CANADIAN ASSOCIATION OF GENERAL SURGEONS AND ACS,EVIDENCE-BASED REVIEWS IN SURGERY

Is Chlorhexidine-Alcohol More Effective thanPovidone-Iodine?Elijah Dixon, MD, William G Cheadle, MD, Rachael G Khadaroo, MD, PhD, for Members of the

Evidence-Based Reviews in Surgery Group

The term evidence-based medicine was first coined by Sack-ett and colleagues1 as “the conscientious, explicit and judi-cious use of current best evidence in making decisionsabout the care of individual patients.”The key to practicingevidence-based medicine is applying the best currentknowledge to decisions in individual patients. Medicalknowledge is continually and rapidly expanding and it isimpossible for an individual clinician to read all the medi-cal literature. For clinicians to practice evidence-basedmedicine, they must have the skills to read and interpret themedical literature so that they can determine the validity,reliability, credibility and utility of individual articles.These skills are known as critical appraisal skills. Generally,critical appraisal requires that the clinician have someknowledge of biostatistics, clinical epidemiology, decisionanalysis, and economics as well as clinical knowledge.

The Canadian Association of General Surgeons (CAGS)and the American College of Surgeons (ACS) jointly spon-sor a program entitled “Evidence-Based Reviews in Sur-gery” (EBRS), supported by an educational grant fromEthicon Inc and Ethicon Endo Surgery Inc. The primaryobjective of this initiative is to help practicing surgeonsimprove their critical appraisal skills. During the academicyear, 8 clinical articles are chosen for review and discussion.They are selected not only for their clinical relevance togeneral surgeons, but also because they cover a spectrum ofissues important to surgeons; for example, causation or risk

factors for disease, natural history or prognosis of disease,

Setting: Six university affiliated hospitals in the United States.

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374© 2012 by the American College of SurgeonsPublished by Elsevier Inc.

how to quantify disease (measurement issues), diagnostictests and the diagnosis of disease, and the effectiveness oftreatment. Both methodologic and clinical reviews of thearticle are performed by experts in the relevant areas andposted on the EBRS website. A listserve discussion is heldwhere participants can discuss the monthly article. Fellowsand candidates of the College can access Evidence-BasedReviews in Surgery through the American College of Sur-geons website (www.facs.org). All journal articles and re-views are available electronically through the website. Cur-rently we have a library of 50 articles and reviews, whichcan be accessed at any time. Each October, a new set ofarticles will be available each month until May. Surgeonswho participate in the current (modules) packages canreceive CME credits by completing a series of multiplechoice questions. Additional information about EBRS ison the ACS website or by email to the administrator,Marg McKenzie at mmckenzie@mtsinai.on.ca.

In addition to making the reviews available through theACS and CAGS websites, 4 of the reviews are published incondensed versions in the Canadian Journal of Surgery, 4 inthe Journal of the American College of Surgeons, and 4in Diseases of Colon and Rectum each year.

REFERENCE

1. Evidence Based Medicine Working Group. Evidence-based med-

icine. JAMA 1992;268:2420–2425.

SELECTED ARTICLE

Chlorhexidine-Alcohol versus Povidone-Iodinefor Surgical Site AntisepsisDarouiche RO, Wall MJ, Itani KMF et al. New Engl J Med2010;362:18–26.

Question: Is chlorhexidine-alcohol more effective thanpovidone-iodine for preoperative skin cleansing?

Design: Multicenter randomized controlled trial.

Patients: Eight hundred forty-nine patients who un-erwent clean-contaminated surgery (colorectal, small in-estinal, gastroesophageal, biliary, thoracic, gynecologic orrologic operations performed under controlled condi-ions without substantial spillage or unusual contamina-ion) were enrolled.

Intervention: Patients were randomly assigned to havethe skin at the surgical site preoperatively scrubbed with2% chlorhexidine gluconate and 70% isopropyl alcohol orscrubbed and painted with an aqueous solution of 10%

povidone-iodine, from April 2004 to May 2008.

