EBQ:A comparison of Vasopressin and Epinephrine for Out-of-Hospital Cardiopulmonary Resuscitation

incomplete Journal Club Article

Volker Wenzel, M.D., Anette C. Krismer, M.D., H. Richard Arntz, M.D., Helmut Sitter, Ph.D., Karl H. Stadlbauer, M.D., and Karl H. Lindner, M.D., for the European Resuscitation Council Vasopressor during Cardiopulmonary Resuscitation Study Group*. "A Comparison of Vasopressin and Epinephrine for Out-of-Hospital Cardiopulmonary Resuscitation". NEJM. 2004. 350(2):105-113.
PubMed PDF

Clinical Question

• Does 2 injections of vasopressin 40 IU versus epinephrine 1mg followed by additional treatment of epinephrine if needed improve out-of-hospital cardiac arrest patients survival to hospital admission and hospital discharge?

Conclusion

• In ventricular fibrillation (Vfib) and pulseless electrical activity, vasopressin and epinephrine have similar effects
• In asystole, vasopressin is superior to epinephrine in patients with asystole
• In refractory cardiac arrest, more prudent to use vasopressin then epinephrine over epinephrine alone

Major Points

• Vasopressin may offer improved outcomes in specific subgroups of cardiac arrest, particularly asystole.

• Combination therapy (vasopressin followed by epinephrine) in refractory cases improves both hospital admission and discharge rates.

• Survival benefits are more pronounced in witnessed arrests and when basic life support (BLS) is initiated within 10 minutes.

Study Design

• Type: Double-blind, prospective, multicenter, randomized controlled trial
• Duration: June 1999 – March 2002
• Randomization: Block randomization (blocks of 10), stratified by center
• Blinding: Study drug assignment was unknown to providers unless required post-resuscitation
• Setting: Prehospital EMS in 33 communities across Austria, Germany, and Switzerland
• Drug Protocol:
  • Two ampules of either 1 mg epinephrine or 40 IU vasopressin
  • If no ROSC after the first dose, the second dose of the same drug was given
  • Additional epinephrine allowed afterward as needed
  • IV administration
  • Other medications (e.g., amiodarone, lidocaine, fibrinolytics) given at physician discretion

Population

• 33 communities in Austria, Germany, and Switzerland

Inclusion Criteria

• Adults with out-of-hospital cardiac arrest presenting with Vfib, PEA, or asystole
• Required CPR and vasopressor therapy

Exclusion Criteria

• Successful defibrillation without vasopressors
• Terminal illness
• No IV access
• Hemorrhagic shock
• Pregnancy
• Trauma-related cardiac arrest
• Age < 18
• Presence of a DNR order

Interventions

• Group 1: Vasopressin 40 IU (x2 doses) ± epinephrine
• Group 2: Epinephrine 1 mg (x2 doses) ± additional epinephrine

Outcomes

Primary Outcome

Survival to hospital admission

Vfib:

• Epinephrine: 46.2%
• Vasopressin: 43%
• No significant difference

PEA:

• Epinephrine: 33.7%
• Vasopressin: 30.5%
• No significant difference

Asystole:

• Epinephrine: 20.3%
• Vasopressin: 29.0%
• Vasopressin significantly better

Secondary Outcomes

Among patients requiring additional epinephrine (no ROSC after initial doses):

Hospital admission:

• Vasopressin group: 25.7%
• Epinephrine group: 16.4%
• Statistically significant

Hospital discharge:

• Vasopressin group: 6.2%
• Epinephrine group: 1.7%
• Statistically significant

• Overall survival to discharge (all patients): 9.7%
• Comatose at discharge: 2.2%
• Best outcomes: Witnessed arrest + BLS within 10 minutes

Criticisms & Further Discussion

• Fewer patients randomized than originally planned
• Survival to admission is a limited outcome; neurologic recovery not well-assessed
• Cause of arrest often unknown — different etiologies could affect response
• No data on post-arrest hypothermia, which may influence neurologic outcomes
• There is currently no vasopressin in ACLS guidelines

External Links

http://emergencymedicinecases.com/acls-guidelines-2015-cardiac-arrest/

Funding

• Supported in part by a Founders Grant for Training in Clinical Critical Care Research, Society of Critical Care Medicine, Des Plaines, Ill.; by Science Funds No. 7280 of the Austrian National Bank, Vienna, Austria; by the Dean's Office of the Leopold-Franzens University College of Medicine, Innsbruck, Austria; by the Laerdal Foundation for Acute Medicine, Stavanger, Norway; by an Austrian Science Foundation grant (P-14169-MED), Vienna, Austria; by Pfizer, Karlsruhe, Germany; by the Science Foundation of the Tyrolean State Hospitals, Innsbruck, Austria; and by the Department of Anesthesiology and Critical Care Medicine, Leopold-Franzens University, Innsbruck, Austria.