Vinik H R, Kissin I
Department of Anesthesiology, University of Alabama at Birmingham, USA.
Anesth Analg. 1998 Jun;86(6):1307-11. doi: 10.1097/00000539-199806000-00033.
Studies in experimental animals have demonstrated a rapidly developing acute tolerance to the analgesic effect of opioids administered by continuous i.v. infusion. The aim of the present study was to determine whether acute tolerance plays an important role in the analgesic effect of remifentanil provided by i.v. infusion to humans. The analgesic effect of remifentanil, infused at a constant rate of 0.1 microg x kg(-1) x min(-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 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.
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.
对实验动物的研究表明，通过静脉持续输注给予阿片类药物时，会迅速产生对其镇痛作用的急性耐受性。本研究的目的是确定急性耐受性在瑞芬太尼静脉输注对人体的镇痛作用中是否起重要作用。在13名有偿志愿者中，通过热刺激（2℃水）和机械刺激（压力）测量疼痛耐受性，评估以0.1μg·kg⁻¹·min⁻¹的恒定速率输注瑞芬太尼4小时的镇痛效果。瑞芬太尼的恒速输注在两种测试中均使疼痛耐受性提高了三倍。在60 - 90分钟达到最大值后，尽管恒速输注，瑞芬太尼的镇痛效果仍开始下降，输注3小时后，仅为峰值的四分之一。以输注期间恢复到50%的时间来衡量，冷水测试的急性耐受性发展的比较速率为129±27分钟（平均值±标准差），压力测试为138±39分钟。我们得出结论，在目标控制输注的计算中应考虑耐受性的发展。
我们的研究表明，瑞芬太尼输注期间对镇痛的耐受性很强且发展非常迅速。基于目标控制输注的麻醉期间阿片类药物的给药应包括对耐受性发展的校正。
