Daily chlorhexidine washes?

Do your inpatients have a bath every day? In Chlorhexidine?

The question arose during an Intensive Care ward round: despite clinicians washing their hands multiple times per patient per day, could an unwashed patient pose an infection risk to themselves or others? Another quiet voice at the back wondered if there was any merit to having patients wash with chlorhexidine.

Chlorhexidine is used widely throughout hospitals in handwashes, surgical preparation, antiseptics, or impregnated into some catheters. This is a brief review of three papers examining chlorhexidine bathing across three clinical settings.

Bottom Line

Chlorhexidine washes appear to reduce the skin bioburden in patients.

There are a number of preparations and application methods for chlorhexidine washes.

There may be benefits in daily washing for at-risk patients in the intensive care setting; particularly those with central venous catheters.

Chlorhexidine may be used in umbilical cord care, however, in the developed world hospital setting, the benefit is negligible.

Chlorhexidine may not be an acceptable whole-body cleaning agent due to skin reactions or parental concerns.

So, across three age groups, we’ll have a look at the potential benefits of chlorhexidine bathing.

In the first paper, O’Horo et al. undertook a meta-analysis of studies to assess the efficacy of daily bathing with chlorhexidine gluconate (CHG) for the prevention of healthcare-associated bloodstream infections in adults across medical, surgical, and ICU settings. In fact, there are several studies of chlorhexidine washes in adults; this review provided a nice recent snapshot of the practice.

O’Horo JC, et al. The efficacy of daily bathing with chlorhexidine for reducing healthcare-associated bloodstream infections: a meta-analysis. Infect Control Hosp Epidemiol. 2012 Mar;33(3):257-67.

The premise “that chlorhexidine bathing will reduce healthcare-associated blood-stream infections “(HCABSIs) is biologically plausible because heavy skin bacterial colonisation on patients facilitates transmission by healthcare workers to other susceptible patients, and decreased skin bioburden would be expected to interrupt or minimise healthcare-associated transmission.

Moreover, CHG bathing may reduce contamination of healthcare workers’ hands, further limiting the likelihood of transmission.

Methods

This review included both individual or cluster RCTs, quasi-experimental studies that evaluated either; daily CHG vs soap & water or standard of care washing, in ICUs and non-ICU settings were eligible. 12 studies were analysed, dating from 2005-2010. 11 were from the USA, 1 and French. 10 in the ICU setting.

All trials involved at least daily chlorhexidine washing, with either 2% CHG-impregnated rags; 4% CHG diluted 1:2 with tap water, allowed to dry, with no rinsing; or 4% CHG bathing solution, with or without rinsing. Several studies also had intranasal mupirocin 2%, active hand hygiene and other MRSA eradication interventions.

Endpoints

Central line-associated bloodstream infection (for 7 of 12 studies)

All bloodstream infections (for 4 of 12 studies)

A. Baumanii colonisation (for 1 of 12)

Results

HCABSI in 557 patients in the control arm over 69617 patient days

HCABSI in 291 patients in the chlorhexidine arm over 67775 patient days

The random effects model gave an odds ratio of 0.44 (95% CI 0.32-0.59 p<0.00001) for washing with chlorhexidine

There was no significant difference in mortality. A subgroup analysis showed no difference between impregnated cloths vs liquid chlorhexidine. There was no difference between using Central Line-Associated Bloodstream Infection (CLABSI) and all bloodstream infections (bacteremia) as endpoints.

Although there was no undue influence from any single study, the studies generally assessed confounding factors only to a limited extent and were fairly heterogeneous.

Adverse events

Adverse events were reported in six studies: 0.6-1% had a rash, ~1% had skin dryness, and 4.6% had an ‘allergy’ to chlorhexidine gluconate. Of note, these results are not generalisable to the paediatric population, and one study in surgical patients showed no benefit.

Conclusion

Notably, Egger’s test indicates significant bias in the results, suggesting a tendency to support a benefit of chlorhexidine. The paper’s discussion makes much of whether chlorhexidine should be rinsed after being used as a wash. The study concludes that the current data support the practice of daily chlorhexidine bathing in adult medical ICUs.

The second paper, a Cochrane review published in March 2013, looked at ‘umbilical cord antiseptics for preventing sepsis and death in newborns.’

Sinha A, et al. Chlorhexidine skin care for the prevention of infection in term neonates. Cochrane Database of Systematic Reviews 2009, Issue 2. Art. No.: CD007835.

Why?

Before the separation, the remaining stump can be considered to be a healing wound and thus a possible route for infection through the vessels into the baby’s bloodstream.

Tracking of bacteria along the umbilical vessels is not obvious to the eye but can cause septicaemia or lead to other focal infections via blood-borne spread, such as septic arthritis.

Traditionally, a number of agents have been used for cord care, including chlorhexidine, 70% alcohol, mustard oil, turmeric, charcoal, grease, cow dung, dried banana, clay powder, and fuchsine, to name a few. These agents appear to have different properties, some drying the cord out and promoting separation, others with perceived antiseptic properties.

Methods

This review looked at 34 trials in community and hospital settings, covering 22 interventions in total, including chlorhexidine, 70% alcohol, and other agents such as katotexin, clay powder, and fuchsine. The aim was to identify good practices in cord care in both high and low-income countries. Studies involving hexachlorophene and combinations of antibiotics and antiseptic therapies were excluded. Hexachlorophene, although previously used, has been shown to be absorbed through the skin and is potentially neurotoxic!

