Uses
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Edema
Bumetanide is used for the management of edema associated with heart failure or hepatic or renal disease (including nephrotic syndrome). The drug may be effective in some patients whose condition is unresponsive or refractory to other diuretics. In a limited number of patients, approximately 60% of those with edema refractory to other diuretic therapy showed an improved diuretic response with bumetanide. Patients who had received 80-160 mg of furosemide daily with little or no diuretic response showed a marked diuresis with 2-6 mg of bumetanide daily; however, in some of these patients, improvement observed during initial therapy did not continue during maintenance therapy with bumetanide. Further study is needed to determine the role of bumetanide in the management of edema refractory to other diuretics.
Careful etiologic diagnosis should precede the use of any diuretic. Because the potent diuretic effect of loop diuretics may result in severe electrolyte imbalance and excessive fluid loss, hospitalization of the patient during initiation of therapy is advisable, especially for patients with hepatic cirrhosis and ascites or chronic renal failure. In prolonged diuretic therapy, intermittent use of the loop diuretics for only a few days each week may be advisable.
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Heart Failure
Bumetanide is effective for the short- and long-term management of edema associated with heart failure. In addition to decreasing edema, the drug relieves other signs and symptoms of heart failure such as dyspnea, rales, and hepatomegaly. Bumetanide appears to be as effective as furosemide in reducing edema, body weight, abdominal girth, rales, hepatomegaly, blood pressure, and heart rate in patients with heart failure.
Most experts state that all patients with symptomatic heart failure who have evidence for, or a history of, fluid retention generally should receive diuretic therapy in conjunction with moderate sodium restriction, an agent to inhibit the renin-angiotensin-aldosterone-aldosterone (RAA) system (e.g., angiotensin-converting enzyme [ACE] inhibitor, angiotensin II receptor antagonist, angiotensin receptor-neprilysin inhibitor [ARNI]), a β-adrenergic blocking agent (β-blocker), and in selected patients, an aldosterone antagonist. Some experts state that because of limited and inconsistent data, it is difficult to make precise recommendations regarding daily sodium intake and whether it should vary with respect to the type of heart failure (e.g., reduced versus preserved ejection fraction), disease severity (e.g., New York Heart Association [NYHA] class), heart failure-related comorbidities (e.g., renal dysfunction), or other patient characteristics (e.g., age, race). The American College of Cardiology Foundation (ACCF) and American Heart Association (AHA) state that limiting sodium intake to 1.5 g daily in patients with ACCF/AHA stage A or B heart failure may be reasonable. While data currently are lacking to support recommendation of a specific level of sodium intake in patients with ACCF/AHA stage C or D heart failure, ACCF and AHA state that limiting sodium intake to some degree (e.g., less than 3 g daily) in such patients may be considered for symptom improvement. Diuretics play a key role in the management of heart failure because they produce symptomatic benefits more rapidly than any other drugs, relieving pulmonary and peripheral edema within hours or days compared with weeks or months for cardiac glycosides, ACE inhibitors, or β-blockers. However, since there are no long-term studies of diuretic therapy in patients with heart failure, the effects of diuretics on morbidity and mortality in such patients are not known. Although there are patients with heart failure who do not exhibit fluid retention in the absence of diuretic therapy and even may develop severe volume depletion with low doses of diuretics, such patients are rare and the unique pathophysiologic mechanisms regulating their fluid and electrolyte balance have not been elucidated.
