The Pupillary Effects of Intravenous Morphine, Codeine, and Tramadol in Volunteers

In Brief Opioid analgesics have pharmacological effects in many organ systems, including the eye. Because the metabolites of morphine and codeine contribute to their overall pharmacological effect pupil diameter measurements were made over a 6-h period. We studied the pupillary effects of IV morphine (0.125 mg/kg), codeine (1 mg/kg), tramadol (1.25 mg/kg), or placebo (10 mL 0.9% w/v sodium chloride) in 10 healthy volunteers. Pupil diameter was measured every 30 min using a pupil densitometer. Comparisons of the change in pupil diameter for each drug were made using analysis of variance with repeated measures. No significant change in pupil diameter was observed after placebo. After IV morphine and codeine administration there was a 26% decrease in pupil diameter (P < 0.001). Over the course of the study period, pupil diameter gradually returned to baseline values. After administration of tramadol there were no significant changes in pupil diameter until 150 min after administration, after which there was a significant reduction for the remainder of the study period (P < 0.01). The changes in pupil diameter may be explained in part by the pharmacokinetic profiles of the opioids studied. Measurement of pupil diameter may have a place in monitoring the central effect of opioids. IMPLICATIONS: The effect of several opioid analgesics on pupillary size has been studied. The results may be explained by differences in metabolism and pharmacokinetics of the drugs used. The data may be of use in defining a marker for the central effect of opioids and when assessing the degree of opioid toxicity.