Effects of codeine on the respiratory responses to exercise in healthy subjects

In six healthy subjects, respiration and the sensation of breathlessness were assessed during submaximal exercise and the subsequent recovery. The overall responses were expressed by the relationship of breathlessness to minute volume. Because of the high subjective component in the assessments, validation of the method in these particular subjects was an integral part of the study. The relationship of breathlessness to ventilation during identical periods of exercise was highly reproducible and sensitivity was demonstrated by an alteration in this relationship in the presence of an inspiratory resistance. Codeine at a dose of 60 mg by mouth was compared with placebo, each treatment being given on two occasions. The study was conducted in a double-blind fashion with randomization of the order of treatments. Codeine at this dose allowed higher levels of carbon dioxide to be tolerated during breath-holding; oxygen uptakes at rest and during exercise were unaffected. Ventilation and breathlessness at the end of exercise were each slightly but significantly reduced by codeine but the relationship between breathlessness and ventilation was not changed. Codeine did not prevent detection of an inspiratory resistance.