Intensive Care Medicine

, Volume 38, Issue 6, pp 950–958 | Cite as

Adverse cardiac events during catecholamine vasopressor therapy: a prospective observational study

  • Christian A. Schmittinger
  • Christian Torgersen
  • Günter Luckner
  • Daniel C. H. Schröder
  • Ingo Lorenz
  • Martin W. Dünser



To determine the incidence of and risk factors for adverse cardiac events during catecholamine vasopressor therapy in surgical intensive care unit patients with cardiovascular failure.


The occurrence of any of seven predefined adverse cardiac events (prolonged elevated heart rate, tachyarrhythmia, myocardial cell damage, acute cardiac arrest or death, pulmonary hypertension-induced right heart dysfunction, reduction of systemic blood flow) was prospectively recorded during catecholamine vasopressor therapy lasting at least 12 h.


Fifty-four of 112 study patients developed a total of 114 adverse cardiac events, an incidence of 48.2 % (95 % CI, 38.8–57.6 %). New-onset tachyarrhythmia (49.1 %), prolonged elevated heart rate (23.7 %), and myocardial cell damage (17.5 %) occurred most frequently. Aside from chronic liver diseases, factors independently associated with the occurrence of adverse cardiac events included need for renal replacement therapy, disease severity (assessed by the Simplified Acute Physiology Score II), number of catecholamine vasopressors (OR, 1.73; 95 % CI, 1.08–2.77; p = 0.02) and duration of catecholamine vasopressor therapy (OR, 1.01; 95 % CI, 1–1.01; p = 0.002). Patients developing adverse cardiac events were on catecholamine vasopressors (p < 0.001) and mechanical ventilation (p < 0.001) for longer and had longer intensive care unit stays (p < 0.001) and greater mortality (25.9 vs. 1.7 %; p < 0.001) than patients who did not.


Adverse cardiac events occurred in 48.2 % of surgical intensive care unit patients with cardiovascular failure and were related to morbidity and mortality. The extent and duration of catecholamine vasopressor therapy were independently associated with and may contribute to the pathogenesis of adverse cardiac events.


Catecholamines Vasopressor Adverse cardiac event Tachyarrhythmia Prolonged elevated heart rate Myocardial ischemia 


Conflicts of interest

The authors declare that they have no competing interests.