Outcome measures

Primary outcomes were mortality, confirmed or suspected sepsis, omphalitis and tetanus, with secondary outcomes of bacterial colonisation and time to cord separation. Subgroup analyses of preterm neonates across hospital versus community and geographic settings were planned.

Results

Results were generally positive for chlorhexidine but mixed for other agents.

In the community, chlorhexidine reduced mortality by 23% (ARR 0.77; 0.63-0.9) and decreased omphalitis, with reductions ranging from 27-56% depending on infection severity. Chlorhexidine reduced colonisation with Staph, Streptococcus, and Enterococci in the community. Cord separation took about 36 hours longer, on average, with chlorhexidine care.

In the hospital setting, studies looked only at omphalitis, for which there was no change in numbers. For the secondary outcomes of bacterial colonisation, chlorhexidine reduced the rates of Staph aureus and E.coli. There was no difference in streptococcal colonisation in the hospital setting. Several other agents actually increased the rate of colonisation.

Dry cord care was the equivalent of soap and water in the hospital setting. Compared with a single application, multiple applications of antiseptics were associated with lower rates of omphalitis.

The hospital studies were subject to potential bias, as they were conducted mostly in developed countries, which are more likely to be associated with antenatal care and generally have higher hygiene standards. This may account for the apparent loss of chlorhexidine cord care’s protective effects.

Thus, the articles reviewed had a moderate risk of bias.

Conclusion

Thus, the review recommends using chlorhexidine washes for cord care in the community setting in the developing world. In developed-world hospital settings, chlorhexidine cord care cannot currently be recommended based on this review.

Trial number three is the ‘SCRUB‘ trial, which examined daily chlorhexidine washes in PICU patients to answer the question: “Does daily bathing with chlorhexidine vs standard practice reduce bacteremia in critically ill children?“

Milstone AM, (Pediatric SCRUB Trial Study Group) et al;. Daily chlorhexidine bathing to reduce bacteraemia in critically ill children: a multicentre, cluster-randomised, crossover trial. Lancet. 2013 Mar 30;381(9872):1099-106.

A total of 4947 of 6482 eligible PICU admissions were enrolled. Patients were >2 months of age, and admitted to PICU for > 2 days, excluding those with in situ epidural, severe skin disease or burns or known chlorhexidine allergy.

Methods

Participating ICUs were randomised to 6 months on or off and then swapped, with a two-week changeover period. Washing was undertaken with cloths impregnated with 2% chlorhexidine. (Unlike the O’ Horo analysis mentioned earlier, there’s not much detail, with respect to rinsing or otherwise.)

The endpoint was a positive blood culture, including commensal skin organisms. An additional distinct event occurred if a patient had 7 days of negative results and was subsequently positive for a differing organism, or 14 days of negative results and then positive for the same organisms.

Notably, the study was complicated early on by a batch of contaminated chlorhexidine cloths that grew Burkholderia cepacia! Additionally, one arm of the study had a much higher rate of ‘refused to consent for treatment’; this lead the authors to undertake both intention to treat analysis and per-protocol analysis (excluding those who had declined to participate). This raises concerns about the acceptability of chlorhexidine washes among parents, but it is not fully discussed in the paper.

Results

Results in the intention-to-treat analysis: a non-significant reduction in the incidence of bacteremia was associated with chlorhexidine bathing. In a per-protocol analysis, this result became significant.

Subgroups showed:

• Analysis excluding skin commensals showed the benefit of chlorhexidine washes
• Admissions with central venous catheters showed the benefit of chlorhexidine washes

The incidence of chlorhexidine associated skin-reactions was 1.2 per 1000.

Conclusion

The authors summarise

“In this cluster-randomised trial, children underwent daily bathing with either CHG or standard procedures. Because the rate of non-consent was high in our trial, a third of eligible admissions were not bathed with CHG. Those who did receive daily CHG bathing had a 36% reduction in incidence of bacteraemia. If we include in our analysis admitted children who were eligible to receive bathing but who did not have consent to participate, the reduction in bacteraemia was not significant. However, the estimated effect of daily CHG bathing on bacteraemia was similar whether we compared all patients in the treatment group (intention-to-treat population) to controls or all patients on treatment (per-protocol population) to controls, suggesting a clinically significant and relevant result. Furthermore, CHG bathing was a safe and well tolerated procedure that could be quickly and widely implemented to prevent morbidity and costs associated with bacteraemia in this vulnerable population.”

This conclusion seems overly positive but is unsurprising given the two styles of analysis. There remain potential benefits to chlorhexidine washes, although several factors in this study seem to have downplayed their potential.

So, combining these findings, chlorhexidine washes appear to reduce skin bioburden among patients and healthcare staff. There are a number of preparations and application methods for chlorhexidine washes. There may be benefits in daily washing for at-risk patients in the intensive care setting, particularly those with central venous catheters. 

Chlorhexidine may be used in umbilical cord care; however, in developed-world hospital settings, the benefit is negligible. Chlorhexidine may not be accepted as a viable whole-body cleaning agent due to skin reactions or parental concerns.