Obesity and Pulmonary Complications in Critically Injured Adults

Original Research Original Research CRITICAL CARE MEDICINE CRITICAL CARE MEDICINE

Obesity and Pulmonary Complications Obesity and Injured Pulmonary Complications in Critically Adults* in Critically Injured Adults* Lesly A. Dossett, MD, MPH; Daithi Heffernan, MD; Michelle Lightfoot, BS; J. Diaz, MD; Robert G.MD; Sawyer, MD;Lightfoot, BS; BryanA.Collier, MD; Jose Lesly Dossett, MD, MPH; Daithi Heffernan, Michelle and Addison May, MD J. Diaz, MD; Robert G. Sawyer, MD; Bryan Collier,K.MD; Jose and Addison K. May, MD Background: Pulmonary compli~tions following injury significantly contribute to subsequent mortality. Obese patientscomplications have preexisting risk factors pulmonary contribute complications, and are at Background: Pulmonary following injuryforsignificantly to subsequent risk for these complications following elective surgery.for Whether or not obesity contributes to mortality. Obese patients have preexisting risk factors pulmonary complications, and are at pulmonary complications after critical injury is poorly understood. risk for these complications following elective surgery. Whether or not obesity contributes to Methods: A complications secondary analysis a prospective study of critically injured adults requiring at pulmonary afterofcritical injury iscohort poorly understood. least 48 h A ofsecondary intensive care was performed. Patients werestudy classified into theinjured following bodyrequiring mass index Methods: analysis of a prospective cohort of critically adults at 2 groups:::S; 18.5 kglm 2 care (underweight); 18.5 toPatients 24.9 kglm (normal); 25 to the 29.9following kglm2 (overweight); 30.0 least 48 h of intensive was performed. were classified into body mass index 2 2 2 to 39.9 kglm and ~ 40.0 kglm obese). Outcomes included the2 rates of ARDS 30.0 and groups:::S; 18.5(obese); kglm 2 (underweight); 18.5(severely to 24.9 kglm (normal); 25 to 29.9 kglm (overweight); 2the placement of a tracheostomy 2 pneumonia, tube, and in-hospital mortality rate. to 39.9 kglm (obese); and ~ 40.0 kglm (severely obese). Outcomes included the rates of ARDS and Results: A total 1,291 patients were availabletube, for analysis, and 30%mortality of these patients were classified pneumonia, theofplacement of a tracheostomy and in-hospital rate. or1,291 severely obese. Theavailable age-, gender-, and severity-adjusted of ARDS lower as eitherAobese Results: total of patients were for analysis, and 30% of theserate patients werewas classified in severely obese patients (odds ratio, 0.36; 95% confidence interval [CI], 0.13 to 0.99) compared to as either obese or severely obese. The age-, gender-, and severity-adjusted rate of ARDS was lower normal weight patients. The rates of pneumonia (37%), tracheostomy (10%), and in-hospital mortality in severely obese patients (odds ratio, 0.36; 95% confidence interval [CI], 0.13 to 0.99) compared to (11%) did not patients. differ among the of groups. Despite no tracheostomy difference in (10%), pulmonary complications, the normal weight The rates pneumonia (37%), and in-hospital mortality severely obese an ICU of stay that was 4.8 days (95% CI, 1.8 to 7.7complications, days) longer than (11 %) did not group differ had among the length groups. Despite no difference in pulmonary the the normal weight group. severely obese group had an ICU length of stay that was 4.8 days (95% CI, 1.8 to 7.7 days) longer than Conclusion: Obesity does not appear to be an independent risk factor for increased pulmonary the normal weight group. complicationsObesity after critical injury, but severely patients are to for require longerpulmonary ICU stays. Conclusion: does not appear to be anohese independent risklikely factor increased Trial registration: Identifier: 2008; 134:974-980) complications afterClinicaltrials.gov critical injury, but severely NCTOO170560 ohese patients are likely(CHEST to require longer ICU stays. Trial registration: Clinicaltrials.gov Identifier: NCTOO170560 (CHEST 2008; 134:974-980) Key words: ARDS; epidemiology; obesity; pneumonia; trauma

Key words: ARDS; epidemiology; obesity; pneumonia; trauma Abbreviations: AIS = abbreviated injury score; APACHE = acute physiology and mass index; CI = confidence interval; IQR = interquartiJe range; ISS = injury Abbreviations: AIS = abbreviated injury score; APACHE = acute physiology and TRISS = trauma-related injury severity score mass index; CI = confidence interval; IQR = interquartiJe range; ISS = injury TRISS = trauma-related injury severity score

Obesity is a pervasive disease affecting > 30% of Americans of all disease ages and socioeconomic Obesity is a pervasive affecting > 30% of groupS.l.2 Its implications include increased risks of Americans of all ages and socioeconomic cancer, diabetes, dyslipidemia, heart disease, hypergroupS.l.2 Its implications include increased risks of cancer, diabetes, dyslipidemia, heart disease, hyper'From the the Department of Surgery (Drs. Dossett, Heffernan, Collier, Diaz, and May, and Ms. Lightfoot), Division of Trauma 'From the the Department of Surgety (Drs. Dossett, Heffernan, & Surgical Critical Care, Vanderbilt University Medical Center, Collier, Diaz, and May, and Ms. Lightfoot), Division of Trauma Nashville, TN; and the Department of Surgery (Dr. Sawyer), & Surgical Critical Care, Vanderbilt University Medical Center, University of Virginia Health System, Charlottesville, VA. Nashville, TN; and the Department of Surgery (Dr. Sawyer), Portions of these data were presented in poster form at the 2008 University of Virginia Health System, Charlottesville, VA. Society for Critical Care Medicine Congress, Honolulu, HI. Portions of these data were presented in poster form at the 2008 This work was supported by National Institutes of Health grant RO1 Society for Critical Care Medicine Congress, Honolulu, HI. AI49989-0l and Agency for Healthcare Research and Quality grant This work was supported by National Institutes of Health grant RO1 T32 HS 013833. AI49989-0l lffid Agency for Healthcare Research and Quality grant The authors have reported to the ACCP that no Significant T32 HS 013833. conflicts of interest exist with any companies/organizations whose The authors have reported to the ACCP that no Significant products or services may be discussed in this article. conflicts of interest exist with any companies/organizations whose products or services may be discussed in this article. 974

974

chronic health evaluation; BMI = body severity score; LOS = length of stay; chronic health evaluation; BMI = body severity score; LOS = length of stay;

tension, insulin resistance, and death." While the 3 While conassociation between obesity and and these tension, insulin resistance, death. chronic the there is still considerable debate ditions is clear, association between obesity and these chronic conregarding the role of obesity outcomes debate in the is clear, there is still on considerable ditions critical care setting and after trauma. A number of regarding the role of obesity on outcomes in the documented worse outcomes in obese authors care have setting critical and after trauma. A number of after trauma;5-8 patients in the documented critical care settingi authors have worse and outcomes in obese patients in the critical care settingi and after trauma;5-8 Manuscript received January 10, 2008; revision accepted June 14, 2008. Manuscript received January 10, 2008; revision accepted June 14, Reproduction of this article is prohibited without written permission 2008. from the American College of Chest Physicians (www.chestjoumal. Reproduction of this article is prohibited without written pennission orglmisclreprints.shtml). Physicians (www.chestjoumal. from the Americanto:College Correspondence Lesly of A.Chest Dossett, MD, MPH, 404 Medical orglmisclreprints.shtml). Arts BUilding, 1211 Twenty-First Ave South, Nashville, TN Correspondence to: Lesly A. Dossett, MD, MPH, 404 Medical 37212; e-mail: [email protected] Arts BUilding, 1211 Twenty-First Ave South, Nashville, TN DOl: 1O.1378/chest.08-0079 37212; e-mail: [email protected] DOl: 1O.1378/chest.08-0079 Original Research Original Research

