Summary of a systematic literature review on surgical site preparation

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Global Guidelines for the Prevention of Surgical Site Infection. Geneva: World Health Organization; 2018.

Global Guidelines for the Prevention of Surgical Site Infection.

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Web Appendix 8Summary of a systematic literature review on surgical site preparation

1. Introduction

Surgical site preparation refers to the preoperative treatment of the intact skin of the patient within the operating room. Preparation includes not only the immediate site of the intended surgical incision, but also a broader area of the patient’s skin, and usually takes place when the patient is already positioned on the operating table. The aim of this procedure is to reduce the microbial load on the patient’s skin as much as possible before incising the skin barrier. The most widely-used agents are chlorhexidine gluconate (CHG) and iodophors (for example, povidone iodine [PVP-I]) in alcohol-based solutions, which are effective against a wide range of bacteria, fungi and viruses. Aqueous solutions, particularly those containing iodophors, are also widely used, notably in developing countries.

Application techniques for preoperative surgical site preparation are also a topic of interest. However, 3 trials investigating the effect of the application technique with comparable antiseptic compounds showed no difference in surgical site infection (SSI) rates¹^–³. Despite current knowledge of the antimicrobial activity of many antiseptic agents and application techniques, it remains unclear what is the best approach to preoperative site preparation⁴^,⁵.

Several guidelines, such as those published by the Society for Healthcare Epidemiology of America (SHEA)/Infectious Diseases Society of America (IDSA)⁶, the United Kingdom (UK) National Institute for Health and Care Excellence (NICE)⁷ or the Royal College of Physicians of Ireland⁸, recommend the use of an alcohol-based solution for surgical site preparation. However, these recommendations are not based upon a systematic review of the literature and meta-analysis or a rigorous evaluation of the quality of the available evidence.

The objective of this systematic review is to assess the available evidence on the efficacy of solutions and antiseptic agents used for surgical site skin preparation.

2. PICO question

In surgical patients, should alcohol-based antiseptic or aqueous solutions be used for skin preparation and, more specifically, should CHG or PVP-I solutions be used?

Population: patients of any age undergoing any type of surgical procedures
Intervention: alcohol-based preparations
Comparator: aqueous preparations
Outcome: SSI, SSI-attributable mortality

3. Methods

The following databases were searched: Medline (PubMed); Excerpta Medica Database (EMBASE/Ovid), Cumulative Index to Nursing and Allied Health Literature (CINAHL); Cochrane Central Register of Controlled Trials (CENTRAL); and WHO regional medical databases. The time limit for the review was between 1 January 1960 and 15 August 2014. Language was restricted to English, French and Spanish. A comprehensive list of search terms was used, including Medical Subject Headings (MeSH) (Appendix 1).

Two independent reviewers screened the titles and abstracts of retrieved references for potentially relevant studies. The full text of all potentially eligible articles was obtained. Two authors independently reviewed the full text articles for eligibility based on inclusion criteria. Duplicate studies were excluded.

Two authors extracted data in a predefined evidence table (Appendix 2) and critically appraised the retrieved studies using the Cochrane Collaboration tool to assess the risk of bias of randomized controlled trials (RCTs)⁹ (Appendix 3). Any disagreements were resolved through discussion or after consultation with the senior author, when necessary.

Meta-analyses of available comparisons were performed using Review Manager version 5.3 as appropriate¹⁰ (Appendix 4). Adjusted odds ratios (OR) and mean differences with 95% confidence intervals (CI) were extracted and pooled for each comparison with a random effects model. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology¹¹^,¹² (GRADE Pro software; http://gradepro.org/) was used to assess the quality of the body of retrieved evidence (Appendix 5).

4. Study selection

Flow chart of the study selection process

* 16 studies were included from the original search (up to 15 August 2014) and one was exceptionally included later as this was a relevant trial published on 4 February 2016.

