European Journal of Cardio-Thoracic Surgery Advance Access published January 29, 2016
ORIGINAL ARTICLE
European Journal of Cardio-Thoracic Surgery (2016) 1–6 doi:10.1093/ejcts/ezv483
The association between body mass index and outcome after coronary artery bypass grafting operations Jagan Devarajana, Amaresh Vydyanathanb, Jing Youc,d, Meng Xue, Daniel I. Sesslerd, Joseph F. Sabikf and C. Allen Bashourd,g,* a b c d e f g
Medina Hospital, Anesthesiology Institute, Cleveland Clinic, Cleveland, OH, USA Montefiore Medical Center/Albert Einstein College of Medicine, Bronx, NY, USA Department of Quantitative Health Sciences, Cleveland Clinic, Cleveland, OH, USA Department of Outcomes Research, Cleveland Clinic, Cleveland, OH, USA Department of Biostatistics, Vanderbilt University, Nashville, TN, USA Department of Cardiothoracic Surgery, Cleveland Clinic, Cleveland, OH, USA Department of Cardiothoracic Anesthesia, Cleveland Clinic, Cleveland, OH, USA
* Corresponding author. Department of Cardiothoracic Anesthesia, Cleveland Clinic, 9500 Euclid Avenue/J4, Cleveland, OH 44195, USA. Tel: +1-216-4457417; fax: +1-216-4451328; e-mail: [email protected] (C.A. Bashour). Received 31 March 2015; received in revised form 18 December 2015; accepted 22 December 2015
Abstract OBJECTIVES: This investigation was undertaken to analyse the association between body mass index (BMI) and morbidity after coronary artery bypass graft (CABG) operations. METHODS: The setting was a cardiovascular intensive care unit (ICU) of a tertiary medical referral centre. This was a retrospective review; patients were classified according to their BMI into five groups: underweight 35 kg/m2. We included patients who underwent isolated CABG between January 3, 2006 and March 8, 2011. After including only the initial operation or admission in patients with more than one operation or hospital admission and excluding patients with any missing variable, 3470 patients remained in the analyses. The primary outcomes analysed were hospital mortality and pulmonary and infection morbidities. We secondarily assessed the association between BMI category and each of the three outcomes. RESULTS: Respective mortality, and pulmonary and infection morbidity occurrence rates were: 8.7, 13.0 and 13.0% for the underweight; 2.4, 8.0 and 4.8% for the overweight; 1.8, 10.9 and 5.6% for the Class I obesity group; and 2.7, 11.1 and 5.7% for the Class II/III obesity group, vs 2.3, 7.0 and 6.2% for the normal weight group. Class I and II/III obesity patients were more likely to have pulmonary morbidity compared with the normal weight group, after adjusting for the potential confounding variables. CONCLUSIONS: Class I and Class II/III obesity (BMI ≥30 kg/m2) was associated with increased pulmonary morbidity after CABG operations. There was no difference in mortality or infection morbidity in any BMI group compared with the normal group. Keywords: CABG surgery • BMI • Outcome • Morbidity • Critical care • Anesthesia
INTRODUCTION Obesity is a rapidly growing health-care problem and is becoming a national epidemic [1]. The occurrence of obesity more than doubled from 12% in 1989 to 28% in 2008 and if the current trend continues [2, 3], it is estimated that by 2018, 103 million people in the USA will be obese and that the associated health-care costs will be over 340 billion dollars [4]. The annual cost percentage increase associated with patients who have greater than normal body mass indices (BMIs) is 36% [5, 6]. Obesity is a risk factor for coronary artery disease [7] and many obese patients require coronary artery bypass graft (CABG) operations [8, 9]. There are inconsistent reports on the association
between BMI and outcome after CABG operations; several studies have shown that obesity is associated with increased morbidity following CABG [10, 11], and other studies have not [12–16]. This investigation was undertaken to analyse the association between BMI and morbidity after CABG operations at a single institution.
MATERIALS AND METHODS Institutional Review Board approval was obtained for this investigation and the requirement for individual patient informed consent was waived. Patient information was retrieved from a patient registry that is collected and maintained by the Anesthesiology
© The Author 2016. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.
ADULT CARDIAC
Cite this article as: Devarajan J, Vydyanathan A, You J, Xu M, Sessler DI, Sabik JF et al. The association between body mass index and outcome after coronary artery bypass grafting operations. Eur J Cardiothorac Surg 2016; doi:10.1093/ejcts/ezv483.
