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Obesity as a Risk Factor for Nosocomial Infections

in Trauma Patients
Pablo E Serrano, MD, MPH, MSBS, Sadik A Khuder, PhD, MPH, John J Fath, MD, MPH, FACS, FCCM
Obesity, like multiple trauma, is associated with an inflammatory condition that leads to an
immunodeficient state. Obese trauma patients are thus thought to be at higher risk of infection
compared to patients of normal body mass. Despite this risk, studies to date have not defined
obesity as an independent risk factor for infection in trauma patients.
STUDY DESIGN: Retrospective data were collected on 1,024 patients admitted to a Level I trauma center
during a 12-month period. Obesity was defined as a body mass index (BMI) 30 kg/m2.
Outcomes analyzed included urinary tract infection, pneumonia, septicemia, and wound
infection and Clostridium difficile infection. Multiple logistic regression was used to evaluate the contribution of each BMI category to infection while adjusting for comorbidities,
age, gender, Injury Severity Score (ISS), hospital and ICU lengths of stay, and number of
ventilator days.
RESULTS:
Obesity prevalence was 30.6%. Obese patients had longer hospital length of stay, with
similar ISS, number of ventilator days, and ICU length of stay. The overall rate of infections
was 8.7%. Variables independently associated with increased risk of infections were BMI,
age, ISS, ICU length of stay, hospital length of stay, and multiple comorbidities. The risks
of infections according to each BMI category were: BMI 25 kg/m2, 4.2%, BMI 25 to 29
kg/m2, 9.5%, odds ratio (OR) 2.65 (CI 0.72 to 5.72); BMI 30 to 39 kg/m2, 12%, OR 4.69
(CI 2.18 to 10.08); and BMI 40 kg/m2, 20.3%, OR 5.91 (CI 2.18 to 16.01). Pulmonary
and wound infections were significantly more frequent in obese patients.
CONCLUSIONS: In this retrospective study, obesity was shown to be an independent risk factor for nosocomial
infection after trauma. Prospective studies would clarify the reasons associated with this increased risk of infections in obese trauma patients. (J Am Coll Surg 2010;211:6167. 2010
by the American College of Surgeons)
BACKGROUND:

During the past 20 years there has been a dramatic increase


in the rate of obesity in the United States. In 2004, only one
state had a rate of obesity less than 20%. The majority
of states had an obesity rate of at least 25%, with 6 of those
states rates reaching an alarming 30% or higher.1,2 Obesity
has been shown to increase morbidity and mortality, primarily from cardiovascular disease, cancer, and other metabolic diseases.3-6 Obese patients have a higher risk of community acquired7 and nosocomial infections in the
ICU.8-11 Obesity is also associated with an increased num-

ber of ventilator days, as well as increased ICU and hospital


lengths of stay, factors that further increase the risk of nosocomial infections12-14 and in-hospital mortality.15,16
The etiology of the increased risk of infections in obesity
is not clear. It is thought that obesity is associated with a
state of chronic low grade systemic inflammation because
of the highly expressed cytokines that are found in the
bloodstream of obese people.17,18 The adipocyte is considered to be a cell that secretes large amounts of inflammatory (interleukin [IL]-1, tumor necrosis factor [TNF]-a,
IL6, C-reactive protein, leptin, visfatin)19,20 and antiinflammatory mediators (adiponectin, IL10).21 Inflammation is further increased by the induction of innate
immune toll-like receptors TLR2 and TLR4 by saturated free fatty acids and other metabolic compounds
that are elevated in obese patients, leading to the secretion of inflammatory cytokines.22-24
Multiple trauma leads to a state of immunosuppression
characterized by the release of proinflammatory cytokines
(IL1, IL6, IL8, IL18, TNF-a, C-reactive protein, and oth-

Disclosure Information: Nothing to disclose.


