From the FDA Drug Label
As with any effective diuretic, electrolyte depletion may occur during Furosemide tablets therapy, especially in patients receiving higher doses and a restricted salt intake Hypokalemia may develop with Furosemide tablets, especially with brisk diuresis, inadequate oral electrolyte intake, when cirrhosis is present, or during concomitant use of corticosteroids, ACTH, licorice in large amounts, or prolonged use of laxatives. All patients receiving Furosemide tablets therapy should be observed for these signs or symptoms of fluid or electrolyte imbalance (hyponatremia, hypochloremic alkalosis, hypokalemia, hypomagnesemia or hypocalcemia)
The causes of elevated bicarbonate levels without an elevated anion gap (hyperbicarbonatemia) include hypochloremic alkalosis, which may occur during Furosemide tablets therapy, especially with brisk diuresis or inadequate oral electrolyte intake.
- Hypochloremic alkalosis is a condition that can lead to elevated bicarbonate levels.
- Brisk diuresis and inadequate oral electrolyte intake are potential causes of hypochloremic alkalosis in patients receiving Furosemide tablets therapy 1.
From the Research
Elevated bicarbonate without an elevated anion gap is typically caused by metabolic alkalosis, which can result from several distinct mechanisms, including vomiting or nasogastric suction, diuretic use, excessive alkali administration, severe hypokalemia, primary hyperaldosteronism, Cushing's syndrome, Bartter and Gitelman syndromes, milk-alkali syndrome, and post-hypercapnic states. The most common causes of elevated bicarbonate levels without an elevated anion gap include:
- Vomiting or nasogastric suction leading to loss of gastric acid
- Diuretic use, particularly loop and thiazide diuretics which increase renal bicarbonate reabsorption
- Excessive alkali administration such as sodium bicarbonate or citrate
- Severe hypokalemia which promotes hydrogen ion movement into cells
- Primary hyperaldosteronism causing increased renal acid excretion
- Cushing's syndrome with excess cortisol
- Bartter and Gitelman syndromes which mimic diuretic effects
- Milk-alkali syndrome from excessive calcium and absorbable alkali intake
- Post-hypercapnic states where the kidneys have compensated for chronic respiratory acidosis Clinically, patients may present with symptoms like confusion, muscle cramps, and cardiac arrhythmias, as noted in various studies 2, 3, 4, 5, 6. Treatment should target the underlying cause, such as discontinuing diuretics, correcting electrolyte imbalances (especially potassium and chloride), or addressing hormonal disorders, as discussed in 5. In severe cases with significant symptoms, careful administration of dilute hydrochloric acid or ammonium chloride may be necessary under close monitoring, as suggested by 4. Understanding the pathophysiology helps guide appropriate management, as metabolic alkalosis represents a compensatory response to maintain acid-base homeostasis. The most recent and highest quality study, 5, provides guidance on the approach to patients with high anion gap metabolic acidosis, which can inform the management of metabolic alkalosis. However, it is essential to note that the provided studies primarily focus on metabolic acidosis, and the information on metabolic alkalosis is largely based on the understanding of the underlying pathophysiology and clinical experience. Therefore, the treatment of elevated bicarbonate levels without an elevated anion gap should prioritize addressing the underlying cause and correcting electrolyte imbalances, as this approach is most likely to improve patient outcomes in terms of morbidity, mortality, and quality of life.