Subcutaneous Furosemide in Heart Failure: a Systematic Review

Overview

Journal Eur Heart J Cardiovasc Pharmacother

Publisher Oxford University Press

Date 2024 Nov 9

PMID 39520561

Authors

Joanna Osmanska

Mark C Petrie

Kieran F Docherty

Matthew M Y Lee

John J V McMurray

Ross T Campbell

Affiliations

Soon will be listed here.

Abstract

Background And Aim: Intravenous loop diuretics are the primary treatment for congestion in patients with decompensated heart failure (HF). Furosemide is the most commonly used loop diuretic and is licensed for administration either orally, intramuscularly or intravenously but not subcutaneously. Recently developed, pH-neutral, concentrated, and 'skin-friendly' preparations of furosemide have been developed which allow subcutaneous administration. In this systematic review, we summarize and critically appraise the current evidence for subcutaneous furosemide in patients with HF.

Methods And Results: The electronic databases MEDLINE, EMBASE, the Cochrane Library, and ClinicalTrials.gov registry were searched up to 30 September 2024. Of the 17 studies identified, 5 were randomized controlled trials (RCTs), 2 were non-randomized controlled studies, 3 were prospective observational cohort studies, and 7 were retrospective observational studies.All RCTs utilized novel pH-neutral, subcutaneous preparations of furosemide. Bioavailability of novel subcutaneous preparations were similar to intravenous furosemide 10 mg/mL: 99.7% for an 8 mg/mL preparation and 112% for a 30 mg/mL preparation. Natriuresis and diuresis were also similar with novel subcutaneous and conventional intravenous furosemide. Adverse events related to novel preparations included infusion site pain or discomfort, localized skin erythema and minimal swelling. All studies of subcutaneous conventional furosemide were non-randomized with very few data regarding bioavailability or diuretic and natriuretic effect. Subcutaneous conventional furosemide was associated with substantial skin irritation (affecting 3-23% of patients), and skin infections requiring treatment with antibiotics (3-17%).

Conclusion: Novel, pH-neutral preparations of subcutaneous furosemide achieved similar diuresis, natriuresis, and bioavailability to intravenous furosemide, and were well tolerated. Novel preparations may be a treatment option for patients with HF.

References

Afari M, Aoun J, Khare S, Tsao L . Subcutaneous furosemide for the treatment of heart failure: a state-of-the art review. Heart Fail Rev. 2019; 24(3):309-313. DOI: 10.1007/s10741-018-9760-6. View

Bahar J, Rahman A, Wong G, Sankaranarayanan R, Ahmed F, Taylor R . Outpatient treatment of decompensated heart failure: A systematic review and study level meta-analysis. ESC Heart Fail. 2024; . DOI: 10.1002/ehf2.14841. View

Greene S, Wilson L, Abbasi S, Yusuf A, Hammill B . Outpatient Intravenous Diuretic Therapy for Heart Failure in the United States. J Am Coll Cardiol. 2019; 73(9):1101-1103. PMC: 7085417. DOI: 10.1016/j.jacc.2018.12.034. View

Galindo-Ocana J, Romero-Mena J, Castillo-Ferrando J, Aguilera-Gonzalez C, Bernabeu-Wittel M, Ollero-Baturone M . Subcutaneous furosemide as palliative treatment in patients with advanced and terminal-phase heart failure. BMJ Support Palliat Care. 2014; 3(1):7-9. DOI: 10.1136/bmjspcare-2012-000296. View

Civera J, de la Espriella R, Heredia R, Minana G, Santas E, Conesa A . Efficacy and Safety of Subcutaneous Infusion of Non-formulated Furosemide in Patients with Worsening Heart Failure: a Real-World Study. J Cardiovasc Transl Res. 2021; 15(3):644-652. PMC: 9213343. DOI: 10.1007/s12265-021-10173-1. View

Allen L, Turer A, Dewald T, Stough W, Cotter G, OConnor C . Continuous versus bolus dosing of Furosemide for patients hospitalized for heart failure. Am J Cardiol. 2010; 105(12):1794-7. PMC: 3900281. DOI: 10.1016/j.amjcard.2010.01.355. View

Mullens W, Damman K, Harjola V, Mebazaa A, Brunner-La Rocca H, Martens P . The use of diuretics in heart failure with congestion - a position statement from the Heart Failure Association of the European Society of Cardiology. Eur J Heart Fail. 2019; 21(2):137-155. DOI: 10.1002/ejhf.1369. View

