中华急诊医学杂志  2019, Vol. 28 Issue (9): 1088-1092   DOI: 10.3760/cma.j.issn.1671-0282.2019.09.006
平均动脉压对脓毒性休克患者发生急性肾损伤的影响
李玉婷 , 李洪祥 , 郭健杏 , 谷莉娜 , 张东     
吉林大学第一医院重症医学科, 长春 130021
摘要: 目的 研究平均动脉压(mean arterial pressure, MAP)水平对脓毒性休克患者发生急性肾损伤(acute kidney injury, AKI)的影响,确定最佳的复苏目标MAP,以防止脓毒症相关AKI的发生或进展。方法 纳入2016年1月至2019年1月收入吉林大学第一医院重症医学科(ICU)的168例脓毒性休克成人患者(年龄≥18岁),采用回顾性研究,比较无AKI组(n=57)和AKI组(n=111)患者的临床资料,采用多因素logistic回归分析筛选和检验脓毒性休克患者AKI相关危险因素。结果 ①ΔMAP(复苏前MAP-复苏后MAP)的第1个四分位区间为-24.3~3.9 mmHg(1 mmHg=0.133 kPa),第2个四分位区间为4.0~12.3 mmHg,第3个四分位区间为12.4~19.8 mmHg,第4个四分位区间为19.9~43.5 mmHg。第2~4四分位区间为ΔMAP≥4 mmHg。②两组患者的年龄、体质量指数、性别、复苏前MAP、复苏1 h MAP、SOFA评分、标本培养阳性比例、标本培养阴性比例、高血压、外周血管疾病、脑血管意外、慢性阻塞性肺疾病、消化道溃疡、肝硬化、肿瘤等指标比较,差异均无统计学意义(P > 0.05)。两组患者的复苏后MAP(P=0.01)、APACHE Ⅱ评分(P=0.02)、糖尿病(P=0.01)、液体平衡(P=0.01)、ΔMAP在第2~4四分位区间(P=0.03)等指标比较,差异均有统计学意义。③ΔMAP≥4 mmHg(OR=0.26,95%CI:0.12~0.57,P=0.01)、糖尿病(OR=6.03,95%CI:1.35~44.16,P=0.04)、APACHE Ⅱ评分高(OR=0.96,95%CI:0.84~0.97,P=0.02)为脓毒性休克患者AKI发病率升高的影响因素。而复苏后MAP、液体平衡对脓毒性休克患者AKI发病率无明显影响。结论 ΔMAP≥4 mmHg、APACHE Ⅱ评分和糖尿病是脓毒性休克患者AKI发病率的独立危险因素。复苏后MAP比复苏前MAP低4 mmHg以上的脓毒性休克患者AKI发病率明显增加。
关键词: 脓毒性休克    平均动脉压    急性肾损伤    危险因素    
Effect of mean arterial pressure on acute kidney injury in patients with septic shock
Li Yuting , Li Hongxiang , Guo Jianxing , Gu Lina , Zhang Dong     
Intensive Care Unit, the First Hospital of Jilin University, Changchun 130021, China
Abstract: Objective To study the effect of mean arterial pressure (MAP) level on acute kidney injury (AKI) in patients with septic shock, and to determine the best resuscitation target MAP to prevent the occurrence or progression of sepsis- associated AKI. Methods The study subjects included 168 adult patients with septic shock (age≥65 years) who were admitted to the Department of Intensive Care Unit (ICU) of the First Hospital of Jilin University from January 2016 to January 2019. The clinical data of all enrolled patients were retrospectively analyzed. The baseline data were compared between the AKI group (n=111) and non-AKI group (n=57). Multivariate logistic regression analysis was used to determine the risk factors of AKI in patients with septic shock. Results ① The first, second, third, and forth quartile of ΔMAP (pre-resuscitation MAP minus post-resuscitation MAP) were -24.3-3.9 mmHg, 4.0-12.3 mmHg, 12.4-19.8 mmHg, and 19.9-43.5 mmHg, respectively. The second to fourth quartile interval wasΔMAP ≥4 mmHg.② There were no significant differences in age, body mass index, sex, pre-resuscitation MAP, MAP at first hour, SOFA score, positive culture ratio, negative culture ratio, hypertension, peripheral vascular disease, cerebrovascular accident, chronic obstructive pulmonary disease, gastrointestinal ulcer, liver cirrhosis, and tumor between the two groups (P > 0.05). There were significant differences in post-resuscitation MAP (P=0.01), APACHEⅡ score (P=0.02), diabetes mellitus (P=0.01), fluid balance (P=0.01), and ΔMAP from the second to fourth quartile (P=0.03) between the two groups.③ ΔMAP ≥4 mmHg (OR=0.26, 95%CI: 0.12-0.57, P=0.01), diabetes (OR=6.03, 95%CI: 1.35-44.16, P=0.04), and high APACHE Ⅱ score (OR=0.96, 95%CI: 0.84-0.97, P=0.02) were closely related to the increased incidence of AKI in patients with septic shock. Post-resuscitation MAP and fluid balance had no significant effect on the incidence of AKI in patients with septic shock. Conclusions ΔMAP ≥4 mmHg, APACHE Ⅱ score and diabetes were independent risk factors for the incidence of AKI in patients with septic shock. The incidence of AKI in septic shock patients with post-resuscitation MAP 4 mmHg or more lower than pre-resuscitation MAP is significantly increased.
Key words: Septic shock    Mean arterial pressure    Acute kidney injury    Risk factors    

