From the Guidelines
Acetazolamide is a useful adjunct in treating contraction alkalosis by promoting the excretion of bicarbonate and helping to normalize blood pH, typically administered at doses of 250-500 mg orally or intravenously once or twice daily. When patients develop contraction alkalosis, they have elevated serum bicarbonate levels and alkaline blood pH, often due to volume depletion and diuretic use. Acetazolamide inhibits carbonic anhydrase in the kidneys, which increases bicarbonate excretion and promotes acidification of the blood 1. This mechanism directly reduces serum bicarbonate levels and helps normalize pH.
Key Considerations
- The medication also promotes sodium, potassium, and water excretion, so electrolytes should be monitored during treatment.
- For optimal results, the underlying cause of contraction alkalosis should be addressed simultaneously, usually by restoring appropriate fluid volume with normal saline.
- Acetazolamide works quickly, often showing effects within hours, but should be used cautiously in patients with liver or kidney dysfunction, as it may worsen electrolyte imbalances if used inappropriately.
- According to the most recent study, the ADVOR trial, acetazolamide administered for 72 hours on top of standard care resulted in more efficient decongestion, but this did not affect all-cause mortality and heart failure rehospitalizations 1.
Clinical Application
- In clinical practice, acetazolamide may be considered for patients with contraction alkalosis who are not responding to traditional treatments or have significant volume overload.
- However, its use should be carefully weighed against the potential risks, including worsening renal function, as seen in the ADVOR and CLOROTIC trials 1.
- As noted in the KDIGO 2021 clinical practice guideline, acetazolamide may be helpful in treating metabolic alkalosis, but it is a weak diuretic and should be used in conjunction with other treatments 1.
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 intravenously corrected serum pH and decreased serum bicarbonate levels 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 randomized, double-blind trial of 40 mechanically ventilated patients found that a single dose of 500 mg acetazolamide was as effective as multiple doses of 250 mg in reversing metabolic alkalosis 5
Dosage and Efficacy
- The effective dosage of acetazolamide for metabolic alkalemia has been calculated to be around 7-12 mg/kg in vivo 6
- A study of critically ill pediatric patients found that acetazolamide reduced pHco-3 concentration in noncardiac patients, but not in cardiac patients 7
- The efficacy of acetazolamide in treating metabolic alkalosis may depend on the underlying condition and patient population 7