5. Summary of the findings

Overall, 17 RCTs²^,¹³^–²⁸ comparing antiseptic agents (PVP-I and CHG) in aqueous and alcohol-based solutions with an SSI outcome were identified. Although the time limit for inclusion was set to a publication date of up to 15 August 2014, a relevant trial²⁸ published on 4 February 2016 was exceptionally included after discussion with the World Health Organization (WHO) Guidelines Review Committee and the Guidelines Development Group.

Included studies focused on adult patients and no study was available in the paediatric population. Most studies used isopropyl alcohol at a concentration of 70–74%. Concentrations of the iodophor compound ranged from 0.7–10% and from 0.5–4% for CHG. As there was heterogeneity among the included studies concerning the composition of the solution used for surgical site preparation, the research group decided to focus the evaluation on the following comparisons:

-: PVP-I vs. CHG, both in alcohol-based solutions
-: PVP-I in an aqueous solution vs. PVP-I in an alcohol-based solution
-: CHG in an aqueous solution vs. CHG in an alcohol-based solution
-: CHG vs. PVP-I, both in aqueous solutions.

However, a search of the literature did not identify any studies that compared CHG in an aqueous solution with CHG in an alcohol-based solution or CHG with PVP-I, both in aqueous solutions. The available studies included in the review made it possible to carry out the following comparisons:

Alcohol-based antiseptic solutions vs. aqueous solutions
1. CHG in an alcohol-based solution vs. PVP-I in an aqueous solution
2. PVP-I in an alcohol-based solution vs. PVP-I in an aqueous solution
CHG vs. PVP-I, both in alcohol-based solutions.

The results of the meta-analysis based on these comparisons are shown in Appendix 4.

Twelve RCTs²^,¹³^–²³ compared alcohol-based vs. aqueous antiseptic solutions in preoperative surgical site preparation. Meta-analysis of these 12 studies (Appendix 4, comparison 1) showed that alcohol-based antiseptic solutions are more effective compared to aqueous solutions in reducing the risk of SSI (OR: 0.60; 95% CI: 0.45–0.78).
The overall quality of evidence of this comparison was moderate due to the risk of bias (Appendix 5).
1. Among these 12 trials, 7^§ RCTs compared CHG in an alcohol-based solution with PVP-I in an aqueous solution. Most trials found either no difference between the groups¹³^–¹⁶ or there were no SSI events reported¹⁷^,¹⁸. One trial found an increased risk for SSI in the PVP-I group²³ (see Appendices 2 and 4). Meta-analysis of these 7 studies (Appendix 4, comparison 1a) showed a significant benefit in reducing the risk of SSI with CHG in alcohol-based solutions compared to PVP-I in an aqueous solution (OR: 0.65; 95% CI: 0.47–0.90).
  The quality of the evidence was moderate for this comparison due to the risk of bias (Appendix 5).
2. Six^§ of the 12 RCTs compared alcohol-based vs. aqueous PVP-I. The trials found either no difference between the groups²^,¹⁹^,²⁰ or there were no SSI events reported¹⁸^,²¹^,²². Meta-analysis of these 6 studies (Appendix 4, comparison 1b) showed no significant difference between the groups (OR: 0.61; 95% CI: 0.19–1.92).
  The quality of evidence was very low for this comparison due to the risk of bias and imprecision (Appendix 5).
Six RCTs compared CHG with PVP-I in alcohol-based solutions. Most trials found either no difference between the groups²⁴^,²⁵ or there were no SSI events reported¹⁸^,²⁶. Two trials²⁷^,²⁸ found an increased risk for SSI in the PVP-I group. Meta-analysis of these studies (Appendix 4, comparison 2) showed a significant reduction of risk of SSI with the use of alcohol-based CHG compared to PVP-I in alcohol-based solutions (OR: 0.58; 95% CI: 0.42–0.80). However, 4 of the 6 trials¹⁸^,²⁴^–²⁶ reported no SSI events in at least one of the study arms and most studies reported the number of colony-forming units as the primary outcome and not SSI.
The quality of evidence was low for this comparison due to the risk of bias and imprecision (Appendix 5).

