Respiratory Center Output following Zopiclone or Diazepam Administration in Patients with Pulmonary Disease

Abstract

Mouth occlusion pressure at 0.1 s (P_0.1) and minute ventilation (VE) were measured at rest and during progressive hypercapnia in 32 patients. Under double-blind conditions and according to a 2 × 2 Latin-square design, half the patients received one oral dose of diazepam and its placebo. Using the same design, the other half received zopiclone and its placebo. Normocapnic and moderately hypoxemic patients between the ages of 21 and 69 with moderate to severe chronic obstructive pulmonary disease were included in the study. Diazepam produced a statistically significant decrease (p < 0.05) over its placebo in ΔP_0.1/ΔPE_ΤCO2 values following CO₂ rebreathing. Zopiclone did not influence either ΔP₀.₁/ΔP_ETCO2 or ΔVE/ΔP_ETCO2, but produced a significant increase in respiratory frequency. However, no statistically significant differences were observed between the two active treatments

Benzodiazepine drug use and adverse respiratory outcomes among older adults with COPD

“…Our results are consistent with previous studies that have reported links with benzodiazepines and a variety of adverse respiratory physiology outcomes in COPD [6][7][8][9][10][11][12]. Benzodiazepines are also reported to decrease arousability in healthy individuals during sleep [29], which may prolong the duration of respiratory physiological abnormalities or contribute to aspiration.…”

“…In addition, a true relationship between benzodiazepine use and adverse respiratory outcomes in the older COPD population is supported by biological plausibility (benzodiazepine use is associated with negative respiratory physiology markers) [6][7][8][9][10][11][12].…”

“…Benzodiazepines have been linked with a variety of adverse respiratory physiology outcomes in COPD, including decreased minute ventilation [6][7][8], hypoxaemia and/or hypercapnea [6][7][8][9][10][11], dulling of central respiratory drive and chemoreceptor responsiveness to hypercapnea [8,11,12], decreased respiratory muscle strength [7], and ventilation-perfusion mismatch [6]. Based on this evidence, joint American Thoracic Society/European Respiratory Society guidelines recommend that hypnotics, such as benzodiazepines, be avoided in patients with severe COPD [13].…”

Effect of zopiclone on sleep, night-time ventilation, and daytime vigilance in upper airway resistance syndrome

“…The most likely explanation for this reduction is a fall in resting ventilation. On the other hand, it has been demonstrated that zopiclone has no significant effects on control of breathing in patients with severe chronic obstructive pulmonary disease [17]. Nevertheless, in our seven other patients with UARS, none of the respiratory parameters were substantially affected by zopiclone ( figure 1).…”

“…Zopiclone is a short-acting cyclopyrrolone that appears to differ clinically from benzodiazepines in several ways: it preserves slow wave sleep (SWS) [14], it does not impair daytime performance in normal subjects [15,16], it has no significant effect on the control of breathing during quiet sleep, quiet wakefulness, or induced hyperventilation in patients with pulmonary disease [17], and it has only minimal deleterious effects on respiration in patients with OSAS [18].…”