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Do we need an individual approach to atrial fibrillation and adrenergic overload in the critically ill?


1University of Ljubljana, Faculty of Medicine, Ljubljana, Slovenia

2 Department of Cardiovascular Surgery, University Medical Centre Ljubljana, Slovenia

3 Department of Cardiac Surgery, Cardiovascular Center, Klinikum Nuernberg-Paracelsus Medical University, Nuremberg, Germany

4 Clinical Department for Anaesthesiology and Surgical Intensive Care, University Medical Centre Ljubljana, Slovenia

DOI: 10.22514/SV141.042018.9 Vol.14,Issue 1,March 2018 pp.53-58

Published: 27 March 2018

*Corresponding Author(s): PODBREGAR MATEJ E-mail:


Despite catecholamines being lifesaving drugs, they can also be harmful. Adrenergic overload is one of the major promoters of supra- and ventricular arrhythmias, which induce hemodynamic instability in the crit-ically ill. In this paper we will focus on the pathophysiology of atrial fibrillation (AF), the importance of adrenergic overload for triggering AF, the importance of the auto-nomic nervous system and finally, we will challenge the importance of decreasing adrenergic load with selective and non-selective β-blockers, which have different effects on the metabolism in the severely ill. We will also emphasize the importance of an individual approach due to pharma-cogenetic differences in β-adrenergic sig-nalling.  


catecholamine, atrial fibrillation, beta-blocker, metabolism, resting energy ex-penditure

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KALIŠNIK JURIJ MATIJA,PODBREGAR MATEJ. Do we need an individual approach to atrial fibrillation and adrenergic overload in the critically ill?. Signa Vitae. 2018. 14(1);53-58.


1. Seguin P, Launey Y. Atrial fibrillation is not just an artefact in the ICU. Crit Care 2010;14:182.

2. Ivanovic J, Maziak DE, Ramzan S, McGuire AL, Villeneuve PJ, Gilbert S, et al. Incidence, severity and perioperative risk factors for atrial fibrillation following pulmonary resection. Interact Cardiovasc Thorac Surg 2014 Mar;18(3):340-6.

3. Maisel WH, Rawn JD, Stevenson WG. Atrial fibrillation after cardiac surgery. Ann Intern Med 2001;135:1061–73.

4. Walsh SR, Tang T, Gaunt ME, Schneider HJ. New arrhythmias after non-cardiothoracic surgery. BMJ 2006;333:715.

5. Walkey AJ, Wiener RS, Ghobrial JM, Curtis LH, Benjamin EJ. Incident stroke and mortality associated with new-onset atrial fibrilla-tion in patients hospitalized with severe sepsis. JAMA 2011 Nov 23;306(20):2248-54.

6. Auer J, Weber T, Berent R, Ng CK, Lamm G, Eber B. Risk factors of postoperative atrial fibrillation after cardiac surgery. J Card Surg 2005;20(5):425-31.

7. Marinsek M, Larkin GL, Zohar P, Bervar M, Pekolj-Bicanic M, Mocnik FS, et al. Efficacy and impact of monophasic versus biphasic countershocks for transthoracic cardioversion of persistent atrial fibrillation. Am J Cardiol 2003 Oct 15;92(8):988-91.

8. Nabar A, Pathan I. Pathophysiology of Atrial Fibrillation-current Concepts. J Assoc Physicians India 2016;64(8):11-15.

9. Healey JS, Baranchuk A, Crystal E. Prevention of atrial fibrillation with angiotensin converting enzyme inhibitors and angiotensin receptor blockers: a meta-analysis. J Am Coll Cardiol 2005;45:1832–41.

10. Yue L, Xie J, Nattel S. Molecular determinants of cardiac fibroblast electrical function and therapeutic implications for atrial fibrilla-tion. Cardiovasc Res 2011;89:744– 53.

11. Ehrlich JR, Cha TJ, Zhang L. Cellular electrophysiology of canine pulmonary vein cardiomyocytes: action potential and ionic current properties. J Physiol 2003;551:801–14.

12. Wijffels MC, Kirchhof CJ, Dorland R, Allessie MA. Atrial fibrillation begets atrial fibrillation. A study in awake chronically instru-mented goats. Circulation 1995;92:1954–2022.

13. Stillitano F, Lonardo G, Zicha S, , Mugelli A, Natell S. Molecular basis of funny current (If ) in normal and failing human heart. J Mol Cell Cardiol 2008;45:289–99.