Abstract presented at the American College of Surgeons 95th Annual Clinical
Congress, Surgical Forum, Chicago, IL, October 2009.
Received January 19, 2010; Revised February 21, 2010; Accepted March 3,
2010.
From the Department of Surgery (Serrano) and Department of Medicine
(Khuder), University of Toledo, Toledo, OH and the Oakwood Hospital and
Medical Center, Dearborn, MI (Fath).
Correspondence address: John Fath, MD, MPH; 18101 Oakwood Blvd,
Dearborn, MI 48123.

2010 by the American College of Surgeons


Published by Elsevier Inc.

61

ISSN 1072-7515/10/$36.00
doi:10.1016/j.jamcollsurg.2010.03.002

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Serrano et al

Trauma, Obesity, and Nosocomial Infections

J Am Coll Surg

ers: complement factors, coagulation cascade factors, acute


phase proteins, and neuroendocrine mediators). At the
same time, anti-inflammatory mediators are induced and
highly expressed (IL-4, IL-10, IL-13, transforming growth
factor [TGF]-), resulting in a state of post-traumatic
immunoparalysis, a compensatory anti-inflammatory
response syndrome with an anergic immune response that is
not effective against pathogens and immunizations.17,25-27
Theoretically, these conditions should place obese
trauma patients at an extremely high risk of infection. Despite this potential, studies to date have not defined obesity
as an independent risk factor for infection in the general
trauma population. The purpose of this study was to review
the risk factors for infection in trauma patients and to
evaluate the importance of obesity as an independent risk
factor for nosocomial infections in this population.

not possible because a large proportion of trauma patients


were lost to follow-up.
Variables analyzed included demographics, comorbidities of diabetes mellitus (DM), hypertension, coronary
artery disease (CAD), congestive heart failure (CHF),
chronic obstructive pulmonary disease (COPD), asthma,
and history of stroke. Characteristics of severity of injury
and use of resources that were analyzed were Injury Severity
Score (ISS) at admission, hospital length of stay, ICU
length of stay, and number of ventilator days. ICU length
of stay and number of ventilator days are reported for the
subsets of patients using those resources. Infections were
identified according to the Centers for Disease Control
definitions for nosocomial infections: urinary tract infections (UTI), pneumonia, surgical site infections (SSI) or
wound infections, primary blood stream infections, and
Clostridium difficile infections.28
BMI was calculated for each patient. Patients were divided into 4 groups: normal weight, BMI 24.9 kg/m2;
overweight, BMI 25 to 29.9 kg/m2; obese, BMI 30 to 39.9
kg/m2; and extremely obese, BMI 40 kg/m2. The software used for statistical analysis was the Statistical Package
for the Social Sciences (SPSS for Windows, SPSS Inc, version 9.0). In the preliminary analyses, univariate statistical
methods were used to determine which risk factors were
significant for nosocomial infections. Data were analyzed
using the chi-squared test. Statistical association was assessed using the odds ratio (OR). The OR of nosocomial
infection was estimated from raw data and multiple logistic
regression analysis, adjusting for potential confounders.

METHODS
Data on body mass index in kg/m2 body surface area (BMI)
were prospectively collected and retrospectively reviewed
using the trauma service registry at the University of Toledo
Medical Center. The Medical Center is an American College of Surgeons verified Level I Trauma Center. From
January 1, 2008 to December 31, 2008, 1,294 patients
were included in the study. This period was chosen in order
to obtain the minimum number of obese patients (n
275) required to obtain an 80% power in order to detect a
10% difference in the infection rate between the subjects
(obese patients) and the controls (nonobese individuals).
Patients less than 18 years of age and pregnant or postpartum patients were excluded because the BMI in these
populations is not reflective of their degree of obesity. Patients admitted to the hospital for short observation and
transferred or discharged in less than 24 hours were also
excluded from the study because the actual origin of the
infection could not be assessed. This study focused on the
nosocomial infection rates. Postdischarge evaluation was