13 have have been but others 99 -- 13 been unable unable to to demonstrate demonstrate but others differences in in outcomes outcomes related obesity. differences related to to obesity. An e-qual amount amount of of ambiguity ambiguity surrounds surrounds the An e-qual the relationship between relationship between pulmonary pulmonary complications complications after after trauma trauma and and during during critical critical illness. illness. At At baseline, baseline, obese obese patients patients have have aa compromised compromised pulmonary pulmonary status status that that is characterized by by reduced reduced lung lung volumes volumes and and comcomis characterized pliance, as ventilation-perfusion mismatchpliance, as well well as as ventilation-perfusion mismatch14 Artificial ing. difficult to to ing. 14 Artificial airways airways are are often often more more difficult maintain in in obese and radiographic radiographic imagmaintain obese patients.t" patients,15 and imagreduced reliability reliability and and delay delay recognirecogniing may have have reduced ing may tion of impending impending complications.l complications.l''6 Obese Obese patients tion of patients of chest chest trauma, may also also experience experience higher may higher rates rates of trauma, rib rib fractures, and aa trend trend fractures, and and pulmonary pulmonary contusions, contusions, and toward more more severe severe chest chest injury.1O·17 injury.1O·17 Despite Despite the the toward presumption presumption that that obese obese patients patieI1ts are are at at high high risk risk for for pulmonary pulmonary complications, complications, very very few few studies studies have have spespecifically addressed addressed these Our objective objective Cifically these outcomes. outcomes. Our was to to determine determine whether whether obesity obesity represents was represents an an independent of independent risk risk factor factor for for the the development development of pulmonary after critical We pulmonary complications complications after critical injury. injury. We hypothesized that and severely severely obese obese patients hypotheSized that obese obese and patients would be be at at increased increased risk would risk for for pulmonary pulmonary complicacomplications tions following follOwing critical critical injury. injury.

MATERIALS AND AND METHODS METHODS MATERIALS

summed to to produce produce the the ISS. ISS. ISS ISS have their their scores scores squared squared and and summed have ranges ranges from from 00 to to 75. 75. The The trauma-related trauma-related ISS ISS (TRISS) (TRISS) determines determines the the ISS ISS and trauma score score the probability probability of of survival survival from from the and revised revised trauma weighted for for patient patient age age and and mechanism mechanism of The revised revised weighted of injury. injury. The trauma score score is is aa physiologic physiologic score score based based on on the the Glasgow Glasgow coma coma trauma scale, the the systolic systolic BP, BP, and and the the respiratory respiratory rate rate on on first first contact contact scale, 22 with the the patient. patient. 2211..22 with

Outcome Measures Outcome Measures The primary primary outcomes outcomes of of interest The interest were were ARDS, ARDS, pneumonia, pneumonia, placement number of of ventilator placement of of aa tracheostomy tracheostomy tube, tube, and and the the number ventilator days. days. ARDS ARDS was was classified classified according according to to the the following following standard standard definition-'': the presence presence of of bilateral bilateral patchy patchy infiltrates infiltrates seen seen on on aa definition23 : the chest radiograph; radiograph; aa Paoifraction Paoyfraction of of inspired chest inspired oxygen oxygen ratio ratio of of < 200; of cardiogenic < 200; and and the the absence absence of cardiogenic pulmonary pulmonary edema. edema. RadioRadiographs graphs were were classified classified by by critical critical care care specialists specialists who who were were not not aa part of of the the patient part patient care care team. team. Hospital-acquired Hospital-acquired pneumonia pneumonia was was diagnosed when aa predominant predominant organism organism was was isolated isolated from from an diagnosed when an appropriately obtained obtained culture culture in in the the setting setting of sputum appropriately of purulent pumlent sputum production, aa new production, new or or changing changing infiltrate infiltrate seen seen on on chest chest radioradiograph, of infection. graph, and and systemic systemic evidence evidence of infection. Quantitative Quantitative endotraendotracheal used at at the the University University of of Virginia Virginia (a cheal suction suction was was routinely routinely used (a concentration organisms per per milliliter milliliter was was considered considered to to concentration of of > > 10 1055 organisms be be positive positive for for infection), infection), and and quantitative quantitative BAL BAL was was routinely routinely used of> 10 1044 organorganused at at Vanderbilt Vanderbilt University University (a (a concentration concentration of> isms per per milliliter milliliter was was considered considered to to be be positive positive for for infection). infection). isms The placement placement of of aa tracheostomy tracheostomy tube tube was was defined defined as any new new The as any tracheostomy tube tube that that was was placed placed during during hospitalization, hospitalization, the the tracheostomy need for for which which was was determined determined by by aa multidisciplinary multidisciplinary team team of of need critical care care physicians. physicians. Secondary Secondary outcomes outcomes included included all-cause all-cause critical in-hospital mortality, mortality, and and hospital hospital and and leu leu length length of of stay in-hospital stay (LOS). (LOS).

Study Design Design and and Participating Study Participating Centers Centers

Statistical Analysis Statistical Analysis

This study study represents represents aa secondary secondary analysis analysis of of aa prospective prospective This cohort study study of of critically critically injured injured adults. adults. The The detailed detailed methods methods of of cohort this study study have have been been previously previously outlined. outlined. 1" 1" Briefly, Briefly, patients patients 2: 2: 18 this 18 years of of age, been admitted admitted to to the trauma ICUs ICUs of of either either years age, who who had had been the trauma Vanderbilt University University Medical Medical Center Center or or the the University University of of VirVirVanderbilt ginia were eligible eligible for for study study ginia Health Health Systems Systems for for at at least least 48 48 h h were enrollment. Patients Patients who who died died before before 48 as were enrollment. 48 h h were were excluded excluded as were patients had been h. patients who who had been discharged discharged from from the the ICU ICU prior prior to to 48 48 h. The minimum minimum stay stay of of 48 intended to to exclude exclude postoperative postoperative The 48 h h was was intended surgical patients patients with with short short observational observational stays stays as well as surgical as well as patients patients who of modem modem critical critical who died died rapidly rapidly from from illness illness beyond beyond the the aid aid of care. Patient Patient care care was was at at the the discretion discretion of of the the attending attending physician physician care. according to to established established critical critical care care protocols protocols in in the the respective respective according ICUs. ICUs.