14. Johnson JN, Tester DJ, Perry J, Salisbury BA, Reed CR, Ackerman MJ. Prevalence of early-onset atrial fibrillation in congenital long QT syndrome. Heart Rhythm 2008;5:704–9.

15. Yeh YH, Wakili R, Qi XY, Chartier D, Boknik P, Kääb S, et al. Calcium-handling abnormalities underlying atrial arrhythmogenesis and contractile dysfunction in dogs with congestive heart failure. Circ Arrhythm Electrophysiol 2008;1(2):93-102.

16. Chang CM, Wu TJ, Zhou S, Doshi RN, Lee MH, Ohara T, et al. Nerve sprouting and sympathetic hyperinnervation in a canine model of atrial fibrillation produced by prolonged right atrial pacing. Circulation. 2001 Jan 2;103(1):22-5.

17. Aurora R. Recent insights into the role of the autonomic nervous system in the creation of substrate for atrial fibrillation – Implica-tions for therapies targeting the atrial autonomic nervous system. Circ Arrhythm Electrophysiol 2012;5:850-9.

18. Amar D, Zhang H, Miodownik S. Competing autonomic mechanisms precede the onset of postoperative atrial fibrillation. J Am Coll Cardiol 2003;7:1262-8.

19. Kališnik JM, Hrovat E, Hrastovec A, Avbelj V, Žibert J, Geršak B. Severe cardiac autonomic derangement and altered ventricular repolarization pave the way to postoperative atrial fibrillation. Innovations 2015;10:398-405.

20. Arrigo M, Bettex D, Rudiger A. Management of atrial fibrillation in criticallyill patients. Crit Care Res Pract 2014;2014:840615.

21. Andreis DT, Singer M. Catecholamines for inflammatory shock: a Jekyll-and-Hyde conundrum. Intensive Care Med 2016 Sep;42(9):1387-97.

22. Farrugia FA, Martikos G, Tzanetis P, Charalampopoulos A, Misiakos E, Zavras N, et al. Pheochromocytoma, diagnosis and treat-ment: Review of the literature. Endocr Regul 2017;51(3):168-81.

23. Dawson DK. Acute stress-induced (takotsubo) cardiomyopathy. Heart. 2017 Aug 20. pii: heartjnl-2017-311579. doi: 10.1136/heartjnl-2017-311579.

24. Ostrowski SR, Pedersen SH, Jensen JS, Mogelvang R, Johansson PI. Acute myocardial infarction is associated with endothelial glyco-calyx and cell damage and a parallel increase in circulating catecholamines. Crit Care 2013 Feb 22;17(1):R32.

25. Feibel JH, Hardy PM, Campbell RG, Goldstein MN, Joynt RJ. Prognostic value of the stress response following stroke. JAMA. 1977 Sep 26;238(13):1374-6.

26. Rhodes A, Evans LE, Alhazzani W, Levy MM, Antonelli M, Ferrer R et al. Surviving Sepsis Campaign: International Guidelines for Management of Sepsis and Septic Shock:2016. Intensive Care Med 2017;43(3):304-77.

27. Myburgh JA, Higgins A, Jovanovska A, Lipman J, Ramakrishnan N, Santamaria J;CAT Study investigators. A comparison of epineph-rine and norepinephrine in critically ill patients. Intensive Care Med 2008;34(12):2226-34.

28. Abraham WT, Adams KF, Fonarow GC, Costanzo MR, Berkowitz RL, Le Jemtel TH et al; ADHERE Scientific Advisory Committee and Investigators; ADHERE Study Group. In-hospital mortality in patients with acute decompensated heart failure requiring intra-venous vasoactive medications: an analysis from the Acute Decompensated Heart Failure National Registry (ADHERE). J Am Coll Cardiol 2005 Jul 5;46(1):57-64.

29. Shahin J, DeVarennes B, Tse CW, Amarica DA, Dial S. The relationship between inotrope exposure, six-hour postoperative physi-ological variables, hospital mortality and renal dysfunction in patients undergoing cardiac surgery. Crit Care 2011 Jul 7;15(4):R162.

30. Brown SM, Lanspa MJ, Jones JP, Kuttler KG, Li Y, Carlson R, et al. Survival after shock requiring high-dose vasopressor therapy. Chest 2013 Mar;143(3):664-71.

31. Leibovici L, Gafter-Gvili A, Paul M, Almanasreh N, Tacconelli E, Andreassen S et al; TREAT Study Group. Relative tachycardia in patients with sepsis: an independent risk factor for mortality. QJM 2007;100(10):629-34.

