Peri-Operative Method of Applying Chlorhexidine and Iodine as Skin Preparation Solutions: Does It Matter? A Literature Review

Abstract

Background:

Surgical site infection (SSI) is an adverse event that can lead to increased pain, increased cost, risk of death, and decreased patient satisfaction. Studies have investigated the best solutions to prevent SSI. Chlorhexidine has been suggested as the most efficacious antiseptic. However, scant data exist on application of antiseptic solutions and effectiveness of concentric versus back-and-forth strokes. Because a specific method may result in better outcomes, we aimed to review the literature to compare these two techniques.

Methods:

PubMed-indexed articles were reviewed using specific keywords, including “back-and-forth,” “concentric circle,” “chlorhexidine,” “iodine,” “surgical site infection,” “antiseptic,” and “skin preparation.” Because data showing the correlation between SSI and application method of skin preparation solutions were scant, studies that described skin preparation method but analyzed other types of infection, bacteremia, or colonization were also included in this review.

Results:

No consensus was found regarding the application method. Two articles showed the superiority of chlorhexidine applied using the back-and-forth technique, whereas one demonstrated the superiority of iodine applied in concentric circles.

Conclusions:

The method of applying antiseptic solution may be just as important as the choice of solution. More studies are needed to assess method of antiseptic application.

Surgical site infection (SSI), defined by the World Health Organization as an infection in the skin or subcutaneous tissue around an incision that occurs within 30 days after surgery,^{1, 2} is a common preventable adverse effect of surgical procedures.³ Surgical site infections represent 38% of hospital-acquired infections in surgical patients,⁴ and the prevalence of SSI is approximately 5% in patients undergoing a surgical procedure.^3,5 The rates are even higher when follow-up after discharge is considered.⁶ Surgical site infection doubles the chance of death after surgery,⁴ decreases patient satisfaction, and increases post-surgical pain.⁷ Moreover, the costs of surgery increase by up to fourfold when SSI occurs.^8,9 Alfonso et al.¹⁰ found that the healthcare cost for each patient with SSI in the United States is $97,433, which covers hospital care, medical examinations, prescription drugs, and ambulatory care.

Several studies focused on the best approach to prevent SSI have found that skin preparation before procedures is among the most important factors to consider to avoid poor outcomes.^3,11,12 The choice of solution for skin preparation has been well debated; in a meta-analysis, Privitera et al.¹³ analyzed 19 studies and compared the effectiveness of chlorhexidine (CHX) and iodine-based preparations, finding CHX superior in preventing SSI. However, scant data exist on the application method for the abovementioned solutions (i.e., on the solutions' effectiveness when applied using concentric vs. back-and-forth strokes). A specific application method may result in better outcomes for SSI prevention. Thus, we aimed to review the literature to compare the effects of concentric vs back-and-forth stroke solution application in the prevention of SSI.

Methods

We established a protocol with inclusion and exclusion criteria, search strategy, and methodology. Two authors (R.A.O.B and T.G.O.B) performed a literature review using PubMed as a single database search on May 1, 2020. No restrictions were set for the publication date, but only articles published in the English language were included. The search strategy included the following keywords: (“back-and-forth” [TiAb] OR “concentric circle” [TiAb] OR “chlorhexidine” [TiAb] OR “iodine” [TiAb]) AND (“surgical site infection” [TiAb] OR “antiseptic” [TiAb] OR “skin preparation” [TiAb]).

All retrieved articles were screened by titles and abstracts. The studies were included after reviewing the full articles following the selection criteria below. Eligible studies from the reference list of the included articles were also included in this review. In the event of disagreement between the two reviewing authors, a third author (G.G.A.P.) checked the accuracy of the data.

Selection criteria included studies comparing antiseptic skin preparation techniques (back-and-forth or concentric circles) with a description of the outcomes regarding infection or colonization rates, bacterial growth, or bacteremia. Studies reporting on at least one skin preparation technique applied with either stroke method were included in this review. Either iodine or CHX-based solutions had to be described in the study to be considered for inclusion. Furthermore, only trials and prospective studies were included; systematic reviews, meta-analyses, book chapters, surveys, abstracts, and case reports were excluded. Additionally, studies with no clear description of the skin preparation techniques, those with insufficient data, and those not published in the English language were excluded.

