A critical review of the literature regarding the use of povidone iodine and chlorhexidine gluconate for preoperative surgical skin preparation.
Abstract: This paper presents a critical analysis of studies regarding the effectiveness of preoperative skin preparation solutions. The aim was to allow evidence based practice at a local level.

KEYWORDS Chlorhexidine / Povidone iodine / Alcohol / Surgical antisepsis / Skin preparation / Evidence based practice / Critical analysis
Article Type: Clinical report
Subject: Chlorhexidine (Dosage and administration)
Chlorhexidine (Patient outcomes)
Infection control (Methods)
Povidone (Dosage and administration)
Povidone (Patient outcomes)
Iodine (Properties)
Author: Scowcroft, Tammy
Pub Date: 03/01/2012
Publication: Name: Journal of Perioperative Practice Publisher: Association for Perioperative Practice Audience: Academic Format: Magazine/Journal Subject: Health; Health care industry Copyright: COPYRIGHT 2012 Association for Perioperative Practice ISSN: 1750-4589
Issue: Date: March, 2012 Source Volume: 22 Source Issue: 3
Product: Product Code: 2819941 Iodine & Compounds NAICS Code: 325188 All Other Basic Inorganic Chemical Manufacturing SIC Code: 2819 Industrial inorganic chemicals, not elsewhere classified
Geographic: Geographic Scope: United Kingdom Geographic Code: 4EUUK United Kingdom
Accession Number: 283274427
Full Text: The aim of this critical analysis of published literature is to clarify the use of surgical skin preparation solutions and to evaluate their effectiveness in order to implement a local policy for surgical skin preparation.

The purpose of preoperative skin antisepsis is to remove soil, transient and resident microorganisms from the skin surface, and to prevent wound contamination on incision (Edwards et al 2004, AORN 2008, Veiga et al 2008, Hemani & Lepor 2009). A surgical site infection can cause distress and possible long term effects to a patient, and have huge financial implications to healthcare institutions (Edwards et al 2004, Zinn et al 2010). It has also been suggested that robust surgical site skin preparation may reduce the reliance on antibiotic therapy (Leaper 2010).

Methods of surgical site skin preparation

Soil and transient organisms can be removed by social washing using soap and water, but resident microorganisms require a more robust removal method. The use of both mechanical and chemical methods is required for efficient removal of resident organisms (AACN 2005, NICE 2008).

The mechanical process involves the application of skin antisepsis solution with adequate friction of the applicator to ensure that all the cracks and fissures in the skin are sufficiently coated with the solution. A back and forwards motion, concentrating on the incision site for around 30 seconds is the recommendation, as there is no evidence to support the use of concentric circling pattern used traditionally (AACN 2005, Care Fusion 2010).

The chemical process involves both the destruction of microorganisms and the prevention of rebound colonisation (a quick recovery and re growth of an organism - see also Box 1) after cleansing. Various antiseptic solutions have been developed to do this adequately and efficiently (Noorani et al 2010). The American Urological Association (2007) state that, whichever skin antisepsis is chosen, it 'should be effective against organisms characteristic of the operative site'.

Box 1

Rebound colonisation is the tendency of a micro-organism to repopulate an area following decontamination, over a much quicker period of time than the original colonisation took place.

The two common antisepsis solutions in clinical use are chlorhexidine gluconate (CHG) and povidone iodine (PovI), either as aqueous solution or alcoholic. CHG has been shown to have a persistent action (it continues to impart antiseptic properties for some time after application). It is inactivated by iodine, should not be used on mucous membranes, may cause chemical burns in neonates and is ototoxic (harmful to the ear) (Fletcher et al 2007, Milstone et al 2008, Sivathasan et al 2010). Iodine is inactivated by biomaterials, but is effective while the colouration is present. It should not be used on open wounds or dressings because of its toxicity against fibroblasts and keratinocytes (Fletcher et al 2007, Milstone et al 2008). Alcohol dries rapidly, appears to be more effective than aqueous solution, has no residual activity, is highly flammable, but acts as a secondary antiseptic agent (Fletcher et al 2007).

How to critique a research paper

Lipp & Edwards (2010) state that best practice for a study is as follows:

* Subjects should be randomised to reduce bias.

* The groups within the study should be comparable groups.

* Treatment, other than the intervention to be studied, should be standardised.

* A low (less than 20%) 'drop out' rate is required during the study in order to prevent skewing of the results.

