What is the relationship between contraction alkalosis and furosemide (Lasix)?

From the Guidelines

Lasix (furosemide) can contribute to contraction alkalosis, which is a metabolic alkalosis resulting from volume contraction, and its management typically involves addressing the underlying volume depletion with appropriate fluid replacement, particularly with chloride-containing solutions like normal saline, as well as careful monitoring of electrolytes and acid-base status, with potential dose adjustments or addition of potassium-sparing diuretics to minimize these effects. When Lasix is administered, it inhibits sodium and chloride reabsorption in the loop of Henle, causing increased excretion of these electrolytes along with water. This diuretic effect leads to volume depletion or "contraction" of extracellular fluid. As volume decreases, the kidneys attempt to conserve sodium by increasing hydrogen and potassium excretion, resulting in alkalosis. Additionally, the loss of chloride from Lasix therapy is significant because low chloride levels stimulate bicarbonate reabsorption in the kidneys, further contributing to alkalosis.

Some key points to consider in the management of patients on Lasix therapy include:

• Monitoring of electrolytes, particularly potassium and chloride, to prevent hypokalemia and hypochloremia, which can worsen alkalosis 1
• Use of potassium-sparing diuretics, such as spironolactone, to minimize the risk of hypokalemia and alkalosis 1
• Careful monitoring of acid-base status, with potential dose adjustments or addition of potassium-sparing diuretics to minimize these effects 1
• Addressing the underlying volume depletion with appropriate fluid replacement, particularly with chloride-containing solutions like normal saline, to prevent further volume contraction and alkalosis 1

Overall, the management of contraction alkalosis in patients on Lasix therapy requires careful attention to electrolyte and acid-base balance, as well as monitoring for potential complications such as hypokalemia and volume depletion.

From the FDA Drug Label

As with any effective diuretic, electrolyte depletion may occur during furosemide therapy, especially in patients receiving higher doses and a restricted salt intake Hypokalemia may develop with furosemide, 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 therapy should be observed for these signs or symptoms of fluid or electrolyte imbalance (hyponatremia, hypochloremic alkalosis, hypokalemia, hypomagnesemia or hypocalcemia)

The use of Lasix (furosemide) can lead to contraction alkalosis due to hypochloremic alkalosis, which is a sign of fluid or electrolyte imbalance.

• Key points:
  • Electrolyte depletion may occur during furosemide therapy.
  • Hypokalemia may develop with furosemide, especially with brisk diuresis.
  • Patients should be observed for signs or symptoms of fluid or electrolyte imbalance, including hypochloremic alkalosis. 2

From the Research

Contraction Alkalosis and Lasix

• Contraction alkalosis is a condition that can occur due to the use of diuretics such as Lasix (furosemide) 3, 4, 5.
• However, a study published in the Journal of the American Society of Nephrology suggests that it is more accurate to refer to this condition as chloride depletion alkalosis, rather than contraction alkalosis 6.
• The use of Lasix can lead to metabolic alkalosis, which is characterized by an increase in blood pH and bicarbonate levels 3, 4.
• This can occur due to the activation of the renin-angiotensin system, chloride depletion, increased distal sodium delivery, hypokalemia, and increased urine acidification 4.
• Treatment of metabolic alkalosis typically involves the elimination of generation and maintenance factors, chloride and potassium repletion, and enhancement of renal bicarbonate excretion 4, 5.

Mechanism of Action

• Lasix works by inhibiting sodium chloride transport in the thick ascending limb of Henle, leading to a sharp reduction in extracellular fluid volume 5.
• This can result in a range of biochemical complications, including electrolyte and acid-base disorders, glucose and lipid abnormalities, and hypokalemia 3, 5.
• The development of these complications can be minimized with careful monitoring, dosage adjustment, and replacement of electrolyte losses 5.

Chloride Depletion Alkalosis

• Chloride depletion alkalosis is a condition that occurs when there is a depletion of chloride ions in the body, leading to an increase in blood pH and bicarbonate levels 6.
• This condition can be corrected by repleting chloride ions, even in the presence of persisting alkali loading, volume contraction, and potassium and sodium depletion 6.
• The corrective response is thought to be orchestrated in the collecting duct, which has several transporters integral to acid-base regulation, including pendrin, a luminal Cl/HCO(3)(-) exchanger 6.