International Journal of Surgery 39 (2017) 221e228

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International Journal of Surgery

journal homepage: www.journal-surgery.net

Review

Preoperative chlorhexidine reduces the incidence of surgical site

infections in total knee and hip arthroplasty: A systematic review and
meta-analysis
Yuanzhen Cai, Ke Xu, Weikun Hou, Zhi Yang, Peng Xu*
Department of Joint Surgery Hong-Hui Hospital, Xi'an Jiaotong University College of Medicine, Xian, 710054, China

h i g h l i g h t s

To assess the incidence of surgical site infection between chlorhexidine skin preparation and traditional skin preparation.

Only high quality studies were selected.

Preoperative chlorhexidine skin preparation appears to reduce the risk of infection and incidence of revision surgery.

a r t i c l e i n f o a b s t r a c t

Article history: Objective: This meta-analysis aims to assess the incidences of surgical site infection of patients who
Received 9 December 2016 applied preadmission chlorhexidine skin preparation, versus those who applied the traditional skin
Received in revised form preparation before undergoing total knee and hip arthroplasty.
14 January 2017
Methods: A systematic search is carried out through Medline (1966e2016.11), PubMed (1966e2016.11),
Accepted 5 February 2017
Available online 9 February 2017
Embase (1980e2016.11), ScienceDirect (1985e2016.11) and the Cochrane Library. Only high quality
studies are identified. Meta-analysis is conducted with the use of Stata 11.0 software.
Results: One RCT and five retrospective studies, published between 2010 and 2016, are included in the
Keywords:
Chlorhexidine
present meta-analysis. The present meta-analysis indicates that there are significant differences in
Surgical site infection surgical site infection rate (RD ¼ 0.02, 95% CI: 0.02 to 0.01, P < 0.00001), revision surgery rate
Total knee arthroplasty (RD ¼ 0.01, 95% CI: 0.01 to 0.01, P < 0.00001) and length of stay (MD ¼ 0.29, 95% CI: 0.48
Total hip arthroplasty to 0.11, P ¼ 0.002) between groups.
Meta-analysis Conclusion: Preoperative chlorhexidine skin preparation appears to reduce the risk of infection, the
incidence of revision surgery, and the length of stay for patients undergoing total knee and hip
arthroplasty. No adverse effects, such as DVT or PE, appear to be related to chlorhexidine preparation.
Due to the limited quality of the evidence currently available, high quality RCTs with better study de-
signs, larger sample sizes and longer follow-ups are needed.
© 2017 IJS Publishing Group Ltd. Published by Elsevier Ltd. All rights reserved.

1. Introduction subsequent revision surgeries which are a financial burden. It has

Total joint arthroplasty (TJA) is a popular surgical procedure
which provides excellent functional results and reduces pain in
patients who suffer from osteoarthritis of the knee and hip. How-
ever, periprosthetic joint infection is a devastating complication
that is a deep concern for patients and surgeons alike. Infection may
lead to prolonged hospital stays, delayed recoveries and
* Corresponding author.
E-mail address: xupeng1967@163.com (P. Xu).
been reported that the infection rate of total knee arthroplasty
(TKA) is 1%e3% and 0.7%e2.5% for total hip arthroplasty (THA)
[1e6]. With the aging population, the number of joint arthroplasty
surgeries is expected to rise which is to say that more patients will
be at risk for periprosthetic infection. Avoiding infectious compli-
cations is therefore a pressing issue at hand.
Periprosthetic infection following a TJA may find its source in
operating room air and skin flora [7e10]. A multiple strategies
have been reported to decrease the risk of surgical site infections
following TKA and THA. Over the past few years, we have focused
on laminar airflow, positive air pressure and body exhaust suits,