J. Devarajan et al. / European Journal of Cardio-Thoracic Surgery
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Institute at our institution. Specific demographic, historic and baseline variables obtained from the registry were: age, sex, weight, BMI [calculated by dividing mass (kg) by height (m2)], hypertension, carotid artery disease, myocardial infarction [(MI) within the specified time frame prior to the date of surgery as documented on either the history and physical or on the catheterization report], congestive heart failure, cardiogenic shock, pulmonary hypertension, chronic obstructive pulmonary disease (COPD), smoking, diabetes, renal failure and albumin (mg%). Although the use of BMI as a proxy for body fat percentage due to obesity is controversial, it is a simple measure and used in this investigation to classify patient populations. Data were collected prospectively by trained personnel and were regularly audited for quality maintenance and improvement. Data validations are built into the registry to maintain data quality. Additional mechanized validations are performed quarterly to identify quality issues that may have not been identified by built-in validations. All patients who undergo cardiac operations at our institution are included in the registry. All patients who underwent isolated CABG with and without cardiopulmonary bypass (CPB) between 3 January 2006 and 8 March 2011 were included in this investigation. Patients who underwent valve or combined CABG and valve operations were excluded. Paediatric patients less than 18 years of age and patients with missing BMI values or any potential confounding factors (Table 1) were also excluded. Research coordinators collected patient information daily by bedside review of the patient’s medical history, physical assessment record, anaesthesia records and clinical care notes during the patient’s postoperative stay in the cardiovascular intensive care unit (CVICU). Data were not obtained after the patient was discharged from the CVICU. Supplemental demographic and clinical data available
in other institutional databases are imported into the registry through manual and mechanized interfaces. Patients were classified according to their BMI into five groups: underweight 35 kg/m2. The same standardized ventilator weaning protocol was applied across all groups. The primary outcomes analysed were hospital mortality (death by any cause occurring during hospital stay) and the pulmonary and infection morbidities. Pulmonary morbidities included respiratory distress or insufficiency, respiratory failure, aspiration pneumonia and pulmonary embolism, and infection morbidities included bacteraemia, septic shock, sepsis syndrome, catheter-related blood stream infection, fungaemia, mediastinitis, sternal wound infection and urinary tract infection (Table 2). The set of primary outcomes was not analysed as a collapsed composite of ‘any-versus-none’. Rather, a multivariate (i. e. multiple outcomes per patient) analysis was used to simultaneously capture complete information for each component and patient, and the correlations among components. The heterogeneity of the association between BMI category and hospital mortality, and any pulmonary or infection morbidity was analysed by testing the BMI-by-outcome interactions in a ‘distinct effects’ generalized estimating equation (GEE) model with an unstructured covariance matrix [17]. Since the associations with BMI were consistent across the above three outcomes (interaction P = 0.14), for our main analysis a common effect GEE model was conducted. A common odds ratio (OR) across the three outcomes was estimated for each of the four non-normal weight groups versus the normal weight group with adjustment of 22 prespecified potential confounding variables listed in Table 1 (‘inferior
Table 1: Demographics and baseline characteristics among 3470 adult patients who underwent isolated CABG operations by their body mass index categorya Variable
Underweight (n = 23)
Normal (n = 755)
Overweight (n = 1316)
Obesity I (n = 851)
Obesity II/III (n = 525)
Age (years) Gender, male (%) Smoking, yes (%) COPD/asthma, yes (%) Pulmonary hypertension, yes (%) Myocardial infarction, yes (%) Congestive heart failure, yes (%) Hypertension, yes (%) Diabetes, yes (%) Vascular disease, yes (%) Carotid disease, yes (%) Dialysis, yes (%) Cardiogenic shock, yes (%) Preop IABP, yes (%) Preop assisted ventilation, yes (%) Preop creatinine (mg/dl) Preop albumin (U/l) Redo number, yes (%) Emergency, yes (%) LIMA graft, yes (%) RIMA graft, yes (%) Inferior epigastric, yes (%) Radial artery graft, yes (%)
68 [64, 77] 48 57 22 30 48 43 91 22 13 57 9 0 0 4 1.0 [0.7, 1.5] 3.5 ± 0.5 13 0 78 9 0 0
70 [61, 78] 70 58 14 17 48 32 77 29 18 28 5 2 4 1 1.0 [0.8, 1.3] 3.9 ± 0.6 16 3 71 13 0 5
67 [60, 74] 79 58 11 12 44 25 81 37 16 23 3 4 5 1 1.0 [0.9, 1.2] 4.0 ± 0.6 17 3 75 18 0 7
66 [58, 73] 77 56 12 12 45 22 85 49 15 23 3 2 2 1 1.0 [0.9, 1.2] 4.0 ± 0.5 17 2 75 16 0 8
62 [56, 69] 65 54 15 11 49 29 88 65 18 21 4 2 2 1 1.0 [0.9, 1.3] 3.9 ± 0.5 14 3 78 7 0 9
COPD: chronic obstructive pulmonary disease; IABP: intra-aortic balloon pump; LIMA: left internal mammary artery; RIMA: right internal mammary artery; BMI: body mass index. a BMI—underweight: 35 kg/m2.
