Fisher D M, Szenohradszky J, Wright P M, Lau M, Brown R, Sharma M
Department of Anesthesia, University of California, San Francisco 94143-0648, USA.
Anesthesiology. 1997 Mar;86(3):558-66. doi: 10.1097/00000542-199703000-00007.
After bolus doses of nondepolarizing muscle relaxants, the adductor pollicis recovers from paralysis more slowly than the diaphragm and the laryngeal adductors, suggesting that the adductor pollicis is more sensitive than the respiratory muscles to effects of those drugs. In contrast, during onset, the respiratory muscles are paralyzed more rapidly than the adductor pollicis, suggesting that the respiratory muscles are more sensitive than the adductor pollicis. To reconcile these apparently conflicting findings, we determined vecuronium's pharmacokinetics and its pharmacodynamics at both the adductor pollicis and the laryngeal adductors.
Six volunteers were studied on two occasions during anesthesia with propofol. Mechanical responses to train-of-four stimulation were measured at the adductor pollicis and at the laryngeal adductors. Vecuronium (15-60 micrograms/kg) was given and arterial plasma samples were obtained from 0.5-60 min. Vecuronium doses differed by twofold on the two occasions. A pharmacokinetic model accounting for the presence and potency of vecuronium's 3-desacetyl metabolite and a sigmoid e-max pharmacodynamic model were fit to the resulting plasma concentration and effect (adductor pollicis and laryngeal adductors) data to determine relative sensitivities and rates of equilibration between plasma and effect site concentrations.
The steady-state plasma concentration depressing laryngeal adductor twitch tension by 50% was approximately 1.5 times larger than that for the adductor pollicis. The equilibration rate constant between plasma and laryngeal adductor concentrations was about 1.5 faster than that between plasma and adductor pollicis concentrations. The Hill factor (gamma) that describes the steepness of the laryngeal adductor concentration-effect relation was approximately 0.6 times that of the adductor pollicis.
More rapid equilibration between plasma and laryngeal adductor vecuronium concentrations explains why onset is more rapid at the laryngeal adductors than at the adductor pollicis. During recovery, both rapid equilibration and lesser sensitivity of the laryngeal adductors contribute to earlier recovery.
给予大剂量非去极化肌松药后，拇收肌从麻痹状态恢复的速度比膈肌和喉内收肌慢，这表明拇收肌比呼吸肌对这些药物的作用更敏感。相比之下，在起效过程中，呼吸肌比拇收肌更快出现麻痹，这表明呼吸肌比拇收肌更敏感。为了调和这些明显相互矛盾的发现，我们测定了维库溴铵在拇收肌和喉内收肌的药代动力学及其药效学。
6名志愿者在丙泊酚麻醉期间接受了两次研究。在拇收肌和喉内收肌测量对四个成串刺激的机械反应。给予维库溴铵（15 - 60微克/千克），并在0.5 - 60分钟采集动脉血浆样本。两次给药时维库溴铵剂量相差两倍。将一个考虑维库溴铵3 - 去乙酰代谢产物的存在和效力的药代动力学模型以及一个S形E最大药效学模型与所得血浆浓度和效应（拇收肌和喉内收肌）数据进行拟合，以确定相对敏感性以及血浆与效应部位浓度之间的平衡速率。
使喉内收肌抽搐张力降低50%的稳态血浆浓度约为拇收肌的1.5倍。血浆与喉内收肌浓度之间的平衡速率常数比血浆与拇收肌浓度之间的平衡速率常数快约1.5倍。描述喉内收肌浓度 - 效应关系陡峭程度的希尔系数（γ）约为拇收肌的0.6倍。
血浆与喉内收肌维库溴铵浓度之间更快的平衡解释了为什么喉内收肌的起效比拇收肌更快。在恢复过程中，快速平衡以及喉内收肌较低的敏感性都有助于更早恢复。
