Respiratory consequences of methadone: the response to added resistance to breathing

Respiratory responses to hypercapnia and added airway resistance were studied before and after methadone intake in 7 normal subjects (Group I) and 7 subjects receiving chronic methadone maintenance therapy (Group II). Before taking the drug, both groups exhibited similar ventilatory responses to CO2 without the resistance and equivalent augmentation of the airway occlusion pressure or "respiratory drive" responses to CO2 with the resistance. In Group I subjects, analgesic dosages of methadone depressed ventilation and ventilatory responsiveness to hypercapnia, and abolished the increase in respiratory drive elicited by the resistance. In contrast, patients receiving methadone maintance therapy exhibited no changes in either ventilatory responses or respiratory drive after intake of their daily doses of the drug. The data show that narcotic drugs may abolish the respiratory compensation, i.e., the enhanced ventilatory drive that accompanies increased airway resistance, although tolerance develops with chronic use. Because this compensation has been reported to play an important role in the respiratory response to diffuse obstructive disease, the findings suggested a mechanism for the frequent inordinate respiratory depressant effects of narcotic drugs in such diseases.