- Email: [email protected]
Operative risk and preoperative hematocrit in bypass graft surgery: Role of gender and blood transfusion
Cardiovascular Revascularization Medicine xxx (2015) xxx–xxx
Contents lists available at ScienceDirect
Cardiovascular Revascularization Medicine
Operative risk and preoperative hematocrit in bypass graft surgery: Role of gender and blood transfusion Niv Ad ⁎, Sari D. Holmes, Paul S. Massimiano, Dan Spiegelstein, Deborah J. Shuman, Graciela Pritchard, Linda Halpin Inova Heart and Vascular Institute, 3300 Gallows Road, Suite 3100, Falls Church, VA 22042, USA
a r t i c l e
i n f o
Article history: Received 22 May 2015 Accepted 15 July 2015 Available online xxxx Keywords: Blood management Outcomes CABG Gender
a b s t r a c t Background: The association between lower preoperative hematocrit (Hct) and risk for morbidity/mortality after cardiac surgery is well established. We examined whether the impact of low preoperative Hct on outcome is modified by blood transfusion and operative risk in women and men undergoing nonemergent CABG surgery. Methods: Patients having nonemergent, first-time, isolated CABG were included (N = 2757). Logistic regressions assessed effect of hematocrit on major perioperative morbidity/mortality separately by males (n = 2232) and females (n = 525). Results: Mean age was 63.2 ± 10.1 years, preoperative hematocrit was 38.9 ± 4.8%, and STS risk score was 1.3 ± 1.8%. Blood transfusion was more likely in female patients (26% vs. 12%, P b 0.001). Multivariate analyses revealed that lower body mass index and lower preoperative hematocrit predicted transfusion in males and females, whereas older age (OR = 1.03, P = 0.017) also predicted transfusion in females. Major morbidity was also more likely in female patients (12% vs. 7%, P b 0.001). In multivariate analyses, blood transfusion was the only predictive factor for major morbidity in females (OR = 4.56, P b 0.001). In males, higher body mass index (OR = 1.07, P b 0.001), lower hematocrit (OR = 0.94, P = 0.017), interaction of STS score with hematocrit (OR = 1.02, P = 0.045), and blood transfusion (OR = 9.22, P b 0.001) were significant predictors for major morbidity. Conclusions: This study showed females were more likely to have blood transfusion and major morbidities after nonemergent CABG. Traditional factors that have been found to predict outcomes, such as hematocrit and STS risk, were related only to major morbidity in male patients. However, blood transfusion negatively impacted major outcome after nonemergent CABG surgery across all STS risk levels in both genders. © 2015 Elsevier Inc. All rights reserved.
1. Introduction Cardiac surgery accounts for the majority of blood transfusions in the United States each year [1,2]. Nearly 50,000 coronary artery bypass graft (CABG) procedures were performed in the United States in 2008 [3], about half of which involved transfusion of blood products [4]. Despite the overall decline in CABG morbidity and mortality since the procedure was first performed [5], a disproportionate number of operative deaths and major adverse outcomes still occur in women who undergo this surgery [6–8]. Women make up less than one-third of all patients undergoing CABG but account for nearly twice as many operative deaths than men [5,6,9]. In light of these statistics, it is not surprising that female gender has been shown to be an independent risk factor for perioperative mortality in isolated CABG [9–12]. Particularly in patients undergoing CABG surgery, the association between preoperative low hematocrit (Hct) and the risk of transfusion and adverse surgical outcomes is well established [13–20]. Low ⁎ Corresponding author at: Cardiac Surgery Research, Inova Heart and Vascular Institute, 3300 Gallows Road, Suite 3100, Falls Church, VA 22042, USA. Tel.: +1 703 776 8025; fax: +1 703 776 8303. E-mail address: [email protected] (N. Ad).
preoperative Hct is one of the most frequent indications for intraoperative transfusion in CABG patients [21], and transfusion is itself a wellknown risk factor for adverse outcomes in CABG [22–25]. In this study, we examined whether the impact of low preoperative Hct on outcomes was gender specific for patients undergoing nonemergent isolated CABG, taking blood transfusion and operative risk into account. We hypothesized that the factors that are important in the relationship of Hct and outcomes would differ for male and female patients. 2. Materials and methods 2.1. Study sample The sample for this observational study consisted of all consecutive patients who underwent nonemergent, first-time, isolated CABG between January 2007 and October 2014 (N = 2757). CABG surgery was performed with cardiopulmonary bypass by standard surgical procedure, using a midsternotomy approach. Data were collected prospectively as part of our local Society of Thoracic Surgeons (STS) Adult Cardiac Surgery database, and all patients included in analyses had complete data on the variables of interest. An additional 388 patients met inclusion criteria during this time frame but were missing Hct or STS risk
http://dx.doi.org/10.1016/j.carrev.2015.07.007 1553-8389/© 2015 Elsevier Inc. All rights reserved.
Please cite this article as: Ad N, et al, Operative risk and preoperative hematocrit in bypass graft surgery: Role of gender and blood transfusion, Cardiovasc Revasc Med (2015), http://dx.doi.org/10.1016/j.carrev.2015.07.007
2
N. Ad et al. / Cardiovascular Revascularization Medicine xxx (2015) xxx–xxx
score values and were excluded from analyses. STS-predicted risk of mortality was calculated for all patients, using the model that was prospectively available at the time of surgery for each patient [26]. This study was approved by our institutional review board, and a waiver of consent was granted (IRB no. 06.022 and 12.055). The primary outcome was a composite variable that included any major morbidity and was defined as one or more of the following STSdefined events: perioperative myocardial infarction, deep sternal wound infection, permanent stroke, prolonged ventilation (N 24 hours), pneumonia, reoperation for bleeding, perioperative renal failure, reoperation for cardiac reasons, and operative mortality (b30 days) [26]. Blood product transfusion was defined as the receipt of any blood product during the intraoperative and postoperative period prior to discharge. Our institutional protocol for blood product transfusion has been described previously [27].
