血尿素氮與白蛋白比值與膿毒癥合并急性呼吸衰竭患者死亡的相關(guān)性分析

管曉月，原夢(mèng)，鐘磊，閔婕，周慶

血尿素氮與白蛋白比值與膿毒癥合并急性呼吸衰竭患者死亡的相關(guān)性分析

管曉月1，原夢(mèng)2，鐘磊2，閔婕2，周慶2

1.湖州市中心醫(yī)院醫(yī)院感染管理部，浙江湖州 313000；2.湖州市中心醫(yī)院重癥醫(yī)學(xué)科，浙江湖州 313000

探討血尿素氮與白蛋白比值（blood urea nitrogen to albumin ratio，B/A）與膿毒癥合并急性呼吸衰竭（acute respiratory failure，ARF）患者住院期間死亡的相關(guān)性?；仡櫺苑治雒绹?guó)重癥醫(yī)學(xué)數(shù)據(jù)庫(kù)Ⅳ中2008～2019年重癥監(jiān)護(hù)病房（intensive care unit，ICU）的膿毒癥合并ARF患者3806例的臨床資料，根據(jù)住院30d內(nèi)結(jié)局將其分為存活組（=2677）和死亡組（=1129）。使用Kaplan-Meier法和log-rank檢驗(yàn)評(píng)價(jià)生存風(fēng)險(xiǎn)，Cox比例風(fēng)險(xiǎn)回歸分析探討膿毒癥合并ARF患者住院期間死亡的危險(xiǎn)因素。死亡組患者的年齡顯著大于存活組，序貫器官衰竭評(píng)估評(píng)分、血尿素氮、B/A、陰離子間隙、白細(xì)胞、血肌酐及連續(xù)性腎臟替代治療、機(jī)械通氣、合并慢性腎臟病、急性腎損傷、心臟驟停和急性心肌梗死的比例均顯著高于存活組，白蛋白、紅細(xì)胞、血小板均顯著低于存活組，總住院時(shí)間顯著短于存活組（<0.05）。生存曲線顯示，隨著B(niǎo)/A的上升，患者住院期間累積生存率逐漸降低（2=82.700，<0.001）。多因素Cox回歸分析顯示，B/A>4.34是膿毒癥合并ARF患者住院期間死亡的獨(dú)立危險(xiǎn)因素（=1.450，95%1.208～1.742，<0.001）。入住ICU時(shí)B/A>4.34是膿毒癥合并ARF患者住院期間死亡的獨(dú)立危險(xiǎn)因素，早期識(shí)別并及時(shí)干預(yù)有助于降低膿毒癥合并ARF患者的死亡風(fēng)險(xiǎn)。

血尿素氮與白蛋白比值；膿毒癥；急性呼吸衰竭；全因死亡率

在中國(guó)，每年有數(shù)以百萬(wàn)人罹患膿毒癥，多年來(lái)其發(fā)病率居高不下，是患者入住重癥監(jiān)護(hù)病房（intensive care unit，ICU）的主要病因之一[1]。膿毒癥病情發(fā)展迅速，如未能及時(shí)干預(yù)可迅速出現(xiàn)休克、器官衰竭等情況，病死率高達(dá)35%～40%，是僅次于心臟疾病的重癥患者死亡原因[2]。膿毒癥患者中最重要的感染源為肺部感染，約占64%[3]。血尿素氮（blood urea nitrogen，BUN）和血清白蛋白（albumin，Alb）均是簡(jiǎn)單易得的生化指標(biāo)。研究顯示，BUN與Alb比值（B/A）對(duì)重癥肺炎等疾病的預(yù)后有一定預(yù)測(cè)價(jià)值[4]，但其對(duì)伴有急性呼吸衰竭（acute respiratory failure，ARF）的膿毒癥患者的預(yù)后是否同樣具有預(yù)測(cè)作用暫無(wú)研究數(shù)據(jù)。為此，本研究擬探討入住ICU時(shí)B/A對(duì)伴有ARF的膿毒癥患者預(yù)后的預(yù)測(cè)價(jià)值，為臨床及護(hù)理工作提供參考。

1 資料與方法

1.1 研究對(duì)象

本研究從美國(guó)重癥醫(yī)學(xué)數(shù)據(jù)庫(kù)Ⅳ（Medical Information Mart for Intensive Care Ⅳ，MIMIC-Ⅳ）中提取數(shù)據(jù)，采用國(guó)際疾病分類編碼（ICD-9和ICD-10）中膿毒癥及急性呼吸衰竭的診斷編碼在數(shù)據(jù)庫(kù)中進(jìn)行檢索，從而獲得所需研究對(duì)象。診斷標(biāo)準(zhǔn)符合2016年提出的膿毒癥和感染性休克的第三次國(guó)際共識(shí)定義（Sepsis 3.0）[5]。

