Elsevier

The Lancet

Volume 386, Issue 10008, 21–27 November 2015, Pages 2069-2077
The Lancet

Articles
Skin antisepsis with chlorhexidine–alcohol versus povidone iodine–alcohol, with and without skin scrubbing, for prevention of intravascular-catheter-related infection (CLEAN): an open-label, multicentre, randomised, controlled, two-by-two factorial trial

https://doi.org/10.1016/S0140-6736(15)00244-5Get rights and content

Summary

Background

Intravascular-catheter-related infections are frequent life-threatening events in health care, but incidence can be decreased by improvements in the quality of care. Optimisation of skin antisepsis is essential to prevent short-term catheter-related infections. We hypothesised that chlorhexidine–alcohol would be more effective than povidone iodine–alcohol as a skin antiseptic to prevent intravascular-catheter-related infections.

Methods

In this open-label, randomised controlled trial with a two-by-two factorial design, we enrolled consecutive adults (age ≥18 years) admitted to one of 11 French intensive-care units and requiring at least one of central-venous, haemodialysis, or arterial catheters. Before catheter insertion, we randomly assigned (1:1:1:1) patients via a secure web-based random-number generator (permuted blocks of eight, stratified by centre) to have all intravascular catheters prepared with 2% chlorhexidine–70% isopropyl alcohol (chlorhexidine–alcohol) or 5% povidone iodine–69% ethanol (povidone iodine–alcohol), with or without scrubbing of the skin with detergent before antiseptic application. Physicians and nurses were not masked to group assignment but microbiologists and outcome assessors were. The primary outcome was the incidence of catheter-related infections with chlorhexidine–alcohol versus povidone iodine–alcohol in the intention-to-treat population. This study is registered with ClinicalTrials.gov, number NCT01629550 and is closed to new participants.

Findings

Between Oct 26, 2012, and Feb 12, 2014, 2546 patients were eligible to participate in the study. We randomly assigned 1181 patients (2547 catheters) to chlorhexidine–alcohol (594 patients with scrubbing, 587 without) and 1168 (2612 catheters) to povidone iodine–alcohol (580 patients with scrubbing, 588 without). Chlorhexidine–alcohol was associated with lower incidence of catheter-related infections (0·28 vs 1·77 per 1000 catheter-days with povidone iodine–alcohol; hazard ratio 0·15, 95% CI 0·05–0·41; p=0·0002). Scrubbing was not associated with a significant difference in catheter colonisation (p=0·3877). No systemic adverse events were reported, but severe skin reactions occurred more frequently in those assigned to chlorhexidine–alcohol (27 [3%] patients vs seven [1%] with povidone iodine–alcohol; p=0·0017) and led to chlorhexidine discontinuation in two patients.

Interpretation

For skin antisepsis, chlorhexidine–alcohol provides greater protection against short-term catheter-related infections than does povidone iodine–alcohol and should be included in all bundles for prevention of intravascular catheter-related infections.

Funding

University Hospital of Poitiers, CareFusion.

Introduction

Catheter-related bloodstream infections are common infections in health care settings that are associated with high mortality.1 Skin at the insertion site and the catheter hub or connector are the main sources of pathogens for infection, with skin the main source when catheters are placed for a shorter duration of time and the hub or connector being the main source in longer timeframes.2 Therefore, optimum skin antisepsis is crucial during short-term catheter insertion and maintenance. Alcohol has the greatest immediate efficacy, with 70% isopropyl alcohol being microbiologically superior to 69% ethanol, but does not have persistency on skin.3 The action of chlorhexidine or povidone iodine is slower, less profound, and chlorhexidine has substantial persistency on skin.4, 5, 6 Use of chlorhexidine–alcohol at chlorhexidine concentrations higher than 0·5% has been advocated as the first-line solution for catheter insertion-site antisepsis in USA7 and English8 guidelines because it combines the immediate microbicidal activity of alcohol and the persistent (residual) activity on skin of chlorhexidine. However, the authors of these recommendations point out that few head-to-head comparisons of chlorhexidine and povidone iodine in alcoholic formulations are available and that a large-scale randomised trial would be helpful. French guidelines9 recommend an alcoholic formulation of either chlorhexidine or povidone iodine in this setting with no advantage of one product over the other.

