Do your inpatients have a bath every day? In Chlorhexidine?
The question popped up on an Intensive Care ward round when it was posed that despite clinicians washing their hands multiple times per patient per day, whether an unwashed patient could 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 looking at chlorhexidine bathing in three clinical settings.
Chlorhexidine washes appear to reduce the skin bioburden in patients.
There are a number of preparations and methods of application 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 in 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 decrease contamination of the hands of healthcare workers, further limiting the likelihood of transmission.
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 that was allowed to dry, 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.
Central line-associated bloodstream infection (for 7 of 12 studies)
All blood-stream infections (for 4 of 12 studies)
A. Baumanii colonisation (for 1 of 12)
HCABSI in 557 patients in the control arm over 69617 patient days
HCABSI in 291 patients in 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 in using Central Line Associated Blood-stream Infection (CLABSI) vs all blood-stream infections (bacteremia) as an endpoint.
Although there was no undue influence from a single study, the studies generally had a limited assessment of confounding factors and were pretty heterogeneous.
Adverse events were described in six studies: 0.6-1% had a rash, ~1% had dryness of the skin 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.
Notably, Egger’s test shows significant bias in the results; there is a suggestion of bias towards supporting a benefit from 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 supports 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.
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 result in other focal infections as a result of 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, fuchsine, to name a few. These agents appear to have different properties, some drying the cord out and promoting separating, others with perceived antiseptic properties.
This review looked at 34 trials in the community and hospital settings, covering 22 interventions total, including chlorhexidine, 70% alcohol, and some other agents including katotexin, clay powder and fuchsine. The aim was to identify good practices in cord care in both high and low-income countries. Studies using hexachlorophene and a combination of antibiotics and antiseptic therapies were excluded. Hexachlorophene, although previously used, has been shown to be absorbed through the skin and is potentially neurotoxic!
Primary outcomes were mortality, confirmed or suspected sepsis, omphalitis and tetanus; with secondary outcomes of bacterial colonization and time to cord separation. Subgroup analyses on preterm neonates, hospital versus community and geographic settings were planned.
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 ranging from 27-56% depending on the severity of the infection. Chlorhexidine reduced colonization with Staph, streptococcus and enterococci in the community. Cord separation took about 36hrs 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 colonization, chlorhexidine reduced the rates of Staph aureus and E.coli. There was no difference in colonisation with streptococci in the hospital setting. Several other agents actually increased the rate of colonization.
Dry cord care was the equivalent of soap and water in the hospital setting. By comparison to a single application, multiple applications of antiseptics were associated with decreased rates of omphalitis.
The hospital studies were subject to potential bias, as they were conducted mostly in developed countries, more likely to be associated with antenatal care and generally improve hygiene standards. This may account for the apparent loss of protective effects of chlorhexidine cord care.
Thus, the articles reviewed had a moderate risk of bias.
Thus, the review recommends using chlorhexidine washes for cord care in the community setting in the developing world. For developed world hospital settings, chlorhexidine cord care cannot currently be recommended based on this review.
Trial number three is the ‘SCRUB‘ trial, which looked specifically at daily chlorhexidine washes for 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.
Participating ICUs were randomized 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 negative and was subsequently positive for a differing organism, or 14 days negative and then positive for the same organisms.
Notably, the study was complicated early on by a batch of contaminated chlorhexidine cloths, which grew Burkholderia cepeciae! 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 some concerns over the acceptability of chlorhexidine washes to parents, but this is not fully discussed within the paper.
Results in the intention to treat analysis: a non-significant reduction in the incidence of bacteremia was associated with chlorhexidine bathing. When a per-protocol analysis was done, this result became significant.
- 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.
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 some potential benefits from chlorhexidine washes, although several factors of this study seem to have undersold the potential.
So, to combine all these findings: chlorhexidine washes appear to reduce the skin bioburden in patients and healthcare staff. There are a number of preparations and methods of application 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 accepted as a viable whole-body cleaning agent due to skin reactions or parental concerns.