Skip to main content

Advertisement

Log in

Efficacy and safety of loop diuretic therapy in acute decompensated heart failure: a clinical review

  • Published:
Heart Failure Reviews Aims and scope Submit manuscript

Abstract

Intravenous loop diuretics are widely used to treat the symptoms and signs of fluid overload in acute heart failure (AHF). Although diuretic therapy is widely used and strongly recommended by most recent clinical guidelines, prospective studies and randomized clinical trials are lacking and so reliable evidence is missing about the best therapy in terms of doses and methods of administration. In addition, clinical efficacy and safety outcomes are often affected by the presence of contrasting evidence. The efficacy of loop diuretics is impaired by diuretic resistance characterized by a decreased diuretic and natriuretic effect. This review focuses on the current management of AHF with diuretic therapy. Continuous diuretic infusion seems to be a good choice, from a pharmacokinetic point of view, when fluid overload is refractory to conventional therapy. Some available evidence comparing bolus injection to continuous infusion of loop diuretics proved the latter to be an effective and safe method of administration. Continuous infusion seems to produce a constant plasmatic concentration of drug with a more uniform daily diuretic and natriuretic effect and a greater safety profile (fewer adverse events such as worsening renal failure, electrolyte imbalances, ototoxicity). The analyses of the published studies did not provide conclusive data about the effects on clinical outcomes (mortality, rate of hospital readmissions, length of hospital stay and adverse events). Furthermore, recent studies focus their attention on alternative strategies of fluid removal, such as vasopressin antagonists, adenosine antagonists and ultrafiltration but available data are often inconclusive.

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

Access this article

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

Instant access to the full article PDF.

Fig. 1

Similar content being viewed by others

References

  1. Adams KF, Zannad F (1998) Clinical definition and epidemiology of advanced heart failure. Am Heart J 135(Suppl):S204–S215

    Article  PubMed  Google Scholar 

  2. Felker GM, Adams KF, Konstam MA, O’Connor CM, Gheorghiade M (2003) The problem of decompensated heart failure: nomenclature, classification, and risk stratification. Am Heart J 145:S18–S25

    Article  PubMed  Google Scholar 

  3. Members of the Statistics C, Stroke Statistics S, Thom T, Haase N, Rosamond W et al (2006) Heart disease and stroke statistics—2006 update: a report from the American heart association statistics committee and stroke statistics subcommittee. Circulation 113:e85–151.151

    Google Scholar 

  4. Emerman CL, Marco TD, Costanzo MR, Peacock WF, for the ASAC (2004) Impact of intravenous diuretics on the outcomes of patients hospitalized with acute decompensated heart failure: insights from the ADHERE(R) registry. J Card Fail 10:S116–S117

    Article  Google Scholar 

  5. Jessup M, Abraham WT, Casey et al (2009) Focused update: ACCF/AHA guidelines for the diagnosis and management of heart failure in adults: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines Developed in Collaboration With the International Society for Heart and Lung Transplantation. J Am Coll Cardiol 53:1343–1382

  6. Dickstein K, Cohen-Solal A, Filippatos G et al (2008) ESC guidelines for the diagnosis and treatment of acute and chronic heart failure 2008: the task force for the diagnosis and treatment of acute and chronic heart failure 2008 of the European Society of Cardiology. Developed in collaboration with the Heart Failure Association of the ESC (HFA) and endorsed by the European Society of Intensive Care Medicine (ESICM). Eur Heart J 29(19):2388–2442

    Google Scholar 

  7. Valentine JF, Brater DC, Krejs GJ (1986) Clearance of furosemide by the gastrointestinal tract. J Pharmacol Exp Ther 236(1):177–180

    CAS  PubMed  Google Scholar 

  8. Brater DC, Chennavasin P, Seiwell R (1980) Furosemide in patients with heart failure: shift in dose–response curves. Clin Pharmacol Ther 28(2):182–186

