The Forgotten Role of Alcohol: A Systematic Review and Meta-Analysis of the Clinical Efficacy and Perceived Role of Chlorhexidine in Skin Antisepsis

BACKGROUND Skin antisepsis is a simple and effective measure to prevent infections. The efficacy of chlorhexidine is actively discussed in the literature on skin antisepsis. However, study outcomes due to chlorhexidine-alcohol combinations are often attributed to chlorhexidine alone. Thus, we sought to review the efficacy of chlorhexidine for skin antisepsis and the extent of a possible misinterpretation of evidence. METHODS We performed a systematic literature review of clinical trials and systematic reviews investigating chlorhexidine compounds for blood culture collection, vascular catheter insertion and surgical skin preparation. We searched PubMed, CINAHL, the Cochrane Library, the Agency for Healthcare Research and Quality website, several clinical trials registries and a manufacturer website. We extracted data on study design, antiseptic composition, and the following outcomes: blood culture contamination, catheter colonisation, catheter-related bloodstream infection and surgical site infection. We conducted meta-analyses of the clinical efficacy of chlorhexidine compounds and reviewed the appropriateness of the authors' attribution. RESULTS In all three application areas and for all outcomes, we found good evidence favouring chlorhexidine-alcohol over aqueous competitors, but not over competitors combined with alcohols. For blood cultures and surgery, we found no evidence supporting chlorhexidine alone. For catheters, we found evidence in support of chlorhexidine alone for preventing catheter colonisation, but not for preventing bloodstream infection. A range of 29 to 43% of articles attributed outcomes solely to chlorhexidine when the combination with alcohol was in fact used. Articles with ambiguous attribution were common (8-35%). Unsubstantiated recommendations for chlorhexidine alone instead of chlorhexidine-alcohol were identified in several practice recommendations and evidence-based guidelines. CONCLUSIONS Perceived efficacy of chlorhexidine is often in fact based on evidence for the efficacy of the chlorhexidine-alcohol combination. The role of alcohol has frequently been overlooked in evidence assessments. This has broader implications for knowledge translation as well as potential implications for patient safety.