1. Benzodiazepines What are the Best Non-IV Parenteral Options for a Seizing Patient? William C. Dalsey, MD, FACEP, MBA Department of Emergency Medicine Robert Wood Johnson University Hospital New Jersey

2. William Dalsey, MD, MBA Case #1 Presentation 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. William Dalsey, MD, MBA Case 2 Presentation 24 year old male with IVDA brought by police with generalized tonic- clonic seizures and no IV access

4. William Dalsey, MD, MBA Critical Questions What is this best first-line treatment? What if I can’t obtain IV access? Complicating Factors: Status Epilepticus? Hypoxia, Hypoglycemia, Fever

5. William Dalsey, MD, MBA What does the literature show? Benzodiazepines Phenytoin/Fosphenytoin Phenobarbital Valproate Anesthetics

6. William Dalsey, MD, MBA 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

7. William Dalsey, MD, MBA What do Clinical Policies/Guidelines and the literature support? Class A recommendation: both IV diazepam followed by phenytoin or the use of IV lorazepam are acceptable acute treatment strategies Is lorazepam better? Treiman. NEJM 1998; 339:792-798

8. William Dalsey, MD, MBA What else does the literature show? Class B Recommendations: 1.All benzodiazepines are highly effective. In pediatric patients lorazepam may be preferred due to less risk of respiratory suppression Treiman. Epilepsia 1989:30;4-10 Treiman. Epilepsia 1989:30;4-10 Prensky. NEJPM 1967; 276:779-784 Prensky. NEJPM 1967; 276:779-784 Leppik. JAMA 1983; 249:1452-1454 Leppik. JAMA 1983; 249:1452-1454

9. William Dalsey, MD, MBA 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, MBA 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 Double blind placebo controlled studies have demonstrated its effectiveness Dieckmann. Ann Emerg Med 1994; 23:216-224 Cereghino. Neurology 1998;51:1274-1282 Remy. Epilepsia 1992;22(2):3530358

11. William Dalsey, MD, MBA 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

12. William Dalsey, MD, MBA 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

13. William Dalsey, MD, MBA Intranasal Midazolam Randomized controlled clinical trials support the effectiveness of treating status epilepticus in pediatric patients with dosages of.2mg/kg Faster and perhaps more effective than rectal diazepam in RCTs Lahat, Eli. British Medical Journal 32(7253) 8 July 2000 p 83-86. Scott RC. Lancet 1999;353:623-62. Fisgin, Tunc. Child Neur 17;2; Feb 2002, p.123-126.

14. William Dalsey, MD, MBA Intramuscular Midazolam Water soluble; well absorbed Adult dose 10 - 15 mg (.2mg/kg) Case reports Jawad. J Neurol Neurosurg Psych 1986; 49:1050-1054 Chamberlain. Pediatr Emerg Care 1997; 13:92-94

15. William Dalsey, MD, MBA 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, MBA Conclusions When the IV access is unavailable: IN or IM midazolam Rectal diazepam IM fosphenytoin