Catecholamines have been the mainstay of pharmacological treatment of cardiogenic shock (CS). Recently, use of epinephrine has been associated with detrimental outcomes. In the present study we aimed to evaluate the association between epinephrine use and short-term mortality in all-cause CS patients.
We performed a meta-analysis of individual data with prespecified inclusion criteria: (1) patients in non-surgical CS treated with inotropes and/or vasopressors and (2) at least 15% of patients treated with epinephrine administrated alone or in association with other inotropes/vasopressors. The primary outcome was short-term mortality.
Measurements and results
Fourteen published cohorts and two unpublished data sets were included. We studied 2583 patients. Across all cohorts of patients, the incidence of epinephrine use was 37% (17–76%) and short-term mortality rate was 49% (21–69%). A positive correlation was found between percentages of epinephrine use and short-term mortality in the CS cohort. The risk of death was higher in epinephrine-treated CS patients (OR [CI] = 3.3 [2.8–3.9]) compared to patients treated with other drug regimens. Adjusted mortality risk remained striking in epinephrine-treated patients (n = 1227) (adjusted OR = 4.7 [3.4–6.4]). After propensity score matching, two sets of 338 matched patients were identified and epinephrine use remained associated with a strong detrimental impact on short-term mortality (OR = 4.2 [3.0–6.0]).
In this very large cohort, epinephrine use for hemodynamic management of CS patients is associated with a threefold increase of risk of death.
This is a preview of subscription content, log in to check access.
Buy single article
Instant access to the full article PDF.
Price includes VAT for USA
Reynolds HR, Hochman JS (2008) Cardiogenic shock: current concepts and improving outcomes. Circulation 117:686–697. https://doi.org/10.1161/CIRCULATIONAHA.106.613596
Prondzinsky R, Unverzagt S, Russ M et al (2012) Hemodynamic effects of intra-aortic balloon counterpulsation in patients with acute myocardial infarction complicated by cardiogenic shock: the prospective, randomized IABP shock trial. Shock 37:378–384. https://doi.org/10.1097/SHK.0b013e31824a67af
Ponikowski P, Voors AA, Anker SD et al (2016) 2016 ESC guidelines for the diagnosis and treatment of acute and chronic heart failure. Rev Esp Cardiol 69:1167. https://doi.org/10.1016/j.rec.2016.11.005
Van Diepen S, Katz JN, Albert NM et al (2017) Contemporary management of cardiogenic shock: a scientific statement from the American Heart Association. Circulation 136:e232–e268
Mebazaa A, Parissis J, Porcher R et al (2011) Short-term survival by treatment among patients hospitalized with acute heart failure: the global ALARM-HF registry using propensity scoring methods. Intensive Care Med 37:290–301. https://doi.org/10.1007/s00134-010-2073-4
Mebazaa A, Motiejunaite J, Gayat E et al (2018) Long-term safety of intravenous cardiovascular agents in acute heart failure: results from the European Society of Cardiology Heart Failure Long-Term Registry. Eur J Heart Fail 20:332–341. https://doi.org/10.1002/ejhf.991
Kirsch M, Vermes E, Radu C et al (2008) Impact of preoperative hemodynamic support on early outcome in patients assisted with paracorporeal Thoratec ventricular assist device. Eur J Cardiothorac Surg 34:262–267. https://doi.org/10.1016/j.ejcts.2008.03.057
Schreiber W, Herkner H, Koreny M et al (2002) Predictors of survival in unselected patients with acute myocardial infarction requiring continuous catecholamine support. Resuscitation 55:269–276
Tarvasmäki T, Lassus J, Varpula M et al (2016) Current real-life use of vasopressors and inotropes in cardiogenic shock—adrenaline use is associated with excess organ injury and mortality. Crit Care 20:208. https://doi.org/10.1186/s13054-016-1387-1
Levy B, Perez P, Perny J et al (2011) Comparison of norepinephrine-dobutamine to epinephrine for hemodynamics, lactate metabolism, and organ function variables in cardiogenic shock. A prospective, randomized pilot study. Crit Care Med 39:450–455. https://doi.org/10.1097/CCM.0b013e3181ffe0eb
Levy B, Clere-Jehl R, Legras A, Morichau-Beauchant T, Leone M, Ganster F, Quenot JP, Kimmoun A, Cariou A, Lassus J, Harjola VP, Meziani F, Louis G, Rossignol P, Duarte K, Girerd N, Mebazaa A, Vignon P. Epinephrine versus norepinephrine in cardiogenic shock after acute myocardial infarction. A double-blind, multicenter randomized study. J Am Coll Cardiol. In press.
