The Science Journal of the American Association for Respiratory Care

2003 OPEN FORUM Abstracts

A Comparison of Maintenance Tiotropium and Salmeterol on Arterial Blood Gas Tensions in Patients with COPD


Gross NJ, MD PhD1; Paulson D, MD2; Kennedy D, PharmD2; Korducki L, MS3; Kesten S, MD31Loyola University of Chicago and Hines VAH, Hines, IL USA, 2Hunter Holmes McGuire Medical Center, Richmond, VA USA 3Boehringer Ingelheim, Ridgefield, CT USA.


Background:
 Bronchodilators improve ventilation by relaxing airway smooth muscle. In patients with obstructive lung diseases, beta-agonists may dilate the pulmonary vasculature, leading to worsening ventilation-perfusion mismatching and increasing alveolar-arterial oxygen gradient. Anticholinergic agents do not affect the smooth muscle of the pulmonary vascular bed and therefore hold a potential advantage over beta-agonists.

Method: We conducted a double-blind, double-dummy, 4-week crossover study of tiotropium (TIO) 18 mcg daily and salmeterol (SAL) 50 mcg bid in patients with COPD (n=36). Pre-dose arterial blood gases (ABGs) were measured every 5 minutes by drawing blood samples using a catheter inserted into the radial artery until a stable baseline value for PaO2 was achieved. Subsequent draws were made at 30, 45, 60, 75, 90 and 105 minutes after study drug administration. This procedure was performed after 4 weeks of treatment with either salmeterol or tiotropium with a 30 day washout separating treatment periods. Supplemental oxygen was not permitted.

RESULTS:
 All patients were men and had a mean age of 68 years and mean FEV1 = 1.35 L (46.4% predicted). Baseline PaO2 and PaCO2 were 71.9 and 40.9 mmHg respectively. Comparative data was available in 32 subjects. In general, the PaO2 at individual time points was higher with tiotropium with the largest difference occurring at 45 minutes (2.76±1.37 mmHg, p=0.053). The difference between treatment groups (TIO - SAL) PaO2 AUC0-105 was 0.86±1.00 mmHg (p=0.4). At all time points post-dose, the alveolar-arterial (A-a) oxygen gradient was lower with tiotropium but this only reached statistical significance at 45 minutes (TIO=24.9±1.6, SAL=29.0±1.6 mmHg, p=0.008). The mean maximum A-a oxygen gradients for tiotropium and salmeterol were 30.7 and 32.7 mmHg, respectively (p=0.07).

CONCLUSION:
 While differences from SAL were small and in general, not statistically significant, TIO was associated with trends suggesting a superior outcome on arterial blood oxygenation and A-a gradient.

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