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肺叶切除术中尿量对术后AKI的影响探析

时间:2020-12-29作者:孟昭婷 穆东亮
本文导读:这是一篇关于肺叶切除术中尿量对术后AKI的影响探析的文章,急性肾损伤(acute kidney injury, AKI)是围术期常见并发症,根据手术类型的不同,其发生率为5%~30%,其中胸外科手术围术期AKI发生率仅次于心脏手术和普外科手术。

  摘    要: 目的:探索术中尿量对术后急性肾损伤(acute kidney injury, AKI)的影响,以及术后AKI发生的独立危险因素。方法:选择2017年7月至2019年6月于北京大学第一医院在全身麻醉下接受择期肺叶切除术的患者作为研究对象进行回顾性队列研究。将入组患者按照是否发生术后AKI分为AKI组和对照组。首先对围术期各变量进行单因素分析,探讨其与术后AKI的关系;其次,采用受试者工作特征曲线(receiver operating characteristic curve,ROC curve)分析术中尿量对术后AKI的预测价值,并以约登(Youden)指数为最大值时的上下4个界值[以0.1 mL/(kg?h)为间隔]为少尿界值,采用单因素分析探索各界值定义下的少尿与AKI发生风险的关系,并取OR值最大者为少尿界值;最后,将单因素分析中P<0.10的围术期各变量共同代入多因素Logistic回归模型,分析术后AKI的独立危险因素。结果:共1 393名患者最终纳入研究,术后AKI发生率为2.2%。ROC曲线显示术中单位尿量用于预测术后AKI的曲线下面积为0.636(P=0.009),约登指数为最大值时(约登指数0.234,敏感度48.4%,特异度75.0%)的少尿界值为0.785 mL/(kg?h)。进一步取0.7、0.8、0.9、1.0 mL/(kg?h)以及传统界值0.5 mL/(kg?h)为少尿界值分析少尿对术后AKI的影响。单因素分析显示,以小于0.8 mL/(kg?h)为少尿界值时,少尿患者发生AKI的风险增加最为显着(OR=2.774, 95%CI 1.357~5.671, P=0.004)。多因素回归分析显示术中尿量<0.8 mL/(kg?h)(OR=2.698,95%CI 1.260~5.778, P=0.011)是术后AKI发生的独立危险因素,另两个独立危险因素为术前血红蛋白≤120.0 g/L(OR=3.605, 95%CI 1.545~8.412, P=0.003)以及术前估计肾小球滤过率<30 mL/(min?1.73 m2)(OR=11.009, 95%CI 1.813~66.843, P=0.009)。结论:对于肺叶切除术,术中少尿是术后AKI发生的独立危险因素,且尿量<0.8 mL/(kg?h)是可能的筛选标准。

  关键词: 肺叶切除术; 少尿; 急性肾损伤;