§ Numbers do not add up to 12 as some studies were included in multiple analyses

In conclusion, the retrieved evidence can be summarized as follows:

Overall, there is a lack of robust, high-quality studies that evaluate the efficacy of alcohol-based vs. aqueous solutions or the antiseptic compound in the solutions.

Overall, a moderate quality of evidence shows that alcohol-based antiseptic solutions are more effective compared to aqueous solutions in reducing the risk of SSI.
1. Overall, a moderate quality of evidence shows a significant benefit in reducing the risk of SSI with alcohol-based CHG compared to PVP-I in an aqueous solution.
2. Overall, a very low quality of evidence shows that surgical site skin preparation with alcohol-based PVP-I is neither beneficial nor harmful in reducing SSI rates compared to aqueous PVP-I.
Overall, a low quality of evidence shows a significant benefit in reducing the risk of SSI with the use of alcohol-based CHG compared to alcohol-based PVP-I.

Several limitations can be observed in the available studies. The criteria for SSI were comparable, but the definitions of SSI were not identical between the studies. Most studies had a considerable risk of bias, particularly related to the blinding of outcome assessors. Although most included studies used isopropyl alcohol at a concentration of 70–74% in the alcohol-based solution, some authors¹³^,²⁷ did not specify the type of concentration used; one study¹⁴ used 70% ethanol. The concentration of antiseptic agent varied between the studies and the iodophor compound ranged from 0.7–10% and CHG from 0.5–4%. The study arms in the trials comparing aqueous vs. alcohol-based PVP-I had variations in the application method (aqueous “scrub and paint” vs. alcohol-based “paint”).

Appendices

Appendix 1. Search terms

Medline (via PubMed)

(“surgical wound infection”[Mesh] OR surgical site infection* [TIAB] OR “SSI” OR “SSIs” OR surgical wound infection* [TIAB] OR surgical infection*[TIAB] OR post-operative wound infection* [TIAB] OR postoperative wound infection* [TIAB] OR wound infection*[TIAB]) OR ((“preoperative care”[Mesh] OR “preoperative care” OR “pre-operative care” OR “perioperative care”[Mesh] OR “perioperative care” OR “peri-operative care” OR perioperative OR intraoperative OR “perioperative period”[Mesh] OR “intraoperative period”[Mesh]) AND (“infection”[Mesh] OR infection [TIAB])) AND (“skin preparation” [TIAB] OR “skin preparations” [TIAB] OR skin prep [TIAB] OR “baths”[Mesh] OR bath*[TIAB] OR ((“povidone-iodine”[Mesh] OR povidone OR “iodophors”[Mesh] OR iodophor OR iodophors OR “iodine”[Mesh] OR iodine OR betadine OR “triclosan”[Mesh] OR triclosan OR “chlorhexidine”[Mesh] OR chlorhexidine OR hibiscrub OR hibisol OR alcohol OR alcohols OR Gel OR “soaps”[Mesh] OR soap [TIAB] OR soaps [TIAB]) AND skin AND (disinfectants OR “antisepsis”[Mesh] OR antisepsis OR antiseptics OR detergents OR cleaning OR cleansing)))

EMBASE and CINAHL

((ssi) OR (surgical site infection) OR (surgical site infections) OR (wound infection) OR (wound infections) OR (postoperative wound infection)) AND (“skin preparation” OR “skin preparations” OR skin prep OR “baths” OR bath* OR ((“povidone-iodine” OR povidone OR “iodophors” OR iodophor OR iodophors OR “iodine” OR iodine OR betadine OR “triclosan” OR triclosan OR “chlorhexidine” OR chlorhexidine OR hibiscrub OR hibisol OR alcohol OR alcohols OR gel OR “soaps” OR soap OR soaps) AND skin AND (disinfectants OR “antisepsis” OR antisepsis OR antiseptics OR detergents OR cleaning OR cleansing)))

