Bragg P, Fisher D M, Shi J, Donati F, Meistelman C, Lau M, Sheiner L B
Department of Anesthesia, University of California, San Francisco 94143-0648.
Anesthesiology. 1994 Feb;80(2):310-9. doi: 10.1097/00000542-199402000-00011.
Although the respiratory muscles (the diaphragm and the laryngeal adductors) recover from paralysis more rapidly than does the adductor pollicis, patients can develop complete paralysis of the respiratory muscles, but not of the adductor pollicis, after bolus administration of vecuronium. The authors used a pharmacodynamic model not requiring muscle relaxant plasma concentrations to reconcile these findings.
The pharmacodynamic model is based on the traditional model, in which: (1) vecuronium concentration at the neuromuscular junction (C(effect)) is a function of the plasma concentration versus time curve and a rate constant for equilibration between plasma and the neuromuscular junction (k(eo)); and (2) effect is a function of C(effect), the steady-state plasma concentration that produces 50% effect (C50), and a factor to explain the sigmoid relationship between concentration and effect. In the absence of vecuronium plasma concentrations, an empiric model (rather than the usual effect compartment model) can be used to mimic the time delay (proportional, but not identical, to 1/k(eo)) between dose and effect. The model can be used to estimate the steady-state infusion rate that produces 50% effect (IR50), equal to the product of C50 and vecuronium plasma clearance; IR50 for different muscle groups then can be compared to assess relative sensitivity. The authors applied this model to published effect data for subjects given 40-70 micrograms/kg vecuronium in whom paralysis of three muscle groups was measured during opioid/propofol anesthesia.
For IR50, the ratio of values for the larynx:diaphragm:adductor pollicis was 1.4:1.2:1; for the equilibration constant (inversely proportional to the time delay), the ratio for the respiratory muscles to the adductor pollicis was 2.5:1.
Vecuronium concentrations peak earlier at the respiratory muscles than at the adductor pollicis, possibly the result of greater perfusion to these organs, leading to earlier onset of paralysis. The observation that bolus injection of vecuronium produces greater paralysis of the respiratory muscles than of the adductor pollicis, despite greater resistance of the respiratory muscles, can be explained by differential rates of equilibration between plasma and various muscles.
尽管呼吸肌（膈肌和喉内收肌）比拇内收肌从麻痹状态恢复得更快，但在静脉推注维库溴铵后，患者可能会出现呼吸肌完全麻痹，而拇内收肌不会。作者使用了一种不需要肌肉松弛剂血浆浓度的药效学模型来解释这些发现。
该药效学模型基于传统模型，其中：（1）神经肌肉接头处的维库溴铵浓度（C（效应））是血浆浓度随时间变化曲线以及血浆与神经肌肉接头之间平衡速率常数（k（eo））的函数；（2）效应是C（效应）、产生50%效应的稳态血浆浓度（C50）以及解释浓度与效应之间S形关系的一个因子的函数。在没有维库溴铵血浆浓度的情况下，可以使用经验模型（而非通常的效应室模型）来模拟剂量与效应之间的时间延迟（与1/k（eo）成比例，但不完全相同）。该模型可用于估计产生50%效应的稳态输注速率（IR50），其等于C50与维库溴铵血浆清除率的乘积；然后可以比较不同肌肉群的IR50以评估相对敏感性。作者将该模型应用于已发表的给予40 - 70微克/千克维库溴铵的受试者的效应数据，这些受试者在阿片类药物/丙泊酚麻醉期间测量了三组肌肉的麻痹情况。
对于IR50，喉：膈肌：拇内收肌的值的比例为1.4:1.2:1；对于平衡常数（与时间延迟成反比），呼吸肌与拇内收肌的比例为2.5:1。
维库溴铵在呼吸肌处的浓度峰值早于拇内收肌，这可能是由于这些器官灌注量更大，导致麻痹起效更早。尽管呼吸肌阻力更大，但静脉推注维库溴铵后呼吸肌麻痹比拇内收肌更严重这一观察结果，可以通过血浆与不同肌肉之间平衡速率的差异来解释。
