Skip to main content
SpringerLink
Log in

Propafenone versus amiodarone for supraventricular arrhythmias in septic shock: a randomised controlled trial

  • Original
  • Published:
Intensive Care Medicine Aims and scope Submit manuscript

Abstract

Purpose

Acute onset supraventricular arrhythmias can contribute to haemodynamic compromise in septic shock. Both amiodarone and propafenone are available interventions, but their clinical effects have not yet been directly compared.

Methods

In this two-centre, prospective controlled parallel group double blind trial we recruited 209 septic shock patients with new-onset arrhythmia and a left ventricular ejection fraction above 35%. The patients were randomised in a 1:1 ratio to receive either intravenous propafenone (70 mg bolus followed by 400–840 mg/24 h) or amiodarone (300 mg bolus followed by 600–1800 mg/24 h). The primary outcomes were the proportion of patients who had sinus rhythm 24 h after the start of the infusion, time to restoration of the first sinus rhythm and the proportion of patients with arrhythmia recurrence.

Results

Out of 209 randomized patients, 200 (96%) received the study drug. After 24 h, 77 (72.8%) and 71 (67.3%) were in sinus rhythm (p = 0.4), restored after a median of 3.7 h (95% CI 2.3–6.8) and 7.3 h (95% CI 5–11), p = 0.02, with propafenone and amiodarone, respectively. The arrhythmia recurred in 54 (52%) patients treated with propafenone and in 80 (76%) with amiodarone, p  < 0.001. Patients with a dilated left atrium had better rhythm control with amiodarone (6.4 h (95% CI 3.5; 14.1) until cardioversion vs 18 h (95% CI 2.8; 24.7) in propafenone, p = 0.05).

Conclusion

Propafenone does not provide better rhythm control at 24 h yet offers faster cardioversion with fewer arrhythmia recurrences than with amiodarone, especially in patients with a non-dilated left atrium. No differences between propafenone and amiodarone on the prespecified short- and long-term outcomes were observed.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

Abbreviations

AF:

Atrial fibrillation

APACHE II:

Acute physiologic and chronic health evaluation

AV:

Atrio-ventricular

CRRT:

Continuous renal replacement therapy

CRP:

C reactive protein

DC:

Direct current cardioversion

EF_LV:

Ejection fraction of left ventricle

ICU:

Intensive care unit

K+:

Plasmatic potassium

LA:

Left atrium

LAVI:

Indexed end-systolic left atrial volume

LV:

Left ventricle/left ventricular

LVOT:

Left ventricular outflow tract

Mg2+ :

Plasmatic magnesium

PAPs:

Pulmonary artery systolic pressure

PCT:

Procalcitonin

PRCT:

Prospective controlled randomized trial

RV:

Right ventricle

SIRS:

Systemic inflammatory response syndrome

SOFA:

Sequential organ function assessment

APACHE II:

Acute physiology and chronic health evaluation

LOS:

Length of stay

SR:

Sinus rhythm

SV:

Supraventricular

TAPSE:

Tricuspid annular plane systolic excursion

TTE:

Transthoracic echocardiography

VTI:

Velocity–time integral

References

  1. Arrigo M, Bettex D, Rudiger A (2014) Management of atrial fibrillation in critically ill patients. Crit Care Res Prac 2014:840615

    Google Scholar 

  2. Klein Klouwenberg PM FJ, Kuipers S, Ong DS, Peelen LM, van Vught LA, Schultz MJ, van der Poll T, Bonten MJ, Cremer OL, MARS Consortium (2016) Incidence, predictors and outcomes of new-onset atrial fibrillation in critically ill patients with sepsis: a cohort study. Am J Respir Crit Care Med

  3. Kuipers S, Klein Klouwenberg P, Cremer OL (2014) Incidence, risk factors and outcomes of new-onset atrial fibrillation in patients with sepsis: a systematic review. Crit Care 18:688