  1. 1.
    Mayr VD, Dünser MW, Greil V, Jochberger S, Luckner G, Ulmer H, Friesenecker BE, Takala J, Hasibeder WR (2006) Causes of death and determinants of outcome in critically ill patients. Crit Care 10:R154PubMedCrossRefGoogle Scholar
  2. 2.
    Dellinger RP, Levy MM, Carlet JM et al (2008) Surviving sepsis campaign: international guidelines for management of severe sepsis and septic shock. Crit Care Med 36:296–327PubMedCrossRefGoogle Scholar
  3. 3.
    Torgersen C, Dünser MW, Schmittinger CA, Pettilä V, Ruokonen E, Wenzel V, Jakob SM, Takala J (2011) Current approach to the haemodynamic management of septic shock patients in European intensive care units: a cross-sectional, self-reported questionnaire-based survey. Eur J Anaesthesiol 28:284–290PubMedGoogle Scholar
  4. 4.
    Mebazaa A, Parissis J, Porcher R, Gayat E, Nikolaou M, Boas FV, Delgado JF, Follath F (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 37:290–301PubMedCrossRefGoogle Scholar
  5. 5.
    Dünser MW, Hasibeder WR (2009) Sympathetic overstimulation during critical illness: adverse effects of adrenergic stress. J Intensive Care Med 24:293–316PubMedCrossRefGoogle Scholar
  6. 6.
    Torgersen C, Dünser MW, Wenzel V, Jochberger S, Mayr V, Schmittinger CA, Lorenz I, Schmid S, Westphal M, Grander W, Luckner G (2010) Comparing two different arginine vasopressin doses in advanced vasodilatory shock: a randomized, controlled, open-label trial. Intensive Care Med 36:57–65PubMedCrossRefGoogle Scholar
  7. 7.
    Le Gall JR, Lemeshow S, Saulnier F (1993) A new Simplified Acute Physiology Score (SAPS II) based on a European/North American multicenter study. JAMA 270:2957–2963PubMedCrossRefGoogle Scholar
  8. 8.
    Vincent JL, Moreno R, Takala J, Willatts S, De Mendonça A, Bruining H, Reinhart CK, Suter PM, Thijs LG (1996) The SOFA (Sepsis-related Organ Failure Assessment) score to describe organ dysfunction/failure. On behalf of the Working Group on Sepsis-Related Problems of the European Society of Intensive Care Medicine. Intensive Care Med 22:707–710PubMedCrossRefGoogle Scholar
  9. 9.
    Russell JA, Walley KR, Singer J, Gordon AC, Hébert PC, Cooper DJ, Holmes CL, Mehta S, Granton JT, Storms MM, Cook DJ, Presneill JJ, Ayers D, VASST Investigators (2008) Vasopressin versus norepinephrine infusion in patients with septic shock. N Engl J Med 358:877–887PubMedCrossRefGoogle Scholar
  10. 10.
    Dünser MW, Mayr AJ, Ulmer H, Ritsch N, Knotzer H, Pajk W, Luckner G, Mutz NJ, Hasibeder WR (2001) The effects of vasopressin on systemic hemodynamics in catecholamine-resistant septic and postcardiotomy shock: a retrospective analysis. Anesth Analg 93:7–13PubMedCrossRefGoogle Scholar
  11. 11.
    Dünser MW, Mayr AJ, Stallinger A, Ulmer H, Ritsch N, Knotzer H, Pajk W, Mutz NJ, Hasibeder WR (2002) Cardiac performance during vasopressin infusion in postcardiotomy shock. Intensive Care Med 28:746–751PubMedCrossRefGoogle Scholar
  12. 12.
    Annane D, Vignon P, Renault A, Bollaert PE, Charpentier C, Martin C, Troché G, Ricard JD, Nitenberg G, Papazian L, Azoulay E, Bellissant E, CATS Study Group (2007) Norepinephrine plus dobutamine versus epinephrine alone for management of septic shock: a randomised trial. Lancet 370:676–684PubMedCrossRefGoogle Scholar
  13. 13.
    De Backer D, Biston P, Devriendt J, Madl C, Chochrad D, Aldecoa C, Brasseur A, Defrance P, Gottignies P, Vincent JL, SOAPII Investigators (2010) Comparison of dopamine and norepinephrine in the treatment of shock. N Engl J Med 362:779–789PubMedCrossRefGoogle Scholar
  14. 14.
    Dünser MW, Ruokonen E, Pettilä V, Ulmer H, Torgersen C, Schmittinger CA, Jakob S, Takala J (2009) Association of arterial blood pressure and vasopressor load with septic shock mortality: a post hoc analysis of a multicenter trial. Crit Care 13:R181PubMedCrossRefGoogle Scholar
  15. 15.
    Bay M, Kirk V, Parner J, Hassager C, Nielsen H, Krogsgaard K, Trawinski J, Boesgaard S, Aldershvile J (2003) NT-proBNP: a new diagnostic screening tool to differentiate between patients with normal and reduced left ventricular systolic function. Heart 89:150–154PubMedCrossRefGoogle Scholar
  16. 16.
    Talwar S, Squire IB, Downie PF, Mccullough AM, Campton MC, Davies JE, Barnett DB, Ng LL (2000) Profile of plasma N-terminal proBNP following acute myocardial infarction; correlation with left ventricular systolic dysfunction. Eur Heart J 21:1514–1521PubMedCrossRefGoogle Scholar
  17. 17.
    Chua G, Kang-Hoe L (2004) Marked elevations in N-terminal brain natriuretic peptide levels in septic shock. Crit Care 8:R248–R250PubMedCrossRefGoogle Scholar
  18. 18.
    Januzzi JL, Morss A, Tung R, Pino R, Fifer MA, Thompson BT, Lee-Lewandrowski E (2006) Natriuretic peptide testing for the evaluation of critically ill patients with shock in the intensive care unit: a prospective cohort study. Crit Care 10:R37PubMedCrossRefGoogle Scholar
  19. 19.
    Wolff B, Haase D, Lazarus P, Machill K, Graf B, Lestin HG, Werner D (2007) Severe septic inflammation as a strong stimulus of myocardial NT-pro brain natriuretic peptide release. Int J Cardiol 122:131–136PubMedCrossRefGoogle Scholar
  20. 20.
    Ronco C (2011) Cardio-renal syndromes: from foggy bottoms to sunny hills. Heart Fail Rev 16:509–517Google Scholar
