经皮肾造瘘术治疗输尿管梗阻继发的尿源性脓毒血症死亡危险因素分析

    袁小旭?叶啸?邓健?谢群?庞国福

    【摘要】目的 探討经皮肾造瘘术治疗输尿管梗阻继发的尿源性脓毒血症的全因死亡危险因素。方法 回顾性分析164例经皮肾造瘘术治疗输尿管梗阻继发的尿源性脓毒血症患者的临床资料,进行入院到出院后30 d内的死亡危险因素分析,当变量在单因素分析中有统计学意义时,采用多因素Logistic回归分析。结果 164例中11例(6.7%)在住院期间或出院后30 d内死亡。与幸存组患者比较,死亡组患者在ICU时间更长,淋巴细胞数更低,碱性磷酸酶、直接胆红素、总胆红素和血浆渗透压均更高(P均< 0.05)。肾积水面积以及经皮肾造瘘术当日、术后第2日的序贯器官衰竭估计评分(SOFA)和术后第2日SOFA升高值与病死率相关(P均< 0.05)。术后呼吸频率更快、快速SOFA更高的患者病死率更高(P均< 0.05)。PCN前后呼吸频率变化、精神状态变化和快速SOFA变化与病死率相关(P均< 0.05)。多因素Logistic回归分析显示,经皮肾造瘘术后第2日的SOFA与死亡率相关(P = 0.001)。结论 对于经皮肾造瘘术治疗的输尿管梗阻继发尿源性脓毒血症患者,术后第2日的SOFA是其入院到出院30 d内全因死亡的最重要的危险因素。

    【关键词】死亡危险因素;尿源性脓毒血症;输尿管梗阻;经皮肾造瘘术

    Risk factors of mortality in patients with urosepsis secondary to ureteral obstruction manipulated by percutaneous nephrostomy Yuan Xiaoxu, Ye Xiao, Deng Jian, Xie Qun, Pang Guofu. Department of Urology, Zhuhai Peoples Hospital, Zhuhai 519000, China

    Corresponding author, Pang Guofu, E-mail: pangguofu010919@ 163. com

    【Abstract】Objective To explore the significant risk factors associated with the all-cause mortality in patients with urosepsis secondary to ureteral obstruction manipulated by percutaneous nephrostomy.Methods Clinical data of 164 patients with urosepsis secondary to ureteral obstruction undergoing percutaneous nephrostomy were retrospectively analyzed. The risk factors of mortality rate before admission and within 30 d after discharge were analyzed. The significant variables identified by univariate analysis were subject to multivariate Logistic regression analysis. Results Eleven (6.7%) of 164 patients with urosepsis secondary to ureteral obstruction manipulated by percutaneous nephrostomy died during hospitalization or within 30 d after discharge. The mortality rate of patients with longer length of ICU stay was significantly increased (P = 0.001). Patients with higher mortality rate presented with lower lymphocyte count, alkaline phosphatase, direct bilirubin, higher total bilirubin and Plasma osmolality(all P < 0.05). Hydronephrosis, sequential organ failure assessment (SOFA) scores on the day of percutaneous nephrostomy and postoperative 2 d and the increase in SOFA score at 2 d after percutaneous nephrostomy were significantly correlated with the mortality rate (all P < 0.05). Patients with higher respiration rate and quick SOFA (qSOFA) score after percutaneous nephrostomy showed higher mortality rate (both P < 0.05). The changes of respiration rate before and after percutaneous nephrostomy, mental status and the changes of qSOFA scores before and after percutaneous nephrostomy were significantly correlated with the mortality rate (all P < 0.05). Multivariate Logistic regression analysis showed that SOFA score at 2 d after percutaneous nephrostomy was significantly associated with the mortality rate (P = 0.001). Conclusion SOFA score at 2 d after percutaneous nephrostomy is the most significant risk factor of the all-cause mortality rate in patients with urosepsis secondary to ureteral obstruction undergoing percutaneous nephrostomy.