RESULTS
Complete data were available for 1,024 patients. There
were 382 (37.3%) normal weight patients, 328 (32.01%)
overweight, 250 (24.44%) obese, and 64 (16%) morbidly
obese patients. There were 392 (38.3%) women and 632
(61.7%) men. There was no difference in the obesity rate
between men and women. Average age was 48.8 years, with
a range from 18 to 102 years. BMI ranged from 14.8 to
66.4 kg/m2, with an average of 27.97 kg/m2. The overall
infection rate for the population was 8.78%. A total of 104
nosocomial infections were identified in 90 patients, distributed as 55 pulmonary infections, 14 wound infections
or SSIs, 27 UTIs, 5 bloodstream infections, and 3 cases of
Clostridium difficile colitis.
Multivariate analyses showed that obese and morbidly
obese patients had a higher rate of nosocomial infections
compared with normal weight patients. Significant differences were found in pulmonary and wound infections (p
0.01) (Figs. 1, 2, and 3).
Obese patients had higher rate of multiple comorbidi-

Abbreviations and Acronyms

BMI
CAD
CHF
DM
ICU
IL
ISS
OR
SSI
TNF
UTI

body mass index


coronary artery disease
congestive heart failure
diabetes mellitus
intensive care unit
interleukin
Injury Severity Score
odds ratio
surgical site infection
tumor necrosis factor
urinary tract infection

Vol. 211, No. 1, July 2010

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Trauma, Obesity, and Nosocomial Infections

63

Figure 1. Distribution of nosocomial infections based on body mass


index (BMI).

Figure 2. Distribution of pulmonary infections based on body mass


index (BMI).

ties. Comorbidities that were statistically significantly


higher were hypertension, asthma, CHF, DM, and history
of stroke. Those not associated with obesity were COPD,
CAD, and chronic renal failure (Table 1).
Multivariate logistic regression analyses showed that the
independent variables that proved to be significant risk
factors associated with infection were obesity, age, ISS,
ICU length of stay, hospital length of stay, and multiple
comorbidities (a variable created by combining the incidences of DM, CHF, COPD, and CAD). Even after controlling for age and comorbidities, obesity was still found to
be a risk factor for infection. Factors not associated with
increased risk of infections were gender, number of ventilator days, and each of the comorbidities listed as separate:
DM, COPD, hypertension, CAD, chronic renal failure,
history of stroke, and asthma (Table 2).
Obesity and multiple comorbidities combined were
both independent statistically significant factors associated

with increased risk of infections after trauma. For obese and


morbidly obese patients, there was a significant increase in
the percentage of nosocomial infections with either the
presence or absence of multiple comorbidities.
Adjusted odds ratios for the risk of infection after trauma
according to each BMI category showed that overweight
patients did not illustrate a statistically significant difference compared with controls (normal weight individuals).
Significant differences were found in obese individuals,
who had a 4.7-fold higher risk of infection than controls
and morbidly obese individuals, who had an almost 6-fold
higher risk of infection compared with normal weight patients (Fig. 4).
Table 1. Distribution of Risk Factors and Comorbidities
Based on Body Mass Index
Risk factors and
comorbidities

n
COPD, %
Coronary disease, %
Chronic renal failure, %
Hypertension, %*
Asthma, %*
Heart failure, %*
Diabetes, %*
History of stroke, %*
Injury Severity Score
ICU length of stay, d
Ventilator, d
Hospital length of
stay, d*
Figure 3. Percentage of wound infections based on body mass
index (BMI).

Body mass index, kg/m2


<25
2529
3039
>40
kg/m2
kg/m2
kg/m2
kg/m2

382
6.8
14.1
2.1
23.3
6.3
3.9
6.5
3.9
6.35
4.85
4.1

328
5.8
12.5
3
29.9
5.2
5.2
11
5.2
7.52
5.38
4.26

250
3.2
15.2
1.6
38.8
7.6
3.6
17.2
2.8
6.66
5.67
6.31

64
9.4
21.9
3.1
48.4
18.8
14.1
29.7
10.9
6.70
5.40
3.20

3.71

3.75

3.99

5.75

ICU length of stay and ventilator days reported only for patients requiring
those services.
*p 0.05.

