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First Line Therapy in Acute Seizure Management William C. Dalsey, MD, MBA, FACEP Department of Emergency Medicine Robert PowerPoint Presentation
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First Line Therapy in Acute Seizure Management William C. Dalsey, MD, MBA, FACEP Department of Emergency Medicine Robert Wood Johnson University Hospital New Jersey. Case.

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First Line Therapy in Acute Seizure Management

William C. Dalsey, MD, MBA, FACEP

Department of Emergency Medicine

Robert Wood Johnson University Hospital

New Jersey

slide2
Case
  • A seven year old with spina bifida and arnold chiari fell and hit her head. She has intermittent generalized tonic clonic seizures without return to baseline. IV access can’t be obtained.
slide3
Case
  • A twenty-seven year old male presents with five minutes of generalized tonic clonic seizures. What is the best choice for initial treatment?
what is the best initial treatment for seizure
What is the best initial treatment for seizure?
  • Benzodiazepines
    • Lorazepam
    • Diazepam
    • Midazolam
  • Phenytoin
  • Phenobarbital
va cooperative study
VA Cooperative Study
  • Compared lorazepam to diazepam + phenytoin to phenytoin to phenobarbital
  • 12 hour and 30 day outcomes were the same in all groups
  • Lorazepam recommended as the drug of choice because of efficacy and ease of administration

Treiman. NEJM 1998; 339:792-798

which benzodiazepine is the best
Which benzodiazepine is the best?
  • Rate of Success
  • Duration
  • Side effects/Complications
benzodiazepines
Benzodiazepines
  • Review of 47 clinical trials involving 1346 patients
  • 79% control rate of seizure
    • Higher rate than the VA Cooperative Study probably because of selection bias
  • No superiority of one benzo over the other in terminating seizures

Treiman. Epilepsia 1989:30;4-10

benzodiazepines8
Benzodiazepines
  • Lorazepam .1 mg / kg vs diazepam .2 mg / kg
  • Lorazepam has a smaller volume of distribution = longer duration of anticonvulsant action
      • 12 hours for lorazepam vs 20 minutes for diazepam
      • Seizure recurrence 50% with diazepam vs 20% with lorazepam
      • If diazepam used, second AED must be started
  • Lorazepam may have less respiratory depression

Prensky. NEJM 1967; 276:779-784

Leppik. JAMA 1983; 249:1452-1454

if you have no iv access are there alternatives routes for benzodiazepines administration
If you have no IV access, are there alternatives routes for benzodiazepines administration?
  • Intranasal (Midazolam)
  • Buccal (Midazolam)
  • IM (Lorazepam, Midazolam)
  • Rectal (Diazepam, Midazolam)
  • ET (Diazepam)
intramuscular midazolam
Intramuscular Midazolam
  • Water soluble; well absorbed
  • Adult dose 10 - 15 mg
  • Case reports

Jawad. J Neurol Neurosurg Psych 1986; 49:1050-1054

Chamberlain. Pediatr Emerg Care 1997; 13:92-94

rectal diazepam
Rectal Diazepam
  • Diazepam well absorbed rectally: gel or solution better than suppositories
      • Tmax 17 minutes with therapeutic effect earlier
  • May provide longer acting anticonvulsant effect than intravenous administration due to slower absorption rate
  • Has been used effectively by EMS

Dieckmann. Ann Emerg Med 1994; 23:216-224

rectal diazepam12
Rectal Diazepam
  • Diazepam get (Diastat)
  • Indicated for children with acute repetitive seizures
  • Double blind placebo controlled studies have demonstrated its effectiveness
  • Main side effect: Somnolence

Cereghino. Neurology 1998;51:1274-1282

rectal diazepam13
Rectal Diazepam
  • Dosing is age dependent:
    • 2 -5 years: .5 mg / kg
    • 6 - 11 years: .3 mg / kg
    • > 11 years: .2 mg /kg
  • Prepackaged commercial syringes available in 2.5, 5, 10, 20 mg
alternative treatments when iv access is not available
Alternative treatments when IV access is not available
  • Fosphenytoin (IM)
  • Paraldehyde (Rectal, IM)
intramuscular fosphenytoin
Intramuscular Fosphenytoin
  • 100 % bioavailable
  • 20 PE /kg: 20 cc intragluteal
  • Therapeutic levels at 1 hours
  • Pruritis and paresthesias most common side effects
  • Cardiac monitoring not necessary

DeToledo. Emerg Med 1996; supplement:26-31

paraldehyde
Paraldehyde
  • Can be given IM or PR: parenteral preparation no longer available in the US
  • Old literature reports effectiveness but was used before availability of phenytoin or benzodiazepines
  • Can cause heart failure, hypotension, pulmonary hemorrhage, tissue necrosis
  • 80% bioavailable when given rectally

Ramsay. Epilepsia 1989;30(suppl):S1-S3

conclusions
Conclusions
  • Lorazepam is the preferred first line agent for seizure control due to its long lasting anticonvulsant properties.
  • Diazepam is equally effective but requires that a concomitant, long acting AED be administered.
  • When the IV access is unavailable:
    • IM midazolam
    • Rectal diazepam
    • IM fosphenytoin