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Chlorhexidine 2% and choice of transparent dressing increase skin reactions at central venous catheter insertion sites
ARTICLE IN PRESS American Journal of Infection Control ■■ (2016) ■■-■■
Contents lists available at ScienceDirect
American Journal of Infection Control
American Journal of Infection Control
j o u r n a l h o m e p a g e : w w w. a j i c j o u r n a l . o r g
Brief Report
Chlorhexidine 2% and choice of transparent dressing increase skin reactions at central venous catheter insertion sites Mark Loewenthal MB, BS, DTM&H, MMedSci, FRACP a,b,*, Pauline Dobson RN, CNS Cert, MHSc (HIV Stud) a,b, Michael Boyle MB, BS, MD, FRACP, FRCPA a,b a b
Immunology and Infectious Disease Unit, John Hunter Hospital, New Lambton Heights, NSW, Australia Faculty of Health and Medicine, University of Newcastle, Newcastle, NSW, Australia
Key Words: Central venous catheter infection skin reaction chlorhexidine catheter dressing transparent film dressing
Infection at central venous catheter (CVC) sites remains a common problem, particularly with longterm use. This report discusses the influence of choice of transparent dressing type and chlorhexidine concentration on skin reactions at CVC insertion sites. A concentration of 2% chlorhexidine is associated with a higher rate of skin reactions than either 0.5% or 1% chlorhexidine. Higher chlorhexidine concentrations may not decrease the number of central line–associated bloodstream infections. © 2016 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Elsevier Inc. All rights reserved.
BACKGROUND Infection at central venous catheter (CVC) sites remains a common problem, particularly with long-term use.1 Chlorhexidine gluconate (CHG) is the preferred solution for disinfection because of its greater efficacy than povidone-iodine solution or alcohol.2,3 Despite CHG’s popularity, it can cause irritation, erosive contact dermatitis,4 and in rare cases, anaphylaxis. Studies comparing different CVC dressings have focused on reducing the microbial burden under the dressing, reducing the number of infections, and their acceptability to nursing staff. Few have examined the propensity of transparent film dressings to cause local skin irritation. The aim of this study was to determine if the concentration of CHG and CVC dressing type are independent predictors of local skin reactions. MATERIALS AND METHODS The study was conducted in the Out & About Home IV Therapy Program, based at a 700-bed acute tertiary referral hospital in Newcastle, NSW, Australia. The program manages pediatric and adult patients with serious infections requiring long-term intravenous an-
tibiotics administered at home. All patients included in the study had a CVC in place: a peripherally inserted CVC, nontunneled shortterm CVC, implantable port, or tunneled CVC (Hickman or Broviac). None of the catheters were impregnated with antibiotics or antiseptics. In the decade under study, the CVC dressing materials (solutions and transparent film) altered (Table 1), but the techniques for cleansing the exit site and the frequency of routine dressing change remained the same (7-day changeover), as did most of the nursing staff. Dressing 1 was IV3000 - Standard (Smith & Nephew Medical Ltd., Hull, UK), and dressing 2 was Mepore Film (Mo˝lnlycke Health Care, Göteborg, Sweden). Both dressings were polyurethane films with a polyacrylate adhesive. Site cleansing materials used were 0.5% solution (0.5% CHG in 70% ethanol [Riotane; Orion, Balcatta, Australia]), 1% solution (1% CHG in 75% ethanol [Persist Plus Swabstick; BD]), and 2% solution (2% CHG in 70% isopropyl alcohol [Solu-I.V. Swabstick; Les Enterprises Solumed Inc., Laval, Canada]).
Table 1 Periods of use of transparent skin dressing and skin preparation agents
Period * Address correspondence to Mark Loewenthal, MB, BS, DTM&H, MMedSci, FRACP, Immunology and Infectious Diseases Unit, John Hunter Hospital, Lookout Rd, New Lambton Heights, Newcastle NSW 2305, Australia. E-mail address: [email protected] (M. Loewenthal). Funding/Support: Supported by a trust fund held by Hunter New England Local Health District on behalf of M.B. Conflicts of Interest: None to report.