急性肾损伤(AKI)在危重病患者中经常发生[1-2],是常见的合并症之一,脓毒症是AKI常见的原因之一。为了尽量减少死亡和终末器官衰竭的风险,拯救脓毒症运动指南推荐脓毒性休克患者平均动脉压(MAP)的复苏目标为≥65 mmHg(1 mmHg=0.133 kPa)(1C级推荐)[3]。然而,这一推荐并未得到实质性证据的支持,65 mmHg的目标MAP是否适合所有患者仍然存在争议[4-5]

脓毒症相关AKI是一种常见的危重症疾病。重症监护室(ICU)中42%~48%的AKI与脓毒症相关[6-7]。与非脓毒症相关AKI相比,脓毒症相关AKI与较高的ICU和住院病死率相关[6]。严重脓毒症合并AKI患者90 d病死率明显高于单纯严重脓毒症患者[8]。脓毒症患者即使血清肌酐轻度增加,患者的医疗费用、住院时间和死亡风险也明显增加[9],因此对于脓毒性休克患者需要确定最佳的复苏策略以防止脓毒症相关AKI的发生或进展。

脓毒性休克患者复苏的目标MAP始终存在争议,有研究表明复苏前的血压可能有助于确定复苏的最佳MAP。到目前为止,关于复苏后目标MAP应该接近还是高于复苏前MAP的相关研究仍较少。本回顾性研究旨在明确脓毒性休克患者复苏前后MAP水平对AKI发生率的影响。

1 资料与方法 1.1 一般资料

回顾性分析2016年1月至2019年1月吉林大学第一医院重症医学科(ICU)收治的脓毒性休克成人患者(年龄≥18岁)602例。脓毒性休克的诊断标准为:脓毒症患者经充分容量复苏后仍存在持续性低血压,需血管活性药物维持MAP≥ 65 mmHg且血清乳酸水平 > 2 mmol/L[10]。排除标准:终末期肾病; 入院前存在AKI; 未留置导尿管; 信息不全; 留置输尿管支架; 膀胱造瘘; 双侧肾盂穿刺引流; 复苏过程中少尿; 无法获得入院前MAP的患者。从脓毒性休克发生开始观察48 h内有无AKI发生,期间排除患者434例,最后符合纳入标准患者168例(图 1)。所有患者治疗前均获得患者或家属签署知情同意书。

图 1 患者入组流程图 Fig 1 Flow chart of enrolled patients
1.2 相关定义

复苏前MAP定义为脓毒性休克患者入ICU前1年到入ICU前7 d的所有MAP的中位数。复苏后MAP定义为从复苏开始到复苏7 h所有MAP的中位数。ΔMAP定义为复苏前MAP与复苏后MAP的差值。因此,如果复苏后MAP较复苏前MAP高,ΔMAP为负值; 相反,如果复苏后MAP较复苏前MAP低,ΔMAP为正值。AKI定义根据KDIGO指南[11],血肌酐48 h内升高≥0.3 mg/dL,或血肌酐≥1.5倍基线水平,或尿量 < 0.5 mL/(kg·h)。

1.3 统计学方法

应用SPSS 19.0统计软件,正态分布的计量资料用均数±标准差(Mean±SD)表示,两组间比较采用LSD-t检验; 非正态分布的计量资料以中位数(四分位数)[M(P25, P75)]表示,两组间比较比较采用Mann-Whitney U检验。计数资料以频数(百分率)表示,组间比较采用χ2检验或Fisher精确检验。脓毒性休克患者AKI相关危险因素的分析采用多因素logistic回归分析,以P < 0.05为差异有统计学意义。

