Fluid management system aids in safe, controlled decongestion in acute heart failure
A device-based fluid management system to guide diuretic therapy supports safe and effective regulation of fluid loss in acute heart failure (AHF) patients with preserved systolic blood pressure and pre-existing chronic renal disease, according to early data from the TARGET-1 and TARGET-2 studies.
Named Reprieve, the system continuously monitors urine output and delivers a sufficient volume of hydration fluid to maintain the set fluid balance rate. This facilitates greater control of fluid loss during diuretic administration.
“In both studies, we met the efficacy endpoint of preventing excess fluid loss with fully controlled net volume removal. Of note, it follows our desired goal – in TARGET-1 smaller doses of furosemide were deliberately used as it was a safety/feasibility study, whereas in TARGET-2 furosemide doses were higher to promote/facilitate negative fluid balance,” the investigators said.
The study population comprised 19 AHF patients (mean age, 67 years; 94.7 percent male), with mean ejection fraction of 34 percent and median N‐terminal pro‐B‐type natriuretic peptide of 4,492 pg/mL. Patients served as their own controls, with each undergoing 24 hours of standard diuretic therapy followed by another 24 hours of diuretics guided by Reprieve (normal saline was used for matched volume replacement).
In all 19 patients (100 percent), actual fluid loss did not exceed the target fluid loss at the end of therapy. The mean total diuresis was 6,284 mL during the 24 hours in which the Reprieve system was in place as compared with 1,966 mL in the 24 hours prior and 2,053 mL after (p-both<0.0001). [Eur J Heart Fail 2019;doi:10.1002/ejhf.1533]
The investigators explained that the significant increase in urine production observed during Reprieve therapy was likely due to the higher doses of furosemide used in TARGET-2 (262 mg during vs 76 mg before and 80 mg after; p-both<0.0001).
The major concern of clinicians to use diuretics more aggressively was the risk of potential rapid, uncontrolled intravascular volume depletion, which comes with deleterious consequences. According to the investigators, Reprieve reduced the reluctance to administer high doses of diuretics by allowing real-time adjustment of fluid balance (net negative balance) during treatment.
Not a renal replacement therapy
“Despite high rates of urine production during the entire period of Reprieve therapy, no signs of haemodynamic instability were seen,” the investigators noted.
Mean systolic blood pressure remained unchanged, while mean creatinine dropped from 1.45 mg/dL at baseline to 1.26 mg/dL after Reprieve (p<0.001). There were no changes in biomarkers of renal injury observed during treatment, nor were there occurrences of procedural complications, infections, deaths or serious adverse events.
At the end of therapy, patient global assessment improved from a mean of 7.7 to 3.0 points (p<0.001), central venous pressure fell from 15.5 to 12.8 mm Hg (p 0.05), and the median urine sodium loss was 9.7 mmol/h.
“It is worth noting that Reprieve therapy is not any form of renal replacement therapy. We would rather call it a ‘support’ intervention, which means it needs (good enough) renal function to respond to diuretics,” the investigators pointed out.
“Thus, the effect of therapy depends on diuretic responsiveness, diuretic dose, Reprieve therapy itself, and set net negative volume. However, it allows clinicians to control the process of smooth decongestion,” ie, preventing fast, uncontrolled removal of intravascular volume to eliminate deleterious consequences of overdiuresis, they added.
Given that the current study was designed to evaluate treatment safety and accumulate data on device performance, the investigators underscored the need for additional studies to explore whether an approach based on careful monitoring of hourly diuresis with concomitant adjustment of diuretics without Reprieve would be equally efficient.
Additionally, caution must be exercised regarding furosemide efficacy, as the diuretic regimen used in TARGET-1 and TARGET-2 was not controlled by any protocol.