Ketamine antagonises alfentanil-induced hypoventilation in healthy male volunteers

Background: The effects of ketamine on respiration, alone, or in combinatio n with opioids, have not been completely clarified. Both stimulant and depr essant effects have been reported, as well as attenuation of opioid-induced hypoventilation at the expense of increased oxygen consumption. These conf licting results might partly be due to dose-dependent mechanisms. We have, therefore, determined the ventilatory effects of ketamine, in combination w ith alfentanil, using infusions to different pseudo steady-state concentrat ions. Methods: On two separate days, eight healthy male volunteers were given alf entanil as a continuous computer-controlled infusion, aiming at a plasma co ncentration of 50 ng . mL(-1). After reaching apparent steady-state for alf entanil, racemic ketamine or placebo was administered in a protocol randomi sed for the two days. On the ketamine days a computer-controlled infusion, aiming for escalating ketamine plasma concentrations of 50, 100 and 200 ng . mL(-1), was added to the alfentanil infusion. On the placebo days saline was added. Using a face-mask with an occlusion valve, respiratory parameter s were measured during air-breathing and after 6 repetitive 30-s CO2 challe nges. Results: The alfentanil infusion induced hypoventilation by decreasing resp iratory rate, while tidal volume and respiratory drive were unaffected. Thi s hypoventilation was antagonised by ketamine in a concentration-dependent manner mainly through an increase in respiratory rate. The CO2 response was not affected by alfentanil or ketamine. Conclusion: in the dose range of interest for postoperative, intensive-care and pain-clinic settings, ketamine antagonises the resting hypoventilation induced by alfentanil.