【作者】 任柏林；

【导师】 董铁立；

【作者基本信息】 郑州大学 ， 麻醉学， 2011， 硕士

【摘要】 背景和目的：顺式阿曲库铵是阿曲库铵的1-R构型和1’-R构型的顺式异构体,通过Hofmann降解反应而代谢,并且代谢不受年龄影响,属于中时效神经肌肉阻滞剂。其活性大约是阿曲库铵的四倍,在临床剂量范围内顺式阿曲库铵不会像阿曲库铵那样引起组胺释放,目前被广泛应用于老年患者。循证医学的实践要求临床医师应该常用客观监测量化说明神经肌肉的阻滞程度,如果在手术操作结束时不能客观地证实神经肌肉功能充分恢复(四个成串反应比值即TOF≥0.9),神经肌肉阻滞就必须拮抗。对于长时效和中时效肌肉松弛剂,由于难于判定在手术后是否残存轻微的神经肌肉阻滞作用,因此应常规使用抗胆碱酯酶药物予以拮抗。然而对于老年患者,由于病理生理的特殊改变,什么时间给予何种剂量的新斯的明合适目前还不是很清楚,在本试验中通过观察不同剂量新斯的明在不同时机拮抗老年患者应用顺式阿曲库铵时的肌松残余作用,探讨较佳的拮抗时机和拮抗剂量,使老年患者平稳度过麻醉恢复期,为临床合理安全使用肌松拮抗剂提供理论依据。方法：选择90例择期手术患者,男44例,女46例,年龄65-75岁,体重指数(BMI)在正常范围(18～25kg/m2),ASAⅠ～Ⅱ级,随机分为两组：T1值(TOF中第一个颤搐反应)恢复至10%时给予新斯的明组(T1a组),T1值恢复至25%时给予新斯的明组(T1b组),每组病人45例,每组又按新斯的明不同剂量分为三个亚组(n=15)：T1恢复到10%时给予新斯的明拮抗,新斯的明20μg/kg组(T1aN20组),新斯的明35μg/kg组(T1aN35组),新斯的明50μg/kg组(T1aN50组)；T1恢复到25%时给予新斯的明拮抗,新斯的明20μg/kg组(T1bN20组),35μg/kg组(T1bN35组),50μg/kg组(T1bN50组)。六组患者麻醉用药及麻醉方法相同,六组均以新斯的明：阿托品=2：1剂量伍用阿托品,术毕记录给予新斯的明前即刻,给药后1min、3min、5min、7min、10min、15min时的平均动脉压(MAP)、心率(HR)；四个成串反应比值(TOF)恢复到75%、90%时间。结果：1.患者一般情况,如性别、年龄、体重指数、给予新斯的明前即刻MAP、HR等比较均无统计学意义(p>0.05)。2.血流动力学变化比较各组患者MAP、HR在给予新斯的明阿托品前即刻比较无统计学差异(p>0.05)。在T1a和T1b组中,各亚组给药后1min,3min时间点MAP出现增高；HR出现增快,但20μg/kg和35μg/kg组虽然MAP增高、HR增快,但变化与给药前即刻相比无统计学意义(p>0.05);50μg/kg组MAP增高和HR增快的变化与给药前即刻相比具有统计学意义(p<0.05)。3.TOF恢复指数的比较组内比较：T1aN50组、T1aN35组与T1aN20组比较,TOF恢复到75%和90%时间缩短,且缩短幅度具有统计学意义(p<0.05)；T1aN50组与T1aN35组比较,TOF恢复到75%和90%时间缩短,但缩短幅度无统计学意义(p>0.05)。T1bN50组、T1bN35组与T1bN20组比较,TOF恢复到75%和90%时间缩短,且缩短幅度具有统计学意义(p<0.05)；T1bN50组与T1bN35组比较,TOF恢复到75%和90%时间缩短,但缩短幅度无统计学意义(p>0.05)。组间比较：T1bN20组与T1aN20组比较,TOF恢复到75%和90%时间缩短,且缩短幅度具有统计学意义(p<0.05)；T1bN35组与T1aN35组比较,TOF恢复到75%和90%时间缩短,且缩短幅度具有统计学意义(p<0.05)；T1bN50组与T1aN50组比较,TOF恢复到75%和90%时间缩短,且缩短幅度具有统计学意义(p<0.05)。结论：1.拮抗老年患者顺式阿曲库铵残余肌松作用推荐适宜的新斯的明剂量是35μg/kg(同时以新斯的明：阿托品=2：1剂量伍用阿托品),可以得到较快TOF恢复速度和较稳定的血流动力学变化。2.在T1恢复到25%时给予新斯的明拮抗老年患者顺式阿曲库铵残余肌松作用是较适宜时机。更多还原