    Article  PubMed  PubMed Central  Google Scholar 

  4. Arrigo M, Jaeger N, Seifert B, Spahn DR, Bettex D, Rudiger A (2015) Disappointing success of electrical cardioversion for new-onset atrial fibrillation in cardiosurgical ICU patients. Crit Care Med 43:2354–2359

    Article  PubMed  Google Scholar 

  5. Balik M, Kolnikova I, Maly M, Waldauf P, Tavazzi G, Kristof J (2017) Propafenone for supraventricular arrhythmias in septic shock-Comparison to amiodarone and metoprolol. J Crit Care 41:16–23

    Article  CAS  PubMed  Google Scholar 

  6. O’Bryan LJ, Redfern OC, Bedford J, Petrinic T, Young JD, Watkinson PJ (2020) Managing new-onset atrial fibrillation in critically ill patients: a systematic narrative review. BMJ Open 10:e034774

    Article  PubMed  PubMed Central  Google Scholar 

  7. Allen LaPointe NM, Dai D, Thomas L, Piccini JP, Peterson ED, Al-Khatib SM (2015) Antiarrhythmic drug use in patients <65 years with atrial fibrillation and without structural heart disease. Am J Cardiol 115:316–322

    Article  PubMed  Google Scholar 

  8. Balik M, Matousek V, Maly M, Brozek T (2017) Management of arrhythmia in sepsis and septic shock. Anaesthesiol Intensive Ther 49:419–429

    Article  PubMed  Google Scholar 

  9. Hindricks G, Potpara T, Dagres N, Arbelo E, Bax JJ, Blomström-Lundqvist C, Boriani G, Castella M, Dan GA, Dilaveris PE, Fauchier L, Filippatos G, Kalman JM, La Meir M, Lane DA, Lebeau JP, Lettino M, Lip GYH, Pinto FJ, Thomas GN, Valgimigli M, Van Gelder IC, Van Putte BP, Watkins CL (2021) 2020 ESC Guidelines for the diagnosis and management of atrial fibrillation developed in collaboration with the European Association for Cardio-Thoracic Surgery (EACTS): the Task Force for the diagnosis and management of atrial fibrillation of the European Society of Cardiology (ESC) Developed with the special contribution of the European Heart Rhythm Association (EHRA) of the ESC. Eur Heart J 42:373–498

    Article  PubMed  Google Scholar 

  10. Wetterslev M, Møller MH, Granholm A, Hassager C, Haase N, Aslam TN, Shen J, Young PJ, Aneman A, Hästbacka J, Siegemund M, Cronhjort M, Lindqvist E, Myatra SN, Kalvit K, Arabi YM, Szczeklik W, Sigurdsson MI, Balik M, Keus F, Perner A (2022) Management of acute atrial fibrillation in the intensive care unit: an international survey. Acta Anaesthesiol Scand 66:375–385

    Article  PubMed  Google Scholar 

  11. Gwag HB, Chun KJ, Hwang JK, Park SJ, Kim JS, Park KM, On YK (2018) Which antiarrhythmic drug to choose after electrical cardioversion: a study on non-valvular atrial fibrillation patients. PLoS ONE 13:e0197352

    Article  PubMed  PubMed Central  Google Scholar 

  12. Kirchhof P, Benussi S, Kotecha D, Ahlsson A, Atar D, Casadei B, Castella M, Diener HC, Heidbuchel H, Hendriks J, Hindricks G, Manolis AS, Oldgren J, Popescu BA, Schotten U, Van Putte B, Vardas P (2016) 2016 ESC Guidelines for the management of atrial fibrillation developed in collaboration with EACTS. Eur Heart J 37:2893–2962

    Article  PubMed  Google Scholar 

  13. Echt DSLP, Mitchell LB, Peters RW, Obias-Manno D, Barker AH, Arensberg D, Baker A, Friedman L, Greene HL et al (1991) Mortality and morbidity in patients receiving encainide, flecainide, or placebo. The Cardiac Arrhythmia Suppression Trial. NEJM 324:781–788