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Outcome
Definition
Mortality Pulmonary morbidity Aspiration pneumonia
All-cause mortality
80 (2.3)
Clinical diagnosis requires a documented episode of aspiration and infiltrate on chest X-ray consistent with diagnosis V/Q scan or angiography either provides definitive diagnosis or indicates that the patient has a high probability of having a pulmonary embolus Patient requires one or more of the following: FiO2 ≥80% for ≥24 h or mask CPAP intubation Patient’s PaCO2 is >50 mmHg and patient requires reintubation
13 (0.4)
Pulmonary embolus Respiratory distress/insufficiency Respiratory failure Any pulmonary morbidity Infectious morbidity Fungaemia Bacteraemia Line sepsis Sepsis syndrome
Septic shock
Mediastinitis
Sternal wound infection Wound Pneumonia
Urinary tract infection
No. (%)
Patient has a fungal infection that is treated with an antifungal medication. Documented by Infectious Disease Bacteria grown from blood cultures that are treated with appropriate therapy. Must be documented by Infectious Disease Documented by Infectious Disease or ICU team in the progress notes along with positive line culture tips Sepsis with evidence of altered organ perfusion. Must be documented by Infectious Disease or the ICU service. It may be expressed as tachycardia, fever or hypothermia, tachypnoea and evidence of inadequate organ perfusion A sepsis syndrome characterized by hypotension (systolic BP 40 mmHg). Patient should have increased cardiac output. BP is responsive to fluids and drugs Sternal click, open sternal wound, drainage from the mediastinal incision, with elevated temperature. Sternal click alone does not qualify. Patient is returned to the operation theatre with operative note diagnosing mediastinitis or sternectomy with muscle flap grafts to the affected area. Diagnosis should include organism isolated from the cultures along with elevated temperature, elevation of WBCs and the institution of antimicrobial therapy and possibly Betadine irrigation of the area Sternal wound infection other than mediastinitis, documented with positive cultures, requiring intervention Excludes mediastinal wounds. Purulent drainage with positive cultures and institution of therapy. Wound may dehisce or be opened by surgeons Documented by Infectious Disease. Patient presents with fever >38°C, elevation in WBCs, increase in sputum production, infiltrate on chest X-ray that does not clear in 24 h and has a positive sputum culture Documented by Infectious Disease. Patient is diagnosed with a positive urine culture followed by appropriate therapy
Any infectious morbidity
6 (0.2) 224 (6.5) 109 (3.1) 312 (9.0) 6 (0.2) 86 (2.5) 22 (0.6) 50 (1.4)
24 (0.7)
11 (0.3)
32 (0.9) 23 (0.7) 69 (2.0)
70 (2.0) 191 (5.5)
ICU: intensive care unit; FiO2: fraction of inspired oxygen; PaCo2: partial pressure of carbon dioxide in the arterial blood; WBCs: white blood cells; BP: blood pressure; CPAP: continuous positive airway pressure.
epigastric’ was excluded due to zero occurrences). Bonferroni correction for the four comparisons was employed to control for Type I error at 0.05, so that P < 0.0125 was considered significant (i.e. 0.05/4 = 0.0125). Secondarily, we assessed the association between BMI category and each of the three outcomes individually using a distinct effects GEE model with the same covariable adjustment as the above. P < 0.004 was considered significant (Bonferroni correction for 12 comparisons, i.e. four comparisons for each of the three outcomes). SAS software version 9.2 for Windows (SAS Institute, Cary, NC, USA) and R software version 2.12.0 for Windows (the R Foundation for Statistical Computing, Vienna, Austria) were used for all statistical analyses.
RESULTS A total of 4653 patients underwent isolated CABG during the investigation period. There were 4591 patients after including only
the initial operation or admission in patients with more than one operation or hospital admission. After excluding patients with any missing variable, 3470 patients remained in the analyses in the following BMI class distribution: underweight = 23 (0.6%); normal weight = 755 (21%); overweight = 1316 (38%); Class I obesity = 851 (24.5%); and Class II/III obesity = 525 (15%). Definitions and the overall occurrences of primary outcomes are shown in Table 2. Respective mortality, and pulmonary and infection morbidity occurrence rates were: 8.7, 13.0 and 13.0% for the underweight; 2.4, 8.0 and 4.8% for the overweight; 1.8, 10.9 and 5.6% for the Class I obesity group; and 2.7, 11.1 and 5.7% for the Class II/III obesity group, versus 2.3, 7.0 and 6.2% for the normal weight group (Table 3). Table 4 shows a comparison across the three primary outcomes of each of the BMI groups versus the normal BMI group. The association with BMI was consistent across the primary outcomes (interaction P = 0.14). The Class I and Class II/III obesity groups were more likely to experience a major morbidity compared with the normal weight group, after adjusting for the potential
ADULT CARDIAC
Table 2: Definition and occurrence of in-hospital mortality and the composite and individual in-hospital pulmonary and infectious morbidities (n = 3470)
J. Devarajan et al. / European Journal of Cardio-Thoracic Surgery
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Table 3: Occurrences of primary outcomes by BMI category (n = 3470) Incidence (%) Primary outcome
Underweight (n = 23)
Normal (n = 755)
Overweight (n = 1316)
Obesity I (n = 851)
Obesity II/III (n = 525)
In-hospital mortality Any major pulmonary morbidity Any major infectious morbidity Any of the above
8.7 13.0 13.0 26.1
2.3 7.0 6.2 11.5
2.4 8.0 4.8 12.2
1.8 10.9 5.6 15.6
2.7 11.1 5.7 16.6
BMI: body mass index. BMI—underweight: 35 kg/m2.
a
Table 4: Primary results—common odds ratios across the three primary outcomesa for each non-normal weight groupb versus normal weight groupc (n = 3470)
Table 5: Secondary results—association between BMI categorya and each primary outcomeb (n = 3470) Comparison (versus normal weight group)
Comparison (versus normal weight group)
OR (98.75% CI )
P
Underweight group Overweight group Class I obesity group Class II/III obesity group
2.31 (0.61, 8.77) 1.16 (0.80, 1.69) 1.57 (1.06, 2.33) 1.64 (1.05, 2.56)
0.12 0.31 0.004 0.005
d
e
ORc (99.96% CId)
Pd
e
BMI: body mass index; OR: odds ratio; CI: confidence interval. a In-hospital mortality, any major in-hospital pulmonary morbidity and any major in-hospital infectious morbidity (as defined in Table 1). b BMI—underweight: 35 kg/m2. c Normal weight group: BMI 18.5–24.9 kg/m2. d Common ORs across the three primary outcomes were estimated using a generalized estimating equation model with unstructured covariance matrix. We adjusted for 22 prespecified potential confounding variables listed in Table 2 (except for inferior epigastric due to very rare incidence). e The CIs were adjusted for multiple comparisons using the Bonferroni correction, so that P < 0.0125 was considered significant (i.e. 0.05/ 4 = 0.0125).