Data were extracted from full-length articles by two authors (R.A.O.B and T.G.O.B). A standardized data extraction form prepared in Excel™ (Microsoft, Inc., Redmond, WA) was used to assess the completeness of the information collected from included articles. The following data were retrieved from each included study: study design, sample size, year of publication, objective of the study, description of the procedure, antiseptic skin solutions (iodine or CHX-based solutions), skin preparation technique (back-and-forth or concentric circular circles), and main findings (infection or colonization rates, bacterial growth, or bacteremia). As data showing the correlation between SSI and application method of skin preparation solutions were scant, studies that described the skin preparation method, but analyzed other types of infection, bacteremia, or colonization were also included in this review.

Results

From the 1,860 articles retrieved from the primary search, nine fulfilled the eligibility criteria: seven randomized studies,^14–20 one non-randomized study,²¹ and one prospective study.²² One randomized trial²³ was included through the reference list of an included article. Therefore, a total of 10 articles met eligibility criteria. Tables 1 and 2 describe the characteristics and results of these studies, respectively. Table 3 summarizes the search strategy.

Table 1.

Characteristics of the Ten Included Studies

Author (year)	Design	Procedure
Broach et al. (2017)	Blinded randomized trial (n = 788)	Colorectal surgery
Calfee and Farr (2002)	Blinded randomized trial (n = 12,692)	Percutaneous blood drawing from venipuncture site for culture
Casey et al. (2015)	Non-blinded randomized trial (n = 100)	CABG with planned harvest of long saphenous vein
Hibbard et al. (2002)	Non-blinded randomized trial (n = 190)	Volunteers (no procedure)
Humar et al. (2000)	Blinded randomized trial (n = 242)	Central venous catheter
Mimoz et al. (2015)	Non-blinded randomized trial (n = 2,349)	Catheter insertion
Story-Roller and Weinstein (2016)	Non-blinded randomized study (n = 6,095)	Percutaneous blood drawing from venipuncture site for culture
Swenson et al. (2009)	Prospective study (n = 3,135)	General surgical procedures
Tepus et al. (2008)	Non-blinded, non-randomized study (n = 14,764)	Cultures of blood obtained from the venipuncture site
Washer et al. (2013)	Blinded randomized trial (n = 3,879)	Phlebotomy

CABG = coronary artery bypass graft.

Table 2.

Results for Antiseptic Skin Solutions and Application Methods and Conclusions of Each Study

Author (year)	Antiseptic skin solutions	Technique	Conclusion
Broach et al. (2017)	1) 0.7% iodine +74% IPA 2) 2% CHX +70% IPA	(1) Single pass (2) Several passes Both performed in a circular motion	No difference
Calfee et al. (2002)	1) 2% iodine +47% ethyl alcohol 2) 70% IPA 3) 10% PI 4) PI +70% ethyl alcohol	Concentric strokes in an outward direction (3 times, 3 different swabs)	No difference
Casey et al. (2015)	1) 0.5% CHX gluconate +70% IPA 2) 2% CHX +70% IPA	Back-and-forth strokes	2% CHX +70% IPA
Hibbard et al. (2002)	1) 2% CHX +70% IPA 2) 70% IPA 3) 2% CHX	Back-and-forth strokes	2% CHX +70% IPA
Humar et al. (2000)	1) 10% PI 2) 0.5% CHX	Two rounds of back-and-forth strokes, with the second round administered perpendicular to the first	No difference
Mimoz et al. (2015)	1) 2% CHX +70% IPA (± previous scrubbing with 4% CHX) 2) 5% PI +69% ethanol (± previous scrubbing with 4% PI)	(1) Back-and-forth strokes (2) Concentric strokes	2% CHX +70% IPA
Story-Roller and Weinstein (2016)	1) 2% iodine 2) 2% CHX gluconate	(1) Concentric strokes (2) Back-and-forth strokes	No difference
Swenson et al. (2009)	1) 7.5% PI +70% IPA 2) 2% CHX +70% IPA 3) Iodine povacrylex in IPA	(1) Concentric strokes (2) Back-and-forth strokes (3) Single uniform application	Iodine povacrylex in IPA
Tepus et al. (2008)	1) 2% CHX +70% isopropanol 2) Iodine	(1) Back-and-forth strokes (2) Outward circular motion	2% CHX +70% isopropanol
Washer et al. (2013)	1) 2% iodine +2% sodium iodide diluted in 50% ethanol 2) 2% CHX gluconate +70% IPA 3) 10% PI	(1) Concentric strokes (2) Back-and-forth strokes (3) Concentric strokes	No difference

CHX = chlorhexidine; IPA = isopropyl alcohol; PI = povidone-iodine.