1.2 研究方法

通過(guò)PostgreSQL軟件進(jìn)入MIMIC-Ⅳ數(shù)據(jù)庫(kù)，提取2008～2019年的所需研究資料。納入標(biāo)準(zhǔn)：①首次在ICU住院；②年齡≥18歲；③膿毒癥合并ARF患者。排除標(biāo)準(zhǔn)：①ICU住院時(shí)間<2d；②總住院時(shí)間>30d；③BUN、Alb等關(guān)鍵數(shù)值缺失。以患者總住院期間全因死亡率作為臨床終點(diǎn)指標(biāo)，將患者分為存活組和死亡組。依據(jù)三分位數(shù)法將B/A分為<2.16（=1272）、2.16～4.34（=1269）和>4.34（=1265）三組。

1.3 統(tǒng)計(jì)學(xué)方法

2 結(jié)果

2.1 兩組患者的臨床資料比較

本研究共納入3806例患者，其中存活組2677例，死亡組1129例。死亡組患者的年齡顯著大于存活組，序貫器官衰竭評(píng)估（sequential organ failure assessment，SOFA）評(píng)分、BUN、B/A、陰離子間隙、白細(xì)胞、血肌酐及連續(xù)性腎臟替代治療、機(jī)械通氣、合并慢性腎臟病、急性腎損傷、心臟驟停和急性心肌梗死的比例均顯著高于存活組，Alb、紅細(xì)胞、血小板均顯著低于存活組，總住院時(shí)間顯著短于存活組（<0.05），見(jiàn)表1。

表1 兩組患者的臨床資料比較

續(xù)表1

注：1mmHg=0.133kPa

表2 膿毒癥合并ARF患者住院期間預(yù)后情況Cox回歸分析

注：模型1未控制任何因子；模型2控制了年齡、SOFA評(píng)分、陰離子間隙、動(dòng)脈血氧分壓、白細(xì)胞、紅細(xì)胞、血小板、肌酐、連續(xù)性腎臟

替代治療、機(jī)械通氣、慢性腎臟病、心臟驟停、急性心肌梗死和急性腎損傷等因子

2.2 Kaplan-Meier生存曲線分析

Kaplan-Meier生存曲線顯示，隨著B(niǎo)/A的上升，患者住院期間累積生存率逐漸降低，log-rank檢驗(yàn)差異有統(tǒng)計(jì)學(xué)意義（2=82.700，<0.001），見(jiàn)圖1。

圖1 三組患者住院期間累積生存率比較

2.3 Cox回歸分析

單因素Cox回歸分析（模型1）顯示，高B/A特別是當(dāng)B/A>4.34時(shí)患者死亡風(fēng)險(xiǎn)明顯增高，差異有統(tǒng)計(jì)學(xué)意義（<0.05）。多因素Cox回歸分析（模型2）顯示，B/A>4.34是膿毒癥合并ARF患者住院期間死亡的獨(dú)立危險(xiǎn)因素（=1.450，95%1.208～1.742，<0.001），見(jiàn)表2。

3 討論

膿毒癥是一種由感染引起的全身反應(yīng)失調(diào)及器官功能障礙綜合征，其特點(diǎn)是嚴(yán)重的循環(huán)及代謝失調(diào)[5]。當(dāng)發(fā)生感染時(shí)，免疫系統(tǒng)會(huì)對(duì)感染進(jìn)行識(shí)別，同時(shí)激活相應(yīng)的促炎和抗炎途徑，產(chǎn)生細(xì)胞因子[6]，而膿毒癥則是促炎和抗炎途徑不協(xié)調(diào)所導(dǎo)致的“細(xì)胞因子風(fēng)暴”，造成病理性的血管擴(kuò)張及通透性增加，使心、肺、腎等重要器官灌注不足，導(dǎo)致多臟器功能衰竭[7]。血管通透性增加直接導(dǎo)致Alb流向組織間隙，感染應(yīng)激使Alb與其他物質(zhì)結(jié)合避免過(guò)氧化，Kendall等[8]研究發(fā)現(xiàn)入院時(shí)低Alb是膿毒癥嚴(yán)重程度的獨(dú)立危險(xiǎn)因素。BUN主要在腎臟代謝，當(dāng)膿毒癥患者存在急性腎損傷時(shí)BUN排泄障礙，隨著B(niǎo)UN升高，膿毒癥患者病死率明顯增加[9]。既往研究已證實(shí)B/A在腹部感染導(dǎo)致的大腸桿菌菌血癥預(yù)后預(yù)測(cè)方面有一定價(jià)值[10]；在其他部位感染相關(guān)的膿毒癥目前尚未發(fā)現(xiàn)相關(guān)研究數(shù)據(jù)。

