Subcutaneous furosemide in heart failure: a systematic review.

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, '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 31 December 2023. Of the 17 studies identified, 5 were randomised controlled trials (RCTs), 2 were non-randomised controlled studies, 3 were prospective observational cohort studies, and 7 were retrospective observational studies.All RCTs utilised 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 of novel preparations included infusion site pain or discomfort, localised skin erythema and minimal swelling. All studies of conventional subcutaneous furosemide were non-randomised with very limited data re bioavailability or diuretic and natriuretic effect. Conventional subcutaneous furosemide was associated with substantial skin irritation (affecting 3-23% of patients), and skin infections requiring treatment with antibiotics (3-17%).

Conclusions: 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.