    Article  CAS  PubMed  Google Scholar 

  9. Gottlieb SS, Brater DC, Thomas I et al (2002) BG9719 (CVT-124), An A(1) adenosine receptor antagonist, protects against the decline in renal function observed with diuretic therapy. Circulation 105:1348–1353

    Article  CAS  PubMed  Google Scholar 

  10. Vasko MR, Cartwright DB, Knochel JP, Nixon JV, Brater DC (1985) Furosemide absorption altered in decompensated congestive heart failure. Ann Intern Med 102(3):314–318

    Article  CAS  PubMed  Google Scholar 

  11. Felker GM (2011) Loop diuretics in heart failure. Heart Fail Rev, 2011 April 23. Epub ahead of print

  12. Cowie MR, Komajda M, Murray-Thomas T, Underwood J, Ticho B (2006) POSH Investigators. Prevalence and impact of worsening renal function in patients hospitalized with decompensated heart failure: results of the prospective outcomes study in heart failure (POSH). Eur Heart J 27:1216–1222

    Article  PubMed  Google Scholar 

  13. Hasselblad V, Stough WG, Shah MR, Lokhnygina Y, O’Connor CM, Califf RM, Adams Jr KF (2007) Relation between dose of loop diuretics and outcomes in a heart failure population: results of the ESCAPE Trial. Eur J Heart Fail 9(10):1064–1069

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  14. Yilmaz MB, Gayat E, Mebazaa A et al (2011) Impact of diuretic dosing on mortality in acute heart failure using a propensity-matching analysis. Eur J Heart Fail 13:1244–1252

    Article  CAS  PubMed  Google Scholar 

  15. Butler J, Forman DE, Abraham WT et al (2004) Relationship between heart failure treatment and development of worsening renal function among hospitalized patients. Am Heart J 147(2):331–338

    Article  PubMed  Google Scholar 

  16. Testani JM, Jennifer Chen BS et al (2010) Potential effects of aggressive decongestion during the treatment of decompensated heart failure on renal function and survival. Circulation 122:265–272

    Article  PubMed Central  PubMed  Google Scholar 

  17. Aronson D, Burger AJ (2010) The relationship between transitory and persistent worsening renal function and mortality in patients with acute decompensated heart failure. J Card Fail 16:541–547

    Article  PubMed  Google Scholar 

  18. Cooper HA, Dries DL, Davis CE, Shen YL, Domanski MJ (1999) Diuretics and risk of arrhythmic death in patients with left ventricular dysfunction. Circulation 100:1311–1315

    Article  CAS  PubMed  Google Scholar 

  19. Ahmed A, Husain A, Love TE et al (2006) Heart failure, chronic diuretic use, and increase in mortality and hospitalization: an observational study using propensity score methods. Eur Heart J 27:1431–1439

    Article  PubMed Central  PubMed  Google Scholar 

  20. Parrinello G, Paterna S, Di Pasquale P et al (2011) Changes in estimating echocardiography pulmonary capillary wedge pressure after hypersaline plus furosemide versus furosemide alone in decompensated heart failure. J Card Fail 17(4):331–339

    Article  CAS  PubMed  Google Scholar 

  21. Kim GH (2004) Long-term adaptation of renal ion transporters to chronic diuretic treatment. Am J Nephrol 24:595–605

    Article  CAS  PubMed  Google Scholar 

  22. Ellison DH (1991) The physiologic basis of diuretic synergism: its role in treating diuretic resistance. Ann Intern Med 114:886–894

    Article  CAS  PubMed  Google Scholar 

  23. Loon NR, Wilcox CS, Unwin RJ (1989) Mechanism of impaired natriuretic response to furosemide during prolonged therapy. Kidney Int 36:682–689

