Abstract: Thirteen studies were eligible for inclusion, but only 12 studies contributed data, with a total of 3446 CVCs assessed. The total number of participants enrolled was unclear as some studies did not provide such information. The participants were mainly adults admitted to intensive care units, haematology oncology units or general wards. Most studies assessed skin antisepsis prior to insertion and regularly thereafter during the in-dwelling period of the CVC, ranging from every 24 h to every 72 h. The methodological quality of the included studies was mixed due to wide variation in their risk of bias. Most trials did not adequately blind the participants or personnel, and four of the 12 studies had a high risk of bias for incomplete outcome data. Three studies compared different antisepsis regimens with no antisepsis. There was no clear evidence of a difference in all outcomes examined, including catheter-related BSI, septicaemia, catheter colonisation and number of patients who required systemic antibiotics for any of the three comparisons involving three different antisepsis regimens (aqueous povidone-iodine, aqueous chlorhexidine and alcohol compared with no skin antisepsis). However, there were great uncertainties in all estimates due to underpowered analyses and the overall very low quality of evidence presented.There were multiple head-to-head comparisons between different skin antiseptic agents, with different combinations of active substance and base solutions. The most frequent comparison was chlorhexidine solution versus povidone-iodine solution (any base). There was very low quality evidence (downgraded for risk of bias and imprecision) that chlorhexidine may reduce catheter-related BSI compared with povidone-iodine (RR of 0.64, 95% CI 0.41 to 0.99; ARR 2.30%, 95% CI 0.06 to 3.70%). This evidence came from four studies involving 1436 catheters. None of the individual subgroup comparisons of aqueous chlorhexidine versus aqueous povidone-iodine, alcoholic chlorhexidine versus aqueous povidone-iodine and alcoholic chlorhexidine versus alcoholic povidone-iodine showed clear differences for catheter-related BSI or mortality (and were generally underpowered). Mortality was only reported in a single study. There was very low quality evidence that skin antisepsis with chlorhexidine may also reduce catheter colonisation relative to povidone-iodine (RR of 0.68, 95% CI 0.56 to 0.84; ARR 8%, 95% CI 3% to 12%; ; five studies, 1533 catheters, downgraded for risk of bias, indirectness and inconsistency). Evaluations of other skin antiseptic agents were generally in single, small studies, many of which did not report the primary outcome of catheter-related BSI. Trials also poorly reported other outcomes, such as skin infections and adverse events. It is not clear whether cleaning the skin around CVC insertion sites with antiseptic reduces catheter related blood stream infection compared with no skin cleansing. Skin cleansing with chlorhexidine solution may reduce rates of CRBSI and catheter colonisation compared with cleaning with povidone iodine. These results are based on very low quality evidence, which means the true effects may be very different. Moreover these results may be influenced by the nature of the antiseptic solution (i.e. aqueous or alcohol-based). Further RCTs are needed to assess the effectiveness and safety of different skin antisepsis regimens in CVC care; these should measure and report critical clinical outcomes such as sepsis, catheter-related BSI and mortality.

Plain-language summary: In May 2016 we searched medical databases to find randomised controlled trials looking at the use of skin antiseptics in people with CVCs. We included 13 studies in this review, although only 12 studies contributed data for a total of 3446 CVCs. The study participants were mainly adults in intensive care units or other specialist hospital units. We reported our findings in terms of the number of catheters, as some studies did not provide the number of patients assessed, and some patients had more than one CVC.One study was funded by a national research body, five studies were funded in whole or in part by at least a pharmaceutical company, and in the remaining seven studies funding sources were not stated. Three studies examined the effect of cleansing versus no cleansing, and found no clear evidence of differences in blood infections, infections in the catheter and need for antibiotics between patients who received cleansing compared to those who did not. Chlorhexidine solution may reduce blood infections associated with the catheter compared with povidone-iodine solution (reducing the infection rate from 64 cases per 1000 patients with a CVC with povidone iodine to 41 cases of infection per 1000 with chlorhexidine). This translates into the need to treat 44 people to avoid one additional bloodstream infection. Chlorhexidine solution may (compared with povidone iodine solution) also reduce the presence of infectious organisms within the catheter (reduced from 240 infected catheters per 1000 people to 189 infected catheters per 1000 people). It is unclear whether antiseptic skin cleansing influences mortality rates as only one study reported this and although similar death rates were observed with povidone iodine and chlorhexidine, small numbers mean a difference cannot be ruled out. The overall quality of evidence was poor due to flaws in the way the studies were designed, small study sizes, inconsistency of the results between the included studies and the nature of the outcomes reported. These flaws have reduced our confidence in the results of the studies. This means we cannot be certain whether cleaning the skin around CVC insertion sites with antiseptic reduces catheter-related blood stream infection and other harmful effects, such as overall blood infections and mortality compared with no skin cleansing. Cleansing with chlorhexidine solution may be more effective than povidone iodine but the quality of the evidence was very low.