ISSN 1072-7515/12/$36.00doi:10.1016/j.jamcollsurg.2011.12.006

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375Vol. 214, No. 3, March 2012 Evidence-Based Reviews in Surgery

Main outcomes measure: Surgical site infectionwithin 30 days after operation.

Results: The overall rate of surgical site infection wassignificantly lower in the chorhexidine-alcohol group thanin the povidone-iodine group (9.5% vs 16.1%; p � 0.004;relative risk, 0.59; 95% CI, 0.41 to 0.85). Chlorhexidine-alcohol was significantly more protective than povidone-iodine against both superficial incisional infections (4.2%vs 8.6%, p � 0.008) and deep incisional infections (1% vs3%, p � 0.005) but not against organ-space infections(4.4% vs 4.5%).

Conclusions: Preoperative cleansing of the patient’sskin with chlorhexidine-alcohol is superior to cleansingwith povidone-iodine for preventing surgical site infectionafter clean-contaminated surgery.

Commentary: The study by Darouiche and colleagues1

is a multicenter randomized clinical trial comparing theeffectiveness of chlorhexidine-alcohol and povidone-iodine in preventing postoperative surgical site infections(SSI) in patients undergoing operations with wounds clas-sified as clean-contaminated. Surgical site infection is in-creasingly being appreciated as an important outcome thathas implications with regard to short- and long-term pa-tient morbidity and mortality, the costs of care, and lengthof stay. The rates of SSI in relation to the degree of contam-ination are reproducible.2 Consequently, the rates of SSI

er the degree of wound contamination are being used as auality indicator to measure and benchmark the quality ofurgical care delivered. Despite the importance of SSI,here have been few high quality studies that critically assesshe various surgical site preparation solutions. This trial isherefore both timely and relevant. The authors demon-trated that overall rates of SSI were 9.5% in thehlorhexidine-alcohol group, and 16.1% in the povidone-odine group (p � 0.004).

This study has some important methodologic strengths.t is multicenter (6 participating centers) and included aroad variety of intracavitary surgical procedures that crossurgical disciplines, which increases the external validity ofhe findings. The use of randomization to control for bothnown and unknown confounders appears to have worked,s shown in Table 1. There was equal distribution of knownotential confounders between the 2 arms of the trial. Therial had a clearly defined primary outcome that was mea-ured by observers who were blinded to group assignment,educing the possibility of measurement bias. In addition,he study had adequate sample size to detect a clinically andtatistically significant difference in outcomes.

There are, however, some limitations and interesting un-

nswered questions. First, the use of chlorhexidine-alcohol

nd povidone-iodine raises some questions about whatight be the compound that is active. Is it the chlorhexi-

ine, the alcohol, or the combination of the two? Is itossible that many of the other commercially available pre-aratory solutions might result in similar rates of SSI if theyontained 70% alcohol? The only other high quality studyhat has looked at skin preparation solutions was per-ormed by Swenson and associates.3 In this study 3 solu-

tions were compared: povidone-iodine (Betadine [PurdueProducts Inc]) with isopropyl alcohol; iodine povacrylex inisopropyl alcohol (DuraPrep [3M]); and 2% chlorhexidineand 70% alcohol (ChloraPrep [CareFusion]).They showedthat in patients with clean-contaminated wounds, the ratesof SSI were 8.1%, 6.5%, and 10.1%, respectively. Theseresults led the authors to conclude that alcohol in combi-nation with iodophor-based compounds are superior tochlorhexidine-based solutions. This study used a sequentialinclusion protocol, which is not as strong methodologi-cally. However, it leaves the question unanswered — whichcompound is most effective in decreasing the rates of SSI— and confirms the need for a randomized controlled trialcomparing alcohol in combination with an iodine-basedsolution with a chlorhexidine-based solution.

