【作者】 张婧；

【导师】 刘华琴；

【作者基本信息】 河北医科大学 ， 麻醉学（专业学位）， 2019， 硕士

【摘要】 目的:夜间泵注右美托咪定对老年肿瘤患者围术期神经认知障碍的影响方法:选择择期行外科手术的肿瘤患者80例,年龄≥65岁,性别不限,ASA分级为Ⅰ或Ⅱ级。心肺功能无中度及以上异常,无头颅手术或外伤史,符合筛选标准,签署知情同意书。每位患者术前一日访视,用睡眠状况自评量表（Self-Rating Scale of Sleep,SRSS）评估患者术前睡眠情况,用认知表格^[1]评估患者术前认知状况,检测血浆皮质醇含量。所有患者均采用静吸复合全身麻醉,且不使用术前药物。患者入手术室后常规建立上肢静脉通路,监测其脉搏氧饱和度（SpO₂）和心电图（ECG）,监测中心静脉压（CVP）和有创动脉压（ABP）。面罩通气下给氧去氮。麻醉诱导:静脉注射舒芬太尼0.2¹.0μg/kg,依托咪酯0.2⁰.3mg/kg,顺式阿曲库铵0.2⁰.3mg/kg,呼吸消失5min后经口明视插入单腔硅胶气管导管（男性7.5#,女性7.0#）,听诊两肺呼吸音一致后固定导管。麻醉维持采用瑞芬太尼和七氟醚静吸复合全身麻醉,瑞芬太尼泵注速度为0.1⁰.3μg?kg^-1?h^-1,七氟醚吸入浓度为1%³%,脑电双频指数（BIS）维持在40⁶0。每30⁴0min静脉追加顺式阿曲库铵0.05mg/kg。手术结束即麻醉结束,恢复自主呼吸且意识清醒可听从指令后拔除气管导管,送回病房。用随机数字表分组,将患者分为4组:安慰剂组,右美托咪定0.1μg?kg^-1?h^-1组（1组）,右美托咪定0.2μg?kg^-1?h^-1组（2组）,右美托咪定0.3μg?kg^-1?h^-1组（3组）。于术日、术后第1日于21:00给与右美托咪定泵注,1组,2组,3组泵注速度分别为0.1、0.2和0.3μg?kg^-1?h^-1,维持泵注至次日晨6:00结束;安慰剂组泵注相同剂量的生理盐水。术后访视:采用视觉模拟评分（VAS）评估患者疼痛情况,确认患者VAS评分0³分。术后第1日、第2日、第7日访视患者睡眠情况。术后第2日、第7日检测血浆皮质醇含量（皮质醇测定时间为上午8点,下午4点）。术后7日访视患者,用认知表格评估患者术后认知情况。记录患者的一般资料,ASA分级,手术时间,以及SRSS睡眠评分,认知表格的结果,患者术后睡眠情况,皮质醇水平。其中认知表格包括:简明精神状态量表（Mini-mental state examination,MMSE）,词语流畅性测试（verbal fluency test,VFT）,数字广度测试（digit span test,DST）,连线测试（trail making test,TMT）和画钟测试（clock drawing test,CDT）。同时设置对照组（C组）,选择同期住院的非手术患者10例纳入C组,患者纳入条件同试验组。由同一名研究者于同一时间点对试验组和对照组患者进行认知功能测试。并记录结果。结果:1.基本情况:4组患者年龄、ASA分级比例、BMI和手术时间比较差异无统计学意义（P>0.05）2.4组患者术后认知障碍发生率比较。安慰剂组出现认知障碍的比例为55%,1组认知障碍比例40%,2组认知障碍比例25%,3组认知障碍比例15%。3组认知情况明显改善,认知障碍比例降低。3.4组患者不同时间点皮质醇的变化经重复测量设计的方差分析析,不同组别间差异有统计学意义（F=3.454,P=0.021）,不同时间点间差别有统计学意义（F=3.621,P=0.032）,组别与时间点间存在交互作用（F=2.505,P=0.025）。进一步分析单独效应,除第一时间点四组差别无统计学意义（P>0.05）,其余各时间点四组差异均有统计学意义（P>0.05）。且随着时间的延长,波动水平逐渐降低。两两比较结果显示除0组与1组无差别外（P=0.696）,2组（P=0.016）、3组（P=0.017）与0组比较有差别,但2组与3组间无差别（P=0.981）,可见随着用药量的增加波动水平逐渐降低,2组用药效果最佳。4.4组患者术前SRSS比较差异无统计学意义（P>0.05）,术后第2日夜间觉醒次数,经重复测量设计的方差分析,不同组别间差异有统计学意义（F=2.888,P=0.041）。两两比较结果显示0组、1组、2组均与3组比较有差别,P分别为0.009、0.026、0.039。右美托咪定用药使术后第2日觉醒次数减少,其中3组觉醒次数明显减少。其余组别,指标无统计学差异（P>0.05）5.夜间输注0.3μg?kg^-1?h^-1的右美托咪定心动过缓发生率明显升高（P=0.026）结论:1.夜间输注0.2、0.3μg?kg^-1·h^-11的右美托咪定均可以有效改善老年肿瘤患者术后睡眠质量,促进皮质醇内分泌昼夜节律的恢复;2.夜间输注0.3μg?kg^-1?h^-1的右美托咪定降低术后转入外科监护病房的老年肿瘤患者围术期神经认知障碍的发生率;3.围术期睡眠-觉醒周期、皮质醇内分泌等近日节律的改善有助于防止老年肿瘤患者术后神经认知障碍的发生;4.夜间输注0.2μg?kg-1?h-1的右美托咪定对术后转入外科监护病房的老年肿瘤患者安全性更优。更多还原

【Abstract】 Objective:To study the effect of nocturnal dexmedetomidine twice postoperatively on perioperative neurocognitive disorders in elderly patients with malignant tumor.Methods:Eighty consecutive eligible and consenting patients with malignant tumor undergoing elective surgery under general anesthesia and postoperatively admitted to surgical monitored ward,American Society of Anesthesiologists physical status I or II,aged 65 yrs or over,were enrolled,whose cardiopulmonary function was not severe abnormal and claimed no history of head surgery or trauma.Patients were divided into 4 groups by random number table:placebo group（group 0）,dexmedetomidine0.1μg?kg^-1?h^-1 