Normally distributed distributed continuous continuous variables variables were were summarized summarized Normally by reporting reporting the the mean mean and and SD. SD. Continuous Continuous variables variables that that were were by not normally normally distributed distributed were were presented presented by by reporting reporting the the median median not For comparisons comparisons among among multimultiand interquartile interquartile ranges ranges (IQRs). (IQRs). For and ple groups, groups, analysis analysis of of variance Bonferroni ple variance was was used used with with aa Bonferroni correction. To To estimate estimate the the relationship relationship between between outcomes outcomes and and correction. BMI group, group, multivariate multivariate linear linear and BMI and logistic logistic regression regression was was used used to to determine determine regression regression coefficients coefficients and and odds odds ratios, ratios, respectively. respectively. In In these these models, models, BMI BMI was was fit fit in in the the logistic logistic models models as as aa dummy dummy variable variable (BMI (BMI groups). groups). Variables Variables that that were were found found to to have have statisstatistically < 0.10 0.10 or or parameter parameter estimates estimates tically significant significant associations associations (p (p < outside of of the the 95% confidence interval interval [CI] [CI] of of the the comparison comparison outside 95% confidence group) with with BMI BMI group group were were selected selected for for inclusion inclusion in in the the group) multivariate logistic logistic models. models. To To further further explore explore the the nonlinear nonlinear multivariate relationship between between BMI BMI and and outcomes, outcomes, restricted restricted cubic cubic spline spline relationship were determined determined using using aa statistical statistical software software program. program. covariates were

Measure of of Obesity Obesity Measure Body mass Body mass index index (BMI) (BMI) was was determined determined at at hospital hospital admission admission by by dividing dividing the the weight weight in in kilograms kilograms by by the the height height in in meters meters squared. squared. Patients Patients were were classified classified into into the the following follOwing BMI BMI groups groups according according to to the the National National Heart, Heart, Lung, Lung, and and Blood Blood Institute Institute guidelines (underweight); 18.5 guidelines 19: 19: s 18.5 18.5 kglm kglm 22 (underweight); 18.5 to to 24.9 24.9 kg/m" kglm 2 (normal); (overweight); 30.0 kg/m"2 (normal); 25 25 to to 29.9 29.9 kglm kglm 22 (overweight); 30.0 to to 39.9 39.9 kglm 22 (obese); and and 2: 2: 40.0 (severely obese). obese). (obese); 40.0 kglm kglm (severely

Measures of of Injury Injury Seventy Measures Seventy The injury based on on an an anatomic The injury severity severity score score (ISS) (ISS) is is based anatomic grading grading of severiry.s" Each Each of of six body regions regions (head (head and and neck, neck, face, face, of injury injury severity.20 six body chest, abdomen, abdomen, extremity, extremity, and and external) external) is assigned an chest, is aSSigned an abbreviabbreviated The three three most most severely injured regions regions ated injury injury score score (AIS). (AIS). The severely injured www.chestjournal.org www.chestjournal.org

Detectable Alternatives Alternatives Calculations Calculations Detectable Detectable alternatives alternatives were were calculated calculated given given the the following following Detectable available patients total; total; 236 236 patients patients available data data and and assumptions: assumptions: 1,219 1,219 patients with aa BMI BMI > > 30 case (obese (obese patient)-to-control patient)-to-control (nono(nonowith 30 kglm kglm 22 ;; aa case bese patient) patient) ratio ratio of of 2.3:1: 2.3:1: aa type type II error error of of 0.05; and aa type type II bese 0.05; and II error of of 0.20 power). Given Given the the observed observed rates rates of error 0.20 (80% (80% power). of pulmopulmonary nary outcomes outcomes in in nonobese nonobese patients, patients, we we had had 80% 80% power power to to detect detect aa difference of ± ± 8%, difference in in pneumonia pneumonia difference in in ARDS ARDS rates rates of 8%, aa difference rates of of ± ± 9%, and aa difference difference in in the the rate rate of of tracheostomy tracheostomy tube tube rates 9%, and placement of of ± ± 5%. The The analysis analysis is is powered powered to to detect detect aa ± ± 6% placement difference difference in in mortality. mortality. A A statistical statistical software software program program (Stata, (Stata, version version 9.2; 9.2; Stata Stata Corp; Corp; College was used used for College Station, Station, TX) was for analysis. analysis. Tests Tests for for statistical statistical CHEST /134 /134 // 5 5 // NOVEMBER, NOVEMBER, 2008 CHEST 2008

975 975

significance were were two two sided sided with with an an ex ex of of 0.05. 0.05. The The study study was was significance approved by by the the institutional institutional review review board board of of Vanderbilt Vanderbilt University University approved Medical Center. Center. All data are Medical All data are maintained maintained in in aa secure, secure, password password protected the Health Health Insurance Insurance protected database database that that is is compliant compliant with with the Portability and and Accountability Accountability Act Act of of 1996 patient 1996 (or (or HIPAA). HIPAA). All All patient Portability prior to to analysis and reporting. information is is deidentified deidentified prior information analysis and reporting.

RESULTS RESULTS A total patients were were enrolled enrolled into into the the A total of of 2,291 2,291 patients original cohort. cohort. Patients Patients admitted admitted to to the the lCU lCU for for aa original diagnosis = 883) 883) were were exexdiagnOSiS other other than than trauma trauma (n (n = cluded from from the the study. study. Of Of the the 1,406 1,406 trauma trauma patients, patients, cluded 187 (15%) (15%) were were excluded The 187 excluded for for missing missing BMI BMI data. data. The demographics and and clinical clinical characteristics characteristics of of the the demographics 1,219 remaining remaining patients patients by by BMI BMI group are disdis1,219 group are patients fell fell into into played in in Table Table 1. The majority played 1. The majority of of patients the normal normal (35%) (35%) and and overweight the overweight categories categories (33%), (33%), but the the prevalence prevalence of of obeSity obesity (23%) (23%) and and severe severe but

obesity (7%) (7%) was also high. high. The The overweight overweight group group was also obesity was made made up up of of significantly significantly more more male male patients patients was < 0.001), 0.001), while the patients patients in in the normal weight weight (p while the the normal (p < < 0.001). 0.001). There There was was no no group were younger (p group were younger (p < the groups groups according according to to blunt blunt or or difference difference among among the penetrating mechanism, mechanism, or or acute acute physiology physiology and and penetrating chronic II score. score. Anachronic health health evaluation evaluation (APACHE) (APACHE) II Anatomic injury higher tomic injury severity severity (ISS) (ISS) was was statistically statistically higher = 0.008) 0.008) and (p (p = and the the predicted predicted survival survival (TRlSS) (TRlSS) was was 0.006) in Significantly in the the normal normal weight weight Significantly lower lower (p (p == 0.006) group. group. Anatomic Anatomic injury injury pattern pattern did did not not Significantly Significantly differ of head head differ between between the the groups groups with with the the exception exception of injuries. injuries. The The underweight underweight and and normal normal weight weight groups groups had had aa higher higher AIS AIS head head and and neck neck score score than than the the other other < 0.001). 0.001). With With regard regard to to pre-lCU pre-lCU comorcomorgroups groups (p (p < bidities, underweight underweight patients patients were were more bidities, more likely likely to to experience experience chronic chronic renal renal insufficiency insufficiency and and dialysis dialysis dependence, dependence, while while severely severely obese obese patients patients were were