confounding variables (P = 0.004 and P = 0.005, respectively). The corresponding common ORs across the primary outcomes for Class I and Class II/III obesity groups were 1.57 (98.75% CI: 1.06, 2.33) and 1.64 (98.75% CI: 1.05, 2.56), respectively (Table 4). However, with regard to individual primary outcomes, Class I and II/III obesity patients were more likely to have only pulmonary morbidity compared with the normal weight group, after adjusting for the potential confounding variables [OR (99.96% CI)]: Class I: 2.12 (1.22, 3.70), P < 0.001; and Class II/III: 2.10 (1.12, 3.91), P = 0.001 (Table 5). The two obesity groups did not differ on mortality or infection morbidities compared with the normal weight group.
DISCUSSION Class I obesity and Class II/III obesity (BMI ≥30 kg/m2) were associated with increased pulmonary morbidity after CABG operations. There was no difference in mortality or infection morbidity in any BMI group compared with the normal group. The literature
In-hospital mortality Underweight group Overweight group Class I obesity group Class II/III obesity group Any major pulmonary morbiditya Underweight group Overweight group Class I obesity group Class II/III obesity group Any major infectious morbiditya Underweight group Overweight group Class I obesity group Class II/III obesity group
3.90 (0.36, 42.1) 1.24 (0.52, 2.97) 0.98 (0.35, 2.74) 1.47 (0.51, 4.28)
0.10 0.49 0.95 0.29
1.83 (0.26, 12.8) 1.36 (0.79, 2.32) 2.12 (1.22, 3.70) 2.10 (1.12, 3.91)
0.37 0.10 30 kg/m2 was associated with increased pulmonary morbidity after CABG operations, and the ESC/EACTS guidelines above, it is reasonable to ask patients with above-normal BMIs undergoing elective CABG operations to aim to achieve a preoperative BMI of 25–30 kg/m2. The association between infectious complications and BMI after CABG is unclear. In some investigations higher BMI patients had increased risk of superficial [10] and deep (mediastinitis) sternal wound as well as saphenous vein harvest site infections [19]. Obesity, bilateral internal mammary artery harvesting and prolonged mechanical ventilation are reported to be associated with postoperative sternal wound infection. Operation time is associated with infectious complications [20] and higher BMI patients may have longer operations [19]. High BMI patients are at increased infection risk due to a higher occurrence of diabetes and because of decreased oxygen delivery at the operative sites. In spite of these mechanisms, BMI and infection morbidities were not associated, which is consistent with other reports [21]. We used a multivariate (multiple outcome components per patient) analysis which adjusts for and takes advantage of the correlations among outcome components, which typically improves power when compared with the traditional methods including
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analysing the outcomes as a collapsed composite or separately. This investigation was limited, however, in that it was not a prospective randomized investigation. As with all retrospective studies, we only controlled for the observed (available) potential confounding variables and those unaccounted for may have affected the results. Many baseline pulmonary variables were analysed; however, other variables such as gender, history of diabetes, pulmonary function studies, medication profile (e.g. bronchodilators), history of obstructive sleep apnoea and haemoglobin oxygen saturation, preoperative and postoperative ventricular function and reoperation for bleeding were not included in the analysis; intraoperative variables such as transfusion requirements, total operation length (including CPB and cross-clamp times) and intraoperative fluid administration were not included and could impact postoperative pulmonary function. Further, this was a single-centre study; results may differ in other settings or populations. The small number of patients in the underweight BMI group (n = 23), and the low incidence of deep sternal wound infection [n = 11 (0.3%)] may have affected the results. The use of BMI as a proxy for obesity has been questioned since it does not account for distribution of body fat.
CONCLUSION Patients with above normal BMIs who underwent CABG operations experienced increased postoperative pulmonary morbidities, but not increased infectious morbidities nor increased mortality. Aggressive respiratory therapy and adequate pain control after tracheal extubation is important in all patients and especially in those with above normal BMIs. Prevention of pulmonary morbidity in obese patients following CABG operations can lead to an improved postoperative course and overall outcome. Conflict of interest: none declared.
