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.
Highlights
Intravenous loop diuretics are a cornerstone of therapy in acutely decompensated heart failure (ADHF)
The use of intravenous loop diuretics is a cornerstone of therapy for acutely decompensated heart failure (ADHF) treatment, especially in patients admitted with pulmonary congestion and volume overload
Baseline characteristics A total of 128 patients were consecutively admitted and screened with diagnosis of ADHF; of these patients 22 were excluded for preserved ejection fraction, 8 for recent myocardial infarction, 8 for incomplete laboratory assessments at baseline, and 6 for severe renal disease
Summary
Intravenous loop diuretics are a cornerstone of therapy in acutely decompensated heart failure (ADHF). The use of intravenous loop diuretics is a cornerstone of therapy for acutely decompensated heart failure (ADHF) treatment, especially in patients admitted with pulmonary congestion and volume overload. Some studies have provided guidelines for the administration of these drugs in clinical practice, but data interpretation remains challenging due to the frequent exclusion of patients with kidney disease from major ADHF clinical trials. It is not clear if continuous infusion is better than intermittent boluses in terms of decongestion, maintenance of renal filtration function, and prognosis [6,7]. For the same reasons, continuous infusion is associated with sustained neuroendocrine activation and electrolyte imbalance that could potentially be reduced by intermittent administration
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