  Abstract: Objective: To explore the influence of intraoperative urine volume on postoperative acute kidney injury (AKI) and the independent risk factors of AKI. Method: This was a retrospective cohort study recruiting patients who received selective pulmonary resection under general anesthesia in Peking University First Hospital from July, 2017 to June, 2019. The patients were pided into the AKI grouPand the control group according to whether they developed postoperative AKI ORnot. Firstly, Univariate analysis was used to analyze the relationshiPbetween perioperative variables and postoperative AKI. Secondly, receiver operating characteristic (ROC) curve was used to explore the predictive value of intraoperative urine output fORpostoperative AKI. The nearest four cutoff values [with the interval of 0.1 mL/(kg?h)] at maximum Youden index were used as cutoff values of oliguria. Then univariate analysis was used to explore the relationshiPbetween oliguria defined by these four cutoff values and the risk of AKI. And the cutoff value with maximum ORwas chosen as the threshold of oliguria in this study. Lastly, the variables with P<0.10 in the univariate analysis were selected fORinclusion in a multivariate logistic model to analyze the independent predictors of postoperative AKI. Results: A total of 1 393 patients were enrolled in the study. The incidence of postoperative AKI was 2.2%. ROC curve analysis showed that area under curve (AUC) of intraoperative urine volume used fORpredicting postoperative AKI was 0.636 (P=0.009), and the cutoff value of oliguria was 0.785 mL/(kg?h) when Youden index was maximum (Youden index =0.234, sensitivity =48.4%, specificity =75.0%). Furthermore, 0.7, 0.8, 0.9, 1.0 mL/(kg?h) and the traditional cutoff value of 0.5 mL/(kg?h) were used to analyze the influence of oliguria on postoperative AKI. Univariate analysis showed that, when 0.8 mL/(kg?h) was selected as the threshold of oliguria, patients with oliguria had the most significantly increased risk of AKI (AKI group 48.4% vs. control group 25.3%, OR=2.774, 95%CI 1.357-5.671, P=0.004). Multivariate regression analysis showed that intraoperative urine output <0.8 mL/(kg?h) was one of the independent risk factors of postoperative AKI (OR=2.698,95%CI 1.260-5.778, P=0.011). The other two were preoperative hemoglobin ≤120.0 g/L (OR=3.605, 95%CI 1.545-8.412, P=0.003) and preoperative estimated glomerular filtration rate <30 mL/(min?1.73 m2) (OR=11.009, 95%CI 1.813-66.843, P=0.009). Conclusion: Oliguria is an independent risk factORof postoperative AKI after pulmonary resection, and urine volume <0.8 mL/(kg?h) is a possible screening criteria.

  Keyword: Pulmonary lobectomy; Oliguria; Acute kidney injury;
 

肺叶切除术中尿量对术后AKI的影响探析
 

  急性肾损伤(acute kidney injury, AKI)是围术期常见并发症,根据手术类型的不同,其发生率为5%~30%[1,2,3],其中胸外科手术围术期AKI发生率仅次于心脏手术和普外科手术[4]。有研究显示,肺癌手术后AKI发生率约为3%~9%[5]。AKI的发生及其严重程度与患者不良预后独立相关,可能造成患者并发症发病率及病死率增加、住院时间延长、医疗花费增加[2,3,6]。但是,围术期AKI的发生却常被忽视[7]。术中尿量被视为反映器官灌注情况的重要指标之一。灌注不足是导致围术期少尿的主要原因,主要是与麻醉和手术引起的有效循环血量不足和低灌注压有关。尽管少尿被认为是AKI发生的重要标志,但是关于术中少尿的定义仍不清楚[8]。多数研究采用尿量小于0.5 mL/(kg?h)作为术中少尿的标准[9],但是关于不同手术人群的研究显示该指标的敏感性较差,不同术式应采用不同的诊断界值,如关于体外循环下心脏手术患者的研究显示术中尿量小于1.5 mL/(kg?h)与AKI密切相关[10];而关于腹部外科手术的研究显示术中尿量小于0.3 mL/(kg?h)与AKI密切相关[11]。限制性液体管理策略可以显着降低术后急性肺损伤发生风险,因此被广泛应用于围术期管理[12],但这可能加重有效循环容量不足,增加术中少尿和术后AKI的发生风险。而尿量还受交感张力、醛固酮和抗利尿激素分泌等多种因素的影响,因此术中少尿并不总是意味着术后AKI的发生[4,13]。分析何种程度的术中少尿与术后AKI发生相关不仅可以帮助医护人员早期识别AKI发生的倾向,还可以提示治疗措施对肾功能恢复的效果。本研究旨在通过队列研究探索接受肺叶切除术的患者术中尿量对术后AKI的影响,以及术后AKI发生的独立危险因素。

  1 、材料与方法

  本研究为回顾性队列研究,研究方案获得北京大学第一医院伦理委员会批准(批准号2019[161])。所有数据均从病历资料中获得,经伦理委员会同意免除患者知情同意,涉及患者个人隐私的信息均严格保密。