【Abstract】 Background and Objective:Cisatracurium is the 1R cis-1’-R cis isomer of atracurim.Cisatracurium is metabolized by Hofmann elimination and is unaffected by age.Cisatracurium is belongs to intermediate-acting muscule relaxants.It is approximately four times as potent as atracurium,and unlike atracurium.it does not cause histamine release in the clinical dose range.It is now widely used in elderly patients.Good evidence-based practice dictates that clinicans should always quantitate the exent of neuromuscular blockade using objective monitoring.If sufficient recovery (train-of-four rate TOF≥0.9)has not been documented objectively at the end of surgical procedure,the neuromuscular block should be antagonized.For all long-time acting and intermediate-acting muscule relaxants,because of the inability to detect subtle neuromuscular blocks clinically and persistence at the end of surgical procedure.The reversal by anticholinesterase drugs should be routine.Since specific changes in the pathophysiology of elderly patients,recommendations regarding the timing and dose of administration of neositigmine remain unclear.The purpose of this experiment is to explore more proper timing and dose of neostigmine by observing the effect of different doses of neostigmine using at different time on antagonizing residual neuromuscular blockade induced by cisatracurium in elderly patients, to make fo the smooth recovery from anesthesia in elderly patients and to provide theoretical basis for the proper use of the neuromuscular blockade antagonists in clinical practice.Method:90 patients scheduled for surgery included 44 males and 46 females, aged 65-75 years with the normal BMI range(18～25kg/m2) and ASAⅠ～Ⅱ. They were randomly divided into 2 groups with 45 cases each and given with neostigmine when T1 had recovered to 10%(T1a group) or 25%(T1b group) respectively. In each group, three subgroup (15 cases each) were given neostigmine 20μg/kg(T1aN20, T1bN20), 35μg/kg(T1aN35, T1bN35), or 50μg/kg (T1aN50, T1bN50) respectively. The cases in six groups were treated with the same anesthetic and anesthesia method.Neostigmine and atropine were administered for the six groups(The ratio of neostigmine and atropine is 1:2,when the surgery was finished, the MAP and HR were recorded at the time before using neostigmine as well as 1 min,3min,5min,7min, 10min,15min after neostigmine respectively. And the time were recorded when TOF had recovered to75% and 90%.Results:1. The patients showed significantly no differences in gender, age, BMI, and the MAP,HR before treated with neostigmine(p>0.05).2. There was no statistical difference in the MAP,HR before all the cases were treated with neostigmine(p>0.05).In the two group T1a and T1b, the HR, MAP were higher than the basic value at the time lmin and 3min after they were given neostigmine.The HR, MAP were higher in the subgroup of 20μg/kg (T1aN20, T1bN20),35μg/kg(T1aN35,T1bN35), but there was no statistical difference in the MAP,HR compared to the level before the cases were treated with neostigmine (p>0.05); And the MAP, HR changes in the subgroup of 50μg/kg showed significantly differences compared to the level before the cases were treated with neostigmine(p<0.05). 3. The comparison of the recovery index of TOF intra-group comparison: Compared to the group of T1aN20, the time of TOF recovering to75% and 90% were shortened in the group of T1aN50 and T1aN35, and there were statistical differences(p<0.05). The time of TOF recovering to 75% and 90% were shorter in the group of T1aN50 than the group of T1aN35, but the changes had no significance; Group comparison:Compared to the group of T1aN2o, TlaN35 and T1aN50, the time of TOF recovering to75% and 90% were shortened in the group of T1bN20, T1bN35 and T1bN50 respectively, and there were all statistical differences(p<0.05).Conclusion:1. The recommend appropriate dose of neostigmine antagonizing residual neuromuscular blockade induced by cisatracurium is 35μg/kg in the elderly patients (the atropine were used compatiblely with neostigmine and the ratio of neostigmine/atropine is 1/2), which could induce the better recovery index of TOF as well as more stable hemodynamic changes.2. The more proper timing to give neostigmine antagonizing residual neuromuscular blockade induced by cisatracurium was the time when T1 had recovered to 25% in the elderly patients.更多还原