August 21, 2004-August 21, 2009 August 22, 2009-March 1, 2010 March 2, 2010-June 6, 2011 June 7, 2011-July 31, 2012 August 1, 2012-July 17, 2014
Film dressing
% CHG with alcohol
Dressing 1* Dressing 2 Dressing 2 Dressing 2 Dressing 1
0.5% + 70% ethanol* 0.5% + 70% ethanol 2% + 70% isopropyl alcohol 1% + 75% ethanol 1% + 75% ethanol
CHG, chlorhexidine gluconate. *Dressing 1 and 0.5% solution is the comparator.
0196-6553/© 2016 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.ajic.2016.06.020
ARTICLE IN PRESS M. Loewenthal et al. / American Journal of Infection Control ■■ (2016) ■■-■■
2
Table 2 IRRs for the number of skin reactions and bloodstream infections during the various study phases Skin reactions Dressing + CHG concentration (%)
No. of patient days
Skin reactions per 1,000 patient days*
Dressing 1 + 0.5% Dressing 2 + 0.5% Dressing 2 + 2% Dressing 2 + 1% Dressing 1 + 1%
39,785 4,361 9,467 9,862 16,851
0.232 1.34 1.25 3.88 1.25
Bloodstream infections IRR
95% confidence interval for IRR
Days of Observation
No. of CRBSI
IRR
P value
95% confidence interval for IRR
1 (Reference) 5.92 5.82 18.1 5.52
1.8-19 2.1-16 7.7-42 2.3-13.1
39,973 4,416 9,773 10,303 17,147
6 1 1 2 0
1 2.32 1.00 1.82 -
Reference .476 .998 .503 .997
0.23-23 0.11-9.6 0.32-10 0
CHG, chlorhexidine gluconate; CRBSI, catheter related blood stream infection; IRR, incidence rate ratio. *Adjusted for multiple admissions.
Nurses documented any skin reaction, including inflammation, itching, or burning, or those that required substitution of the skin cleansing solution or brand of transparent skin dressing. Skin reactions to the adhesive tape securing the catheter close to the dressing site were excluded. Patient details were entered into a Microsoft Access database (Microsoft, Redmond, WA) at the time of admission. After admission, the medical record was independently reviewed for adverse events by a data nurse with extensive experience in hospital in the home. Patients admitted during a changeover period between products (Table 1) were excluded from the analysis. Patients with >1 reaction during the period only had their initial skin reaction included in the analysis. Subsequent reactions were excluded, and as a result the number of patient days differs between the analysis of skin reactions and bloodstream infections. The Centers for Disease Control and Prevention definition for central line–associated bloodstream infection (CLABSI) was used to define definite infection.5 Statistical analysis Age-adjusted (<60 and ≥60 years) incidence rates for skin reactions and bloodstream infections in the 5 periods were compared using Poisson regression. A random effects term on medical record number was included, given some patients had multiple admissions. Coefficients were compared using Wald tests. Results are expressed as skin reactions per 1,000 patient days. Incidence rate ratios (IRRs) were calculated with dressing 1 and 0.5% solution as comparator. Analyses were conducted using Stata version 13 (StataCorp, College Station, TX). RESULTS During the period, 2,688 patients were admitted. Sixty were excluded (admitted during a changeover period). Of the 2,628 patients included, there were 3,723 admissions and 80,326 patient days of observation. The median age of patients was 58.7 years (range, 0.296.5 years). Sixty-nine skin reactions were reported (Table 2). Changing the dressing type, without changing the CHG concentration, was associated with an almost 6-fold increase in risk (IRR, 5.92; 95% confidence interval [CI], 1.8-19) of skin reactions; increasing CHG concentrations from 0.5% to 1% without changing the dressing type did not increase skin reactions (IRR, 5.92; 95% CI, 1.819 vs IRR, 5.82; 95% CI, 2.1-16; P = .977), but increasing CHG from 1% to 2% led to a significant increase in skin reactions (IRR, 3.10; 95% CI, 1.34-7.24; P = .008) (Table 2). Skin reactions usually occurred within the first week (data not shown). Eleven definite CLABSIs occurred in 8 patients, including one during the changeover period from dressing 1 to dressing 2. This infection was excluded. There was no difference in the incidence of CLABSI between the groups (Table 2).
