First Line Therapy in Acute Seizure Management William C. Dalsey, MD, MBA, FACEP Department of Emergency Medicine Robert

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

2. 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.

3. Case • A twenty-seven year old male presents with five minutes of generalized tonic clonic seizures. What is the best choice for initial treatment?

4. What is the best initial treatment for seizure? • Benzodiazepines • Lorazepam • Diazepam • Midazolam • Phenytoin • Phenobarbital

5. 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

6. Which benzodiazepine is the best? • Rate of Success • Duration • Side effects/Complications

7. 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

8. 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

9. 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)

10. 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

11. 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

12. 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

13. 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

14. Alternative treatments when IV access is not available • Fosphenytoin (IM) • Paraldehyde (Rectal, IM)

15. 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

16. 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

17. 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