    Article  CAS  PubMed  Google Scholar 

  14. Chevalier PD-DA, Burri H, Cucherat M, Kirkorian G, Touboul P (2003) Amiodarone versus placebo and class Ic drugs for cardioversion of recent-onset atrial fibrillation: a meta-analysis. J Am Coll Cardiol 41:255–262

    Article  CAS  PubMed  Google Scholar 

  15. Courand PYSF, Ranc S, Mullier A, Kirkorian G, Bonnefoy E (2013) Arrhythmogenic effect of flecainide toxicity. Cardiol J 20:203–205

    Article  PubMed  Google Scholar 

  16. Varon J, Marik PE (2008) Irwin and Rippe’s intensive care medicine. In: Rippe JM (ed) Irwin RS. Wolters Kluwer Health/Lippincott Williams & Wilkins, Philadelphia, pp 1855–1869

    Google Scholar 

  17. Ganetsky M (2008) Antiarythmic agents. In: Irwin RS (ed) Intensive care medicine. Wolters Kluwer/Lippincott, Williams & Wilkins, Philadelphia, pp 1486–1498

  18. Stoschitzky K, Stoschitzky G, Lercher P, Brussee H, Lamprecht G, Lindner W (2016) Propafenone shows class Ic and class II antiarrhythmic effects. Europace 18:568–571

    Article  PubMed  Google Scholar 

  19. Lafuente-Lafuente C, Valembois L, Bergmann JF, Belmin J (2015) Antiarrhythmics for maintaining sinus rhythm after cardioversion of atrial fibrillation. Cochrane Database Syst Rev Cd005049

  20. Valembois L, Audureau E, Takeda A, Jarzebowski W, Belmin J, Lafuente-Lafuente C (2019) Antiarrhythmics for maintaining sinus rhythm after cardioversion of atrial fibrillation. Cochrane Database Syst Rev 9:Cd005049

    PubMed  Google Scholar 

  21. Balik M, Waldauf P, Maly M, Matousek V, Brozek T, Rulisek J, Porizka M, Sachl R, Otahal M, Brestovansky P, Svobodova E, Flaksa M, Stach Z, Pazout J, Duska F, Smid O, Stritesky M (2019) Efficacy and safety of 1C class antiarrhythmic agent (propafenone) for supraventricular arrhythmias in septic shock compared to amiodarone: protocol of a prospective randomised double-blind study. BMJ Open 9:e031678

    Article  PubMed  PubMed Central  Google Scholar 

  22. Singer MDC, Seymour CW, Shankar-Hari M, Annane D, Bauer M, Bellomo R, Bernard GR, Chiche JD, Coopersmith CM, Hotchkiss RS, Levy MM, Marshall JC, Martin GS, Opal SM, Rubenfeld GD, van der Poll T, Vincent JL, Angus DC (2016) The third international consensus definitions for sepsis and septic shock (Sepsis-3). JAMA 315:801–810

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Team RC (2022) A language and environment for statistical computing

  24. Team P (2022) RStudio: integrated development environment for R. Posit Software

  25. Bonora A, Turcato G, Franchi E, Taioli G, Dilda A, Zerman G, Maccagnani A, Pistorelli C, Olivieri O (2017) Efficacy and safety in pharmacological cardioversion of recent-onset atrial fibrillation: a propensity score matching to compare amiodarone vs class IC antiarrhythmic drugs. Intern Emerg Med 12:853–859

    Article  PubMed  Google Scholar 

  26. Manning WJ, Silverman DI, Katz SE, Riley MF, Come PC, Doherty RM, Munson JT, Douglas PS (1994) Impaired left atrial mechanical function after cardioversion: relation to the duration of atrial fibrillation. J Am Coll Cardiol 23:1535–1540

    Article  CAS  PubMed  Google Scholar 

  27. Grundvold I, Tveit A, Smith P, Seljeflot I, Abdelnoor M, Arnesen H (2008) The predictive value of transthoracic echocardiographic variables for sinus rhythm maintenance after electrical cardioversion of atrial fibrillation. Results from the CAPRAF study, a prospective, randomized, placebo-controlled study. Cardiology 111:30–35

