Kissin I, Vinik H R, Castillo R, Bradley E L
Department of Anesthesiology, School of Medicine, University of Alabama, Birmingham 35294.
Anesth Analg. 1990 Jul;71(1):65-9. doi: 10.1213/00000539-199007000-00011.
The effects of alfentanil on the midazolam dose-response curve for hypnosis was studied with response to the verbal command as an end point in 95 patients. The analgesic effect of alfentanil was studied by measuring the threshold for pain caused by pressure on the trapezius muscle with the use of a dolorimeter in 21 patients. The study was randomized, double-blind, and performed on the unpremedicated patients with ASA physical status I or II. Alfentanil was found to reduce the midazolam ED50 value for the induction of anesthesia in a dose-dependent fashion. The smallest dose of alfentanil (3 micrograms/kg) that caused a marked shift of the midazolam dose-response curve to the left along the dose axis (from the ED50 of 270 micrograms/kg to the ED50 of 142 micrograms/kg, P less than 0.0005) represents approximately 2% of the alfentanil ED50 for induction of unconsciousness (130 micrograms/kg). Alfentanil (10 micrograms/kg) caused only a tendency for increase in the pain threshold, whereas a dose of 15 micrograms/kg significantly increased the pain threshold by 37% (P less than 0.05). The results demonstrate that alfentanil potentiates the hypnotic effect of midazolam in very small doses. The high potency of alfentanil in this respect, as compared to its analgesic potency, suggests a very specific mechanism of alfentanil-midazolam hypnotic interaction, one that most likely is based on a functional relationship between the GABA receptor-benzodiazepine receptor system and the opioid receptor system in mediation of hypnosis.
以对言语指令的反应作为终点，在95例患者中研究了阿芬太尼对咪达唑仑催眠剂量-反应曲线的影响。通过使用痛觉计测量21例患者斜方肌受压所致疼痛的阈值，研究了阿芬太尼的镇痛效果。该研究为随机、双盲，且在未使用术前药的ASA身体状况I或II级患者中进行。结果发现，阿芬太尼以剂量依赖方式降低了咪达唑仑诱导麻醉的ED50值。使咪达唑仑剂量-反应曲线沿剂量轴明显左移（从ED50为270μg/kg至ED50为142μg/kg，P<0.0005）的最小阿芬太尼剂量（3μg/kg）约占阿芬太尼诱导意识丧失ED50（130μg/kg）的2%。阿芬太尼（10μg/kg）仅使疼痛阈值有升高趋势，而15μg/kg剂量可使疼痛阈值显著升高37%（P<0.05）。结果表明，阿芬太尼以极小剂量增强了咪达唑仑的催眠作用。与镇痛效能相比，阿芬太尼在这方面的高效能提示了阿芬太尼-咪达唑仑催眠相互作用的一种非常特殊的机制，很可能是基于γ-氨基丁酸（GABA）受体-苯二氮䓬受体系统与阿片受体系统在介导催眠过程中的功能关系。
