Gomez de Segura I A, Criado A B, Santos M, Tendillo F J
Department of Experimental Surgery, University Hospital La Paz, Madrid, Spain.
Anesthesiology. 1998 Dec;89(6):1489-94. doi: 10.1097/00000542-199812000-00027.
The combination of opioids and nonsteroidal antiinflammatory drugs is more analgesic than the summed effect of each drug administered separately. This synergism has been used to obtain analgesia in the postoperative period at doses at which side effects are minimal. The aim of this study is to evaluate the analgesic interaction between aspirin and morphine in the rat during isoflurane anesthesia. The reduction in minimum alveolar concentration of isoflurane (MAC(ISO)) was used as an objective measure of the analgesic potency of individual drugs and their use in combination.
Thirty-seven male Wistar rats were anesthetized with isoflurane in oxygen, and the MAC(ISO) was determined before and after the intravenous administration of aspirin and morphine. Rats were administered morphine alone (1, 3, and 10 mg/kg) or morphine (1 and 3 mg/kg) and aspirin (30 mg/kg). The MAC(ISO) was determined from alveolar gas samples at the time of tail clamp. The duration of MAC(ISO) reduction was recorded.
Aspirin did not have an effect on MAC(ISO), (average, 1.35+/-0.1%), whereas the combination of morphine (1 and 3 mg/kg) and aspirin (30 mg/kg) produced a reduction in the dose of morphine needed to produce the same degree of MAC(ISO) reduction. Actual MAC(ISO+drug) data were as follows: 1 mg/kg morphine, 1.17+/-0.14%; 3 mg/kg morphine, 0.98+/-0.15%; 1 mg/kg morphine plus aspirin, 0.90+/-0.04%; 10 mg/kg morphine, 0.63+/-0.13%; and 3 mg/kg morphine plus aspirin, 0.64+/-0.06%.
The synergistic effects of aspirin and morphine allow a clinically significant reduction in the requirements of isoflurane and isoflurane plus morphine, and these drug combinations may decrease the side effects associated with the use of single higher, equianalgesic doses of these drugs.
阿片类药物与非甾体抗炎药联合使用的镇痛效果比单独使用每种药物的效果总和更强。这种协同作用已被用于在副作用最小的剂量下实现术后镇痛。本研究的目的是评估在异氟烷麻醉期间阿司匹林与吗啡在大鼠体内的镇痛相互作用。异氟烷最低肺泡浓度（MAC(ISO)）的降低被用作个体药物及其联合使用时镇痛效力的客观指标。
37只雄性Wistar大鼠用氧气中的异氟烷麻醉，在静脉注射阿司匹林和吗啡前后测定MAC(ISO)。大鼠单独给予吗啡（1、3和10mg/kg）或吗啡（1和3mg/kg）与阿司匹林（30mg/kg）。在夹尾时从肺泡气体样本中测定MAC(ISO)。记录MAC(ISO)降低的持续时间。
阿司匹林对MAC(ISO)无影响（平均为1.35±0.1%），而吗啡（1和3mg/kg）与阿司匹林（30mg/kg）联合使用可降低产生相同程度MAC(ISO)降低所需的吗啡剂量。实际的MAC(ISO+药物)数据如下：1mg/kg吗啡，1.17±0.14%；3mg/kg吗啡，0.98±0.15%；1mg/kg吗啡加阿司匹林，0.90±0.04%；10mg/kg吗啡，0.63±0.13%；3mg/kg吗啡加阿司匹林，0.64±0.06%。
阿司匹林与吗啡的协同作用可使异氟烷以及异氟烷加吗啡的需求量在临床上显著降低，并且这些药物组合可能会减少与单独使用这些药物较高等效镇痛剂量相关的副作用。
