Restrict Na⁺ to 2 g (88 mEq) or 5 g (85 mEq) salt diet. Avoid salt substitutes because they contain K⁺ and hyperkalemia is possible in patients with renal dysfunction. Salt restriction improves diuretic and angiotensin-converting-enzyme inhibitor (ACE-I)’s effectiveness.

Restrict water to avoid hyponatremia, if patients are on thiazide diuretics.

Use diuretics, preferably loop diuretics, if salt and water restriction fail. Start furosemide at 20 mg orally twice daily, and follow natriuresis and diuresis. Increase the dose, if necessary. Bumetanide or torsemide can be substituted for furosemide, if patient is noncompliant to a twice-daily dose or long-acting loop diuretic is needed.

Addition of a thiazide diuretic (metolazone) to loop diuretic may be helpful in some patients. Like furosemide, metolazone works in patients with low GFR.

Suspect diuretic resistance in a compliant patient when the patient is gaining weight and signs and symptoms of edema are not improving on adequate regimen of diuretics. Patients develop diuretic resistance with acute or chronic use of loop diuretics. This happens immediately following the first dose of furosemide, which induces more Na⁺ and water loss than intake. A new steady state is reached in < 1 week, and additional doses of diuretic do not increase any electrolyte loss than intake. This is called the breaking phenomenon. The mechanism for this lack of response is not clearly understood; however, diuretic-induced renin secretion by macula densa independent of volume status and also volume depletion which activates sympathetic nervous system seems to stimulate postdiuretic Na⁺ reabsorption. Were it not for the breaking phenomenon, the patient would lose all the fluid and salt and become extremely volume depleted .

Diuretic resistance due to chronic use is related to several factors. First, general volume depletion promotes Na⁺ reabsorption in the proximal tubule with less delivery to other segments of the nephron. Second, loop diuretics are protein-bound and are not filtered but secreted in the proximal tubule. Hypoalbuminemic conditions impair this secretion, causing less delivery of the diuretic to their site of action (thick ascending limb of Henle’s loop). Third, the duration of action of furosemide is short so that postdiuretic Na⁺ reabsorption is enhanced, and finally, loop diuretics deliver more Na⁺ to the distal tubule. As a result, hyperplasia and hypertrophy of thiazide-sensitive epithelial cells occur, and these cells increase their Na⁺ reabsorption. Low urinary Na⁺ levels may indicate diuretic resistance.

Do NOT stop diuretic abruptly without restricting salt intake to avoid avid Na⁺ reabsorption.

Diuretics promote excretion of water soluble vitamins, and long-term therapy in CHF patients reduces folate and thiamine levels. Supplementation is, therefore, recommended.

Weight and orthostatic blood pressure and pulse rate are mandatory during each visit in patients on diuretics .

Acute decompensated heart failure (ADHF) is the most common cause of hospital admission in elderly patients. For these patients, i.v. furosemide (5–10 mg/h) should be started until an optimal volume status is achieved. Continuous i.v. is superior to i.v. boluses, as the former infusion method was associated with good urine output, reduced hospital stay, and reduced mortality. Follow serum albumin concentration. A combination of albumin (25–50 g of 5 % albumin) and 40–60 mg of furosemide can be tried for hypoalbuminemic patients. Note that this combination may not cause natriuresis and diuresis in all patients .

In addition to loop diuretics, nesiritide (brain natriuretic factor, BNP) can be given i.v. with or without furosemide to improve pulmonary capillary wedge pressure. Note that excessive diuresis by BNP can raise serum creatinine levels and precipitate acute cardiorenal syndrome.

If edema does not improve and patient has hyponatremia, oral vasopressin receptor (V2) antagonist, such as tolvaptan (15 mg) can be given. This results in water excretion (aquaresis) with improvement in serum sodium and weight.

When diuretic resistance is evident and nesiritide treatment no longer helps the patient and renal function worsens, ultrafiltration using continuous veno-venous hemofiltration for fluid removal should be considered. Several advantages of hemofiltration over diuretic therapy have been reported, as shown below .