  1.1、研究对象

  选择2017年7月至2019年6月于北京大学第一医院在全身麻醉下接受择期全肺、肺叶或肺叶部分切除术的患者作为研究对象进行回顾性队列研究。病例排除标准:(1)年龄小于18岁;(2)术前合并有终末期肾病[即估计肾小球滤过率estimated glomerular filtration rate, eGFR<15 mL/(min?1.73 m2)或接受透析治疗,eGFR根据慢性肾病流行病学合作研究组肌酐方程进行计算[14]];(3)同时行心脏或泌尿外科手术;(4)术中使用利尿药(呋塞米或甘露醇);(5)术后7 d内行二次手术。。

  1.2、AKI定义

  根据改善全球肾病预后组织(Kidney Disease: Improving Global Outcomes, KDIGO)指南,AKI被定义为术后48 h内血肌酐值升高26.5 μmol/L,或术后7 d内血肌酐值升高到基础值的1.5倍,术前最后一次血肌酐值被视为基础值。AKI的KDIGO分级标准为:1级,血肌酐值升高≥26.5 μmol/L或升高1.5~1.9倍;2级,血肌酐值升高2.0~2.9倍;3级,血肌酐值升高≥3倍或升高≥353.6 μmol/L,或需要启动肾替代治疗,或患者<18岁eGFR降低至<35 mL/(min?1.73 m2)。

  1.3、资料收集和病例分组

  首先通过麻醉信息系统查找于上述时间内在全身麻醉下接受择期肺叶切除术的患者,然后利用电子病案查询系统完善资料收集。术前基础资料包括人口学资料(性别、年龄、身高、体质量)、入院诊断、既往病史、化验检查结果、用药及手术治疗史;术中资料包括手术类型、手术风险、手术时间、麻醉方法、麻醉时间、术中液体出入量、低血压及低氧饱和度发生情况、升压药及麻醉药使用情况等;术后资料包括术后48 h内及7 d内血肌酐水平最高值以及是否需要肾替代治疗。术中液体单位入量是术中液体总入量除以患者体质量,再除以麻醉时间所得的计算结果,而术中单位尿量则是术中总尿量除以患者体质量,再除以麻醉时间所得的计算结果,均以mL/(kg?h)为单位。根据是否发生术后AKI,将患者分为AKI组和对照组。

  1.4、统计学分析

  采用SPSS 19.0软件,将入组患者按照是否发生AKI分为AKI组和对照组进行分析,计量资料以平均值±标准差或中位数(四分位间距)表示,组间比较采用t检验或Mann-Whitney U检验。计数资料及等级资料以例数(%)表示,计数资料组间比较采用卡方检验或Fisher精确检验,等级资料组间比较采用趋势卡方检验。使用受试者工作特征曲线(receiver operating characteristic curve,ROC curve)分析术中尿量对术后AKI的预测价值,以约登指数为最大值时的上下4个界值[以0.1 mL/(kg?h)为间隔]为少尿界值,采用单因素分析探索各界值定义下的少尿与AKI发生风险的关系,并取OR值最大者为本研究的少尿界值。将单因素分析中P<0.10的围术期各变量共同代入多因素Logistic回归模型,分析术后AKI的独立危险因素,P<0.05为差异有统计学意义。

  2、 结果

  2.1、患者入组情况及一般情况

  2017年7月1日至2019年6月30日共有1 581例患者于北京大学第一医院在全身麻醉下接受了择期肺叶切除术,其中1 577例符合入选及排除标准,有1 393例完整记录了术中尿量以及术前、术后血肌酐值纳入本研究(图1)。

  发生术后AKI者31例,发生率为2.2%,其中AKI分级为1级的患者有27例(87.0%),2级的患者有2例(6.5%),3级的患者有2例(6.5%,其中1名患者需要肾替代治疗)。

  根据患者是否发生AKI,将患者分为AKI组和对照组。AKI组患者合并糖尿病(32.3% vs. 17.4%,P=0.032)、术前血红蛋白≤120.0 g/L(38.7% vs. 12.6%,P<0.001)、eGFR<30 mL/(min?1.73 m2)(9.7% vs. 0.3%,P<0.001)、以及ASA分级Ⅲ~Ⅳ级(32.3% vs. 13.7%,P=0.007)的比例显着高于对照组(表1)。两组患者的围术期资料见表2,AKI组患者术中单位尿量显着低于对照组[0.9 (0.6~1.4) vs. 1.2 (0.8~1.9),P=0.009]。

