Effect of Furosemide on Potassium
Furosemide causes hypokalemia (low potassium) by inhibiting sodium and chloride reabsorption in the ascending limb of the loop of Henle, which increases urinary potassium excretion. 1
Mechanism of Action
Furosemide acts on the Na-K-2Cl receptors in the thick ascending limb of Henle's loop, blocking sodium and chloride reabsorption. 1 This mechanism inherently increases potassium excretion in the urine, leading to potassium depletion. 1
Clinical Significance of Hypokalemia
Hypokalemia is one of the most common adverse effects of furosemide therapy, occurring in 25-36% of hospitalized patients. 2, 3
- Hypokalemia develops especially with brisk diuresis, inadequate oral electrolyte intake, presence of cirrhosis, or during concomitant use of corticosteroids, ACTH, or prolonged laxative use. 4
- In chronic lung disease patients, thiazide and loop diuretics can cause hypokalemia and metabolic alkalosis, which can exacerbate CO2 retention. 1
- Most biochemical changes are slight, with only 3.9% of patients experiencing furosemide-induced decrease in serum potassium to less than 3.0 mmol/L. 2
- Furosemide should be stopped if severe hypokalemia (<3 mmol/L) develops. 1
Paradoxical Hyperkalemia Risk
Surprisingly, 24.5% of patients receiving furosemide can develop hyperkalemia when potassium supplements or potassium-sparing diuretics (like spironolactone) are administered concurrently. 2
- When spironolactone (which causes potassium retention) is combined with furosemide and ACE inhibitors or ARBs, hyperkalemia exceeding 5.5 mEq/L can occur even with low-dose spironolactone (25 mg/day). 5
- Aldosterone antagonists should be stopped if severe hyperkalemia (serum potassium >6 mmol/L) develops. 1
Management Strategy
The combination of spironolactone and furosemide in a 100:40 mg ratio is designed to maintain normokalemia by balancing the potassium-wasting effects of furosemide with the potassium-sparing effects of spironolactone. 1
Monitoring Requirements
- Serum electrolytes (particularly potassium), CO2, creatinine, and BUN should be determined frequently during the first few months of furosemide therapy and periodically thereafter. 4
- Serum and urine electrolyte determinations are particularly important when the patient is vomiting profusely or receiving parenteral fluids. 4
- A significant proportion of patients develop diuretic-induced complications during the first weeks of treatment, necessitating frequent measurements of serum potassium during this period. 1
Potassium Supplementation
- Adequate KCl supplementation is the best method to prevent and treat furosemide-induced hypokalemia and metabolic alkalosis. 1
- Among furosemide recipients who also received potassium supplements or potassium-sparing diuretics, hypokalemia was less frequent, less severe, and of slower onset. 3
- Digitalis therapy may exaggerate metabolic effects of hypokalemia, especially myocardial effects, making potassium monitoring even more critical in these patients. 4
Important Caveats
- Potassium depletion reduces the diuretic effects of furosemide by diminishing furosemide delivery to its tubule site of action, creating a vicious cycle. 6
- Furosemide can be temporarily withheld in patients presenting with hypokalemia, particularly those with alcoholic hepatitis where hypokalemia is very common. 1
- Life-threatening hyperkalemia can occur late during treatment when furosemide is combined with ACE inhibitors and potassium supplements, requiring ongoing vigilance even if initial parameters are normal. 7