Practical Applications of Intravenous Diuretic Therapy in Decompensated Heart Failure

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Abstract

Intravenous (IV) loop diuretics play an important role in the treatment of decompensated heart failure (DHF). They inhibit the Na+-K+-2Cl− reabsorptive pump in the thick ascending limb of the loop of Henle, and the resultant natriuresis and diuresis decreases volume load, improves hemodynamics, and reduces DHF symptoms. However, loop diuretics have a short half-life and their efficacy may be limited by postdiuretic sodium rebound during the period between doses in which the tubular diuretic concentration is subtherapeutic. Moreover, they can produce electrolyte abnormalities, neurohormonal activation, intravascular volume depletion, and renal dysfunction. Several studies have reported an association between diuretic therapy and increased morbidity and mortality. In addition, many patients, especially those with more advanced forms of heart failure (HF), are resistant to standard doses of loop diuretics. These high-risk, resistant patients may benefit from pharmacologic and/or nonpharmacologic interventions to improve hemodynamic performance, treatment of renovascular disease, discontinuation of aspirin and other sodium-retaining drugs, manipulation of the route of delivery or combination of diuretic classes, or hemofiltration. Despite >50 years of use, many questions regarding the use of intravenous diuretic agents in patients with DHF are still unanswered, and there remains a compelling need for well-designed randomized, controlled clinical trials to establish appropriate treatment regimens that maximize therapeutic benefit while minimizing morbidity and mortality.

Section snippets

Randomized controlled trials of diuretics

Two prospective, randomized trials, both conducted nearly 20 years ago, have evaluated the immediate hemodynamic effects of IV diuretics in patients with heart failure (HF) secondary to myocardial infarction.9, 10 In the first trial, Verma and associates10 compared the effects of an IV diuretic (furosemide, 1 mg/kg), a venodilator (isosorbide dinitrate, 50 to 200 μg/kg per hr), an arteriolar dilator (hydralazine, 0.15 mg/kg), and a positive inotropic agent (prenalterol, 50 to 200 μg/kg per hr)

Standard use of intravenous diuretics

Diuretics differ significantly in their site and mechanism of action.12, 13 Carbonic anhydrase inhibitors inhibit carbonic anhydrase in the proximal tubule. Osmotic agents have an osmotic effect in both the proximal tubule and the thick ascending limb of Henle. Loop diuretics inhibit the Na+-K+-2Cl− reabsorptive pump in the thick ascending limb of the loop of Henle. Thiazide diuretics inhibit electroneutral NaCl reabsorption in the distal convoluted tubule, and potassium-sparing diuretics

Expected response to intravenous diuretics

Loop diuretics enhance the excretion of sodium, chloride, potassium, and other ions, increasing urine volume, decreasing intravascular and extracellular fluid, and reducing total body sodium.20, 22, 28, 29 With bolus therapy, urine output peaks within 1 to 2 hours and declines to baseline level within 6 hours when assessed using urinary catheters, with changes in sodium excretion mirroring those of urine output (Figure 2).12, 29, 30, 31

In healthy volunteers, an IV dose of 40 mg furosemide, 20

Potential deleterious effects of intravenous diuretics

Diuretics, and especially their overuse, produce several deleterious effects that can influence clinical outcomes. A frequent consequence of diuretic therapy is electrolyte disturbances. 4, 6, 13, 20, 22 Loop diuretics increase urinary excretion of potassium, magnesium, and calcium, reducing total body stores of these essential cations, causing secondary hyperparathyroidism, and potentially increasing the risk of arrhythmic mortality.20, 22, 33, 34 Patients with advanced HF and long-term

Failure to respond to standard diuretic doses

Diuretic resistance, i.e., the failure to adequately respond to standard doses of diuretics, is a major issue in the management of patients with advanced HF. It is frequently seen in patients with severe symptoms, hypotension, hyponatremia, renal dysfunction, and/or significant cardiac dysfunction, and it has been associated with increased mortality.23, 47, 48, 50

Currently, the management of patients with diuretic resistance must be guided by the available limited data and theoretical

Summary

IV loop diuretics are considered the standard of care in patients with DHF. They decrease volume overload, improve hemodynamics, and reduce symptoms. However, they also can produce electrolyte abnormalities, neurohormonal activation, intravascular volume depletion, and renal dysfunction, leading to increased morbidity and mortality. In addition, many patients are resistant to the effects of standard doses of loop diuretics. These patients may benefit from the reduction or elimination of factors

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