Managing Seizure Patientsin the

Emergency Department

Managing Seizure Patientsin the

Emergency Department

James Wheless, MDDirector, Texas Comprehensive

Epilepsy ProgramUniversity of Texas - Houston

James Wheless, MDDirector, Texas Comprehensive

Epilepsy ProgramUniversity of Texas - Houston

Question #1:Question #1:

When is an antiepileptic drug

(AED) loading dose necessary?

Question #1:Question #1:

When is an antiepileptic drug

(AED) loading dose necessary?

Acute Seizures That Needa Loading Dose

Acute Seizures That Needa Loading Dose

• Seizures secondary to partial compliance

Dose (mg) = weight (Kg) x VD (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 VD (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, atonicMyoclonic, tonic, absence, atonic

Acute Seizures That NeedAcute Seizures That Needa Loading Dosea Loading Dose

Acute Seizures That NeedAcute Seizures That Needa Loading Dosea 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

Acute Seizures That May Not Need a Loading Dose

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)

Question #2:Question #2:

What medications are bestfor an AED loading dose?

Question #2:Question #2:

What medications are bestfor an AED loading dose?

Question #3:Question #3:

What is the empirical therapy

for acute seizures?

Question #3:Question #3:

What is the empirical therapy

for acute seizures?

Question #4:Question #4:

What antiepileptic drugs are useful for nonconvulsive

status epilepticus (SE)(altered mental status presenting

as SE)?

Question #4:Question #4:

What antiepileptic drugs are useful for nonconvulsive

status epilepticus (SE)(altered mental status presenting

as SE)?

Question #5:Question #5:

When do we use:1. Fosphenytoin?2. Phenobarbital?3. IV Valproate?

Question #5:Question #5:

When do we use:1. Fosphenytoin?2. Phenobarbital?3. IV Valproate?

Question #6:Question #6:

What parenteral medicationscan be given if no IV access is available?

Question #6:Question #6:

What parenteral medicationscan be given if no IV access is available?

Development of a Rapid-Development of a Rapid-Onset Intranasal DeliveryOnset Intranasal Delivery

of Diazepamof Diazepam

Development of a Rapid-Development of a Rapid-Onset Intranasal DeliveryOnset Intranasal Delivery

of Diazepamof 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

Pediatric Status Epilepticus:IM Midazolam

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

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

Pharmacokinetics of Pharmacokinetics of Midazolam by Intranasal (IN) Midazolam by Intranasal (IN)

AdministrationAdministration

Pharmacokinetics of Pharmacokinetics of Midazolam by Intranasal (IN) Midazolam by Intranasal (IN)

AdministrationAdministration Subjects (6) had irritation, general discomfort

Suggested doses for status epilepticus:- children 0.2 mg/Kg IN- adults 5-10 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- adults 5-10 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

Parenteral Formulation toParenteral Formulation toAvoid for IM UseAvoid for IM Use

Parenteral Formulation toParenteral Formulation toAvoid for IM UseAvoid for IM Use

Depacon (IV Valproate)IM – muscle necrosis

Phenytoin

IM – muscle necrosis

Phenobarbitalslow onset

Depacon (IV Valproate)IM – muscle necrosis

Phenytoin

IM – muscle necrosis

Phenobarbitalslow onset

Question #7:Question #7:

How do pediatric and adultcases of acute seizures and

status epilepticus differ?

Question #7:Question #7:

How do pediatric and adultcases of acute seizures and

status epilepticus differ?