Diuretics - High dose vs. Low dose (Adult study)

Diuretic Strategies in Patients with Acute Decompensated Heart Failure
G. Michael Felker, M.D., et al. for the NHLBI Heart Failure Clinical Research Network
N Engl J Med 2011; 364:797-805
March 3, 2011

Background
Loop diuretics are an essential component of therapy for patients with acute decompensated heart failure, but there are few prospective data to guide their use.

Methods
In a prospective, double-blind, randomized trial, we assigned 308 patients with acute decompensated heart failure to receive furosemide administered intravenously by means of either a bolus every 12 hours or continuous infusion and at either a low dose (equivalent to the patient's previous oral dose) or a high dose (2.5 times the previous oral dose). The protocol allowed specified dose adjustments after 48 hours. The coprimary end points were patients' global assessment of symptoms, quantified as the area under the curve (AUC) of the score on a visual-analogue scale over the course of 72 hours, and the change in the serum creatinine level from baseline to 72 hours.

Results
In the comparison of bolus with continuous infusion, there was no significant difference in patients' global assessment of symptoms (mean AUC, 4236±1440 and 4373±1404, respectively; P=0.47) or in the mean change in the creatinine level (0.05±0.3 mg per deciliter [4.4±26.5 μmol per liter] and 0.07±0.3 mg per deciliter [6.2±26.5 μmol per liter], respectively; P=0.45). In the comparison of the high-dose strategy with the low-dose strategy, there was a nonsignificant trend toward greater improvement in patients' global assessment of symptoms in the high-dose group (mean AUC, 4430±1401 vs. 4171±1436; P=0.06). There was no significant difference between these groups in the mean change in the creatinine level (0.08±0.3 mg per deciliter [7.1±26.5 μmol per liter] with the high-dose strategy and 0.04±0.3 mg per deciliter [3.5±26.5 μmol per liter] with the low-dose strategy, P=0.21). The high-dose strategy was associated with greater diuresis and more favorable outcomes in some secondary measures but also with transient worsening of renal function.

Conclusions
Among patients with acute decompensated heart failure, there were no significant differences in patients' global assessment of symptoms or in the change in renal function when diuretic therapy was administered by bolus as compared with continuous infusion or at a high dose as compared with a low dose. (Funded by the National Heart, Lung, and Blood Institute; ClinicalTrials.gov number, NCT00577135.)

Editorial on the above article:
Comparative Effectiveness of Diuretic Regimens
Gregg C. Fonarow, M.D.
N Engl J Med 2011; 364:877-878
March 3, 2011

Acute decompensated heart failure is associated with substantial morbidity, mortality, and health care expenditures.1 Most patients present with symptoms related to fluid overload, which may be complicated by concomitant renal dysfunction.2 Treating the signs and symptoms of heart failure while preserving or improving renal function is a crucial therapeutic goal.
For more than five decades, the administration of intravenous loop diuretics has been the mainstay of therapy to reduce congestion, decrease ventricular filling pressures, and improve symptoms of heart failure, with such therapy becoming an empirically accepted standard of care for this condition.1,3,4 However, there is little evidence . . .

Diuretics: Sequential blockade (Diuril-Lasix) "misconception"

JACC 2010;56:1527-34

Combination of Loop Diuretics With Thiazide-Type Diuretics in Heart Failure

Jacob C. Jentzer, MD,Tracy A. DeWald, RD, PharmD, BCPS andAdrian F. Hernandez, MD

Volume overload is an important clinical target in heart failure management, typically addressed using loop diuretics. An important and challenging subset of heart failure patients exhibit fluid overload despite significant doses of loop diuretics. One approach to overcome loop diuretic resistance is the addition of a thiazide-typediuretic to produce diuretic synergy via "sequential nephron blockade," first described more than 40 years ago. Although potentially able to induce diuresis in patients otherwise resistant to high doses of loop diuretics, this strategy has not been subjected to large-scale clinical trials to establish safety and clinical efficacy. We summarize the existing literature evaluating the combination of loop and thiazide diuretics in patients with heart failure in order to describe the possible benefits and hazards associated with this therapy. Combinationdiuretic therapy using any of several thiazide-type diuretics can more than double daily urine sodium excretion to induce weight loss and edema resolution, at the risk of inducing severe hypokalemia in addition to hyponatremia, hypotension, and worsening renal function. We provide considerations about prudent use of this therapy and review potential misconceptions about this long-used diuretic approach. Finally, we seek to highlight the need for pragmatic clinical trials for this commonly used therapy.