Table I-Demographic I-Demographic and and Clinical Clinical Characteristics Characteristics of of Patients Patients by by BMI BMI Group* Group* Table BMI Groups Groups BMI Variables Variables Age, yr yr Age, % Male Male gender, gender, % BMI, kglm kglm22 BMI, % Blunt injury, injury, % Blunt APACHE II II score score APACHE TRISS TRISS ISS ISS AIS AIS Face Face Head Head Chest Chest Abdomen Abdomen Extremity Extremity External External Pre-ICU admission admission disease disease Pre-ICU % prevalence, % prevalence, Diabetes mellitus mellitus Diabetes Cardiac disease disease Cardiac Cerebrovascular disease disease Cerebrovascular Pulmonary disease disease Pulmonary Chronic renal renal insufficiency insufficiency Chronic Dialysis dependence dependence Dialysis mV/AIDS mV/AIDS Malignancy Malignancy Hepatic insufficiency insufficiency Hepatic Hyperlipidemia Hyperlipidemia Hypertension Hypertension Peripheral vascular vascular disease Peripheral disease Rheumatic/connective Rheumatic/connective tissue tissue disorder disorder Thyroid ThyrOid disease disease Long-term Long-term corticosteroid corticosteroid use use Inflammatory bowel bowel disease Inflammatory disease

II

Underweight Underweight = 23) 23) (n =

Normal Normal = 426) 426) (n =

Overweight Overweight (n = 403) 403) (n =

Obese Obese (n = 286) 286) (n =

Severely Obese Obese Severely (n = = 81) 81) (n

44:':: 23 23 44:':: 48 48 18 18 87 87 17:':: 17:':: 77 0.82 (0.63-0.94) (0.63-0.94) 0.82 28:':: 99 28:'::

46:':: 19 19 46:':: 72 72 23 23 89 89 18:':: 18:':: 66 0.73 (0.30-0.94) (0.30-0.94) 0.73 31:':: 12 31:':: 12

45:':: 19 45:':: 19 79 79 27 27 87 87 17:':: 17:':: 66 0.80 (0.52--0.95) 0.80 (0.52--0.95) 30:':: 30:':: 12 12

47:':: 19 19 47:':: 73 73 33 33 89 89 18:':: 18:':: 66 0.87 0.87 (0.46--0.96) (0.46--0.96) 29 :':: 12 29 :':: 12

44:':: 18 18 44:':: 62 62 45 45 93 93 16 :':: 55 16 :':: 0.90 0.90 (0.52--0.97) (0.52--0.97) 26:':: 11 26:':: 11

0(0-2) 0(0-2) (0-4) 3 (0-4) 3 3 (0-3) 3 (0-3) 0(0--3) 0(0--3) 2 (0-2) (0-2) 2 0(0-1) 0(0-1)

0(0-2) 0(0-2) 33 (2-4) (2-4) 33 (0-4) (0-4) (0-3) 22 (0-3) 0(0--3) 0(0--3) 0(0-1) 0(0-1)

9 9 22 22 4 4 13 13 99 44 00 00 00 99 26 26 00 44

33 77 33 99 00 00 00 22 00 22 11 11 33 11

99 44 00

11 00 00

P Valuet Value] P

< 0.001 0.001 < 0.001 0.001

< 0.001 0.001 < 0.65 0.65 0.35 0.35 0.006 0.006 0.008 0.008

0(0-2) 0(0-2) (0-4) 33 (0-4) 3(2-4) 3(2-4) (0-3) 22 (0-3) (0-3) 2.5 2.5 (0-3) 0(0-0) 0(0-0)

0(0-1) 0(0-1) (0-3) 11 (0-3) 3(2-4) 3(2-4) (0-3) 22 (0-3) (0-3) 33 (0-3) 0(0-1) 0(0-1)

88 15 15 33 10 10 11 00 11 33 00 22 20 20 22 11

11 11 13 13 22 10 10 11 00 00 44 11 66 31 31 11 11

26 26 26 26 22 99 44 11 00 00 00 10 10 33 33 44 11

< 0.001 0.001 < < 0.001 0.001 <

22 11 00

22 22 00

00 11 00

0.08 0.08 0.Q7 0.Q7 0.77 0.77

0(0-2) 0(0-2) (0-4) 33 (0-4) 33 (0-4) (0-4) (0-3) 22 (0-3) 22 (0--3) (0--3) 0(0--0) 0(0--0)

0.21 0.21

< 0.001 0.001 < 0.68 0.68 0.46 0.46 0.26 0.26 0.91 0.91

0.90 0.90 0.38 0.38 0.001 0.001 0.006 0.006 0.74 0.74 0.20 0.20 0.86 0.86 0.001 0.001 < 0.001 0.001 < 0.30 0.30 0.65 0.65

:':: SO SO or or median median (IQR), (IQR), unless otherwise indicated. indicated. *Values are given given as the mean as the mean :':: unless otherwise *Values are [Comparisons tComparisons made made using using one-way one-way analysis analysis of of variance variance with with Bonferroni Bonferroni correction. correction.

976 976

Original Research Original Research

Table 2-Demographic 2-Demographic and and Clinical Clinical Characteristics Characteristics by by Outcome* Outcome* Table Variables Variables

yr Age, yr Age, % Male gender, gender, % Male kg/m22 BMI, kg/m BMI, Blunt injury, injury, % % Blunt II score score APACHE II APACHE TRISS TRISS ISS ISS AIS AIS Face Face Head Head Chest Chest Abdomen Abdomen Extremity Extremity External External % Mortality, % Mortality, Time spent spent receiving receiving Time ventilation, dd ventilation, ICU LOS, LOS, dd ICU Hospital LOS, LOS, dd Hospital

No No ARDS ARDS

ARDS ARDS

Value PP Value

No No Pneumonia Pneumonia

Pneumonia Pneumonia

Value pp Value

No No Tracheostomy Tracheostomy

Tracheostomy Tracheostomy

43 ± ± 19 19 43 76 76 28 ± ± 77 28 86 86 17 ± ± 66 17 0.81 0.81 31 ± ± 11 11 31

43 ± ± 19 19 43 71 71 28 ± ± 66 28 89 89 18 ± ± 66 18 0.82 0.82 33 ± ± 13 13 33

0.48 0.48 0.15 0.15 0.58 0.58 0.23 0.23 < 0.001 0.001 < 0.58 0.58 0.02 0.02

44 ± ± 19 19 44 71 71 28 ± ± 88 28 88 88 15 ± ± 66 15 0.85 0.85 ± 12 12 29 ± 29

42 ± ± 18 18 42 78 78 28 ± ± 77 28 89 89 17 ± ± 66 17 0.78 0.78 31 ± ± 12 12 31

0.36 0.36 0.002 0.002 0.74 0.74 0.39 0.39 < 0.001 0.001 < 0..33 0..33 0.001 0.001

± 19 19 44 ± 44 73 73 ± 77 28 ± 28 89 89 ± 66 16 ± 16 0.83 0.83 ± 12 12 29 ± 29

45 ± ± 19 19 45 81 81 27 ± ± 66 27 86 86 18 ± ± 66 18 0.79 0.79 31 ± ± 12 12 31

0(0-2) 0(0-2) (0-4) 33 (0-4) (0-4) 33 (0-4) 2(0-3) 2(0-3)

0(0-1) 0(0-1) (0-4) 33 (0-4) (3-4) 44 (3-4) 2(0-3) 2(0-3) (0-3) 33 (0-3) {l~I) 0(0-1) 14 14

0(0-2) 0(0-2) (0-4) 33 (0-4) (2-4) 33 (2-4) 2(0-3) 2(0-3) (0-3) 22 (0-3) 0(0-1) 0(0-1) 12 12 66

