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Comparison of Acetazolamide and Medroxyprogesterone as Respiratory Stimulants in Hypercapnic Patients With COPD^*

^* From the Department of Pulmonary Diseases (Drs. Wagenaar, Vos, Heijdra, and Folgering), Dekkerswald, University of Nijmegen; and Department of Physiology (Dr. Teppema), Leiden University Medical Center, the Netherlands.

Correspondence to: M. Wagenaar, MD, PhD, Department of Pulmonary Diseases, Dekkerswald, University of Nijmegen, PO Box 9001, 6560 GB Groesbeek, the Netherlands; e-mail: m.wagenaar{at}ulc.umcn.nl

Background: Acetazolamide and medroxyprogesterone acetate (MPA) are two respiratory stimulants that can be used in patients with stable hypercapnic COPD.

Design and methods: The effects of acetazolamide, 250 mg bid, and MPA, 30 mg bid, on daytime and nighttime blood gas values and the influences on the hypercapnic and hypoxic ventilatory and mouth occlusion pressure (P_0.1) at 100 ms response were studied in a crossover design in 12 hypercapnic patients with stable COPD (FEV₁, 33 ± 4% predicted [mean ± SEM]).

Results: Daytime PaCO₂ decreased from 47.3 ± 0.8 mm Hg (placebo) to 42.0 ± 1.5 mm Hg during acetazolamide treatment (p < 0.05) and to 42.8 ± 1.5 mm Hg during MPA treatment (p < 0.05). Daytime PaO₂ improved with acetazolamide from 65.2 ± 2.3 to 75.0 ± 3.0 mm Hg (p < 0.05), whereas no significant changes were seen with MPA. Mean nocturnal end-tidal carbon dioxide tension decreased with both treatments, from 42.0 ± 2.3 to 35.3 ± 2.3 mm Hg with acetazolamide (p < 0.05) and to 34.5 ± 0.8 mm Hg with MPA (p < 0.05). The percentage of time that the nocturnal arterial oxygen saturation was < 90% was reduced significantly with acetazolamide, from 34.9 ± 10.7% to 16.3 ± 7.5% (p < 0.05). Mean nocturnal saturation did not change with MPA. Resting minute ventilation increased significantly only with MPA from 9.6 ± 0.7 to 10.8 ± 0.8 L/min (p < 0.05). The slope of the hypercapnic ventilatory response did not change during acetazolamide and MPA therapy. The hypoxic ventilatory response increased from - 0.2 ± 0.05 to - 0.4 ± 0.1 L/min/% during acetazolamide (p < 0.05) and to - 0.3 ± 0.1 L/min/% during MPA (p < 0.05). The hypoxic P_0.1 response improved with acetazolamide treatment from - 0.05 ± 0.008 to - 0.15 ± 0.02 mm Hg/% (p < 0.05).

Conclusions: This study shows that acetazolamide and MPA both have favorable effects on daytime and nighttime blood gas parameters in ventilatory-limited patients with stable COPD. However, the use of acetazolamide is preferred because of its extra effect on nocturnal saturation.

Key Words: acetazolamide • COPD • hypercapnia • medroxyprogesterone acetate

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