2.2. Statistical analyses All analyses were conducted using SPSS 17.0 software (SPSS Inc., Chicago, IL), and a two-sided P of b0.05 was considered statistically significant. Continuous data are presented as mean ± standard deviation, and categorical data are presented as frequency (percent), unless otherwise noted. Comparisons of male and female patients on preoperative characteristics and perioperative outcomes were evaluated using chisquare test or Fisher’s exact test for categorical variables and Student’s t test or Mann–Whitney U test for continuous variables, as appropriate given the assumptions of each test. Univariate logistic regressions were conducted to examine the unadjusted impact of preoperative Hct on major morbidity. Spline curve graphs were constructed by plotting the predicted probabilities calculated from these analyses against the preoperative Hct level using spline interpolation to illustrate the effects in graphical form separately by gender. Multivariate logistic regressions examining predictors for blood product transfusion selected a priori were conducted separately by gender and included the predictor variables of age, body mass index (BMI), STS risk score, preoperative Hct, and the interaction of STS risk score with preoperative Hct. Similarly, multivariate logistic regressions that examined the predictors for major morbidity selected a priori were conducted separately by gender and included the predictor variables of age, BMI, STS risk score, preoperative Hct, and the interaction of STS risk score with preoperative Hct. In a second step of the multivariate analyses examining predictors for major morbidity, blood product transfusion was added to these gender-specific models as a predictor for major morbidity. All regression equations were conducted using the “Enter” method.
3. Results The mean age of the patients in this sample was 63.2 ± 10.1 years, the mean STS risk score was 1.3 ± 1.8%, and 19% of patients were female. The female patients were older (65 vs. 63 years, P b 0.001) and had greater STS operative risk (2.3% vs. 1.1%, P b 0.001) and lower preoperative Hct (35.4% vs. 39.7%, P b 0.001) than male patients (Table 1). Female patients also had a higher prevalence of preoperative comorbid conditions such as diabetes, hypertension, and previous cerebrovascular accident (P b 0.001). 3.1. Blood transfusion Blood transfusion at any point during hospital stay was more likely in female patients than in male patients (26% vs. 12%, P b 0.001), and this relationship remained when patients were divided into those receiving intraoperative (15% vs. 6%, P b 0.001) and postoperative (18% vs. 9%, P b 0.001) blood products. Red blood cells (RBC) were more likely to be transfused in female patients than in male patients (26% vs. 10%, P b 0.001), but females and males were similar on non-RBC blood product transfusion (9% vs. 8%, P = 0.362). Multivariate regression analyses by gender revealed that lower BMI (odds ratio [OR] = 0.94, 95% confidence interval [CI] = 0.91–0.96, P b 0.001) and lower preoperative Hct (OR = 0.87, 95% CI = 0.84–0.91, P b 0.001) were predictive of blood transfusion in male patients, whereas older age (OR = 1.03, 95% CI = 1.01–1.05, P = 0.017), lower BMI (OR = 0.95, 95% CI = 0.91–0.98, P = 0.003), and lower Hct (OR = 0.86, 95% CI = 0.80–0.92, P b 0.001) were predictive of blood transfusion in female patients. 3.2. Major morbidity Incidence of major morbidity was greater in female patients than in male patients (12% vs. 7%, P b 0.001). Among patients who experienced an event classified as a major morbidity (n = 212), 70% had a single event, whereas the other 30% had more than one event. No differences were seen in the percentages of females and males who experienced multiple major events (33% vs. 29%, P = 0.600). When the incidences of individual outcomes included in the composite of major morbidity were compared, operative mortality was found to be similar for female and male patients (1.1% vs. 0.7%, P = 0.266), but females had a greater incidence of permanent stroke (2.3% vs. 0.7%, P = 0.001) and prolonged ventilation (N 24 hours; 7% vs. 4%, P b 0.001) than male patients (Table 2). The observed-to-expected (O/E) ratio for operative mortality for the total sample was 0.57; the O/E ratio was 0.49 for females and 0.60 for males.
Table 1 Patient characteristics by gender. Characteristic
All Patients (N = 2757)
Male (n = 2232)
Female (n = 525)
P
Age (years) STS-predicted mortality risk (%) Preoperative Hct (%) BMI (kg/m2) Ejection fraction (%) Ejection fraction b30% Congestive heart failure Hypertension Dyslipidemia Diabetes mellitus Chronic pulmonary disease Peripheral vascular disease Previous cerebrovascular accident Preoperative creatinine N2 mg/dL Dialysis Cardiopulmonary bypass time (min) Urgent status
63.2 ± 10.1 1.3 ± 1.8 38.9 ± 4.8 29.3 ± 5.6 53.6 ± 11.6 111 (4) 310 (11) 2259 (82) 2364 (86) 1132 (41) 555 (20) 282 (10) 151 (5) 126 (5) 79 (3) 90.1 ± 26.6 1491 (54)
62.7 ± 9.9 1.1 ± 1.4 39.7 ± 4.5 29.2 ± 5.3 53.4 ± 11.5 94 (4) 219 (10) 1801 (81) 1906 (85) 861 (39) 435 (20) 219 (10) 105 (5) 91 (4) 53 (2) 91.0 ± 26.8 1186 (53)
65.1 ± 10.4 2.3 ± 2.9 35.4 ± 4.5 29.7 ± 6.8 54.4 ± 11.9 17 (3) 91 (17) 458 (87) 458 (87) 271 (52) 120 (23) 63 (12) 46 (9) 35 (7) 26 (5) 85.8 ± 25.2 305 (58)
b0.001 b0.001 b0.001 0.077 0.077 0.307 b0.001 b0.001 0.277 b0.001 0.083 0.137 b0.001 0.011 0.001 b0.001 0.040
Please cite this article as: Ad N, et al, Operative risk and preoperative hematocrit in bypass graft surgery: Role of gender and blood transfusion, Cardiovasc Revasc Med (2015), http://dx.doi.org/10.1016/j.carrev.2015.07.007
N. Ad et al. / Cardiovascular Revascularization Medicine xxx (2015) xxx–xxx Table 2 Incidence of individual outcomes comprising major morbidity by gender.
3
Table 3 Multivariate logistic regression models predicting major morbidity by gender.