DISCUSSION There are economic and clinical benefits of using CHG instead of povidone-iodine, including improvements in the incidence of catheter-related bloodstream infections and deaths attributable to these infections.6 Hypersensitivity reactions seem to be limited to those with localized skin reactions, such as erythema and erosive contact dermatitis, and may be a result of prolonged or repeated exposure.7 However, such reactions are poorly reported.8 Those that have reported hypersensitivity reactions after CHG use suggest skin inflammation rates of between 3% and 17%.9,10 Interestingly, a Cochrane review of gauze and tape, and transparent polyurethane dressings for CVCs, has reported a greater incidence of catheterrelated bloodstream infections with polyurethane dressings compared with gauze and tape,8 suggesting that visual inspection of the insertion site may not be an accurate way of identifying infection. Our study has some limitations, including the observational nature of the data, that the initial period (comparator) was longer than the other dressing periods, and the fact that the different transparent dressing and CHG concentrations under study were used sequentially not contemporaneously. Additionally, the degree of prior exposure to chlorhexidine, which may lead to sensitization, was unknown.11 CONCLUSIONS A concentration of 2% CHG is associated with a higher rate of skin reactions than either 0.5% or 1% CHG. Higher CHG concentrations may not decrease the number of CLABSIs. Dressing 2 was associated with a higher incidence of skin reactions than dressing 1 when used in combination with CHG solutions to dress CVC sites. Acknowledgments We thank the nursing staff of the Out & About IV Therapy Program who diligently recorded all skin reactions, and Kellie Schneider, RN, for entering, interpreting, and maintaining the clinical data. We also thank Dr Belinda Butcher, CMPP, WriteSource Medical Pty Ltd, for medical writing assistance, which was funded from a trust fund held by Hunter New England Local Health District on behalf of M.B. References 1. Theaker C. Infection control issues in central venous catheter care. Intensive Crit Care Nurs 2005;21:99-109. 2. Maki DG, Ringer M, Alvarado CJ. Prospective randomised trial of povidone-iodine, alcohol, and chlorhexidine for prevention of infection associated with central venous and arterial catheters. Lancet 1991;338:339-43.
ARTICLE IN PRESS M. Loewenthal et al. / American Journal of Infection Control ■■ (2016) ■■-■■
3. Chaiyakunapruk N, Veenstra DL, Lipsky BA, Saint S. Chlorhexidine compared with povidone-iodine solution for vascular catheter-site care: a meta-analysis. Ann Intern Med 2002;136:792-801. 4. Weitz NA, Lauren CT, Weiser JA, LeBoeuf NR, Grossman ME, Biagas K, et al. Chlorhexidine gluconate-impregnated central access catheter dressings as a cause of erosive contact dermatitis: a report of 7 cases. JAMA Dermatol 2013;149:195-9. 5. Centers for Disease Control and Prevention. 2016 NHSN patient safety component manual. Available from: http://www.cdc.gov/nhsn/pdfs/pscmanual/pcsmanual _current.pdf. Accessed June 3, 2016. 6. Chaiyakunapruk N, Veenstra DL, Lipsky BA, Sullivan SD, Saint S. Vascular catheter site care: the clinical and economic benefits of chlorhexidine gluconate compared with povidone iodine. Clin Infect Dis 2003;37:764-71. 7. Calogiuri GF. Chlorhexidine hypersensitivity: a critical and updated review. J Allergy Ther 2013;4:141.
3
8. Webster J, Gillies D, O’Riordan E, Sherriff KL, Rickard CM. Gauze and tape and transparent polyurethane dressings for central venous catheters. Cochrane Database Syst Rev 2011;(11):CD003827. 9. Valles J, Fernandez I, Alcaraz D, Chacon E, Cazorla A, Canals M, et al. Prospective randomized trial of 3 antiseptic solutions for prevention of catheter colonization in an intensive care unit for adult patients. Infect Control Hosp Epidemiol 2008;29:847-53. 10. Mimoz O, Lucet J-C, Kerforne T, Pascal J, Souweine B, Goudet V, et al. 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. Lancet 2015;386:2069-77. 11. Liippo J, Kousa P, Lammintausta K. The relevance of chlorhexidine contact allergy. Contact Dermatitis 2011;64:229-34.