0(0-2) 0(0-2) 3(0-4) 3(0-4) (2-4) 33 (2-4) (0-3) 22 (0-3) 2(0-3) 2(0-3) 0(0-1) 0(0-1) 99 11 11

0.37 0.37 0.62 0.62 0.002 0.002 0.39 0.39 0.05 0.05 0.81 0.81 0.07 0.07 < 0.001 0.001 <

0(0-1) 0(0-1) 3(0-4) 3(0-4) (1-4) 33 (1-4) (0-3) 22 (0-3) (0-3) 22 (0-3) 0(0-1) 0(0-1) 12 12 77

(0-2) 11 (0-2) (0-5) 33 (0-5) (0-4) 33 (0-4)

10 10

0.06 0.06 0.01 0.01 < 0.001 0.001 < 0.00.5 0.00.5 0.07 0.07 0.88 0.88 0.79 0.79 < 0.001 0.001 <

11 11 19 19

< 0.001 0.001 < < 0.001 0.001 <

(0-3) 22 (0-3)

0(0-1) 0(0-1) 13 13 66 88 16 16

77 15 15

< 0.001 0.001 < < 0.001 0.001 <

14 14 23 23

99 18 18

Value] pp Valuet 0.40 0.40 0.07 0.07 0.06 0.06 0.34 0.34 0.004 0.004 0.51 0.51 0.21 0.21

< 0.001 0.001 < 0.05 0.05 0.75 0.75 < 0.001 0.001 < 0.002 0.002 0.64 0.64 0.62 0.62 0.88 0.88

2(0-3) 2(0-3) (0-3) 22 (0-3)

0(0-1) 0(0-1) 10 10

77

0.58 0.58 0.27 0.27

99 19 19

*Values are are given given as as the the mean mean ± ± SD SD or or median median (IQR), (IQR), unless unless otherwise otherwise indicated. indicated. *Values tComparisons were were made made using using two-sample two-sample tt test, test, X X22 test, test, or or Wilcoxon Wilcoxon rank rank sum sum test. test. tComparisons

more likely likely to to experience experience diabetes diabetes mellitus, mellitus, cardiac cardiac more disease, hyperlipidemia, hyperlipidemia, and and hypertension. hypertension. Individual Individual disease, comorbidities were were not not included included in in the the regression regression comorbidities models since since they they are are summarized summarized by by the the chronic chronic models health score score of of the the APACHE APACHE II II score. score. Table Table 22 health summarizes demographic demographic and and clinical clinical characteristics characteristics summarizes of patients patients by by pulmonary pulmonary outcomes. outcomes. of Unadjusted rates rates of of primary primary and and secondary secondary outoutUnadjusted comes by by BMI BMI group group are are summarized summarized in in Table Table 3. 3. comes The overall overall rate rate of of ARDS ARDS was was 27%. 27%. The The unadjusted unadjusted The rate of of ARDS ARDS was was Significantly Significantly lower lower in in the the severely severely rate obese group group (11%) (11%) compared compared to to the the obese obese group group obese (32%; pp = = 0.02). 0.02). While While aa difference difference was was also also sugsug(32%; gested between between the the severely severely obese obese group group and and the the gested underweight, normal normal weight, weight, and and overweight overweight groups, groups, underweight, this difference difference was was not not statistically statistically significant. significant. When When this compared to to the the normal normal weight weight group, group, the the age-, age-, compared gender-, and and severity-adjusted severity-adjusted odds odds of of ARDS ARDS reregender-,

mained lower lower in in the the severely severely obese obese group group (odds (odds mained ratio, 0.36; 0.36; 95% 95% CI, CI, 0.13 0.13 to to 0.99) 0.99) [Table [Table 4]. 4]. The The rates rates ratio, of pneumonia, pneumonia, tracheostomy tracheostomy tube tube placement, placement, and and of mortality were were 37%, 37%, 10%, 10%, and and 11%, 11%, respectively respectively mortality (Table 5). 5). There There was was no no difference difference in in these these rates rates by by (Table BMI group group in in either either the the univariate univariate or or multivariate multivariate BMI analyses. analyses. The median median mechanical mechanical ventilation ventilation requirement requirement The of the the cohort cohort was was 77 days days (IQR, (IQR, 44 to to 12 12 days), days), and and the the of number of of days days spent spent receiving receiving mechanical mechanical ventilaventilanumber tion did did not not differ differ by by BMI BMI group. group. These These relationships relationships tion did not not differ differ when when nonsurvivors nonsurvivors were were excluded. excluded. The The did median ICU ICU LOS LOS was was 99 days, days, and and the the median median median hospital LOS LOS was was 18 18 days. days. After After adjusting adjusting for for age, age, hospital gender, head head injury injury severity, severity, and and predicted predicted survival, survival, gender, the severely severely obese obese group group had had an an ICU ICU LOS LOS that that was was the 4.8 days days (95% (95% cr, Cl, 1.8 1.8 to to 7.7) 7.7) longer longer than than the the normal normal 4.8 weight group group (Table (Table 3). 3). weight

Table 3-Clinical 3-Clinical Outcomes Outcomes by by BMI BMI Group Group Table BMI Groups Groups BMI II

Variables Variables

% ARDS, % ARDS, Pneumonia. % % Pneumonia. Tracheostomy, % % Tracheostomy, Mortality rate, rate, % % Mortality Time spent spent receiving receiving ventilation, ventilation, dd Time ICU LOS, LOS, dd ICU Hospital LOS, LOS, dd Hospital

Underweight Underweight (n == 23) 23) (n 21 21 22 22 10 10

13 13 7.5 7.5 88 14 14

II

Normal Weight Weight Normal (n == 426) 426) (n

Overweight Overweight (n = = 403) 403) (n

Obese Obese (n == 286) 286) (n

26 26 37 37 12 12 11 11 77 99 17 17

28 28 39 39

36 36

36 36

88 10 10 88 10 10 19 19

44 11 11 88 10 10 20 20

10 10

12 12 77 99 18 18

32 32

Severely Obese Obese Severely (n = = 81) 81) (n 11 11

P Value* Value* P 0.04 0.04 0.57 0.57 0.18 0.18 0.94 0.94 0.04 0.04 < 0.001 0.001 < 0.14 0.14

*Comparisons were were made made using using one-way one-way analysis analysis of of variance variance with with Bonferroni Bonferroni correction. correction. pp Values Values represent represent composite composite analysis analysis of of variance. variance. *Comparisons www.chestjournal.org www.chestjournal.org

CHEST /134/5/ /134/5/ NOVEMBER, NOVEMBER, 2008 2008 CHEST

977 977

Table 4-Adjusted 4-Adjusted Values Values for for Pulmonary Pulmonary Outcomes Outcomes and and Death Death by by BMI BMI Group* Group* Table BMI BMI Groups Groups II

Variables Variables

Underweight UndelWeight = 23) 23) (n (n =

Normal Normal (n = = 426) 426) (n

Overweight OvelWeight (n = = 403) 403) (n

Obese Obese (n = = 286) 286) (n

Severely Obese Severely Obese (n = = 81) 81) (n

HL GOFt GOFt HL

Area Under Area Under ROC Curve ROC Curve

ARDS ARDS Pneumonia Pneumonia Tracheostomy Tracheostomy Mortality Mortality

0.86 (0.22-3.4) (0.22-3.4) 0.86 0.36 (0.10-1.3) (0.10-1.3) 0.36 0.44 (0.06-3.4) (0.06-3.4) 0.44 1.5 (0.31-7.1) (0.31-7.1) 1.5