    Article  PubMed  Google Scholar 

  28. Otto C (2012) The role of echocardiography in atrial fibrillation and flutter. In: Otto C (ed) The practice of clinical echocardiography. Elsevier Health Sciences, Philadelphia, pp 821–827

    Google Scholar 

  29. Balik M, Rulisek J, Leden P, Zakharchenko M, Otahal M, Bartakova H, Korinek J (2012) Concomitant use of beta-1 adrenoreceptor blocker and norepinephrine in patients with septic shock. Wien Klin Wochenschr 124:552–556

    Article  CAS  PubMed  Google Scholar 

  30. Morelli A, Ertmer C, Westphal M, Rehberg S, Kampmeier T, Ligges S, Orecchioni A, D’Egidio A, D’Ippoliti F, Raffone C, Venditti M, Guarracino F, Girardis M, Tritapepe L, Pietropaoli P, Mebazaa A, Singer M (2013) Effect of heart rate control with esmolol on hemodynamic and clinical outcomes in patients with septic shock: a randomized clinical trial. JAMA 310:1683–1691

    Article  PubMed  Google Scholar 

  31. Wyse DG, Waldo AL, DiMarco JP, Domanski MJ, Rosenberg Y, Schron EB, Kellen JC, Greene HL, Mickel MC, Dalquist JE, Corley SD (2002) A comparison of rate control and rhythm control in patients with atrial fibrillation. N Engl J Med 347:1825–1833

    Article  CAS  PubMed  Google Scholar 

  32. Gillinov AM, Bagiella E, Moskowitz AJ, Raiten JM, Groh MA, Bowdish ME, Ailawadi G, Kirkwood KA, Perrault LP, Parides MK, Smith RL 2nd, Kern JA, Dussault G, Hackmann AE, Jeffries NO, Miller MA, Taddei-Peters WC, Rose EA, Weisel RD, Williams DL, Mangusan RF, Argenziano M, Moquete EG, O’Sullivan KL, Pellerin M, Shah KJ, Gammie JS, Mayer ML, Voisine P, Gelijns AC, O’Gara PT, Mack MJ (2016) Rate control versus rhythm control for atrial fibrillation after cardiac surgery. N Engl J Med 374:1911–1921

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Van Gelder IC, Hagens VE, Bosker HA, Kingma JH, Kamp O, Kingma T, Said SA, Darmanata JI, Timmermans AJ, Tijssen JG, Crijns HJ (2002) A comparison of rate control and rhythm control in patients with recurrent persistent atrial fibrillation. N Engl J Med 347:1834–1840

    Article  PubMed  Google Scholar 

  34. McLean AS, Taccone FS, Vieillard-Baron A (2016) Beta-blockers in septic shock to optimize hemodynamics? No. Intensive Care Med 42:1610–1612

    Article  PubMed  Google Scholar 

  35. McIntyre WF, Um KJ, Alhazzani W, Lengyel AP, Hajjar L, Gordon AC, Lamontagne F, Healey JS, Whitlock RP, Belley-Côté EP (2018) Association of vasopressin plus catecholamine vasopressors vs catecholamines alone with atrial fibrillation in patients with distributive shock: a systematic review and meta-analysis. JAMA 319:1889–1900

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Balik M (2018) New-onset atrial fibrillation in critically ill patients—implications for rhythm rather than rate control therapy? Int J Cardiol 266:147–148

    Article  CAS  PubMed  Google Scholar 

  37. Sterling SA, Puskarich MA, Glass AF, Guirgis F, Jones AE (2017) The impact of the sepsis-3 septic shock definition on previously defined septic shock patients. Crit Care Med 45:1436–1442

    Article  PubMed  PubMed Central  Google Scholar 

  38. Levy MM, Fink MP, Marshall JC, Abraham E, Angus D, Cook D, Cohen J, Opal SM, Vincent JL, Ramsay G (2003) 2001 SCCM/ESICM/ACCP/ATS/SIS international sepsis definitions conference. Crit Care Med 31:1250–1256

    Article  PubMed  Google Scholar 

Download references

Acknowledgements

The initiators of the trial express their gratitude to the unblinded study teams: Eva Kavkova, Zuzana Prazakova, Romana Pucholtova from the General University Hospital and Katerina Topkova, Irena Kozakova from the Kralovske Vinohrady University Hospital. We also thank to M. C. Mokotedi for proofreading and English editing.

