergency Department

• Neurology input may be needed to modulate doses

Conclusion

Status Epilepticus:• Newer definition has shortened duration of seizure activity

to 5 minutes• Aggressive therapy to rapidly break seizures crucial• As seizures become prolonged-more difficult to control

(kindling theory)• IV formulations of valproate and levetiracetam now

available• Preliminary studies suggest role for these agents in

refractory status epilepticus before intitating phenobarbital

Conclusion

Drug Related Seizures (intoxications, withdrawal):

• Majority Toxicology concensus is to first maximize benzodiazepines

• Phenobarbital generally preferred over phenytoin for second line therapy