2 结果 2.1 无AKI组与AKI组脓毒性休克患者的基线资料比较

两组患者的年龄、体质量指数、性别、复苏前MAP、复苏1 h MAP、SOFA评分、培养阳性比例、培养阴性比例、高血压、外周血管疾病、脑血管意外、慢性阻塞性肺疾病、消化道溃疡、肝硬化、肿瘤等指标比较,差异均无统计学意义(P > 0.05),见表 1

表 1 根据脓毒性休克患者是否存在AKI分层的基线资料 Table 1 Baseline data on AKI stratification in septic shock patients
指标 无AKI组(n=57) AKI组(n=111) 统计值 P
年龄(岁)a 66.5(56.2,80.9) 71.9(59.8,81.8) 4.51 0.25
体质量指数(kg/m2a 22.2(18.8,25.6) 23.0(19.2,28.1) 5.32 0.08
男性(例,%)a 35(61.4) 58(52.3) 2.12 0.21
复苏前MAP(mmHg)a 81.8(74.0,89.5) 78.4(73.3,87.5) 5.34 0.05
复苏1 h MAP(mmHg)a 62.1(57.0,73.1) 63.1(55.7,70.8) 8.14 0.22
复苏后MAP(mmHg)a 71.2(66.2,79.3) 65.6(61.0,72.8) 2.13 0.01
APACHE Ⅱ评分a 17(15,21) 23(17,29) 4.45 0.02
SOFA评分a 6(4,9) 7(4,10) 3.15 0.40
培养阳性(例,%) 24(42.1) 58(52.3) 7.34 0.30
培养阳性样本来源(例,%)
  血液 6(10.5) 12(10.9)
  尿液 3(5.2) 10(9.0)
  呼吸道 12(21.1) 25(22.5)
  伤口 1(1.8) 2(1.8)
  其他 2(3.5) 9(8.1)
培养阴性(例,%) 33(57.9) 53(47.7) 4.56 0.20
合并症(例,%)
  高血压 25(43.9) 45(40.5) 6.32 0.35
  外周血管疾病 3(5.3) 4(3.6) - 0.87
  脑血管意外 15(26.3) 25(22.5) 8.27 0.63
  慢性阻塞性肺疾病 8(14.0) 20(18.0) 9.12 0.21
  糖尿病 11(19.3) 43(38.7) 7.56 0.01
  消化道溃疡 4(7.0) 10(9.9) - 0.38
  肝硬化 3(5.3) 6(5.4) - 0.91
  肿瘤 1(1.8) 3(2.7) - 0.29
正性肌力药物(例,%) 6(10.5) 16(14.4) - 0.32
液体平衡(mL)a 4 845(2 018,8 272) 6 484(3 668,10 800) 7.23 0.01
ΔMAP在第2~4四分位区间(例,%) 35(61.4) 87(78.4) 8.15 0.03
注:a为中位数(四分位数); SOFA评分,序贯器官衰竭估计评分; APACHE Ⅱ评分,急性生理与慢性健康评分; MAP,平均动脉压

两组患者的复苏后MAP(P=0.01)、APACHE Ⅱ评分(P=0.02)、糖尿病(P=0.01)、液体平衡(P=0.01)、ΔMAP在第2~4四分位区间(P=0.03)等指标比较,差异均有统计学意义,见表 1

ΔMAP的第1个四分位区间为-24.3~3.9 mmHg,第2个四分位区间为4.0~12.3 mmHg,第3个四分位区间为12.4~19.8 mmHg,第4个四分位区间为19.9~43.5 mmHg。因此第2~4四分位区间为ΔMAP≥4 mmHg。

