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Int J Cancer Manag. In Press(In Press):e88551.
Published online 2019 December 7.
doi: 10.5812/ijcm.88551.
Research Article
Evaluation of the Effect of Perioperative Blood Sugar Level on Surgical
Site Infections in Patients Undergoing Total Mastectomy
Dawood Mafinezhad 1, Reza Taheri1, Seyed Esmaeil Nezhad Hoseini 1and Mohammadreza Motie
1, 2, *
1Surgical Oncology Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
2Surgery Department, Surgery Imam Reza Hospital, Mashhad, Iran
*Corresponding author: Surgery Department, Surgery Imam Reza Hospital, Mashhad, Iran. Tel: +98-5138022677, Fax: +98-5138525255, Email: motiem@mums.ac.ir
Received 2019 January 01; Revised 2019 August 22; Accepted 2019 August 31.
Abstract
Background: Stress hyperglycemia during surgeries has been reported to increase the possibility of surgical site infections (SSIs)
and worsen the patient’s prognosis.
Objectives: The aim of the present study was to evaluate the correlation between perioperative blood sugar level and SSIs in patients
undergoing mastectomy.
Methods: In this prospective case-control study, 158 female patients undergoing mastectomy were included with diabetes as an
exclusion criterion. Blood glucose levels were measured in 5 phases for each patient.
Results: Among 158 studied patients, 8 (5.5%) developed SSIs. Four patients (2.74%) in the control group and 4 patients (50%) in
the case group had hyperglycemia in at least one of the stages. Logistic regression analysis demonstrated associations between SSI
development and any blood glucose value of more than 150 mg/dL. It seems that age, medical history, current smoking, tumor char-
acteristics, previous chemoradiotherapy, surgical duration, administration of prophylactic antibiotics, and other surgical factors
have not been significantly correlated with SSI.
Conclusions: As hyperglycemia is an easily controllable factor, the control of blood sugar levels during the perioperative period is
recommended in patients undergoing breast surgeries to decrease SSI rates.
Keywords: Blood Sugar Level, Mastectomy, Surgical Site Infection
1. Background
Surgical site infections (SSIs) are among the common
causes of postoperative morbidity, which also increase
mortality, hospital re-admission, and hospitalization dura-
tion in patients undergoing surgery (1,2). Hyperglycemia
during hospitalization, especially in traumas and surg-
eries, occurs approximately in one-third of patients. Acute
transient (stress) hyperglycemia during surgeries has been
reported to increase the possibility of SSIs and worsen the
patient prognosis as well (1,3-5). Previous studies have re-
ported that regardless of the history of diabetes, higher
blood glucose values are associated with higher risks of
SSIs and glycemic control has been shown to reduce the
risk of SSIs in various types of surgeries (6,7). However,
glycemic control is not well established in postoperative
care strategies (8). Although mastectomies, which are the
most common oncologic surgeries, are considered clean
surgeries and low rates of SSIs are expected in these pro-
cedures, SSI rates for mastectomies are quite significant.
The growing incidence of resistant bacterial strains in
hospital-acquired infections is also a matter of concern in
this regard (9-11).
2. Objectives
The aim of the present study was to evaluate the associ-
ation between perioperative blood glucose levels and SSIs
in patients undergoing mastectomy.
3. Methods
3.1. Study Population
In this prospective case-control study, 158 female pa-
tients with the diagnosis of breast cancer, who were candi-
dates for a total mastectomy, were included. This investiga-
tion was conducted at the general surgery department of
Imam Reza Hospital of Mashhad, Mashhad, Iran, between
March 2013 and March 2016. The study protocol was ap-
proved by the Ethics Committee of Mashhad University of
Copyright © 2019, Author(s). This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International License
(http://creativecommons.org/licenses/by-nc/4.0/) which permits copy and redistribute the material just in noncommercial usages, provided the original work is properly
cited.
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Mafinezhad D et al.
Medical Sciences (code number: 900850). All participants
gave full informed written consent prior to inclusion in
the study. Patients with a previously-diagnosed diabetes
mellitus, a history of antibiotic use within the previous 30
days, under treatment with corticosteroids, and those who
were reluctant to participate in the study, were excluded.
The demographic data, including age and a full history of
medical conditions consisting of hypertension, hyperlipi-
demia, ischemic heart disease (IHD), previous chemother-
apy or radiotherapy, previous breast surgery, other phar-
macologic cancer therapies (steroids, etc.), current smok-
ing, alcohol use, and American Society of Anesthesiolo-
gists (ASA) score, were provided for each patient. Patients
with SSIs were considered as cases and patients, who were
infection-free by the 30th postoperative day, were consid-
ered as controls.
