Continuous versus bolus intermittent loop diuretic infusion in acutely decompensated heart failure: a prospective randomized trial

Abstract

IntroductionIntravenous loop diuretics are a cornerstone of therapy in acutely decompensated heart failure (ADHF). We sought to determine if there are any differences in clinical outcomes between intravenous bolus and continuous infusion of loop diuretics.MethodsSubjects with ADHF within 12 hours of hospital admission were randomly assigned to continuous infusion or twice daily bolus therapy with furosemide. There were three co-primary endpoints assessed from admission to discharge: the mean paired changes in serum creatinine, estimated glomerular filtration rate (eGFR), and reduction in B-type natriuretic peptide (BNP). Secondary endpoints included the rate of acute kidney injury (AKI), change in body weight and six months follow-up evaluation after discharge.ResultsA total of 43 received a continuous infusion and 39 were assigned to bolus treatment. At discharge, the mean change in serum creatinine was higher (+0.8 ± 0.4 versus -0.8 ± 0.3 mg/dl P <0.01), and eGFR was lower (-9 ± 7 versus +5 ± 6 ml/min/1.73 m2P <0.05) in the continuous arm. There was no significant difference in the degree of weight loss (-4.1 ± 1.9 versus -3.5 ± 2.4 kg P = 0.23). The continuous infusion arm had a greater reduction in BNP over the hospital course, (-576 ± 655 versus -181 ± 527 pg/ml P = 0.02). The rates of AKI were comparable (22% and 15% P = 0.3) between the two groups. There was more frequent use of hypertonic saline solutions for hyponatremia (33% versus 18% P <0.01), intravenous dopamine infusions (35% versus 23% P = 0.02), and the hospital length of stay was longer in the continuous infusion group (14. 3 ± 5 versus 11.5 ± 4 days, P <0.03). At 6 months there were higher rates of re-admission or death in the continuous infusion group, 58% versus 23%, (P = 0.001) and this mode of treatment independently associated with this outcome after adjusting for baseline and intermediate variables (adjusted hazard ratio = 2.57, 95% confidence interval, 1.01 to 6.58 P = 0.04).ConclusionsIn the setting of ADHF, continuous infusion of loop diuretics resulted in greater reductions in BNP from admission to discharge. However, this appeared to occur at the consequence of worsened renal filtration function, use of additional treatment, and higher rates of rehospitalization or death at six months.Trial registrationClinicalTrials.gov NCT01441245. Registered 23 September 2011.

Diuretic Treatment in Heart Failure

“…32 Although these data do not support using continuous diuretic infusions for acute decompensated heart failure, several caveats should be mentioned. Continuous infusions were not routinely preceded by loading doses in the DOSE trial, which speed achievement of steady state.…”

Continuous infusion vs. intermittent bolus injection of furosemide in acute decompensated heart failure: systematic review and meta‐analysis of randomised controlled trials

“…Several recent randomised controlled trials (RCTs) have investigated the efficacy and safety profiles of modes of administration (continuous infusion vs. bolus) of i.v. furosemide in heart failure populations, but results have been conflicting . Continuous infusion of furosemide is believed to confer additional benefits over bolus injection, with less variability in peak plasma furosemide concentration resulting in a consistent, predictable urine output and less risk of electrolyte disturbance.…”

“…However, the largest multi‐centre RCT comparison, conducted by Felker et al found no significant difference in mortality and other clinical end‐points between continuous infusion or bolus injection of furosemide in heart failure. Several recent trials have suggested a higher incidence of potentially harmful effects with continuous infusions, namely transient hypotension, electrolyte disturbance and acute kidney injury . Thus, it remains unclear whether one method of furosemide administration is superior to the other in the heart failure population.…”

The prognostic combined role of B-type natriuretic peptide, blood urea nitrogen and congestion signs persistence in patients with acute heart failure

“…27 In contrast, our study showed that a significant BNP reduction during loop diuretic treatment was not associated with reduced mortality or rehospitalization in patients with both reduced and preserved renal function. 28,29 Different results in several studies could be influenced by several variables: they could ride on the hemodynamic picture and left ventricular filling pressure levels; they could depend on water and sodium overload entity as well as on different response to treatment. Finally, they could depend on baseline characteristic of patients enrolled: gender, body weight, presence of renal dysfunction and co-morbidities are all potential confounding factors.…”