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Treatment of refractory edema in adults

D Craig Brater, MD
Section Editors
Richard H Sterns, MD
Michael Emmett, MD
Deputy Editor
John P Forman, MD, MSc


Generalized edema can occur in a variety of disorders, including heart failure, cirrhosis (where ascites is usually most prominent), the nephrotic syndrome, and renal failure; when massive, the excess fluid accumulation is called anasarca. Edematous patients generally respond to the combination of dietary sodium restriction and diuretic therapy, usually with a loop diuretic. Some patients, however, are resistant to this regimen.

A variety of factors can account for persistent fluid retention, including inadequate diuretic dose or frequency, excess sodium intake, delayed intestinal absorption of oral diuretics, decreased diuretic excretion into the urine, and increased sodium reabsorption at sites in the nephron other than those inhibited by the diuretic [1-4]. Nonsteroidal anti-inflammatory drugs, which reduce the synthesis of vasodilator and natriuretic prostaglandins, can impair diuretic responsiveness. Thus, these agents should be discontinued, if possible, in edematous patients [4,5].

The treatment of refractory edema in adults will be reviewed here. The initial therapy of edema, treatment of the different major edematous states, the clinical manifestations and diagnosis of edema in adults, and the evaluation and management of edema in children are discussed separately. (See "General principles of the treatment of edema in adults" and "Use of diuretics in patients with heart failure" and "Ascites in adults with cirrhosis: Initial therapy" and "Ascites in adults with cirrhosis: Diuretic-resistant ascites" and "Pathophysiology and treatment of edema in patients with the nephrotic syndrome" and "Clinical manifestations and diagnosis of edema in adults" and "Evaluation and management of edema in children".)


Edematous patients are typically treated with one of the sulfonamide-based loop diuretics – furosemide, bumetanide, and torsemide. Ethacrynic acid, which is not a sulfonamide, is rarely used because it may be more ototoxic than the sulfonamide diuretics in high doses and its relative insolubility makes it complicated to administer intravenously.

The primary indication for the use of ethacrynic acid is in patients who are allergic to sulfonamide-based diuretics, including thiazide diuretics. There is minimal evidence of allergic cross-reactivity between sulfonamide antimicrobials and non-antimicrobials. Thus, patients with a history of allergy to sulfonamide antimicrobial drugs would be expected to tolerate non-antimicrobial sulfonamides such as loop diuretics. Allergic reactions that do occur appear to be related to a predisposition to allergic reactions rather than sulfonamide cross-reactivity [6]. (See "Sulfonamide allergy in HIV-uninfected patients", section on 'Between sulfonamide antimicrobials and nonantimicrobials'.)

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Literature review current through: Oct 2017. | This topic last updated: Oct 21, 2016.
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