3.2. Patient Management
Blood glucose levels were measured in 5 phases for
each patient. (1) before entering the operating room; (2)
at the time of anesthesia induction; (3) during the surgery;
(4) in the recovery room; (5) 24 hours postoperatively by
capillary glucometer. The patients would be categorized
in the hyperglycemic group if they had any glucose value
of more than 150 mg/dL. Otherwise, the patients were in-
cluded in the normo-glycemic group. The patients were
randomly selected by each surgical team to be operated on.
All patients were managed by the standard protocol and
the routine surgical procedure. Antibiotic prophylaxis was
used. At the end of the surgery, the wound was closed and
a drain was placed at the anterior chest wall and axilla as
needed. Wound care strategies were done after surgery. Af-
ter discharge, patients were educated to wash the wound
every 24 hours with soap and water and covered it by sterile
gauze pads. They were also trained to measure the amount
of the drain. Intraoperative variables, including duration
of surgery, type of mastectomy (radical vs. modified rad-
ical mastectomy), prophylactic and postoperative antibi-
otics, estimated blood loss, drains used, and lymph node
dissection were recorded as well.
Postoperatively, the patients were visited daily in the
hospital ward and, then, followed up by phone calls or
direct observation in the outpatient clinic for at least 30
days. They were followed with the cancer staging re-
ports, postoperative antibiotics, and other wound compli-
cations, such as flap necrosis, dehiscence, hematoma, and
seroma formation. An SSI would be diagnosed clinically if
any sign of SSI occurred, including pain or tenderness, lo-
calized swelling, redness or heat, purulent drainage from
the superficial or deep incision, and fever more than 38ºC.
3.3. Statistical Analysis
All statistical analyses were performed, using SPSS 19
statistical software. Continuous variables were reported
as mean ±SD. Categorical variables were reported as ab-
solute numbers and percentages. Analysis of the data
distribution was assessed by the Kolmogorov-Smirnov
test. Normally-distributed continuous variables were com-
pared, using the unpaired t-test. The Mann-Whitney U test
was used for those variables that were not normally dis-
tributed. Categorical variables were analyzed, using either
the chi-square test or Fisher’s exact test. Logistic regres-
sion analysis was conducted to obtain adjusted estimates
of the odds ratio and to identify the association between
blood glucose level and SSIs, using SPSS. Two-sided P values
of less than 0.05 were considered to indicate statistical sig-
nificance for all statistical tests.
4. Results
Among 158 studied patients, 8 (5.5%) developed SSIs.
The mean ±SD age of the patients was 48.2 ±11.9 years,
53.75 ±11.61 years for cases, and 48.12 ±11.75 for the con-
trol group; 5 patients were current smokers and 8 were ad-
dicted to some kinds of opiate. Ninety patients (56.96%)
denied the history of medical conditions, 36 had a history
of hypertension, 17 had dyslipidemia, and 13 had a positive
history of IHD. The detailed characteristics of patients are
presented in Table 1.
Among the patients, 5.1% (8 patients) had a history of
breast cancer in the contralateral breast, 152 (96.2%) were
presented as primary tumors, and 6 (3.8%) had the recur-
rence of a primary tumor. A total of 39 of 158 patients
(25.3%) had preoperative chemoradiotherapy. According to
the ASA physical status classification system, 142 of the pa-
tients (89.9%) were categorized as ASA I and 16 (10.1%) as ASA
II (Table 2).
Prophylactic antibiotics were prescribed for 12 patients
(7.6%). All patients took cefazolin and cephalexin postop-
eratively; 55 of the patients (34.8%) underwent total mas-
tectomy and 103 (65.2%) had modified radical mastectomy.
The mean ±SD duration of surgery was 2.92 ±0.65 hours
overall, 3.25 ±0.65 hours in the case group, and 2.89 ±
0.64 in the control group. In 55 of the patients (34.8%),
axillary lymph node dissection (ALND) accompanied mas-
tectomy. No patient underwent sentinel lymph node dis-
section. Pectoral surgical drains were inserted in 27 pa-
tients (17.1%) and combined pectoral and axillary drains
were placed in 131 patients (82.9%) (Table 3).
A total of 36 of the patients (22.8%) had at least one
blood glucose value over 150 mg/dL and were considered as
hyperglycemic; the other 122 patients (77.2%) were included
in the normo-glycemic group. Four patients (2.74%) in the
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Mafinezhad D et al.