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J Am Coll Surg

Table 2. Multivariate Analysis of Predictive Parameters of


Nosocomial Infections
Predictors of infection

Odds ratio

Obesity*
Age*
Injury Severity Score*
ICU length of stay*
Hospital length of stay*
Gender
Ventilator days
Diabetes
Congestive heart failure
Coronary artery disease
COPD
Hypertension
Chronic renal failure
History of stroke
Comorbidities
combined*

4.69
1.02
1.12
1.15
1.19
1.25
0.99
1.39
3.62
2.32
3.25
2.12
2.82
3.11

2.1810.1
1.011.03
1.091.16
1.041.28
1.131.26
0.722.19
0.841.17
0.712.59
0.657.43
0.343.93
0.546.45
0.333.35
0.818.09
0.326.71

CI

p Value

0.03
0.0072
0.01
0.008
0.01
0.43
0.93
0.36
0.1
0.07
0.45
0.4
0.62
0.48

1.26

1.051.51

0.01

*p 0.05.

DISCUSSION
Obesity worldwide has reached epidemic proportions. In
the United States, which has one of the highest rates of
obesity among developed countries, the prevalence of obesity has increased among all ages, gender, racial, and ethnic
groups.1 From 1960 to 2004, the prevalence of overweight
individuals increased from 44.8% to 66% in US adults
older than 20 years of age. The prevalence of obesity during
this same time period doubled from 13.3% to 32.1%.2
Nosocomial infections are complications that severely
affect outcomes and that increase costs to all hospitalized
patients. They increase the hospital length of stay and place
a burden on hospital resources.29 Risk factors that increase
the likelihood of nosocomial infections should be identified and prevented (eg, central lines, urinary catheters, ventilator days).
Studies performed on severely injured trauma patients
(ISS 16) have suggested that obesity is associated with an
increased risk of mortality and morbidity (including infections) in the ICU.8,30 Despite these findings, obesity is not
recognized as a risk factor for infection in the general
trauma population, perhaps because until now, there has
been no study to evaluate this problem.
Newell and colleagues8 established a relationship between obesity and increased risk of UTIs and pneumonia.
Similarly, Dossett and associates9 found an association with
catheter and bloodstream infections in the critically ill
obese trauma patient. In the surgical patient, obesity is
associated with an increased risk of SSI.31-33 In this study,
obesity was associated with an overall increased risk of nosocomial infections. Infections that had a statistically signif-

Figure 4. Adjusted risk (odds ratio, OR) of infection according to


body mass index (BMI).

icant association with obesity were pneumonia and wound


infections. The other 3 types of infections analyzed did not
reach statistical significance. This may be due to the low
number of bloodstream infections and cases of Clostridium
difficile colitis found in the study population. UTIs were
not shown to increase in obese patients, although they were
statistically significantly increased in the morbidly obese
group (6.2%) as compared with normal weight (1.8%),
overweight (3.4%), and obese (2.0%) groups.
Reasons for the increased risk of infections in obese patients are not known, but are considered multifactorial.
Included are factors such as prolonged immobility after
trauma,34 leading to prolonged use of urinary catheters and
difficult intravenous access requiring the use of central lines
more often and for prolonged periods of time.35 Obese
patients are known to require an increased number of ventilator days due to their respiratory and intra-abdominal
pathophysiology,36-38 a factor that increases the risk of
pneumonia. Mechanical factors could contribute to an increase in SSI rates in obese patients after surgery. These
would include an increase in local tissue trauma due to a
larger amount of adipose tissue and increased retraction,
prolonged operative times, and tissue hypoxemia.39 Metabolic factors such as hyperglycemia related to the insulin
resistance characteristic of the obese patient may also depress resistance to infection.10,40-42 Different injury patterns
in the obese patient could contribute to an increased risk of
infections.43,44 Our study did not look at each Abbreviated
Injury Score (AIS), although there was no difference
among each BMI category and the ISS.
In this study, the risk of infections after trauma was
increased 4.7-fold in obese patients and almost 6-fold in
morbidly obese individuals compared with controls. The
chronic inflammatory state seen in obese individuals is associated with the metabolic syndrome: insulin resistance,
hypertension, and dyslipidemia.45 The level of inflamma-

