Use of Acetazolamide in COPD Patients

Christine Campbell Reardon, MD

Disclosures

October 07, 2002

Question

I'm a doctor in Ho Chi Minh City, Vietnam. In my department (Pulmonology), some doctors prescribe acetazolamide for the patients with COPD who have edema and chronic respiratory failure. What is the role of acetazolamide in these patients?

Response from Christine Campbell Reardon, MD

Some patients with chronic obstructive pulmonary disease (COPD) develop carbon dioxide (CO2) retention and hypoxemia. There are multiple factors that lead to the development of CO2 retention. One of the major factors is an alteration of ventilation and perfusion matching leading to an increase in dead space. The diaphragm may function at an anatomical disadvantage in patients with COPD. In the setting of hyperinflation caused by airflow obstruction, the diaphragm is flattened and generates less pressure than what would occur under normal circumstances. In addition, hypercapnic patients demonstrate a breathing pattern characterized by a lower tidal volume and higher respiratory rate, which increases dead space. The lower tidal volume is caused by a shorter inspiratory time rather than a decrease in respiratory drive. It had previously been thought that hypercapnic COPD patients had a blunted central respiratory drive and this was the major cause of CO2 retention. From this idea, the use of carbonic anhydrase inhibitors -- such as acetazolamide for hypercapnic COPD patients -- developed.

Reversible inhibition of carbonic anhydrase results in the reduction of hydrogen ion secretion at the renal tubule and an increased renal secretion of sodium, potassium, bicarbonate, and water. Acetazolamide will block the conversion of CO2 into bicarbonate, which will acutely increase the levels of carbon dioxide in the tissues and blood. The induction of a metabolic acidosis by acetazolamide will increase respiratory drive in patients able to increase their ventilation, with a resultant decrease in arterial PCO2. Some patients with severe COPD may not be able to increase their ventilation adequately and will develop a severe acidosis for which they cannot compensate.[1]

A meta-analysis was performed of clinical trials involving acetazolamide in the treatment of hypercapnic ventilatory failure due to COPD.[2] Four trials were included in the analysis; they were of mixed design and of short duration, and the total patient number was 84. In the 2 randomized parallel studies, acetazolamide caused a metabolic acidosis and produced a nonsignificant decrease in the PCO2 and a significant increase in the PO2. The conclusions of the reviewers were that acetazolamide can produce a small increase in arterial PO2 and fall in PCO2, but that it is not known whether this physiologic improvement is associated with clinical benefit. These conclusions were based on a few small short studies of varying design and quality.

The effects of acetazolamide on ventilation and cerebral blood volume in normocapnic and hypercapnic patients with COPD have recently been published.[3] The investigators examined the response of inspired ventilation, mouth occlusion pressure, and cerebral blood volume to short-term changes in arterial PCO2 induced by acetazolamide as well as furosemide. The investigators found that normocapnic and chronic hypercapnic COPD patients have the same ventilatory and cerebrovascular CO2 responsiveness to acetazolamide.

From the evidence in the existing literature, acetazolamide has not been demonstrated in large controlled trials to have significant clinical benefit for the long-term management of hypercapnia in COPD patients. However, acetazolamide may play a role in the treatment of an acute metabolic alkalosis caused by diuresis or steroids in patients with hypercapnic COPD. In this setting, a short course of acetazolamide will correct the underlying metabolic alkalosis that may be precipitating a worsening of the hypercapnia.

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