Funding

The trial had received a four-year (2018–2022) support from the Czech Health Research Council, AZV No. NV18-06-00417, commencing on the 1st of May 2018.

Author information

Authors and Affiliations

  1. Department of Anesthesiology and Intensive Care, 1st Faculty of Medicine, Charles University and General University Hospital in Prague, U Nemocnice 2, 128 00, Prague 2, Czech Republic

    Martin Balik, Michal Maly, Tomas Brozek, Jan Rulisek, Michal Porizka, Robert Sachl, Michal Otahal, Petr Brestovansky, Eva Svobodova, Marek Flaksa, Zdenek Stach, Jan Horejsek, Lukas Volny, Ivana Jurisinova, Adam Novotny, Pavel Trachta, Jan Kunstyr & Petr Kopecky

  2. Department of Anesthesiology and Intensive Care, 3rd Faculty of Medicine, Charles University and Kralovske Vinohrady University Hospital in Prague, Prague, Czech Republic

    Tomas Tencer, Jaroslav Pazout, Frantisek Duska, Adela Krajcova & Petr Waldauf

  3. 2nd Department of Medicine, Department of Cardiovascular Medicine, 1st Faculty of Medicine, Charles University and General University Hospital in Prague, Prague, Czech Republic

    Jan Belohlavek

Authors
  1. Martin Balik
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Michal Maly
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Tomas Brozek
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Jan Rulisek
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Michal Porizka
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Robert Sachl
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Michal Otahal
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Petr Brestovansky
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Eva Svobodova
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Marek Flaksa
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Zdenek Stach
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Jan Horejsek
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. Lukas Volny
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. Ivana Jurisinova
    View author publications

    You can also search for this author in PubMed Google Scholar

  15. Adam Novotny
    View author publications

    You can also search for this author in PubMed Google Scholar

  16. Pavel Trachta
    View author publications

    You can also search for this author in PubMed Google Scholar

  17. Jan Kunstyr
    View author publications

    You can also search for this author in PubMed Google Scholar

  18. Petr Kopecky
    View author publications

    You can also search for this author in PubMed Google Scholar

  19. Tomas Tencer
    View author publications

    You can also search for this author in PubMed Google Scholar

  20. Jaroslav Pazout
    View author publications

    You can also search for this author in PubMed Google Scholar

  21. Jan Belohlavek
    View author publications

    You can also search for this author in PubMed Google Scholar

  22. Frantisek Duska
    View author publications

    You can also search for this author in PubMed Google Scholar

  23. Adela Krajcova
    View author publications

    You can also search for this author in PubMed Google Scholar

  24. Petr Waldauf
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

MB study coordinator, concept and design, drafting, revisions and approval of articles, provision of funding, data collection. PW, FD concept and design, electronic case report form, statistics, article revisions, data collection. MP, JR, MO, VM, MM, TB, RS, JP, PB, ES, MF, ZS, MS data collection, article revisions. JB article revisions, unblinded team coordination.

Corresponding author

Correspondence to Martin Balik.

Ethics declarations

Conflicts of interest

None.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary Information

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Balik, M., Maly, M., Brozek, T. et al. Propafenone versus amiodarone for supraventricular arrhythmias in septic shock: a randomised controlled trial. Intensive Care Med 49, 1283–1292 (2023). https://doi.org/10.1007/s00134-023-07208-3

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00134-023-07208-3

Keywords

Search

Navigation