  2.2 、术中尿量与术后AKI 的关系

  ROC曲线分析显示,术中单位尿量用于预测术后AKI的曲线下面积为0.636(P=0.009),约登指数为最大值时(约登指数0.234,敏感度48.4%,特异度75.0%)的少尿界值为0.785 mL/(kg?h)(图2)。本研究进一步取0.7、0.8、0.9、1.0 mL/(kg?h)以及传统界值0.5 mL/(kg?h)为少尿界值分析少尿对术后AKI的影响。单因素分析显示,以小于0.8 mL/(kg?h)为少尿界值时,少尿患者发生AKI的风险增加最为显着(OR=2.774, 95%CI 1.357~5.671, P=0.004,表3)。

  2.3、术后AKI的独立危险因素

  将单因素分析中P小于0.10的因素代入多因素Logistic回归分析,结果显示术中尿量<0.8 mL/(kg?h)是术后AKI发生的独立危险因素之一(OR=2.698, 95%CI 1.260~5.778, P=0.011),另两个独立危险因素为术前血红蛋白≤120.0 g/L(P=0.003)以及术前eGFR<30 mL/(min?1.73 m2)(P=0.009,表4)。

  3、 讨论

  本研究表明,在肺叶切除术中,术中尿量<0.8 mL/(kg?h)是术后AKI发生的独立危险因素,此外,术前血红蛋白≤120.0 g/L以及术前eGFR<30 mL/(min?1.73 m2)也是术后AKI发生的独立危险因素。

  本研究术后AKI总体发生率为2.2%。由于本研究为回顾性研究,无法获得患者术后的尿量变化,仅采用血清肌酐变化作为AKI的诊断标准,因此可能导致AKI发生率被低估[5],但是此方法被大多数研究所采用,而且研究结果显示以血肌酐值为依据作出的AKI诊断与不良预后密切相关[15,16]。

  术中尿量与术后AKI的关系一直存在争议。对评价肾功能而言,尿量是一个古老而有效的功能性评价指标[17]。围术期少尿的原因主要包括有效循环血量不足、长时间低血压引起肾低灌注,以及抗利尿激素和醛固酮分泌增加等。对重症患者而言,少尿常常由肾低灌注所致,被认为是肾损伤的早期标志,预示着血肌酐的升高[18];而对围术期患者而言,全身麻醉术中少尿则可能由疼痛、恶心等非肾损伤因素引起的抗利尿激素分泌增加所致,也可能由手术导致的液体分布、排出改变所致,并不总意味着术后AKI的发生[8,19]。

  本研究71.8%的患者术前接受了椎旁神经阻滞镇痛,5.5%的患者术前接受了硬膜外镇痛。尽管有研究显示[20],椎旁神经阻滞或硬膜外阻滞可以削弱抗利尿激素分泌增加对术中尿量的影响,从而使术中尿量更多的依赖有效循环血量以及肾灌注压,但是本研究并未发现麻醉方式与AKI的发生有相关性。

  既往研究中,少尿一般被定义为尿量<0.5 mL/(kg?h),而有些研究没有得出少尿是术后AKI独立危险因素,可能与该界值的设定有关[11]。不同人群中少尿的定义是不同的,如有研究显示[10],体外循环下心脏手术中引起术后AKI发生率增加的术中少尿阈值为1.5 mL/(kg?h),而普外科手术中该阈值为0.3 mL/(kg?h) [11]。本研究采用ROC曲线分析术中尿量对术后AKI的预测作用时,ROC曲线的曲线下面积为0.636(P=0.009),介于0.5~0.7之间,提示术中尿量对术后AKI的发生仅有较低的预测价值。而以尿量<0.8 mL/(kg?h)为少尿界值时,诊断AKI的敏感度仅为48.4%,这也印证了术后AKI的发生是多种围术期因素共同作用的结果,而少尿是其中一部分因素的体现,该少尿界值还需其他研究进一步验证。

