北京地区脓毒症合并急性肾损伤重症患者的多中心临床研究——发病率、临床特征和结局

A multicenter clinical study of critically ill patients with sepsis complicated with acute kidney injury in Beijing: incidence, clinical characteristics and outcomes

目的探讨北京地区脓毒症合并急性肾损伤(AKI)重症监护病房(ICU)患者的流行病学特点和预后,分析危重患者院内死亡的相关危险因素。方法基于北京急性肾损伤课题组(BAKIT)数据库,收集2012年3月1日至8月31日北京地区28家三级医院30个ICU连续收治的9049例患者的临床资料。根据有无AKI或脓毒症将患者分为无AKI无脓毒症组、有AKI无脓毒症组、无AKI有脓毒症组、有AKI有脓毒症组。记录各组患者的临床数据,包括人口学特征、入ICU主要原因、伴随疾病、入ICU 24 h内序贯器官衰竭评分(SOFA)和急性生理学与慢性健康状况评分Ⅱ(APACHEⅡ)、生理学与实验室指标、ICU住院期间治疗情况、基于改善全球肾脏病预后组织(KDIGO)的AKI分期,以及ICU住院时间、总住院时间、ICU和院内病死率等预后指标。观察终点为出院或院内死亡。采用多因素Logistic回归分析探讨影响ICU患者院内死亡的危险因素;绘制Kaplan-Meier生存曲线分析ICU患者住院期间累积生存情况。结果最终纳入3107例重症患者,其中无AKI无脓毒症组1259例、有AKI无脓毒症组931例、无AKI有脓毒症组264例、有AKI有脓毒症组653例。与其他3组比较,有AKI有脓毒症组患者的年龄更大,平均动脉压(MAP)更低,APACHEⅡ评分、SOFA评分、血尿素氮(BUN)和血肌酐(SCr)水平及接受机械通气、血管活性药物、肾脏替代治疗(RRT)的比例更高(均P<0.01)。3107例患者中有1584例(51.0%)诊断为AKI,且脓毒症患者AKI发生率明显高于无脓毒症患者〔71.2%(653/917)比42.5%(931/2190),P<0.01〕。无脓毒症患者中KDIGO 0期人群占比最高(57.5%),脓毒症患者中,KDIGO 3期人群占比最高(32.2%)。在同一KDIGO分期中,脓毒症患者的院内病死率明显高于无脓毒症患者〔0期:17.8%比3.1%,1期:36.3%比7.4%,2期:42.7%比17.1%,3期:54.6%比28.6%,AKI:46.1%比14.2%,均P<0.01〕。有AKI有脓毒症组患者的ICU病死率(38.7%)和院内病死率(46.1%)明显高于其他3组(均P<0.01)。Kaplan-Meier生存曲线进一步显示,有AKI有脓毒症组患者的住院期间累积生存率显著低于无AKI无脓毒症组、有AKI无脓毒症组和无AKI有脓毒症组(53.9%比96.9%、85.8%、82.2%,Log-Rank:χ2=379.901,P<0.001)。亚组分析显示,存活患者中,有AKI有脓毒症组患者的ICU住院时间和总住院时间明显高于其他3组(均P<0.01)。多因素回归分析显示,年龄、入ICU 24 h内APACHEⅡ评分和SOFA评分、冠心病、AKI、脓毒症、脓毒症合并AKI是ICU患者院内死亡的独立危险因素(均P<0.05);校正协变量后,AKI、脓毒症、脓毒症合并AKI均与较高的ICU病死率和院内病死率显著相关,而脓毒症合并AKI患者的ICU病死率〔校正优势比(OR)=14.82,95%可信区间(95%CI)为8.10~27.12;Hosmer-Lemeshow检验:P=0.816〕和院内病死率(校正OR=7.40,95%CI为4.94~11.08;Hosmer-Lemeshow检验:P=0.708)均最高。结论脓毒症患者的AKI发病率高,脓毒症合并AKI患者的疾病负担更高,生理学和实验室指标异常情况更多,且ICU病死率和院内病死率明显增高。存活患者中,脓毒症合并AKI患者的ICU住院时间和总住院时间也更长。年龄、入ICU 24 h内APACHEⅡ评分、SOFA评分、冠心病、AKI及脓毒症是ICU患者院内死亡的独立危险因素。