Contents lists available at ScienceDirect
American Journal of Infection Control
American Journal of Infection Control
j o u r n a l h o m e p a g e : w w w. a j i c j o u r n a l . o r g
Brief Report
Chlorhexidine 2% and choice of transparent dressing increase skin reactions at central venous catheter insertion sites Mark Loewenthal MB, BS, DTM&H, MMedSci, FRACP a,b,*, Pauline Dobson RN, CNS Cert, MHSc (HIV Stud) a,b, Michael Boyle MB, BS, MD, FRACP, FRCPA a,b a b
Immunology and Infectious Disease Unit, John Hunter Hospital, New Lambton Heights, NSW, Australia Faculty of Health and Medicine, University of Newcastle, Newcastle, NSW, Australia
Key Words: Central venous catheter infection skin reaction chlorhexidine catheter dressing transparent film dressing
Infection at central venous catheter (CVC) sites remains a common problem, particularly with longterm use. This report discusses the influence of choice of transparent dressing type and chlorhexidine concentration on skin reactions at CVC insertion sites. A concentration of 2% chlorhexidine is associated with a higher rate of skin reactions than either 0.5% or 1% chlorhexidine. Higher chlorhexidine concentrations may not decrease the number of central line–associated bloodstream infections. © 2016 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Elsevier Inc. All rights reserved.
BACKGROUND Infection at central venous catheter (CVC) sites remains a common problem, particularly with long-term use.1 Chlorhexidine gluconate (CHG) is the preferred solution for disinfection because of its greater efficacy than povidone-iodine solution or alcohol.2,3 Despite CHG’s popularity, it can cause irritation, erosive contact dermatitis,4 and in rare cases, anaphylaxis. Studies comparing different CVC dressings have focused on reducing the microbial burden under the dressing, reducing the number of infections, and their acceptability to nursing staff. Few have examined the propensity of transparent film dressings to cause local skin irritation. The aim of this study was to determine if the concentration of CHG and CVC dressing type are independent predictors of local skin reactions. MATERIALS AND METHODS The study was conducted in the Out & About Home IV Therapy Program, based at a 700-bed acute tertiary referral hospital in Newcastle, NSW, Australia. The program manages pediatric and adult patients with serious infections requiring long-term intravenous an-
tibiotics administered at home. All patients included in the study had a CVC in place: a peripherally inserted CVC, nontunneled shortterm CVC, implantable port, or tunneled CVC (Hickman or Broviac). None of the catheters were impregnated with antibiotics or antiseptics. In the decade under study, the CVC dressing materials (solutions and transparent film) altered (Table 1), but the techniques for cleansing the exit site and the frequency of routine dressing change remained the same (7-day changeover), as did most of the nursing staff. Dressing 1 was IV3000 - Standard (Smith & Nephew Medical Ltd., Hull, UK), and dressing 2 was Mepore Film (Mo˝lnlycke Health Care, Göteborg, Sweden). Both dressings were polyurethane films with a polyacrylate adhesive. Site cleansing materials used were 0.5% solution (0.5% CHG in 70% ethanol [Riotane; Orion, Balcatta, Australia]), 1% solution (1% CHG in 75% ethanol [Persist Plus Swabstick; BD]), and 2% solution (2% CHG in 70% isopropyl alcohol [Solu-I.V. Swabstick; Les Enterprises Solumed Inc., Laval, Canada]).
Table 1 Periods of use of transparent skin dressing and skin preparation agents
Period * Address correspondence to Mark Loewenthal, MB, BS, DTM&H, MMedSci, FRACP, Immunology and Infectious Diseases Unit, John Hunter Hospital, Lookout Rd, New Lambton Heights, Newcastle NSW 2305, Australia. E-mail address: [email protected] (M. Loewenthal). Funding/Support: Supported by a trust fund held by Hunter New England Local Health District on behalf of M.B. Conflicts of Interest: None to report.