    【Key words】Risk factor of mortality;Urosepsis;Ureteral obstruction;Percutaneous

    尿源性脓毒血症是由泌尿生殖道感染引起的脓毒血症。尽管与过去相比,尿源性脓毒血症的病死率有所降低,但尿源性脓毒血症仍然是院内死亡的重要原因之一,住院病死率为2% ~ 33%[1-8]。

    大多数尿源性脓毒血症继发于输尿管梗阻,除了输尿管内支架置入,经皮肾造瘘术(PCN)也是解除梗阻的方法之一。本研究组探讨了PCN治疗输尿管梗阻继发的尿源性脓毒血症患者的死亡危险因素。

    对象与方法

    一、研究对象

    回顾性分析珠海市人民医院2015年1月至2020年12月收治的164例行PCN解除梗阻继发尿源性脓毒症的患者的资料,将其分为死亡组与幸存组。根据国际公认的第3版脓毒症和脓毒症休克的定义,将尿源性脓毒血症定义为尿路感染和序贯器官衰竭估计评分(SOFA)≥2。本研究获得珠海市人民医院医学伦理委员会的批准(LW-2020-15)。

    二、研究方法

    收集患者人口学资料、临床数据,包括患者在入院时、尿源性脓毒血症起病时、送介入室前、送回普通病房或ICU后的快速SOFA(qSOFA)和生命体征等数据,行PCN当日及术后第2日的SOFA,肾积水、结石、糖尿病、最高体温、体温超过38℃的总时间、Charlson合并症指数等资料。收集实验室数据,包括血常规、电解质、肝功能、肾功能、尿常规、尿/血培养、心肌酶、凝血试验、CRP和降钙素原(PCT)。如果诊断24 h内给予的抗生素包含至少1种体外实验敏感的抗生素[根据临床与实验室标准学会(CLSI)指南],则判定初始经验性抗生素是“适当的”,否则判定为“不适当的”。诊断后24 h内给予的初始经验性抗生素是否包括碳青霉烯类也予以记录。分析入院到出院后30 d内的死亡危险因素。

    三、统计学处理

    采用SPSS 19.0进行检验。计量资料先用Kolmogorov-Smirnov检验做正态性统计分析,符合正态分布者以表示,组间比较采用独立t检验;不符合正态分布的计量资料以中位数(下四分位数,上四分位数)表示,组间比较采用Mann-Whitney U检验。采用Fisher确切概率法、χ2检验分析无序分类变量。采用Mann-Whitney U检验对有序分类变量进行分析。将单因素分析中P < 0.05的变量纳入多因素二元Logistic回归, 采用向前偏似然估计法计算影响病死率的独立危险因素。P < 0.05为差异有统计学意义。

    结果

    一、死亡组与幸存组尿源性脓毒血症患者的基本资料及臨床数据比较

    164例患者中11例(6.5%)在住院期间或出院后30 d内死亡。死亡组与幸存组患者肾积水面积、ICU住院日数比较差异有统计学意义(P均 < 0.05)

    二、死亡组与幸存组尿源性脓毒血症患者的实验室数据比较

    死亡组与幸存组患者的淋巴细胞、碱性磷酸酶、直接胆红素、总胆红素和血浆渗透压比较差异均有统计学意义(P均 < 0.05)

    三、死亡组与幸存组尿源性脓毒血症患者的生命体征及SOFA比较

    死亡组与幸存组患者行PCN后呼吸频率、行PCN后的qSOFA、PCN前后呼吸频率变化、PCN前后神志变化、PCN前后qSOFA变化比较差异均有统计学意义(P均 < 0.05),见表3。2组行PCN当日的SOFA、PCN术后第2日的SOFA及PCN术后2 d SOFA的变化值比较差异均有统计学意义(P均 < 0.05)。

    四、多因素Logistic回归分析独立死亡危险因素

    单因素回归分析中有统计学意义的危险因素包括:ICU住院时间、淋巴细胞数、总胆红素、直接胆红素、碱性磷酸酶、血浆渗透压、PCN当日的SOFA、PCN术后第2日的SOFA、行PCN后呼吸频率、行PCN后的qSOFA、PCN前后呼吸频率变化、PCN前后神志变化和PCN前后qSOFA变化。将这些因素纳入多因素二元Logistic回归,结果显示,PCN术后第2日的SOFA与入院到出院后30 d内的病死率相关(P = 0.001),是独立的死亡危险因素。

