How much furosemide should be administered to prevent transfusion-associated circulatory overload? Results of a dose-finding study.

Abstract

Background and objectives: Transfusion-associated circulatory overload (TACO) is a common and life-threatening transfusion complication. Because of uncertainty regarding dosing, pre-transfusion furosemide prophylaxis is not widely endorsed. The aim of this study was to generate a furosemide dose-response curve in TACO-susceptible patients using the multiple comparisons procedure and modelling (MCP-Mod) methodology.

Materials and methods: Inpatients aged ≥50 years receiving intravenous (IV) furosemide were screened for eligibility at two academic hospitals. Exclusion criteria were active bleeding, haemodynamic instability, glomerular filtration rate (GFR) < 30 mL/min/1.73 m² and diuretic therapy administered within 24 h or albumin administered within 8 h. The primary outcome measure was 6-h urine output post furosemide administration. After incorporation of age, sex, chronic diuretic use, mean arterial pressure, GFR and serum albumin as covariates of diuretic response, MCP-Mod was applied after every 50th enrolment until a weight-adjusted dose-response curve was identified with 100 mL precision.

Results: One-hundred forty-nine patients were enrolled. Urine output varied widely at each furosemide dose. Because of the presence of outliers and a paucity of patients receiving higher doses, only those receiving doses up to 0.6 mg/kg (n = 132) were included. After incorporating covariates, linear-log was identified as the best fitting model. Application of this formula revealed that, depending upon patient characteristics, 10-40 mg of furosemide IV would be required to achieve a diuresis volume of 400 mL, which is sufficient to offset 1 red blood cell unit.

Conclusion: We report a novel furosemide dose-response model for TACO-susceptible patients. Once validated, this model will guide furosemide dosing for a planned controlled trial evaluating furosemide for TACO prevention.