* Double blinding i.e. neither the researchers nor the patient know which intervention was used is ideal, but this is difficult when the skin preparation solutions are different colours.

* Results should be tabulated and discussed in the text. The 'p' values (Box 2) and confidence intervals (Box 3) should be stated. A p value gives an indication of whether the result occurred because of the intervention or was due to chance. A p value of <0.05 indicates a viable intervention. A confidence interval is the percentage of results that will fall into an expected range. The range should be small, and a confidence interval is usually quoted at 95% (see www.engageinresearch.ac.uk).

Box 2

p-value

* A numerical indicator of statistical significance i.e. the probability of the results of the study occurring by chance. It is quoted as a figure between 0 and 1.

* The p value shows the number of times that the results of a study are expected to be replicated when the study is repeated and shows how 'true' the result is. So for a study that was carried out 100 times, with a p-value quoted as 0.05, the results should be the same 95 times out of 100, meaning that there is a 1 in 20 chance that the result occurred by chance.

* Most studies use the figure 0.05 as the 'cut-off' point for valid results, but the p-value can be quoted as any number between 0-1. The lower the figure quoted, the less likely it is that the result occurred by chance, and more likely that the intervention is valid.

For further information see the following websites: www.engageinresearch.ac.uk; www.statsoft.com/textbook/elementary-statistics-concepts; www.ehow.com

Box 3

Confidence interval

* A confidence interval is used to show how confident you are that the absolute value described by the results is true.

* The confidence interval is the number of percentage points above or below the proportion that you find in your study that the true proportion should be within i.e. the range of numbers within which the majority of your data will fall.

* This range should be small e.g. 3%; the smaller the range, the more confident you are in your results.

For further information see the following websites: www.engageinresearch.ac.uk; www.statsoft.com/textbook/elementary-statistics-concepts; www.ehow.com

* Follow ups should be standardised.

* The study should be large enough to minimise the play of chance and a power calculation (Box 4) may be included which confirms that the sample size in the study was adequate for detecting a clinically relevant difference (see www.engageinresearch.ac.uk).

Box 4

Power calculation

* A power calculation is used to estimate the number of participants required for a study in order that the results of the study are meaningful, and are not skewed by chance or variables within the participants of the study.

* If there are not enough participants, the study could be flawed and underpowered, and statistical differences may not easily be observed. The study may also be dismissed, as chance has not been eliminated.

* An over large study size will be more expensive to carry out.

* In order to carry out a power calculation, a hypothesis has to be determined, the size of the population to study should be known (e.g. total number of surgical patients in the hospital at a given period), an acceptable confidence interval decided upon, and an appropriate statistical software package utilised.

For further information see the following websites: www.engageinresearch.ac.uk; www.statsoft.com/textbook/elementary-statistics-concepts; www.ehow.com

* The study should have external validity or applicability i.e. it should be useful for actual practice.

Discussion of the studies

In a review of seven trials: including one concerning bathing using CHG impregnated cloths (Evans et al 2010) and one from 1973 (Byatt & Henderson 1973), CHG in alcohol was judged to be the most effective skin preparation agent in four of the cases (Ostrander et al 2005, Darouiche et al 2010, Saltzman et al 2009, Evans et al 2010). One study reported better efficacy using an iodophor based product (Swenson et al 2009), one found no statistical difference (Veiga et al 2008), and one found that alcohol based preparations are preferable (Byatt & Henderson 1973). Most of these studies were carried out in America, where surgical skin preparation is performed differently than in the UK. In America the surgical site is actively 'scrubbed' for a procedure (Lipp & Edwards 2010) by a non sterile staff member (AORN 2008). This is not part of the guidelines in the UK, where 'painting' by scrubbed staff takes place.

Analysis of the studies

Byatt & Henderson (1973) carried out a small (n=67) study comparing skin preparation solutions on episiotomy sites; episiotomy is considered to be clean contaminated surgery (Fortunato 2000). The exclusion criteria meant that the actual sample size was reduced to 54 after the women were swabbed to ascertain their normal bacterial load. Only those with a low bacterial load prior to surgical site preparation were included.

There are some doubts as to the reliability of this study. The sample size is too small to eliminate chance and no indication of randomisation was made. The study was carried out nearly 30 years ago, and is therefore considered out of date. The study did not report actual rates of infection, only growth of microorganisms on an agar plate, which Salgado & Farr (2006) note could be an unreliable indicator of rate of infection. The style of reporting of the results made analysis difficult. The authors stated that nine preparations of six antiseptic substances were applied, but listed eight and reported results for ten. For these reasons, the study was judged to be neither robust nor valid, and therefore not applicable for inclusion into current practice.

