Vasopressin combined with epinephrine during cardiac resuscitation: a solution for the future?
© BioMed Central Ltd 2006
Published: 22 February 2006
Epinephrine given during cardiopulmonary resuscitation (CPR) may cause beta-mimetic complications in the postresuscitation phase. Vasopressin may be an alternative vasopressor drug during CPR. A subgroup analysis of a large prospective CPR investigation and of retrospective CPR studies suggests that vasopressin may be especially beneficial when combined with epinephrine. Beneficial effects of adding vasopressin were observed in other catecholamine-refractory shock states as well, such as vasodilatory shock and haemorrhagic shock. In order to maximize effects of any vasopressor during CPR, rapid aggressive chest compressions must be ensured to maximize blood flow and to enable advanced cardiac life support drugs to reach the arterial vasculature. We suggest alternating injections of 1 mg epinephrine i.v. and 40 IU vasopressin i.v. every 3–5 minutes during CPR until spontaneous circulation can be achieved or CPR efforts are terminated.
Epinephrine has been employed for cardiac resuscitation for approximately 100 years , although it is known that this drug increases myocardial oxygen consumption during cardiopulmonary resuscitation (CPR) and increases the likelihood of cardiac failure after restoration of spontaneous circulation . In contrast, vasopressin proved to be beneficial over epinephrine as regards improving coronary perfusion pressure during CPR and as regards improving neurological recovery in the CPR laboratory [3, 4]. It was then hoped that vasopressin may also be better than epinephrine in large prospective clinical CPR trials , but these assumptions could not be proven in an inhospital CPR trial in Canada  and in an out-of-hospital CPR trial in Europe . A large subgroup (n = 732) in the European vasopressin trial  and a retrospective analysis of CPR patients from Pittsburgh, PA, USA , however, suggested possible beneficial effects of a combination of vasopressin and epinephrine when given during CPR. This strategy is currently being studied in an ongoing, very large (> 2,000 patients), out-of-hospital prospective CPR trial in France.
The exciting retrospective study of Grmec and Mally from Slovenia adds further support to the hypothesis that a combination of vasopressin and epinephrine given during CPR may be more effective than epinephrine alone . While the authors acknowledge limitations of their investigation, such as a lack of randomizing and subgroup analysis of myocardial infarction patients, it is very impressive that 530 patients were studied in a very difficult setting without any funding. This investigation is in full agreement with studies showing that adding vasopressin in catecholamine-refractory shock states was beneficial during CPR , vasodilatory shock , and hemorrhagic shock . Similar to balanced anaesthesia, it may be valuable to combine two drugs during CPR instead of increasing the dose of one drug. Accordingly, the Slovenian data confirm that the cumulative epinephrine dosage was significantly lower when additional vasopressin was employed. If the authors had used 2 × 40 IU vasopressin i.v. instead of only 1 × 40 IU vasopressin i.v., as in the present study, this effect would most probably have been even greater.
Disappointment about advanced cardiac life support drugs is probably due to both complex effects of global ischaemia during CPR  and our own lack of understanding about CPR treatment effects. While we know in the laboratory that only continuous, aggressive chest compressions are able to improve vital organ perfusion to levels that render successful defibrillation likely, we failed to enforce laboratory CPR quality on the streets and on the wards [14, 15]. Insufficient CPR is unfortunately occurring very often in hospitals and in the emergency medical service ; for example, chest compressions were performed less than 50% of the available time, therefore greatly underutilizing CPR possibilities. If blood does not flow during CPR, a given vasopressor is less likely to reach the target organ arterial vasculature, rendering beneficial effects of advanced cardiac life support drugs less likely. In one study of ventricular fibrillation victims, 75% of the surviving patients had a return of spontaneous circulation without injection of a vasopressor ; the remaining 25% of patients who required a vasopressor indicated that, if basic life support does not restore spontaneous circulation, the general outcome is most probably poor. Accordingly, once advanced cardiac life support drugs are necessary, rescuers need to understand that the chance the patient will be discharged from the hospital is <10% .
Supported by the Science Foundation of the Austrian National Bank grant 11448, Vienna, Austria.