32. Dünser MW, Ruokonen E, Pettilä V, Ulmer H, Torgersen C, Schmittinger CA, et al. Association of arterial blood pressure and vaso-pressor load with septic shock mortality: a post hoc analysis of a multicenter trial. Crit Care 2009;13(6):R181.

33. Asfar P, Meziani F, Hamel JF, Grelon F, Megarbane B, Anguel N et al; SEPSISPAM Investigators. High versus low blood-pressure target in patients with septic shock. N Engl J Med 2014 Apr 24;370(17):1583-93.

34. Gattinoni L, Brazzi L, Pelosi P, Latini R, Tognoni G, Pesenti A et al. A trial of goal-oriented hemodynamic therapy in critically ill patients. SvO2 Collaborative Group. N Engl J Med 1995 Oct 19;333(16):1025-32.

35. Landesberg G, Gilon D, Meroz Y, Georgieva M, Levin PD, Goodman S, et al. Diastolic dysfunction and mortality in severe sepsis and septic shock. Eur Heart J 2012 Apr;33(7):895-903.

36. Hanley CM, Robinson VM, Kowey PR. Status of Antiarrhythmic Drug Development for Atrial Fibrillation: New Drugs and New Molecular Mechanisms. Circ Arrhythm Electrophysiol 2016 Mar;9(3):e002479.

37. Nia AM, Caglayan E, Gassanov N, Zimmermann T, Aslan O, Hellmich M, et al. Beta1-adrenoceptor polymorphism predicts fle-cainide action in patients with atrial fibrillation. PLoS One 2010 Jul 2;5(7):e11421

38. O'Connor CM, Fiuzat M, Carson PE, Anand IS, Plehn JF, Gottlieb SS et al. Combinatorial pharmacogenetic interactions of bucindo-lol and β1, α2C adrenergic receptor polymorphisms. PLoS One 2012;7(10):e44324

39. Liggett SB, Mialet-Perez J, Thaneemit-Chen S, Weber SA, Greene SM, Hodne D, et al. A polymorphism within a conserved beta(1)-adrenergic receptor motif alters cardiac function and beta-blocker response in human heart failure. Proc Natl Acad Sci U S A 2006 Jul 25;103(30):11288-93.

40. Oral H, Crawford T, Frederick M, Gadeela N, Wimmer A, Dey S, et al. Inducibility of paroxysmal atrial fibrillation by isoproterenol and its relation to the mode of onset of atrial fibrillation. J Cardiovasc Electrophysiol 2008;19:466–70.

41. Aleong RG, Sauer WH, Davis G, Murphy GA, Port JD, Anand IS, et al. Prevention of atrial fibrillation by bucindolol is dependent on the beta1389 Arg/Gly adrenergic receptor polymorphism. JACC Heart Fail 2013 Aug;1(4):338-344.

42. Kao DP, Davis G, Aleong R, O'Connor CM, Fiuzat M, Carson PE, et al. Effect of bucindolol on heart failure outcomes and heart rate response in patients with reduced ejection fraction heart failure and atrial fibrillation. Eur J Heart Fail 2013 Mar;15(3):324-33.

43. Parvez B, Chopra N, Rowan S, Vaglio JC, Muhammad R, Roden DM, et al. A common β1-adrenergic receptor polymorphism pre-dicts favorable response to rate-control therapy in atrial fibrillation. J Am Coll Cardiol 2012;59:49–56.

44. Lalevée N, Nargeot J, Barrére-Lemaire S, Gautier P, Richard S. Effects of amiodarone and dronedarone on voltage-dependent sodium current in human cardiomyocytes. J Cardiovasc Electrophysiol 2003;14:885–90.

45. Kirchhof P, Benussi S, Kotecha D, Ahlsson A, Atar D, Casadei B, et al. 2016 ESC Guidelines for the management of atrial fibrillation developed in collaboration with EACTS. Europace 2016 Nov;18(11):1609-78.

46. Andrade JG, Macle L, Nattel S, Verma A, Cairns J. Contemporary Atrial Fibrillation Management: A Comparison of the Current AHA/ACC/HRS, CCS, and ESC Guidelines. Can J Cardiol 2017 Aug;33(8):965-76.

47. Shibata SC, Uchiyama A, Ohta N, Fujino Y. Efficacy and Safety of Landiolol Compared to Amiodarone for the Management of Post-operative Atrial Fibrillation in Intensive Care Patients. J Cardiothorac Vasc Anesth 2016 Apr;30(2):418-22.

