Effects of the opioid remifentanil on olfactory function in healthy volunteers

The effects of opioids on human subjective olfactory function have rarely been investigated. This is despite the fact that opioid receptors are widely distributed throughout the olfactory systems. Using an established validated test of subjective olfactory function, olfactory threshold, odor discrimination and odor identification performance were tested in 16 healthy volunteers before opioid administration and at steady state after 3 hours remifentanil infusion. Each one man and one women were assigned randomly to one out of eight predefined remifentanil target plasma concentrations: 0, 1.2, 1.8, 2.4, 3, 3.6, 4.8, and 6 ng/ml. In the thirteen subjects that had completed the tests, olfactory thresholds were elevated with increasing remifentanil dose, and this correlated statistically significant with the remifentanil dose. Remifentanil plasma concentrations were linearly related to changes in olfactory thresholds. In contrast, effects of remifentanil on odor discrimination and identification were not statistically significant. However, remifentanil target plasma concentrations were also significantly correlated with the subjects' ratings of tiredness and drowsiness, although only drowsiness was significantly correlated with the differences in odor thresholds. We conclude that opioid administration leads to impaired olfactory function expressed in raised olfactory thresholds. This is compatible with previously reported opioidergic effects at the level of the olfactory bulb.