Vol. 211, No. 1, July 2010

tion correlates with the degree of obesity. Adipocytes secrete large amounts of proinflammatory (leptin, IL-6,
C-reactive protein, TNF-, IL-1)46 and anti-inflammatory
mediators (adiponectin),47 which eventually lead to an altered immune response with impaired numbers of natural
killer (NK), B and T cells, and neutrophils.48,49 This loss of
balance in the immune system and the impaired inflammatory immune response may also play a role in the increased
risk of infections in obese patients.47
The chronic inflammation found in states of obesity is
considered to be the basis for the multiple associated comorbidities of the obese patient, including DM, hypertension, CAD, and asthma.48-50 As previously indicated, this
study found that obese patients had higher rates of multiple
comorbidities.4,51 Individual comorbidities did not show
an increased risk of infections; however, when combined as
a single factor, there was a statistically significant increased
risk of nosocomial infections. Previous reports have not
shown individual comorbidities to be associated with an
increased risk of nosocomial infections. Hyperglycemia,
the presence of urinary or central line catheters, ICU and
hospital length of stay, and number of ventilator days have
been linked to nosocomial infections.52,53 The minimum
number of comorbidities associated with an increased risk
of infection was 4, particularly DM, CHF, COPD, and
CAD. Other comorbidities included in the model that
were not statistically significant were: asthma, chronic renal
failure, history of stroke, and hypertension.
There was no difference in the number of ventilator days
or the ICU length of stay among the 4 BMI categories.
Although when considering only 2 groups, obese and
nonobese individuals, there was a statistically significant
increase in the number of ventilator days and ICU length of
stay, consistent with the current literature on obesity and
critical care.12
In our series, obesity was associated with an increased
risk of infections after trauma, even after adjusting for
known risk factors of infection, suggesting that the chronic
inflammation found in obese trauma patients may have
clinical consequences. Because obesity is a factor that cannot be modified in trauma patients, research should focus
on the etiology of the association between obesity and
infection.
Limitations of the study are mostly related to the retrospective review of data, which limits the variables that can
be included in the model. For example, we were unable to
assess the effectiveness of glycemic control efforts because
that information is not included in the Trauma Registry.
Factors not included that may have had an impact on the
results include glycemic level, Abbreviated Injury Score,
degree of mobility, and psychological factors after trauma.

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Trauma, Obesity, and Nosocomial Infections

65

In conclusion, the analyses of this study suggest obesity


as a major risk factor for nosocomial infections in the general trauma population admitted to the hospital. This finding adds valuable data to already existing research concerning the impact of obesity on the incidence of infections.
Multiple previous studies have found an association between obesity and the increased risk of postoperative complications, including SSIs, pneumonia, UTIs, and catheter
infections. Studies on obesity and trauma have been performed with critically ill and severely injured patients,
showing similar results.
There has not been any study to date analyzing the outcomes of infections in the general trauma patient population. This study corroborates previous findings that have
suggested obesity as a risk factor for infection in both surgical and nonsurgically treated trauma patients. In the era
of nonoperative trauma, recognition of risk factors for infections is crucial in order to provide the best care possible
for patients in the hospital. Primary prevention has been
and will continue to be the best approach to treating nosocomial infections.
Additional prospective studies with larger populations
and different methodologies are needed in order to identify
the reasons underlying the association of an increased risk
of infections in obese trauma patients. Also needed are
evaluations that focus on the importance and contribution
of factors found in obese patients, such as cytokine overexpression, an impaired immune system, and hyperglycemia
or insulin resistance. In addition, the contributions of mechanical factors must be analyzed: factors that include the
decreased mobility common in obese and morbidly obese
patients, as well as the duration of urinary and central
catheters in this population.
A knowledge of the risk factors of infections improves
the understanding of the pathophysiology of nosocomial
infections and thereby provides innovative ideas on how to
prevent them more efficiently.

Author Contributions

Study conception and design: Khuder, Serrano


Acquisition of data: Fath, Serrano
Analysis and interpretation of data: Serrano, Khuder, Fath
Drafting of manuscript: Serrano, Fath
Critical revision: Fath, Serrano, Khuder

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