Abstract
Background
Diuretic resistance is a common issue in patients with acute decompensation of advanced chronic heart failure (ACHF). The aim of this trial was to compare boluses and continuous infusion of furosemide in a selected population of patients with ACHF and high risk for diuretic resistance.
Methods
In this single-centre, double-blind, double-dummy, randomized trial, we enrolled 80 patients admitted for acute decompensation of ACHF (NYHA IV, EF ≤ 30%) with criteria of high risk for diuretic resistance (SBP ≤ 110 mmHg, wet score ≥ 12/18, and sodium ≤ 135 mMol/L). Patients were assigned in a 1:1 ratio to receive furosemide by bolus every 12 h or by continuous infusion. Diuretic treatment and dummy treatment were prepared by a nurse unassigned to patients’ care. The study treatment was continued for up to 72 h. Coprimary endpoints were total urinary output and freedom from congestion at 72 h.
Results
80 patients were enrolled with 40 patients in each treatment arm. Mean daily furosemide was 216 mg in continuous-infusion arm and 195 mg in the bolus intermittent arm. Freedom from congestion (defined as jugular venous pressure of < 8 cm, with no orthopnea and with trace peripheral edema or no edema) occurred more in the continuous infusion than in the bolus arm (48% vs. 25%, p = 0.04), while total urinary output after 72 h was 8612 ± 2984 ml in the bolus arm and 10,020 ± 3032 ml in the continuous arm (p = 0.04). Treatment failure occurred less in the continuous-infusion group (15% vs. 38%, p = 0.02), while there was no significant difference between groups in the incidence of worsening of renal function.
Conclusion
Among patients with acute decompensation of ACHF and high risk of diuretic resistance, continuous infusion of intravenous furosemide was associated with better decongestion.
DRAIN trial
ClinicalTrials.gov number NCT03592836.
Graphic abstract
Similar content being viewed by others
References
Neuberg GW, Miller AB, O’Connor CM, Belkin RN, Carson PE, Cropp AB, Frid DJ, Nye RG, Pressler ML, Wertheimer JH, Packer M (2002) Diuretic resistance predicts mortality in patients with advanced heart failure. Am Heart J 144:31–38
Testani JM, Brisco MA, Turner JM, Spatz ES, Bellumkonda L, Parikh CR et al (2014) Loop diuretic efficiency: a metric of diuretic responsiveness with prognostic importance in acute decompensated heart failure. Circ Heart Fail 7(2):261–270
Ellison DH, Felker GM (2017) Diuretic treatment in heart failure. N Engl J Med 377:1964–1975
Thomson MR, Nappi JM, Dunn SP, Hollis IB, Rodgers JE, Van Bakel AB (2010) Continuous versus intermittent infusion of furosemide in acute decompensated heart failure. J Card Fail 16:188–193
Allen LA, Turer AT, DeWald T et al (2010) Continuous versus bolus dosing of furosemide for patients hospitalized for heart failure. Am J Cardiol 105(12):1794–1797
Felker GM, Lee KL, Bull DA, Redfield MM, Stevenson LW, Goldsmith SR et al (2011) Diuretic strategies in patients with acute decompensated heart failure. N Engl J Med 364:797–805
Kuriyama A, Urushidani S (2019) Continuous versus intermittent administration of furosemide in acute decompensated heart failure: a systematic review and meta-analysis. Heart Fail Rev 24(1):31–39
Metra M, Ponikowski P, Dickstein K et al (2007) Advanced chronic heart failure: a position statement from the study group on advanced heart failure of the heart failure association of the ESC. Eur J Heart Fail 9:684–694
Gheorghiade M, Follath F, Ponikowski P et al (2010) European society of cardiology; European society of intensive care medicine. Assessing and grading congestion in acute heart failure: a scientific statement from the acute heart failure committee of the heart failure association of the European society of cardiology and endorsed by the European society of intensive care medicine. Eur J Heart Fail 12:423–433
ESC Scientific Document Group (2016) ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure: the task force for the diagnosis and treatment of acute and chronic heart failure of the European society of cardiology (ESC). Eur Heart J 37:2129–2200