http://dx.doi.org/10.1016/j.ijsu.2017.02.004
1743-9191/© 2017 IJS Publishing Group Ltd. Published by Elsevier Ltd. All rights reserved.
222 Y. Cai et al. / International Journal of Surgery 39 (2017) 221e228
each have been reported to have positive effects. Unfortunately,
these methods cannot reduce potential risk factors from skin
flora. Chlorhexidine is a broad-spectrum biocide that has bacte-
ricidal functions, and guards against Gram-positive and Gram-
negative bacteria. Previous studies have reported that preoper-
ative chlorhexidine showers can significantly reduce surgical site
infection when compared to no chlorhexidine shower [11e13].
However, some reports criticized chlorhexidine showers for
reducing chlorhexidine concentration on the skin because the
solution is washed off. Thus, a 2% chlorhexidine gluconate no-
rinse cloth has been introduced, which has a potentially supe-
rior bacterial effect and higher patient compliance.
Despite this previous research, whether preoperative chlor-
hexidine skin preparation is superior to standard skin preparation
in terms of infection rate remains unclear due to a lack of published
studies and limited sample sizes. Therefore, we have performed the
present systemic review and meta-analysis to assess the incidences
of surgical site infection of the patients undergoing TKA and THA
Fig. 1. Search results and the selection procedure.
who applied preadmission chlorhexidine skin preparation versus
those who applied traditional skin preparation.
2. Methods
2.1. Search strategy
We systematically searched electronic databases including
Embase (1980e2016.11), MEDLINE (1966e2016.11), PubMed
(1966e2016.11),, ScienceDirect (1985e2016.11), Web of Science
(1950e2016.11) and Cochrane Library for potentially relevant ar-
ticles. Grey academic studies were also identified from the refer-
ences of identified studies. There was no language restriction. The
following terms were used as key words in combination with
Boolean operators AND or OR: “Total knee replacement OR
arthroplasty”, “Total hip replacement OR arthroplasty”, “chlor-
hexidine”, and “infection’’. The retrieval process is presented in
Fig. 1.
 Y. Cai et al. / International Journal of Surgery 39 (2017) 221e228 223

2.2. Inclusion and exclusion criteria
Studies were considered eligible if they met the following
criteria: 1) Published clinical randomized controlled trials (RCTs) or
non-randomized controlled trials (non-RCTs); 2) Patients under-
going TKA or THA surgery, where the experimental group received
chlorhexidine cloth for preoperative skin preparation and the
control group received standard perioperative disinfection; 3) Re-
ported surgical outcomes, including surgical site infection rate,
incidence of revision surgery and length of stay. Studies were
excluded from the meta-analysis if they had incomplete data, cases
report, and review articles.
2.3. Selection criteria
Two reviewers independently reviewed the abstracts of the
potential studies. After an initial decision, the full text of the studies
that potentially met the inclusion criteria were reviewed before a
final decision was made. A senior reviewer was consulted in cases
involving disagreement.
2.4. Data extraction
Two reviewers independently extracted the relevant data from
the included studies. When incomplete data were encountered, the
corresponding author was consulted. The following data were
extracted: first author names, publication year, study design,
comparable baseline, anesthesia methods and duration of follow
up. Outcome parameters included the surgical site infection rate,
incidence of revision surgery and length of stay. Other relevant data
were also extracted from individual studies.
2.5. Quality assessment
The quality assessment of the included studies was performed
by two reviewers independently. The modified Jadad score which
was based on the Cochrane Handbook for Systematic Reviews of
Interventions was used for the assessment of the RCTs. Studies with
scores greater than four points were considered to be high-quality.
We created a “risk of bias” table that included the following key
points: random sequence generation, allocation concealment,
blinding, incomplete outcome data, free of selective reporting and
other bias. The Methodological Index for Non-Randomized Studies
(MINORS) scale was used to assess non-RCTs with scores ranging
0 to 24. Consensus was reached through a discussion.
2.6. Data analysis and statistical methods
All calculations were completed in Stata 11.0 (The Cochrane
Collaboration, Oxford, United Kingdom). Statistical heterogeneity
was assessed based on the value of P and I2 using a standard chi-
square test. When I2>50%, P < 0.1 was considered to indicate sig-
nificant heterogeneity. A random-effect model was used in the
meta-analysis. Otherwise, a fixed-effect model was utilized. If
possible, a sensibility analysis was conducted to explore the origins
of the heterogeneity. The results of any test with a dichotomous
outcomes was expressed as a risk difference (RD) with a 95% con-
fidence interval (CI). For continuous outcomes, the mean difference

Table 1
Trials characteristics.

