1. First Line Therapy in Acute Seizure Management William C. Dalsey, MD, FACEP, MBA Department of Emergency Medicine Robert Wood Johnson University Hospital New Jersey sparkledmd@aol.com 215-654-1190

2. Case Presentations 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 hours of generalized tonic clonic seizures. What is the best choice for initial treatment?

4. Critical Questions How do you evaluate and treat a patient with a seizure? Complicating Factors: Status Epilepticus? Hypoglycemia, Febrile Seizures, Alcohol Withdrawal, Trauma, Eclampsia

5. Critical Critical Questions (cont.) Alcohol Withdrawal Seizures Febrile Seizures What is the best treatment?

6. What is best? Efficacy of Treatment? Safety? Complications? Side Effects? Route of Administration? Costs?

7. What are the choices of initial treatment for seizure? Benzodiazepines –Lorazepam –Diazepam –Midazolam Phenytoin/Fosphenytoin Phenobarbital Valproate Anesthetics

8. What does the literature show? Benzodiazepines Phenytoin/Fosphenytoin Phenobarbital Valproate Anesthetics

9. 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

10. Which benzodiazapine is the best? Rate of Success Duration Side effects/Complications

11. 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

12. 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

13. 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)

14. 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

15. 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

16. 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

17. 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

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

19. 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

20. 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

21. 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

22. So, what would I (you) do? Ativan (Lorazepam) Dilantin Phenobarbital

23. What if there is no IV access? IM Versed/Ativan Rectal Valium IM Fosphenytoin