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CE: A.G.; ANNSURG-D-16-01402; Total nos of Pages: 6;
ANNSURG-D-16-01402
Broach et al. Annals of Surgery Volume XX, Number XX, Month 2017
incision open, ongoing radiation or chemotherapy, history of lapa- representation in the 2 treatment arms. The study statistician created
rotomy within 60 days, current abdominal wall infection, and known a computer generated list of random assignments by hospital block.
allergy to chlorhexidine gluconate or iodine. Patients were excluded The clinical trial coordinator delivered sequentially numbered,
if they were participating in any concomitant preoperative antibiotic randomized opaque envelopes to the sites in a block. The study
or skin antisepsis trial. Women who were pregnant or breast feeding coordinator opened the sequentially numbered, opaque envelope
were excluded. Patients were recruited into the study by attending containing the randomization assignment postinduction of anesthesia
surgeons or advanced practitioners in the preoperative clinic setting when in the operating room.
simultaneously with discussions about, and consent for, surgery. Training in use of each skin preparation was conducted by the
study coordinator and the operating room staff compliance and
Interventions quality officers. Every surgeon, resident, fellow, and nurse involved
The patients were randomized in a 1:1 ratio to undergo skin in a study case was required to attend or view an online training
preparation with either iodine povacrylex-alcohol, a 26 mL single- module detailing the appropriate use of each skin preparation. The
use applicator containing iodine povacrylex [0.7% available iodine]/ study coordinator or attending surgeon was present for every prep-
74% isopropyl alcohol (w/w) or chlorhexidine-alcohol, a 26 mL aration application to ensure quality control. A single applicator was
single-use applicator containing 2% chlorhexidine gluconate (w/v) used for most patients. Those who were morbidly obese required a
and 70% isopropyl alcohol (v/v). Both skin preps contain isopropyl second applicator. The IPA arm involved single pass application
alcohol that has strong immediate antimicrobial effects but no whereas the chlorhexidine-alcohol arm involved several passes of the
appreciable residual activity on skin. Each contains a second com- applicator in a circular motion. Both were allowed to dry for 3
ponent that offers residual activity up to 48 hours. minutes before draping. All preparation sticks were used according
Block randomization, based on hospital site, was used to to manufacturer’s instructions by attending surgeons, residents or
insure that each site would have statistically proportionate fellows who underwent live and video training.
Copyright © 2017 Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited.
CE: A.G.; ANNSURG-D-16-01402; Total nos of Pages: 6;
ANNSURG-D-16-01402
Annals of Surgery Volume XX, Number XX, Month 2017 Skin Antisepsis in Colorectal Surgery
Copyright © 2017 Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited.
CE: A.G.; ANNSURG-D-16-01402; Total nos of Pages: 6;
ANNSURG-D-16-01402
Broach et al. Annals of Surgery Volume XX, Number XX, Month 2017
(mITT) manner. This sample was defined as those subjects who were The baseline patient characteristics by treatment group are
randomized and underwent a clean-contaminated surgery and had no displayed in Table 1. There were no significant differences among the
reoperation before SSI within 30 days postdischarge. The differences patients in each group with regard to demographics, diagnoses,
between patient factors between the 2 treatment arms were evaluated surgical techniques, preoperative medical therapies, or perioperative
using the F test for continuous variables and x2 test for categorical antibiotics. The types of operation were also comparable (data not
variables. shown). Of note, all patients received antibiotics within an hour of
To examine the primary outcome, the overall rate of wound incision and almost all received antibiotics consistent with the
infection was compared by treatment arm using the Fisher exact test. Surgical Care Improvement Project guidelines as specified in
Secondary outcomes, including the rate of each individual type of the protocol.
wound infection and organ space infection were evaluated separately The overall rate of SSI (superficial and deep SSI) was 17.3%
between subjects in each treatment arm. Length of stay was com- and did not differ significantly between the treatment arms (Table 2).
