First Line Therapy in Acute Seizure Management: Focusing on the Pediatric Patient

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

2. Case 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. Critical Questions • How do you evaluate and treat a pediatric patient with a seizure? • What is this best first-line treatment? • What if I can’t obtain IV access? Complicating Factors: Status Epilepticus? Hypoxia, Hypoglycemia, Febrile Seizures

4. What does the literature support? • Class A recommendation: both diazepam followed by phenytoin or the use of lorazepam are acceptable acute treatment strategies • Is lorazepam better? Treiman. NEJM 1998; 339:792-798

5. 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 Prensky. NEJPM 1967; 276:779-784 Leppik. JAMA 1983; 249:1452-1454

6. Class B Evidence: • Phenobarbital is an effective alternative to the use of phenytoins in status epilepticus. Treiman. NEJM 1998; 339:792-798

7. Class C Evidence: • Fosphenytoin is water soluble and may be preferred over phenytoin when safety concerns or speed of administration are concerns • High dose phenytoins to 30 mgt/kg may be more effective in treating status than standard doses • IV propofol or barbituates may be considered in refractory status

8. Do the Clinical Guidelines Address Our Patient? • What do they say? • What don’t they tell us?

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. 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 • 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. 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. 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.

13. 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

14. 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

15. 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: • IN or IM midazolam • Rectal diazepam • IM fosphenytoin