48. Okajima M, Takamura M, Taniguchi T. Landiolol, an ultra-short-acting β1-blocker, is useful for managing supraventricular tachyar-rhythmias in sepsis. World J Crit Care Med 2015 Aug 4;4(3):251-7.

49. Morelli A, Ertmer C, Westphal M, Rehberg S, Kampmeier T, Ligges S, et al. Effect of heart rate control with esmolol on hemodynamic and clinical outcomes in patients with septic shock: a randomized clinical trial. JAMA 2013 Oct 23;310(16):1683-91.

50. Ikeshita K, Nishikawa K, Toriyama S, Yamashita T, Tani Y, Yamada T, et al. Landiolol has a less potent negative inotropic effect than esmolol in isolated rabbit hearts. J Anesth. 2008;22(4):361-6.

51. Morelli A, Donati A, Ertmer C, Rehberg S, Kampmeier T, Orecchioni A, et al. Microvascular effects of heart rate control with esmolol in patients with septic shock: a pilot study. Crit Care Med 2013 Sep;41(9):2162-8.

52. Suzuki T, Morisaki H, Serita R, Yamamoto M, Kotake Y, Ishizaka A, et al. Infusion of the beta-adrenergic blocker esmolol attenuates myocardial dysfunction in septic rats. Crit Care Med 2005 Oct;33(10):2294-301.

53. Heilbrunn SM, Shah P, Bristow MR, Valantine HA, Ginsburg R, Fowler MB. Increased beta-receptor density and improved hemo-dynamic response to catecholamine stimulation during long-term metoprolol therapy in heart failure from dilated cardiomyopathy. Circulation 1989 Mar;79(3):483-90.

54. Gore DC, Wolfe RR. Hemodynamic and metabolic effects of selective beta1 adrenergic blockade during sepsis. Surgery 2006 May;139(5):686-94.

55. Zusman O, Theilla M, Cohen J, Kagan I, Bendavid I, Singer P. Resting energy expenditure, calorie and protein consumption in criti-cally ill patients: a retrospective cohort study. Critical Care 2016;20:367.

56. Podbregar M, Voga G. Effect of selective and nonselective β-blockers on resting energy production rate and total body substrate utilization in chronic heart failure. J Card Fail 2002;8:369–78.

57. Lainscak M, Podbregar M, Anker SD. How does cachexia influence survival in cancer, heart failure and other chronic diseases? Curr Opin Support Palliat Care 2007 Dec;1(4):299-305.

58. Lamont LS, Romito RA, Finkelhor RS, Kalhan SC. β-1-Adrenoreceptors regulate resting metabolic rate. Med Sci Sports Exerc 1997;29(6):769–74.

59. Wallhaus TR, Taylor M, DeGrado TR, Russell DC, Stanko P, Nickles RJ, et al. Myocardial free fatty acid and glucose use after carve-dilol treatment in patients with congestive heart failure. Circulation 2001 May 22;103(20):2441-6.

60. Kovacic D, Marinsek M, Gobec L, Lainscak M, Podbregar M. Effect of selective and non-selective beta-blockers on body weight, insulin resistance and leptin concentration in chronic heart failure. Clin Res Cardiol 2008 Jan;97(1):24-31.

61. Salamon S, Podbregar E, Kubatka P, Büsselberg D, Caprnda M, Opatrilova R, et al. Glucose Metabolism in Cancer and Ischemia: Possible Therapeutic Consequences of the Warburg Effect. Nutr Cancer 2017 Feb-Mar;69(2):177-83.

62. Pearen MA, Myers SA, Raichur S, Ryall JG, Lynch GS, Muscat GEO. The orphan nuclear receptor, NOR-1, a target of β-adrenergic signaling, regulates gene expression that controls oxidative metabolism in skeletal muscle. Endocrinology 2008;149(6):2853–65.

63. Wischmeyer PE, San-Millan I. Winning the war against ICU-acquired weakness: new innovations in nutrition and exercise physiol-ogy. Critical Care 2015;19(Suppl 3):S6. doi:10.1186/cc14724.

64. Clark AL, Coats AJS, Krum H, Katus HA, Mohacsi P, Salekin D, et al. Effect of beta-adrenergic blockade with carvedilol on cachexia in severe chronic heart failure: results from the COPERNICUS trial. J Cachexia Sarcopenia Muscle 2017 Aug;8(4):549-56.

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