pared using an F test. Time from date of surgery to date of wound The rate of overall SSI was 18.7% in the IPA arm and 15.9% in the
infection was graphed using the product-limit method with subjects chlorhexidine-alcohol group (P ¼ 0.30). The difference in SSI rate
censored at the date of follow up if no SSI was observed. Differences between chlorhexidine-alcohol and IPA was 2.8%. The upper bound
between groups were evaluated using the log-rank test. All P values of the 2.5% confidence interval was 8.9%, which is greater than the
were 2-sided. The organisms identified in wound cultures were prespecified noninferiority margin of 6.6%. When examined indi-
compared descriptively. As not all subjects with infection were vidually, there were no differences in the rate of superficial SSI or
cultured and some subjects had more than one microorganism deep SSI or cellulitis between the 2 treatment groups. Cellulitis was
identified, no statistical test was performed. diagnosed in 4.8% of the IPA patients and in 3.6% of the chlorhex-
idine-alcohol patients.
Secondary endpoints including organ space infection, length
RESULTS of stay, and time to diagnosis of wound infection were analyzed.
A total of 802 subjects were randomized (402 to IPA and 400 Organ space infections were identified in 4.0% of IPA patients and
to chlorhexidine-alcohol). Ten subjects were excluded because of 5.1% of chlorhexidine-alcohol patients (P ¼ 0.50). Length of stay
reoperation within 30 days (4 IPA and 6 chlorhexidine-alcohol); 4 was identical between the 2 treatment arms. The average length of
were excluded because the case was aborted and no resection was stay for patients in the IPA arm was 6.8 days (s.d. 3.7), compared with
done. In total, 788 patients (396 patients in the IPA arm and 392 in the 7.0 (s.d. 3.9) days for patients in the chlorhexidine-alcohol arm (P ¼
chlorhexidine-alcohol arm) were included in the mITT analysis 0.45).
(Fig. 1). Eighteen patients in the IPA arm and 12 patients in the Time to infection is displayed graphically in Figure 3. The
chlorhexidine-alcohol arm did not complete the 15 and/or 30 day average time from surgery to diagnosis was 8.7 days (s.e 0.6 days) in
follow up. They were included, however, in the mITT cohort for the IPA arm and 8.0 days (s.e. 0.7 days) in the chlorhexidine-alcohol
analysis based on the information available at time of latest contact. arm (P ¼ 0.21). The result is notable for the wide range of times in
Copyright © 2017 Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited.
CE: A.G.; ANNSURG-D-16-01402; Total nos of Pages: 6;
ANNSURG-D-16-01402
Annals of Surgery Volume XX, Number XX, Month 2017 Skin Antisepsis in Colorectal Surgery
both arms; there were infections diagnosed as soon as 3 days post- prospectively, with rigorous documentation procedures in place,
operatively, and as long as 37 days after surgery. the use of IPA compared with chlorhexidine for patients undergoing
Finally, we examined the bacteria identified in the cultured clean-contaminated elective colorectal fails to meet the criterion for
wounds. Overall, only 69 wounds were cultured. In 59 wounds, 1 noninferiority for our primary outcome, overall SSI.