Lozano Bahamonde A, Escolar Perez V, Echebarria Chousa A, Azcona Lucio A, Alfambra Vicente S, Rodriguez Rodriguez B . Subcutaneous Furosemide in Patients With Refractory Heart Failure. Rev Esp Cardiol (Engl Ed). 2018; 72(6):500-502. DOI: 10.1016/j.rec.2018.06.012. View

Sica D, Muntendam P, Myers R, Ter Maaten J, Sale M, de Boer R . Subcutaneous Furosemide in Heart Failure: Pharmacokinetic Characteristics of a Newly Buffered Solution. JACC Basic Transl Sci. 2018; 3(1):25-34. PMC: 6059009. DOI: 10.1016/j.jacbts.2017.10.001. View

10.

Zatarain-Nicolas E, Lopez-Diaz J, de la Fuente-Galan L, Garcia-Pardo H, Recio-Platero A, San Roman-Calvar J . Subcutaneous infusion of furosemide administered by elastomeric pumps for decompensated heart failure treatment: initial experience. Rev Esp Cardiol (Engl Ed). 2014; 66(12):1002-4. DOI: 10.1016/j.rec.2013.06.008. View

11.

Gilotra N, Princewill O, Marino B, Okwuosa I, Chasler J, Almansa J . Efficacy of Intravenous Furosemide Versus a Novel, pH-Neutral Furosemide Formulation Administered Subcutaneously in Outpatients With Worsening Heart Failure. JACC Heart Fail. 2017; 6(1):65-70. DOI: 10.1016/j.jchf.2017.10.001. View

12.

Brown A, Westley K, Robson J, Armstrong L, Matthews I, Runnett C . Furosemide in end-stage heart failure: community subcutaneous infusions. BMJ Support Palliat Care. 2020; 12(e6):e763-e766. DOI: 10.1136/bmjspcare-2019-002158. View

13.

Salvador D, Rey N, Ramos G, Punzalan F . Continuous infusion versus bolus injection of loop diuretics in congestive heart failure. Cochrane Database Syst Rev. 2005; (3):CD003178. PMC: 8094162. DOI: 10.1002/14651858.CD003178.pub3. View

14.

Goenaga M, Millet M, Sanchez E, Garde C, Carrera J, Arzellus E . Subcutaneous furosemide. Ann Pharmacother. 2004; 38(10):1751. DOI: 10.1345/aph.1E172. View

15.

Lozano Bahamonde A, Escolar Perez V, Laskibar Asua A, Rodriguez Rodriguez M, Murga Eizagaechevarria N . Subcutaneous furosemide in patients with refractory heart failure. BMJ Support Palliat Care. 2018; 8(3):354-355. DOI: 10.1136/bmjspcare-2018-001570. View

16.

Wu M, Chang N, Su C, Hsu Y, Chen T, Lin Y . Loop diuretic strategies in patients with acute decompensated heart failure: a meta-analysis of randomized controlled trials. J Crit Care. 2013; 29(1):2-9. DOI: 10.1016/j.jcrc.2013.10.009. View

17.

Lopez-Vilella R, Sanchez-Lazaro I, Husillos Tamarit I, Monte Boquet E, Villota J, Donoso Trenado V . Administration of Subcutaneous Furosemide in Elastomeric Pump vs. Oral Solution for the Treatment of Diuretic Refractory Congestion. High Blood Press Cardiovasc Prev. 2021; 28(6):589-596. DOI: 10.1007/s40292-021-00476-4. View

18.

Birch F, Boam E, Parsons S, Ghosh J, Johnson M . Subcutaneous furosemide in advanced heart failure: service improvement project. BMJ Support Palliat Care. 2021; 13(1):112-116. DOI: 10.1136/bmjspcare-2020-002803. View

19.

Palazzuoli A, Pellegrini M, Ruocco G, Martini G, Franci B, Campagna M . Continuous versus bolus intermittent loop diuretic infusion in acutely decompensated heart failure: a prospective randomized trial. Crit Care. 2014; 18(3):R134. PMC: 4227080. DOI: 10.1186/cc13952. View

20.

Konstam M, Massaro J, Dhingra R, Walsh M, Ordway L, Pursley M . Avoiding Treatment in Hospital With Subcutaneous Furosemide for Worsening Heart Failure: A Pilot Study (AT HOME-HF). JACC Heart Fail. 2024; 12(11):1830-1841. DOI: 10.1016/j.jchf.2024.07.015. View