【作者】 徐艳；

【导师】 姜春玲；

【作者基本信息】 四川大学 ， 麻醉学（专业学位）， 2021， 硕士

【副题名】一项基于倾向性评分匹配的回顾性队列研究

【摘要】 目的:自1963年全球首例肝移植开展以来,手术结束后保留患者气管导管,转入重症监护病房（Intensive care unit,ICU）继续给予机械通气支持,待患者血流动力学稳定后再拔除气管导管,已成为肝移植术后的常规流程,并被大部分移植中心所采用。然而,机械通气是一把双刃剑,为患者提供呼吸支持的同时,亦通过削弱机体的咳嗽反射和纤毛运动能力,降低黏膜的免疫屏障功能等机制,导致肺部并发症的发生;同时还可通过增加胸内压减少心输出量等机制导致低血压和肾脏灌注不足,诱导急性肾损伤（Acute kidney injury,AKI）的发生,进而与患者术后近期死亡率的增加密切相关。为此,Rossaint团队于1990年首次尝试了在肝移植手术结束后实施手术室内早期拔管,缩短患者术后机械通气时间。随着肝移植手术的不断开展,在手术室内成功实施早期拔管的病例及经验逐渐增多,其安全性也已得到证实;与此同时,有关早期手术室内拔管对患者近期预后影响的研究也渐有报道。然而,大部分研究主要关注的是早期拔管对患者术后肺部并发症的影响,有关其对AKI、30天全因死亡率等其他机械通气相关不良事件的关注较少。因此,本研究旨在通过采用倾向性评分匹配法对组间的混杂因素进行匹配,使组间混杂因素分布尽可能均衡,进而来探索肝移植术后手术室内拔管对患者术后AKI、30天全因死亡率及住院期间中-重度肺部并发症等机械通气相关复合不良事件的影响。通过本研究,有望为肝移植术后早期拔管的进一步推广提供更多的循证医学依据。方法:本研究对2016年1月1日到2019年12月31日期间在四川大学华西医院行肝移植手术的患者的临床数据资料进行回顾性分析。根据术后拔管时间将患者分为手术室拔管组和ICU拔管组。使用包括患者的人口统计学资料、体重指数（Body mass index,BMI）、吸烟史、饮酒史、美国麻醉医师协会（American society of anesthesiologists,ASA）分级、合并症（包括心血管疾病、呼吸系统疾病、卒中、肾功能异常、糖尿病）、终末期肝病的原因、终末期肝病模型（Model for end-stage liver disease,MELD）评分、术前是否需人工肝支持、基础氧饱和度（pulse oxygen saturation,Sp O₂）、术前血常规、术前凝血、术前肝功、手术时间、术中尿量、术中红细胞悬液（Packed red blood cells,PRBC）、术中血管活性药物最大剂量以及术中乳酸最高值等资料作为协变量,按照最邻近匹配法,将手术室拔管组和ICU拔管组患者按1:2的比例进行匹配,卡钳值设为0.2。采用匹配后组间协变量分布均衡的数据,比较两组患者的临床结局指标。主要结局指标是由术后30天全因死亡率、术后住院期间AKI（2期或3期）及术后住院期间中-重度肺部并发症组成的机械通气相关复合不良事件;次要结局指标为术后住院期间中-重度感染性并发症发生率、术后住院时间、ICU住院时间、住院总费用及非计划再插管发生率。本研究同时采用多因素Logistic回归分析对倾向性评分匹配法估计的效应值进行验证。此外,本研究还通过多因素Logistic回归分析,对影响手术室内顺利拔管的因素进行了探索。结果:共有438例患者符合纳入标准,经过倾向性评分匹配后,手术室拔管组有94例患者,ICU拔管组有148例患者;两组患者的基线资料在组间分布均衡（P>0.05）。匹配后,手术室拔管组患者术后机械通气相关复合不良事件的发生率较ICU拔管组低（19.1%vs31.8%;比值比（Odds Ratio,OR）,0.509;95%可信区间（Confidence Interval,CI）,0.274～0.946;P=0.031）。多因素Logistic回归分析也得出了一致的结果,即手术室拔管的患者术后发生机械通气相关复合不良事件的风险,较ICU拔管组患者显著降低（OR,0.514;95%CI,0.270～0.981;P=0.044）。同时,研究发现手术室拔管组患者与ICU拔管组患者相比,ICU住院时间更短（中位数（median,M）4,四分位间距（Interquartile range,IQR）,（3～6）vs M 6,IQR（4～8）;P<0.001）,住院总费用更低（M 2.5 IQR（2.3～3.0）10万元vs M 2.7,IQR（2.5～3.3）10万元;P<0.021）;且手术室拔管组患者术后非计划再插管的发生率,相较于ICU拔管组患者并没有显著增加。但两组患者在术后住院期间中-重度感染性并发症发生率以及术后住院时间上的差异没有显著性（P>0.05）。此外,根据多因素Logistic回归分析结果,本研究得到了7个可作为评估手术室顺利拔管的参考因素,包括MELD评分,术前是否需要人工肝支持,术前血红蛋白水平,手术时间,术中尿量,术中PRBC输注量及最大血管活性药物剂量。结论:1、肝移植术后手术室拔管的患者与ICU拔管的患者相比,术后机械通气相关复合不良事件的发生率更低,术后ICU住院时间更短,住院总费用更低,且手术室拔管并未增加术后非计划再插管的发生率。倾向性评分匹配法估计的结果与多因素Logistic回归分析结果一致。2、通过多因素Logistic回归分析,本研究最后得到了7个潜在的影响肝移植术后手术室内顺利拔管的因素,包括MELD评分,术前是否需要人工肝支持,术前血红蛋白水平,手术时间,术中尿量,术中PRBC输注量及最大血管活性药物剂量,这7个因素均可作为评估手术室早期拔管的参考。更多还原

