Dauthier C, Gaudy J H, Willer J C
Ann Anesthesiol Fr. 1980;21(4):421-30.
The search for a technique making it possible to dissociate the analgesia and ventilatory depression of central analgesics led to a comparison of the effects of naloxone, a specific morphinomimetic antagonist, with almitrine, a ventilatory stimulant with a peripheral action, on muzzle opening reflex and blood gases. Five male dogs (Beagles, aged one year), anaesthetised with Alfetesine were treated separately with the two drugs used alone and after fentanyl analgesia (injection of fractionnated doses up to the threshold of apnoea). The association of the two drugs was also tested in tyhe dog after analgesia. The parameters studied were muzzle opening reflex, as an indication of analgesia, and blood gases, and were observed for 45 minutes, including 15 minutes control.
1 - The intravenous injection of 1,2 mg of naloxone had the effect of increasing the surface area of muscle potentials with a maximum of 7 per cent (p 0.001) at the 15 th minute. By contrast, no significant change in blood gases was seen. In the same dogs given fentanyl analgesia, naloxone not only reversed respiratory depression but had a stimulatory effect on MOR reaching 7 per cent (p 0.001) at the 30 th minute. 2 - The effects of 1 mg.kg-1 of almitrine were characterised by a fall in MOR for a period equal to that of the study and a minimum of 7.8 per cent (p 0.001) at the 20 th minute. At the same time, marked ventilatory stimulation was seen. PO2 rose by 22.7 per cent (p 0.02) at the 5 th minute. PCO2 fell during the 30 minutes studied with a minimum of 39.6 per cent (p 0.01) at the 20 th minute. Almitrine did not antagonise the depression of MOR caused by fentanyl but reversed the respiratory depression of the analgesic, increasing PO2 by 26 per cent (p 0.01) and decreasing PCO2 by 25.7 per cent (p 0.01). 3 - The combination of both drugs cancelled out the abolition of the reflex by fentanyl then facilitated it up to 24.7 per cent (p 0.001) in comparison with the animal not receiving any analgesic. By contrast, the ventilatory action of almitrine was not potentialised by naloxone. In view of these data, and in the absence of any emergency, the choice of naloxone as an antagonist of ventilatory depression of central analgesics should not be preferential in order to avoid the rebound effect.
为寻找一种能够使中枢镇痛药的镇痛作用与呼吸抑制作用分离的技术，对纳洛酮（一种特异性阿片样物质拮抗剂）和阿米三嗪（一种具有外周作用的呼吸兴奋剂）对张口反射和血气的影响进行了比较。选用5只雄性比格犬（1岁），用阿法沙秦麻醉后，分别单独给予这两种药物，并在芬太尼镇痛后（注射分次剂量直至呼吸暂停阈值）给予。镇痛后还在犬身上测试了两种药物的联合使用。所研究的参数为作为镇痛指标的张口反射和血气，并观察45分钟，包括15分钟的对照期。
1 - 静脉注射1.2毫克纳洛酮可使肌肉电位表面积增加，在第15分钟时最大增加7%（p<0.001）。相比之下，血气未见明显变化。在给予芬太尼镇痛的同一只犬中，纳洛酮不仅逆转了呼吸抑制，而且对张口反射有刺激作用，在第30分钟时达到7%（p<0.001）。2 - 1毫克/千克阿米三嗪的作用特点是在研究期间张口反射下降，在第20分钟时最低下降7.8%（p<0.001）。同时，可见明显的呼吸刺激作用。第5分钟时动脉血氧分压（PO2）升高22.7%（p<0.02）。在研究的30分钟内动脉血二氧化碳分压（PCO2）下降，在第20分钟时最低下降39.6%（p<0.01）。阿米三嗪不能拮抗芬太尼引起的张口反射抑制，但可逆转镇痛药的呼吸抑制，使PO2升高26%（p<0.01），PCO2降低25.7%（p<0.01）。3 - 两种药物联合使用消除了芬太尼对反射的抑制作用，然后与未接受任何镇痛药的动物相比，使反射增强达24.7%（p<0.001）。相比之下，纳洛酮并未增强阿米三嗪的呼吸作用。鉴于这些数据，且在无任何紧急情况时，为避免反跳效应，不应优先选择纳洛酮作为中枢镇痛药呼吸抑制的拮抗剂。