Table 3.

Search Strategy

Identification	Records identified through database searching	n = 1860
Screening and exclusion	Records screened by title and abstract after duplicates removed. Records excluded after abstract screening.	n = 1851
Inclusion	Records identified through reference list of included studies	n = 1
Final selection	Studies included	n = 10

Eight of 10 included articles are randomized trials with low risk of bias considering selection, performance, and detection bias. One prospective study and one non-randomized trial have high risk of bias because of the nature of the study design.

Concentric strokes (two studies)

Broach et al.¹⁴ conducted a randomized blinded trial to evaluate whether skin preparation with combination iodine povacrylex (0.7% iodine) and 74% isopropyl alcohol (IPA) is non-inferior to combination 2% CHX gluconate and 70% IPA in preventing SSI in colorectal surgery. In this study, the skin preparation solutions were applied in a single-pass circular stroke in the iodine-IPA group (n = 396), and in several circular passes by an applicator in the CHX-IPA group (n = 392). The overall rate of SSI (both superficial and deep) was 17.3%. The SSI rate was 18.7% in the iodine-IPA group and 15.9% in the CHX-IPA group, but the difference was not significant. The upper limit of the 2.5% confidence interval was 8.9%, which was greater than the prespecified non-inferiority margin of 6.6%. Therefore, the study failed to support the non-inferiority of iodine-IPA to CHX-IPA as a pre-operative skin preparation solution and favored the application of CHX-IPA in a single-pass circular motion to prevent superficial and deep SSI.¹⁴

Calfee and Farr^14,15 published a randomized, cross-over, investigator-blinded study comparing the effectiveness of skin antisepsis during percutaneous blood draws in the emergency and inpatient care units of a university hospital with 10% povidone-iodine (PI), 70% IPA, tincture of iodine (2% iodine and 2% potassium iodide in 47% ethyl alcohol), or PI with 70% ethyl alcohol. Scrubbing was first performed directly over the site of venipuncture, followed by the use of three different swabs applied three times in circular strokes in an outward direction. Of the 12,692 cultures analyzed, 333 (2.62%) were found to be contaminated. The individual contamination rates were 2.93% for PI, 2.58% for tincture of iodine, 2.50% for IPA, and 2.46% for PI with 70% ethyl alcohol, demonstrating that the relative efficacies of these antiseptics did not differ significantly.

Back-and-forth strokes (three studies)

A blinded randomized trial including 242 patients compared 10% PI (n = 117) with 0.5% CHX (n = 125).²³ Before central venous catheter insertion, both skin preparations were performed in two rounds of back-and-forth strokes, with the direction in the second round perpendicular to that in the first. The incidence of local catheter infection was 34% in the CHX group and 27% in the PI group; the difference was not significant.²³

Hibbard et al.¹⁷ conducted a randomized, parallel-group, active-control clinical trial investigating the effect of immediate and persistent antimicrobial efficacy. The study compared the efficacy and safety of the combination of 2% aqueous CHX and 70% IPA with that of either 70% IPA or 2% aqueous CHX alone as pre-operative skin preparations. Each antiseptic was applied in back-and-forth strokes by an applicator for approximately 30 seconds on the abdomen and two minutes on the groin.

Antimicrobial efficacy was measured in 85 patients by determining the change in the mean number of colony-forming units per square centimeter of skin from baseline to 10 minutes after antiseptic application (i.e., immediate activity) and at six and 24 hours after application (i.e., persistent activity). The antiseptic solutions substantially and immediately reduced the microbial counts; however, at 24 hours after application, the combination was associated with significantly lower colony-forming unit counts compared with IPA and aqueous CHX alone.¹⁷

A non-blinded randomized trial conducted by Casey et al.¹⁶ compared 0.5% and 2% CHX as skin preparation solutions applied with back-and-forth strokes in 100 patients undergoing coronary artery bypass graft with planned harvest of the long saphenous vein. The surgical site preparation using 2% CHX resulted in a substantially lower incidence of microbial positivity in cultures compared with 0.5% CHX (4% vs. 17% at two minutes after antisepsis and 12.5% vs. 33.3% after incision closure).¹⁶

Combined concentric and back-and-forth strokes (five studies)