Table1. Detailed Characteristics of Patients in the Case and Control Groupsa
Values Control Group CaseGroup P Value (Fisher’s Exact Test)
Smoking 5 (3.16) 5 0 1.000
Addiction 8 (5.06) 6 2 0.057
No previous medical disease 93 (58.9) 87 3 0.278
Hypertension 36 (22.78) 34 2 1.000
Hyperlipidemia 17 (10.76) 14 3 0.054
Ischemic heart disease 13 (8.23) 11 2 0.138
aValues are expressed as No. (%).
Table2. Presentation and ASA Classification in the Control and Case Groupsa
Values ControlGroup Case Group P Value (Fisher’s Exact Test)
Presentation 0.138
Primary tumor 152 (96.2) 145 7
Recurrence 6 (3.8) 5 1
Previous chemoradiotherapy 39 (25.3) 35 4 0.191
ASA classification 0.568
ASA I 142 (89.9) 135 7
ASA II 16 (10.1) 15 1
aValues are expressed as No. (%).
Table3. Type of Surgery and Surgical Drains in the Control and Case Groupsa
Values Control Group Case Group P Value (Fisher’s Exact Test)
Typeof surgery 0.051
Total mastectomy 55(34.8) 55 0
MRM 103 (65.2) 95 8
ALND 55 (34.8) 55 0 0.051
Surgical drains 0.352
Pectoral 27 (17.1) 27 0
Pectoral + axillary 131 (82.9) 119 8
aValues are expressed as No. (%).
control group and 4 (50%) in the case group had hyper-
glycemia during at least one stage. The mean glucose levels
in every 5 phases of measurement in the case and control
groups are summarized in Table 4.
Table4. Blood Glucose in the Control and Case Groupsa
Total Control Group Case Group
BG1 107.91 ±35.33 106.12±32.72 150.5 ±58.45
BG2 117.86 ±43.68 115.5 ±36.54 179.12 ±99.00
BG3 120.75 ±45.54 117.93 ±38.08 184.88 ±105.77
BG4 120.97 ±34.75 119.27 ±32.45 163.00 ±53.67
BG5 114.49 ±39.09 111.94 ±34.76 145.88 ±60.35
aValues are expressed as mean ±SD.
A comparison of the mean age of cases and con-
trols showed no statistically significant difference between
these groups (independent sample t-test: P = 0.220). There
was no significant difference between the case and control
groups considering the history of smoking, addiction, his-
tory of hypertension, IHD, and dyslipidemia.
Variables associated with tumor characteristics, in-
cluding primary tumor versus the recurrence of a primary
tumor, ASA score, and previous chemoradiotherapy were
similar in the case and groups. There was no significant dif-
ference between groups regarding the history of cancer in
the contralateral breast. Factors regarding surgical proce-
dure, which included the mean duration of surgery (Mann-
Whitney U test; P = 0.183), prescription of prophylactic an-
tibiotics (Fisher’s exact test: P = 0.647), type of surgery,
ALND, and type of the used surgical drains, did not have sig-
nificant association with the development of SSI.
Logistic regression analysis demonstrated associa-
tions between SSI development and any blood glucose
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Mafinezhad D et al.
value of more than 150 mg/dL (Table 5).
Table5. AssociationsBetween SSI Development and any Blood Glucose Value of More
Than 150 mg/dL
Odd Ratio 95% Confidence Interval P Value
BG1 6.32 1.35 - 29.5 0.019
BG2 5.81 1.35 - 25 0.018
BG3 3.68 0.82 - 16.6 0.089
BG4 5.81 1.35 - 25 0.018
BG5 2.60 0.49 - 13.9 0.26
5. Discussion
Several studies have demonstrated a significant associ-
ation between perioperative blood glucose level and SSI de-
velopment in different eras, including cardiovascular and
general surgery, ICU, and trauma patients, regardless of
the history of diabetes (8,12-16). These studies are limited
among patients undergoing mastectomy. Vilar-Compte
et al. (1) in 2008 indicated that in patients undergoing
mastectomy, elevated blood glucose values during surgery
and/or the immediate postoperative period correlate with
the increased risk of SSI. They showed that any blood glu-
cose of more than 150 mg/dL increases the risk of devel-
oping postoperative SSIs (1). In the present study, logistic
regression analysis demonstrated an association between
SSI development and any blood glucose value of more than
150 mg/dL as well. In Ruiz-Tovar’s study, a cut-off point of
128 mg/dL was established with patients, whose glucose
exceeded this having a 4.7-fold higher risk of SSI (6). The
analysis of the quantitative correlation between the blood
glucose levels and infection rate has also been established
in some studies (1,8,14). This issue was not concerned in
our study. In the current study, age, medical history, cur-
rent smoking, tumor characteristics, previous chemora-
diotherapy, duration of surgery, and other surgical factors,
as well as prophylactic antibiotic did not seem to have a
significant association with the SSI post-surgically. Vilar-
Compte et al. reported different results; age more than 50
and preoperative chemoradiotherapy were risk factors for
infection occurrence (1,11). They explained the role of ad-
vanced age with the progressive incidence of medical con-
ditions, especially diabetes and hypertension, in older pa-
tients. Advanced age, chemoradiotherapy, and duration of
surgery have been mentioned as risk factors for infection
in other studies (15,17). The effect of solo radiotherapy and
chemotherapy was not explored in our analysis. Davis re-
ported ASA score of 3 or higher, surgical time of 2 hours or
longer, and current smoking status as significant risk fac-
tors (18). In our study, we found no association between
ASA score and SSI development, although no patient had
ASA score of 3 or higher. As shown in previous articles (18),
ALND was not a risk factor for SSI occurrence.
