Influence of oral tramadol on the dynamic ventilatory response to carbon dioxide in healthy volunteers

We tested the effect of tramadol on ventilatory control by quantifying its effect on the steady-state ventilatory carbon dioxide response and by locating its site of respiratory action within the ventilatory control system. We imposed square-wave changes in end-tidal carbon dioxide (similar to1 kPa; end-tidal oxygen concentration kept constant at resting levels) in 10 healthy volunteers (six men, four women) before and after oral ingestion of 100 mg tramadol, and measured the ventilatory responses. Each hypercapnic response was separated into a fast, peripheral and a slow, central component. Two control and two tramadol carbon dioxide studies were performed in each subject. Tramadol reduced the total ventilatory carbon dioxide sensitivity by similar to 30% from 12.8 (6.1) [lower (25%) and upper (75%) quartiles 7.4 and 16.6 litre min(-1) kPa(-1)] to 9.1 (5.3) (5.3-14.1) litre min(-1) kPa(-1) (P<0.001). The fast and slow response gains were reduced by 23 (46) (3-54)% (P<0.05) and 30 (22) (15-54)% (P<0.01) respectively. The ratio of these carbon dioxide sensitivities and the apnoeic threshold were not significantly changed by tramadol. We suggest that tramadol affects the ventilatory control system by acting at the <mu>-opioid receptors in the respiratory integrating centres within the brainstem.