Characteristic
All Patients (N = 2757)
Male (n = 2232)
Female (n = 525)
P
Variable
Myocardial infarction Deep sternal wound infection Permanent stroke Prolonged ventilation Pneumonia Reoperation for bleeding Reoperation for cardiac reason Renal failure Operative mortality (b30 days)
1 (0.04) 7 (0.3) 28 (1) 123 (5) 39 (1) 28 (1) 14 (0.5) 33 (1) 21 (0.8)
1 (0.04) 7 (0.3) 16 (0.7) 84 (4) 28 (1) 22 (1) 12 (0.5) 23 (1) 15 (0.7)
0 0 12 (2) 39 (7) 11 (2) 6 (1) 2 (0.4) 10 (2) 6 (1)
N0.999 0.359 0.001 b0.001 0.142 0.747 N0.999 0.097 0.266
Age (years) BMI (kg/m2) STS mortality risk (%) Preoperative Hct (%) STS risk by preoperative Hct Blood transfusion
In univariate analyses, lower preoperative Hct was significantly predictive of major morbidity in both males (OR = 0.89, 95% CI = 0.86–0.92, P b 0.001) and females (OR = 0.92, 95% CI = 0.87–0.98, P = 0.005; Fig. 1). Multivariate analyses by gender, before blood transfusion was included, revealed that in males, higher BMI (OR = 1.04, 95% CI = 1.01–1.07, P = 0.004) and lower preoperative Hct (OR = 0.90, 95% CI = 0.85–0.94, P b 0.001) were significant predictors of major morbidity (c-statistic = 0.70). However, in females, none of the factors in the model predicting major morbidity (age, BMI, STS risk score, preoperative Hct) were significant when evaluated together (c-statistic = 0.66). 3.3. Effect of blood transfusion on major morbidity The addition of blood transfusion to these multivariate models resulted in two different predictive models for the two genders (Table 3). In females, none of the other predictors for major morbidity were significant, but major morbidity was found to be 4.5 times more likely in female patients with blood transfusions (OR = 4.56, 95% CI = 2.43–8.55, P b 0.001; c-statistic = 0.76). In males, higher BMI (OR = 1.07, 95% CI = 1.04–1.10, P b 0.001), lower preoperative Hct (OR = 0.94, 95% CI = 0.90–0.99, P = 0.017), and the interaction of STS score with Hct (OR = 1.02, 95% CI = 1.001–1.04, P = 0.045) were all significant predictors for major morbidity, whereas blood transfusion was also found to be a strong predictor (OR = 9.22, 95% CI = 6.20–13.69, P b 0.001; c-statistic = 0.79). These analyses found that major morbidity was more than 9 times more likely in male patients who had blood transfusion at some point during their hospital stay. Among female patients, those who received blood transfusion had an O/E ratio for operative mortality of 1.19 (P = 0.67), whereas those
Male (n = 2232)
Female (n = 525)
OR
95% CI
OR
95% CI
0.99 1.07 0.62 0.94 1.02 9.22
0.97–1.007 1.04–1.10 0.33–1.19 0.90–0.99 1.001–1.04 6.20–13.69
0.995 1.02 1.09 0.97 1.00 4.56
0.97–1.03 0.97–1.06 0.55–2.17 0.89–1.06 0.98–1.02 2.43–8.55
who did not receive blood transfusion had an O/E ratio of 0 (P = 0.007). Among male patients, those who received blood transfusion had an O/E ratio for operative mortality of 1.57 (P = 0.17), whereas those who did not receive blood transfusion had an O/E ratio of 0.31 (P = 0.003). These analyses showed that significantly fewer patients died during the operative period than would be expected according to STSpredicted risk, but only if they did not receive blood product transfusion. 4. Discussion In this retrospective analysis, we looked at operative outcomes for patients who underwent first-time, nonemergent, isolated CABG at our institution between 2007 and 2014. We found that predictors for major morbidity differed between men and women when blood transfusion was added to the multivariate analysis. In women, blood transfusion was the only factor in the model that was predictive of major morbidity; however, in men, lower preoperative Hct and the interaction between STS score and Hct, in addition to blood transfusion, were predictive of major morbidity. The female patients were older and had lower preoperative Hct and greater preoperative morbidity than male patients. In this respect, our patients reflected the findings of other studies showing that women are older and at a later stage in the disease process than men at the time of CABG [11]. It may be that when women present for cardiac surgery, the disease process is too far advanced for other factors to ameliorate their risk. Our results reflect the known differences between women and men in outcomes of CABG surgery [6,7,28]. Although it has been observed that the differences in CABG outcomes are influenced by differences in preoperative clinical characteristics of women and men [7], we found that in women, none of the factors in the model predicting for major morbidity (age, BMI, STS risk score, preoperative Hct) were significant when evaluated together. In contrast, BMI and lower preoperative Hct were significant predictors of major morbidity in men. Similarly, we found a significant difference between men and women in the likelihood of perioperative blood transfusion. However, only lower preoperative Hct was predictive of blood transfusion in male patients, whereas older age in addition to low Hct were predictive of blood transfusion in females. Numerous studies have found female sex to be an independent predictor of operative mortality [6,9,10,12,28] and blood transfusion [18,21,29] in CABG. Our results add a unique observation to what is known about this gender discrepancy by illuminating differences in major outcomes that were not attributable to preoperative clinical characteristics in the patient population we studied. Further studies should focus on gender-specific factors that increase the risks of perioperative morbidity and mortality in women undergoing CABG. 4.1. Limitations
Fig. 1. Predicted probability of major morbidity by preoperative Hct level in males (solid line) and females (dashed line).
