The Effects of Nitrazepam and Flunitrazepam on Oxygen Desaturation During SleepThe severity of oxygen desaturation during sleep in patients with COPD is mainly a function of their position on the oxyhemoglobin dissociation curve. Patients with stable COPD seem not to decrease their ventilation during sleep more than normal subjects. However, due to the shape of the dissociation curve, any factor increasing the hypoventilation during sleep will have more profound effects in COPD patients with hypoxemia already during wakefulness.

Benzodiazepines may cause hypoventilation in patients with severe COPD, probably due to a decrease in the ventilatory response to carbon dioxide, although there may be important differences within the benzodiazepine group. There are several reports of serious respiratory depression induced by benzodiazepines in COPD patients. On the other hand, the use of hypnotics or sedatives seems to be an uncommon cause of acute respiratory failure in COPD. This is compatible with the common clinical observation that many patients with severe COPD use benzodiazepine hypnotics regularly (often despite their doctors advice) without any obvious clinical impairment.
Overnight sleep studies can be used to quantify the risk of hypoxemia from hypnotics in COPD patients. Previous authors, investigating flurazepam (single doses), have only been able to show a minor effect. This may, in part, be due to the fact that the patients were not severely hypoxemic (mean Sa02, 9.9 kPa, or 74 mm Hg in studies of Cummiskey et al and Block et al). To test the hypothesis that harmful hypoxemia may occur from benzodiazepines in more severely hypoxemic COPD patients, we studied the effects of two widely used benzodiazepine hypnotics (nitrazepam and flunitrazepam) in 14 COPD patients with mean Pa02 of 8.4 kPa or 63 mm Hg. We intentionally used the highest recommended doses for the age group in question. Like Block et al and Cummiskey et al, we studied only patients with hypoxemia associated with significant airflow obstruction, thus avoiding the subset of bronchitic patients with hypoxemia due to other factors (obesity, cardiac failure, hypoventilation, etc).