August 21, 2004-August 21, 2009 August 22, 2009-March 1, 2010 March 2, 2010-June 6, 2011 June 7, 2011-July 31, 2012 August 1, 2012-July 17, 2014
Film dressing
% CHG with alcohol
Dressing 1* Dressing 2 Dressing 2 Dressing 2 Dressing 1
0.5% + 70% ethanol* 0.5% + 70% ethanol 2% + 70% isopropyl alcohol 1% + 75% ethanol 1% + 75% ethanol
CHG, chlorhexidine gluconate. *Dressing 1 and 0.5% solution is the comparator.
0196-6553/© 2016 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.ajic.2016.06.020
ARTICLE IN PRESS M. Loewenthal et al. / American Journal of Infection Control ■■ (2016) ■■-■■
2
Table 2 IRRs for the number of skin reactions and bloodstream infections during the various study phases Skin reactions Dressing + CHG concentration (%)
No. of patient days
Skin reactions per 1,000 patient days*
Dressing 1 + 0.5% Dressing 2 + 0.5% Dressing 2 + 2% Dressing 2 + 1% Dressing 1 + 1%
39,785 4,361 9,467 9,862 16,851
0.232 1.34 1.25 3.88 1.25
Bloodstream infections IRR
95% confidence interval for IRR
Days of Observation
No. of CRBSI
IRR
P value
95% confidence interval for IRR
1 (Reference) 5.92 5.82 18.1 5.52
1.8-19 2.1-16 7.7-42 2.3-13.1
39,973 4,416 9,773 10,303 17,147
6 1 1 2 0
1 2.32 1.00 1.82 -
Reference .476 .998 .503 .997
0.23-23 0.11-9.6 0.32-10 0
CHG, chlorhexidine gluconate; CRBSI, catheter related blood stream infection; IRR, incidence rate ratio. *Adjusted for multiple admissions.
Nurses documented any skin reaction, including inflammation, itching, or burning, or those that required substitution of the skin cleansing solution or brand of transparent skin dressing. Skin reactions to the adhesive tape securing the catheter close to the dressing site were excluded. Patient details were entered into a Microsoft Access database (Microsoft, Redmond, WA) at the time of admission. After admission, the medical record was independently reviewed for adverse events by a data nurse with extensive experience in hospital in the home. Patients admitted during a changeover period between products (Table 1) were excluded from the analysis. Patients with >1 reaction during the period only had their initial skin reaction included in the analysis. Subsequent reactions were excluded, and as a result the number of patient days differs between the analysis of skin reactions and bloodstream infections. The Centers for Disease Control and Prevention definition for central line–associated bloodstream infection (CLABSI) was used to define definite infection.5 Statistical analysis Age-adjusted (<60 and ≥60 years) incidence rates for skin reactions and bloodstream infections in the 5 periods were compared using Poisson regression. A random effects term on medical record number was included, given some patients had multiple admissions. Coefficients were compared using Wald tests. Results are expressed as skin reactions per 1,000 patient days. Incidence rate ratios (IRRs) were calculated with dressing 1 and 0.5% solution as comparator. Analyses were conducted using Stata version 13 (StataCorp, College Station, TX). RESULTS During the period, 2,688 patients were admitted. Sixty were excluded (admitted during a changeover period). Of the 2,628 patients included, there were 3,723 admissions and 80,326 patient days of observation. The median age of patients was 58.7 years (range, 0.296.5 years). Sixty-nine skin reactions were reported (Table 2). Changing the dressing type, without changing the CHG concentration, was associated with an almost 6-fold increase in risk (IRR, 5.92; 95% confidence interval [CI], 1.8-19) of skin reactions; increasing CHG concentrations from 0.5% to 1% without changing the dressing type did not increase skin reactions (IRR, 5.92; 95% CI, 1.819 vs IRR, 5.82; 95% CI, 2.1-16; P = .977), but increasing CHG from 1% to 2% led to a significant increase in skin reactions (IRR, 3.10; 95% CI, 1.34-7.24; P = .008) (Table 2). Skin reactions usually occurred within the first week (data not shown). Eleven definite CLABSIs occurred in 8 patients, including one during the changeover period from dressing 1 to dressing 2. This infection was excluded. There was no difference in the incidence of CLABSI between the groups (Table 2).
