Treatment of Seizures Without IV Access Robert R' Clancy, MD The Pediatric Regional Epilepsy Program

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Treatment of Seizures Without IV Access Robert
R. Clancy, MDThe Pediatric Regional Epilepsy
Programof the Childrens Hospital of
Philadelphiaand the University of
PennsylvaniaSchool of Medicine
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Best Chance of Seizure Response AEDs

• Early and effective AED treatment
• Speed and reliability of IV route for AED
  administration is generally preferred, but
• Advanced care sometimes unavailable or remote or,
  
• Available but unable to establish IV access
• Optional routes without IV access interosseous,
  PR, IM, nasal, buccal and SL

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Which of the Following Choices Are Suitable for
IM AED Administration for Acute Seizure Control?

• Phenobarbital, lorazepam and phenytoin
• Fosphenytoin, phenobarbital and diazepam
• Phenobarbital, midazolam and fosphenytoin
• Valproate, lorazepam and fosphenytoin

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What is the recommended dose of rectal diazepam
for a 2-year old child?

• 0.04 mg/kg/dose
• 0.10 mg/kg/dose
• 0.50 mg/kg/dose
• 2.50 mg/kg/dose

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Which of the following statements about the risk
of respiratory depression after acute AED
administration is FALSE?

• The risk is higher when benzodiazepine is
  co-administered with phenobarbital.
• The risk with lorazepam is higher than diazepam.
• The risk is increased when the seizures are
  caused by an acute, severe brain injury.
• The risk is generally proportional to the speed
  of AED bolus administration.

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A 14-year old high school student has
post-traumatic epilepsy and occasional prolonged
seizures in the classroom. The school nurse asks
for management guidelines. You recommend

• Home schooling
• Rectal diazepam, as needed
• Buccal midazolam, as needed
• Rectal diazepam for the school nurse, as needed

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Routes for Urgent AED Administration Without IV
Access

• Aborts seizure clusters
• Avoids progression to status epilepticus
• May reduce visits to ED hospitalizations
• Lower urgency (PR, IM, nasal, buccal, SL)
• Higher urgency interosseous
• Available AEDs diazepam, lorazepam, phenytoin,
  fosphenytoin and phenobarbital

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Rectal Administration of AEDs

• Absorption occurs by passive diffusion through
  lipoidal membranes
• Optimal drug is lipid-soluble and non-ionized
• Absorption of solutions gt suppositories
• AEDs absorbed by middle and inferior rectal veins
  which bypass portal circulation and avoids
  first-pass hepatic elimination

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Rectal Administration of AEDs

• Drawbacks
• Loss of administered AED into stool
• Expulsion from cathartic effect
• Social implications from administration by
  non-family member
• Embarrassment
• Commercial kit expensive

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Nasal Administration

• Drugs may be rapidly absorbed via solution
  instilled in nasal mucosa
• Existing practice and literature supports use in
  anesthesia and acute seizures
• Drawback increase mucous production and nasal
  discharge during seizures pre-existing nasal
  congestion from URI etc.

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Buccal and Sublingual Administration

• Buccal absorption of small volumes of AEDs
• Just a pinch between cheeks and gums
• Concerns for provoking gagging, coughing,
  aspiration or oral loss of drug
• Sublingual may be used between serial seizures
  not useful when teeth clenched

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Diazepam

• Available routes are IV and rectal
• PO and IM administration inadequate if prompt
  response needed
• Rectal administration
• Peak serum concentration in 6 min
• 96 effective if given in first 15 min of sz
• May need repeat doses (short-acting) or second
  AED
• May be repeated in 10 min

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Rectal Doses of Diazepam for Children

• 2-5 years 0.5 mg/kg/dose
• 6-11 years 0.3 mg/kg/dose
• 12 years 0.2 mg/kg/dose
• Formulations IV diazepam 2 ml vials with 5 mg/ml
  (dont forget to remove the needle)
• Prepackaged commercial kits with 2.5 mg, 5.0 mg,
  10 mg, 15 mg or 20 mg

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Lorazepam

• May have some advantages over diazepam if given
  IV
• Lower risk of respiratory depression
• Longer duration of desired AED effects
• Marginally better seizure response
• Rectal dose 0.2 mg/kg/dose
• Intravenous form ideally refrigerated
• Sublingual administration also reported

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Midazolam

• May be given IV, IM, rectal, buccal or nasal
• Ideal for IM injection
• Pediatric dose 0.1-0.3 mg/kg may repeat in 15
  min
• Adult dose 5-10 mg
• 80-100 IM dose absorbed
• Peak effect in 25 min
• Similar speed and effect as IV diazepam to abort
  EEG seizures

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Midazolam

• Available in 2 ml IV ampules (5 mg/ml)
• Dose for buccal administration 10 mg (studies
  in children gt 5 years)
• Nasal administration 0.2 mg/kg/dose

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Fosphenytoin

• Prodrug of phenytoin
• IV fosphenytoin achieves a free phenytoin level
  of 2 µg/ml in 15 min compared to 25 min with
  phenytoin (after 20 mg/kg load)
• Well absorbed by IM route therapeutic in 3 min)
• No requirement for cardiac monitoring

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Other AEDs That Can Be Administered Rectally But
Slowly Achieve Therapeutic Blood Levels

• Valproate syrup _at_ 20 mg/kg (diluted 11 by
  volume with tap water) gt90 bioavailable
• Lamotrigine (63 bioavailable)
• Phenobarbital elixir

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Which of the Following Choices Are Suitable for
IM AED Administration for Acute Seizure Control?

• Phenobarbital, lorazepam and phenytoin
• Fosphenytoin, phenobarbital and diazepam
• Phenobarbital, midazolam and fosphenytoin (Best)
• Valproate, lorazepam, fosphenytoin

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What is the Recommended Dose of Rectal Diazepam
for a 2-Year Old Child?

• 0.04 mg/kg/dose
• 0.10 mg/kg/dose
• 0.50 mg/kg/dose (Best)
• 2.50 mg/kg/dose

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Which of the Following Statements About the Risk
of Respiratory Depression After Acute AED
Administration is FALSE?

• The risk is higher when a benzo is coadministered
  with phenobarbital.
• The risk with lorazepam is higher than diazepam.
  (False)
• The risk is increased when the seizures are
  caused by an acute, severe brain injury.
• The risk is generally proportional to the speed
  of AED bolus administration.

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A 14-year old high school student has
post-traumatic epilepsy and occasional prolonged
seizures in the classroom. The school nurse asks
for management guidelines. You recommend

• Home schooling
• Rectal diazepam, as needed
• Buccal midazolam, as needed (Best)
• Rectal diazepam for the school nurse, as needed
• (Dont even go there)