Kissin I, Lee S S, Arthur G R, Bradley E L
Department of Anesthesia, Harvard Medical School, Brigham and Women's Hospital, Boston, Massachusetts 02115, USA.
Anesth Analg. 1996 Sep;83(3):600-5. doi: 10.1097/00000539-199609000-00029.
The time course of the development of acute tolerance to alfentanil was characterized in rat experiments using various algorithms of continuous infusion of the drug. To maintain analgesia at a constant level (tail compression test), alfentanil use was steadily increased: Time to 50% increase in alfentanil use was 255 +/- 98 min with analgesia maintained at a level of 50% increase in the pressure threshold, and 203 +/- 116 min with analgesia maintained at a level of 200% increase. With the use of the alfentanil infusion regimen designed to rapidly achieve and maintain the constant alfentanil plasma concentration (120 ng/mL), the rate of development of acute tolerance, measured in terms of time to 50% recovery during continuing infusion, was 81 +/- 26 min with the compression test and 88 +/- 38 min with the hot-plate test, but 374 +/- 46 min with the rotarod test (P < 0.0001). Thus we demonstrated rapid development of acute tolerance to continuously infused alfentanil with different methods of tolerance assessment. The results also indicate that the time course of tolerance development does not depend on the type of noxious stimulation (mechanical versus thermal) if the response is organized predominantly supraspinally, and that acute tolerance to the direct effect of alfentanil on motor functions does not mask the rapid development of tolerance to its analgesic effect.
在大鼠实验中，使用不同的阿芬太尼持续输注方案，对阿芬太尼急性耐受性的发展时间进程进行了表征。为了将镇痛维持在恒定水平（尾部压迫试验），阿芬太尼的用量稳步增加：在压力阈值增加50%的水平维持镇痛时，阿芬太尼用量增加50%的时间为255±98分钟；在压力阈值增加200%的水平维持镇痛时，阿芬太尼用量增加50%的时间为203±116分钟。采用旨在快速达到并维持阿芬太尼恒定血浆浓度（120 ng/mL）的阿芬太尼输注方案时，在持续输注期间，以恢复至50%所需时间衡量的急性耐受性发展速率，在压迫试验中为81±26分钟，在热板试验中为88±38分钟，但在转棒试验中为374±46分钟（P<0.0001）。因此，我们证明了在不同的耐受性评估方法下，持续输注阿芬太尼时急性耐受性发展迅速。结果还表明，如果反应主要由脊髓上组织介导，耐受性发展的时间进程不依赖于有害刺激的类型（机械性与热性），并且阿芬太尼对运动功能的直接作用的急性耐受性不会掩盖其镇痛作用耐受性的快速发展。