Ambrosio G, Di Lenarda A, Fedele F, Gabrielli D, Metra M, Oliva F, Perna G, Senni M, De Maria R (2009) Inotrope therapy in acute heart failure: a critical review of clinical and scientific evidence for levosimendan in the context of traditional treatment. Giomale Ital Cardiol 10:422–433
Frea S, Pidello S, Canavosio FG et al (2015) Clinical assessment of hypoperfusion in acute heart failure: evergreen or antique? Circ J 79:398–405
Frea S, Bovolo V, Pidello S, Canavosio FG, Botta M, Bergerone S, Gaita F (2015) Clinical and prognostic role of ammonia in advanced decompensated heart failure. The cardio-abdominal syndrome? Int J Cardiol 15(195):53–60
Frea S, Centofanti P, Pidello S, Giordana F, Bovolo V, Baronetto A, Franco B, Cingolani MM, Attisani M, Morello M, Bergerone S, Rinaldi M, Gaita F (2018) Noninvasive assessment of hemodynamic status in Heart-Ware left ventricular assist device patients: validation of an echocardiographic approach. JACC Cardiovasc Imaging. https://doi.org/10.1016/j.jcmg.2018.01.026
Frea S, Pidello S, Bovolo V, Iacovino C, Franco E, Pinneri F, Galluzzo A, Volpe A, Visconti M, Peirone A, Morello M, Bergerone S, Gaita F (2016) Prognostic incremental role of right ventricular function in acute decompensation of advanced chronic heart failure. Eur J Heart Fail 18(5):564–572
Valente M, Voors A, Damman K et al (2014) Diuretic response in acute heart failure: clinical characteristics and prognostic significance. Eur Heart J 35:1284–1293
Matsue Y, Ter Maaten JM, Suzuki M, Goldsmith SR et al (2017) Early treatment with tolvaptan improves diuretic response in acute heart failure with renal dysfunction. Clin Res Cardiol 106(10):802–812
Bekfani T, Westphal F, Schulze PC (2018) Therapeutic options in advanced heart failure. Clin Res Cardiol 107(2):114–119
Schulz KF, Altman DG, Moher D, For the CONSORT Group (2010) CONSORT statement: updated guidelines for reporting parallel group randomised trials. BMJ 340:c332
Llorens P, Miró O, Herrero P et al (2014) Clinical effects and safety of different strategies for administering intravenous diuretics in acutely decompensated heart failure: a randomised clinical trial. Emerg Med J 31:706–713
Ng KT, Yap JLL (2018) Continuous infusion vs. intermittent bolus injection of furosemide in acute decompensated heart failure: systematic review and meta-analysis of randomised controlled trials. Anaesthesia 73(2):238–247
Mullens W, Abrahams Z, Francis GS et al (2009) Importance of venous congestion for worsening of renal function in advanced decompensated heart failure. J Am Coll Cardiol 53:589–596
Metra M, Davison B, Bettari L, Sun H, Edwards C, Lazzarini V, Piovanelli B, Carubelli V, Bugatti S, Lombardi C, Cotter G, Dei Cas L (2012) Is worsening renal function an ominous prognostic sign in patients with acute heart failure? The role of congestion and its interaction with renal function. Circ Heart Fail 5(1):54–62
Brisco MA, Zile MR, Hanberg JS et al (2016) Relevance of changes in serum creatinine during a heart failure trial of decongestive strategies: insights from the DOSE trial. J Card Fail. 22:753–760
Sanjay S, Ra Annigeri, Seshadri R et al (2008) The comparison of the diuretic and natriuretic efficacy of continuous and bolus intravenous furosemide in patients with chronic kidney disease. Nephrology 13(3):247–250
Ng T, Konopka E, Hyderi AF et al (2013) Comparison of bumetanide- and metolazone-based diuretic regimens to furosemide in acute heart failure. J Cardiovasc Pharmacol Ther 18:345–356
Sica D (2003) Metolazone and its role in edema management. CHF 9:100–105
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Conflict of interest
The author declares that they have no competing interests.
Electronic supplementary material
Below is the link to the electronic supplementary material.
Rights and permissions
About this article
Cite this article
Frea, S., Pidello, S., Volpe, A. et al. Diuretic treatment in high-risk acute decompensation of advanced chronic heart failure—bolus intermittent vs. continuous infusion of furosemide: a randomized controlled trial. Clin Res Cardiol 109, 417–425 (2020). https://doi.org/10.1007/s00392-019-01521-y
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00392-019-01521-y