Most experts state that loop diuretics (e.g., bumetanide, ethacrynic acid, furosemide, torsemide) are the diuretics of choice for most patients with heart failure. However, thiazides may be preferred in some patients with concomitant hypertension because of their sustained antihypertensive effects. If resistance to diuretics occurs, IV administration of a diuretic or concomitant use of 2 or more diuretics (e.g., a loop diuretic and metolazone, a loop diuretic and a thiazide diuretic) may be necessary; alternatively, short-term administration of a drug that increases blood flow (e.g., a positive inotropic agent such as dopamine) may be necessary. ACCF and AHA state that IV loop diuretics should be administered promptly to all hospitalized heart failure patients with substantial fluid overload to reduce morbidity. In addition, ACCF and AHA state that low-dose dopamine infusions may be considered in combination with loop diuretics to augment diuresis and preserve renal function and renal blood flow in patients with acute decompensated heart failure, although data are conflicting and additional study and experience are needed. For additional information,
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Hepatic Disease
Bumetanide is used for the short- and long-term management of edema and ascites associated with hepatic disease (e.g., cirrhosis). Short-term administration of 2-4 mg of bumetanide daily or long-term administration of up to 6 mg daily has produced appreciable diuretic and natriuretic effects without substantial serum electrolyte disturbance in some patients with this condition. Patients with hepatic ascites reportedly have responded to an initial bumetanide dosage of 1 mg daily with weight loss averaging about 0.6 kg daily and a marked increase in urinary volume and natriuresis. The major complications observed during bumetanide therapy in these patients included hypokalemia and hyponatremia; however, electrolyte disturbances are commonly observed in patients with severe hepatic disease who are receiving diuretic therapy. Some patients developed encephalopathy during bumetanide administration.
(See Cautions: Hepatic Effects.) Bumetanide appears to be as effective as furosemide in reducing body weight and in causing diuresis and increased urinary excretion of sodium, potassium, and chloride in patients with hepatic cirrhosis and ascites. Following IV administration, single 0.5-mg doses of bumetanide were as effective as 20-mg doses of furosemide in patients with refractory ascites.
In most clinical studies in patients with hepatic cirrhosis and ascites, patients received concomitant therapy with bumetanide and potassium salts or potassium-sparing diuretics to prevent hypokalemia.
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Renal Disease
Bumetanide is used for the management of edema in patients with impaired renal function. In patients with severe renal impairment (i.e., GFR less than 10 mL/minute), high dosages of the drug may be needed to produce an adequate diuretic response.
(See Dosage in Renal and Hepatic Impairment in Dosage and Administration.) Bumetanide (1-10 mg orally daily) appears to be as effective as furosemide (40-400 mg orally daily) in reducing edema, body weight, and abdominal girth in patients with edema secondary to renal disease. However, in one study, substantial reductions in body weight, edema, and mean arterial pressure were observed in patients with severe renal impairment who received oral bumetanide dosages of 1-18 mg daily but not in those who received oral furosemide dosages of 20-480 mg daily.
Oral bumetanide dosages of 2-6 mg daily appear to be as effective as oral furosemide dosages of 40-160 mg daily in reducing edema in patients with nephrotic syndrome; however, in some patients with nephrotic syndrome and moderately impaired renal function (i.e., creatinine clearance of 4-34 mL/minute), a decreased response compared with that of patients with nephrotic syndrome and normal renal function has been reported.
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Other Edematous Conditions
Bumetanide has been used for the management of postoperative or premenstrual edema and edema associated with disseminated carcinoma.
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Hypertension
Bumetanide has been used orally for the management of hypertension, especially when complicated by heart failure, acute pulmonary edema, or renal disease. Bumetanide has been used as monotherapy or in combination with other classes of antihypertensive agents. Because of established clinical benefits (e.g., reductions in overall mortality and in adverse cardiovascular, cerebrovascular, and renal outcomes), ACE inhibitors, angiotensin II receptor antagonists, calcium-channel blockers, and thiazide diuretics generally are considered the preferred drugs for the initial management of hypertension in adults. However, loop diuretics (e.g., furosemide, bumetanide, torsemide) may be particularly useful in patients with renal impairment (as an alternative to thiazide diuretics) or heart failure (for management of fluid retention). For additional information on the use of loop diuretics in the management of hypertension, see Uses: Hypertension, in 40:28.08.
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Other Uses
Bumetanide has been used to enhance the elimination of drugs or toxic substances following intoxication. Like furosemide, bumetanide has been used as an adjunct in forced alkaline diuresis to enhance salicylate elimination following acute aspirin intoxication. IV bumetanide and IV sodium bicarbonate have reportedly produced a more rapid decrease in blood salicylate concentration compared with parenteral fluid therapy alone.