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中国循证儿科杂志

中国循证儿科杂志 ›› 2020, Vol. 15 ›› Issue (5): 333-344.

• 论著 • 上一篇    下一篇

抗菌药物封管对留置中心静脉导管患儿降低导管相关血流感染发生风险的系统评价和Meta分析

王颖雯1a，王文超1b，李丹钰2，康琼芳1c，顾莺1b，季福婷1d，王瑞1e，张玉侠3，张崇凡1e   

  1. 1 复旦大学附属儿科医院  上海，201102，a 血液肿瘤科，b 护理部，c 肿瘤外科，d 新生儿科，e 临床实践指南制作和评价中心；2复旦大学护理学院上海，200032；3 复旦大学附属中山医院护理部上  海，200032
  • 收稿日期:2020-10-14 修回日期:2020-10-14 出版日期:2020-10-25 发布日期:2020-10-25
  • 通讯作者: 张崇凡；张玉侠

Antimicrobial lock technique in reducing the risk of catheter-related bloodstream infections for children with central venous access devices: A systematic review and meta-analysis

 WANG Yingwen1a, WANG Wenchao1b,LI Danyu2, KANG Qiongfang1c, GU Ying1b, JI Futing1d, WANG Rui1e, ZHANG Yuxia3, ZHANG Chongfan1e   

  1. 1 Children's Hospital of Fudan University, Shanghai 201102, China, a. Department of Hematology and Oncology, b. Nursing Department, c. Department of Surgical Oncology, d. Department of Neonatology, e. Center for Clinical Practice Guideline Development and Evaluation; 2 School of Nursing Fudan University, Shanghai 20032, China; 3 Nursing Department, Zhongshan Hospital of Fudan University, Shanghai 200032, China
  • Received:2020-10-14 Revised:2020-10-14 Online:2020-10-25 Published:2020-10-25
  • Contact: ZHANG Chongfan；ZHANG Yuxia

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摘要： 目的：探讨儿科不同人群置入中心静脉导管（CVAD）后用不同抗菌药物封管干预对降低导管相关血流感染发生风险的效果。方法：纳入住院、门诊和居家CVAD的适用儿科人群，干预组予抗菌药物封管和/或系统静脉抗生素治疗，对照组予非抗菌药物封管和/或系统静脉抗生素治疗，以疑似、可能和确定的导管相关血流感染发生密度为主要结局指标。在英文数据库（PubMed、Ovid-EMBASE等）和中国生物医学文献服务系统检索，检索时间为建库至2020年9月24日，检索词：抗菌药物封管、中心静脉导管、导管相关血流感染、儿童，RCT和非RCT分别采用Cochrane风险偏倚评估工具和ROBINS-I行偏倚风险评价。结果：30篇文献进入本文分析。以干预开始时点有无明确的导管相关性血流感染分为预防（30篇）和治疗（1篇）。RCT 17篇，非RCT 13篇。研究人群为肠衰竭患儿9篇，肿瘤患儿13篇，PICU和/或NICU人群4篇，其他人群4篇。基于29 篇封管液(乙醇、牛磺罗定、尿激酶和抗生素)预防导管相关血流感染总的发生密度，RR=0.32（95%CI：0.24~0.43），I2=75%。8篇RCT抗生素封管，RR=0.38（95%CI：0.18~0.82），I2=70%;临床异质性可能来源于肿瘤和免疫抑制人群、万古霉素。2篇RCT和1篇非RCT尿激酶封管，RR=0.71（95%CI：0.53~0.95），I2=0。10篇非RCT乙醇封管，RR=0.31（95%CI：0.22~0.43），I2=57%, 临床异质性可能来源于肠衰竭人群。 8篇非RCT牛磺罗定封管，RR=0.23（95%CI：0.12~0.42），I2=72%，临床异质性可能来源于肠衰竭、自定义高危人群、手术等。1篇非RCT以盐酸封管治疗导管相关血流感染的发生风险事件，RR=0.84（95%CI：0.52~1.37），差异无统计学意义（P=0.49）。次要结局指标中仅牛磺罗定封管导管细菌定植干预组和对照组差异有统计学意义。抗菌药物封管后出现的不良反应包括味觉异常、呕吐、恶心、头晕和脸红。结论：采用不同封管液预防可降低68%的CVAD相关血流感染发生密度，预防效果从好到差依次是牛磺罗定、乙醇、抗生素和尿激酶。但抗菌药物封管的效果可能被夸大，进一步研究极有可能影响该疗效评估结果的可信度。

Abstract: ObjectiveTo explore the effect of different antibacterial drugs on reducing the risk of catheter-related bloodstream infections for different populations of pediatrics with a central venous access device (CVAD). MethodsPediatric patients applicable to CVADs were included from inpatient, outpatient and home settings. With antimicrobial lock and/or systemic intravenous antibiotic therapy in the intervention group, the control group was treated with non-antimicrobial lock and/or systemic intravenous antibiotic therapy. Suspected, possible and confirmed catheter-related bloodstream infections were the primary outcome. Literature was searched in both of English and Chinese databases including PubMed, Ovid-EMBASE and SinoMed from the establishment to September 24, 2020. Search terms were antimicrobial lock, central venous catheter, catheter-related bloodstream infection and children. Cochrane risk-of-bias tool for randomized trials and ROBINS-I were used to evaluate the risk of bias for RCTs and non-RCTs respectively. ResultsA total of 30 studies were included into the analysis with 17 RCTs and 13 non-RCTs. According to whether there was a clear catheter-related bloodstream infection at the beginning of the intervention, they were divided into the category of prevention (n=30) and treatment (n=1). In terms of study populations, there were 9 studies for children with intestinal failure, 13 for children with tumors, 4 for PICU and/or NICU, and 4 for others. Based on 29 studies focusing on different locking fluids (ethanol, taurolidine, urokinase, and antibiotics) to prevent catheter-related bloodstream infections, the overall risk density was RR=0.32(95%CI: 0.24-0.43) with statistically significant differences (P<0.01). Random effect model was used with I2=75%. Among them, there were 8 RCTs taking antibiotics as the locking fluid (RR=0.38, 95%CI: 0.18-0.82, P<0.05, I2=70%). Clinical heterogeneity was likely to come from patients with tumors, immunosuppression and vancomycin. Three RCTs were about urokinase (RR=0.71, 95%CI: 0.53-0.95, I2=0). Ten studies were about ethanol (RR=0.31, 95%CI: 0.22-0.43, P< 0.01, I2=57%) and clinical heterogeneity was likely to come from patients with intestinal failure. Eight studies were about (RR=0.23, 95%CI: 0.12-0.42, P<0.01,I2=72%) and clinical heterogeneity was likely to come from patients with intestinal failure, surgery and customized high-risk patients. One study was about catheter-related bloodstream infections treated with hydrochloric acid as the locking fluid (RR=0.84, 95%CI: 0.52-1.37, P=0.49). Among the secondary outcomes, there were statistically significant differences between the intervention group of catheter bacterial colonization and the control group only when taurolidine was used as the locking fluid. Adverse reactions after antimicrobial lock therapy included abnormal taste, vomiting, nausea, dizziness, and flushing. ConclusionThe use of locking fluids can reduce the risk density of CVAD-related bloodstream infections by 68%. Taurolidine has the best preventive effect, followed by ethanol, antibiotics and urokinase in a descending order. However, the effect of antimicrobial lock therapy may be overstated, and further research is likely to affect the credibility of the results of this efficacy evaluation.