Hayashida Masakazu, Fukunaga Atsuo, Hanaoka Kazuo
*Department of Anesthesiology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan; and the †Department of Anesthesiology, Harbor UCLA Medical Center, Torrance, California.
Anesth Analg. 2003 Nov;97(5):1347-1352. doi: 10.1213/01.ANE.0000083370.80416.38.
Although acute tolerance to analgesia develops rapidly with remifentanil, it is unknown whether acute tolerance also develops to its nonanalgesic effects. We investigated the analgesic and cardiorespiratory effects of remifentanil during a continuous infusion in a rabbit model. Ten tracheotomized New Zealand White rabbits with arterial and venous accesses were placed on a sling that allowed for reasonably free movement. In spontaneously breathing conscious animals, remifentanil was infused IV at a constant-rate of 0.3 microg kg(-1)x min(-1) for 360 min. Sedative/analgesic and cardiorespiratory variables were assessed repeatedly during remifentanil infusion, including the number of animals behaviorally unresponsive to clamping the forepaw (nonresponders) and subcutaneous electrical stimulation thresholds required to elicit head lift (HLT: pain detection/arousal threshold) and escape movement responses (EMT: pain tolerance threshold). Within 60-120 min of starting the infusion, the number of nonresponders, HLT, EMT, and PaCO(2) increased significantly, whereas blood pressure, heart rate, and respiratory rate decreased. Thereafter, all variables returned towards preinfusion levels despite continuing infusion. These results indicate that during a remifentanil infusion acute tolerance develops for both its analgesic and cardiorespiratory effects.
Using a new rabbit model, we found that during continuous, constant-rate remifentanil infusion acute tolerance developed within the first few hours, not only to its analgesic but also to its cardiovascular and respiratory effects, albeit in slightly different time courses.
尽管瑞芬太尼会迅速产生急性镇痛耐受性，但其非镇痛作用是否也会产生急性耐受性尚不清楚。我们在兔模型中研究了瑞芬太尼持续输注期间的镇痛和心肺效应。十只经气管切开的新西兰白兔，有动脉和静脉通路，被放置在一个允许适度自由活动的吊床上。在自主呼吸的清醒动物中，以0.3微克·千克⁻¹·分钟⁻¹的恒定速率静脉输注瑞芬太尼360分钟。在瑞芬太尼输注期间反复评估镇静/镇痛和心肺变量，包括对夹前爪无行为反应的动物数量（无反应者）以及引起抬头所需的皮下电刺激阈值（HLT：疼痛检测/觉醒阈值）和逃避运动反应（EMT：疼痛耐受阈值）。在开始输注的60 - 120分钟内，无反应者数量、HLT、EMT和PaCO₂显著增加，而血压、心率和呼吸频率下降。此后，尽管继续输注，所有变量都恢复到输注前水平。这些结果表明，在瑞芬太尼输注期间，其镇痛和心肺效应都会产生急性耐受性。
使用一种新的兔模型，我们发现，在持续、恒速输注瑞芬太尼期间，急性耐受性在最初几小时内就会产生，不仅对其镇痛作用，而且对其心血管和呼吸作用都会产生，尽管时间进程略有不同。
