Effects of opioid dependence and tobacco use on ventilatory response to progressive hypercapnia

Respiratory depression is a serious medical risk of opioid use. Most opioid abusers also smoke cigarettes, perhaps further compromising breathing. Differences in ventilatory response to nonhypoxic hypercapnia were studied in healthy volunteers with limited substance use (LU), tobacco smokers (SM), and opioid-dependent, methadone-maintained smokers (OD). The last two groups had similar current cigarette use and all groups were similar in gender and body mass index. Because previous data suggest that SM are sensitive to hypoxia but not hypercapnia, it was predicted that only the OD group would exhibit decreased carbon dioxide (CO(2)) sensitivity. All subjects rebreathed CO(2) during three identical sessions (four trials per session). Fractional end-tidal (Fet) CO(2) levels during repeated 4-min exposures to progressive hypercapnia (6% to 10%) were similar across groups. Ventilatory response (breathing rate, tidal volume and minute volume) linearly increased with FetCO(2) concentration and did not differ significantly across sessions. Relative to the LU and SM groups (which did not significantly differ), the CO(2)-minute volume and CO(2)-breathing rate functions were significantly shifted rightward (decrease in intercept but not slope) for OD subjects. These data are consistent with the hypothesis that chronic opioid exposure and/or short-term methadone maintenance (but not tobacco or nicotine use) produces a specific decrease in CO(2) sensitivity, primarily through an inhibitory effect on respiratory frequency.