Obesity as a Risk Factor for Nosocomial Infections in Trauma Patients

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) ⱖ 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 ⱕ 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 ⱖ 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;211:61–67. © 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.

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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

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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 25–29 30–39 >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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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

2.18–10.1 1.01–1.03 1.09–1.16 1.04–1.28 1.13–1.26 0.72–2.19 0.84–1.17 0.71–2.59 0.65–7.43 0.34–3.93 0.54–6.45 0.33–3.35 0.81–8.09 0.32–6.71

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

1.05–1.51

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-

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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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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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