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. William Dalsey, MD 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 cant be obtained.

3. William Dalsey, MD 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. William Dalsey, MD What is the best initial treatment for seizure? Benzodiazepines –Lorazepam –Diazepam –Midazolam Phenytoin Phenobarbital

5. William Dalsey, MD 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. William Dalsey, MD Which benzodiazepine is the best? Rate of Success Duration Side effects/Complications

7. William Dalsey, MD 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. William Dalsey, MD 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. William Dalsey, MD 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. William Dalsey, MD 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. William Dalsey, MD Rectal Diazepam Diazepam well absorbed rectally: gel or solution better than suppositories T max 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. William Dalsey, MD 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. William Dalsey, MD 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. William Dalsey, MD Alternative treatments when IV access is not available Fosphenytoin (IM) Paraldehyde (Rectal, IM)

15. William Dalsey, MD 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. William Dalsey, MD 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. William Dalsey, MD 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