  术中液体管理策略对于术中尿量及术后AKI发生的影响一直存在争议[21,22]。近期一项大型前瞻性多中心研究将3 000名接受腹部大手术的患者随机分入限制输液组和自由输液组[22],限制输液组患者在术后24 h内输入液体总量为3.7 (2.9~4.9) L,自由输液组输入液体总量为6.1(5.0~7.4) L。研究发现,限制输液策略会增加围术期少尿和AKI发生率。本研究AKI组术中输液量为4.0(3.3~5.2) L,对照组术中输液量为4.9(3.9~6.2) L,差异虽无统计学意义(P=0.083),但AKI组较对照组输液量有减少趋势,提示术后AKI的发生或与术中限制性输液策略有关,但仍需大样本量研究进行验证。

  本研究尚存在不足:第一,本研究是回顾性且仅采用血清肌酐作为AKI诊断标准,因此可能会低估AKI发生率;第二,回顾性研究未能在术中定时记录尿量,单位尿量只能通过计算得出,因而难以估计术中少尿持续时间,未能探讨该因素对术后AKI的影响;第三,本研究为单中心研究,需要开展多种心研究进一步验证此研究假设。

  综上所述,本回顾性队列研究分析表明,在肺叶切除术中,术中少尿是术后AKI发生的独立危险因素,且尿量<0.8 mL/(kg?h)是可能的筛选标准。

  (本文编辑:王蕾)

  表1 两组患者术前基本资料
表1 两组患者术前基本资料
表1 两组患者术前基本资料

  Results are presented as mean ± standard deviation, number (%) or median (interquartile range). AKI, acute kidney injury; BMI, body mass index; ACEI, angiotensin-converting enzyme inhibitor; ARB, angiotension II receptORblocker; Hb, hemoglobin; Alb, albumin; eGFR, estimated glomerular filtration rate; SBP, systolic blood pressure; DBP, diastolic blood pressure; ASA, American Society of Anesthesiologists.a, unilateral nephrectomy or partial nephrectomy; b, dehydration index=88.4×blood urea nitrogen&pide;3.55&pide;serum creatinine; c, blood pressure measured for the first time after admission.

  表2 两组患者围术期相关资料
表2 两组患者围术期相关资料
表2 两组患者围术期相关资料

  Results are presented as mean ± standard deviation, number (%) or median (interquartile range). AKI, acute kidney injury; SBP, systolic blood pressure; SpO2, pulse oxygen saturation.a, calculated infusion= total intraoperative input&pide;body weight&pide;anesthesia duration; b, calculated urine output=total intraoperative urine output&pide;body weight&pide;anesthesia duration; c, SBP<90 mmHg or SBP decreased by more than 20% of the preoperative value.

  表3 术中尿量对术后AKI的预测价值
表3 术中尿量对术后AKI的预测价值

  Results are presented as number (%). AKI, acute kidney injury. a, calculated urine output=total intraoperative urine output&pide;body weight&pide;anesthesia duration.

  表4术后AKI的独立危险因素
表4术后AKI的独立危险因素

  AKI, acute kidney injury; eGFR, estimated glomerular filtration rate; ASA, American Society of Anesthesiologists. a, calculated infusion= total intraoperative input&pide;body weight&pide;anesthesia duration; b, calculated as the control group minus the AKI group.

  图1 入组流程图  
图1 入组流程图

  Figure 1 Flowchart of study

  AKI, acute kidney disease.a The estimated glomerular filtration rate (eGFR) was calculated using the chronic kidney disease epidemiology collaboration creatinine equation[14]. End-stage renal disease was defined as eGFR<15 mL/(min?1.73 m2) or receiving hemodialysis. b Furosemide or mannitol.

  图2 术中单位尿量用于预测术后AKI的ROC曲线
图2 术中单位尿量用于预测术后AKI的ROC曲线

  Figure 2 The ROC of intraoperative calculated urine output fORprediction of postoperative AKI

  AUC, area under curve; ROC, receiver operating characteristic curve; AKI, acute kidney injury.

  参考文献

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