ACLS Guideline Update: Vanishing Vasopressin

NOVEMBER 09, 2015
Vasopressin has gone the way of atropine in the updated ACLS guidelines.
 
Vasopressin has gone the way of atropine in the updated 2015 American Heart Association (AHA) Advanced Cardiac Life Support (ACLS) guidelines.1 
 
Does this mean you should suggest at your next critical care meeting that vasopressin be removed from your hospital’s crash carts? No, it’s does not.
 
First and foremost, when comparing vasopressin to epinephrine, remember that the comparison agent (epinephrine) has not been shown to improve patient-oriented outcomes such as neurologically intact survival.2-5 This is true particularly for out-of-hospital cardiac arrest (OHCA) and somewhat less consistent with in-hospital cardiac arrest (IHCA).
 
In fact, the role of vasopressin in cardiac arrests has potential benefit in IHCA or OHCA with initial rhythms of asystole.6-9 The leading theories include improved coronary perfusion in these subgroups, particularly with epinephrine where there may be a synergistic effect.6,7,10 
 
In IHCA in particular, vasopressin may be used in a lower 20-IU dose with epinephrine and methylprednisolone followed by hydrocortisone, which is suggested in the updated AHA ACLS guidelines.1,6,7 Where vasopressin has fallen short in OHCA, however, is in patients with ventricular fibrillation and pulseless ventricular tachycardia (VFib/pVT). This subgroup demonstrates improved or similar return of spontaneous circulation (ROSC), but not improved survival to hospital discharge compared with epinephrine.
 
Secondly, similar to atropine, vasopressin has been removed from the ACLS algorithm not because of evidence showing harm, but rather evidence showing a lack of clear benefit. AHA’s objective here is to focus ACLS-trained providers towards interventions that have evidence to improve survival, such as early and high-quality cardiopulmonary resuscitation (CPR) and defibrillation.1
 
Resuscitation can go beyond what’s recommended in these updated ACLS guidelines. They are guidelines, after all—not gospel.
 
Critical examination of the primary literature cited in the 2010 and 2015 ACLS guidelines shows that only 2 additional papers are referenced (J Emerg Med, 2011; Resuscitation, 2012).1,11

The Clinical Core of the 2010 and 2015 AHA ACLS Guidelines
2010 AHA ACLS Guideline Evidence 2015 AHA ACLS Guideline Evidence What the What?
  Lindner KH, et al.Randomised comparison of epinephrine and vasopressin in patients with out-of-hospital ventricular fibrillation. Lancet. 1997;349:535–537. Perhaps it was included in the review article that the 2010 guideline cited below.
Wenzel V, et al; European Resuscitation Council Vasopressor during Cardiopulmonary Resuscitation Study Group. A comparison of vasopressin and epinephrine for out-of-hospital cardiopulmonary resuscitation. N Engl J Med. 2004;350:105–113. Wenzel V, et al; European Resuscitation Council Vasopressor during Cardiopulmonary Resuscitation Study Group. A comparison of vasopressin and epinephrine for out-of-hospital cardiopulmonary resuscitation. N Engl J Med. 2004;350:105–113.  
Stiell IG, et al. Vasopressin versus epinephrine for inhospital cardiac arrest: a randomised controlled trial. Lancet. 2001;358:105–109.   Not sure where this one went.
Aung K, Htay T. Vasopressin for cardiac arrest: a systematic review and meta-analysis. Arch Intern Med. 2005;165:17–24.   Review article, so it rightfully shouldn’t have been included.
Callaway CW, et al. Usefulness of vasopressin administered with epinephrine during out-of-hospital cardiac arrest. Am J Cardiol. 2006;98:1316–1321. Callaway CW, et al. Usefulness of vasopressin administered with epinephrine during out-of-hospital cardiac arrest. Am J Cardiol. 2006;98:1316–1321.  
Gueugniaud PY, et al. Vasopressin and epinephrine vs. epinephrine alone in cardiopulmonary resuscitation. N Engl J Med. 2008;359:21–30. Gueugniaud PY, et al. Vasopressin and epinephrine vs. epinephrine alone in cardiopulmonary resuscitation. N Engl J Med. 2008;359:21–30.  
Mukoyama T, Kinoshita K, Nagao K, Tanjoh K. Reduced effectiveness of vasopressin in repeated doses for patients undergoing prolonged cardiopulmonary resuscitation. Resuscitation. 2009;80:755–761. Mukoyama T, Kinoshita K, Nagao K, Tanjoh K.Reduced effectiveness of vasopressin in repeated doses for patients undergoing prolonged cardiopulmonary resuscitation. Resuscitation. 2009;80:755–761.  
  Ducros L, et al. Effect of the addition of vasopressin or vasopressin plus nitroglycerin to epinephrine on arterial blood pressure during cardiopulmonary resuscitation in humans. J Emerg Med. 2011;41:453–459. Published after 2010
  Ong ME, et al. A randomised, double-blind, multi-centre trial comparing vasopressin and adrenaline in patients with cardiac arrest presenting to or in the Emergency Department. Resuscitation. 2012;83:953–960. Published after 2010
 
