Am. J. Respir. Crit. Care Med., Volume 160, Number 5, November 1999, 1592-1597

Acetazolamide and Breathing
Does a Clinical Dose Alter Peripheral and Central CO₂ Sensitivity?

LUC J. TEPPEMA and ALBERT DAHAN

Departments of Physiology and Anesthesiology, Leiden University Medical Center, Leiden, The Netherlands

Improvement of blood gases with the carbonic anhydrase inhibitor acetazolamide in some patients with chronic obstructive pulmonary disease (COPD) is believed to result from an effect on the ventilatory control system. Carbonic anhydrase is ubiquitously present within the body, particularly in tissues involved in the control of breathing. Because low inhibitor concentrations are sufficient to block the enzyme in many tissues, it is of interest to document the effect of clinical doses of acetazolamide on the CO₂ sensitivities of the peripheral and central chemoreflex loops. In this study we measured the effect of chronic acetazolamide (250 mg by way of mouth, every 8 h during 3 days) on the dynamic ventilatory response to step changes in end-tidal PCO₂ in nine healthy volunteers. Data were analyzed using a two-compartment model comprising a fast peripheral and slow central compartment, enabling us to separate drug effects on the peripheral and central chemoreflex loops, respectively. Compared with placebo, acetazolamide did not change the CO₂ sensitivities and time constants of both chemoreflex loops. However, mean (± SD) resting ventilation increased from 12.22 ± 2.41 to 14.01 ± 1.85 L · min¹, resulting in a decrease in end-tidal PCO₂ from 40.0 ± 4.7 to 33.3 ± 3.5 mm Hg. Base excess decreased from 0.08 ± 1.20 to 7.48 ± 2.07 mmol · L¹, indicating metabolic acidosis and explaining a leftward shift of the CO₂ response curve by 7.3 mm Hg. Possible clinical implications of these results are discussed. Teppema LJ, Dahan A. Acetazolamide and breathing: does a clinical dose alter peripheral and central CO₂ sensitivity?

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