Prophylactic furosemide to prevent transfusion-associated circulatory overload: a randomized controlled study in rats

Abstract

Transfusion-associated circulatory overload (TACO) is the leading cause of transfusion related morbidity and mortality. The only treatment is empirical use of furosemide. Our aim was to investigate if furosemide can prevent TACO. A randomized controlled trial was performed using a previously validated two-hit rat model for TACO. Volume incompliance was induced (first hit) in anemic, anesthetized Lewis rats. Rats were randomized to placebo, low-dose (5 mg kg^-1) or high-dose (15 mg kg^-1) furosemide-administered prior to transfusion (second-hit) and divided over two doses. Primary outcome was change in left-ventricular end-diastolic pressure (∆LVEDP) pre- compared to post-transfusion. Secondary outcomes included changes in preload, afterload, contractility and systemic vascular resistance, as well as pulmonary outcomes. Furosemide treated animals had a significantly lower ∆LVEDP compared to placebo (p = 0.041), a dose-response effect was observed. ∆LVEDP in placebo was median + 8.7 mmHg (IQR 5.9-11), + 3.9 (2.8-5.6) in the low-dose and 1.9 (- 0.6 to 5.6) in the high-dose group. The effect of furosemide became apparent after 15 min. While urine output was significantly higher in furosemide treated animals (p = 0.03), there were no significant changes in preload, afterload, contractility or systemic vascular resistance. Furosemide rapidly and dose-dependently decreases the rise in hydrostatic pulmonary pressure following transfusion, essential for preventing TACO.

Figure 1

Effect of furosemide on LVEDP. (A) The change of LVEDP over the course of the transfusion is given per animal. Animals receiving the placebo group show the greatest increase in ΔLVEDP compared to low and high-dose furosemide. The decrease in LVEDP is dose-dependent and is apparent within 15-min. (B) The change of LVEDP over the course of the experiment. Animals receiving placebo have a greater increase in LVEDP post-transfusion and this remains higher through-out the follow-up period. ΔLVEDP difference between LVEDP at timepoint compared to baseline, Trx transfusion.

Figure 2

Urine output and P/F-ratios per treatment group. (A) There is a dose–effect response to the administration of furosemide and total urine output following randomization. (B) P/F-ratio shown between treatment groups.

Figure 3

Experimental design. Rats under general anesthesia are made anemic. The first-hit is a myocardial infarction rendering rats volume incompliant. Randomization to placebo, low or high-dose furosemide is performed and prior to transfusion half of the product is administered. Subsequently two RBC units (2.0 mL) are transfused followed by a subsequent dose and transfusion of the remaining two units (2.0 mL). Rats are monitored up to 1 h post-transfusion. PV-catheter pressure–volume catheter, Art.line arterial line, CVC central venous cannula, Circ.vol circulating volume, LAD left-anterior descending coronary artery.