Veiga et al (2008) carried out a randomised controlled trial comparing PovI and CHG in alcohol for clean plastic surgery. The inclusion criteria were clearly stated, and standardised mechanical cleansing was carried out. However, the sample size was small (125 allocated to each solution), and no power calculation was carried out to ascertain a statistically relevant sample size. Again, bacterial growth on an agar plate was the study outcome, not actual infection rate. The study indicated no statistical difference between the two skin preparation solutions, but the authors stated a preference for CHG in alcohol because of its residual effect. The lack of statistically relevant results means that this study is essentially irrelevant to clinical practice.

Swenson et al (2009) carried out a large size (n=3209) study comparing three different skin preparation agents used at a single hospital. The study inclusion criteria were: all adult patients undergoing either elective or emergency general surgical procedures. The demographic mix of each of the three groups was tabulated and indicated relatively similar groupings. The main study outcome was actual infection, recorded up to 30 days postoperatively.

Preoperative standardisation of treatment was implemented and the standardisation was listed in the text, but the actual mechanical preparation differed as per the manufacturer's instructions. The preoperative standardisation had already been put into action as part of an infection control policy that had been introduced before the study, and which had already reduced surgical site infections within that institution.

The study allocated patients sequentially i.e. all patients in a particular time frame received one treatment, rather than carrying out a randomised allocation. Crosby (2010) noted that a sequential allocation may cause a skew in the results because of staff rotation, the type of surgery and even an awareness of previous results using different skin preparation solutions.

Though the actual difference is small, it was also noted by Crosby (2010) that the trial involving CHG contained 2% more dirty surgical wounds with a higher propensity for infection, and that the trial of Povacrylex took place with shorter operating times. Though contamination cannot be compared to length of operation, these two factors could create enough of a skew in the results to affect the conclusions of the study. One bias that may have influenced the result is the compliance with the type of antiseptic to be used in each period. Seventy percent compliance was achieved for the CHG solution, 64% for the Povacrylex, and 98% for PovI. The variation was acknowledged by the authors who suggested that this may reflect on actual practice where the protocols were to be implemented. The study size was large enough to minimise a chance result, and a power calculation was included to show this. All patients were followed up in the same way after their surgery and the results of the trial were clearly tabulated. The limitations of the study were noted and recommendations for future studies were suggested.

The outcome of the study formed the basis for a change of practice in the use of iodine Povacrylex in isopropyl alcohol for general surgery at the authors' hospital, and the study has both applicability and validity for inclusion into current practice.

Darouiche et al (2010) studied 849 adults undergoing clean contaminated surgery. Each participant was randomly allocated either CHG in alcohol or aqueous Povl. A power calculation was completed in order to determine this figure as an appropriate study size. The study enrolled participants from six hospital sites, enabling a much broader mix of population, but this could have caused a skewed result because of inter hospital differences. To combat this, each hospital was allocated an equal number of either antiseptic solution (stratification by hospital), following which computer generated randomisation took place. A comparison was made of the demographics of each group and it was stated that the groups were similar. Losses in each group were identified, but were not statistically significant enough to affect the results. No standardisation other than antibiotic prophylaxis was implemented, and each hospital followed local policies for preoperative care.

The primary study outcome was measurement of actual surgical site infections within 30 days after surgery and from their results it was extrapolated that CHG in alcohol was 17 times more effective than aqueous Povl, confirming their expectations.

The study was based on the hypothesis that chlorhexidine in alcohol would be more effective against infection than Povl. However, of the 12 authors of the study, seven were sponsored by the manufacturers of the chlorhexidine applicator, and one author was employed by the manufacturer. This would indicate a bias in the study and conclusions. A further bias appears to be the lack of a Povl in alcohol, or an aqueous CHG skin preparation agent. Byatt and Henderson (1973) and Ostrander et al (2005) both indicate that an alcohol base for a cleansing solution is more effective than an aqueous one. The conflict of interest is reported, however, and the results confirm the original hypothesis.

Although accessibility is not one of the 'best practice' criteria advocated by Lipp and Edwards (2010), this article was difficult to understand by someone who has no knowledge of statistical analysis. It was a demanding read, and required a lot of background reading to merely understand the text, and some of the conclusions made by this author were made on an incomplete understanding of the reporting technique. The authors reported that the superiority of chlorhexidine alcohol was probably due to its persistent activity despite exposure to bodily fluid, and its residual effect. It has also been noted that CHG has an immediate bactericidal action that exceeds that of Povl (Atiyeh et al 2009). Although there may be some concerns regarding bias, the results of this study are valid and applicable to current practice.

