Second-Generation central venous catheter in the prevention of bloodstream infection: a systematic review 1

Abstract Objective: to evaluate the effectiveness and safety in the use of second-generation central venous catheters impregnated in clorhexidine and silver sulfadiazine when compared with other catheters, being them impregnated or not, in order to prevent the bloodstream infection prevention. Method: systematic review with meta-analysis. Databases searched: MEDLINE, EMBASE, CINAHL, LILACS/SciELO, Cochrane CENTRAL; search in Congress Proceedings and records from Clinical Trials. Results: 1.235 studies were identified, 97 were pre-selected and 4 were included. In catheter-related bloodstream infection, there was no statistical significance between second-generation impregnated catheter compared with the non-impregnated ones, absolute relative risk 1,5% confidence interval 95% (3%-1%), relative risk 0,68 (confidence interval 95%, 0,40-1,15) and number needed to treat 66. In the sensitivity analysis, there was less bloodstream infection in impregnated catheters (relative risk 0,50, confidence interval 95%, 0,26-0,96). Lower colonization, absolute relative risk 9,6% (confidence interval 95%, 10% to 4%), relative risk 0,51 (confidence interval 95% from 0,38-0,85) and number needed to treat 5. Conclusion: the use of second-generation catheters was effective in reducing the catheter colonization and infection when a sensitivity analysis is performed. Future clinical trials are suggested to evaluate sepsis rates, mortality and adverse effects.

In Brazil, second-generation, clorhexidine and silver sulfadiazine-impregnated CVC's are approved for use, by the National Agency for Health Surveillance (ANVISA) through register number 10216830036 with double and triple lumen 7 Fr. x 20 cm (11) .
The evaluation of the evidence on the effectiveness of this catheter in preventing bloodstream infection prevention is still scarce and in that sense the proposal of the present research was to search for evidence to support the decision-making process for introducing this catheter in the clinical practice.
Taking into account the specificity in the use of these devices in hospitalized patients, this research had the aim to evaluate the effectiveness and safety of the use of second-generation CVC's, impregnated in clorhexidine and silver sulfadiazine, as compared with other catheters being them impregnated or not, in the bloodstream infection prevention.

Methods
This is a systematic review with meta-analysis, following the recommendations of the Cochrane Collaboration Handbook. To formulate the review question, a PICO (12)    In the case of duplicate studies, the one with more complete or recent information was included.
The degree of concordance between reviewers was measured through the Kappa coefficient (13) and the index was 0,988 with a p=<0,001, showing high concordance between the two reviewers (13) .
For the primary outcome CRBSI, were considered those patients or catheters with lab evidence of CRBSI, defined as those with isolated micro-organisms, from one or more positive blood cultures, collected separately (from peripheral blood and catheter) without any other identifiable infection source (5,14) .
Other diagnostic criteria were considered as long as they were justified by valid sources.
The secondary outcomes were defined as follows: -Colonization -patients with CVC colonization, identified through positive culture defined with semiquantitative culture (≥15UFC per catheter segment) positive or quantitative (≥10 2 UFC per catheter segment) proximal or distal from the catheter segment presenting the same microorganism that was isolated in the blood and in the catheter (5,14). Other criteria adopted by the authors of the studies were considered, as long as their definitions were justified in valid sources. The clinical heterogeneity was assessed through the type of participants, interventions and outcomes of each study. The meta-analysis was performed by outcome. The statistical heterogeneity was calculated through chi-squared test with significance level set at 10% (p<0,10) (13) . The heterogeneity test was only calculated when the meta-analysis had two or more studies and then was computed the I 2 test. The heterogeneity was considered as important when I 2 was larger that 50%.
The rates of CRBSI per 1.000 catheter/day were calculated using the methods as stated in chapter 9.4.8 of Cochrane Handbook (13) . Firstly the RR was calculated by dividing the intervention group rate by the control group rate. The relative risk logarithm (log

Results
Of the 1.235 studies identified, 97 were pre-   In the first domain results happened because the study authors did not provide enough information regarding the blinding of the participants that handled the catheter (characteristic).
In the second domain, the incomplete data about losses and exclusions were the cause of the rise of the attrition bias rates and put the studies in high bias risk. There was a 50% of uncertain bias risk linked to allocation concealment, due to the lack of details about the methodology that, even though described the studies as controlled or blind, did not specified the research design data, impeding a good evaluation of the results quality.  (Figure 4).    Practices Advisory Committee) support the use of clorhexidine and silver sulfadiazine impregnated CVC's for preventing the CRBSI (5,8) .

Conclusions
Regarding the practice implications, the selected studies that used second-generation, clorehexidine and silver sulfadiazine impregnated CVC's evidenced We recommend studies with infants to determine the effectiveness of second-generation, clorhexidine and silver sulfadiazine impregnated CVC's in this population, and to estimate the CRBSI that is linked to the use of such catheter, as well as colonization, sepsis, mortality, adverse effects and costs.