Can Lasix (furosemide) cause hyponatremia, especially in older patients with pre-existing electrolyte imbalances or impaired renal function?

Can Lasix Cause Hyponatremia?

Yes, Lasix (furosemide) can cause hyponatremia, particularly during the first few days of therapy or dose escalation, though this risk is substantially lower than with thiazide diuretics and may even be protective with ongoing use. 1

Mechanism and Timing of Hyponatremia Risk

Loop diuretics like furosemide cause significant electrolyte shifts within the first 3 days of initiation, typically leading to both hypokalemia and hyponatremia. 2 The FDA label explicitly lists hyponatremia as a recognized electrolyte imbalance that all patients receiving furosemide should be monitored for, along with hypochloremic alkalosis, hypokalemia, hypomagnesemia, and hypocalcemia. 1

The mechanism involves:

• Promotion of sodium excretion through action on Na-K-2Cl receptors in the thick ascending limb of Henle's loop 2
• Compensatory aldosterone release that paradoxically worsens hyponatremia through free water retention 2
• Impaired ability of kidneys to excrete free water, particularly in patients with cirrhosis and ascites (8-30% incidence) 2

Critical Distinction: Loop vs. Thiazide Diuretics

The hyponatremia risk profile differs dramatically between furosemide and thiazide diuretics. 3, 4

While thiazides are one of the most common causes of severe symptomatic hyponatremia requiring hospitalization, furosemide shows a paradoxical pattern:

• Newly initiated furosemide (≤90 days): Modest increased risk with adjusted odds ratio of 1.23 4
• Ongoing furosemide use: Protective effect with adjusted odds ratio of 0.52, suggesting an inverse correlation with hospitalization for hyponatremia 4

A direct comparison study demonstrated that a patient who developed severe symptomatic hyponatremia after 5 days of thiazide therapy could safely receive furosemide without recurrent hyponatremia, with calculated maximal daily electrolyte-free water clearance of 10,166 mL with furosemide versus only 888 mL with thiazides. 3

High-Risk Populations Requiring Vigilant Monitoring

Elderly patients are at substantially elevated risk for diuretic-associated hyponatremia. 5, 6, 7

Specific risk factors include:

• Age: Each 10-year increment doubles the risk (hazards ratio 2.14) 7
• Low body weight: Each 5 kg decrease increases odds by 30% (odds ratio 0.77) 7
• Low serum potassium: One standard deviation increase in potassium (0.84 mmol/L) decreases risk by 63% (odds ratio 0.37) 7
• Physical immobility and institutionalization 7
• Impaired renal function (CrCl <30 mL/min) 5

The European Heart Journal guidelines specifically identify elderly patients (≥75 years) as requiring extra caution with loop diuretics due to risks of hypovolaemia, postural hypotension, falls, dehydration, and electrolyte disturbances including hyponatremia. 5

Mandatory Monitoring Protocol

Monitor serum sodium, potassium, and creatinine within the first 3 days of diuretic initiation or dose escalation, as the greatest electrolyte shifts occur during this period. 2

The FDA mandates:

• Serum electrolytes (particularly potassium), CO2, creatinine, and BUN determined frequently during the first few months of therapy and periodically thereafter 1
• Serum and urine electrolyte determinations particularly important when patients are vomiting profusely or receiving parenteral fluids 1
• Abnormalities should be corrected or the drug temporarily withdrawn 1

In patients with cirrhosis, if serum sodium decreases below 125 mmol/L, diuretics should be carefully reduced or discontinued. 2

Clinical Significance and Prognostic Impact

Hyponatremia associated with diuretic therapy carries substantial morbidity and mortality, particularly in elderly patients. 6 In cirrhotic patients, hyponatremia is associated with higher prevalence of refractory ascites, hepatic encephalopathy, spontaneous bacterial peritonitis, hepatorenal syndrome, and mortality—which is why the MELD-Na score now incorporates serum sodium. 2

Common Pitfall to Avoid

Do not confuse the hyponatremia risk profile of furosemide with that of thiazides. 3, 8, 4 Thiazides should be avoided in frail elderly patients with chronically high water intake or those who depend on excretion of maximally dilute urine to maintain fluid balance. 8 However, if treatment with furosemide precedes the development of hyponatremia by some time, other causes of hyponatremia should be sought, as ongoing furosemide use is inversely correlated with hyponatremia. 4

The American Heart Association notes that older patients are at increased risk for diuretic-induced electrolyte abnormalities including hyponatremia, requiring careful monitoring of volume status, renal function, electrolytes, and orthostatic blood pressures. 5