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[18] Vassiliades TA Jr, Nielsen JL, Lonquist JL. Effects of obesity on outcomes in endoscopically assisted coronary artery bypass operations. Heart Surg Forum 2003;6:99–101. [19] Alam M, Siddiqui S, Lee VV, Elayda MA, Nambi V, Yang EY et al. Isolated coronary artery bypass grafting in obese individuals: a propensity matched analysis of outcomes. Circ J 2011;75:1378–85. [20] Orhan G, Bicer Y, Aka SA, Sargin M, Simşek S, Senay S et al. Coronary artery bypass graft operations can be performed safely in obese patients. Eur J Cardiothorac Surg 2004;25:212–7. [21] Engel AM, McDonough S, Smith JM. Does an obese body mass index affect hospital outcomes after coronary artery bypass graft surgery? Ann Thorac Surg 2009;88:1793–800. [22] Zerah F, Harf A, Perlemuter L, Lorino H, Lorino AM, Atlan G. Effects of obesity on respiratory resistance. Chest 1993;103:1470–6. [23] Salome CM, King GG, Berend N. Physiology of obesity and effects on lung function. J Appl Physiol 2010;108:206–11. [24] Apostolakis EE, Koletsis EN, Baikoussis NG, Siminelakis SN, Papadopoulos GS. Strategies to prevent intraoperative lung injury during cardiopulmonary bypass. J Cardiothorac Surg 2010;5:1. [25] Kolh P, Windecker S, Alfonso F, Collet JP, Cremer J, Falk V et al. 2014 ECS/ EACTS Guidelines on myocardial revascularization. Eur J Cardiothorac Surg 2014;46:517–92.
ORIGINAL ARTICLE
European Journal of Cardio-Thoracic Surgery (2016) 1–6 doi:10.1093/ejcts/ezv483
The association between body mass index and outcome after coronary artery bypass grafting operations Jagan Devarajana, Amaresh Vydyanathanb, Jing Youc,d, Meng Xue, Daniel I. Sesslerd, Joseph F. Sabikf and C. Allen Bashourd,g,* a b c d e f g
Medina Hospital, Anesthesiology Institute, Cleveland Clinic, Cleveland, OH, USA Montefiore Medical Center/Albert Einstein College of Medicine, Bronx, NY, USA Department of Quantitative Health Sciences, Cleveland Clinic, Cleveland, OH, USA Department of Outcomes Research, Cleveland Clinic, Cleveland, OH, USA Department of Biostatistics, Vanderbilt University, Nashville, TN, USA Department of Cardiothoracic Surgery, Cleveland Clinic, Cleveland, OH, USA Department of Cardiothoracic Anesthesia, Cleveland Clinic, Cleveland, OH, USA
* Corresponding author. Department of Cardiothoracic Anesthesia, Cleveland Clinic, 9500 Euclid Avenue/J4, Cleveland, OH 44195, USA. Tel: +1-216-4457417; fax: +1-216-4451328; e-mail: [email protected] (C.A. Bashour). Received 31 March 2015; received in revised form 18 December 2015; accepted 22 December 2015
Abstract OBJECTIVES: This investigation was undertaken to analyse the association between body mass index (BMI) and morbidity after coronary artery bypass graft (CABG) operations. METHODS: The setting was a cardiovascular intensive care unit (ICU) of a tertiary medical referral centre. This was a retrospective review; patients were classified according to their BMI into five groups: underweight 35 kg/m2. We included patients who underwent isolated CABG between January 3, 2006 and March 8, 2011. After including only the initial operation or admission in patients with more than one operation or hospital admission and excluding patients with any missing variable, 3470 patients remained in the analyses. The primary outcomes analysed were hospital mortality and pulmonary and infection morbidities. We secondarily assessed the association between BMI category and each of the three outcomes. RESULTS: Respective mortality, and pulmonary and infection morbidity occurrence rates were: 8.7, 13.0 and 13.0% for the underweight; 2.4, 8.0 and 4.8% for the overweight; 1.8, 10.9 and 5.6% for the Class I obesity group; and 2.7, 11.1 and 5.7% for the Class II/III obesity group, vs 2.3, 7.0 and 6.2% for the normal weight group. Class I and II/III obesity patients were more likely to have pulmonary morbidity compared with the normal weight group, after adjusting for the potential confounding variables. CONCLUSIONS: Class I and Class II/III obesity (BMI ≥30 kg/m2) was associated with increased pulmonary morbidity after CABG operations. There was no difference in mortality or infection morbidity in any BMI group compared with the normal group. Keywords: CABG surgery • BMI • Outcome • Morbidity • Critical care • Anesthesia
INTRODUCTION Obesity is a rapidly growing health-care problem and is becoming a national epidemic [1]. The occurrence of obesity more than doubled from 12% in 1989 to 28% in 2008 and if the current trend continues [2, 3], it is estimated that by 2018, 103 million people in the USA will be obese and that the associated health-care costs will be over 340 billion dollars [4]. The annual cost percentage increase associated with patients who have greater than normal body mass indices (BMIs) is 36% [5, 6]. Obesity is a risk factor for coronary artery disease [7] and many obese patients require coronary artery bypass graft (CABG) operations [8, 9]. There are inconsistent reports on the association
between BMI and outcome after CABG operations; several studies have shown that obesity is associated with increased morbidity following CABG [10, 11], and other studies have not [12–16]. This investigation was undertaken to analyse the association between BMI and morbidity after CABG operations at a single institution.
MATERIALS AND METHODS Institutional Review Board approval was obtained for this investigation and the requirement for individual patient informed consent was waived. Patient information was retrieved from a patient registry that is collected and maintained by the Anesthesiology
© The Author 2016. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.
ADULT CARDIAC
Cite this article as: Devarajan J, Vydyanathan A, You J, Xu M, Sessler DI, Sabik JF et al. The association between body mass index and outcome after coronary artery bypass grafting operations. Eur J Cardiothorac Surg 2016; doi:10.1093/ejcts/ezv483.