group（group 1）,dexmedetomidine 0.2μg?kg^-1?h^-1 group（group2）,dexmedetomidine 0.3μg?kg^-1?h^-1 group（group 3）.Each patient was interviewed on the day before surgery,and the preoperative sleep level was assessed using the Self-Rating Scale of Sleep.The neuropsychological testing was assessed and plasma cortisol concentration were measured preoperatively.All patients underwent combined anesthesia with intravenous inhalation and without preoperative medication.After entering the operation room,an upper limb venous line and right internal jugular venous line were inserted.The pulse oximetry（SpO₂）,electrocardiogram（ECG）,central venous pressure（CVP）and invasive arterial pressure（ABP）were monitored.Then the patient was anesthetized by a rapid induction proceeded by sufentanil（0.2¹μg/kg）,etomidate（0.2⁰.3mg/kg）and cisatracurium（0.2⁰.3mg/kg）,and be intubated with a single-lumen endotracheal tube（7.5#for male and 7.0#for female）.During the maintenance of anesthesia,remifentanil 0.1-0.3μg?kg^-1?h^-11 was continuously administered intravenously and sevoflurane1%-3%was adjusted to keep BIS from 40 to 60.Cisatracurium 0.05mg/kg was given intravenously every 30⁴0 minutes.When the spontaneous breathing was recovered,and the patient could obey the instruction,the tracheal tube was removed and the patient was sent back to the monitored ward.The dexmedetomidine was administered intravenously from 9:00 pm to the following 6:00 am at the surgery day and the first day after surgery at the speed of 0.1,0.2 and 0.3μg?kg^-1?h^-11 in group 1,2 and 3 respectively.The VAS score was used to assess the patient’s pain and the remedy analgesics were used when VAS score was over 3 points.On the first day,the second day and the seventh day after surgery the patient’s sleep quality was evaluated.On the second day and the seventh day after surgery,the plasma concentration of cortisol was measured（measurement time was 8 am,4 pm）.On the 7th day,the neuropsychological testing was assessed again.The patient’s general information and ASA score,operative time was recorded.The SRSS sleep score,as well as the results of the cognitive results,postoperative sleep quality and the concentration of plasm cortisol was recorded.The neuropsychological testings include:Simple Intelligence State Examination（MMSE）,Clock drawing test（CDT）,Trail making test（TMT）,Animal Fluency Experiment（AFT）,Verbal fluency test（VFT）.Ten non-surgical in-patient patients at the same time were selected into group C.Cognitive function tests were performed on the experimental and control patients at the same time by the same investigator.Results:1.Patients’baseline characteristics:there were no significant differences in age,ASA,BMI and operative time among the 4 groups（P>0.05）.2.Among the 4 groups the incidence of cognitive impairment was 55%in group 0,40%in group 1,25%in group 