Studies type Cases Mean age Female patient Anesthesia Surgical Traditional skin Antibiotic Follow up
methods preparation prophylaxis
(C/T) (C/T) (C/T)

Johnson 2010 retrospective study 157/897 58/58 80/425 general anesthesia THA shaving, combination √, NS 2 months
iodine poyacrylex/alcohol
preparation (DuraPrep
solution; 3M, St Paul, Minn)
on the day of surgery
Zywiel 2011 retrospective study 136/711 63/63 90/490 spinal anesthesia TKA combination iodine √, NS 6 months
povacrylex/alcohol
(DuraPrep solution, 3M, St.
Paul, MN, USA) on the day
of surgery
Johnson 2012 retrospective study 478/1735 63/63 274/998 general anesthesia TKA disinfection with a √, NS NS
combination solution of
0.7% iodine povacrylex and
74% isopropyl alcohol on
the day of surgery
Kapadia 2013 retrospective study 557/1901 56/58 557/1901 NS THA shaving and disinfection √, NS NS
with a combination
solution of 0.7% iodine
povacrylex and 74%
isopropyl on the day of
surgery
Bhaveen 2016 retrospective study 991/2726 62/62 991/2726 general anesthesia TKA alcohol and subsequently √, NS 6 months
with a combination of
iodine povacrylex/alcohol
(DuraPrep solution; 3M, St
Paul, MN, USA) on the day
of surgery
Kapadia 2016 randomized 275/279 61/62 171/169 NS TKA & THA shaving and disinfection √, 1 g cefazolin 12 months
controlled trial with iodine povacrylex and
isopropyl alcohol solution
(DuraPrep Surgical
Solution, The 3M Company,
Saint Paul, MN) on the day
of operation

C: chlorhexidine skin preparation, T: traditional skin preparation, NS: not state.

224 Y. Cai et al. / International Journal of Surgery 39 (2017) 221e228
(MD) or standard mean difference (SMD) with a 95% confidence
interval (CI) was used in the assessment.
3. Results
3.1. Search result
A total of 398 studies were identified through the initial search.
By scanning the abstracts, 392 reports that did not meet inclusion
criteria were excluded from the current meta-analysis. No grey
literature was included. Finally, one RCT [14] and five retrospective
studies [15e19] which published between 2010 and 2016 were
included in the present meta-analysis; these studies included 2593
patients in the experimental groups and 8237 patients in the
control groups. The search strategy is presented in Fig. 1.
3.2. Study characteristics
Statistically similar baseline characteristics were observed be-
tween groups (Table 1). The sample sizes ranged from 539 to 3717.
Only studies that included patients with primary total knee or total
hip arthroplasty were included in the present meta-analysis. In
these studies, the experimental groups received preadmission
chlorhexidine skin preparation and the control groups received
traditional skin preparation. The characteristics of the included
studies are reported in Table 1. Four studies performed general
anesthesia and one was spinal anesthesia [15]. All included studies
applied antibiotic prophylaxis, however, only one studies [14]
pointed out 1 g cefazolin was used. All of them suggest the
Table 2
Methodological quality of the randomized controlled trials.
outcomes for at least 95% of the patients. Four [14e16,18] studies
reported the follow-up period which ranged from 2 to 12 months.
3.3. Quality assessment
Modified Jadad score which was based on Cochrane Handbook
for Systematic Reviews of Interventions is used for assessment of
RCTs (Table 2). Only one RCT was included. It provides clear in-
clusion and exclusion criteria and suggest a methodology of
randomization that was generated from computer. However, allo-
cate concealment was not stated in the study. The surgeon and the
patients were blinded except assessors. The Methodological Index
for Non-Randomized Studies (MINORS) scale was used to assess
non-RCTs with scores ranging 0 to 24 (Table 3).
3.4. Outcome for meta-analysis
3.4.1. Surgical site infections rate
Six articles [14e19] reported the outcomes of surgical site in-
fections following TJA. There was no significant heterogeneity
among the studies (c2 ¼ 3.85, df ¼ 5, I2 ¼ 0%, P ¼ 0.57), therefore a
fixed-effects model was used. Pooled results demonstrated that
surgical site infections rate in control groups was significantly
higher than in experimental groups (RD ¼ 0.02, 95% CI: 0.02
to 0.01, P < 0.00001; Fig. 2).
3.4.2. Revision surgery rate
Four studies [15,16,18,19] reported the outcomes of revision
surgery following TJA. There was no significant heterogeneity
 Y. Cai et al. / International Journal of Surgery 39 (2017) 221e228 225

Table 3
Methodological quality of the non-randomized controlled trials.

Quality assessment for non-randomized trials Johnson 2010 Zywiel 2011 Johnson 2012 Kapadia 2013 Bhaveen 2016

A clearly stated aim 2 2 2 2 2

Inclusion of consecutive patients 2 2 2 2 2
Prospective data collection 2 2 2 2 2
Endpoints appropriate to the aim of the study 2 2 2 2 2
Unbiased assessment of the study endpoint 0 0 0 0 0
A follow-up period appropriate to the aims of study 2 2 1 2 2
Less than 5% loss to follow-up 2 2 2 2 2
Prospective calculation of the sample size 0 2 0 2 0
An adequate control group 2 2 2 2 2
Contemporary groups 0 1 0 0 0
Baseline equivalence of groups 2 2 2 2 2
Adequate statistical analyses 2 2 2 2 2
Total score 18 21 17 21 18

Fig. 2. Forest plot diagram showing surgical site infections following TJA.

among the studies (c2 ¼ 1.45, df ¼ 3, I2 ¼ 0%, P ¼ 0.694), therefore a
fixed-effects model was used. Pooled results demonstrated that
revision surgery rate in control groups was significantly higher than
in experimental groups (RD ¼ 0.01, 95% CI: 0.01 to 0.01,
P < 0.00001; Fig. 3).
3.4.3. Length of stay
Four studies [15,17e19] reported the outcomes of length of stay
following TJA. There was no significant heterogeneity among these
studies (c2 ¼ 3.60, df ¼ 3, I2 ¼ 16.6%, P ¼ 0.308), therefore a fixed-
effects model was used. Pooled results demonstrated that there
was significant difference between groups regarding length of stay
(MD ¼ 0.29, 95% CI: 0.48 to 0.11, P ¼ 0.002; Fig. 4).
4. Discussion
Meta-analysis is used as major statistical method in this study. It
can strengthen statistical power and enlarger sample size by
pooling results of published studies, which could point out stronger
evidence. Moreover, no guidelines have been proposed for skin
preparation before total knee and hip arthroplasty. Therefore, there
is a need for an evidence base to help surgeons make clinical
226 Y. Cai et al. / International Journal of Surgery 39 (2017) 221e228
Fig. 3. Forest plot diagram showing revision surgery rate following TJA.
decisions and develop appropriate methods of skin preparation
before joint arthroplasty surgery.
To our knowledge, this is the first meta-analysis which assesses
the incidence of surgical site infection of the patients undergoing
TKA or THA who applied preadmission chlorhexidine skin prepa-
ration versus those who applied traditional skin preparation. The
most important finding of this meta-analysis is that chlorhexidine
cloth application can significantly reduce the risk of surgical site
infection, the rate of subsequent joint arthroplasty and length of
stay following total knee and hip arthroplasty. Furthermore, no
adverse effects, such as DVT or PE, are associated with preoperative
chlorhexidine preparation.
Currently, debates around appropriate treatment of peri-
prosthetic joint infection still exists. It was considered as the most
disastrous postoperative complication and placed a huge burden on
patients and surgeons following total knee and hip arthroplasty.
Greater efforts have been made to reduce contamination so as to
decrease the risk of infection including preoperative prophylactic
antibiotic, operating room management, strict policy of operative
procedure and appropriate antiseptic skin preparation [20e22].
However, conclusive information for optimal preoperative, at-
home preparation remain controversial. Previous studies has
demonstrated that many times of preoperative disinfection
showers should be performed to minimize the risk of surgical site
infection but it potentially led to less compliance of patients.
Recently, chlorhexidine has shown superior efficacy at reducing
pathogenic bacteria and subsequently decreased the risk of surgical
site infections. It has placed iodophor as standard antiseptic skin
preparation due to rapid bactericidal effect and long-lasting
residual effects, thus, the microorganism on the skin was inacti-
vated. Eiselt [13] compared the infection rate in 727 patients who
applied povidone-iodine wash to 736 patients who applied chlor-
hexidine wash the night before surgery and showed a decreased
incidence of surgical site infections from 3.2% with povidone-iodine
wash to 1.6% under chlorhexidine wash. Zywiel [15] found that
preadmission chlorhexidine skin preparation was associated with a
decreased incidence of surgical site infections following chlorhex-
idine cloth use compared those who received standard skin prep-
aration in total knee arthroplasty.
Skin asepsis is a crucial strategy for reducing risk of surgical site
infections. The chlorhexidine cloth wipes provided better outcome
than chlorhexidine washes in recent studies. Edmiston [23]
assessed the chlorhexidine shin surface concentration in different
groups and found that it was 51.6e119.6 ppm in wash group
compared to 907e1049.6 in the cloth group. By cloth application,
chlorhexidine shin surface concentration is significant higher than
with the wash. They concluded that chlorhexidine cloth wipes was
the first choice for preadmission skin preparation currently in total
knee and hip arthroplasty. However, Swenson [24] reported that
povidoneeiodine scrub-paint combination or an iodine povacrylex
in isopropyl alcohol was superior compared with 2% chlorhexidine
regarding infections. The present meta-analysis indicated that
preadmission chlorhexidine protocol was an effective way to
reduce surgical site infection in total knee and hip arthroplasty.
The aging population contributes to the increased incidence of
joint arthroplasties. Infections are considered the most severe
complication. It is reported that the current infection rate in total
knee arthroplasty is 1e2.3% [5]. There is an estimated that
 Y. Cai et al. / International Journal of Surgery 39 (2017) 221e228 227

