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 locat ing its site of respiratory action within the ventilatory control system. W e imposed square-wave changes in end-tidal carbon dioxide (similar to1 kPa; end-tidal oxygen concentration kept constant at resting levels) in 10 heal thy volunteers (six men, four women) before and after oral ingestion of 100 mg tramadol, and measured the ventilatory responses. Each hypercapnic resp onse was separated into a fast, peripheral and a slow, central component. T wo control and two tramadol carbon dioxide studies were performed in each s ubject. Tramadol reduced the total ventilatory carbon dioxide sensitivity b y 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 thes e carbon dioxide sensitivities and the apnoeic threshold were not significa ntly changed by tramadol. We suggest that tramadol affects the ventilatory control system by acting at the <mu>-opioid receptors in the respiratory in tegrating centres within the brainstem.