1.0 1.0 1.0 1.0 1.0 1.0 1.0 1.0

0.97 (0.63-1.5) (0.63-1.5) 0.97 l.l (0.75-1.5) (0.75-1.5) l.l 0.83 (0.48-1.4) (0.48-1.4) 0.83 1..5 (0.83-2.6) 1..5 (0.83-2.6)

1.0 (0.64-1.7) (0.64-1.7) 1.0 0.96 (0.64-1.4) (0.64-1.4) 0.96 0.67 (0.36-1.3) (0.36-1.3) 0.67 0.90 (0.46-1.8) (0.46-1.8) 0.90

0.36 (0.13-0.99) (0.13-0.99) 0.36 0.89 (0.46-1.7) (0.46-1.7) 0.89 0.30 (0.07-1.3) (0.07-1.3) 0.30 1.5 (0.5-4.2) (0.5-4.2) 1.5

576.9; 0.41 576.9; 0.41 776.3; 0.41 776.3; 0.41 744.3; 0.44 744.3; 0.44 751.0; 0.66 751.0; 0.66

0.58 0.58 0.55 0.55 0.61 0.61 0.72 0.72

*Values gender, TRISS, TRISS, and = receiver HL-GOF = = *Values are are given given as as odds odds ratio ratio (95% (95% CI) CI) adjusted adjusted for for age, age, gender, and AIS AIS head head score. score. ROC ROC = receiver operating operating characteristic; characteristic; HL-GOF Hosmer-Lemeshow goodness of of fit. Hosmer-Lemeshow goodness fit. [Values value. tValues are are given given as as X22 statistic; statistic; pp value.

Figure 11 summarizes summarizes the the unadjusted unadjusted relationship relationship Figure between BMI between BMI and and dichotomous dichotomous outcomes outcomes with with aa concurrent summary of anatomic injury severity (as concurrent summary of anatomic injury severity (as estimated by the ISS). The unadjusted relationships estimated by the ISS). The unadjusted relationships among ARDS, ARDS, pneumonia, pneumonia, and and tracheostomy tracheostomy tube tube among placement closely parallel anatomic injury severity placement closely parallel anatomic injury severity the entire entire spectrum spectrum of of BMI, BMI, suggesting suggesting no no across the across independent and these independent relationship relationship between between BMI BMI and these outcomes. In In contrast, contrast, for for patients of outcomes. patients with with aa BMI BMI of 2 > 3,5 kglm 2 while injury > 3,5 kglm , mortality mortality increases increases while injury severity severity decreases. trend was was detected detected in in the the BMI BMI group group decreases. This This trend analysis, but it was was not not Significant since patients patients with with but it significant since analysis, those with with aa BMI BMI of of the highest highest mortality mortality rates rates (ie, the (ie, those 2 > ,50 ,50 kglm kglm 2 represent only only 26% of patients patients (21 (21 of of 81 81 > )) represent 26% of patients) in in the the severely severely obese obese group. group. patients)

DISCUSSION DISCUSSION

Conventional wisdom wisdom holds holds that that obesity obesity increases increases Conventional the number of adverse adverse outcomes outcomes during during critical critical the number of illness, but but an an independent independent effect effect of of obesity obesity on on illness, outcome from from critical critical illness illness has has never never been been concluconcluoutcome reports,5-7 suggested that sively demonstrated. Early reports'v" obesity played aa large large role role in in determining determining outcomes outcomes obesity played in the the ICU ICU and and after after trauma, trauma, but but more more recently recently in reports 99 ,10,12,13 have suggested no relationship, The conclusions from published literature literature are are limited limited conclusions from the the published by retrospective studies and by by varying defiby mostly mostly retrospective studies and varying definitions and and rates rates of of obeSity. obesity. We We sought sought to to describe describe nitions the relationship of obesity the relationship of obesity to to pulmonary pulmonary complicacomplica-

tions in aa large, large, prospective prospective population of trauma trauma tions in population of the patients with with aa prevalence prevalence of of obesity obesity that that reflects reflects the patients general population. population. general Despite these risk factors factors for for pulmoDespite these underlying underlying risk pulmonary complications,14 complications.l" we nary we did did not not detect detect aa difference difference in in pulmonary pulmonary complications complications that that was was related related to to BMI BMI group. since obesity obesity is is aa group. Some Some have have speculated speculated that that since chronic inflammatory inflammatory condition, condition, severe severe injury injury may may chronic incite incite aa second-hit second-hit phenomenon, phenomenon, which which would would prepre"inflammatory" complicadispose dispose obese obese patients patients to to "inflammatory" complications such such as and multiple multiple system system organ organ as ARDS ARDS and tions lO In failure.'? In this this study, study, we we demonstrate demonstrate the the opposite opposite failure. phenomenon; have phenomenon; that that severely severely obese obese patients patients may may have It is not clear clear from from these these data data lower rate rate of of ARDS. ARDS. It is not aa lower what accounts accounts for for this this observation. observation. It It is is possible possible that that what an abundance of subcutaneous subcutaneous fat fat provides provides aa cushion cushion an abundance of and lessens pulmonary injury; we, not and lessens pulmonary injury; we, however, however, did did not detect difference in chest injury BMI group group as detect aa difference in chest injury by by BMI as measured the AIS AIS chest chest score. score. It It is also possible measured by by the is also possible that that this this represents represents aa type type II error. error. We detect differences differences in in pneumonia pneumonia rereWe did did not not detect BMI group group or or the the placement placement of of aa tracheostracheoslated to to BMI lated tomy tube. tube. The The need need for for ventilator support was tomy ventilator support was longer longer for for the the obese obese group group (but (but not not the the severely severely obese obese group). group). One One might might speculate speculate that that obese obese papatients tients continue continue to to receive receive mechanical mechanical ventilation ventilation for for longer. of time time because because clinicians clinicians fear fear airway airway longer. periods periods of complications associated associated with with reintubation. reintubation. With With complications standard ventilator ventilator weaning weaning protocols protocols and and strategies, strategies, standard this is account for for differences differences among among this is unlikely unlikely to to account

Table 5-Adjusted 5-Adjusted Continuous Continuous Outcomes Outcomes by by BMI BMI Group* Group* Table BMI BMI Groups Groups Underweight U ndelWeight (n = = 23) 23) (n

Normal Normal = 426) 426) (n =

Overweight OvelWeight (n == 403) 403) (n

Obese Obese (n = = 286) 286) (n

Severely Obese Severely Obese

Variables Variables Time Time spent spent receiving receiving ventilation, ventilation, d d ICU LOS, ICU LOS, d d Hospital Hospital LOS, LOS, d d

0.10 (-3.7 (-3.7 to 3.9) 0.10 to 3.9) -1.6 (-6.3 (-6.3 to 3.1) -1.6 to 3.1) -2.0 (-17 (-17 to 13.0) -2.0 to 13.0)

00 00 00

0.33 (-0.98 to 1.7) 0.33 (-0.98 to 1.7) 0.60 (-l.l to 2.3) 0.60 (-l.l to 2.3) -2.3 (-7.6 (-7.6 to 3.1) -2.3 to 3.1)

1.4 (0.09 2.8) 1.4 (0.09 to to 2.8) 1.6 (-0.23 (-0.23 to 3.5) 1.6 to 3.5) (-0.83 to ll) 5.2 (-0.83 to ll) 5.2

1.3 (-0.97 (-0.97 to 3.6) 1.3 to 3.6) to 7.7) 7.7) 4.8 (1.8 4.8 (1.8 to 2,1 (-7.4 (-7.4 to to 12) 12) 2,1

(n = = 81) 81) (n

*Values (9,5% CI) adjusted for for age, gender, TRISS, TRISS, and and AIS AIS head head score. *Values are are given given as as l3-coefficient l3-coefficient (9.5% CI) adjusted age, gender, score.

