BenzodiazepinesBenzodiazepinesWhat are the Best Non-IV Parenteral What are the Best Non-IV Parenteral Options for a Seizing Patient?Options for a Seizing Patient?

William C. Dalsey, MD, FACEP, MBAWilliam C. Dalsey, MD, FACEP, MBA

Department of Emergency MedicineDepartment of Emergency Medicine

Robert Wood Johnson University HospitalRobert Wood Johnson University HospitalNew JerseyNew Jersey

William Dalsey, MD, MBA

Case #1 PresentationCase #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.

William Dalsey, MD, MBA

Case 2 PresentationCase 2 Presentation

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

William Dalsey, MD, MBA

Critical QuestionsCritical Questions

• What is this best first-line treatment?

• What if I can’t obtain IV access?

Complicating Factors: Status Epilepticus? Hypoxia, Hypoglycemia, Fever

William Dalsey, MD, MBA

What does the literature show?What does the literature show?

• Benzodiazepines

• Phenytoin/Fosphenytoin

• Phenobarbital

• Valproate

• Anesthetics

William Dalsey, MD, MBA

BenzodiazepinesBenzodiazepines

• 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

William Dalsey, MD, MBA

What do Clinical Policies/Guidelines What do Clinical Policies/Guidelines and the literature support?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

William Dalsey, MD, MBA

What else does the literature show?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;4-10Treiman. Epilepsia 1989:30;4-10

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

William Dalsey, MD, MBA

If you have no IV access, are there alternatives If you have no IV access, are there alternatives routes for benzodiazepines administration?routes for benzodiazepines administration?

• Intranasal (Midazolam)• Buccal (Midazolam)• IM (Lorazepam,

Midazolam)• Rectal (Diazepam,

Midazolam)• ET (Diazepam)

William Dalsey, MD, MBA

Rectal DiazepamRectal 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 effectivenessDieckmann. Ann Emerg Med 1994; 23:216-224Cereghino. Neurology 1998;51:1274-1282Remy. Epilepsia 1992;22(2):3530358

William Dalsey, MD, MBA

Rectal DiazepamRectal 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

William Dalsey, MD, MBA

ParaldehydeParaldehyde

• 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-S3Ramsay. Epilepsia 1989;30(suppl):S1-S3

William Dalsey, MD, MBA

Intranasal MidazolamIntranasal 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.

William Dalsey, MD, MBA

Intramuscular MidazolamIntramuscular Midazolam

• Water soluble; well absorbed

• Adult dose 10 - 15 mg (.2mg/kg)

• Case reports

Jawad. J Neurol Neurosurg Psych 1986; 49:1050-1054Chamberlain. Pediatr Emerg Care 1997; 13:92-94

William Dalsey, MD, MBA

Intramuscular FosphenytoinIntramuscular Fosphenytoin

• 100 % bioavailable• 20 PE /kg: 20 cc intragluteal• Therapeutic levels at 1 hours• Pruritis and paresthesias most

common side effects• Cardiac monitoring not

necessaryDeToledo. Emerg Med 1996; supplement:26-31

William Dalsey, MD, MBA

ConclusionsConclusions

• When the IV access is unavailable:

• IN or IM midazolam

• Rectal diazepam

• IM fosphenytoin