2.2 脓毒性休克患者AKI的相关危险因素分析

比较无AKI组与AKI组患者的临床资料,对单因素分析有统计学意义的变量进行多因素logistic回归分析。各个因素的赋值情况:ΔMAP中“1”代表ΔMAP≥4 mmHg,“0”代表ΔMAP < 4 mmHg; 复苏后MAP中“1”代表复苏后MAP < 65.6 mmHg,“0”代表复苏后MAP≥65.6 mmHg; 糖尿病中“1”代表患有糖尿病,“0”代表不患有糖尿病; 液体平衡中“1”代表液体正平衡 > 6 500 mL, “0”代表液体正平衡≤6 500 mL; APACHE Ⅱ评分中“1”代表APACHE Ⅱ评分≥23,“0”代表APACHE Ⅱ评分 < 23。结果显示,ΔMAP≥4 mmHg(OR=0.26,95%CI:0.12~0.57,P=0.01)、糖尿病(OR=6.03,95%CI:1.35~44.16,P=0.04)、APACHE Ⅱ评分(OR=0.96,95%CI:0.84~0.97,P=0.02)是脓毒性休克患者AKI发病率的独立危险因素。而复苏后MAP、液体平衡对脓毒性休克患者AKI发病率无明显影响,见表 2

表 2 脓毒性休克患者AKI的相关危险因素分析 Table 2 Analysis of risk factors associated with AKI in patients with septic shock
因素 β S.E. OR 95%CI P
ΔMAP≥4 mmHg -0.01 0.01 0.26 0.12~0.57 0.01
复苏后MAP 0.61 0.46 1.12 0.55~2.35 0.78
糖尿病 1.83 0.68 6.03 1.35~44.16 0.04
液体平衡 0.55 0.34 2.01 0.75~5.42 0.17
APACHE Ⅱ评分 1.79 0.68 0.96 0.84~0.97 0.02
3 讨论

MAP是反映组织灌注的指标之一,2016年拯救脓毒症运动指南建议脓毒性休克患者MAP复苏目标至少为65 mmHg以达到优化氧供、满足细胞氧耗的目的。Asfar等[5]研究发现脓毒性休克患者高MAP目标组(80~85 mmHg)和低MAP目标组(65~70 mmHg)的28 d病死率差异无统计学意义。另一项纳入167例合并慢性高血压的脓毒性休克患者的研究表明,高MAP组发生肾功能不全及需要CRRT的比例明显下降[12]。然而,较高的MAP目标组也有较高的房颤发生率, 慢性高血压可导致器官灌注的自动调节压力曲线右移[13]。因此,较高的MAP目标可能会改善既往MAP较高患者的器官灌注[14]。因此,为了明确脓毒性休克患者复苏的最佳MAP目标,需要同时兼顾患者既往的血压情况[15-16]

本研究发现ΔMAP≥4 mmHg是脓毒性休克患者AKI发病率的独立危险因素。换言之,为了避免脓毒症相关AKI的发生,复苏后MAP不应比复苏前MAP低4 mmHg以上。在之前的脓毒症相关AKI研究中,Badin等[14]发现合并AKI的脓毒性休克患者早期MAP水平偏低,本研究结果与此一致。与复苏前MAP相比,复苏后MAP的下降与AKI的发病率密切相关,ΔMAP在第2~4四分位区间是脓毒性休克患者AKI发病率的独立危险因素。本研究结果进一步提示,为了明确每个脓毒性休克患者的最佳MAP复苏目标,需要考虑患者既往的血压情况,如果患者既往有慢性高血压病史,复苏后MAP应该更高一些。尽管较高的MAP目标不会降脓毒性休克患者的病死率,但它与合并慢性高血压的脓毒性休克患者AKI发生率下降密切相关[5]

本研究还发现APACHE Ⅱ评分和糖尿病也是脓毒性休克患者AKI发病率的独立危险因素。Wang等[17]研究发现APACHE Ⅱ评分是脓毒症相关AKI病死率的独立危险因素。APACHE Ⅱ评分是急性循环衰竭患者预后评估的可靠指标[18],APACHE Ⅱ评分越高,往往提示疾病严重程度越高,预后越差,本研究结果与此一致。糖尿病使患者更容易发生感染性并发症,甚至脓毒症。Wang等[19]进行的Meta分析发现糖尿病虽然不会影响脓毒症患者的预后,但是合并糖尿病的脓毒症患者AKI的发生率显著增加。糖尿病可以通过破坏肾脏组织损害肾功能,根据一项动物实验,糖尿病引起的高血糖除了损伤肾脏组织外,还明显增加了脓毒症阶段的NF-κB的激活和氧化应激水平[20],这都是导致糖尿病患者脓毒症相关AKI的发病率更高的原因。

总之,脓毒性休克患者AKI发病率与复苏前后MAP差值密切相关,复苏后MAP比复苏前MAP低4 mmHg以上的脓毒性休克患者AKI发病率明显增加。对于脓毒性休克的患者,临床医生可以通过参考复苏前的MAP,更好地明确复苏阶段个体化的目标MAP。

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