978 978

Original Research Original Research

... ~

c; 'f

,,

,,

,

..... -,

,

\

',-- ....... , ,

I

a

"', ...

~

~

... , ,

-

30*

,,

,

~

,

,.,-:

., ...

...

20

30

lcay au

It

lO l

Iw

'lII:!)

,,

0

/

30*

~

. ;

::s~

30

:0

•

Uaull

',-- .......

... ,

a c:;. ... ...

30*

&

:~

...

40

Q", 15~

"

, ...

... ,

CI

~

...

I~

\.

. ... \.

.. VI

.. ...

30

20

1

FIGGRE FIGGRE

U l II

10 I

S)

9"":!)

::s~

.

60

3O~ ... ,

... ...

is_

...

III

1== 20

. ;

\.

....

!' .. Cl

60

.

.. ...

tI

....

:s~ ... ...

:D

30 1

, II

lO I

S)

2)

60

1. Associations among among BMI, complications after 1. Assodations BMI, mortality, mortality, and and pulmonary pulmonary eomplications after injury. injury.

groups. Severely Severely obese obese patients patients had had aa longer longer ICU ICU groups. LOS (independent (independent of of the the requirements requirements for for mechanmechanLOS ical ventilation), ventilation), but but LOS LOS is is often often confounded confounded by by bed bed ical availability and and insurance insurance status; status; these these results results should should be be availability interpreted in mind. mind. interpreted with with these these limitations limitations in We were were not not able able to to detect detect aa difference difference in in mormorWe tality in the severely obese group of patients comtality in the severely obese group of paticnts compared to to the the normal normal weight weight group group of of patients patients using using pared multivariate analysis. analysis. We We also also did did not not detect detect aa differdiffermultivariate ence in in mortality mortality when when classif)rin~ as ence classif)rin~ the the patients patients as < 30 30 kg/m kg/m )) or or obese obese (BMI (BMI either nonobese nonobese (BMI (BMI < either > 30 30 kg/m kg/m22 ).) . This This is > is similar similar to to some some reportsv':' reports fl . 13 that that have is not not associated associated with with have suggested suggested that that obesity obesity is mortality in in the the injured injured patient. patient. At At least least one one other other mortality 6 report" demonstrated similar findings, suggesting report demonstrated similar findings, suggesting that while while aa cutoff cutoff BMI BMI of of > that > 30 30 kg/rn kg/rn 22 may may be be important in the chronic setting, it may not important in the chronic setting, it may not be be an an accurate in the the critically critically ill ill accurate indicator indicator of of increased increased risk risk in patient. The graph (Fig 1) derived using restricted patient. The graph (Fig 1) derived using restricted cubic higher mortality mortality in in patients patients cubic splines splines suggests suggests aa higher 22 with extreme BMls ) , tie, > 50 kg/m but with extreme BMls (ie, > 50 kg/m ) , but this this is is difficult to demonstrate statistically because of the difficult to demonstrate statistically because of the www.chestjoumal.org www.chestjoumal.org

... ...

"6

I=:

"l

S)

:!)

I

"l

J5

~

~

'

0

60

S)

,"'-,

~

'" II

C't

::s~

.

1=-==

N

g ~0

.

...

... o~

..

~

J5

small of patients small number number of patients with with aa BMI BMI in in this this range. range. As increased, hospitals hospitals As the the prevalence prevalence of of obesity obesity has has increased, and health-care health-care providers providers have have become become more more accusaccusand tomed to to caring caring for for obese obese patients, patients, and and these these findfindtomed ings may may reflect reflect this this difference. ings difference. Hospitals Hospitals are are more more likely likely to to have have special special equipment equipment such such as as specialty specialty beds and larger sized radiology and physical beds and larger sized radiology and physical therapy therapy equipment. equipment. In In addition, addition, improved improved management management of of associated associated chronic chronic morbidities morbidities in in the the outpatient outpatient setsetting (eg, the the aggressive of antiplatelet antiplatelet agents agents and and aggressive use use of ting (eg, lipid agents, agents, and and strict strict glucose glucose control) contro\) and and aa focus focus lipid on hyperglycemia hyperglycemia in in the the ICU ICU may may reduce reduce the the extra extra on morbidity and and mortality mortality that that has has historically historically been been morbidity associated with with obesity. obesity. associated The strengths of this this study study include include its its large large size size The strengths of and prospective classification of pulmonary outand prospective classification of pulmonary outcomes comes in in injured injured patients. patients. Despite Despite these these strengths, strengths, there are several important limitations. there are several important limitations. Although Although BMI BMI correlates correlates with with chronic chronic disease, disease, its its use use in in the the critical care setting has been criticized. Despite critical care setting has been criticized. Despite these these criticisms, are limited, and BMI criticisms, the the alternatives alternatives are limited, and BMI is is correlated with more complicated measures of correlated with more complicated measures of obeobeNOVEMBER, 2008 CHEST /134 / 5 / NOVEMBER,

979 979

sity sity tie, (ie, waist waist circumference circumference and and electrical electrical impedimpedance).24,2.5 ance).24,2.5 Another Another limitation limitation is is that that smoking smoking status status was the was not not measured, measured, and and this this could could confound confound the results. results. Finally, Finally, this this study study was was of of injured injured patients patients only, only, and and these these results results cannot cannot be be generalized generalized to to other other ICU ICU populations. populations.

CONCLUSION CONCLUSION

Neither Neither obesity obesity nor nor severe severe obesity obesity appears appears to to be be an an independent independent risk risk factor factor for for pulmonary pulmonary complicacomplications tions after after injury. injury. Improvements Improvements in in the the care care of of the the obese obese patient patient both both in in the the inpatient inpatient and and outpatient outpatient settings settings may may account account for for this this observation. observation.