Cochrane CENTRAL

(wound infection or surgical wound infection) AND skin antisepsis

WHO Global Library

ti:: title;
ab:: abstract

Appendix 2. Evidence table

Download PDF (280K)

Appendix 3. Risk of bias assessment for included studies

RCT, author, year	Sequence generation	Allocation concealment	Participants and personnel blinded	Outcome assessors blinded	Incomplete outcome data	Selective outcome reporting	Other sources of bias
Berry, 1982²⁷	LOW	LOW	LOW	LOW	LOW	LOW	LOW
Bibbo, 2005¹⁷	UNCLEAR	UNCLEAR	LOW	LOW	LOW	LOW	UNCLEAR
Cheng, 2009²⁶	LOW	UNCLEAR	LOW	UNCLEAR	LOW	UNCLEAR	UNCLEAR
Darouiche, 2010²³	LOW	LOW	LOW	LOW	UNCLEAR	LOW	LOW
Gilliam, 1990²²	UNCLEAR	UNCLEAR	UNCLEAR	UNCLEAR	UNCLEAR	UNCLEAR	UNCLEAR
Hort, 2002²¹	UNCLEAR	UNCLEAR	UNCLEAR	UNCLEAR	LOW	LOW	UNCLEAR
Howard, 1991²⁰	HIGH	HIGH	UNCLEAR	UNCLEAR	LOW	LOW	UNCLEAR
Paocharoen, 2009¹⁶	UNCLEAR	UNCLEAR	UNCLEAR	UNCLEAR	LOW	LOW	UNCLEAR
Roberts, 1995¹⁹	UNCLEAR	UNCLEAR	UNCLEAR	UNCLEAR	LOW	LOW	UNCLEAR
Rodrigues, 2013¹³	HIGH	HIGH	UNCLEAR	UNCLEAR	LOW	LOW	UNCLEAR
Saltzman, 2009¹⁸	LOW	LOW	UNCLEAR	UNCLEAR	LOW	UNCLEAR	LOW
Savage, 2012²⁴	LOW	LOW	UNCLEAR	UNCLEAR	LOW	LOW	LOW
Segal, 2002²	LOW	UNCLEAR	UNCLEAR	UNCLEAR	LOW	LOW	UNCLEAR
Sistla, 2010¹⁴	LOW	LOW	LOW	LOW	UNCLEAR	UNCLEAR	UNCLEAR
Srinivas, 2014¹⁵	UNCLEAR	UNCLEAR	UNCLEAR	UNCLEAR	LOW	LOW	LOW
Veiga, 2008²⁵	UNCLEAR	UNCLEAR	UNCLEAR	UNCLEAR	LOW	LOW	UNCLEAR
Tuuli, 2016²⁸	LOW	UNCLEAR	UNCLEAR	LOW	LOW	LOW	UNCLEAR

Appendix 4. Meta-analyses

Comparison 1Alcohol-based solutions vs. aqueous solutions - overall RCTs, outcome SSI

Funnel plot 1Alcohol-based solutions vs. aqueous solutions - overall RCTs, outcome SSI

Comparison 1aCHG + alcohol vs. aqueous PVP-I (as sub-analysis of comparison 1), outcome SSI

Funnel plot 1aCHG + alcohol vs. aqueous PVP-I (as sub-analysis of comparison 1), outcome SSI

Comparison 1bPVP-I + alcohol vs. aqueous PVP-I (as sub-analysis of comparison 1), outcome SSI

Funnel lot 1bPVP-I + alcohol vs. aqueous PVP-I (as sub-analysis of comparison 1), outcome SSI

Comparison 2CHG + alcohol vs. PVP-I + alcohol, outcome SSI

Funnel plotCHG + alcohol vs. PVP-I + alcohol, outcome SSI

RCT: randomized controlled trial; SSI: surgical site infection; M-H: Mantel-Haenszel (test), CI: confidence interval; CHG: chlorhexidine gluconate; PVP-I: povidone-iodine.

