Advertisement

Springer Nature is making SARS-CoV-2 and COVID-19 research free. View research | View latest news | Sign up for updates

Epinephrine and short-term survival in cardiogenic shock: an individual data meta-analysis of 2583 patients

Abstract

Objective

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.

Design

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Fourteen published cohorts and two unpublished data sets were included.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]).

Conclusions

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.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Change history

  • 13 September 2018

    Because of a technical error, the code corresponding to the outcome for the Basir et al. cohort was mis-implemented in the original version of our article. Characteristics of the cohort are in fact the followings.

References

  1. 1.

    Reynolds HR, Hochman JS (2008) Cardiogenic shock: current concepts and improving outcomes. Circulation 117:686–697. https://doi.org/10.1161/CIRCULATIONAHA.106.613596

  2. 2.

    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

  3. 3.

    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

  4. 4.

    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

  5. 5.

    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

  6. 6.

    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

  7. 7.

    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

  8. 8.

    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

  9. 9.

    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

  10. 10.

    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

  11. 11.

    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.

  12. 12.

    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

  13. 13.

    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

  14. 14.

    Viechtbauer W (2010) Conducting meta-analyses in R with the metafor package. J Stat Softw 36:1–48

  15. 15.

    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

  16. 16.

    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

  17. 17.

    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

  18. 18.

    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

  19. 19.

    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

  20. 20.

    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

  21. 21.

    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

  22. 22.

    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

  23. 23.

    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

  24. 24.

    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

  25. 25.

    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

  26. 26.

    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

  27. 27.

    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

  28. 28.

    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

  29. 29.

    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

  30. 30.

    Vincent J-L, De Backer D (2013) Circulatory shock. N Engl J Med 369:1726–1734. https://doi.org/10.1056/NEJMra1208943

  31. 31.

    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

  32. 32.

    Tang W, Weil MH, Sun S et al (1995) Epinephrine increases the severity of postresuscitation myocardial dysfunction. Circulation 92:3089–3093

  33. 33.

    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

  34. 34.

    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

  35. 35.

    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

Download references

Author information

Correspondence to Alexandre Mebazaa.

Ethics declarations

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.

Authors' comment

One of the two unpublished data set-the one of Basir-was published after data extraction, and is refered as [35].

Additional information

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.

Supplementary material 1 (DOCX 144 kb)

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

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

Download citation

Keywords

  • Meta-analysis
  • Cardiogenic shock
  • Epinephrine
  • Prognosis