REFERENCES REFERENCES 11 Kuczmarski Kuczmarski RJ, RJ, Flegal Flegal KM, KM, Campbell Campbell SM, SM, et et al. al. Increasing Increasing prevalence prevalence of of overweight overweight among among US US adults: adults: the the National National Health Health and and Nutrition Nutrition Examination Examination Surveys, Surveys, 1960 1960 to to 1991. 1991. JAMA JAMA 1994; 1994; 272:205-211 272:205-211 22 Mokdad Mokdad AH, AH, Serdula Serdula MK, MK, Dietz Dietz WH, WH, et et al. al. The The continuing continuing epidemic of obesity obesity in in the the United United States. States. JAMA JAM A 2000; 2000; epidemic of 284:1650-1651 284:1650-1651 33 Calle Calle EE, EE, Thun Thun MJ, MJ, Petrelli Petrelli JM, JM, et et al. al. Body-mass Body-mass index index and and mortality mortality in in aa prospective prospective cohort cohort of of US US adults. adults. N N Engl Engl JJ Med Med 1999; 1999; 341:1097-1105 341:1097-1105 44 Bercault Bercault N, N, Boulain Boulain T, T, Kuteifan Kuteifan K, K, et et al. al. Obesity-related Obesity-related excess excess mortality mortality rate rate in in an an adult adult intensive intensive care care unit: unit: aa risk-adjusted risk-adjusted matched matched cohort cohort study. study. Crit Crit Care Care Med Med 2004; 2004; 32:998-1003 32:998-1003 55 Neville Neville AL, AL, Brown Brown CV, CV, Weng Weng J, J, et et al. al. Obesity Obesity is is an an indepenindependent dent risk risk factor factor of of mortality mortality in in severely severely injured injured blunt blunt trauma trauma patients. patients. Arch Arch Surg Surg 2004; 2004; 139:983-987 139:983-987 66 Byrnes Byrnes MC, MC, McDaniel McDaniel MD, MD, Moore Moore MB, MB, et et al. al. The The effect effect of of obesity obesity on on outcomes outcomes among among injured injured patients. patients. JJ Trauma Trauma 2005; 2005; 58:232-237 58:232-237 77 Choban Choban PS, PS, Weireter Weireter LJ LJ Jr, Jr, Maynes Maynes C. C. Obesity Obesity and and increased increased mortality mortality in in blunt blunt trauma. trauma. JJ Trauma Trauma 1991; 1991; 31:1253-1257 31:1253-1257 88 Bochicchio Bochicchio CV, CV, Joshi Joshi M, M, Bochicchio Bochicchio K, K, et et al. al. Impact Impact of of obesity obesity in in the the critically critically ill ill trauma trauma patient: patient: aa prospective prospective study. study. JJ Am Am Coll Coll Surg Surg 2006; 2006; 203:533-538 203:533-538

980 980

99 Duane Duane TM, TM, Dechert Dechert T, T, Aboutanos Aboutanos MB, MB, et et al. al. Obesity Obesity and and outcomes outcomes after after blunt blunt trauma. trauma. JJ Trauma Trauma 2006; 2006; 61:1218-1221 61:1218-1221 10 10 Brown Brown CV, CV, Rhee Rhee P, P, Neville Neville AL, AL, et et al. al. Obesity Obesity and and traumatic traumatic brain brain injury. injury. JJ Trauma Trauma 2006; 2006; 61:572-576 61:572-576 11 11 Morris Morris JA JA Jr, Jr, MacKenzie MacKenzie EJ, EJ, Edelstein Edelstein SL. SL. The The effect effect of of preexisting preexisting conditions conditions on on mortality mortality in in trauma trauma patients. patients. JAMA JAMA 1990; 1990; 263:1942-1946 263:1942-1946 12 12 Milzman Milzman DP, DP, Boulanger Boulanger BR, BR, Rodriguez Rodriguez A, A, et et al. al. Pre-existing Pre-existing disease disease in in trauma trauma patients: patients: aa predictor predictor of of fate fate independent independent of of age age and and injury injury severity severity score. score. JJ Trauma Trauma 1992; 1992; 32:236-243 32:236-243 13 13 Alban Alban RF, RF, Lyass Lyass S, S, Margulies Margulies DR, DR, et et al. al. Obesity Obesity does does not not affect affect mortality mortality after after trauma. trauma. Am Am Surg Surg 2006; 2006; 72:966-969 72:966-969 14 14 Varon Varon J, J, Marik Marik P. P. Management Management of of the the obese obese critically critically ill ill patient. patient. Crit Crit Care Care Clin Clin 2001; 2001; 17:187-200 17: 187-200 15 15 Adams Adams JP, JP, Murphy Murphy PC. PC. Obesity Obesity in in anaesthesia anaesthesia and and intensive intensive care. care. Br Br JJ Anaesth Anaesth 2000; 2000; 85:91-108 85:91-108 16 16 Boulanger Boulanger BR, BR, Milzman Milzman DP, DP, Rodriguez Rodriguez A. A. Obesity. ObeSity. Crit Crit Care Care Clin Clin 1994; 1994; 10:613-622 10:613-622 17 17 Boulanger Boulanger BR, BR, Milzman Milzman D, D, Mitchell Mitchell K, K, et et al. al. Body Body habitus habitus as as aa predictor predictor of of injury injury pattern pattern after after blunt blunt trauma. trauma. JJ Trauma Trauma 1992; 1992; 33:228-232 33:228-232 18 AK, Dossett Dossett LA, LA, Norris Norris PR, PR, et et al. al. Estradiol Estradiol is is associated associated 18 May May AK, with with mortality mortality in in critically critically ill ill trauma trauma and and surgical surgical patients. patients. Crit Crit Care Care Med Med 2008; 2008; 36:62-68 36:62-68 19 19 National National Institutes Institutes of of Health, Health, National National Heart, Heart, Lung, Lung, and and Blood Blood Institute. Institute. The The practical practical guide: guide: identification, identification, evaluaevaluation, tion, and and treatment treatment of of overweight overweight and and obesity obesity in in adults. adults. Rockville, of Health, Health, 2000; 2000; NIH NIH Rockville, MD: MD: National National Institutes Institutes of Publication Publication No. No. 00-4084 00-4084 20 20 Baker Baker SP, SP, O'Neill O'Neill B, B, Haddon Haddon W W Jr, Jr, et et al. al. The The injury injury severity severity score: score: aa method method for for describing describing patients patients with with multiple multiple injuries injuries and and evaluating evaluating emergency emergency care. care. JJ Trauma Trauma 1974; 1974; 14:187-196 14:187-196 21 21 Champion Champion HR, HR, Sacco Sacco WJ, WJ, Carnazzo Carnazzo AJ, AJ, et et al. al. Trauma Trauma score. score. Crit Crit Care Care Med Med 1981; 1981; 9:672-676 9:672-676 22 22 Champion Champion HR, HR, Sacco Sacco WJ, WJ, Copes Copes WS, WS, et et al. al. A A revision revision of of the the Trauma Trauma Score. Score. JJ Trauma Trauma 1989; 1989; 29:623-629 29:623-629 23 23 Ware Ware LB, LB, Matthay Matthay MA. MA. The The acute acute respiratory respiratory distress distress synsyndrome. drome. N N Engl Engl JJ Med Med 2000; 2000; 342:1334-1349 342:1334-1349 24 24 Keys Keys A, A, Aravanis Aravanis C, C, Blackburn Blackburn H, H, et et al. al. Coronary Coronary heart heart disease: disease: overweight overweight and and obesity obesity as as risk risk factors. factors. Ann Ann Intern Intern Med Med 1972; 1972; 77:15-27 77:15-27 25 25 Deurenberg Deurenberg P, P, Weststrate Weststrate JA, JA, Seidell Seidell JC. JC. Body Body mass mass index index as as aa measure measure of of body body fatness: fatness: ageage- and and sex-specific sex-specific prediction prediction formulas. formulas. Br Br JJ Nutr Nutr 1991; 1991; 65:105-114 65:105-114

Original Original Research Research