1. Managing Seizure Patients in the Emergency Department Managing Seizure Patients in the Emergency Department James Wheless, MD Director, Texas Comprehensive Epilepsy Program University of Texas - Houston James Wheless, MD Director, Texas Comprehensive Epilepsy Program University of Texas - Houston

2. Question #1: When is an antiepileptic drug (AED) loading dose necessary? Question #1: When is an antiepileptic drug (AED) loading dose necessary?

3. Acute Seizures That Need a Loading Dose Seizures secondary to partial compliance Dose (mg) = weight (Kg) x V D (L/Kg) x D Cp (mg/dL) Seizures with a high rate of recurrence (Some seizures are like potato chips: you can never have just one!!) Seizures secondary to partial compliance Dose (mg) = weight (Kg) x V D (L/Kg) x D Cp (mg/dL) Seizures with a high rate of recurrence (Some seizures are like potato chips: you can never have just one!!) Myoclonic, tonic, absence, atonic

4. Acute Seizures That Need a Loading Dose Progressive neurologic disease Acute symptomatic seizures New onset adult seizures Status epilepticus – depends on etiology (febrile status epilepticus- probably not) Neonatal seizures Progressive neurologic disease Acute symptomatic seizures New onset adult seizures Status epilepticus – depends on etiology (febrile status epilepticus- probably not) Neonatal seizures

5. Acute Seizures That May Not Need a Loading Dose New onset pediatric complex partial, generalized tonic-clonic seizures (not status epilepticus) Febrile seizures Some acute symptomatic seizures (i.e., decreased blood sugar) New onset pediatric complex partial, generalized tonic-clonic seizures (not status epilepticus) Febrile seizures Some acute symptomatic seizures (i.e., decreased blood sugar)

6. Question #2: What medications are best for an AED loading dose? Question #2: What medications are best for an AED loading dose?

8. Question #3: What is the empirical therapy for acute seizures? Question #3: What is the empirical therapy for acute seizures?

18. Question #4: What antiepileptic drugs are useful for nonconvulsive status epilepticus (SE) (altered mental status presenting as SE)? Question #4: What antiepileptic drugs are useful for nonconvulsive status epilepticus (SE) (altered mental status presenting as SE)?

24. Question #5: When do we use: 1. Fosphenytoin? 2. Phenobarbital? 3. IV Valproate? Question #5: When do we use: 1. Fosphenytoin? 2. Phenobarbital? 3. IV Valproate?

39. Question #6: What parenteral medications can be given if no IV access is available? Question #6: What parenteral medications can be given if no IV access is available?

43. Development of a Rapid- Onset Intranasal Delivery of Diazepam Effective nasal delivery volume < 300ml (150ml/nostril) Ethyl laurate-based microemulsion developed Diazepam solubility in microemulsion is 41 mg/ml Bioavailability = ½ of IV diazepam Maximum plasma concentration reached in 2-3 min. Li L et al (B M Squibb), Int. J. Pharm., 2002, 237 (1-2): 77-85 Effective nasal delivery volume < 300ml (150ml/nostril) Ethyl laurate-based microemulsion developed Diazepam solubility in microemulsion is 41 mg/ml Bioavailability = ½ of IV diazepam Maximum plasma concentration reached in 2-3 min. Li L et al (B M Squibb), Int. J. Pharm., 2002, 237 (1-2): 77-85

44. Pediatric Status Epilepticus: IM Midazolam  Children (N = 48) 4 mo.- 14 yrs. (69 episodes)  Midazolam 0.2 mg/Kg IM in ER  35 seizures 10-20 min., 34 > 20 min. duration at presentation in ER  Results: 57 episodes (83%) stopped in 1-5 min. 7 episodes (10%) stopped in 5-10 min. Lahat E et al, Pediatric Neurology, 1992; 8: 215-216  Children (N = 48) 4 mo.- 14 yrs. (69 episodes)  Midazolam 0.2 mg/Kg IM in ER  35 seizures 10-20 min., 34 > 20 min. duration at presentation in ER  Results: 57 episodes (83%) stopped in 1-5 min. 7 episodes (10%) stopped in 5-10 min. Lahat E et al, Pediatric Neurology, 1992; 8: 215-216

46. Chaimberlain JM, Pediatric Emerg. Care, 1997;13, 92

50. Pharmacokinetics of Midazolam by Intranasal (IN) Administration  Subjects (6) had irritation, general discomfort  Suggested doses for status epilepticus: - children 0.2 mg/Kg IN - adults5-10 mg IN  Parenteral midazolam 5 mg/ml  Mean peak plasma conc. reached 14 min. (+5)  Mean bioavailability 0.83 (+0.19) IN Knoester PD et al, Br. J. Clin. Pharmacol., 2002; 53(5): 501-507  Subjects (6) had irritation, general discomfort  Suggested doses for status epilepticus: - children 0.2 mg/Kg IN - adults5-10 mg IN  Parenteral midazolam 5 mg/ml  Mean peak plasma conc. reached 14 min. (+5)  Mean bioavailability 0.83 (+0.19) IN Knoester PD et al, Br. J. Clin. Pharmacol., 2002; 53(5): 501-507

56. Parenteral Formulation to Avoid for IM Use  Depacon (IV Valproate) IM – muscle necrosis  Phenytoin IM – muscle necrosis  Phenobarbital slow onset  Depacon (IV Valproate) IM – muscle necrosis  Phenytoin IM – muscle necrosis  Phenobarbital slow onset

58. Question #7: How do pediatric and adult cases of acute seizures and status epilepticus differ? Question #7: How do pediatric and adult cases of acute seizures and status epilepticus differ?