Ma D, Sapsed-Byrne S M, Chakrabarti M K, Whitwam J G
Department of Anaesthetics and Intensive Care, Imperial College School of Medicine, Hammersmith Hospital London, UK.
Acta Anaesthesiol Scand. 1998 Jul;42(6):670-7. doi: 10.1111/j.1399-6576.1998.tb05300.x.
It has been shown that the depressive effects of both propofol and midazolam on consciousness are synergistic with opioids, but the nature of their interactions on other physiological systems, e.g. respiration, has not been fully investigated. The present study examined the effect of propofol and midazolam alone and in combination with fentanyl on phrenic nerve activity (PNA) and whether such interactions are additive or synergistic.
PNA was recorded in 27 anaesthetised and artificially ventilated rabbits. In three groups, propofol, fentanyl and midazolam were administered intravenously in incremental doses to construct dose-response curves for the depressant effects of each one on PNA. In another two groups, the effect of pretreatment with either fentanyl 1 microgram.kg-1 i.v. or midazolam 0.05 mg.kg-1 i.v. on the effects of propofol and fentanyl respectively on PNA were studied.
Propofol and fentanyl caused a dose-dependent depression of PNA with complete abolition at the highest total doses of 16 mg.kg-1 i.v. and 32 micrograms.kg-1 i.v., respectively. In contrast, midazolam in incremental doses to a total of 0.8 mg.kg-1 reduced mean PNA by 63%, but approximately 12% of PNA remained at a total dose as high as 6.4 mg.kg-1. The mean ED50s, calculated from dose-response curves, were 5.4 mg.kg-1, 3.9 micrograms.kg-1 and 0.4 mg.kg-1 for propofol, fentanyl and midazolam, respectively. Initial doses of either fentanyl 1 microgram.kg-1 i.v. or midazolam 0.05 mg.kg-1 i.v. acted synergistically with subsequent doses of either propofol or fentanyl to abolish PNA at total doses of 8 mg.kg-1 and 8 micrograms.kg-1, respectively.
Fentanyl has a synergistic interaction with both propofol and midazolam on PNA and hence potentially on respiration.
已有研究表明，丙泊酚和咪达唑仑对意识的抑制作用与阿片类药物具有协同效应，但它们对其他生理系统（如呼吸）的相互作用性质尚未得到充分研究。本研究考察了丙泊酚和咪达唑仑单独使用以及与芬太尼联合使用对膈神经活动（PNA）的影响，以及这种相互作用是相加性还是协同性。
记录27只麻醉并人工通气的家兔的PNA。将家兔分为三组，静脉递增注射丙泊酚、芬太尼和咪达唑仑，以构建三者对PNA抑制作用的剂量 - 反应曲线。另设两组，分别研究静脉注射1微克/千克芬太尼或0.05毫克/千克咪达唑仑预处理对丙泊酚和芬太尼各自作用于PNA的影响。
丙泊酚和芬太尼引起PNA剂量依赖性抑制，分别在静脉注射总剂量达16毫克/千克和32微克/千克时完全消除PNA。相比之下，咪达唑仑递增至总剂量0.8毫克/千克时，平均PNA降低63%，但在总剂量高达6.4毫克/千克时仍有约12%的PNA存在。根据剂量 - 反应曲线计算，丙泊酚、芬太尼和咪达唑仑的平均半数有效剂量（ED50）分别为5.4毫克/千克、3.9微克/千克和0.4毫克/千克。静脉注射初始剂量1微克/千克芬太尼或0.05毫克/千克咪达唑仑分别与随后的丙泊酚或芬太尼剂量协同作用，在总剂量分别为8毫克/千克和8微克/千克时消除PNA。
芬太尼与丙泊酚和咪达唑仑在PNA上存在协同相互作用，因此可能对呼吸也有协同作用。