J. Devarajan et al. / European Journal of Cardio-Thoracic Surgery
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Institute at our institution. Specific demographic, historic and baseline variables obtained from the registry were: age, sex, weight, BMI [calculated by dividing mass (kg) by height (m2)], hypertension, carotid artery disease, myocardial infarction [(MI) within the specified time frame prior to the date of surgery as documented on either the history and physical or on the catheterization report], congestive heart failure, cardiogenic shock, pulmonary hypertension, chronic obstructive pulmonary disease (COPD), smoking, diabetes, renal failure and albumin (mg%). Although the use of BMI as a proxy for body fat percentage due to obesity is controversial, it is a simple measure and used in this investigation to classify patient populations. Data were collected prospectively by trained personnel and were regularly audited for quality maintenance and improvement. Data validations are built into the registry to maintain data quality. Additional mechanized validations are performed quarterly to identify quality issues that may have not been identified by built-in validations. All patients who undergo cardiac operations at our institution are included in the registry. All patients who underwent isolated CABG with and without cardiopulmonary bypass (CPB) between 3 January 2006 and 8 March 2011 were included in this investigation. Patients who underwent valve or combined CABG and valve operations were excluded. Paediatric patients less than 18 years of age and patients with missing BMI values or any potential confounding factors (Table 1) were also excluded. Research coordinators collected patient information daily by bedside review of the patient’s medical history, physical assessment record, anaesthesia records and clinical care notes during the patient’s postoperative stay in the cardiovascular intensive care unit (CVICU). Data were not obtained after the patient was discharged from the CVICU. Supplemental demographic and clinical data available
in other institutional databases are imported into the registry through manual and mechanized interfaces. Patients were classified according to their BMI into five groups: underweight 35 kg/m2. The same standardized ventilator weaning protocol was applied across all groups. The primary outcomes analysed were hospital mortality (death by any cause occurring during hospital stay) and the pulmonary and infection morbidities. Pulmonary morbidities included respiratory distress or insufficiency, respiratory failure, aspiration pneumonia and pulmonary embolism, and infection morbidities included bacteraemia, septic shock, sepsis syndrome, catheter-related blood stream infection, fungaemia, mediastinitis, sternal wound infection and urinary tract infection (Table 2). The set of primary outcomes was not analysed as a collapsed composite of ‘any-versus-none’. Rather, a multivariate (i. e. multiple outcomes per patient) analysis was used to simultaneously capture complete information for each component and patient, and the correlations among components. The heterogeneity of the association between BMI category and hospital mortality, and any pulmonary or infection morbidity was analysed by testing the BMI-by-outcome interactions in a ‘distinct effects’ generalized estimating equation (GEE) model with an unstructured covariance matrix [17]. Since the associations with BMI were consistent across the above three outcomes (interaction P = 0.14), for our main analysis a common effect GEE model was conducted. A common odds ratio (OR) across the three outcomes was estimated for each of the four non-normal weight groups versus the normal weight group with adjustment of 22 prespecified potential confounding variables listed in Table 1 (‘inferior
Table 1: Demographics and baseline characteristics among 3470 adult patients who underwent isolated CABG operations by their body mass index categorya Variable
Underweight (n = 23)
Normal (n = 755)
Overweight (n = 1316)
Obesity I (n = 851)
Obesity II/III (n = 525)
Age (years) Gender, male (%) Smoking, yes (%) COPD/asthma, yes (%) Pulmonary hypertension, yes (%) Myocardial infarction, yes (%) Congestive heart failure, yes (%) Hypertension, yes (%) Diabetes, yes (%) Vascular disease, yes (%) Carotid disease, yes (%) Dialysis, yes (%) Cardiogenic shock, yes (%) Preop IABP, yes (%) Preop assisted ventilation, yes (%) Preop creatinine (mg/dl) Preop albumin (U/l) Redo number, yes (%) Emergency, yes (%) LIMA graft, yes (%) RIMA graft, yes (%) Inferior epigastric, yes (%) Radial artery graft, yes (%)
68 [64, 77] 48 57 22 30 48 43 91 22 13 57 9 0 0 4 1.0 [0.7, 1.5] 3.5 ± 0.5 13 0 78 9 0 0
70 [61, 78] 70 58 14 17 48 32 77 29 18 28 5 2 4 1 1.0 [0.8, 1.3] 3.9 ± 0.6 16 3 71 13 0 5
67 [60, 74] 79 58 11 12 44 25 81 37 16 23 3 4 5 1 1.0 [0.9, 1.2] 4.0 ± 0.6 17 3 75 18 0 7
66 [58, 73] 77 56 12 12 45 22 85 49 15 23 3 2 2 1 1.0 [0.9, 1.2] 4.0 ± 0.5 17 2 75 16 0 8
62 [56, 69] 65 54 15 11 49 29 88 65 18 21 4 2 2 1 1.0 [0.9, 1.3] 3.9 ± 0.5 14 3 78 7 0 9
COPD: chronic obstructive pulmonary disease; IABP: intra-aortic balloon pump; LIMA: left internal mammary artery; RIMA: right internal mammary artery; BMI: body mass index. a BMI—underweight: 35 kg/m2.