Other potential issues include the sponsorship of thetrial and the affiliation of the investigators. Although Car-dinal Health was involved in the funding and design of thistrial, they had no role in data collection and analysis; bothsolutions are Cardinal Health products, thereby making ithighly unlikely that the validity of the results is impaired.Third, are the results of the trial generalizable beyondclean-contaminated cases? The rates of SSI in clean casesmay be so low that a preparation solution of higher costcannot be justified. This raises the fourth issue: in additionto assessing differences in the rates of SSI, one of the out-comes should be a cost effectiveness analysis that takes intoconsideration all the costs associated with the care andmanagement of an SSI. The fifth issue is the risk of fire andburns with alcohol-based solutions. The true incidence isunknown, and the costs of even one patient injury are hardto calculate. The issue of whether waiting a certain amountof time can truly avoid this complication is unknown. At aminimum, the alcohol-based preparations should not beused in emergent situations when time is critical.The use ofthe alcohol-based preparation solutions will also increasethe procedural time.

Finally, the trial raises some interesting questions aboutthe relative importance of a strongly positive single trial. Isone trial such as this enough to change practice, and if so, inwhat population? Or, are further confirmatory trials re-quired? And if so, who will fund such a trial? Will surgeons

and investigators be willing to enroll their patients know-

376 Evidence-Based Reviews in Surgery J Am Coll Surg

ing the results of this trial? What is considered adequateequipoise? Some believe that a single trial is not enoughupon which to base change. However, if this is the case, is itpossible to get a confirmatory trial funded and approved byinstitutional review boards, and to convince colleagues toenroll their patients? In relation to the current questionregarding the ideal skin preparation solution to reduce SSI,possibly the ideal trial is one with 3 arms: povidone-iodine,chlorhexidine-alcohol, and povidone-iodine with alcohol.This trial could potentially be both confirmatory and mayhelp answer which alcohol-based solution is best.

In summary, although there are still some issues sur-rounding whether or not this trial alone is enough tochange practice, it is clear the authors have produced astudy of high methodologic quality that shows SSI rates inclean-contaminated operative cases are lower in patientswho underwent surgical site skin preparation usingchlorhexidine-alcohol in comparison with povidone-iodine. When using alcohol-based solutions, care must betaken to avoid fire and burns at the site of skin preparationand areas where the preparation may have pooled. Thesepreparations should probably not be used in emergencyoperations, in which time is of critical importance.

The Evidence-Based Reviews in Surgery GroupComprises:Members of the EBRS Steering Committee

Nancy N Baxter, MD, FACS, Toronto, ON, Canada

Karen J Brasel, MD, FACS, Milwaukee, WI

Carl J Brown, MD, Vancouver, BC, Canada

Prosanto Chaudhury, MD, Montreal, QC, Canada

C Suzanne Cutter, MD, Los Angeles, CA

Celia M Divino, MD, FACS, New York, NY

Elijah Dixon, MD, FACS, Calgary, AB, Canada

Luc Dubois, MD, London, ON, Canada

G William N Fitzgerald, MD, St. Anthony, NL, Canada

Harry J. Henteleff, MD, FACS, Halifax, NS, Canada

Andrew W Kirkpatrick, MD, FACS, Calgary, AB,Canada

Steven Latosinsky, MD, London, ON, Canada

Tara M Mastracci, MD, Cleveland, OH

Anthony R MacLean, MD, FACS, Calgary, AB, Canada

Robin S McLeod, MD, FACS, Toronto, ON, Canada

Arden M Morris, MD, FACS, Ann Arbor, MI

Leigh A Neumayer, MD, FACS, Salt Lake City, UT

Larissa K Temple, MD, FACS, New York, NY

Marg McKenzie, RN, Toronto, ON, Canada

REFERENCES

1. Darouiche RO, Wall MJ, Itani KMF, et al. Chlorhexidine-alcoholversus povidone-iodine for surgical site antisepsis. New EnglJ Med 2010;36;18–26.

2. Mangram AJ, Horan TC, Pearson ML, et al. Guideline for pre-vention of Surgical Site Infection, 1999. Centers for Disease Con-trol and Prevention (CDC) Hospital Infection Control PracticesAdvisory Committee. Am J Infect Control 1999;27:97–132.

3. Swenson BR, Hedrick TL, Metzgar R, et al. Effects of preopera-tive skin preparation on postoperative wound infection rates: aprospective study of 3 skin preparation protocols. Infect Control

Hosp Epidemiol 2009;30:964–971.