Stewart LA, Clarke M, Rovers M et al (2015) Preferred reporting items for systematic review and meta-analyses of individual participant data: the PRISMA-IPD statement. JAMA 313:1657–1665. https://doi.org/10.1001/jama.2015.3656
Wells GA, Shea B, O’Connell D et al (2013) The Newcastle-Ottawa scale (NOS) for assessing the quality of nonrandomized studies in meta-analyses. Ottawa Hosp Res Inst. https://doi.org/10.2307/632432
Viechtbauer W (2010) Conducting meta-analyses in R with the metafor package. J Stat Softw 36:1–48
Gayat E, Pirracchio R, Resche-Rigon M et al (2010) Propensity scores in intensive care and anaesthesiology literature: a systematic review. Intensive Care Med 36:1993–2003. https://doi.org/10.1007/s00134-010-1991-5
Zobel C, Adler C, Kranz A et al (2012) Mild therapeutic hypothermia in cardiogenic shock syndrome. Crit Care Med 40:1715–1723. https://doi.org/10.1097/CCM.0b013e318246b820
Spinar J, Parenica J, Vitovec J et al (2011) Baseline characteristics and hospital mortality in the acute heart failure database (AHEAD) main registry. Crit Care 15:R291. https://doi.org/10.1186/cc10584
Champion S, Gaüzère BA, Vandroux D et al (2014) Dobutamine infusion and absence of pulmonary hypertension are associated with decreased mortality in a cohort of 249 patients with cardiogenic shock. Health 06:2408–2415. https://doi.org/10.4236/health.2014.618277
Chua H-R, Glassford N, Bellomo R (2012) Acute kidney injury after cardiac arrest. Resuscitation 83:721–727. https://doi.org/10.1016/j.resuscitation.2011.11.030
Zannad F, Mebazaa A, Juillière Y et al (2006) Clinical profile, contemporary management and 1-year mortality in patients with severe acute heart failure syndromes: the EFICA study. Eur J Heart Fail 8:697–705. https://doi.org/10.1016/j.ejheart.2006.01.001
Gaudard P, Mourad M, Eliet J et al (2015) Management and outcome of patients supported with Impella 5.0 for refractory cardiogenic shock. Crit Care 19:363. https://doi.org/10.1186/s13054-015-1073-8
Popovic B, Fay R, Cravoisy-Popovic A, Levy B (2014) Cardiac power index, mean arterial pressure, and Simplified Acute Physiology Score II are strong predictors of survival and response to revascularization in cardiogenic shock. Shock 42:22–26. https://doi.org/10.1097/SHK.0000000000000170
Valente S, Lazzeri C, Crudeli E et al (2012) Intraaortic balloon pump: incidence and predictors of complications in the Florence registry. Clin Cardiol 35:200–204. https://doi.org/10.1002/clc.20975
Ouweneel DM, Eriksen E, Sjauw KD et al (2017) Percutaneous mechanical circulatory support versus intra-aortic balloon pump in cardiogenic shock after acute myocardial infarction. J Am Coll Cardiol 69:278–287. https://doi.org/10.1016/j.jacc.2016.10.022
Simonis G, Steiding K, Schaefer K et al (2012) A prospective, randomized trial of continuous lateral rotation (“kinetic therapy”) in patients with cardiogenic shock. Clin Res Cardiol 101:955–962. https://doi.org/10.1007/s00392-012-0484-7
Urban P, Stauffer JC, Bleed D et al (1999) A randomized evaluation of early revascularization to treat shock complicating acute myocardial infarction. The (Swiss) multicenter trial of angioplasty for shock-(S)MASH. Eur Heart J 20:1030–1038. https://doi.org/10.1053/euhj.1998.1353
Napp LC, Kühn C, Bauersachs J (2017) ECMO in cardiac arrest and cardiogenic shock. Herz 42:27–44. https://doi.org/10.1007/s00059-016-4523-4
Huang L, Sun S, Fang X et al (2006) Simultaneous blockade of alpha1- and beta-actions of epinephrine during cardiopulmonary resuscitation. Crit Care Med 34:S483–S485. https://doi.org/10.1097/01.CCM.0000247724.19004.EB
Benthem L, van der Leest J, Meeuwsen WP et al (1990) The effect of epinephrine on oxygen consumption, overall energy metabolism, and substrate utilization in rats. Adv Exp Med Biol 277:851–860
Vincent J-L, De Backer D (2013) Circulatory shock. N Engl J Med 369:1726–1734. https://doi.org/10.1056/NEJMra1208943
Ristagno G, Tang W, Huang L et al (2009) Epinephrine reduces cerebral perfusion during cardiopulmonary resuscitation. Crit Care Med 37:1408–1415. https://doi.org/10.1097/CCM.0b013e31819cedc9
Tang W, Weil MH, Sun S et al (1995) Epinephrine increases the severity of postresuscitation myocardial dysfunction. Circulation 92:3089–3093
Thiele H, Ohman EM, Desch S et al (2015) Management of cardiogenic shock. Eur Heart J 36:1223–1230. https://doi.org/10.1093/eurheartj/ehv051
Schumann J, Henrich EC, Strobl H et al (2018) Inotropic agents and vasodilator strategies for the treatment of cardiogenic shock or low cardiac output syndrome. Cochrane Database Syst Rev. https://doi.org/10.1002/14651858.CD009669.pub3
Basir MB, Schreiber T, Dixon S, Alaswad K, Patel K, Almany S, Khandelwal A, Hanson I, George A, Ashbrook M, Blank N, Abdelsalam M, Sareen N, Timmis SBH, O'Neill WW (2018) Feasibility of early mechanical circulatory support in acute myocardial infarction complicated by cardiogenic shock: the detroit cardiogenic shock initiative. Catheterization and Cardiovascular Interventions 91(3):454–461
Conflict of interest
AM received lecture fees from Novartis, Orion and Abbott, research grants from Roche and consultant fees from Servier and Sanofi. Other coauthors have no conflicts to declare.
One of the two unpublished data set-the one of Basir-was published after data extraction, and is refered as .
Valentine Léopold and Etienne Gayat are co-first authors.
Alexandre Mebazaa and Tahar Chouihed are co-last authors.
Electronic supplementary material
Below is the link to the electronic supplementary material.
About this article
Cite this article
Léopold, V., Gayat, E., Pirracchio, R. et al. Epinephrine and short-term survival in cardiogenic shock: an individual data meta-analysis of 2583 patients. Intensive Care Med 44, 847–856 (2018). https://doi.org/10.1007/s00134-018-5222-9
- Cardiogenic shock