What are the potential side effects of furosemide, especially in elderly patients or those with pre-existing heart failure, liver disease, or impaired renal function?

Furosemide Side Effects

Furosemide carries significant risks of electrolyte depletion, renal deterioration, and cardiovascular complications, particularly in elderly patients and those with heart failure, liver disease, or impaired renal function, requiring close monitoring of electrolytes, renal function, and volume status. 1, 2

Critical Electrolyte Disturbances

The most common adverse reactions are fluid and electrolyte imbalances, occurring in approximately 10% of hospitalized patients. 3

• Hypokalemia develops in 3.6% of patients, especially with brisk diuresis, inadequate oral electrolyte intake, cirrhosis, or concomitant use of corticosteroids, ACTH, or prolonged laxative use 1, 2
• Hyponatremia occurs in 8-30% of patients with cirrhosis and ascites, associated with impaired free water excretion 4
• Hypomagnesemia and hypocalcemia can develop, with rare cases of tetany reported 1, 2
• Hypochloremic alkalosis may occur as part of the electrolyte depletion syndrome 1, 2

Patients receiving potassium supplements or potassium-sparing diuretics experience less frequent and less severe hypokalemia with slower onset. 3

Renal Toxicity and Deterioration

Furosemide is directly associated with worsening renal function, particularly at higher doses. 5

• A 60 mg higher daily furosemide dose is associated with significantly worse renal function compared to lower doses 4, 5
• Worsening renal function during hospitalization increases in-hospital mortality nearly 3-fold (OR 2.7,95% CI 1.6 to 4.6) 4, 5
• In cirrhosis patients with ascites, high-dose IV furosemide causes acute reduction in renal perfusion and azotemia, and repeated use should be minimized 4, 5
• In patients with creatinine clearance <30 mL/min, furosemide has reduced diuretic response due to impaired tubular secretion 5
• Reversible elevations of BUN occur and are associated with dehydration 1, 2

Cardiovascular and Hemodynamic Effects

High-dose furosemide monotherapy paradoxically worsens cardiovascular outcomes in acute heart failure. 4, 5

• Furosemide causes acute worsening of hemodynamics for 1-2 hours after administration, including increased systemic vascular resistance, elevated left ventricular filling pressures, and decreased stroke volume 5
• High-dose furosemide increases risk of myocardial infarction and intubation compared to high-dose nitrate therapy (37% vs 17% MI rate, p<0.05; 40% vs 13% intubation rate, p<0.005) 4, 5
• Intravascular volume depletion occurs in 4.6% of patients, potentially causing circulatory collapse and vascular thrombosis, particularly in elderly patients 1, 2, 3
• Postural hypotension can occur and is usually managed by rising slowly 1, 2

Metabolic Complications

• Hyperglycemia and alterations in glucose tolerance occur, with rare precipitation of diabetes mellitus 1, 2
• Asymptomatic hyperuricemia is common, with gout rarely precipitated 1, 2
• New-onset gout occurred in 4 of 24 patients (17%) receiving high-dose furosemide (≥0.5 g/day) for refractory cardiac failure 6

Ototoxicity

• Tinnitus and hearing loss can occur, particularly with rapid IV administration or high doses 5, 6
• Ototoxicity risk increases with aminoglycoside antibiotics, cisplatin, or ethacrynic acid - these combinations should be avoided except in life-threatening situations 1, 2
• Infusions should be administered over 5-30 minutes to avoid hearing loss 5

Urinary Complications

• Acute urinary retention can occur in patients with bladder emptying disorders, prostatic hyperplasia, or urethral narrowing due to increased urine production 1, 2
• Poor sleep and nocturia are common complaints 5
• Furosemide is ineffective in truly anuric ESRD patients, requiring urgent dialysis/ultrafiltration 5

Special Population Risks

Cirrhosis Patients

• Hepatic encephalopathy occurs in up to 25% of hospitalized cirrhotic patients treated with diuretics 4
• Renal impairment develops in 14-20%, especially without peripheral edema, and is usually reversible with drug discontinuation 4
• Hyperkalaemia can occur in up to 11% of cirrhotic patients 4

Elderly Patients

• Excessive diuresis may cause dehydration, blood volume reduction with circulatory collapse, and vascular thrombosis/embolism, particularly in elderly patients 1, 2

Patients with Hypoproteinemia

• The diuretic effect may be weakened and ototoxicity potentiated in patients with nephrotic syndrome 1, 2

Critical Drug Interactions

• ACE inhibitors or angiotensin II receptor blockers combined with furosemide may lead to severe hypotension and deterioration in renal function, including renal failure - dose reduction or interruption may be necessary 1, 2
• Lithium should generally not be given with furosemide due to reduced lithium clearance and high risk of lithium toxicity 1, 2
• NSAIDs may reduce natriuretic and antihypertensive effects and increase risk of renal dysfunction 2
• Cephalosporins with furosemide increase nephrotoxicity risk even with minor renal impairment 2
• Cyclosporine with furosemide increases risk of gouty arthritis 2

Essential Monitoring Requirements

Serum electrolytes (particularly potassium), CO2, creatinine, and BUN should be determined frequently during the first few months of therapy and periodically thereafter. 1, 2

• Blood pressure monitoring for hypotension 5
• Daily weights to assess fluid status 5
• Urine output quantification 5
• Serum calcium and magnesium levels periodically 1, 2
• Blood and urine glucose in diabetics or those with suspected latent diabetes 1, 2
• In cirrhotic patients, electrolyte monitoring within 5-7 days of initiating therapy 4

Common Pitfalls to Avoid

• Do not use furosemide in anuria 5
• Avoid coadministration with other diuretics as this increases volume depletion risk 3
• Do not exceed 6 mg/kg/day for periods longer than 1 week 5
• Discontinue immediately if anuria develops 5
• In radiocontrast nephropathy risk, furosemide increases deterioration compared to IV hydration alone 1, 2