Kissin I, McGee T, Smith L R
Can Anaesth Soc J. 1981 Nov;28(6):585-90. doi: 10.1007/BF03007157.
In rat experiments, the relative potency an safety of thiopentone, diazepam and etomidate were assessed using different indices of anaesthesia - loss of righting reflex, prevention of movement and heart rate responses to an noxious stimulus. Log-probit dose-response curves for these end-points and for lethal effect were determined. Etomidate proved to be more potent than thiopentone or diazepam; its relative potency figures varied from 5 to 18 with the use of different end-points of anaesthesia. According to the ED50 level of response for the loss of righting reflex and increased of heart rate, diazepam was more potent than thiopentone. At the same time it was less potent in the prevention of movement response. Etomidate has an extremely large standard safety margin (SSM) regarding the loss of righting reflex; with the use of movement response or heart rate response, the SSM for etomidate was close to that of thiopentone. With diazepam, SSM for movement response and heart rate response was negative (anaesthetic dose-response curve partially overlaps the lethal curve); it was positive for the loss of righting reflex. The extreme variability in assessment of relative potency and safety with different end-points of anaesthesia probably indicates that the indices used reflected various components of anaesthesia. It seems likely that for the proper assessment of the potency of intravenous anaesthetics, one index of potency is not sufficient. Several indices of potency corresponding to different components on general anaesthesia must be used.
在大鼠实验中，使用不同的麻醉指标——翻正反射消失、对有害刺激的运动预防和心率反应，评估了硫喷妥钠、地西泮和依托咪酯的相对效价和安全性。确定了这些终点指标以及致死效应的对数几率剂量-反应曲线。结果证明依托咪酯比硫喷妥钠或地西泮更有效；使用不同的麻醉终点指标时，其相对效价值在5到18之间变化。根据翻正反射消失和心率增加的ED50反应水平，地西泮比硫喷妥钠更有效。同时，在预防运动反应方面其效力较低。关于翻正反射消失，依托咪酯具有极大的标准安全 margin（SSM）；使用运动反应或心率反应时，依托咪酯的SSM与硫喷妥钠接近。对于地西泮，运动反应和心率反应的SSM为负（麻醉剂量-反应曲线部分与致死曲线重叠）；翻正反射消失时为正。使用不同的麻醉终点指标评估相对效价和安全性时存在极大差异，这可能表明所使用的指标反映了麻醉的不同组成部分。似乎对于正确评估静脉麻醉药的效力，单一的效力指标是不够的。必须使用与全身麻醉不同组成部分相对应的几个效力指标。