The rate of SSIs in this study was 5.8%, which is ratio-
nal considering the clean base of this kind of surgery (1).
Some studies have reported a higher incidence of postop-
erative wound infections (1,11), which could not be com-
pared due to the lack of firm criteria for diagnosis or could
show a high prevalence of hospital-acquired infections in
their settings.
In the present study, hyperglycemia was associated
with an increased rate of SSIs in each of the 5 levels of mea-
surement. The results of the timing of hyperglycemia in
the literature are inconstant (8,14,19). It seems that hyper-
glycemia during the perioperative period is a consequence
of the stress-induced increase in counter-regulatory hor-
mones, which diminishes immune response as in patients
with diabetes (1). Regarding the role of diabetes as a risk
factor of postoperative infection, 4 types of comparison
have been made in the literature:
1) In some studies, the association between hyper-
glycemia and SSI has been investigated in patients with
diabetes (14,15). Actually, in these studies, the effect of
glycemic control in patients with diabetes was concerned;
the results showed an increased risk of infection in pa-
tients with diabetes, experiencing hyperglycemia in the
perioperative period (20).
2) In some other studies, the comparison has been
made between patients with newly-diagnosed hyper-
glycemia and hyperglycemia in patients with a known
history of diabetes, which have shown a more adverse
outcome in the newly-diagnosed patients (8,21).
3) Diabetes had also been investigated as an indepen-
dent risk factor post-surgically in patients with and with-
out SSIs (1).
4) In our study, diabetes was an exclusion criterion in
order to investigate the net effect of stress-induced hyper-
glycemia. No advantage of perioperative antibiotic pro-
phylaxis has (PAP) been reported in mastectomies (22).
Vilar-Compte et al. (1) found no difference in SSI rates or
other important outcomes associated with PAP in patients
undergoing mastectomy and concluded that not prescrib-
ing PAP is permitted in this group of patients. Similarly,
in our study, the prescription of prophylactic antibiotics
(Fisher’s exact test: P = 0.647) did not have a significant as-
sociation with the development of SSIs. Other wound com-
plications, including necrosis, hematoma, and seroma for-
mation in association with perioperative hyperglycemia
have been concerned in other studies (11), but we did not
discuss this matter. This study was limited by the low num-
ber of participants, which necessitates larger studies in
this matter in the future. Obesity was investigated by most
of the similar articles, which were not probed in our anal-
4Int J Cancer Manag. In Press(In Press):e88551.
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Mafinezhad D et al.
ysis because of too missing data. Another missing aspect
of our study is the microbiology of SSIs, which is recom-
mended to be approached in the future.
5.1. Conclusions
Conclusively, our analysis demonstrated a significant
association between perioperative blood glucose level and
SSI development in all 5 steps of measurement. As hyper-
glycemia is an easily modifiable factor, glycemic control
during the perioperative period is recommended in pa-
tients undergoing breast surgeries to lower SSI rates.
Footnotes
Authors’ Contribution: Project implementation: Da-
wood Mafinezhad, Reza Taheri, and Seyed Esmaeil Nezhad
Hoseini. Idea and project manager; Mohammadreza
Motie.
Conflict of Interests: The authors declare no conflict of
interest.
Funding/Support: This study was funded by Vice-
Chancellor of Research of Mashhad University of Med-
ical Sciences as a grant attributed to a general surgery
graduation thesis of the third author (code: 900850).
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