Benzodiazepines

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 cant 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 cant 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 1989304-10
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 339792-798
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 1989304-10
• Prensky. NEJPM 1967 276779-784
• Leppik. JAMA 1983 2491452-1454

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 23216-224 Cereghin
o. Neurology 1998511274-1282 Remy. Epilepsia
199222(2)3530358
11
Rectal Diazepam

• Dosing is age dependent
• 2 -5 years .5 mg / kg
• 6 - 11 years .3 mg / kg
• gt 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 198930(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 1999353623-62.
• Fisgin, Tunc. Child Neur 172 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
491050-1054 Chamberlain. Pediatr Emerg Care
1997 1392-94
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 supplement26-31
16
Conclusions

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