Appendix 5. GRADE tables

Comparison 1. Alcohol-based solutions vs. aqueous solutions - all RCTs (PDF, 292K)

Comparison 1a. CHG in an alcohol-based solution vs. aqueous PVP-I (as sub-analysis of comparison 1) (PDF, 305K)

Comparison 1b. PVP-I in alcohol-based solution vs. aqueous PVP-I (as sub-analysis of comparison 1) (PDF, 306K)

Comparison 2. CHG in an alcohol-based solution vs. PVP-I in an alcohol-based solution (PDF, 303K)

References

1.: Ellenhorn JD, Smith DD, Schwarz RE, Kawachi MH, Wilson TG, McGonigle KF, et al. Paint-only is equivalent to scrub-and-paint in preoperative preparation of abdominal surgery sites. J Am Coll Surg. 2005;201:737–41. [PubMed: 16256917]
2.: Segal CG, Anderson JJ. Preoperative skin preparation of cardiac patients. AORN J. 2002;76:821–8. [PubMed: 12463081]
3.: Shirahatti RG, Joshi RM, Vishwanath YK, Shinkre N, Rao S, Sankpal JS, et al. Effect of pre-operative skin preparation on post-operative wound infection. J Postgrad Med. 1993;39:134–6. [PubMed: 8051642]
4.: Lowbury EJ. Prevention of postoperative infection. Injury. 1985;16:583–4. [PubMed: 4086094]
5.: Mishriki SF, Law DJ, Jeffery PJ. Factors affecting the incidence of postoperative wound infection. J Hosp. Infect. 1990;16:223–30. [PubMed: 1979572]
6.: Anderson DJ, Podgorny K, Berríos-Torres SI, Bratzler DW, Dellinger EP, Greene L, et al. Strategies to prevent surgical site infections in acute care hospitals: 2014 update. Infect Control Hosp. Epidemiol. 2014;35:605–27. [PMC free article: PMC4267723] [PubMed: 24799638]
7.: A summary of selected new evidence relevant to NICE clinical guideline 74 ‘Prevention and treatment of surgical site infection’ (2008). Evidence update 43. June 2013. London, UK: National Institute for Health and Clinical Excellence (NICE) https://www.nice.org.uk/guidance/cg74/evidence/evidence-update-241969645, accessed 14 May 2016).
8.: Preventing surgical site infections. Key recommendations for practice (2012). Dublin: Joint Royal College of Surgeons in Ireland/Royal College of Physicians of Ireland Working Group on Prevention of Surgical Site Infection (https://www.hpsc.ie/AZ/MicrobiologyAntimicrobialResistance/InfectionControlandHAI/Surveillance/SurgicalSiteInfection Surveillance/CareBundles/File,14019,en.pdf, accessed 13 May 2016).
9.: Higgins JP, Altman DG, Gotzsche PC, Jüni P, Moher D, Oxman AD, et al. The Cochrane Collaboration’s tool for assessing risk of bias in randomised trials. BMJ. 2011;343:d5928. [PMC free article: PMC3196245] [PubMed: 22008217]
10.: The Nordic Cochrane Centre TCC. Review Manager (RevMan). Version 5.3. Copenhagen: The Cochrane Collaboration; 2014.
11.: Guyatt G, Oxman AD, Akl EA, Kunz E, Vist G, Brozek J, et al. GRADE guidelines: 1. Introduction-GRADE evidence profiles and summary of findings tables. J Clin Epidemiol. 2011;64:383–94. [PubMed: 21195583]
12.: GRADEpro Guideline Development Tool. Summary of findings tables, health technology assessment and guidelines. GRADE Working Group, Ontario: McMaster University and Evidence Prime Inc.; 2015 (http://www.gradepro.org, accessed 5 May 2016).
13.: Rodrigues AL, Simoes M de L. Incidence of surgical site infection with pre-operative skin preparation using 10% polyvidone-iodine and 0.5% chlorhexidine-alcohol. Rev Col Bras Cir. 2013;40:443–8. [PubMed: 24573620]