Evans et al (2010) carried out a retrospective study of infection rates in the intensive care setting following the implementation of daily bathing of trauma patients using chlorhexidine (2%) impregnated cloths. The main study outcome was actual bloodstream infection, and although this study is not particularly valid for assessing effectiveness as a surgical site preparation method, the results indicated that CHG had a significant effect on the incidence of methicillin resistant staphylococcus aureus (MRSA) related infections at central venous catheter sites.

Webster and Osborne (2007) noted that there was inconclusive evidence to support preoperative bathing in chlorhexidine, but Evans et al (2010) indicated that the effect of CHG on skin flora has been demonstrated for some time. The sequential allocation of skin cleansing types may have caused a skew in the results, as noted previously by Crosby (2010), however, the authors stated that both patient and staff demographics were essentially similar, with no major changes, and the standardisation of cleansing technique was easy to implement.

This study, while having little applicability for practice as a preoperative surgical site preparation intervention, offers some interesting possibilities for patient involvement post operatively with regard to wound care and infection control.

Ostrander et al (2005) studied 125 patients, using three rotationally selected skin prep solutions: iodine in alcohol, chlorhexidine in alcohol and chloroxylenol (a disinfectant and antiseptic - see the World Health Organisation website http://www.who.int/en/). The main study outcome was bacterial growth on culture plates.

In this small study, chlorhexidine in alcohol was found to be the most effective at reducing bacterial growth for clean orthopaedic surgery of the forefoot. The exclusion and inclusion criteria were clearly stated. The reliability of the evidence was weak due to the study size, but all the procedures were undertaken by one surgeon. This would reduce the skew associated with multiple practitioners but increase the bias if the single practitioner has a preference for one method over another. As with the study by Byatt and Henderson (1973), this study suggests that alcohol may be a more effective base for skin prep solutions than an aqueous base. Though the study was small, the results offer valid implications for surgical skin preparation practices.

Saltzman et al (2009) studied the effect of three types of surgical skin preps on infection rates in 150 shoulder surgeries. Again, only culture plates were used and not actual infection rates. The study involved consecutive patients, with the skin prep used being selected randomly. There was no indication as to 'blinding' of the patients, and the selected groups were dissimilar regarding smoking habits, diabetic status, presence of arthritis, hepatitis or alcoholism. In such a small study, these variables may have an effect on the results. Antibiotic therapy was also not standardised, but depended on allergies or the presence of prosthetic implants. The authors acknowledged the limitations of the study, and suggested that a study to directly evaluate infection rates, and provide quantitative culture data, would be more significant. They also suggested that a much larger patient group would give a more significant result. Again, though the study group is small, and there is little standardisation in patient groups, the study offers interesting implications for skin preparation practice, indicating that CHG in alcohol is most effective for surgical skin preparation for the shoulder region.

Conclusion

It has been demonstrated in this literature review that no single surgical skin preparation agent is superior for use in all instances. The use of an alcohol base seems to enable a more efficient antiseptic action, because it is an additional agent working alongside the main agent of CHG or Povl; CHG seems to be the preferred method of antisepsis due to its residual action. However, new technology in the form of a biofluid resistant form of iodine povacrylex (Swenson et al 2009) could negate the problem of neutralisation of iodine based agents by biological materials.

The contraindications for CHG mean that we cannot rely on it alone for all skin preparation needs, but by having a choice of CHG in alcohol and Povl in alcohol, the incidence of surgical site infection should be reduced.

The implications of this review are that Povl in aqueous solution is the weakest antisepsis solution, and suggest that its use should not be included in local policy. It is also suggested that both CHG in alcohol and Povl in alcohol (povacrylex) skin preparations are trialled locally, and that preoperative showering and/or postoperative use of chlorhexidine impregnated wipes are also trialled so that the incidence of surgical site infections is reduced.

References

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Provenance and Peer review: Unsolicited contribution; Peer Reviewed; Accepted for publication December 2011.

Correspondence address: West Cumberland Hospital, Hensingham, Cumbria, CA28 8JG. Email: tammy.scowcroft@ncuh.nhs.uk

About the author

Tammy Scowcroft RN

Staff Nurse, Theatres, West Cumberland Hospital, Cumbria

No competing interests declared
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