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  • 1. Managing Seizure Patients in the Emergency Department James Wheless, MD Director, Texas Comprehensive Epilepsy Program University of Texas - Houston
  • 2. Question #1: When is an antiepileptic drug (AED) loading dose necessary?
  • 3. Acute Seizures That Need a Loading Dose <ul><li>Seizures secondary to partial compliance </li></ul><ul><li>Dose (mg) = weight (Kg) x V D (L/Kg) x D Cp (mg/dL) </li></ul><ul><li>Seizures with a high rate of recurrence </li></ul><ul><li> (Some seizures are like potato chips: </li></ul><ul><li> you can never have just one!!) </li></ul>Myoclonic, tonic, absence, atonic
  • 4. Acute Seizures That Need a Loading Dose <ul><li>Progressive neurologic disease </li></ul><ul><li>Acute symptomatic seizures </li></ul><ul><li>New onset adult seizures </li></ul><ul><li>Status epilepticus – depends on etiology </li></ul><ul><li>( febrile status epilepticus- probably not) </li></ul><ul><li>Neonatal seizures </li></ul>
  • 5. Acute Seizures That May Not Need a Loading Dose <ul><li>New onset pediatric complex partial, </li></ul><ul><li>generalized tonic-clonic seizures </li></ul><ul><li>( not status epilepticus) </li></ul><ul><li>Febrile seizures </li></ul><ul><li>Some acute symptomatic seizures </li></ul><ul><li>(i.e., decreased blood sugar) </li></ul>
  • 6. Question #2: What medications are best for an AED loading dose?
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  • 8. Question #3: What is the empirical therapy for acute seizures?
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  • 18. Question #4: What antiepileptic drugs are useful for nonconvulsive status epilepticus (SE) (altered mental status presenting as SE)?
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  • 24. <ul><li>Question #5: </li></ul><ul><li>When do we use: </li></ul><ul><li>Fosphenytoin? </li></ul><ul><li>Phenobarbital? </li></ul><ul><li>IV Valproate? </li></ul>
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  • 39. Question #6: What parenteral medications can be given if no IV access is available?
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  • 43. Development of a Rapid- Onset Intranasal Delivery of Diazepam <ul><li>Effective nasal delivery volume < 300ml (150ml/nostril) </li></ul><ul><li>Ethyl laurate-based microemulsion developed </li></ul><ul><li>Diazepam solubility in microemulsion is 41 mg/ml </li></ul><ul><li>Bioavailability = ½ of IV diazepam </li></ul><ul><li>Maximum plasma concentration reached in 2-3 min. </li></ul><ul><li>Li L et al (B M Squibb), Int. J. Pharm., 2002, 237 (1-2): 77-85 </li></ul>
  • 44. Pediatric Status Epilepticus: IM Midazolam <ul><li>Children (N = 48) 4 mo.- 14 yrs. (69 episodes) </li></ul><ul><li>Midazolam 0.2 mg/Kg IM in ER </li></ul><ul><li>35 seizures 10-20 min., 34 > 20 min. duration at </li></ul><ul><li>presentation in ER </li></ul><ul><li>Results: </li></ul><ul><ul><li>57 episodes (83%) stopped in 1-5 min. </li></ul></ul><ul><ul><li>7 episodes (10%) stopped in 5-10 min. </li></ul></ul><ul><ul><li>Lahat E et al, Pediatric Neurology, 1992; 8: 215-216 </li></ul></ul>
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  • 46. Chaimberlain JM, Pediatric Emerg. Care, 1997;13, 92
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  • 50. Pharmacokinetics of Midazolam by Intranasal (IN) Administration <ul><li>Subjects (6) had irritation, general discomfort </li></ul><ul><li>Suggested doses for status epilepticus: </li></ul><ul><li>- children 0.2 mg/Kg IN </li></ul><ul><li>- adults 5-10 mg IN </li></ul><ul><li>Parenteral midazolam 5 mg/ml </li></ul><ul><li>Mean peak plasma conc. reached 14 min. ( + 5) </li></ul><ul><li>Mean bioavailability 0.83 ( + 0.19) IN </li></ul><ul><li>Knoester PD et al, Br. J. Clin. Pharmacol., 2002; 53(5): 501-507 </li></ul>
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  • 56. Parenteral Formulation to Avoid for IM Use <ul><li>Depacon (IV Valproate) </li></ul><ul><li>IM – muscle necrosis </li></ul><ul><li>Phenytoin </li></ul><ul><li>IM – muscle necrosis </li></ul><ul><li>Phenobarbital </li></ul><ul><li>slow onset </li></ul>
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  • 58. Question #7: How do pediatric and adult cases of acute seizures and status epilepticus differ?
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