  21. 21.
    Zardi EM, Abbate A, Zardi DM, Dobrina A, Margiotta D, Van Tassell BW, Afeltra A, Sanyal AJ (2010) Cirrhotic cardiomyopathy. J Am Coll Cardiol 56:539–549PubMedCrossRefGoogle Scholar
  22. 22.
    Iwai-Kanai E, Hasegawa K, Araki M, Kakita T, Morimoto T, Sasayama S (1999) Alpha- and beta-adrenergic pathways differentially regulate cell type-specific apoptosis in rat cardiac myocytes. Circulation 100:305–311PubMedGoogle Scholar
  23. 23.
    Mann DL, Kent RL, Parsons B, Cooper G 4th (1992) Adrenergic effects on the biology of the adult mammalian cardiocyte. Circulation 85:790–804PubMedGoogle Scholar
  24. 24.
    Okamoto T, Adachi K, Muraishi A, Seki Y, Hidaka T, Toshima H (1996) Induction of DNA breaks in cardiac myoblast cells by norepinephrine. Biochem Mol Biol Int 38:821–827PubMedGoogle Scholar
  25. 25.
    Power I, Kam P (2001) Cardiovascular physiology. In: Power I, Kam P (eds) Principles of physiology for the anaesthetist. Arnold, London, pp 99–165Google Scholar
  26. 26.
    Sander O, Welters ID, Foëx P, Sear JW (2005) Impact of prolonged elevated heart rate on incidence of major cardiac events in critically ill patients with a high risk of cardiac complications. Crit Care Med 33:81–88; discussion 241–242PubMedCrossRefGoogle Scholar
  27. 27.
    Opie L (2004) Receptors and signal transduction. In: Opie L (ed) Heart physiology. From cell to circulation. Lippincott Williams and Wilkins, Philadelphia, pp 186–220Google Scholar
  28. 28.
    Flavahan NA, Cooke JP, Shepherd JT, Vanhoutte PM (1987) Human postjunctional alpha-1 and alpha-2 adrenoceptors: differential distribution in arteries of the limbs. J Pharmacol Exp Ther 241:361–365PubMedGoogle Scholar
  29. 29.
    Polito A, Parisini E, Ricci Z, Picardo S, Annane D (2012) Vasopressin for treatment of vasodilatory shock: an ESICM systematic review and meta-analysis. Intensive Care Med 38:9–19PubMedCrossRefGoogle Scholar
  30. 30.
    Schreuder WO, Schneider AJ, Groeneveld AB, Thijs LG (1989) Effect of dopamine vs norepinephrine on hemodynamics in septic shock. Emphasis on right ventricular performance. Chest 95:1282–1288PubMedCrossRefGoogle Scholar
  31. 31.
    Nakada TA, Russell JA, Boyd JH, Aguirre-Hernandez R, Thain KR, Thair SA, Nakada E, McConechy M, Walley KR (2010) β2-Adrenergic receptor gene polymorphism is associated with mortality in septic shock. Am J Respir Crit Care Med 181:143–149PubMedCrossRefGoogle Scholar
  32. 32.
    Levy B, Perez P, Perny J, Thivilier C, Gerard A (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 39:450–455PubMedCrossRefGoogle Scholar
  33. 33.
    Navarro-Sobrino M, Lorita J, Soley M, Ramírez I (2010) Catecholamine-induced heart injury in mice: differential effects of isoproterenol and phenylephrine. Histol Histopathol 25:589–597PubMedGoogle Scholar
  34. 34.
    Zdanowicz JA, Utz AC, Bernasconi I, Geier S, Corti R, Beinder E (2011) “Broken heart” after cesarean delivery. Case report and review of literature. Arch Gynecol Obstet 283(4):687–694PubMedCrossRefGoogle Scholar
  35. 35.
    Culling W, Penny WJ, Cunliffe G, Flores NA, Sheridan DJ (1987) Arrhythmogenic and electrophysiological effects of alpha adrenoceptor stimulation during myocardial ischaemia and reperfusion. J Mol Cell Cardiol 19:251–258PubMedCrossRefGoogle Scholar
  36. 36.
    Mayr A, Knotzer H, Pajk W, Luckner G, Ritsch N, Dünser M, Ulmer H, Schobersberger W, Hasibeder W (2001) Risk factors associated with new onset tachyarrhythmias after cardiac surgery—a retrospective analysis. Acta Anaesthesiol Scand 45:543–549PubMedCrossRefGoogle Scholar
  37. 37.
    Peivandi AA, Dahm M, Opfermann UT, Peetz D, Doerr F, Loos A, Oelert H (2004) Comparison of cardiac troponin I versus T and creatine kinase MB after coronary artery bypass grafting in patients with and without perioperative myocardial infarction. Herz 29:658–664PubMedCrossRefGoogle Scholar
  38. 38.
    Martin C, Viviand X, Arnaud S, Vialet R, Rougnon T (1999) Effects of norepinephrine plus dobutamine or norepinephrine alone on left ventricular performance of septic shock patients. Crit Care Med 27:1708–1713PubMedCrossRefGoogle Scholar
  39. 39.
    Goldspink DF, Burniston JG, Ellison GM, Clark WA, Tan LB (2004) Catecholamine-induced apoptosis and necrosis in cardiac and skeletal myocytes of the rat in vivo: the same or separate death pathways? Exp Physiol 89:407–416PubMedCrossRefGoogle Scholar

Copyright information

© Copyright jointly held by Springer and ESICM 2012

Authors and Affiliations

  • Christian A. Schmittinger
    • 1
    • 2
  • Christian Torgersen
    • 1
    • 3
  • Günter Luckner
    • 3
  • Daniel C. H. Schröder
    • 3
  • Ingo Lorenz
    • 3
  • Martin W. Dünser
    • 4
  1. 1.Department of Intensive Care MedicineInselspital, Bern University Hospital, University of BernBernSwitzerland
  2. 2.Department of Anaesthesiology, Surgical Intensive Care Medicine, and Rescue MedicineLucerne Cantonal HospitalLucerneSwitzerland
  3. 3.Department of Anaesthesiology and Critical Care MedicineInnsbruck Medical UniversityInnsbruckAustria
  4. 4.Department of Anaesthesiology, Perioperative and Intensive Care Medicine, Salzburg General HospitalParacelsus Private Medical UniversitySalzburgAustria

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