Acetazolamide Usage in Severe Chronic Obstructive Pulmonary Disease: Pros and Cons

Abstract

Acetazolamide is a carbonic anhydrase (CA) inhibitor sometimes used as a respiratory stimulant for patients with chronic obstructive pulmonary disease (COPD) with the goal of improving oxygenation, reducing carbon dioxide retention, and aiding liberation from mechanical ventilation and/or attempting to correct a metabolic alkalosis. However, the net effect of CA inhibition is multifactorial and complex, because CA is inhibited in many tissues that may negatively affect the patient with lung disease. The full impact of acetazolamide and other CA inhibitors depends critically on dosing, age, and pulmonary, renal, hepatic, hematological, and respiratory muscle function and reserves. This review examines the literature and indications for acetazolamide use in patients with COPD dating back to its initial release 6 decades ago. There are very few studies specifically designed to address the population with severe COPD, as such patients were frequently excluded from trials. We therefore discuss the complexity of CA inhibition and its potential benefits and dangers and describe ways in which the pathophysiology of patients with severe COPD puts them at considerable risk for serious adverse consequences. We offer guidance on the careful and rational use of acetazolamide in patients with respiratory disorders.

Influence of methazolamide on the human control of breathing: A comparison to acetazolamide

“…According to a recent report, even lower doses (125 and 62.5 mg day −1 ) reduced the incidence of AMS (McIntosh et al., ). It is likely, therefore, that we used a higher AZ dose than necessary, although 250 mg three times daily is not unusual in clinical practice (Adamson & Swenson, ) and in AMS prophylaxis (Kayser et al., ). Owing to the fact that AZ and probably MZ inhibit HPV (Boulet et al., ; Ke et al., ; Teppema et al., ) by a mechanism not dependent on carbonic anhydrase inhibition, it is highly probable that the pharmacokinetics for CA inhibition might be different from that of HPV inhibition by these drugs.…”

“…Acetazolamide (AZ) has been used to stimulate ventilation in patients with chronic obstructive pulmonary disease, to correct metabolic alkalosis (Adamson & Swenson, ), to treat sleep‐disordered breathing (Edwards et al., ; Javaheri, Sands, & Edwards, ) and in the prophylaxis of acute mountain sickness (AMS; Kayser et al., ; Leaf & Goldfarb, ). Another property of AZ is its ability to reduce pulmonary vasoconstriction upon acute exposure to hypoxia (Ke et al., ; Teppema et al., ).…”

“…Another property of AZ is its ability to reduce pulmonary vasoconstriction upon acute exposure to hypoxia (Ke et al., ; Teppema et al., ). The rationale for the use of AZ in chronic obstructive pulmonary disease patients and in correcting metabolic alkalosis, however, is limited and disputed (Adamson & Swenson, ). A recent study showed no effect of intravenous AZ on liberation from mechanical ventilation in patients with chronic obstructive pulmonary disease and hypercapnic respiratory failure (Faisy et al., ).…”

“…A recent study showed no effect of intravenous AZ on liberation from mechanical ventilation in patients with chronic obstructive pulmonary disease and hypercapnic respiratory failure (Faisy et al., ). Weaning failure is more associated with respiratory muscle weakness and airway resistance rather than reduced respiratory drive (Adamson & Swenson, ). In rabbits, low‐dose AZ causes neuromuscular impairment of the diaphragm (Kiwull‐Schöne, Teppema, & Kiwull, ).…”

COVID-19 Lung Injury and High Altitude Pulmonary Edema: A False Equation with Dangerous Implications

“…Higher doses and/or impaired renal function, increase the risk of red cell CA inhibition which can precipitate hypercapnic respiratory failure, as happens in patients with severe COPD and limited respiratory reserve. (37) Another respiratory stimulant, almitrine, has been discussed on social media in relation to COVID-19. Almitrine increases ventilation at high altitude (38) by direct stimulation of the peripheral chemoreceptors.…”