Our results may be limited by a relatively small event rate and reduced sample size when separating the sample by gender. It may be that the effects we observed in male patients are relatively smaller than the results of our analyses suggest or the lack of some significant findings in female patients is due to the smaller sample size. However,
Please cite this article as: Ad N, et al, Operative risk and preoperative hematocrit in bypass graft surgery: Role of gender and blood transfusion, Cardiovasc Revasc Med (2015), http://dx.doi.org/10.1016/j.carrev.2015.07.007
4
N. Ad et al. / Cardiovascular Revascularization Medicine xxx (2015) xxx–xxx
the preoperative characteristics and outcomes we found with regard to gender differences are in line with those reported in the rest of the abundant literature in this area. 4.2. Summary Examining operative outcomes for patients who underwent firsttime, nonemergent, isolated CABG at our institution between 2007 and 2014, we found that predictors for major morbidity differed between men and women, especially when blood transfusion was added to the multivariate analysis. In women, blood transfusion alone was predictive of major morbidity; whereas in men, higher BMI, lower preoperative Hct, and the interaction between STS score and Hct, in addition to blood transfusion, were predictive of major morbidity. These results indicate that preoperative characteristics were not independently predictive of major morbidity in women undergoing first-time, nonemergent, isolated CABG surgery. References [1] U.S. Department of Health and Human Services. 2011 National Blood Collection and Utilization Survey Report. http://www.hhs.gov/ash/bloodsafety/2011-nbcus.pdf. Updated 2013. Accessed November 17, 2014. [2] Bennett-Guerrero E, Zhao Y, O'Brien SM, et al. Variation in use of blood transfusion in coronary artery bypass graft surgery. JAMA 2010;304(14):1568–75. [3] Epstein AJ, Polsky D, Yang F, Yang L, Groeneveld PW. Coronary revascularization trends in the United States, 2001–2008. JAMA 2011;305(17):1769–76. [4] Society of Thoracic Surgeons Blood Conservation Guideline Task ForceFerraris VA, Brown JR, et al. 2011 Update to the Society of Thoracic Surgeons and the Society of Cardiovascular Anesthesiologists Blood Conservation Clinical Practice Guidelines. Ann Thorac Surg 2011;91(3):944–82. [5] Go AS, Mozaffarian D, Roger VL, et al. Heart disease and stroke statistics — 2014 update: a report from the American Heart Association. Circulation 2014;129(3): e28-292. [6] Blankstein R, Ward RP, Arnsdorf M, Jones B, Lou YB, Pine M. Female gender is an independent predictor of operative mortality after coronary artery bypass graft surgery: contemporary analysis of 31 Midwestern hospitals. Circulation 2005; 112(9 Suppl):323–7. [7] Abramov D, Tamariz MG, Sever JY, et al. The influence of gender on the outcome of coronary artery bypass surgery. Ann Thorac Surg 2000;70(3):800–5. [8] Edwards ML, Albert NM, Wang C, Apperson-Hansen C. 1993–2003 gender differences in coronary artery revascularization: has anything changed? J Cardiovasc Nurs 2005; 20(6):461–7. [9] Miskowiec DL, Walczak A, Jaszewski R, Marcinkiewicz A, Ostrowski S. Independent predictors of early mortality after CABG in single centre experience — does the gender matter? Kardiol Pol 2015;73(2):109–17. [10] Bukkapatnam RN, Yeo KK, Li Z, Amsterdam EA. Operative mortality in women and men undergoing coronary artery bypass grafting (from the California Coronary Artery Bypass Grafting Outcomes Reporting Program). Am J Cardiol 2010;105(3): 339–42.
[11] Woods SE, Noble G, Smith JM, Hasselfeld K. The influence of gender in patients undergoing coronary artery bypass graft surgery: an eight-year prospective hospitalized cohort study. J Am Coll Surg 2003;196(3):428–34. [12] Kim C, Redberg RF, Pavlic T, Eagle KA. A systematic review of gender differences in mortality after coronary artery bypass graft surgery and percutaneous coronary interventions. Clin Cardiol 2007;30(10):491–5. [13] Hung M, Besser M, Sharples LD, Nair SK, Klein AA. The prevalence and association with transfusion, intensive care unit stay and mortality of pre-operative anaemia in a cohort of cardiac surgery patients. Anaesthesia 2011;66(9):812–8. [14] Karkouti K, Wijeysundera DN, Beattie WS. Reducing Bleeding in Cardiac Surgery (RBC) Investigators. Risk associated with preoperative anemia in cardiac surgery: a multicenter cohort study. Circulation 2008;117(4):478–84. [15] Kulier A, Levin J, Moser R, et al. Impact of preoperative anemia on outcome in patients undergoing coronary artery bypass graft surgery. Circulation 2007; 116(5):471–9. [16] Loor G, Li L, Sabik JF, Rajeswaran J, Blackstone EH, Koch CG. Nadir hematocrit during cardiopulmonary bypass: end-organ dysfunction and mortality. J Thorac Cardiovasc Surg 2012;144(3):654–662.e4. [17] Swaminathan M, Phillips-Bute BG, Conlon PJ, Smith PK, Newman MF, Stafford-Smith M. The association of lowest hematocrit during cardiopulmonary bypass with acute renal injury after coronary artery bypass surgery. Ann Thorac Surg 2003;76(3): 784–91. [18] van Straten AH, Hamad MA, van Zundert AJ, Martens EJ, Schonberger JP, de Wolf AM. Preoperative hemoglobin level as a predictor of survival after coronary artery bypass grafting: a comparison with the matched general population. Circulation 2009; 120(2):118–25. [19] Williams ML, He X, Rankin JS, Slaughter MS, Gammie JS. Preoperative hematocrit is a powerful predictor of adverse outcomes in coronary artery bypass graft surgery: a report from the Society of Thoracic Surgeons Adult Cardiac Surgery Database. Ann Thorac Surg 2013;96(5):1628–34. [20] Zindrou D, Taylor KM, Bagger JP. Preoperative haemoglobin concentration and mortality rate after coronary artery bypass surgery. Lancet 2002;359(9319):1747–8. [21] Elmistekawy EM, Errett L, Fawzy HF. Predictors of packed red cell transfusion after isolated primary coronary artery bypass grafting — the experience of a single cardiac center: a prospective observational study. J Cardiothorac Surg 2009;4:20. [22] Covin R, O'Brien M, Grunwald G, et al. Factors affecting transfusion of fresh frozen plasma, platelets, and red blood cells during elective coronary artery bypass graft surgery. Arch Pathol Lab Med 2003;127(4):415–23. [23] Koch CG, Li L, Duncan AI, et al. Transfusion in coronary artery bypass grafting is associated with reduced long-term survival. Ann Thorac Surg 2006;81(5):1650–7. [24] Kuduvalli M, Oo AY, Newall N, et al. Effect of peri-operative red blood cell transfusion on 30-day and 1-year mortality following coronary artery bypass surgery. Eur J Cardiothorac Surg 2005;27(4):592–8. [25] Scott BH, Seifert FC, Grimson R. Blood transfusion is associated with increased resource utilisation, morbidity and mortality in cardiac surgery. Ann Card Anaesth 2008;11(1):15–9. [26] Society of Thoracic Surgeons. Society of Thoracic Surgeons Adult Cardiac Surgery Database data specifications, version 2.81. http://www.sts.org/sites/default/files/ documents/STSAdultCVDataSpecificationsV2_81.pdf. [Accessed May 21, 2015]. [27] Ad N, Massimiano PS, Burton NA, et al. Effect of patient age on blood product transfusion after cardiac surgery. J Thorac Cardiovasc Surg 2015;150:209–14. [28] Edwards FH, Carey JS, Grover FL, Bero JW, Hartz RS. Impact of gender on coronary bypass operative mortality. Ann Thorac Surg 1998;66(1):125–31. [29] Karkouti K, Cohen MM, McCluskey SA, Sher GD. A multivariable model for predicting the need for blood transfusion in patients undergoing first-time elective coronary bypass graft surgery. Transfusion 2001;41(10):1193–203.
