Insertion cites of central venous catheter in adult hospitalized patients: a systematic review and network meta-analysis v1
Authors: Sakuraya,MD, MPH Masaaki , Okano Hiromu , Yoshihiro Shodai , Niida Shoko , Kimura Keina 
Published: May 2022

Review question What is the most preferable insertion cite ofcentral venous catheter for reducing infectious, thrombotic and mechanical complications in critically ill adult patients? Searches We will search for the eligible trials in the following databases: 1. MEDLINE via PubMed; 2. The Cochrane Central Register of Controlled Trials (CENTRAL); 3. Web of science; 4. Ichushi, a database of papers in the Japanese language; 5.Clinicaltrials.gov; 6. WHO ICTRP. Types of study to be included We will accept randomized controlled trials of publication status published. The language and the country in which the studies were conducted are not restricted. Randomized crossover trials, cluster randomized trials and quasi-experiment trials will be excluded. Condition or domain being studied Secure and reliable venous access is a cornerstone in the care of hospitalized adult patients, as well as for a variety of outpatient situations. Central venous catheter, which is inserted into deep vein, a key component of this practice. However, there are different complications among insertion sites, including jugular, subclavian, femoral, and peripheral vein. It is unclear which site is the most acceptable for central venous catheter considering various complications in hospitalized patients. It is important for clinicians to estimate the risk of complication, and for manager decreasing complication may be associated with a reduction in health care cost. Participants/population Inclusion We will include hospitalized patients aged 18 years or older who are inserted central venous access using maximal sterile barrier precautions Exclusion 1)Coated catheter（e.g., antimicrobial- impregnated, chlorhexidine/silver sulfadiazine, heparin） 2)Tunneled catheter Venous access port Catheter exchange over guidewire Intervention(s), exposure(s) Internal jugular: Any insertion techniques, any antiseptics and any number of lumenswill beacceptable. Subclavian: Any insertion techniques, any antiseptics and any number of lumens will be acceptable. Femoral: Any insertion techniques, any antiseptics and any number of lumens will be acceptable. Peripherally: The catheter is inserted peripherally, and the tip is placed in central venous. Any insertion techniques, any antiseptics and any number of lumens will be acceptable. If comparingcentral venous catheterwith peripherally insertedcentral venous catheter, we will adopt the most indwelling site, as an insertion site. Comparator(s)/control All above mentioned intervention can be controls. Main outcomes Clinically important infectious complication, which is related with catheter insertion and with systemic symptoms (e.g., sepsis, blood stream infection) Clinically important thrombotic complication with clinical symptoms or which requires treatment Clinically important mechanical complication, which requires procedures or careful observation (e.g., pneumothorax, hemothorax, hematoma, and bleeding) * Measures of effect The number of each outcome and total participant in group to calculate Relative Risk Additional outcome(s) None Data extraction (selection and coding) We will use machine learning algorithms for systematic reviews (high‐sensitivity strategies) to identify RCTs (https://robotsearch.vortext.systems/#).Two of four physicians (HO, SY, SN, KK) will screen the title and abstract at the first screening and the full text at the second screening for relevant studies and will independently extract data from included studies into standardized data recording forms. Disagreements will be resolved by discussion with one of three physicians who did not screen the study. We will ask the original author as necessary. If the study has only abstract and we do not evaluate whether they will meet our review criteria, we will attempt to contact the authors. If there is a discrepancy between the two reviewers, they will be discussed and solved by themselves. Discrepancy will be resolved by discussing with the third reviewer as necessary. We will extract the following study characteristics. We extracted the following study characteristics: Methods: study design, total study duration, number and locations of study centres, study setting, withdrawals, date of study initiation, and funding sources. Participants: number, age, sex, body mass index (BMI), setting, and inclusion/exclusion criteria. Interventions: insertion site, catheter type, duration of catheter placement, operator experience, antiseptic, dressing, and insertion technique. Outcomes: outcomes that were specified and collected and the timepoints reported. One review author (HO) will copy the data from the data collection form into the Review Manager 5 file. Risk of bias (quality) assessment We will assess the risk of bias of primary outcomes in included studies independently by two of four review authors (HO, SY, SN, KK) using Cochrane Risk of Bias tool 2.0 with respect to the following eight domains: (a) random sequence generation, (b) allocation concealment, (c) blinding of participants and personnel, (d) blinding of outcome assessors, (e) incomplete outcome data, (f) selective outcome reporting and (g) other sources of bias. Each bias will be graded as either ‘low-risk’, ‘unclear-risk’ or ‘high-risk’. The risk of bias of secondary outcomes in included studies will be assessed using Cochrane Risk of Bias tool 2.0 with respect to the following six domains: (a) Bias arising from the randomization process, (b) Bias due to deviations from intended interventions, (c) Bias due to missing outcome data, (d) Bias in measurement of the outcome, (e) Bias in selection of the reported result, (f) Overall risk of bias. If there is a discrepancy between the two reviewers, they will be discussed and solved by themselves. Discrepancy will be resolved by discussing with the third reviewer as necessary. Each domain will be evaluated in one of three categories: High risk, Low risk, Some concerns. Strategy for data synthesis Give the planned general approach to be used. Where appropriate a brief outline of analytic approach should be given. Data synthesis: Forest plots will be used for the meta-analysis, and effect size will be expressed as relative risk with 95% confidence interval for categorical data and as weighted mean differences with 95% CI for continuous data. Outcome measures will be pooled using a random effect model to take into account study-specific effects in measures. For all analyses, a two-sided p-value < 0.05 is considered significant. We will synthesize the data using Revman 5.3 (RevMan 2014) for pairwise meta-analysis. Assessment of heterogeneity: Study heterogeneity between trials for each outcome will be assessed by visual inspection of the forest plots and with an I² statistic for quantifying inconsistency (RevMan) (I squared values of 0% to 40%: might not be important; 30% to 60%: may represent moderate heterogeneity; 50% to 90%: may represent substantial heterogeneity; 75% to 100%: considerable heterogeneity). When heterogeneity is identified (I² statistic> 50%), we will investigate the reason. We will quantify it by the χ² test. Network meta-analysis will be performed by a frequentist-based approach with multivariate random effects meta-analysis. Inconsistency of the network model was estimated by using inconsistency factors and their uncertainty. In addition, ranking plots (rankograms) were constructed using the probability that a given treatment had the highest event rate for each outcome. The surface under the cumulative ranking curve (SUCRA), which is a simple transformation of the mean rank, was used to set the hierarchy of the treatments. We will assess the certainty of evidence by using the GRADE Working Group Approach for a network meta-analysis. Analysis of subgroups or subsets If data from the studies are sufficient, we will conduct the following subgroup analyses in order to investigate the impact of bias risk and assess the participants' heterogeneity in each study. Excluding studies comparing central venous catheters inserted in multiple sites withperipherally insertedcentral venous catheter Only for critically ill patients In addition, we will perform post-hoc sensitivity analyses to explore the sources of significant incoherence that were present for the primary outcomes, if necessary. Contact details for further information Masaaki Sakuraya masaaki.sakuraya@gmail.com Organizational affiliation of the review JA Hiroshima General Hospital, Jigozen 1-3-3, Hatsukaichi-city, Hiroshima, 738-8503, Japan Review team members and their organizational affiliations Dr. Masaaki Sakuraya Dr. Hiromu Okano Dr. Shodai Yoshihiro Dr. Niida Shoko Dr. Keina Kimura Funding sources/sponsors Not applicable. Conflicts of interest None known. Language No restriction. Country Japan