A trial involving 2,349 participants conducted by Mimoz et al.¹⁸ compared the use of 2% CHX (n = 1,181) applied in back-and-forth strokes with the use of 5% PI (n = 1,168) applied in concentric strokes during the insertion of arterial, hemodialysis, or central venous catheters. The incidence of infection was lower in the CHX group than in the PI group (0.28 vs 1.77 per 1,000 catheter days; p = 0.0002).¹⁸

Three other studies^19–21 compared 2% CHX applied in concentric strokes and 2% iodine-based solutions applied in back-and-forth strokes. Story-Roller and Weinstein¹⁹ and Tepus et al.²¹ analyzed 6,095 and 14,764 participants, respectively; the participants in both studies received skin preparations in the venipuncture site using 2% iodine and 2% CHX. In a blinded randomized trial involving 3,879 patients, Washer et al.²⁰ determined the rate of blood culture contamination after antisepsis using each technique (either concentric or back-and-forth strokes). In addition to the 2% CHX and 2% iodine groups, the study by Washer et al.²⁰ also included a 10% PI group. Unlike the trial conducted by Mimoz et al.,¹⁸ two studies found no difference in the incidence of positive cultures between the two application techniques.^19–21

Swenson et al.²² conducted a prospective study involving 3,135 patients undergoing general surgical procedures. They investigated the rate of SSI in relation to the use of three preparation solutions: 7.5% PI applied in concentric strokes (n = 1,514), 2% CHX applied in back-and-forth strokes for 30 seconds (n = 827), and iodine povacrylex applied through a single uniform application at the incision site (n = 794). The incidence rate of SSI was substantially higher with CHX applied in concentric strokes (8.2%) than with iodine-based solutions applied in back-and-forth strokes (4.8%).²²

Discussion

Several clinical trials and meta-analyses have already assessed the efficacy of CHX and iodine in preventing skin infections. Chen et al.,²⁴ in a meta-analysis of 30 studies involving 29,000 patients who underwent different types of surgeries, found lower rates of SSI when CHX was used in skin preparation (relative risk, 0.65; 95% confidence interval [CI], 0.55–0.77) rather than iodine. Similarly, a systematic review of 19 studies comparing iodine and CHX supported the use of CHX as pre-operative skin antiseptic because of the lower incidence of SSI (relative risk, 0.70; 95% CI, 0.52–0.92).¹³ However, although numerous trials have compared the two antiseptic solutions, studies assessing the method of application of these solutions, either concentrically or in back-and-forth strokes, are lacking. We were unable to find studies indicating which skin preparation technique led to better patient outcomes.

Concentric stroke has been presumed to be the most efficacious technique in applying antiseptic, beginning at the incision or venipuncture site and moving outward.¹¹ However, given that 20% of skin flora reside in the deep layers of the human skin,²⁵ some studies have suggested that the back-and-forth stroke would allow the preparation solution to reach these deeper layers, leading to more efficacious antisepsis.^3,11,26,27 Therefore, the method of applying the skin preparation solution may be as important as the choice of solution.¹¹ Our review included two studies that compared CHX and iodine; one involved the use of concentric strokes for both solutions,¹⁴ whereas the other used back-and-forth strokes.²³ No difference regarding the incidence of infection was found in these two studies, showing that not only the skin preparation solution but also the technique might influence the rate of infection. It is apparent that a consensus on which skin preparation solution and technique best reduces patient infection rates, morbidity, and mortality cannot be reached with the current literature.

Five studies included in this review compared the efficacy of CHX and iodine, with iodine applied in concentric strokes and CHX applied in back-and-forth strokes.^18-22 Interestingly, the results were mixed. Chlorhexidine was found superior by two studies,^{18, 21} whereas one found iodine superior,²² and two found no differences in the incidence of infection between the solutions.^19,20

Although CHX has been suggested as the most efficacious antiseptic solution,^13,24 its application using different techniques showed contrasting results. Thus, more studies focusing on the application method of each solution are needed; a more effective technique might be suitable for each solution and establishing this correlation may help prevent SSI and lead to better outcomes for patients and healthcare practitioners.

Our literature review, unfortunately, could not show which skin preparation technique led to better outcomes. However, it did show the importance of having further studies investigating this issue because there was no consensus among the included studies, and especially because using the more effective technique might influence a solution's cleaning efficacy. We recognize that there is an ongoing movement toward pre-admission showers and skin cleansing protocols for major surgical procedures. However, it is likely that such practices will take several years to become common practice, perhaps even longer in resource-poor settings. This, and the fact that local cleansing will likely still be the more common approach for minor procedures, supports further study into this topic.