Please cite this article as: Ad N, et al, Operative risk and preoperative hematocrit in bypass graft surgery: Role of gender and blood transfusion, Cardiovasc Revasc Med (2015), http://dx.doi.org/10.1016/j.carrev.2015.07.007
Contents lists available at ScienceDirect
Cardiovascular Revascularization Medicine
Operative risk and preoperative hematocrit in bypass graft surgery: Role of gender and blood transfusion Niv Ad ⁎, Sari D. Holmes, Paul S. Massimiano, Dan Spiegelstein, Deborah J. Shuman, Graciela Pritchard, Linda Halpin Inova Heart and Vascular Institute, 3300 Gallows Road, Suite 3100, Falls Church, VA 22042, USA
a r t i c l e
i n f o
Article history: Received 22 May 2015 Accepted 15 July 2015 Available online xxxx Keywords: Blood management Outcomes CABG Gender
a b s t r a c t Background: The association between lower preoperative hematocrit (Hct) and risk for morbidity/mortality after cardiac surgery is well established. We examined whether the impact of low preoperative Hct on outcome is modified by blood transfusion and operative risk in women and men undergoing nonemergent CABG surgery. Methods: Patients having nonemergent, first-time, isolated CABG were included (N = 2757). Logistic regressions assessed effect of hematocrit on major perioperative morbidity/mortality separately by males (n = 2232) and females (n = 525). Results: Mean age was 63.2 ± 10.1 years, preoperative hematocrit was 38.9 ± 4.8%, and STS risk score was 1.3 ± 1.8%. Blood transfusion was more likely in female patients (26% vs. 12%, P b 0.001). Multivariate analyses revealed that lower body mass index and lower preoperative hematocrit predicted transfusion in males and females, whereas older age (OR = 1.03, P = 0.017) also predicted transfusion in females. Major morbidity was also more likely in female patients (12% vs. 7%, P b 0.001). In multivariate analyses, blood transfusion was the only predictive factor for major morbidity in females (OR = 4.56, P b 0.001). In males, higher body mass index (OR = 1.07, P b 0.001), lower hematocrit (OR = 0.94, P = 0.017), interaction of STS score with hematocrit (OR = 1.02, P = 0.045), and blood transfusion (OR = 9.22, P b 0.001) were significant predictors for major morbidity. Conclusions: This study showed females were more likely to have blood transfusion and major morbidities after nonemergent CABG. Traditional factors that have been found to predict outcomes, such as hematocrit and STS risk, were related only to major morbidity in male patients. However, blood transfusion negatively impacted major outcome after nonemergent CABG surgery across all STS risk levels in both genders. © 2015 Elsevier Inc. All rights reserved.
1. Introduction Cardiac surgery accounts for the majority of blood transfusions in the United States each year [1,2]. Nearly 50,000 coronary artery bypass graft (CABG) procedures were performed in the United States in 2008 [3], about half of which involved transfusion of blood products [4]. Despite the overall decline in CABG morbidity and mortality since the procedure was first performed [5], a disproportionate number of operative deaths and major adverse outcomes still occur in women who undergo this surgery [6–8]. Women make up less than one-third of all patients undergoing CABG but account for nearly twice as many operative deaths than men [5,6,9]. In light of these statistics, it is not surprising that female gender has been shown to be an independent risk factor for perioperative mortality in isolated CABG [9–12]. Particularly in patients undergoing CABG surgery, the association between preoperative low hematocrit (Hct) and the risk of transfusion and adverse surgical outcomes is well established [13–20]. Low ⁎ Corresponding author at: Cardiac Surgery Research, Inova Heart and Vascular Institute, 3300 Gallows Road, Suite 3100, Falls Church, VA 22042, USA. Tel.: +1 703 776 8025; fax: +1 703 776 8303. E-mail address: [email protected] (N. Ad).
preoperative Hct is one of the most frequent indications for intraoperative transfusion in CABG patients [21], and transfusion is itself a wellknown risk factor for adverse outcomes in CABG [22–25]. In this study, we examined whether the impact of low preoperative Hct on outcomes was gender specific for patients undergoing nonemergent isolated CABG, taking blood transfusion and operative risk into account. We hypothesized that the factors that are important in the relationship of Hct and outcomes would differ for male and female patients. 2. Materials and methods 2.1. Study sample The sample for this observational study consisted of all consecutive patients who underwent nonemergent, first-time, isolated CABG between January 2007 and October 2014 (N = 2757). CABG surgery was performed with cardiopulmonary bypass by standard surgical procedure, using a midsternotomy approach. Data were collected prospectively as part of our local Society of Thoracic Surgeons (STS) Adult Cardiac Surgery database, and all patients included in analyses had complete data on the variables of interest. An additional 388 patients met inclusion criteria during this time frame but were missing Hct or STS risk
http://dx.doi.org/10.1016/j.carrev.2015.07.007 1553-8389/© 2015 Elsevier Inc. All rights reserved.