    Article  CAS  PubMed  Google Scholar 

  24. Selektor Y, Weber KT (2008) The salt-avid state of congestive heart failure revisited. Am J Med Sci 335(3):209–218

    Article  PubMed  Google Scholar 

  25. McMurray JJ, Teerlink JR, Cotter G et al (2007) Effects of tezosentan on symptoms and clinical outcomes in patients with acute heart failure: the VERITAS randomized controlled trials. JAMA 298:2009–2019

    Article  CAS  PubMed  Google Scholar 

  26. Gheorghiade M, Konstam MA, Burnett JC Jr, for the Efficacy of Vasopressin Antagonism in Heart Failure Outcome Study With Tolvaptan I et al (2007) Short-term clinical effects of tolvaptan, an oral vasopressin antagonist, in patients hospitalized for heart failure: the EVEREST clinical status trials. JAMA 297:1332–1343

    Article  CAS  PubMed  Google Scholar 

  27. Copeland JG, Campbell DW, Plachetka JR, Salmon NW, Larson DF (1983) Diuresis with continuous infusion of furosemide after cardiac surgery. Am J Surg 146:796

    Article  CAS  PubMed  Google Scholar 

  28. Magovern JA, Magovern GJ Jr (1990) Diuresis in hemodynamically compromised patients: continuous furosemide infusion. Ann Thorac Surg 50(3):482–484

    Article  CAS  PubMed  Google Scholar 

  29. Rudy DW, Voelker JR, Greene PK et al (1991) Loop diuretics for chronic renal insufficiency: continuous infusion is more efficacious than bolus therapy. Ann Intern Med 115:360–366

    Article  CAS  PubMed  Google Scholar 

  30. Lawson DH, Gray JMB, Henry DA, Tilstone WJ (1978) Continuous infusion of furosemide in refractory edema. BMJ 2:476

    Article  CAS  PubMed  Google Scholar 

  31. van Meyel JJ, Smits P, Dormans T, Gerlag PG, Russel FG, Gribnau FW (1994) Continuous infusion of furosemide in the treatment of patients with congestive heart failure and diuretic resistance. J Intern Med 235(4):329–334

    Article  PubMed  Google Scholar 

  32. Salvator DR, Rey NR, Ramos GC, Punzalan FE (2005) Continuous infusion versus bolus injection of loop diuretics in congestive heart failure. Cochrane Database Syst Rev 3: CD003178

  33. Dormans TPJ, van Meyel JJM, Gerlag PGG et al (1996) Diuretic efficacy of high dose furosemide in severe heart failure: bolus injection versus continuous infusion. J Am Coll Cardiol 28:376–382

    Article  CAS  PubMed  Google Scholar 

  34. Lahav M, Regev A, Ra’anani P, Theodor E (1992) Intermittent administration of furosemide vs. continuous infusion preceded by a loading dose for congestive heart failure. Chest 102:725–731

    Article  CAS  PubMed  Google Scholar 

  35. Licata G, Di Pasquale P, Parrinello G et al (2003) Effects of high-doses furosemide and small volume hypertonic saline solution infusion in comparison with a high dose of furosemide as bolus in refractory congestive heart failure: long-term effects. Am Heart J 145:459–466

    Article  CAS  PubMed  Google Scholar 

  36. Aaser E, Gullestad L, Tollofsrud S et al (1997) Effect of bolus injection versus continuous infusion of furosemide on diuresis and neurohormonal activation in patients with severe congestive heart failure. Scand J Clin Lab Investig 57:361–368

    Article  CAS  Google Scholar 

  37. Bagatin J, Sardelic S, Gancevic I et al (1993) Diuretic efficiency of furosemide in continuous intravenous infusion vs. bolus injection in congestive heart failure: results of a pilot study. Pharmaca 31:279–286

    Google Scholar 

  38. Kramer WG, Smith WB, Ferguson J et al (1996) Pharmacodynamics of torsemide administered as intravenous injection and as a continuous infusion to patients with congestive heart failure. J Clin Pharmacol 36:265–270