This study has some limitations. Because our intention was not to perform a systematic review, only a single database search was conducted. Also, the eligibility criteria were broad, leading to the inclusion of studies that reported non-surgical procedures. The included studies also have some limitations: different types of applicator^16,21; possibility of slightly different application techniques, although previous application training was performed^15,17–22; diagnosis of infection was confirmed by the patient's doctor; however, it may have had some subject influence^14,16; the sickest patients (unconscious or intubated) may not have been approached for consent²³; the clinicians were not blinded when applying the antiseptic solutions because they had different colors; however, the infection assessors were blinded^18,21; only specific patient populations were included in the study^14,20,22; and small sample sizes.^16,17,23 Furthermore, non-compliance with specific protocols may have occurred, although it was not mentioned in any included study. Therefore, results should be interpreted with caution.

Based on the available evidence, it appears that the most efficacious antiseptic that can be used pre-operatively is CHX, and that back-and-forth motions using this solution starting from the incision site to the periphery would lead to the best cleaning results. However, there is further need for studies comparing solutions, evaluating combined solutions, and application techniques. We hope that by exposing the lack of literature, more investigators will be encouraged to design studies on skin preparation solutions and techniques.

Surgical site infection is a common, preventable adverse effect in surgical procedures, and skin preparation is the most important factor to consider in its prevention. Therefore, expanding the understanding of antiseptic solutions and application techniques is essential to reduce the incidence of SSI. By decreasing the SSI rate, it may be possible to reduce mortality, improve patient satisfaction, and decrease post-surgical pain and treatment cost.

Footnotes

Authors' Contributions

R.A.O.B. and T.G.O.B. contributed to conceptualization, data curation, formal analysis, investigation, methodology, resources, software, validation, visualization, and writing. T.E.J. contributed to formal analysis, investigation, supervision, validation, and critical review. G.G.A.P. contributed to conceptualization, formal analysis, investigation, methodology, project administration, supervision, validation, writing, and critical review.

Funding Information

This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.

Author Disclosure Statement

The authors declare that there is no conflict of interest.

References

World Health Organization. Global Guidelines for the Prevention of Surgical Site Infection, 2nd ed. Geneva: World Health Organiztion; 2018.

Allegranzi

, Bischoff

, de Jonge

, et al. New WHO recommendations on preoperative measures for surgical site infection prevention: An evidence-based global perspective. Lancet Infect Dis, 2016; 16(12):e276–e287; doi: 10.1016/S1473-3099(16)30398-X.

Silva

. The right skin preparation technique: A literature review. J Perioper Pract, 2014; 24(12):283–285; doi: 10.1177/175045891402401204.

Woods

. Key points in the CDC's surgical site infection guideline. Adv Skin Wound Care, 2005; 18(4):215–220; doi: 10.1097/00129334-200505000-00011.

Leaper

. Surgical-site infection. Br J Surg, 2010; 97(11):1601–1602; doi: 10.1002/bjs.7275.

Reilly

, Allardice

, Bruce

, et al. Procedure-specific surgical site infection rates and postdischarge surveillance in Scotland. Infect Control Hosp Epidemiol, 2006; 27(12):1318–1323; doi: 10.1086/509839.

Cahill

, Shadbolt

, Scarvell

, et al. Quality of life after infection in total joint replacement. J Orthop Surg (Hong Kong), 2008; 16(1):58–65; doi: 10.1177/230949900801600115.

Zimlichman

, Henderson

, Tamir

, et al. Health care-associated infections: a meta-analysis of costs and financial impact on the US health care system. JAMA Intern Med, 2013; 173(22):2039–2046; doi: 10.1001/jamainternmed.2013.9763.

Jenks

, Laurent

, McQuarry

, et al. Clinical and economic burden of surgical site infection (SSI) and predicted financial consequences of elimination of SSI from an English hospital. J Hosp Infect, 2014; 86(1):24–33; doi: 10.1016/j.jhin.2013.09.012.

10.

Alfonso

, Pereperez

, Canoves

, et al. Are we really seeing the total costs of surgical site infections? A Spanish study. Wound Repair Regen, 2007; 15(4):474–481; doi: 10.1111/j.1524-475X.2007.00254.x.

