What are the potential side effects of furosemide (loop diuretic) in patients with pre-existing renal, hepatic, or cardiovascular conditions?

Furosemide Side Effects in High-Risk Populations

Furosemide carries significant risks of electrolyte depletion, renal impairment, and volume depletion, with the severity and type of adverse effects varying substantially based on underlying hepatic, renal, or cardiac disease. 1

Major Side Effects by Organ System

Electrolyte Disturbances

Hypokalemia is the most common electrolyte abnormality, occurring particularly with brisk diuresis, inadequate oral intake, cirrhosis, or concomitant corticosteroid use. 1 This risk is amplified in patients on digitalis therapy, where hypokalemia can exaggerate myocardial effects and precipitate arrhythmias. 1 Loop diuretics also cause hypomagnesemia, which should be monitored periodically as magnesium depletion can worsen potassium losses. 1

Hyponatremia develops in 8-30% of cirrhotic patients treated with diuretics, related to impaired free water excretion. 2 The American Association for the Study of Liver Diseases recommends temporarily withdrawing diuretics when serum sodium falls below 120-125 mmol/L. 2

Hyperkalemia paradoxically occurs in up to 11% of cirrhotic patients, especially when furosemide is combined with spironolactone in patients with reduced renal perfusion. 2

Renal Impairment

Renal deterioration occurs in 14-20% of hospitalized patients treated with diuretics, with particularly high risk in the absence of peripheral edema. 2, 3 The American College of Gastroenterology notes that furosemide carries higher renal risk than spironolactone due to its mechanism causing acute reductions in glomerular filtration rate. 3 This renal impairment is usually moderate and reversible upon discontinuation. 2, 3

In heart failure patients, excessive diuretic use can decrease blood pressure and impair renal function, though these effects may also reflect worsening heart failure rather than pure volume depletion. 2 The key distinction: if signs of fluid retention are absent, hypotension and azotemia likely reflect volume depletion and warrant dose reduction; if fluid retention persists, these findings suggest worsening heart failure. 2

Volume Depletion and Hemodynamic Effects

Excessive diuresis causes dehydration and blood volume reduction with circulatory collapse, vascular thrombosis, and embolism, particularly in elderly patients. 1 Postural hypotension occurs commonly and can usually be managed by rising slowly. 1

In cirrhotic patients, the hemodynamic instability makes them highly susceptible to rapid extracellular fluid volume reductions, predominantly with loop diuretics. 2 This can precipitate hepatic encephalopathy (occurring in up to 25% of hospitalized cirrhotic patients on diuretics) through enhanced renal ammonia production. 2

Ototoxicity

Furosemide increases ototoxic potential of aminoglycoside antibiotics, especially with impaired renal function—this combination should be avoided except in life-threatening situations. 1 Concomitant use with ethacrynic acid is contraindicated due to ototoxicity risk. 1 Cisplatin combined with furosemide also carries ototoxic risk. 1

Metabolic Effects

Hyperglycemia and glucose intolerance occur, with rare precipitation of diabetes mellitus. 1 Diabetic patients should be told furosemide may increase blood glucose and affect urine glucose tests. 1

Asymptomatic hyperuricemia is common, with gout rarely precipitated. 1 When combined with cyclosporine, furosemide increases risk of gouty arthritis through furosemide-induced hyperuricemia and cyclosporine's impairment of renal urate excretion. 1

Hypocalcemia (rarely causing tetany) can occur, requiring periodic monitoring. 1

High-Risk Drug Interactions

• Lithium: Should generally not be given with diuretics due to reduced renal clearance and high lithium toxicity risk. 1
• ACE inhibitors/ARBs: May cause severe hypotension and renal deterioration including renal failure; dose interruption or reduction may be necessary. 1
• NSAIDs: Reduce natriuretic and antihypertensive effects; can increase BUN, creatinine, and potassium with weight gain. 1
• Salicylates: High doses with furosemide may cause salicylate toxicity at lower doses due to competitive renal excretion. 1
• Methotrexate: High-dose treatment of both drugs may elevate serum levels and potentiate mutual toxicity. 1

Special Population Considerations

Cirrhotic Patients

The overall incidence of adverse events is 19-33%, with almost half requiring dose reduction or discontinuation. 2, 3 Beyond renal impairment and encephalopathy, cirrhotic patients experience muscle cramps that can significantly impair quality of life. 2

Heart Failure Patients

Diuretic resistance develops as heart failure advances due to delayed bowel absorption from edema, intestinal hypoperfusion, and impaired drug delivery to renal tubules. 2 This necessitates increasing doses, which amplify side effect risks. 2

Renal Insufficiency

Reversible BUN elevations occur and are associated with dehydration, which should be avoided particularly in patients with baseline renal insufficiency. 1 In patients at high risk for radiocontrast nephropathy, furosemide leads to higher incidence of renal function deterioration compared to IV hydration alone. 1

Monitoring Requirements

Serum electrolytes (particularly potassium), CO2, creatinine, and BUN must be determined frequently during the first few months of therapy and periodically thereafter. 1 Electrolyte determinations are particularly critical when patients are vomiting profusely or receiving parenteral fluids. 1

Urine and blood glucose should be checked periodically in diabetics or those with suspected latent diabetes. 1 Calcium and magnesium levels require periodic monitoring. 1

Other Notable Adverse Effects

• Photosensitivity: Skin may be more sensitive to sunlight. 1
• Blood dyscrasias: Patients should be observed regularly for possible occurrence. 1
• Acute urinary retention: Can occur in patients with bladder emptying disorders, prostatic hyperplasia, or urethral narrowing due to increased urine production. 1
• Systemic lupus erythematosus: Possibility of exacerbation or activation. 1
• Thyroid hormone alterations: High doses (>80mg) may inhibit thyroid hormone binding to carrier proteins, causing transient increases in free thyroid hormones followed by overall decreases in total levels. 1