Teodoro V. Santiago

Control of breathing during methadone addiction

Chemical control of breathing was studied before and after the administration of the daily dose of methadone in 14 former heroin addicts who were enrolled in a methadone maintenance program and taking 60 to 100 mg/day. Two major groups were identified: group 1 in which subjects (n=6) had taken the drug for less than two months, and group 2 in which the subjects (n=6) had taken the drug from eight to 43 months. Prior to the daily dose of methadone, the levels of arterial carbon dioxide tension were significantly higher and ventilatory response to hypoxia significantly lower in group 1 than in group 2. Ventilatory responses to carbon dioxide (CO2) were also lower in group 1, but the difference was not statistically significant. Following the daily dose of methadone, the subjects in group 1 manifested significant reductions of ventilation and arterial oxygen tension, significant increases in arterial carbon dioxide tension and significant depressions of ventilatory responses to both CO2 and hypoxia in comparison to values before the administration of methadone. In contrast, subjects in group 2 manifested only a significant decrease in ventilatory responsiveness to hypoxia with no change in ventilation, arterial blood gas tensions or ventilatory responsiveness to CO2 following the daily dose. Two intermediate subjects (five and seven months) behaved as long-term subjects with regard to arterial carbon dioxide tension and CO2 responses but as short-term subjects with regard to responsiveness to hypoxia. Thus, during the first two months of methadone maintence, there is continual alveolar hypoventilation due to depression o both central (CO2) and peripheral (hypoxia) chemoreception. After five months, alveolar hypoventilation is abolished as the CO2-sensitive chemoreflex acquires full tolerance to methadone at the maintenance dose level. In contrast, tolerance of the hypoxia-sensitive chemoreflex is developed more slowly and is never complete.

Blunted respiratory drive in congenital myopathy

Two patients with clinically mild congenital myopathies presented with chronic respiratory failure. Muscle weakness alone could not account for the respiratory insufficiency since static respiratory pressures were not markedly impaired, ventilation during exercise was normal, and daytime ventilation was normal if ventilatory assistance was provided at night. The ventilatory responses to inhaled carbon dioxide were very low, suggesting that impairment of the central nervous respiratory chemoreceptor contributed to hypoventilation. These patients and others described in the literature suggest that central depression of ventilation may occur more frequently than previously recognized in patients with muscular disorders. Patients with chronic respiratory failure due to central depression of respiratory drive can be effectively managed by assisted ventilation at night.

The Effects of Inhalation of Carbon Monoxide on Some Aspects of Neuromechanical Ventilatory Control

We have been involved in a broad study of the effects of brain hypoxia on the control o f breathing. The two major experimental models which we have used are inhalation of carbon monoxide and restriction of brain blood flow in intact, unanesthetized goats. Our findings to date indicate that brain hypoxia may have both inhibitory and facilitatory influences on ventilation and ventilatory responsiveness to chemical stimuli. Although these phenomena seem complex, and undoubtedly represent the interplay of several mechanisms, they are highly reproducible and may be demonstrated in each of the two different models of brain hypoxia which we have studied. In each model the occurrence of any given manifestation of brain hypoxia may be related to a specific range of 02 tension in cerebral venous blood1–4.