Research in context

Evidence before this study

In their 2011 guidelines for the prevention of intravascular catheter-related infections, the US Centers for Disease Control and Prevention stated that substances for skin preparation before catheter insertion was an unresolved issue. Although evidence was accumulating for use of chlorhexidine for skin preparation before catheter insertion, the higher clinical efficacy of chlorhexidine reported in studies could not be attributed to the chlorhexidine alone, but rather to the combination of chlorhexidine with alcohol, when compared with aqueous povidone iodine. Chlorhexidine in alcohol and povidone iodine in alcohol had not been compared head to head in a large-scale trial. The bactericidal efficacy of povidone iodine might be compromised by the presence of skin biomaterials, with possible partial inactivation of the antiseptic agent and so whether scrubbing before skin antisepsis before surgery should be done was also debated.

Added value of this study

We did a multicentre randomised controlled trial in 11 intensive care units in which all patients due to receive a central venous catheter, arterial catheter, or haemodialysis catheter were enrolled to receive skin preparation with 2% chlorhexidine–70% isopropyl alcohol or 5% povidone iodine–69% ethanol, both preceded or not by skin scrubbing, for antisepsis. Patients assigned to receive the chlorhexidine–alcohol combination had fewer catheter-related infections and catheter-related bloodstream infections compared with those assigned to receive the povidone iodine–alcohol combination. Skin scrubbing before skin antisepsis did not reduce the incidence of catheter colonisation.

Implications of all the available evidence

Chlorhexidine–alcohol combination should now be the standard of skin preparation before catheter insertion. Scrubbing of the skin with detergent should not. Whether the combination should be used for skin preparation before surgery remains to be established, as do the optimum concentration of chlorhexidine and type and concentration of alcohol to be combined with chlorhexidine.

Scrubbing of the skin with antiseptic detergent before application of an antiseptic solution decreases the amount of bacteria and (potentially antiseptic-inhibiting) protein-rich biomaterials on the skin.10 The recommendations of US Centers for Disease Control and Prevention (CDC) do not provide advice on cleansing the skin before application of antiseptic.7 No large randomised trials have tested skin cleansing with a detergent before antisepsis.

We hypothesised that application of 2% chlorhexidine–70% isopropyl alcohol (chlorhexidine–alcohol) was more effective than 5% povidone iodine–69% ethanol (povidone iodine–alcohol) to prevent short-term catheter-related infections. We also hypothesised that scrubbing of the skin with an antiseptic detergent before antiseptic application would not reduce catheter colonisation compared with application of antiseptic alone.

Section snippets

Study design and participants

We did an open-label, multicentre, randomised, controlled, two-by-two factorial design study. The study protocol has been published previously.11 We recruited patients in 11 French intensive-care units in five university hospitals and one general hospital. Five intensive-care units were medical, five surgical, and one medical–surgical. We enrolled consecutive adult patients (≥18 years) who required at least one of an arterial, haemodialysis, or central venous catheter for 48 h or longer unless

Results

Between Oct 26, 2012, and Feb 12, 2014, 2546 patients were eligible to participate in the study; we enrolled 2349 (figure 1). 1181 patients (2547 catheters) were randomly allocated to chlorhexidine–alcohol (594 patients with scrubbing, 587 without) and 1168 (2612 catheters) to povidone iodine–alcohol (580 patients with scrubbing, 588 without; Table 1, Table 2).

We cultured or did culturing to determine the differential time to positivity before catheter removal for 4442 (86%) of the 5159

Discussion

Use of 2% chlorhexidine–alcohol for skin antisepsis was associated with six-fold decreases in the incidences of catheter-related infection and catheter colonisation and a five-fold decrease in the incidence of CR-BSI, compared with 5% povidone iodine–alcohol. Skin scrubbing before antiseptic application was not associated with a further decrease in catheter colonisation. Adverse skin reactions were rare but more common with chlorhexidine–alcohol than with povidone iodine–alcohol.

Previous

References (26)

  • NP O'Grady et al.

    Summary of recommendations: Guidelines for the Prevention of Intravascular Catheter-related Infections

    Clin Infect Dis

    (2011)
  • HP Loveday et al.

    Epic3: national evidence-based guidelines for preventing healthcare-associated infections in NHS hospitals in England

    J Hosp infect

    (2014)
  • [Prevention of hospital-acquired sepsis in intensive care unit (except cross transmission and neonate)]

    Ann Fr Anesth Reanim

    (2009)
  • Cited by (0)

    Investigators listed in the appendix

    View full text