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Outcome
Definition
Mortality Pulmonary morbidity Aspiration pneumonia
All-cause mortality
80 (2.3)
Clinical diagnosis requires a documented episode of aspiration and infiltrate on chest X-ray consistent with diagnosis V/Q scan or angiography either provides definitive diagnosis or indicates that the patient has a high probability of having a pulmonary embolus Patient requires one or more of the following: FiO2 ≥80% for ≥24 h or mask CPAP intubation Patient’s PaCO2 is >50 mmHg and patient requires reintubation
13 (0.4)
Pulmonary embolus Respiratory distress/insufficiency Respiratory failure Any pulmonary morbidity Infectious morbidity Fungaemia Bacteraemia Line sepsis Sepsis syndrome
Septic shock
Mediastinitis
Sternal wound infection Wound Pneumonia
Urinary tract infection
No. (%)
Patient has a fungal infection that is treated with an antifungal medication. Documented by Infectious Disease Bacteria grown from blood cultures that are treated with appropriate therapy. Must be documented by Infectious Disease Documented by Infectious Disease or ICU team in the progress notes along with positive line culture tips Sepsis with evidence of altered organ perfusion. Must be documented by Infectious Disease or the ICU service. It may be expressed as tachycardia, fever or hypothermia, tachypnoea and evidence of inadequate organ perfusion A sepsis syndrome characterized by hypotension (systolic BP 40 mmHg). Patient should have increased cardiac output. BP is responsive to fluids and drugs Sternal click, open sternal wound, drainage from the mediastinal incision, with elevated temperature. Sternal click alone does not qualify. Patient is returned to the operation theatre with operative note diagnosing mediastinitis or sternectomy with muscle flap grafts to the affected area. Diagnosis should include organism isolated from the cultures along with elevated temperature, elevation of WBCs and the institution of antimicrobial therapy and possibly Betadine irrigation of the area Sternal wound infection other than mediastinitis, documented with positive cultures, requiring intervention Excludes mediastinal wounds. Purulent drainage with positive cultures and institution of therapy. Wound may dehisce or be opened by surgeons Documented by Infectious Disease. Patient presents with fever >38°C, elevation in WBCs, increase in sputum production, infiltrate on chest X-ray that does not clear in 24 h and has a positive sputum culture Documented by Infectious Disease. Patient is diagnosed with a positive urine culture followed by appropriate therapy
Any infectious morbidity
6 (0.2) 224 (6.5) 109 (3.1) 312 (9.0) 6 (0.2) 86 (2.5) 22 (0.6) 50 (1.4)
24 (0.7)
11 (0.3)
32 (0.9) 23 (0.7) 69 (2.0)
70 (2.0) 191 (5.5)
ICU: intensive care unit; FiO2: fraction of inspired oxygen; PaCo2: partial pressure of carbon dioxide in the arterial blood; WBCs: white blood cells; BP: blood pressure; CPAP: continuous positive airway pressure.
epigastric’ was excluded due to zero occurrences). Bonferroni correction for the four comparisons was employed to control for Type I error at 0.05, so that P < 0.0125 was considered significant (i.e. 0.05/4 = 0.0125). Secondarily, we assessed the association between BMI category and each of the three outcomes individually using a distinct effects GEE model with the same covariable adjustment as the above. P < 0.004 was considered significant (Bonferroni correction for 12 comparisons, i.e. four comparisons for each of the three outcomes). SAS software version 9.2 for Windows (SAS Institute, Cary, NC, USA) and R software version 2.12.0 for Windows (the R Foundation for Statistical Computing, Vienna, Austria) were used for all statistical analyses.
RESULTS A total of 4653 patients underwent isolated CABG during the investigation period. There were 4591 patients after including only
the initial operation or admission in patients with more than one operation or hospital admission. After excluding patients with any missing variable, 3470 patients remained in the analyses in the following BMI class distribution: underweight = 23 (0.6%); normal weight = 755 (21%); overweight = 1316 (38%); Class I obesity = 851 (24.5%); and Class II/III obesity = 525 (15%). Definitions and the overall occurrences of primary outcomes are shown in Table 2. Respective mortality, and pulmonary and infection morbidity occurrence rates were: 8.7, 13.0 and 13.0% for the underweight; 2.4, 8.0 and 4.8% for the overweight; 1.8, 10.9 and 5.6% for the Class I obesity group; and 2.7, 11.1 and 5.7% for the Class II/III obesity group, versus 2.3, 7.0 and 6.2% for the normal weight group (Table 3). Table 4 shows a comparison across the three primary outcomes of each of the BMI groups versus the normal BMI group. The association with BMI was consistent across the primary outcomes (interaction P = 0.14). The Class I and Class II/III obesity groups were more likely to experience a major morbidity compared with the normal weight group, after adjusting for the potential
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Table 2: Definition and occurrence of in-hospital mortality and the composite and individual in-hospital pulmonary and infectious morbidities (n = 3470)
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Table 3: Occurrences of primary outcomes by BMI category (n = 3470) Incidence (%) Primary outcome
Underweight (n = 23)
Normal (n = 755)
Overweight (n = 1316)
Obesity I (n = 851)
Obesity II/III (n = 525)
In-hospital mortality Any major pulmonary morbidity Any major infectious morbidity Any of the above
8.7 13.0 13.0 26.1
2.3 7.0 6.2 11.5
2.4 8.0 4.8 12.2
1.8 10.9 5.6 15.6
2.7 11.1 5.7 16.6
BMI: body mass index. BMI—underweight: 35 kg/m2.