- Gottlieb R: Über die Wirkung der Nebennierenextrakte auf Herz und Blutdruck. Arch Exp Path Pharm 1897, 38: 99-112. 10.1007/BF01824070View ArticleGoogle Scholar
- Paradis NA, Wenzel V, Southall J: Pressor drugs in the treatment of cardiac arrest. Cardiol Clin 2002, 20: 61-78. viii. 10.1016/S0733-8651(03)00065-1View ArticlePubMedGoogle Scholar
- Mayr VD, Wenzel V, Voelckel WG, Krismer AC, Mueller T, Lurie KG, Lindner KH: Developing a vasopressor combination in a pig model of adult asphyxial cardiac arrest. Circulation 2001, 104: 1651-1656.View ArticlePubMedGoogle Scholar
- Wenzel V, Lindner KH, Krismer AC, Voelckel WG, Schocke MF, Hund W, Witkiewicz M, Miller EA, Klima G, Wissel J, Lingnau W, Aichner FT: Survival with full neurologic recovery and no cerebral pathology after prolonged cardiopulmonary resuscitation with vasopressin in pigs. J Am Coll Cardiol 2000, 35: 527-533. 10.1016/S0735-1097(99)00562-8View ArticlePubMedGoogle Scholar
- Lindner KH, Dirks B, Strohmenger HU, Prengel AW, Lindner IM, Lurie KG: Randomised comparison of epinephrine and vasopressin in patients with out-of-hospital ventricular fibrillation. Lancet 1997, 349: 535-537. 10.1016/S0140-6736(97)80087-6View ArticlePubMedGoogle Scholar
- Stiell IG, Hebert PC, Wells GA, Vandemheen KL, Tang AS, Higginson LA, Dreyer JF, Clement C, Battram E, Watpool I, et al.: Vasopressin versus epinephrine for inhospital cardiac arrest: a randomised controlled trial. Lancet 2001, 358: 105-109. 10.1016/S0140-6736(01)05328-4View ArticlePubMedGoogle Scholar
- Wenzel V, Krismer AC, Arntz HR, Sitter H, Stadlbauer KH, Lindner KH: A comparison of vasopressin and epinephrine for out-of-hospital cardiopulmonary resuscitation. N Engl J Med 2004, 350: 105-113. 10.1056/NEJMoa025431View ArticlePubMedGoogle Scholar
- Guyette FX, Guimond GE, Hostler D, Callaway CW: Vasopressin administered with epinephrine is associated with a return of a pulse in out-of-hospital cardiac arrest. Resuscitation 2004, 63: 277-282. 10.1016/j.resuscitation.2004.05.007View ArticlePubMedGoogle Scholar
- Grmec S, Mally S: Vasopressin improves outcome in out-of-hospital cardiopulmonary resuscitation of ventricular fibrillation and pulseless ventricular tachycardia: a observational cohort study. Crit Care 2006, 10: R13. 10.1186/cc3967PubMed CentralView ArticlePubMedGoogle Scholar
- Krismer AC, Wenzel V, Stadlbauer KH, Mayr VD, Lienhart HG, Arntz HR, Lindner KH: Vasopressin during cardiopulmonary resuscitation: a progress report. Crit Care Med 2004, 32: S432-S435. 10.1097/01.CCM.0000134267.91520.C0View ArticlePubMedGoogle Scholar
- Luckner G, Dunser MW, Jochberger S, Mayr VD, Wenzel V, Ulmer H, Schmid S, Knotzer H, Pajk W, Hasibeder W, Mayr AJ, Friesenecker B: Arginine vasopressin in 316 patients with advanced vasodilatory shock. Crit Care Med 2005, 33: 2659-2666. 10.1097/01.CCM.0000186749.34028.40View ArticlePubMedGoogle Scholar
- Krismer AC, Wenzel V, Voelckel WG, Innerhofer P, Stadlbauer KH, Haas T, Pavlic M, Sparr HJ, Lindner KH, Koenigsrainer A: Employing vasopressin as an adjunct vasopressor in uncontrolled traumatic hemorrhagic shock. Three cases and a brief analysis of the literature. Anaesthesist 2005, 54: 220-224. 10.1007/s00101-004-0793-yView ArticlePubMedGoogle Scholar
- Weisfeldt ML, Becker LB: Resuscitation after cardiac arrest: a 3-phase time-sensitive model. JAMA 2002, 288: 3035-3038. 10.1001/jama.288.23.3035View ArticlePubMedGoogle Scholar
- Wik L, Kramer-Johansen J, Myklebust H, Sorebo H, Svensson L, Fellows B, Steen PA: Quality of cardiopulmonary resuscitation during out-of-hospital cardiac arrest. JAMA 2005, 293: 299-304. 10.1001/jama.293.3.299View ArticlePubMedGoogle Scholar
- Abella BS, Alvarado JP, Myklebust H, Edelson DP, Barry A, O'Hearn N, Vanden Hoek TL, Becker LB: Quality of cardiopulmonary resuscitation during in-hospital cardiac arrest. JAMA 2005, 293: 305-310. 10.1001/jama.293.3.305View ArticlePubMedGoogle Scholar
- Nolan JP, Deakin CD, Soar J, Bottiger BW, Smith G: European Resuscitation Council guidelines for resuscitation 2005. Section 4. Adult advanced life support. Resuscitation 2005,67(Suppl 1):S39-S86. 10.1016/j.resuscitation.2005.10.009View ArticlePubMedGoogle Scholar
- Bunch TJ, White RD, Gersh BJ, Meverden RA, Hodge DO, Ballman KV, Hammill SC, Shen WK, Packer DL: Long-term outcomes of out-of-hospital cardiac arrest after successful early defibrillation. N Engl J Med 2003, 348: 2626-2633. 10.1056/NEJMoa023053View ArticlePubMedGoogle Scholar
- Anonymous: 2005 American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care. Part 7.2: management of cardiac arrest. Circulation 2005, 112: IV58-IV66.Google Scholar