Janum Susanne, Afshari Arash
Department of Neuroanesthesiology and Neurointensive Care 2093, Rigshospitalet, Copenhagen University Hospital, Blegdamsvej 9, Copenhagen, Denmark, 2100.
Cochrane Database Syst Rev. 2016 Jul 11;7(7):CD011195. doi: 10.1002/14651858.CD011195.pub2.
Candida bloodstream infections most often affect those already suffering serious, potentially life-threatening conditions and often cause significant morbidity and mortality. Most affected persons have a central venous catheter (CVC) in place. The best CVC management in these cases has been widely debated in recent years, while the incidence of candidaemia has markedly increased.
The main purpose of this review is to examine the impact of removing versus retaining a CVC on mortality in adults and children with candidaemia who have a CVC in place.
We searched the following databases from inception to 3 December 2015: Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE (Ovid SP), EMBASE (Ovid SP), the Commonwealth Agricultural Bureau (CAB), Web of Science and the Cumulative Index to Nursing and Allied Health Literature (CINAHL). We searched for missed, unreported and ongoing trials in trial registries and in reference lists of excluded articles.
We searched for randomized controlled trials (RCTs) and quasi-RCTs involving adults and children with candidaemia and in which participants were randomized for removal of a CVC (the intervention under study), irrespective of publication status, date of publication, blinding status, outcomes published or language.However, two major factors make the conduct of RCTs in this population a difficult task: the large sample size required to document the impact of catheter removal in terms of overall mortality; and lack of economic interest from the industry in conducting such a trial.
Our primary outcome measure was mortality. Several secondary outcome measures such as required time for clearance of blood cultures for Candida species, frequency of persistent candidaemia, complications, duration of mechanical ventilation and length of stay in the intensive care unit (ICU) and in the hospital were planned, as were various subgroup and sensitivity analyses, according to our protocol. We assessed papers and abstracts for eligibility and resolved disagreements by discussion. However, we were not able to include any RCTs or quasi-RCTS in this review and, as a result, have carried out no meta-analyses. However, we have chosen to provide a brief overview of excluded observational studies.
We found no RCT and thus no available data for evaluation of the primary outcome (mortality) nor secondary outcomes or adverse effects. Therefore, we conducted no statistical analysis.A total of 73 observational studies reported on various clinically relevant outcomes following catheter removal or catheter retention. Most of these excluded, observational studies reported a beneficial effect of catheter removal in patients with candidaemia. None of the observational studies reported results in favour of retaining a catheter. However, the observational studies were very heterogeneous with regards to population, pathogens and interventions. Furthermore, they suffered from confounding by indication and an overall high risk of bias. As a consequence, we are not able to provide recommendations or to draw firm conclusions because of the difficulties involved in interpreting the results of these observational studies (very low quality of evidence, GRADE - Grades of Recommendation, Assessment, Development and Evaluation Working Group).
AUTHORS' CONCLUSIONS: Despite indications from observational studies in favour of early catheter removal, we found no eligible RCTs or quasi-RCTs to support these practices and therefore could draw no firm conclusions. At this stage, RCTs have provided no evidence to support the benefit of early or late catheter removal for survival or other important outcomes among patients with candidaemia; no evidence with regards to assessment of harm or benefit with prompt central venous catheter removal and subsequent re-insertion of new catheters to continue treatment; and no evidence on optimal timing of insertion of a new central venous catheter.
念珠菌血症最常影响那些已经患有严重的、可能危及生命的疾病的患者，并且常常导致显著的发病率和死亡率。大多数受影响的人都有中心静脉导管（CVC）。近年来，在这些病例中最佳的CVC管理方法一直存在广泛争议，而念珠菌血症的发病率已显著增加。
本综述的主要目的是研究拔除与保留CVC对患有念珠菌血症且已留置CVC的成人和儿童死亡率的影响。
我们检索了以下数据库，检索时间从建库至2015年12月3日：Cochrane对照试验中心注册库（CENTRAL）、医学期刊数据库（MEDLINE，Ovid SP）、荷兰医学文摘数据库（EMBASE，Ovid SP）、英联邦农业局数据库（CAB）、科学引文索引数据库（Web of Science）以及护理学与健康照护领域累积索引数据库（CINAHL）。我们在试验注册库以及排除文章的参考文献列表中搜索遗漏、未报告和正在进行的试验。
我们检索了随机对照试验（RCT）和半随机对照试验，这些试验涉及患有念珠菌血症的成人和儿童，且参与者被随机分配接受拔除CVC（本研究的干预措施），无论其发表状态、发表日期、是否设盲、已发表的结果或语言如何。然而，有两个主要因素使得在该人群中开展RCT成为一项艰巨任务：记录拔除导管对总体死亡率影响所需的大样本量；以及行业对开展此类试验缺乏经济利益。
我们的主要结局指标是死亡率。根据我们的方案，还计划了几个次要结局指标，如念珠菌属血培养转阴所需时间、持续性念珠菌血症的发生率、并发症、机械通气持续时间以及在重症监护病房（ICU）和医院的住院时间，同时还计划了各种亚组分析和敏感性分析。我们评估论文和摘要的合格性，并通过讨论解决分歧。然而，我们未能在本综述中纳入任何RCT或半随机对照试验，因此未进行荟萃分析。不过，我们选择对排除的观察性研究进行简要概述。
我们未找到RCT，因此没有可用于评估主要结局（死亡率）以及次要结局或不良反应的数据。因此，我们未进行统计分析。共有73项观察性研究报告了拔除或保留导管后各种临床相关结局。这些排除的观察性研究大多报告了拔除导管对念珠菌血症患者有有益影响。没有观察性研究报告支持保留导管的结果。然而，这些观察性研究在人群、病原体和干预措施方面差异很大。此外，它们存在指征性偏倚，且总体偏倚风险较高。因此，由于解释这些观察性研究结果存在困难（证据质量极低，GRADE - 推荐分级、评估、制定与评价工作组），我们无法提供建议或得出确凿结论。
尽管观察性研究表明支持早期拔除导管，但我们未找到符合条件的RCT或半随机对照试验来支持这些做法，因此无法得出确凿结论。现阶段，RCT没有提供证据支持早期或晚期拔除导管对念珠菌血症患者的生存或其他重要结局有益；没有证据表明关于拔除中心静脉导管并随后重新插入新导管以继续治疗的危害或益处评估；也没有关于插入新中心静脉导管的最佳时机的证据。