Please cite this article as: Ad N, et al, Operative risk and preoperative hematocrit in bypass graft surgery: Role of gender and blood transfusion, Cardiovasc Revasc Med (2015), http://dx.doi.org/10.1016/j.carrev.2015.07.007
2
N. Ad et al. / Cardiovascular Revascularization Medicine xxx (2015) xxx–xxx
score values and were excluded from analyses. STS-predicted risk of mortality was calculated for all patients, using the model that was prospectively available at the time of surgery for each patient [26]. This study was approved by our institutional review board, and a waiver of consent was granted (IRB no. 06.022 and 12.055). The primary outcome was a composite variable that included any major morbidity and was defined as one or more of the following STSdefined events: perioperative myocardial infarction, deep sternal wound infection, permanent stroke, prolonged ventilation (N 24 hours), pneumonia, reoperation for bleeding, perioperative renal failure, reoperation for cardiac reasons, and operative mortality (b30 days) [26]. Blood product transfusion was defined as the receipt of any blood product during the intraoperative and postoperative period prior to discharge. Our institutional protocol for blood product transfusion has been described previously [27].
2.2. Statistical analyses All analyses were conducted using SPSS 17.0 software (SPSS Inc., Chicago, IL), and a two-sided P of b0.05 was considered statistically significant. Continuous data are presented as mean ± standard deviation, and categorical data are presented as frequency (percent), unless otherwise noted. Comparisons of male and female patients on preoperative characteristics and perioperative outcomes were evaluated using chisquare test or Fisher’s exact test for categorical variables and Student’s t test or Mann–Whitney U test for continuous variables, as appropriate given the assumptions of each test. Univariate logistic regressions were conducted to examine the unadjusted impact of preoperative Hct on major morbidity. Spline curve graphs were constructed by plotting the predicted probabilities calculated from these analyses against the preoperative Hct level using spline interpolation to illustrate the effects in graphical form separately by gender. Multivariate logistic regressions examining predictors for blood product transfusion selected a priori were conducted separately by gender and included the predictor variables of age, body mass index (BMI), STS risk score, preoperative Hct, and the interaction of STS risk score with preoperative Hct. Similarly, multivariate logistic regressions that examined the predictors for major morbidity selected a priori were conducted separately by gender and included the predictor variables of age, BMI, STS risk score, preoperative Hct, and the interaction of STS risk score with preoperative Hct. In a second step of the multivariate analyses examining predictors for major morbidity, blood product transfusion was added to these gender-specific models as a predictor for major morbidity. All regression equations were conducted using the “Enter” method.
3. Results The mean age of the patients in this sample was 63.2 ± 10.1 years, the mean STS risk score was 1.3 ± 1.8%, and 19% of patients were female. The female patients were older (65 vs. 63 years, P b 0.001) and had greater STS operative risk (2.3% vs. 1.1%, P b 0.001) and lower preoperative Hct (35.4% vs. 39.7%, P b 0.001) than male patients (Table 1). Female patients also had a higher prevalence of preoperative comorbid conditions such as diabetes, hypertension, and previous cerebrovascular accident (P b 0.001). 3.1. Blood transfusion Blood transfusion at any point during hospital stay was more likely in female patients than in male patients (26% vs. 12%, P b 0.001), and this relationship remained when patients were divided into those receiving intraoperative (15% vs. 6%, P b 0.001) and postoperative (18% vs. 9%, P b 0.001) blood products. Red blood cells (RBC) were more likely to be transfused in female patients than in male patients (26% vs. 10%, P b 0.001), but females and males were similar on non-RBC blood product transfusion (9% vs. 8%, P = 0.362). Multivariate regression analyses by gender revealed that lower BMI (odds ratio [OR] = 0.94, 95% confidence interval [CI] = 0.91–0.96, P b 0.001) and lower preoperative Hct (OR = 0.87, 95% CI = 0.84–0.91, P b 0.001) were predictive of blood transfusion in male patients, whereas older age (OR = 1.03, 95% CI = 1.01–1.05, P = 0.017), lower BMI (OR = 0.95, 95% CI = 0.91–0.98, P = 0.003), and lower Hct (OR = 0.86, 95% CI = 0.80–0.92, P b 0.001) were predictive of blood transfusion in female patients. 3.2. Major morbidity Incidence of major morbidity was greater in female patients than in male patients (12% vs. 7%, P b 0.001). Among patients who experienced an event classified as a major morbidity (n = 212), 70% had a single event, whereas the other 30% had more than one event. No differences were seen in the percentages of females and males who experienced multiple major events (33% vs. 29%, P = 0.600). When the incidences of individual outcomes included in the composite of major morbidity were compared, operative mortality was found to be similar for female and male patients (1.1% vs. 0.7%, P = 0.266), but females had a greater incidence of permanent stroke (2.3% vs. 0.7%, P = 0.001) and prolonged ventilation (N 24 hours; 7% vs. 4%, P b 0.001) than male patients (Table 2). The observed-to-expected (O/E) ratio for operative mortality for the total sample was 0.57; the O/E ratio was 0.49 for females and 0.60 for males.
Table 1 Patient characteristics by gender. Characteristic
All Patients (N = 2757)
Male (n = 2232)
Female (n = 525)
P
Age (years) STS-predicted mortality risk (%) Preoperative Hct (%) BMI (kg/m2) Ejection fraction (%) Ejection fraction b30% Congestive heart failure Hypertension Dyslipidemia Diabetes mellitus Chronic pulmonary disease Peripheral vascular disease Previous cerebrovascular accident Preoperative creatinine N2 mg/dL Dialysis Cardiopulmonary bypass time (min) Urgent status
63.2 ± 10.1 1.3 ± 1.8 38.9 ± 4.8 29.3 ± 5.6 53.6 ± 11.6 111 (4) 310 (11) 2259 (82) 2364 (86) 1132 (41) 555 (20) 282 (10) 151 (5) 126 (5) 79 (3) 90.1 ± 26.6 1491 (54)
62.7 ± 9.9 1.1 ± 1.4 39.7 ± 4.5 29.2 ± 5.3 53.4 ± 11.5 94 (4) 219 (10) 1801 (81) 1906 (85) 861 (39) 435 (20) 219 (10) 105 (5) 91 (4) 53 (2) 91.0 ± 26.8 1186 (53)
65.1 ± 10.4 2.3 ± 2.9 35.4 ± 4.5 29.7 ± 6.8 54.4 ± 11.9 17 (3) 91 (17) 458 (87) 458 (87) 271 (52) 120 (23) 63 (12) 46 (9) 35 (7) 26 (5) 85.8 ± 25.2 305 (58)
b0.001 b0.001 b0.001 0.077 0.077 0.307 b0.001 b0.001 0.277 b0.001 0.083 0.137 b0.001 0.011 0.001 b0.001 0.040
Please cite this article as: Ad N, et al, Operative risk and preoperative hematocrit in bypass graft surgery: Role of gender and blood transfusion, Cardiovasc Revasc Med (2015), http://dx.doi.org/10.1016/j.carrev.2015.07.007
N. Ad et al. / Cardiovascular Revascularization Medicine xxx (2015) xxx–xxx Table 2 Incidence of individual outcomes comprising major morbidity by gender.