The first was a small randomized, controlled trial (n=44)  of epinephrine versus vasopressin with epinephrine versus vasopressin with epinephrine and nitroglycerin that showed the combinations did not achieve a higher diastolic blood pressure than epinephrine alone.12 
 
The second was a larger randomized, controlled trial (n=727) that did not demonstrate a difference in the rate of survival at discharge between patients who received epinephrine or vasopressin upon arrival to the emergency department. In order words, vasopressin was not worse than epinephrine.9

In light of this evidence, pharmacists who practice in an environment that treats IHCA patients should keep vasopressin in crash carts.

References:
1. 2015 American Heart Association Guidelines Update for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care. Circulation. 2015;132(18) Supplement 2.
2. Hagihara A et al. Prehospital Epinephrine Use and Survival Among Patients with OHCA. JAMA. 2012; 307(11):1161-68.
3. Nakahara S et al. Evaluation of pre-hospital administration of adrenaline (epinephrine) by emergency medical services for patients with out of hospital cardiac arrest in Japan: controlled propensity matched retrospective cohort study. BMJ. December 2013.
4. Olasveengen TM, Sunde K, Brunborg C, et al. Intravenous drug administration during out-of-hospital cardiac arrest: a randomized trial. JAMA. 2009; 302:2222–2229.
5. Jacobs IG, Finn JC, Jelinek GA, et al. Effect of adrenaline on survival in out-of hospital cardiac arrest: a randomised double-blind placebo-controlled trial. Resuscitation. 2011; 82:1138–1143.
6. Mentzelopoulos S, Zakynthinos S, Tzoufi M, et al. Vasopressin, epinephrine, and corticosteroids for in-hospital cardiac arrest. Arch Intern Med. 2009;169:15-24. PMID: 19139319.
7. Mentzelopoulos S, Malachias S, Chamos C, et al. Vasopressin, steroids, and epinephrine and neurologically favorable survival after in-hospital cardiac arrest: a randomized clinical trial. JAMA. 2013;310(3):270-9. PMID: 19139319.
8. Varvarousi G, Stefaniotou A, Varavaroussis D, et al. Glucocorticoids as an emergency pharmacologic agent for cardiopulmonary resuscitation. Cardiovasc Drugs Ther. 2014;28:477-88. PMCID: PMC4163188.
9. Ong ME, et al. A randomised, double-blind, multi-centre trial comparing vasopressin and adrenaline in patients with cardiac arrest presenting to or in the Emergency Department. Resuscitation. 2012;83:953-960.
10. Mayr V, et al. Developing a vasopressor combination in a pig model of adult asphyxia cardiac arrest. Circulation. 2001;104:1651-1656.
11. 2010 American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science. Circulation. 2010; 122(18) Supplement 3.
12. Ducros L, et al. Effect of the addition of vasopressin or vasopressin plus nitroglycerin to epinephrine on arterial blood pressure during cardiopulmonary resuscitation in humans. J Emerg Med. 2011;41:453-459.


Craig Cocchio, PharmD
Craig Cocchio, PharmD
Craig Cocchio, PharmD, BCPS, is an Emergency Medicine Clinical Pharmacist at Trinity Mother Frances Hospital in Tyler, Texas. Follow on Twitter @iEMPharmD and on his blog at empharmd.blogspot.com
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