Kelly K J, Clarens D M, Kohls P R, Nahum A, Vance-Bryan K
College of Pharmacy, University of Minnesota, Minneapolis.
Ann Pharmacother. 1993 Jul-Aug;27(7-8):862-5. doi: 10.1177/106002809302700707.
To describe a previously unreported event in which a patient became refractory to atracurium-induced neuromuscular blockade, but subsequently was adequately paralyzed with a standard dosage of pancuronium.
A previously healthy 17-year-old woman who sustained multiple trauma developed tolerance to an atracurium infusion she was receiving while undergoing mechanical ventilation. On day 3 of neuromuscular blockade, she became unresponsive to atracurium as evidenced by excessive physical movement, increased peak airway pressures, and overbreathing assist control ventilation. Repeat boluses and increases in the atracurium infusion rate to a maximum of 1.27 mg/kg/h failed to provide a desired clinical response. A bolus dose of pancuronium 0.15 mg/kg was administered and the constant infusion was then changed to pancuronium 0.078 mg/kg/h. Within minutes, decreased respirations, peak airway pressures, and agitation were noted. The pancuronium infusion rate was then tapered to 0.045 mg/kg/h over 72 hours and continued to maintain adequate neuromuscular blockade.
Potential pharmacokinetic and pharmacodynamic causes of loss of neuromuscular blockade in this patient are postulated. Possible explanations for loss of neuromuscular blockade include increased degradation of atracurium and/or a change in acetylcholine receptor physiology.
The development of resistance to a specific neuromuscular blocking agent in the intensive care setting does not necessarily imply cross-tolerance or resistance to alternative agents. Also, loss of respiratory control by one neuromuscular blocking agent may be overcome by changing agents.
描述一例此前未报道的事件,一名患者对阿曲库铵诱导的神经肌肉阻滞产生耐受,但随后使用标准剂量的潘库溴铵却能实现充分麻痹。
一名既往健康的17岁女性,因多处创伤在接受机械通气时对所输注的阿曲库铵产生耐受。在神经肌肉阻滞第3天,她对阿曲库铵无反应,表现为肢体活动过多、气道峰压升高以及辅助控制通气时呼吸频率过快。重复推注并将阿曲库铵输注速率增至最大1.27mg/kg/h,仍未产生预期的临床效果。给予0.15mg/kg的潘库溴铵推注剂量,随后将持续输注改为0.078mg/kg/h的潘库溴铵。数分钟内,呼吸、气道峰压及躁动均减轻。随后在72小时内将潘库溴铵输注速率减至0.045mg/kg/h,并持续维持充分的神经肌肉阻滞。
推测该患者神经肌肉阻滞失效的潜在药代动力学和药效动力学原因。神经肌肉阻滞失效的可能解释包括阿曲库铵降解增加和/或乙酰胆碱受体生理学改变。
在重症监护环境中,对一种特定神经肌肉阻滞剂产生耐药并不一定意味着对其他药物存在交叉耐受或耐药。此外,更换药物可能克服一种神经肌肉阻滞剂导致的呼吸控制丧失。