What are the most common side effects of furosemide (Lasix), particularly in elderly patients or those with pre-existing renal impairment, and which organ systems are affected?

Most Common Side Effects of Furosemide by Organ System

Furosemide causes adverse reactions in approximately 10% of patients, with electrolyte disturbances and volume depletion being the most frequent complications, affecting primarily the renal, cardiovascular, metabolic, and auditory systems. 1

Renal System Effects

• Intravascular volume depletion occurs in 4.6% of patients, representing the single most common adverse reaction 1
• Azotemia and renal dysfunction develop from excessive diuresis, particularly in elderly patients and those with pre-existing renal impairment 2, 3
• Nephrocalcinosis and nephrolithiasis occur with long-term use due to hypercalciuria, especially in premature infants and pediatric patients 4, 3
• Dose-dependent renal function deterioration is significantly greater with doses ≥60 mg daily compared to lower doses 5
• Creatinine increases >0.3 mg/dL during hospitalization are associated with nearly 3-fold higher in-hospital mortality risk 5

Metabolic and Electrolyte Disturbances

• Hypokalemia affects 3.6% of patients, particularly with brisk diuresis, inadequate oral intake, cirrhosis, or concurrent corticosteroid use 6, 1
• Metabolic alkalosis frequently accompanies electrolyte depletion and can exacerbate CO2 retention in patients with chronic lung disease 4, 6
• Hyponatremia requires immediate diuretic cessation when sodium falls below 120 mEq/L 5
• Hypocalcemia and hypomagnesemia occur with chronic use, with rare cases of tetany reported 3
• The risk of electrolyte depletion is markedly enhanced when two diuretics are used in combination, as enhanced sodium delivery to distal tubules increases cation exchange 6

Cardiovascular System Effects

• Hypotension and orthostatic hypotension result from excessive volume depletion, impairing renal function and exercise tolerance 6, 3
• Initial hemodynamic worsening may occur with IV administration, including transient decrease in stroke volume and increased systemic vascular resistance 6
• Severe hypotension and deterioration in renal function can occur when combined with ACE inhibitors or angiotensin II receptor blockers 3

Auditory System (Ototoxicity)

• Transient or permanent hearing loss occurs particularly with rapid IV administration of high doses (>6 mg/kg/day) or when used concomitantly with aminoglycosides 4, 6
• Tinnitus has been reported in patients receiving high-dose therapy 7
• High-dose furosemide should not be given for periods longer than 1 week, and infusions must be administered over 5-30 minutes to avoid hearing loss 6

Musculoskeletal System

• Gout and hyperuricemia develop from furosemide-induced urate retention, reported in approximately 17% of patients on high-dose therapy 7
• Risk is increased with concomitant cyclosporine use due to impairment of renal urate excretion 3

Hematologic System

• Blood dyscrasias are rare but require regular monitoring 3

Special Considerations for Elderly and Renally Impaired Patients

• Elderly patients require cautious dosing, generally starting at the lower end of the dosing range, due to increased risk of toxic reactions and decreased renal function 2
• Patients with renal impairment show reduced clearance and prolonged half-life, requiring higher doses to achieve therapeutic tubular concentrations when creatinine clearance <30 mL/min 4, 5
• The severity of acute kidney injury significantly affects diuretic response, with reduced drug delivery to the site of action in the tubular lumen 8

Critical Monitoring Requirements

• Serum electrolytes (particularly potassium), CO2, creatinine, and BUN should be determined frequently during the first few months of therapy and periodically thereafter 2, 3
• Creatinine and electrolytes should be checked 1-2 weeks after initiation, then every 1-2 weeks during dose titration 5
• Renal ultrasonography is required in premature infants to monitor for nephrocalcinosis 3

Common Pitfall to Avoid

Concomitant administration of NSAIDs (including COX-2 inhibitors) can block diuretic effects and cause increased BUN, serum creatinine, potassium levels, and weight gain 6, 3. However, ACE inhibitors or potassium-sparing agents like spironolactone can prevent electrolyte depletion and often eliminate the need for long-term oral potassium supplementation 6.