From the Guidelines
Acetazolamide is a useful adjunct in treating contraction (hypovolemic) alkalosis by increasing bicarbonate excretion, thereby correcting the alkalosis, as evidenced by its mechanism of action and clinical use 1.
Mechanism of Action
Acetazolamide works by inhibiting carbonic anhydrase in the kidneys, which leads to an increase in bicarbonate excretion. This action directly addresses the underlying problem of elevated bicarbonate levels that characterize contraction alkalosis. Contraction alkalosis occurs when the body loses fluid volume but retains bicarbonate, leading to metabolic alkalosis.
Clinical Use
Typically, acetazolamide is administered at doses of 250-500 mg orally or intravenously every 6-12 hours. It is particularly useful when the alkalosis persists despite volume repletion or when the patient cannot tolerate large volumes of chloride-containing fluids. The use of acetazolamide in managing edema and its complications, including metabolic alkalosis, is supported by guidelines such as those outlined in the KDIGO 2021 clinical practice guideline for the management of glomerular diseases 1.
Considerations and Side Effects
Patients should be monitored for potential side effects including electrolyte disturbances (particularly hypokalemia), metabolic acidosis if overdosed, and paresthesias. Adequate hydration should be maintained during treatment to prevent complications like kidney stones. The ADVOR trial, although focused on decongestion in acute heart failure, highlights the potential of acetazolamide to cause transient worsening of renal function, underscoring the need for careful patient selection and monitoring 1.
Key Points
- Acetazolamide increases bicarbonate excretion to correct alkalosis.
- It is used in cases where alkalosis persists despite volume repletion or when large volumes of chloride-containing fluids are not tolerated.
- Monitoring for side effects such as electrolyte disturbances and renal function is crucial.
- Adequate hydration is necessary to prevent complications.
From the FDA Drug Label
Acetazolamide is a potent carbonic anhydrase inhibitor... The diuretic effect of acetazolamide is due to its action in the kidney on the reversible reaction involving hydration of carbon dioxide and dehydration of carbonic acid The result is renal loss of HCO3 ion, which carries out sodium, water, and potassium. The answer is: Acetazolamide helps treat contraction (hypovolemic) alkalosis by increasing the renal loss of HCO3 ion, which in turn increases the loss of sodium, water, and potassium. This action reduces alkalosis by promoting the excretion of excess bicarbonate ions 2.
From the Research
Mechanism of Action
- Acetazolamide helps treat contraction (hypovolemic) alkalosis by decreasing the serum strong ion difference (SID) 3
- The decrease in serum SID is explained by an increase in the urinary excretion of sodium without chloride, resulting in an increase in serum chloride 3
- Acetazolamide inhibits carbonic anhydrase in the proximal tubule, leading to a decrease in bicarbonate reabsorption and an increase in chloride reabsorption 3
Clinical Studies
- A study of 15 critically ill patients with metabolic alkalosis found that a single dose of 500 mg acetazolamide effectively corrected metabolic alkalosis by decreasing the serum SID 3
- Another study of 30 ventilated patients found that 500 mg of intravenous acetazolamide decreased total serum bicarbonate and normalized base excess and pH 4
- A study of 68 mechanically ventilated COPD patients found that acetazolamide induced a decrease in serum bicarbonate with a dose-response relationship 5
Dosage and Administration
- The effective dosage of acetazolamide for metabolic alkalemia is experimentally calculated to be around 7-12 mg/kg in vivo 6
- A study found that a single 500-mg dose of acetazolamide reverses nonchloride responsive metabolic alkaloses in medical intensive care unit patients as effectively as multiple doses of 250 mg 7
- The amount of acetazolamide inducing 50% of the putative maximum effect was found to be 117 ± 21 mg 5