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Benzodiazepines

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. Case #1 Presentation.

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Benzodiazepines

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  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. 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. Case 2 Presentation • 24 year old male with IVDA brought by police with generalized tonic-clonic seizures and no IV access

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

  6. 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. 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. What else does the literature show? Class B Recommendations: • 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

  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. 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. 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. 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. 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. Conclusions • When the IV access is unavailable: • IN or IM midazolam • Rectal diazepam • IM fosphenytoin

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