organism was identified; in 9 wounds, 3 organisms were isolated; Two previous prospective trials have examined the relation-
and, in 1 wound, 3 organisms were found. There was no difference in ship between skin preparation and SSI in surgical patients and have
the types of bacteria between the treatment arms (see table, Supple- informed this study to a large degree. Findings from these trials have
mental Digital Content 3, http://links.lww.com/SLA/B194). In both been seminal in driving the national change to alcohol-based skin
groups, Escherichia coli was the most frequent organism isolated, preps for general surgery patients. A study by Swenson et al7
accounting for almost 33% of the organisms identified. compared 3 different dual action skin preparations, all employing
There were no adverse events or serious adverse events isopropyl alcohol, in general surgery (including colorectal) patients
attributed to either skin preparation during the trial. Complications, with SSI as primary outcome. The results demonstrated that both IPA
other than SSI, not related directly to the skin preparation were not and povidone iodine with isopropyl alcohol applied sequentially
different between the 2 groups (data available upon request). were significantly more effective than chlorhexidine-alcohol. This
was followed by a trial from Darouiche et al6 in 2010 that compared
DISCUSSION chlorhexidine-alcohol with single component 10% povidone iodine
Optimal preoperative skin preparation is an important aspect in general surgery patients. This trial demonstrated a 41% reduction
of SSI prevention. Organizations focused on outcome improvement in SSI in the chlorhexidine-alcohol arm. Although elective colorectal
such as the National Quality Forum now recommend use of alcohol procedures comprised a percentage of patients in these trials, there
based skin preparations for surgical procedures but do not specify were a large number of low risks (cholecystectomy) and clean
which to use.13,14 There are numerous studies examining the efficacy procedures (hernia repair) included. The heterogeneity of the groups
of preoperative skin preps in both clean and clean-contaminated made subset analysis of the highest risk group difficult.
procedures, but none prospectively examining only colorectal pro- To better evaluate the comparative efficacy of 2 alcohol based
cedures—those with the highest risk. With relatively a few excep- preps, a study dedicated to those cases at highest risk was required.
tions, most recent studies examining SSI in abdominal surgery are The inclusion of cellulitis as an outcome in the analysis was
retrospective in nature or rely on administrative data from national important. Although it does not meet CDC criteria for SSI, it is a
and state databases. Our group found that when examined clinically meaningful complication that frequently results in use of
Copyright © 2017 Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited.
CE: A.G.; ANNSURG-D-16-01402; Total nos of Pages: 6;
ANNSURG-D-16-01402
Broach et al. Annals of Surgery Volume XX, Number XX, Month 2017
antibiotics. We defined cellulitis as ‘‘erythema, warmth, and pain more objective means of diagnosis compared with review of clinical
requiring antibiotics’’ and only scored erythema as cellulitis if documentation only.
antibiotics were prescribed and the patient had all 3 symptoms. In conclusion, this study statistically fails to support the
Photodocumentation was used in addition to clinical criteria to noninferiority of iodine povacrylex-alcohol to chlorhexidine-alcohol
document and diagnose SSI. Distinctions between cellulitis, super- skin preparation in regard to superficial or deep SSI between patients
ficial, and deep SSI were ultimately aided by visual cues provided by undergoing elective colorectal surgery. Rigorous photodocumenta-
high resolution photographs in addition to knowledge of culture and tion aided standardized assessments, and adherence to the protocol
treatment data (Fig. 2). Blinded review of all study photos allowed was high. It is clear that alcohol based skin preparations are an
for standardization of diagnosis across subjects and sites and important part of SSI prevention in elective colorectal surgery. It is
represents a unique study feature that ensured fidelity to CDC also clear that the absolute differences in SSI prevention between
definitions. Photodocumentation made the most vague and problem- these preparations are not large. However, in light of these findings,
atic of the CDC definitions—‘‘diagnosis by attending surgeon’’ and until further studies are available, chlorhexidine-alcohol is
unnecessary and unused.13 favored to prevent superficial and deep SSI in elective clean con-
The rate of SSI in this study was comparable with other taminated colorectal cases.
prospective datasets but higher when compared with that from
retrospective studies. Although not powered to examine differences
in colorectal procedures, the Darouiche group found rates of SSI ACKNOWLEDGMENTS
ranging from 15.1 to 22.0%.6 Their protocol included 30 day out- The authors would like to thank clinical investigators Robert
comes assessed by weekly telephone encounters to determine wound D Fry, Skandan S Shanmugan, Joshua IS Bleier, Brian R Kann, and
problems. Swenson’s group did not specifically examine rates of Cary B Aarons for their contributions to this study.
wound infection in colorectal surgery but did a subset analysis of
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