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British Journal of Anaesthesia, 2001, Vol. 87, No. 6 860-865
© 2001 The Board of Management and Trustees of the British Journal of Anaesthesia

Clinical Investigations

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

D. Nieuwenhuijs1, J. Bruce2, G. B. Drummond2, P. M. Warren3 and A. Dahan1

1Department of Anesthesiology, Leiden University Medical Center (P5-Q), PO Box 9600, 2300 RC Leiden, The Netherlands. 2Department of Anaesthesia, Critical Care and Pain Medicine, University of Edinburgh, Royal Infirmary, Edinburgh, UK. 3Respiratory Medicine, Department of Medical and Radiological Science, University of Edinburgh, Royal Infirmary, Edinburgh, UK*Corresponding author

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 (~1 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 ~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 µ-opioid receptors in the respiratory integrating centres within the brainstem.

Br J Anaesth 2001; 87: 860–5


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