Monday, November 9, 2015

Vanishing Vasopressin

Vasopressin has gone by the way of atropine in the updated ACLS guidelines.1 But is this a reason to sachet into your next resuscitation/critical care meeting and suggest vasopressin be removed from your hospital’s crash carts? No. Don’t do it. Don’t just read the guidelines; read the primary literature. 


First and foremost, when we’re comparing vasopressin to epinephrine, one must remember the comparison agent (epinephrine) has not been shown to improve patient oriented outcomes, ie, neurologically intact survival.2-5 This is true particularly with 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 (VSE trial) or OHCA with initial rhythms of asystole (theoretical in combination with epi +/- steroids, certainly debatable).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 IHCA in particular, vasopressin may be used in a lower 20 IU dose with epinephrine and methylprednisolone followed by hydrocortisone, which IS suggested in these new 2015 guidelines.1,6,7 However, where vasopressin has fallen short in OHCA is in patients with ventricular fibrillation and pulseless ventricular tachycardia (VFib/pVT). This subgroup demonstrates improved ROSC (or similar rate of ROSC), but not improved survival to hospital discharge vs 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. The objective of the AHA here is to focus ACLS trained providers towards interventions that HAVE evidence to improve survival such as early and high quality CPR, defibrillation.1 Resuscitation can go beyond what’s recommended in these guidelines. They are GUIDElines after all, not gospel.
Critically examining the primary literature cited in the 2010 and 2015 guidelines will demonstrate that there are only two additional papers referenced (J Emerg Med, 2011; Resuscitation, 2012).1,11 The first, briefly, a small (N=44) RCT of epinephrine vs epi+vaso vs epi+vaso+nitro where the combinations did not achieve a higher diastolic blood pressure than did epinephrine.12 The second larger RCT (N=727) did not demonstrate a difference in the rate of survival at discharge between patients who received epi or vasopressin upon arrival to the ED. No difference, but not worse than epinephrine.9
If you practice in an environment where you take care of IHCA patients, vasopressin should remain in the crash/code carts. More awareness of VSE (c’mooooon knowledge translation) needs to happen (RebelEM: great post by Hannah Davis, Pharm.D).

2010 Guidelines
2015 Guidelines
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
Not included in 2010… perhaps it was in the review article they cite 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;165:1724
Review article, 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;80:755761
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

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.