RAPID DEVELOPMENT OF TOLERANCE TO ANALGESIA DURING REMIFENTANIL INFUSION IN HUMANS

Studies in experimental animals have demonstrated a rapidly developing acute tolerance to the analgesic effect of opioids administered by co ntinuous IV infusion. The aim of the present study was to determine wh ether acute tolerance plays an important role in the analgesic effect of remifentanil provided by IV infusion to humans. The analgesic effec t of remifentanil, infused at a constant rate of 0.1 mu g . kg(-1) . m in(-1) for 4 h, was evaluated by measuring pain tolerance with thermal (2 degrees C water) and mechanical (pressure) noxious stimulations in 13 paid volunteers. The constant-rate infusion of remifentanil result ed in a threefold increase in pain tolerance with both tests. After re aching 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 c old water test and 138 +/- 39 min with the pressure test. We conclude that the development of tolerance should be included in the calculatio ns for target-controlled infusions. Implications: Our study shows that tolerance to analgesia during remifentanil infusion is profound and d evelops very rapidly. The administration of opioids during anesthesia based on target-controlled infusions should include corrections for th e development of tolerance.