BACKGROUND This study was designed to examine whether severe aortic regurgitation will affect the pharmacodynamics (PD) and pharmacokinetics (PK) of cisatracurium during anesthetic induction. METHODS A total of 32 patients were divided into two groups: the AR group (n = 16) and the control group (n = 16). Arterial blood samples were drawn before and at 1, 2, 4, 6, 8, 10, 16 and 20 min after intravenous injection of 0.15 mg/kg cisatracurium. TOF tests were applied to determine the onset time of maximal muscle relaxation. The concentration of cisatracurium in plasma was determined by high-performance liquid chromatography. RESULTS The onset time to maximal neuromuscular block was prolonged from 2.07 ± 0.08 min to 4.03 ± 0.14 min, which indicated that the PD responses to cisatracurium were significantly delayed in the AR group (P < 0.05) compared to the control group. A conventional two-compartment PK model showed a higher plasma concentration of cisatracurium among the AR group with markedly reduced intercompartment transfer rate (K12 = 0.19 ± 0.02 and K21 = 0.11 ± 0.01 in the AR group vs. K12=0.26 ± 0.01 and K21 = 0.19 ± 0.01 in the control group, P < 0.01) compared to the control group. CONCLUSION Backward blood flow during diastole in severe AR impaired distribution of cisatracurium from the central compartment to the peripheral compartment, which accounted for the lagged PD responses. Findings in this study underlie the importance of muscular blockade monitoring among patients with severe aortic regurgitation during anesthetic induction. REGISTRATION Name of the registry: Abnormal Cisatracurium Pharmacodynamics and Pharmacokinetics among Patients with Severe Aortic Regurgitation during Anesthetic Induction. TRIAL REGISTRATION NUMBER ChiCTR1800019654. Date of registration: November 20th 2018.

中文翻译：

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麻醉诱导期间发生严重主动脉瓣反流的患者中顺沙曲库铵的药效学和药代动力学异常。

背景技术本研究旨在检查严重的主动脉反流是否会在麻醉诱导过程中影响顺沙曲库的药效学（PD）和药代动力学（PK）。方法将32例患者分为两组：AR组（n = 16）和对照组（n = 16）。静脉注射0.15 mg / kg西沙曲库铵之前，1、2、4、6、8、10、16和20分钟时和之后抽取动脉血样品。使用TOF测试确定最大肌肉松弛的开始时间。通过高效液相色谱法测定血浆中西沙曲库铵的浓度。结果最大神经肌肉阻滞的发作时间从2.07±0.08分钟延长至4.03±0.14分钟，这表明AR组PD对顺沙曲库铵的反应明显延迟（P <0。05）与对照组相比。传统的两室PK模型显示AR组中西沙曲库的血浆浓度较高，室间转移速率明显降低（AR组中K12 = 0.19±0.02和K21 = 0.11±0.01，而K12 = 0.26±0.01和K21 =对照组为0.19±0.01，P <0.01）。结论严重AR患者舒张期血液逆流会削弱顺沙曲库铵从中央室向周围室的分布，这是PD反应滞后的原因。这项研究的发现强调了在麻醉诱导期间对严重主动脉瓣关闭不全的患者进行肌肉阻滞监测的重要性。注册表名称：麻醉诱导期间发生严重主动脉反流的患者中顺沙曲库铵的药效动力学和药代动力学异常。试用注册号ChiCTR1800019654。注册日期：2018年11月20日。