Best Chance of Seizure Response AEDs

1. Treatment of Seizures Without IV AccessRobert R. Clancy, MDThe Pediatric Regional Epilepsy Programof the Children’s Hospital of Philadelphiaand the University of PennsylvaniaSchool of Medicine

2. 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

3. 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

5. 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

7. 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.

9. Home schooling Rectal diazepam, as needed Buccal midazolam, as needed Rectal diazepam for the school nurse, as needed 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:

11. 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

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

13. 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

14. 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.

15. 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

17. 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

20. 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 (don’t forget to remove the needle) • Prepackaged commercial kits with 2.5 mg, 5.0 mg, 10 mg, 15 mg or 20 mg

22. 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

24. 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

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

27. 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

28. Other AEDs That Can Be Administered Rectally But Slowly Achieve Therapeutic Blood Levels • Valproate syrup @ ~20 mg/kg (diluted 1:1 by volume with tap water); >90% bioavailable • Lamotrigine (~63% bioavailable) • Phenobarbital elixir

29. 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

30. 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

31. 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.

32. Home schooling Rectal diazepam, as needed Buccal midazolam, as needed (Best) Rectal diazepam for the school nurse, as needed (Don’t even go there) 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: