Albumin and surgical site infection risk in orthopaedics: a meta-analysis
Yuwen et al. BMC Surgery
Albumin and surgical site infection risk in orthopaedics: a meta-analysis
Peizhi Yuwen 0
Wei Chen 0
0 Equal contributors Department of Orthopedic Surgery, the Third Hospital of Hebei Medical University , No. 139 Ziqiang Road, Qiaoxi District, Shijiazhuang 050051 , People's Republic of China
Backgroud: Surigical site infection has been a challenge for surgeons for many years, the prevalence of serum albumin <3.5g/dL has been reported to be associated with increased orthopaedic complications. However, the prognostic implications and significance of serum albumin <3.5g/dL after orthopaedic surgeries remain ambiguity. In this study, we performed a meta-analysis to access the predictive value of serum albumin level on SSI. Methods: A basic data search was performed in PubMed and Web of Science, in addition, references were manually searched. All of the observational studies contained preoperative albumin, outcomes of SSI or valuable data that could be abstracted and analysed for meta-analysis in orthopaedics. All of the studies were assessed using the classic Newcastle Ottawa Scale (NOS). They conformed to critical quality evaluation standards, and the final data analysis was performed with RevMan 5.2 software. Results: A total of 112,183 patients included in 13 studies were involved. The pooled MD of albumin between the infection group and the non-infection group was MD = −2.28 (95 % CI −3.97-0.58), which was statistically significant (z = 2.63, P = 0.008). The pooled RR of infection when comparing albumin <3.5 with albumin >3.5 was 2.39 (95 % CI 1.57 3.64), which was statistically significant (z = 4.06, P < 0.0001). Heterogeneity were found in the pooled MD of albumin and in the pooled RR for infection (P = 0.05, I2 = 61 % and P = 0.003, I2 = 68 %). No publication bias occurred based on two basically symmetrical funnel plots. Conclusion: Our meta-analysis demonstrated that an albumin level <3.5 g/dL had an almost 2.5 fold increased risk of SSI in orthopaedics, although this conclusion requires well-designed prospective cohort studies to be confirmed further.
The most common complication an orthopaedics patient
can confront is surgical site infection (SSI). SSI has been
a challenge for surgeons for many years, and the trends
currently prefer the development of post-operation
management to decrease the SSI rate. However, can SSI be
predicted using less invasive or more tolerable tests?
Recently, researchers have shown that malnutrition has
links with serious complications in orthopaedics, but as
many as 50 % of cases of pre-existing malnutrition are
unrecognized in the hospital population [1, 2], with a
reasonable explanation being that observable signs of
malnutrition appear only in extreme cases. Because
serum albumin has high sensitivity, it also can be used
to determine and screen for nutritional status [2, 3].
Owoicho Adogwa et al. suggested that preoperative low
albumin (serum albumin <3.5 g/dL) was an independent
risk factor for postoperative SSI in spine fusion , Jason
D. Walls et al. identified 49,475 total hip arthroplasty
(THA) patients and found that low albumin was a
significant risk factor for increased mortality and major
morbidity in THA . However, controversy exists as
well, with Jiong Jiong Guo finding that ALB had only a
weak relationship with delayed wound healing after hip
fractures in the elderly . M. Hedström demonstrated
that preoperative serum albumin could not be used to
predict postoperative deep wound infection . Identical
results regarding the relationship between low albumin
and SSI from large systematic reviews have not yet been
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obtained; therefore, we aim to perform a meta-analysis
to investigate whether low albumin is effective in
predicting SSI and to estimate the relative infection rates in
patients with normal albumin and low albumin.
An online search was performed in two databases (Web
of Science, PubMed) from 1970 to 2015. Selected
references were manually reviewed. The main search terms
were “albumin”, “risk” and “infection”. The search details
in PubMed were as follows: (Etiology/Broad[filter]) and
(“albumin”[tiab]) or (“hypoalbuminemia”[tiab]) and
“infection”[tiab] and ((“spine”[tiab] or “hip”[tiab] or “knee”[tiab]
or “shoulder” [tiab] or “joint” [tiab] or “fracture” [tiab]
or “arthroplasty” [tiab] or “orthopaedics”[tiab]). In
Web of Science, the details were as follows: (Ts =
albumin or Ts = (hypoalbuminemia)) and Ts = infection
and Ts = risk, refined by orthopaedics.
Exclusion and eligibility criteria
Studies were required to meet the following eligibility
criteria: 1) studies regarding surgical site infections (SSI,
superficial SSI, deep SSI, organ space SSI) in
orthopaedics; 2) studies including infection and non-infection
groups subdivided by serum albumin <3.5 g/dL and
serum albumin >3.5 g/dL; 3) studies with sample sizes
with a mean ± standard deviation of albumin between an
infection group and a non-infection group; 4)
crosssectional studies, cohort studies, and cross-sectional,
cohort studies containing assessable data or reported risk
ration (RR) with 95 % confidence interval (CI) of
infection risk between two groups or other cross-sectional
studies, cohort studies, and cross-sectional, cohort
studies containing assessable data; and 5) studies providing
sufficient data to fulfil the contingency tables.
Non-English-language articles, case reports, reviews,
duplicate papers with same results, and conference
reports were excluded. Original articles without control
groups were excluded, and articles with incomplete or
unacceptable information were excluded.
Standardized two-by-two contingency tables were used
to record the following abstracted data: title, first author,
country, publication year, research year, study type,
average age of subjects, surgery type, patient number and
the mean ± standard deviation of albumin in infection
and non-infection groups; Relevant variables were
carefully read and extracted from each study. Missing data
were supplemented by contacting the corresponding
All of the studies were assessed for quality evaluation
standards using the classic Newcastle Ottawa Scale
The Cochrane Collaboration’s RevMan 5.2 software was
used for the data analysis. Pooled mean difference (MD)
with 95 % CIs for continuous variables and enumeration
data for Pooled RR with 95 % CIs were calculated, and
the Z test was performed to determine overall effects. If
the heterogeneity between studies was statistically
significant (I2 > 50 %), a random effects model was used for
further sensitivity analysis; otherwise, a fixed effects
model was used (I2 < 50 %).
Results of literature search and evaluation of
Two authors (Yuwen Peizhi and Chenwei) sorted and
reviewed all of the titles and abstracts of the retrieved
articles; 25 studies finally met the eligibility criteria. Each
full text article was read by two reviewers, and 12 studies
involving 112,183 patients were ultimately placed on the
short list to complete the form. The quality of the
articles was assessed according to the literature quality
evaluation criteria (Fig. 1, Tables 1 and 2).
Albumin difference between the infection and non-infection
Four studies reported available albumin data with
relative higher heterogeneity (P = 0.05, I2 = 61 %). A random
effects model was applied for meta-analysis, and the
results showed that preoperative albumin was significantly
lower in the infection group than in the non-infection
group (OR = −2.28, 95 % CI [−3.97, −0.58], P =0.008)
SSI rate between the infection and non-infection groups
Nine studies (Lan B. MC Phee contain both Albumin
difference and SSI rate) reported the incidence of SSI in
both groups. In SSI group, the infection rate was 2.96 %
(143/4837) in the albumin <3.5 g/dL group and 1.00 %
(1070/106,641) in the albumin >3.5 g/dL group, (RR =
2.39, 95 % CI [1.57 3.64], which was statistically
significant (Z = 4.06, p < 0.0001) in a random model (I2 =
68 %). In superficial SSI subgroup, the infection rate was
1.64 % (45/2745) in the albumin <3.5 g/dL group and
0.67 % (392/58,721) in the albumin >3.5 g/dL group,
(RR = 2.46, 95 % CI [1.81 3.35], Z = 5.73, p < 0.00001 in a
fixed model (I2 = 0 %). In deep SSI subgroup, the
infection rate was 0.61 % (17/2767) in the albumin <3.5 g/dL
group and 0.18 % (108/58,818) in the albumin >3.5 g/dL
group, (RR = 2.62, 95 % CI [1.56 4.42], Z = 3.62, p =
Fig. 1 Flow diagram showing selection of studies
0.0003) in a fixed model (I2 = 0 %). In organ space SSI
subgroup, the infection rate was 0.37 % (10/2688) in the
albumin <3.5 g/dL group and 0.17 % (100/58,642) in the
albumin >3.5 g/dL group, (RR = 2.17, 95 % CI [1.13
4.15], Z = 2.34, p = 0.02 in a fixed model (I2 = 18 %)
Regarding the pooled MD of albumin between the
infection group and the non-infection group was MD = −2.28
(95 % CI −3.97–0.58), which was statistically significant
(z = 2.63, P = 0.008). Regarding the overall effect RR
(95 % CI) of the difference in albumin, the SSI rates
between the compared groups in a random model were
2.39 (95 % CI 1.57, 3.64) (z = 4.06, P < 0.001), superficial
SSI, deep SSI and organ space SSI between the
compared groups in the fixed model were 2.46 (95 % CI
1.81, 3.35), 2.62 (95 % CI 1.56, 4.42) and 2.17 (95 % CI
1.13, 4.15), respectively. All showed statistically
significant (z = 5.73, P < 0.00001; z =3.62, P = 0.0003 and
z =2.34, P = 0.02, respectively), the results were
consistent between the random and fixed effects models,
suggesting that all of the findings in our study were
fundamentally reliable (Figs. 2 and 3).
The funnel plots of pooled MD in albumin levels
between the infection and non-infection groups and in the
incidence of SSI in the two groups were both basically
symmetrical, demonstrating no significant publication
bias (Figs. 4 and 5).
The meta-analysis indicated that an albumin <3.5 mg/dL
had an almost 2.5fold increased risk of SSI in
orthopaedics, and these outcomes were statistically
significant (p < 0.05) and robust. Many factors have been
indicated and proved to have effects on SSI; among
these factors, malnutrition has stood out, and a broad
array of serological laboratory values, such as a serum
albumin <3.5 mg/dL, have presented a significantly
increased risk of infection in spine metastases , spine
fusion , joint arthroplasty  and hip fracture [5, 11].
Theoretically, our wound healing progress was
fundamentally based on our own knowledge of the potential
relationship between nutrition and SSI, which could help us
forecast SSI or even through some potent treatment,
maintain the patient’s nutritional status, which in turn
could promote the body’s resistance to pathogenic
bacteria, obtaining satisfactory clinical results.
Charles LN et al. reported that low serum albumin
had a more dominant association with complications
after TKA than obesity . Carlos J. L et al.
evaluated the standard preoperative laboratory tests of 119
patients and demonstrated that preoperative
nutritional status was an excellent predictor as SSI, as
well as controllable factors for postoperative
complications in patients undergoing joint replacement
surgery . Dickhaut et al. showed that low serum
11/1984–5/1995 not mentioned
spine metastases SSI
Cohort 53.8 ± 17.0
Cohort not mentioned 2006–2013
during hospitalization TKA
Cohort 64.6 ± 15.62
1/-1-31/12, 1997 during hospitalization THA and TKA
Cohort not mentioned 2006–2013
Cohort not mentioned 2011–2013
THA and TKA
First author, Year
Table 1 Characteristics of selected studies for dichotomous variable meta-analysis
Tanzania Cohort 36.11 ± 14.38
Time of Infection
Type of surgery
femoral fractures SSI
No infection group
albumin <3.5 albumin >3.5 albumin <3.5 albumin >3.5
Organ space 7
Organ space 3
First author, Year
Lena Gunningberg, 2008 
M. Hedstrom1, 1998 
George N. Guild MD, 2012 
Lan B.MC Phee, 1998 
Study design Cohort Age (year)
Cohort infection:82 ± 11;
non-infection 81 ± 9
Cohort not mentioned Cohort infection 54 ± 13, primary 53 ± 17
Table 2 Characteristics of selected studies for continuous variable meta-analysis
Type of surgery
No infection group
Orthopaedic surgery Thoracic surgery femoral neck fractures with two Olmed cancellous bone screws
orthopaedic trauma surgery
Fig. 4 Funnel plot for publication bias. The symmetrical panel suggested no publication bias for albumin MD meta-analysis
albumin and a low lymphocyte count increased the
risk of wound complications in ankle amputations
. A shoulder arthroplasty study referred to a
general prevalence of malnutrition of 7.6 %, and TSA
patients with a preoperative albumin <3.5 g/dL
tended to experience greater morbidity after surgery
than patients with albumin in the normal reference
We perceived some heterogeneity between the
included studies, especially in the infection rate
comparison. The most dominant manuscript contributing to the
heterogeneity of SSI incidence was Lan B. MC Phee et
al. (1998) , after removing this study from
consideration, the heterogeneity became relatively lower (P =
0.18, I2 = 33 %), as determined by a fixed effects model.
Other possible reasons for heterogeneity were that low
albumin was not the only susceptibility factor for SSI,
obesity, age, low total lymphocyte counts, transferrin
and combinations of these factors could all exerted an
impact on SSI , and there were inconsistent
factors among these studies. The sources of
heterogeneity of pooled MD with regard albumin consisted
mainly of the study by M. Hedström1 (1998), which
provided only medians and interquartile ranges of
albumin. After removing this study, the adjusted
heterogeneity was P = 0.75 (I2 = 0 %), as determined by a
fixed referenced model, indicating very acceptable,
Despite the existing heterogeneity, we still found
positive findings that low albumin was related to SSI and
that albumin <3.5 g/dL could be seen as a risk factor for
SSI in orthopaedics.
In our study, the incidence of SSI in orthopaedics of
SSI comparison was 1.09 % (1213/111,478), the rate of
Fig. 5 Funnel plot for publication bias. The symmetrical panel suggested no publication bias for infection rate meta-analysis
superficial SSI was 6.8 % (4371/64,466), the rate of deep
SSI was 0.20 % (125/61,585) and the rate of organ space
SSI was 0.18 % (110/61,330). Incidence of SSI in low
albumin group in each comparison were higher than the
normal albumin group [4, 5, 7, 9, 11, 12, 15–20].
Approximately 40 % of admitted adult patients were
undernourished, in particular, 4.3 % of
communitydwelling adults were in the same situation [21–23].
Ozkalkanli MY also referred to similar rates of
malnutrition and morbidity in orthopaedic surgery of 3.5 and
4.1 %, respectively . Normally, SSI rates are generally
higher in orthopaedics patients than in other types of
surgeries due to various and serious types of trauma
[16, 24]. A rate of SSI of 7.1 % in spine surgery was
reported by Satoru Demura . In spinal metastases,
the rate of SSI has been reported to range from 6.8
to 20 % [18, 19, 26, 27]. Huang demonstrated higher
acute infection rate in THA patients with low
albumin . A systematic review indicated the incidence
of SSI after total hip arthroplasty ranged from 0.2 %
before discharge to 1.1 % for the period up to and
including 5 years postoperation . While in TKA,
the rates of superficial and prosthetic joint infections
were 2.9 and 0.80 %, respectively . These findings
identified our consequences, also indicating the
important and severe current situation in orthopaedics.
Given that malnutrition contributes to inadequate and
incomplete wound healing, it could also lead to more
devastating outcomes; parameters such as serum
albumin and TLC are easily obtained, stable, inexpensive
and established biochemical markers of nutritional
status [31–33]. Therefore, we recommend thorough
nutritional consultation for each hospitalized patient
There were several limitations to our meta-analysis.
Firstly, heterogeneity existed due to small search range,
relatively low-quality and fixed literature types. Secondly,
information on potential confounding factors such as age,
general health and co-morbidities were lacking for
different aspects of analysis in included articles. Thirdly, SSI got
many combined influencing factors even though low
albumin can dramatically affects it [1, 3, 10, 13, 20, 21],
interference between those factors was not identified.
Our meta-analysis found that albumin <3.5 g/dL had an
almost 2.5 fold increased risk of SSI in orthopaedics.
Prospective, multicentre studies should be performed to
verify this conclusion.
CI: Confidence interval; MD: Mean difference; NOS: Newcastle Ottawa
Scale; RR: Relative risk; SD: Standard deviation; SSI: Surgical site infection;
THA: Total hip arthroplasty; TKA: Total knee arthroplasty; TSA: Total
The authors wish to thank Dr. Yong Shen, orthopedics, Yi Cui, head nurse, for
their assistance and cooperation in this study.
YZ and PZ designed the study; PZ, WC did the most search work, and PZ,
WC, HZL analyzed data and performed statistical analysis; PZ and WC drafted
the manuscript; CF, YSL, TZ, PH gave specific suggestions about the writing,
JLG, TY, JYS, LL made substantial assisted contributions to this study; YZ had
primary responsibility for final content. All authors read and approved the
The authors declare that they have no competing interests.
Consent for publication
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