Rapid Development of Tolerance to Analgesia During Remifentanil Infusion in Humans

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Abstract
Ovided by IV infusion to humans. The analgesic effect of remifentanil, infused at a constant rate of 0.1 [micro sign]g [center dot] kg-1 [center dot] min-1 for 4 h, was evaluated by measuring pain tolerance with thermal (2[degree sign]C water) and mechanical (pressure) noxious stimulations in 13 paid volunteers. The constant-rate infusion of remifentanil resulted in a threefold increase in pain tolerance with both tests. After reaching its maximum in 60-90 min, the analgesic effect of remifentanil began to decline despite the constant-rate infusion, and after 3 h of infusion, it was only one fourth of the peak value. A comparative rate in the development of acute tolerance measured in terms of time to 50% recovery during infusion was 129 +/- 27 min (mean +/- SD) with the cold water test and 138 +/- 39 min with the pressure test. We conclude that the development of tolerance should be included in the calculations for target-controlled infusions. Implications: Our study shows that tolerance to analgesia during remifentanil infusion is profound and develops very rapidly. The administration of opioids during anesthesia based on target-controlled infusions should include corrections for the development of tolerance. (Anesth Analg 1998;86:1307-11)...