14.: Sistla SC, Prabhu G, Sistla S, Sadasivan J. Minimizing wound contamination in a ‘clean’ surgery: comparison of chlorhexidine-ethanol and povidone-iodine. Chemotherapy. 2010;56:261–7. [PubMed: 20693796]
15.: Srinivas A, Kaman L, Raj P, Gautam V, Dahiya D, Singh G, et al. Comparison of the efficacy of chlorhexidine gluconate versus povidone iodine as preoperative skin preparation for the prevention of surgical site infections in clean-contaminated upper abdominal surgeries. Surg Today. 2015;45:1378–84. [PubMed: 25381486]
16.: Paocharoen V, Mingmalairak C, Apisarnthanarak A. Comparison of surgical wound infection after preoperative skin preparation with 4% chlohexidine and povidone iodine: A prospective randomized trial. J Med Assoc Thai 2009;92:898–902. [PubMed: 19626807]
17.: Bibbo C, Patel DV, Gehrmann RM, Lin SS. Chlorhexidine provides superior skin decontamination in foot and ankle surgery: a prospective randomized study. Clin Orthop Relat Res. 2005;438:204–8. [PubMed: 16131892]
18.: Saltzman MD, Nuber GW, Gryzlo SM, Marecek GS, Koh JL. Efficacy of surgical preparation solutions in shoulder surgery. J Bone Joint Surg Am. 2009;91:1949–53. [PubMed: 19651954]
19.: Roberts A, Wilcox K, Devineni R, Harris R, Osevala M. Skin preparation in CABG surgery: a prospective randomized trial. Complications Surg. 1995;14:741–7.
20.: Howard R. Comparison of a 10-minute aqueous iodophor and 2-minute water-insoluble iodophor in alcohol preoperative skin preparation. Complications Surg. 1991;10.
21.: Hort KR, DeOrio JK. Residual bacterial contamination after surgical preparation of the foot or ankle with or without alcohol. Foot Ankle Int 2002;23:946–8. [PubMed: 12398148]
22.: Gilliam DL, Nelson CL. Comparison of a one-step iodophor skin preparation versus traditional preparation in total joint surgery. Clin Orthop Relat Re. 1990:258–60. [PubMed: 2293938]
23.: Darouiche RO, Wall MJ Jr, Itani KM, Otterson MF, Webb AL, Carrick MM, et al. Chlorhexidine-alcohol versus povidone-iodine for surgical-site antisepsis. New Engl J Med. 2010;362:18–26. [PubMed: 20054046]
24.: Savage JW, Weatherford BM, Sugrue PA, Nolden MT, Liu JC, Song JK, et al. Efficacy of surgical preparation solutions in lumbar spine surgery. J Bone Joint Surg Am. 2012;94:490–4. [PubMed: 22437997]
25.: Veiga DF, Damasceno CA, Veiga-Filho J, Figueiras RG, Vieira RB, Florenzano FH, et al. Povidone iodine versus chlorhexidine in skin antisepsis before elective plastic surgery procedures: a randomized controlled trial. Plast Reconstr Surg. 2008;122:170e-1e. [PubMed: 18971711]
26.: Cheng K, Robertson H, Mart JPS, Leanord A, McLeod I. Quantitative analysis of bacteria in forefoot surgery: a comparison of skin preparation techniques. Foot Ankle Int 2009;30:992–7. [PubMed: 19796594]
27.: Berry AR, Watt B, Goldacre MJ, Thomson JW, McNair TJ. A comparison of the use of povidone-iodine and chlorhexidine in the prophylaxis of postoperative wound infection. J Hosp Infect 1982;3:55–63. [PubMed: 6177735]
28.: Tuuli MG, Liu J, Stout MJ, Martin S, Cahill AG, Odibo AO, et al. A randomized trial comparing skin antiseptic agents at cesarean delivery. New Engl J Med. 2016;374:647–55. [PMC free article: PMC4777327] [PubMed: 26844840]

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