【Abstract】 Objective:It has become a routine strategy in patients after liver transplantation to retain the endotracheal tube,transfer them to the intensive care unit(ICU)for mechanical ventilation support,and remove the endotracheal tube after their hemodynamics is stable.However,mechanical ventilation is a double-edged sword,which can not only provide respiratory support for patients,but also lead to pulmonary complications by weakening the body’s cough reflex and ciliary movement ability,and reducing the mucosal immune barrier function.Simultaneously,mechanical ventilation can lead to hypotension and renal hypoperfusion by increasing intrathoracic pressure and reducing cardiac output,and eventually induce acute kidney injury(AKI).Therefore,mechanical ventilation is also closely related to the increase of short-term postoperative mortality.Thus,Rossaint et.al,first attempted early extubation in the operating room to shorten the postoperative mechanical ventilation time after liver transplantation in 1990.Since then,the cases and experience of extubation in the operating room have been increasing annually.Meanwhile,the effect of early extubation on the short-term prognosis of patients has been reported.However,most studies mainly focused on the effect of operating room extubation on postoperative pulmonary complications,little is known about its effect on other mechanical ventilation-related adverse events,such as AKI and 30-day all-cause mortality.Therefore,the purpose of the present study is to use the propensity score matching method to match the confounding factors between groups,to make the distribution of confounding factors as balanced as possible,and then to explore the effects of extubation in the operating room on composite mechanical ventilation-related adverse events(including AKI(stage 2 or 3),30-day all-cause mortality and moderate to severe pulmonary complications).The study is expected to provide more evidence-based medical basis for promoting early extubation after liver transplantation.Methods:Patients who underwent liver transplantation between January 2016 and December 2019 at our institution were included.According to the timing of extubation,patients were divided into operating room extubation group and ICU extubation group.The demographic data,body mass index(BMI)index,smoking history,drinking history,American society of anesthesiologists(ASA)classification,comorbidities(including cardiovascular disease,respiratory disease,stroke,renal dysfunction,diabetes),etiology of end-stage liver diseases,model for end-stage liver disease(MELD)score,preoperative artificial liver support,pulse oxygen saturation(Sp O2),preoperative laboratory data(hemoglobin,White blood cells,platelet count,Prothrombin time,activated partial thromboplastin time,international normalized ratio,alanine transaminase,total bilirubin,albumin were collected),duration of surgery,urine output,the volume of packed red blood cells(PRBC)transfused,the maximal dose of vasopressors and the maximal lactate level were used as covariates.Patients in the operating room extubation group and ICU extubation group were matched according to the nearest neighbor matching method 1:2,and the caliper value is 0.2.After matching,data with a balanced distribution of covariates between groups were used to compare the outcomes.The primary outcome was the composite mechanical ventilation-related adverse events,which consisted of 30 days all-cause mortality,in hospital AKI(stage 2 or 3)and moderate to severe pulmonary complications during hospitalization.Secondary outcomes included the moderate to severe infectious complications in-hospital,postoperative hospital and ICU length of stay,total hospital cost,and unplanned reintubation rate.Furthermore,multivariate Logistic regression was used to verify the estimated outcome of propensity score matching.Additionally,we used a multivariable logistic regression model to determine the independent factors that affect operating room extubation.Results:A total of 438 patients were involved.After propensity score matching,94 patients were in the operating room extubation group and 148 patients were in the ICU extubation group,and almost all baseline variables were balanced(P>0.05).The incidence of the composite mechanical ventilation-related adverse events was significantly lower in operating room extubation group than that of ICU extubation group(19.1% vs 31.8%;Odds Ratio [OR],0.509;95% Confidence Interval [CI],0.274～0.946;P=0.031).Not surprisingly,the multivariate logistic regression analysis also yielded consistent results.The risk of mechanical ventilation-related adverse events in patients with extubation in the operating room was significantly lower than that of patients in the ICU extubation group(OR,0.514;95%CI,0.270～0.981;P=0.044).Additionally,the ICU length of stay was much shorter in the operating room extubation group than ICU extubation group(median 4,Interquartile range [IQR](3～6)vs median 6,IQR(4～8);P<0.001).Furthermore,extubation in the operating room led to a significant reduction of total hospital cost compared with extubation in the ICU(median 2.5,IQR(2.3～3.0)100,000 yuan vs median 2.7,IQR(2.5～3.3)100,000 yuan;P<0.001).However,the incidence of unplanned reintubation in the operating room extubation group was not increased.And there was no statistical difference in moderate to severe infectious complications during hospitalization and postoperative hospital length of stay between groups.Moreover,according to multivariate logistic regression analyses,7 factors were independent predictors of operating room extubation,including MELD score,preoperative artificial liver support,preoperative-hemoglobin,duration of surgery,intraoperative urine output,perioperative PRBC transfusion units,and perioperative maximal dose of vasopressors.Conclusion:1.Compared with patients extubated in the ICU,patients who were extubated in the operating room after liver transplantation have a lower incidence of the composite mechanical ventilation-related adverse events,shorter ICU length of stay,and lower total hospital cost,without increasing unplanned reintubation rate.And the results of logistic regression analysis were in line with the matched analysis.2.After multi-factor logistic analysis,seven potential factors affecting successful extubation after liver transplantation were obtained,including MELD score,preoperative artificial liver support,preoperative-hemoglobin,duration of surgery,intraoperative urine output,perioperative PRBC transfusion units,and perioperative maximal dose of vasopressors,which can be used as a reference for evaluating early extubation in the operating room.更多还原