DISCUSSION There are economic and clinical benefits of using CHG instead of povidone-iodine, including improvements in the incidence of catheter-related bloodstream infections and deaths attributable to these infections.6 Hypersensitivity reactions seem to be limited to those with localized skin reactions, such as erythema and erosive contact dermatitis, and may be a result of prolonged or repeated exposure.7 However, such reactions are poorly reported.8 Those that have reported hypersensitivity reactions after CHG use suggest skin inflammation rates of between 3% and 17%.9,10 Interestingly, a Cochrane review of gauze and tape, and transparent polyurethane dressings for CVCs, has reported a greater incidence of catheterrelated bloodstream infections with polyurethane dressings compared with gauze and tape,8 suggesting that visual inspection of the insertion site may not be an accurate way of identifying infection. Our study has some limitations, including the observational nature of the data, that the initial period (comparator) was longer than the other dressing periods, and the fact that the different transparent dressing and CHG concentrations under study were used sequentially not contemporaneously. Additionally, the degree of prior exposure to chlorhexidine, which may lead to sensitization, was unknown.11 CONCLUSIONS A concentration of 2% CHG is associated with a higher rate of skin reactions than either 0.5% or 1% CHG. Higher CHG concentrations may not decrease the number of CLABSIs. Dressing 2 was associated with a higher incidence of skin reactions than dressing 1 when used in combination with CHG solutions to dress CVC sites. Acknowledgments We thank the nursing staff of the Out & About IV Therapy Program who diligently recorded all skin reactions, and Kellie Schneider, RN, for entering, interpreting, and maintaining the clinical data. We also thank Dr Belinda Butcher, CMPP, WriteSource Medical Pty Ltd, for medical writing assistance, which was funded from a trust fund held by Hunter New England Local Health District on behalf of M.B. References 1. Theaker C. Infection control issues in central venous catheter care. Intensive Crit Care Nurs 2005;21:99-109. 2. Maki DG, Ringer M, Alvarado CJ. Prospective randomised trial of povidone-iodine, alcohol, and chlorhexidine for prevention of infection associated with central venous and arterial catheters. Lancet 1991;338:339-43.
ARTICLE IN PRESS M. Loewenthal et al. / American Journal of Infection Control ■■ (2016) ■■-■■
3. Chaiyakunapruk N, Veenstra DL, Lipsky BA, Saint S. Chlorhexidine compared with povidone-iodine solution for vascular catheter-site care: a meta-analysis. Ann Intern Med 2002;136:792-801. 4. Weitz NA, Lauren CT, Weiser JA, LeBoeuf NR, Grossman ME, Biagas K, et al. Chlorhexidine gluconate-impregnated central access catheter dressings as a cause of erosive contact dermatitis: a report of 7 cases. JAMA Dermatol 2013;149:195-9. 5. Centers for Disease Control and Prevention. 2016 NHSN patient safety component manual. Available from: http://www.cdc.gov/nhsn/pdfs/pscmanual/pcsmanual _current.pdf. Accessed June 3, 2016. 6. Chaiyakunapruk N, Veenstra DL, Lipsky BA, Sullivan SD, Saint S. Vascular catheter site care: the clinical and economic benefits of chlorhexidine gluconate compared with povidone iodine. Clin Infect Dis 2003;37:764-71. 7. Calogiuri GF. Chlorhexidine hypersensitivity: a critical and updated review. J Allergy Ther 2013;4:141.
3
8. Webster J, Gillies D, O’Riordan E, Sherriff KL, Rickard CM. Gauze and tape and transparent polyurethane dressings for central venous catheters. Cochrane Database Syst Rev 2011;(11):CD003827. 9. Valles J, Fernandez I, Alcaraz D, Chacon E, Cazorla A, Canals M, et al. Prospective randomized trial of 3 antiseptic solutions for prevention of catheter colonization in an intensive care unit for adult patients. Infect Control Hosp Epidemiol 2008;29:847-53. 10. Mimoz O, Lucet J-C, Kerforne T, Pascal J, Souweine B, Goudet V, et al. 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. Lancet 2015;386:2069-77. 11. Liippo J, Kousa P, Lammintausta K. The relevance of chlorhexidine contact allergy. Contact Dermatitis 2011;64:229-34.