Role of duration of diuretic effect in preventing sodium retention

Objective: To determine whether the duration of diuretic effect at the active nephron site enhances ability to excrete an exogenous salt toad. Methods: We conducted a study that involved eight patients with New York Heart Association class II to III congestive heart failure. In a randomized, crossover manner, each patient received 3.25 mg intravenous bumetanide at 0 hours and again at 6 hours or a loading dose of 0.5 mg bumetanide at 0 hours followed by a continuous infusion of 0.5 mg/hr for 6 hours. Response was followed for 12 hours; a total of 6.5 mg of bumetanide was administered in each arm of the study. Eight hours after dosing began, we administered approximately 80 mEq sodium intravenously and examined its excretion over 4 hours. Results: The percentage of the load excreted was 86% +/- 15% versus 29% +/- 30% for the infusion and bolus regimens, respectively (p = 0.0005). More bumetanide was excreted during the infusion (667 +/- 133 mu g versus 240 +/- 121 mu g; p = 0.0002). During the infusion, however, more sodium was excreted relative to amounts of bumetanide, indicating that the efficiency of response was greater during the infusion, 0.10 +/- 0.02 mEq sodium per microgram bumetanide versus 0.07 +/- 0.05 mEq for the bolus (p = 0.0145). Conclusions: These data support the notions that a long-acting loop diuretic maintains its efficacy and that a longer duration of action facilitates excretion of a sodium load, such as that which might occur during dietary indiscretion.