a
Table 4: Primary results—common odds ratios across the three primary outcomesa for each non-normal weight groupb versus normal weight groupc (n = 3470)
Table 5: Secondary results—association between BMI categorya and each primary outcomeb (n = 3470) Comparison (versus normal weight group)
Comparison (versus normal weight group)
OR (98.75% CI )
P
Underweight group Overweight group Class I obesity group Class II/III obesity group
2.31 (0.61, 8.77) 1.16 (0.80, 1.69) 1.57 (1.06, 2.33) 1.64 (1.05, 2.56)
0.12 0.31 0.004 0.005
d
e
ORc (99.96% CId)
Pd
e
BMI: body mass index; OR: odds ratio; CI: confidence interval. a In-hospital mortality, any major in-hospital pulmonary morbidity and any major in-hospital infectious morbidity (as defined in Table 1). b BMI—underweight: 35 kg/m2. c Normal weight group: BMI 18.5–24.9 kg/m2. d Common ORs across the three primary outcomes were estimated using a generalized estimating equation model with unstructured covariance matrix. We adjusted for 22 prespecified potential confounding variables listed in Table 2 (except for inferior epigastric due to very rare incidence). e The CIs were adjusted for multiple comparisons using the Bonferroni correction, so that P < 0.0125 was considered significant (i.e. 0.05/ 4 = 0.0125).
confounding variables (P = 0.004 and P = 0.005, respectively). The corresponding common ORs across the primary outcomes for Class I and Class II/III obesity groups were 1.57 (98.75% CI: 1.06, 2.33) and 1.64 (98.75% CI: 1.05, 2.56), respectively (Table 4). However, with regard to individual primary outcomes, Class I and II/III obesity patients were more likely to have only pulmonary morbidity compared with the normal weight group, after adjusting for the potential confounding variables [OR (99.96% CI)]: Class I: 2.12 (1.22, 3.70), P < 0.001; and Class II/III: 2.10 (1.12, 3.91), P = 0.001 (Table 5). The two obesity groups did not differ on mortality or infection morbidities compared with the normal weight group.
DISCUSSION Class I obesity and Class II/III obesity (BMI ≥30 kg/m2) were associated with increased pulmonary morbidity after CABG operations. There was no difference in mortality or infection morbidity in any BMI group compared with the normal group. The literature
In-hospital mortality Underweight group Overweight group Class I obesity group Class II/III obesity group Any major pulmonary morbiditya Underweight group Overweight group Class I obesity group Class II/III obesity group Any major infectious morbiditya Underweight group Overweight group Class I obesity group Class II/III obesity group
3.90 (0.36, 42.1) 1.24 (0.52, 2.97) 0.98 (0.35, 2.74) 1.47 (0.51, 4.28)
0.10 0.49 0.95 0.29
1.83 (0.26, 12.8) 1.36 (0.79, 2.32) 2.12 (1.22, 3.70) 2.10 (1.12, 3.91)
0.37 0.10 30 kg/m2 was associated with increased pulmonary morbidity after CABG operations, and the ESC/EACTS guidelines above, it is reasonable to ask patients with above-normal BMIs undergoing elective CABG operations to aim to achieve a preoperative BMI of 25–30 kg/m2. The association between infectious complications and BMI after CABG is unclear. In some investigations higher BMI patients had increased risk of superficial [10] and deep (mediastinitis) sternal wound as well as saphenous vein harvest site infections [19]. Obesity, bilateral internal mammary artery harvesting and prolonged mechanical ventilation are reported to be associated with postoperative sternal wound infection. Operation time is associated with infectious complications [20] and higher BMI patients may have longer operations [19]. High BMI patients are at increased infection risk due to a higher occurrence of diabetes and because of decreased oxygen delivery at the operative sites. In spite of these mechanisms, BMI and infection morbidities were not associated, which is consistent with other reports [21]. We used a multivariate (multiple outcome components per patient) analysis which adjusts for and takes advantage of the correlations among outcome components, which typically improves power when compared with the traditional methods including
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analysing the outcomes as a collapsed composite or separately. This investigation was limited, however, in that it was not a prospective randomized investigation. As with all retrospective studies, we only controlled for the observed (available) potential confounding variables and those unaccounted for may have affected the results. Many baseline pulmonary variables were analysed; however, other variables such as gender, history of diabetes, pulmonary function studies, medication profile (e.g. bronchodilators), history of obstructive sleep apnoea and haemoglobin oxygen saturation, preoperative and postoperative ventricular function and reoperation for bleeding were not included in the analysis; intraoperative variables such as transfusion requirements, total operation length (including CPB and cross-clamp times) and intraoperative fluid administration were not included and could impact postoperative pulmonary function. Further, this was a single-centre study; results may differ in other settings or populations. The small number of patients in the underweight BMI group (n = 23), and the low incidence of deep sternal wound infection [n = 11 (0.3%)] may have affected the results. The use of BMI as a proxy for obesity has been questioned since it does not account for distribution of body fat.
CONCLUSION Patients with above normal BMIs who underwent CABG operations experienced increased postoperative pulmonary morbidities, but not increased infectious morbidities nor increased mortality. Aggressive respiratory therapy and adequate pain control after tracheal extubation is important in all patients and especially in those with above normal BMIs. Prevention of pulmonary morbidity in obese patients following CABG operations can lead to an improved postoperative course and overall outcome. Conflict of interest: none declared.
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