    讨论

    输尿管梗阻常常导致肾积水及泌尿系统感染,如长期不解除梗阻,肾盂压力高,病原体可逆向进入肾组织及血液,导致脓毒血症。快速和及时地治疗尿源性脓毒血症包括给予足够的晶体和广谱抗生素,严重的病例需要及时解除尿路梗阻,出现脓毒性休克时使用升压药物也很重要。解除梗阻的常用方式为PCN或输尿管镜下内支架置入术[3]。PCN治疗继发的尿源性脓毒血症患者的死亡危险因素的研究尚无报道,本研究是首项相关研究。

    以前的研究显示尿源性脓毒血症的病死率为1.7% ~ 8%[2, 7]。Qiang等[7]报告,脓毒血症类型和SOFA与患者生存相关。本研究显示,PCN术后第2日的SOFA与PCN治疗的输尿管继发尿源性脓毒血症患者入院到出院后30 d内的病死率相关,这提示及早行PCN引流梗阻所致的器官功能障碍、降低SOFA可提高患者生存率。Lee等[11]认为,X线定位介入PCN引流时,应采取2种方法来避免高肾内压和病原体回流到血液,首先,在注射造影剂之前,应先吸出尿液。其次,为了明确导管定位,在操作结束时应避免做肾造影。我院介入放射科医师在PCN结束时对所有患者进行了肾造影,容易导致肾盂压力升高,细菌及毒素进入血液,死亡组PCN术后生命体征明显改变、qSOFA升高,Seymour等[18]认为qSOFA与病死率密切相关,介入放射科医师的这种操作不当或是本组患者病死率偏高的原因之一。

    Baek等[19]发现感染性急性肾损伤患者内源性碱性磷酸酶活性显著升高。Cheung等[20]报道血碱性磷酸酶和CRP水平显著相关。Hwang等[21]得出结论,血清碱性磷酸酶水平较高的腹膜透析患者感染相关死亡和感染相关住院的风险更高。这些研究表明,碱性磷酸酶可能是较好的感染标志物,这与我们的研究相似。死亡组血浆渗透压升高可能是由于钠、钾、葡萄糖和尿素氮4种电解质浓度不显著升高的累积作用所致,在病理生理方面,死亡组血浆渗透压较高,可能是由于更严重的感染导致更严重的渗出。

    本研究存在一定局限性,首先,样本量较小,这可能使单变量分析中有统计学差异的数据在多因素回归分析中被筛出。其次,本研究是单中心研究,难以防止偏差。此外,回顾性研究所固有的局限不能被忽略,例如因实验数据不完整使纳入尿源性脓毒血症患者不全。综上所述,进一步开展更大规模的多中心随机对照研究以深入探讨PCN治疗输尿管梗阻继发的尿源性脓毒血症患者死亡危险因素十分必要。

    参 考 文 獻

    [1] Ackermann RJ, Monroe PW. Bacteremic urinary tract infection in older people. J Am Geriatr Soc,1996,44(8):927-933.

    [2] Meyers BR, Sherman E, Mendelson MH, Velasquez G, Srulevitch-Chin E, Hubbard M, Hirschman SZ. Bloodstream infections in the elderly. Am J Med,1989,86(4):379-84.

    [3] Rosser CJ, Bare RL, Meredith JW. Urinary tract infections in the critically ill patient with a urinary catheter. Am J Surg,1999,177(4):287-290.

    [4] Chin BS, Kim MS, Han SH, Shin SY, Choi HK, Chae YT, Jin SJ, Baek JH, Choi JY, Song YG, Kim CO, Kim JM. Risk factors of all-cause in-hospital mortality among Korean elderly bacteremic urinary tract infection (UTI) patients. Arch Gerontol Geriatr,2011,52(1):e50-e55.

    [5] Fukunaga A, Nishihara T, Kono Y, Matsumoto K, Matsuoka T, Sugino Y, Okada T, Kawakita M. Risk factors for mortalityin patients with urosepsis. Hinyokika Kiyo,2017,63(5):195-199.

    [6] Kitagawa K, Shigemura K, Yamamichi F, Osawa K, Uda A, Koike C, Tokimatsu I, Shirakawa T, Miyara T, Fujisawa M. Bacteremia complicating urinary tract infection by Pseudomonas aeruginosa: mortality risk factors. Int J Urol,2019,26(3):358-362.