2,and 15%in group 3,respectively.The cognitive function in group 3 was improved significantly（P<0.05）.3.The changes of the concentrations of plasm cortisol in different groups at different time points were analyzed by analysis of variance of repeated measurement design.The changes among groups were statistically difference（F=3.454,P=0.021）.The difference between changes of the concentrations of plasm cortisol at different time points was statistically significant（F=3.621,P=0.032）,there was an interaction between the group and the time point（F=2.505,P=0.025）.The individual effects were further analyzed.There was no significant difference among the four groups except at the first time point（P<0.05）,and in other times,four groups were statistically significant（P>0.05）.And as time goes on,fluctuation gradually decreases.The results of the pairwise comparison showed that there was no difference between the group 0 and the group 1（P=0.696）,while compared with group 0,there is different in the group 2（P=0.016）and in the group 3（P=0.017）,but there was no difference between the group 2 and the group 3（P>0.05）.The data（P=0.981）showed that the fluctuation level gradually decreased with the increase of the dose and there is the best effect in group 2.4.There were no significant differences in preoperative SRSS among the4 groups（P>0.05）.The number of night awakenings on the 2nd day after surgery was analyzed by repeated measures design.The difference between the groups was statistically significant（F=2.888,P=0.041）.The results of the pairwise comparison showed that the group 0,the group 1,and the group 2were all different from the group 3,and P was 0.009,0.026 and 0.039,respectively.The use of dexmedetomidine reduced the number of awakenings on the second day after surgery,that in the third group was significantly reduced.There were no statistical differences in the other groups and indications（P>0.05）.5.Compared with the other three groups,the incidence of bradycardia in group 3 increased significantly（P<0.05）.Conclusion:1.Nocturnal intravenous dexmedetomidine(0.2,0.3μg·kg^-1·h^-1)can effectively improve the postoperative sleep quality of elderly patients with malignant tumors,enhance the circadian rhythm recovery of cortisol endocrine;2.Nocturnal intravenous dexmedetomidine(0.3μg·kg^-1·h^-1)significantly reduce incidence of perioperative neurocognitive disorders in elderly patients with malignant tumors who were transferred to the surgical monitored ward.3.Perioperative sleep-wake cycle,cortisol endocrine and other recent rhythms can help prevent postoperative neurocognitive impairment in elderly patients with malignant tumors.4.It is safer to administer dexmedetomidine(0.2μg·kg^-1·h^-1)at nigthtime twice postoperatively for the elderly patients with malignant tumors who were transferred to the surgical monitored ward..更多还原