Wagenaar Michiel, Vos Petra, Heijdra Yvonne, Teppema Luc, Folgering Hans
Department of Pulmonary Diseases, Dekkerswald, University of Nijmegen, Groesbeek, the Netherlands.
Chest. 2003 May;123(5):1450-9. doi: 10.1378/chest.123.5.1450.
Acetazolamide and medroxyprogesterone acetate (MPA) are two respiratory stimulants that can be used in patients with stable hypercapnic COPD.
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 (FEV(1), 33 +/- 4% predicted [mean +/- SEM]).
Daytime PaCO(2) 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 PaO(2) 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).
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.
乙酰唑胺和醋酸甲羟孕酮（MPA）是两种可用于稳定期高碳酸血症慢性阻塞性肺疾病（COPD）患者的呼吸兴奋剂。
采用交叉设计，对12例稳定期高碳酸血症COPD患者（第1秒用力呼气容积[FEV₁]为预测值的33±4%[均值±标准误]）研究了每日两次服用250mg乙酰唑胺和每日两次服用30mg MPA对日间和夜间血气值的影响，以及对高碳酸血症和低氧通气及100毫秒反应时口腔阻断压（P₀.₁）的影响。
乙酰唑胺治疗期间，日间动脉血二氧化碳分压（PaCO₂）从安慰剂组的47.3±0.8mmHg降至42.0±1.5mmHg（p<0.05），MPA治疗期间降至42.8±1.5mmHg（p<0.05）。乙酰唑胺治疗使日间动脉血氧分压（PaO₂）从65.2±2.3mmHg升至75.0±3.0mmHg（p<0.05），而MPA治疗未见显著变化。两种治疗均使平均夜间呼气末二氧化碳分压降低，乙酰唑胺治疗时从42.0±2.3mmHg降至35.3±2.3mmHg（p<0.05），MPA治疗时降至34.5±0.8mmHg（p<0.05）。乙酰唑胺显著降低夜间动脉血氧饱和度<90%的时间百分比，从34.9±10.7%降至16.3±7.5%（p<0.05）。MPA治疗时平均夜间饱和度未改变。仅MPA使静息分钟通气量显著增加，从9.6±0.7L/分钟增至10.8±0.8L/分钟（p<0.05）。乙酰唑胺和MPA治疗期间，高碳酸血症通气反应斜率未改变。乙酰唑胺治疗期间低氧通气反应从-0.2±0.05L/分钟/%增至-0.4±0.1L/分钟/%（p<0.05），MPA治疗期间增至-0.3±0.1L/分钟/%（p<0.05）。乙酰唑胺治疗使低氧P₀.₁反应从-0.05±0.008mmHg/%改善至-0.15±0.02mmHg/%（p<0.05）。
本研究表明，乙酰唑胺和MPA对通气受限的稳定期COPD患者的日间和夜间血气参数均有有益作用。然而，由于乙酰唑胺对夜间饱和度有额外作用，故更推荐使用。
