What effect does furosemide have on sodium levels?

Effect of Furosemide on Sodium Levels

Furosemide can cause hyponatremia (serum sodium <135 mmol/L) through excessive urinary sodium excretion, particularly when used at high doses or in patients with underlying conditions like cirrhosis or heart failure. 1, 2

Mechanism of Action and Sodium Excretion

• Furosemide primarily inhibits the reabsorption of sodium and chloride in the loop of Henle, as well as in the proximal and distal tubules, leading to increased urinary sodium excretion 2, 3
• The drug acts by blocking the sodium-potassium-chloride cotransporter (NKCC2) in the thick ascending limb of the loop of Henle, resulting in significant natriuresis 4
• The onset of diuretic effect occurs within 5 minutes after intravenous administration and within 1 hour after oral administration, with peak effect within 30 minutes (IV) or 1-2 hours (oral) 2, 3
• Furosemide increases urinary sodium concentration, with measurements 1-2 hours after administration showing significant variability between patients 5

Risk of Hyponatremia

• Excessive diuresis with furosemide can cause electrolyte depletion, including hyponatremia, especially in patients receiving higher doses and restricted salt intake 2
• Hyponatremia is defined as serum sodium <135 mmol/L, with 130-135 mmol/L considered mild, 125-129 mmol/L moderate, and <125 mmol/L severe 1
• Guidelines recommend temporarily discontinuing diuretics if sodium levels fall below 125 mmol/L to prevent further electrolyte imbalance 1
• Patients with cirrhosis are particularly susceptible to hyponatremia, with 21.6% having serum sodium <130 mmol/L in prospective surveys 1

Types of Hyponatremia Related to Furosemide

• Hypovolemic hyponatremia can result from overzealous diuretic therapy with furosemide, characterized by prolonged negative sodium balance with marked loss of extracellular fluid 1
• Management of hypovolemic hyponatremia requires expansion of plasma volume with normal saline and cessation of diuretics 1
• Hypervolemic hyponatremia is more common in cirrhosis, occurring due to non-osmotic hypersecretion of vasopressin and enhanced proximal nephron sodium reabsorption with impaired free water clearance 1

Monitoring and Prevention

• All patients receiving furosemide therapy should be monitored for signs of electrolyte imbalance, including hyponatremia 2
• Symptoms of hyponatremia include dryness of mouth, thirst, weakness, lethargy, drowsiness, restlessness, muscle pains, cramps, hypotension, oliguria, and tachycardia 2
• Serum electrolytes, particularly sodium, should be determined frequently during the first few months of furosemide therapy and periodically thereafter 2
• Measuring urinary sodium concentration 2 hours after furosemide administration can help evaluate diuretic response, with values <50-70 mEq/L indicating insufficient response 6

Dosing Considerations

• Divided dosing regimens (e.g., 20 mg twice daily vs. 40 mg once daily) may produce greater sodium excretion and chloride excretion 7
• Lower diuretic response based on 6-hour sodium excretion after IV furosemide is associated with poor prognosis in patients with acute heart failure 5
• In patients with cirrhosis, furosemide should be started at 40 mg/day and increased up to 160 mg/day if needed, with close monitoring of sodium levels 1
• Fluid restriction is generally not necessary unless serum sodium is less than 120-125 mmol/L 1

Special Populations and Considerations

• Elderly patients may be more susceptible to electrolyte depletion with furosemide due to reduced renal clearance and initial diuretic effect 2, 3
• In patients with heart failure, furosemide activates the renin-angiotensin-aldosterone system (RAAS), which can lead to increased sodium avidity and potentially worsen congestion over time 1
• In patients with syndrome of inappropriate antidiuresis (SIAD), adding furosemide to fluid restriction does not show benefits in correction of sodium levels compared to fluid restriction alone 8
• Patients with hypoproteinemia (e.g., associated with nephrotic syndrome) may experience weakened effects of furosemide 2