11.

Stonecypher

. Going around in circles: is this the best practice for preparing the skin?. Crit Care Nurs Q, 2009; 32(2):94–98; doi: 10.1097/CNQ.0b013e3181a27b86.

12.

Tanner

Methods of skin antisepsis for preventing SSIs. Nurs Times, 2012; 108(37):20, 22.

13.

Privitera

, Costa

, Brusaferro

, et al. Skin antisepsis with chlorhexidine versus iodine for the prevention of surgical site infection: A systematic review and meta-analysis. Am J Infect Control, 2017; 45(2):180–189; doi: 10.1016/j.ajic.2016.09.017.

14.

Broach

, Paulson

, Scott

, et al. Randomized controlled trial of two alcohol-based preparations for surgical site antisepsis in colorectal surgery. Ann Surg, 2017; 266(6):946–951; doi: 10.1097/SLA.0000000000002189.

15.

Calfee

, Farr

. Comparison of four antiseptic preparations for skin in the prevention of contamination of percutaneously drawn blood cultures: A randomized trial. J Clin Microbiol, 2002; 40(5):1660–1665; doi: 10.1128/jcm.40.5.1660-1665.2002.

16.

Casey

, Itrakjy

, Birkett

, et al. A comparison of the efficacy of 70% v/v isopropyl alcohol with either 0.5% w/v or 2% w/v chlorhexidine gluconate for skin preparation before harvest of the long saphenous vein used in coronary artery bypass grafting. Am J Infect Control, 2015; 43(8):816–820; doi: 10.1016/j.ajic.2015.03.034.

17.

Hibbard

, Mulberry

, Brady

. A clinical study comparing the skin antisepsis and safety of ChloraPrep, 70% isopropyl alcohol, and 2% aqueous chlorhexidine. J Infus Nurs, 2002; 25(4):244–249; doi: 10.1097/00129804-200207000-00007.

18.

Mimoz

, Lucet

, Kerforne

, 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(10008):2069–2077; doi: 10.1016/S0140-6736(15)00244-5.

19.

Story-Roller

, Weinstein

. Chlorhexidine versus tincture of iodine for reduction of blood culture contamination rates: A prospective randomized crossover study. J Clin Microbiol, 2016; 54(12):3007–3009; doi: 10.1128/JCM.01457-16.

20.

Washer

, Chenoweth

, Kim

, et al. Blood culture contamination: A randomized trial evaluating the comparative effectiveness of 3 skin antiseptic interventions. Infect Control Hosp Epidemiol, 2013; 34(1):15–21; doi: 10.1086/668777.

21.

Tepus

, Fleming

, Cox

, et al. Effectiveness of Chloraprep in reduction of blood culture contamination rates in emergency department. J Nurs Care Qual, 2008; 23(3):272–276; doi: 10.1097/01.NCQ.0000324593.84213.4f.

22.

Swenson

, Hedrick

, Metzger

, et al. Effects of preoperative skin preparation on postoperative wound infection rates: A prospective study of 3 skin preparation protocols. Infect Control Hosp Epidemiol, 2009; 30(10):964–971; doi: 10.1086/605926.

23.

Humar

, Ostromecki

, Direnfeld

, et al. Prospective randomized trial of 10% povidone-iodine versus 0.5% tincture of chlorhexidine as cutaneous antisepsis for prevention of central venous catheter infection. Clin Infect Dis, 2000; 31(4):1001–1007; doi: 10.1086/318145.

24.

Chen

, Chen

, Guo

, et al. Preoperative antisepsis with chlorhexidine versus povidone-iodine for the prevention of surgical site infection: A systematic review and meta-analysis. World J Surg, 2020; 44(5):1412–1424; doi: 10.1007/s00268-020-05384-7.

25.

Casey

, Badia

, Higgins

, et al. Skin antisepsis: It's not only what you use, it's the way that you use it. J Hosp Infect, 2017; 96(3):221–222; doi: 10.1016/j.jhin.2017.04.019.

26.

Tung

. Best practices for central line insertion. Int Anesthesiol Clin, 2013; 51(1):62–78; doi: 10.1097/AIA.0b013e31827da437.

27.

McDonald

, Lowe

, Roy

, et al. Evaluation of donor arm disinfection techniques. Vox Sang, 2001; 80(3):135–141; doi: 10.1046/j.1423-0410.2001.00029.x.