肺部感染作為膿毒癥最常見(jiàn)的病因，其感染本身足以導(dǎo)致急性肺功能損害[11]，另外其他部位感染所致的膿毒癥使機(jī)體產(chǎn)生的免疫因子也會(huì)導(dǎo)致急性呼吸窘迫綜合征，多種原因均促使患者低氧性呼吸衰竭癥狀的逐步加重[12-13]。這也導(dǎo)致大部分膿毒癥患者入住ICU時(shí)已存在不同程度的呼吸衰竭，且大部分需要機(jī)械通氣治療[14-15]。機(jī)械通氣治療帶來(lái)獲益的同時(shí)也伴隨著一些風(fēng)險(xiǎn)，如呼吸機(jī)致肺部損傷、呼吸機(jī)相關(guān)性肺炎等[16]，可能延長(zhǎng)住院時(shí)間或在原發(fā)疾病基礎(chǔ)上再一次造成致命打擊。既往研究致力于膿毒癥患者發(fā)生呼吸衰竭時(shí)利用更優(yōu)化的機(jī)械通氣治療方案，對(duì)其肺部進(jìn)行保護(hù)性通氣等方式以保護(hù)肺功能、減少肺損傷[6,14]。但已有研究指出，醫(yī)院獲得性膿毒癥在所有住院的膿毒癥患者中占有相當(dāng)大的比例，約接近總體的1/4[17]。對(duì)早期膿毒癥或院內(nèi)獲得性膿毒癥患者，早期識(shí)別和發(fā)現(xiàn)并加以干預(yù)可在一定程度上阻止病情進(jìn)展。B/A作為社區(qū)和醫(yī)院獲得性肺炎患者住院期間死亡的預(yù)測(cè)因子[18-19]，與膿毒癥間存在一定的聯(lián)系。本研究通過(guò)對(duì)MIMIC-Ⅳ中合并ARF的膿毒癥患者的相關(guān)數(shù)據(jù)進(jìn)行分析，發(fā)現(xiàn)與存活組相比，死亡組患者各臟器所遭受的打擊更嚴(yán)重，且B/A明顯升高。通過(guò)生存曲線發(fā)現(xiàn)，隨著B(niǎo)/A的上升，患者住院期間累積生存率逐漸降低。多因素Cox回歸分析顯示B/A>4.34是合并ARF的膿毒癥患者死亡的獨(dú)立危險(xiǎn)因素。

綜上，入院時(shí)B/A水平是合并ARF的膿毒癥患者住院期間死亡的預(yù)測(cè)因子，可通過(guò)B/A對(duì)預(yù)后進(jìn)行初步判斷，對(duì)入住ICU患者膿毒癥進(jìn)行早期預(yù)警，從而進(jìn)行更積極的干預(yù)，幫助改善患者最終預(yù)后。但本研究相關(guān)數(shù)據(jù)均來(lái)自于國(guó)外數(shù)據(jù)庫(kù)，未來(lái)應(yīng)在國(guó)內(nèi)進(jìn)一步研究，以提供更加有力的證據(jù)。

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Correlation analysis of blood urea nitrogen to albumin ratio and mortality in sepsis patients with acute respiratory failure

GUAN Xiaoyue, YUAN Meng, ZHONG Lei, MIN Jie, ZHOU Qing

1.Department of Infection Management, Huzhou Central Hospital, Huzhou 313000, Zhejiang, China; 2.Department of Intensive Care Unit, Huzhou Central Hospital, Huzhou 313000, Zhejiang, China

To investigate the correlation between blood urea nitrogen to albumin ratio (B/A) and in-hospital death in patients with acute respiratory failure (ARF) caused by sepsis.The clinical data of 3806 patients with sepsis complicated with ARF admitted to intensive care unit (ICU) from 2008 to 2019 in the United States Medical Information Mart for Intensive Care Ⅳ were retrospectively analyzed. According to the outcome within 30 days of hospitalization, they were divided into survival group (=2677) and death group (=1129). Kaplan-Meier test and log-rank test were used to evaluate the survival risk. Cox proportional risk regression analysis was used to investigate the risk factors of in-hospital death in patients with sepsis and ARF.Patients in death group were significantly older than those in survival group, sequential organ failure assessment score, blood urea nitrogen, B/A, anion gap, leukocyte, serum creatinine and the rates of continuous renal replacement therapy, mechanical ventilation, combined chronic kidney disease, acute kidney injury, cardiac arrest and acute myocardial infarction were significantly higher than those in survival group, albumin, erythrocyte and platelet were significantly lower than those in survival group, and the total hospital stay was significantly shorter than that in survival group (<0.05). The survival curve showed that with the increase of B/A, the cumulative survival rate decreased gradually during hospitalization (2=82.700,<0.001). Multivariate Cox regression analysis showed that B/A>4.34 was an independent risk factor for in-hospital death in patients with sepsis and ARF (=1.450，95%1.208～1.742,<0.001).B/A>4.34 at ICU admission is an independent risk factor for death during hospitalization in patients with sepsis and ARF. Early identification and timely intervention can help reduce the risk of death in patients with sepsis and ARF.

Blood urea nitrogen to albumin ratio; Sepsis; Acute respiratory failure; All-cause mortality

R631; R563.8

A

10.3969/j.issn.1673-9701.2023.07.004

浙江省醫(yī)藥衛(wèi)生科技計(jì)劃項(xiàng)目（2022KY1222）；湖州市科技計(jì)劃項(xiàng)目（2019GYB10）

周慶，電子信箱：49394121@qq.com.

（2022–09–15）

（2023–01–31）