3
Table 3 Multivariate logistic regression models predicting major morbidity by gender.
Characteristic
All Patients (N = 2757)
Male (n = 2232)
Female (n = 525)
P
Variable
Myocardial infarction Deep sternal wound infection Permanent stroke Prolonged ventilation Pneumonia Reoperation for bleeding Reoperation for cardiac reason Renal failure Operative mortality (b30 days)
1 (0.04) 7 (0.3) 28 (1) 123 (5) 39 (1) 28 (1) 14 (0.5) 33 (1) 21 (0.8)
1 (0.04) 7 (0.3) 16 (0.7) 84 (4) 28 (1) 22 (1) 12 (0.5) 23 (1) 15 (0.7)
0 0 12 (2) 39 (7) 11 (2) 6 (1) 2 (0.4) 10 (2) 6 (1)
N0.999 0.359 0.001 b0.001 0.142 0.747 N0.999 0.097 0.266
Age (years) BMI (kg/m2) STS mortality risk (%) Preoperative Hct (%) STS risk by preoperative Hct Blood transfusion
In univariate analyses, lower preoperative Hct was significantly predictive of major morbidity in both males (OR = 0.89, 95% CI = 0.86–0.92, P b 0.001) and females (OR = 0.92, 95% CI = 0.87–0.98, P = 0.005; Fig. 1). Multivariate analyses by gender, before blood transfusion was included, revealed that in males, higher BMI (OR = 1.04, 95% CI = 1.01–1.07, P = 0.004) and lower preoperative Hct (OR = 0.90, 95% CI = 0.85–0.94, P b 0.001) were significant predictors of major morbidity (c-statistic = 0.70). However, in females, none of the factors in the model predicting major morbidity (age, BMI, STS risk score, preoperative Hct) were significant when evaluated together (c-statistic = 0.66). 3.3. Effect of blood transfusion on major morbidity The addition of blood transfusion to these multivariate models resulted in two different predictive models for the two genders (Table 3). In females, none of the other predictors for major morbidity were significant, but major morbidity was found to be 4.5 times more likely in female patients with blood transfusions (OR = 4.56, 95% CI = 2.43–8.55, P b 0.001; c-statistic = 0.76). In males, higher BMI (OR = 1.07, 95% CI = 1.04–1.10, P b 0.001), lower preoperative Hct (OR = 0.94, 95% CI = 0.90–0.99, P = 0.017), and the interaction of STS score with Hct (OR = 1.02, 95% CI = 1.001–1.04, P = 0.045) were all significant predictors for major morbidity, whereas blood transfusion was also found to be a strong predictor (OR = 9.22, 95% CI = 6.20–13.69, P b 0.001; c-statistic = 0.79). These analyses found that major morbidity was more than 9 times more likely in male patients who had blood transfusion at some point during their hospital stay. Among female patients, those who received blood transfusion had an O/E ratio for operative mortality of 1.19 (P = 0.67), whereas those
Male (n = 2232)
Female (n = 525)
OR
95% CI
OR
95% CI
0.99 1.07 0.62 0.94 1.02 9.22
0.97–1.007 1.04–1.10 0.33–1.19 0.90–0.99 1.001–1.04 6.20–13.69
0.995 1.02 1.09 0.97 1.00 4.56
0.97–1.03 0.97–1.06 0.55–2.17 0.89–1.06 0.98–1.02 2.43–8.55
who did not receive blood transfusion had an O/E ratio of 0 (P = 0.007). Among male patients, those who received blood transfusion had an O/E ratio for operative mortality of 1.57 (P = 0.17), whereas those who did not receive blood transfusion had an O/E ratio of 0.31 (P = 0.003). These analyses showed that significantly fewer patients died during the operative period than would be expected according to STSpredicted risk, but only if they did not receive blood product transfusion. 4. Discussion In this retrospective analysis, we looked at operative outcomes for patients who underwent first-time, nonemergent, isolated CABG at our institution between 2007 and 2014. We found that predictors for major morbidity differed between men and women when blood transfusion was added to the multivariate analysis. In women, blood transfusion was the only factor in the model that was predictive of major morbidity; however, in men, lower preoperative Hct and the interaction between STS score and Hct, in addition to blood transfusion, were predictive of major morbidity. The female patients were older and had lower preoperative Hct and greater preoperative morbidity than male patients. In this respect, our patients reflected the findings of other studies showing that women are older and at a later stage in the disease process than men at the time of CABG [11]. It may be that when women present for cardiac surgery, the disease process is too far advanced for other factors to ameliorate their risk. Our results reflect the known differences between women and men in outcomes of CABG surgery [6,7,28]. Although it has been observed that the differences in CABG outcomes are influenced by differences in preoperative clinical characteristics of women and men [7], we found that in women, none of the factors in the model predicting for major morbidity (age, BMI, STS risk score, preoperative Hct) were significant when evaluated together. In contrast, BMI and lower preoperative Hct were significant predictors of major morbidity in men. Similarly, we found a significant difference between men and women in the likelihood of perioperative blood transfusion. However, only lower preoperative Hct was predictive of blood transfusion in male patients, whereas older age in addition to low Hct were predictive of blood transfusion in females. Numerous studies have found female sex to be an independent predictor of operative mortality [6,9,10,12,28] and blood transfusion [18,21,29] in CABG. Our results add a unique observation to what is known about this gender discrepancy by illuminating differences in major outcomes that were not attributable to preoperative clinical characteristics in the patient population we studied. Further studies should focus on gender-specific factors that increase the risks of perioperative morbidity and mortality in women undergoing CABG. 4.1. Limitations
Fig. 1. Predicted probability of major morbidity by preoperative Hct level in males (solid line) and females (dashed line).