    Article  CAS  PubMed  Google Scholar 

  39. Pivac N, Rumboldt Z, Sardelic S et al (1998) Diuretic effects of furosemide infusion versus bolus injection in congestive heart failure. Int J Clin Pharmacol Res 18(3):121–128

    CAS  PubMed  Google Scholar 

  40. Schuller D, Lynch J, Fine D (1997) Protocol-guided diuretic management: comparison of furosemide by continuous infusion and intermittent bolus. Crit Care Med 25:1969–1975

    Article  CAS  PubMed  Google Scholar 

  41. Allen LA, Turer AT, Dewald T, Stough WG, Cotter G, O’Connor CM (2010) Continuous versus bolus dosing of furosemide for patients hospitalized for heart failure. Am J Cardiol 105:1794–1797

    Article  PubMed Central  PubMed  Google Scholar 

  42. 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

    Article  CAS  PubMed  Google Scholar 

  43. Aziz EF, Alviar CL, Herzog E et al (2011) Continuous infusion of furosemide combined with low-dose dopamine compared to intermittent boluses in acutely decompensated heart failure is less nephrotoxic and carries a lower readmission at thirty days. Hell J Cardiol 52(3):227–235

    Google Scholar 

  44. Felker GM, Lee KL, Bull DA et al (2011) Diuretic strategies in patients with acute decompensated heart failure. N Engl J Med 364(9):797–805

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  45. Amer M, Adomaityte J, Qayyum R (2012) Continuous infusion versus intermittent bolus furosemide in ADHF: an update meta-analysis of randomized control trials. J Hosp Med 7:270–275

    Article  PubMed  Google Scholar 

  46. Konstam MA, Gheorghiade M, Burnett JC Jr, for the Efficacy of Vasopressin Antagonism in Heart Failure Outcome Study With Tolvaptan I et al (2007) Effects of oral tolvaptan in patients hospitalized for worsening heart failure: the EVEREST outcome trials. JAMA 297:1319–1331

    Article  CAS  PubMed  Google Scholar 

  47. Goldsmith SR, Elkayam U, Haught WH et al (2008) Efficacy and safety of the vasopressin V1A/V2-receptor antagonist conivaptan in acute decompensated heat failure: a dose-ranging pilot study. J Card Fail 14(8):641–647

    Article  CAS  PubMed  Google Scholar 

  48. Cotter G, Dittrich HC, Weatherley BD, Protect Steering Committee, Investigators and Coordinators et al (2008) The PROTECT pilot study: a randomized, placebo-controlled, dose-finding study of the adenosine A1 receptor antagonist rolofylline in patients with acute heart failure and renal impairment. J Card Fail 14(8):631–640

    Article  CAS  PubMed  Google Scholar 

  49. Voors AA, Dittrich HC, Massie BM et al (2011) Effects of the adenosine A1 receptor antagonist rolofylline on renal function in patients with acute heart failure and renal dysfunction: results from PROTECT (placebo-controlled Randomized Study of the Selective Adenosine A1 Receptor Antagonist rolofylline for patients hospitalized with acute decompensated heart failure and volume overload to assess treatment effect on congestion and renal function). JACC 57(19):1899–1907

    Article  CAS  PubMed  Google Scholar 

  50. Costanzo MR, Guglin ME, Saltzberg MT et al (2007) Ultrafiltration versus intravenous diuretics for patients hospitalized for acute decompensated heart failure. JACC 49:675–683

    Article  CAS  PubMed  Google Scholar 

Download references

Conflict of interest

Dr. Leto L, Dr. Aspromonte N and Dr. Feola M have no conflicts of interest or financial ties to disclose.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Mauro Feola.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Leto, L., Aspromonte, N. & Feola, M. Efficacy and safety of loop diuretic therapy in acute decompensated heart failure: a clinical review. Heart Fail Rev 19, 237–246 (2014). https://doi.org/10.1007/s10741-012-9354-7

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10741-012-9354-7

Keywords

Navigation