    [7] Qiang XH, Yu TO, Li YN, Zhou LX. Prognosis risk of urosepsis in critical care medicine: a prospective observational study. Biomed Res Int,2016,2016:9028924.

    [8] Tal S, Guller V, Levi S, Bardenstein R, Berger D, Gurevich I, Gurevich A. Profile and prognosis of febrile elderly patients with bacteremic urinary tract infection. J Infect,2005,50(4):296-305.

    [9] Goldsmith ZG, Oredein-McCoy O, Gerber L, Ba?ez LL, Sopko DR, Miller MJ, Preminger GM, Lipkin ME. Emergent ureteric stent vs percutaneous nephrostomy for obstructive urolithiasis with sepsis: patterns of use and outcomes from a 15-year experience. BJU Int,2013 ,112(2):E122-E128.

    [10] Koh D, Lau KK, Teoh E. Are all urgent nephrostomies that urgent? Emerg Radiol,2018,25(4):381-386.

    [11] Lee WJ, Patel U, Patel S, Pillari GP. Emergency percutaneous nephrostomy: results and complications. J Vasc Interv Radiol,1994,5(1):135-139.

    [12] Watson RA, Esposito M, Richter F, Irwin RJ Jr, Lang EK. Percutaneous nephrostomy as adjunct management in advanced upper urinary tract infection. Urology,1999,54(2):234-239.

    [13] 何问理,温海东,罗云. 结石梗阻致尿源性脓毒血症的影响因素及早期诊治策略分析. 新医学,2019,50(12):928-932.

    [14] Borofsky MS, Walter D, Shah O, Goldfarb DS, Mues AC, Makarov DV. Surgical decompression is associated with decreased mortality in patients with sepsis and ureteral calculi.? J Urol, 2013,189(3):946-951.

    [15] Hamasuna R, Takahashi S, Nagae H, Kubo T, Yamamoto S, Arakawa S, Matsumoto T. Obstructive pyelonephritis as a result of urolithiasis in Japan: diagnosis, treatment and prognosis. Int J Urol,2015,22(3):294-300.

    [16] Lang EK, Price ET. Redefinitions of indications for percutaneous nephrostomy. Radiology,1983,147(2):419-426.

    [17] Sammon JD, Ghani KR, Karakiewicz PI, Bhojani N, Ravi P, Sun M, Sukumar S, Trinh VQ, Kowalczyk KJ, Kim SP, Peabody JO, Menon M, Trinh QD. Temporal trends, practice patterns, and treatment outcomes for infected upper urinary tract stones in the United States. Eur Urol,2013,64(1):85-92.

    [18] Seymour CW, Liu VX, Iwashyna TJ, Brunkhorst FM, Rea TD, Scherag A, Rubenfeld G, Kahn JM, Shankar-Hari M, Singer M, Deutschman CS, Escobar GJ, Angus DC. Assessment of clinical criteria for sepsis: for the third international consensus definitions for sepsis and septic shock (Sepsis-3). JAMA,2016,315(8):762-774.

    [19] Baek SD, Kang JY, Yu H, Shin S, Park HS, Kim MS, Lee EK, Kim SM, Chang JW. Change in alkaline phosphatase activity associated with intensive care unit and hospital length of stay in patients with septic acute kidney injury on continuous renal replacement therapy. BMC Nephrol,2018,19(1):243.

    [20] Cheung BM, Ong KL, Cheung RV, Wong LY, Wat NM, Tam S, Leung GM, Cheng CH, Woo J, Janus ED, Lau CP, Lam TH, Lam KS. Association between plasma alkaline phosphatase and C-reactive protein in Hong Kong Chinese. Clin Chem Lab Med,2008,46(4):523-527.

    [21] Hwang SD, Kim SH, Kim YO, Jin DC, Song HC, Choi EJ, Kim YL, Kim YS, Kang SW, Kim NH, Yang CW, Kim YK. Serum alkaline phosphatase levels predict infection-related mortality and hospitalization in peritoneal dialysis patients. PLoS One,2016,11(6):e0157361.

    (收稿日期:2021-02-26)

    (本文編辑:洪悦民)