Objective To investigate the epidemiological characteristics and prognosis of critically ill patients with sepsis combined with acute kidney injury(AKI)in intensive care unit(ICU)in Beijing,and to analyze the risk factors associated with in-hospital mortality among these critically ill patients.Methods Data were collected from the Beijing AKI Trial(BAKIT)database,including 9049 patients consecutively admitted to 30 ICUs in 28 tertiary hospitals in Beijing from March 1 to August 31,2012.Patients were divided into non-AKI and non-sepsis group,AKI and non-sepsis group,non-AKI and sepsis group,AKI and sepsis group.Clinical data recorded included demographic characteristics,primary reasons for ICU admission,comorbidities,sequential organ failure assessment(SOFA),acute physiology and chronic health evaluationⅡ(APACHEⅡ)within 24 hours of ICU admission,physiological and laboratory indexes,treatment in the ICU,AKI staging based on the Kidney Disease:Improving Global Outcomes(KDIGO),as well as the prognostic indicators including length of stay in ICU,length of stay in hospital,ICU and in-hospital mortality.The primary endpoint was discharge or in-hospital death.Multivariate Logistic regression analysis was used to investigate the risk factors for hospital death in ICU patients.Kaplan-Meier survival curve was drawn to analyze the cumulative survival of ICU patients during hospitalization.Results A total of 3107 critically ill patients were ultimately enrolled,including 1259 cases in the non-AKI and non-sepsis group,931 cases in the AKI and non-sepsis group,264 cases in the non-AKI and sepsis groups,and 653 cases in the AKI and sepsis group.Compared with the other three group,patients in the AKI and sepsis group were the oldest,had the lowest mean arterial pressure(MAP),and the highest APACHEⅡscore,SOFA score,blood urea nitrogen(BUN),and serum creatinine(SCr)levels,and they also had the highest proportion of receiving mechanical ventilation,requiring vasopressor support,and undergoing renal replacement therapy(RRT),all P<0.01.Of these 3107 patients,1584(51.0%)were diagnosed with AKI,and the incidence of AKI in patients with sepsis was significantly higher than in those without sepsis[71.2%(653/917)vs.42.5%(931/2190),P<0.01].The highest proportion of KDIGO 0 stage was observed in the non-sepsis group(57.5%),while the highest proportion of KDIGO 3 stage was observed in the sepsis group(32.2%).Within the same KDIGO stage,the mortality of patients with sepsis was significantly higher than that of non-sepsis patients(0 stage:17.8%vs.3.1%,1 stage:36.3%vs.7.4%,2 stage:42.7%vs.17.1%,3 stage:54.6%vs.28.6%,AKI:46.1%vs.14.2%).The ICU mortality(38.7%)and in-hospital mortality(46.1%)in the AKI and sepsis group were significantly higher than those in the other three groups.Kaplan-Meier survival curves further showed that the cumulative survival rate of patients with AKI and sepsis during hospitalization was significantly lower than that of the other three groups(53.9%vs.96.9%,85.8%,82.2%,Log-Rank:χ2=379.901,P<0.001).Subgroup analysis showed that among surviving patients,length of ICU stay and total length of hospital stay were significantly longer in the AKI and sepsis group than those in the other three groups(both P<0.01).Multivariate regression analysis showed that age,APACHEⅡscore and SOFA score within 24 hours of ICU admission,coronary heart disease,AKI,sepsis,and AKI combined with sepsis were independent risk factors for ICU mortality in patients(all P<0.05).After adjusting for covariates,AKI,sepsis,and sepsis combined with AKI were significantly associated with higher ICU and in-hospital mortality,with the highest ICU mortality[adjusted odds ratio(OR)=14.82,95%confidence interval(95%CI)was 8.10-27.12;Hosmer-Lemeshow test:P=0.816]and in-hospital mortality(adjusted OR=7.40,95%CI was 4.94-11.08;Hosmer-Lemeshow test:P=0.708)observed in patients with sepsis combined with AKI.Conclusions The incidence of AKI is high in sepsis patients,and those with both AKI and sepsis have a higher disease burden,more abnormalities in physiological and laboratory indicators,and significantly increased ICU and in-hospital mortality.Among surviving patients,the length of ICU stay and total length of hospital stay are also longer in the AKI and sepsis group.Age,APACHEⅡscore and SOFA score within 24 hours of ICU admission,coronary heart disease,AKI,and sepsis are independent risk factors for in-hospital mortality in ICU patients.