Fig. 4. Forest plot diagram showing length of stay following TJA.

approximately 300,000 wound infections occur in the USA annu- Preoperative skin preparation remains an interesting topic in
ally [25]. Therefore, the demand for improved preventative mea- the field of orthopedics and substantial efforts made to reduce
sures is evident. Revision joint arthroplasty would be performed if postoperative complications. Despite the aforementioned limita-
there was a failure of antibiotic administration, incision and tions, this is the first meta-analysis from published clinical trials to
drainage. Multiple studies have noted that infection is the risk assess the incidence of surgical site infection between the patients
factor for revision of joint arthroplasty which required prolonged who applied preadmission chlorhexidine skin preparation and
treatment and additional medical expense [26,27]. The present traditional skin preparation undergoing TKA or THA. High quality of
meta-analysis showed that there is a decreased rate of revision RCTs with better study design, larger sample size and longer follow-
surgery in chlorhexidine groups compared control groups. up are needed.
Long bedridden periods may rise the medical costs. More
importantly, adverse events, such as, hypostatic pneumonia, DVT
5. Conclusion
and PE are associated with long-term bedridden which would in-
crease the morbidity and mortality especially in elderly individuals
Preoperative chlorhexidine skin preparation appears to reduce
[28]. Early weight-bearing and rehabilitation have been shown to
the risk of infection, the incidence of revision surgery, and the
contribute to better functional outcomes following knee and hip
length of stay for patients undergoing total knee and hip arthro-
arthroplasty [29]. The present meta-analysis indicated that pre-
plasty. No adverse effects, such as DVT or PE, appear to be related to
operative chlorhexidine skin preparation was associated with
chlorhexidine preparation. Due to the limited quality of the evi-
shortened length of stay following joint arthroplasty compared to
dence currently available, high quality RCTs with better study de-
control groups.
signs, larger sample sizes and longer follow-ups are needed.
There were several potential limitations that should be noted.
(1) Only six studies were included, and the sample size was rela-
tively small. (2) Some important outcome parameters, such as Ethical approval
medical costs and range of motion, were not fully described and
could not be included in the meta-analysis. (3) Most included No application.
studies were retrospectives which may cause various types of bias
(4) Short-term follow-up may lead to underestimation of compli- Sources of funding
cations. (5) Publication bias is an inherent weakness that exists in
all meta-analyses. No application.
228 Y. Cai et al. / International Journal of Surgery 39 (2017) 221e228
Author contribution
Yuan zhen Cai and Zhi Yang: Data collections and writing.
Weikun Hou and Ke Xu: Data analysis.
Peng Xu: Study design.
Conflicts of interest
There is no conflicts of interest.
Research registration unique identifying number (UIN)
reviewregistry 173.
Trial registry number e ISRCTN
None.
Guarantor
Peng Xu.
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