Our results may be limited by a relatively small event rate and reduced sample size when separating the sample by gender. It may be that the effects we observed in male patients are relatively smaller than the results of our analyses suggest or the lack of some significant findings in female patients is due to the smaller sample size. However,
Please cite this article as: Ad N, et al, Operative risk and preoperative hematocrit in bypass graft surgery: Role of gender and blood transfusion, Cardiovasc Revasc Med (2015), http://dx.doi.org/10.1016/j.carrev.2015.07.007
4
N. Ad et al. / Cardiovascular Revascularization Medicine xxx (2015) xxx–xxx
the preoperative characteristics and outcomes we found with regard to gender differences are in line with those reported in the rest of the abundant literature in this area. 4.2. Summary Examining operative outcomes for patients who underwent firsttime, nonemergent, isolated CABG at our institution between 2007 and 2014, we found that predictors for major morbidity differed between men and women, especially when blood transfusion was added to the multivariate analysis. In women, blood transfusion alone was predictive of major morbidity; whereas in men, higher BMI, lower preoperative Hct, and the interaction between STS score and Hct, in addition to blood transfusion, were predictive of major morbidity. These results indicate that preoperative characteristics were not independently predictive of major morbidity in women undergoing first-time, nonemergent, isolated CABG surgery. References [1] U.S. Department of Health and Human Services. 2011 National Blood Collection and Utilization Survey Report. http://www.hhs.gov/ash/bloodsafety/2011-nbcus.pdf. Updated 2013. Accessed November 17, 2014. [2] Bennett-Guerrero E, Zhao Y, O'Brien SM, et al. Variation in use of blood transfusion in coronary artery bypass graft surgery. JAMA 2010;304(14):1568–75. [3] Epstein AJ, Polsky D, Yang F, Yang L, Groeneveld PW. Coronary revascularization trends in the United States, 2001–2008. JAMA 2011;305(17):1769–76. [4] Society of Thoracic Surgeons Blood Conservation Guideline Task ForceFerraris VA, Brown JR, et al. 2011 Update to the Society of Thoracic Surgeons and the Society of Cardiovascular Anesthesiologists Blood Conservation Clinical Practice Guidelines. Ann Thorac Surg 2011;91(3):944–82. [5] Go AS, Mozaffarian D, Roger VL, et al. Heart disease and stroke statistics — 2014 update: a report from the American Heart Association. Circulation 2014;129(3): e28-292. [6] Blankstein R, Ward RP, Arnsdorf M, Jones B, Lou YB, Pine M. Female gender is an independent predictor of operative mortality after coronary artery bypass graft surgery: contemporary analysis of 31 Midwestern hospitals. Circulation 2005; 112(9 Suppl):323–7. [7] Abramov D, Tamariz MG, Sever JY, et al. The influence of gender on the outcome of coronary artery bypass surgery. Ann Thorac Surg 2000;70(3):800–5. [8] Edwards ML, Albert NM, Wang C, Apperson-Hansen C. 1993–2003 gender differences in coronary artery revascularization: has anything changed? J Cardiovasc Nurs 2005; 20(6):461–7. [9] Miskowiec DL, Walczak A, Jaszewski R, Marcinkiewicz A, Ostrowski S. Independent predictors of early mortality after CABG in single centre experience — does the gender matter? Kardiol Pol 2015;73(2):109–17. [10] Bukkapatnam RN, Yeo KK, Li Z, Amsterdam EA. Operative mortality in women and men undergoing coronary artery bypass grafting (from the California Coronary Artery Bypass Grafting Outcomes Reporting Program). Am J Cardiol 2010;105(3): 339–42.
[11] Woods SE, Noble G, Smith JM, Hasselfeld K. The influence of gender in patients undergoing coronary artery bypass graft surgery: an eight-year prospective hospitalized cohort study. J Am Coll Surg 2003;196(3):428–34. [12] Kim C, Redberg RF, Pavlic T, Eagle KA. A systematic review of gender differences in mortality after coronary artery bypass graft surgery and percutaneous coronary interventions. Clin Cardiol 2007;30(10):491–5. [13] Hung M, Besser M, Sharples LD, Nair SK, Klein AA. The prevalence and association with transfusion, intensive care unit stay and mortality of pre-operative anaemia in a cohort of cardiac surgery patients. Anaesthesia 2011;66(9):812–8. [14] Karkouti K, Wijeysundera DN, Beattie WS. Reducing Bleeding in Cardiac Surgery (RBC) Investigators. Risk associated with preoperative anemia in cardiac surgery: a multicenter cohort study. Circulation 2008;117(4):478–84. [15] Kulier A, Levin J, Moser R, et al. Impact of preoperative anemia on outcome in patients undergoing coronary artery bypass graft surgery. Circulation 2007; 116(5):471–9. [16] Loor G, Li L, Sabik JF, Rajeswaran J, Blackstone EH, Koch CG. Nadir hematocrit during cardiopulmonary bypass: end-organ dysfunction and mortality. J Thorac Cardiovasc Surg 2012;144(3):654–662.e4. [17] Swaminathan M, Phillips-Bute BG, Conlon PJ, Smith PK, Newman MF, Stafford-Smith M. The association of lowest hematocrit during cardiopulmonary bypass with acute renal injury after coronary artery bypass surgery. Ann Thorac Surg 2003;76(3): 784–91. [18] van Straten AH, Hamad MA, van Zundert AJ, Martens EJ, Schonberger JP, de Wolf AM. Preoperative hemoglobin level as a predictor of survival after coronary artery bypass grafting: a comparison with the matched general population. Circulation 2009; 120(2):118–25. [19] Williams ML, He X, Rankin JS, Slaughter MS, Gammie JS. Preoperative hematocrit is a powerful predictor of adverse outcomes in coronary artery bypass graft surgery: a report from the Society of Thoracic Surgeons Adult Cardiac Surgery Database. Ann Thorac Surg 2013;96(5):1628–34. [20] Zindrou D, Taylor KM, Bagger JP. Preoperative haemoglobin concentration and mortality rate after coronary artery bypass surgery. Lancet 2002;359(9319):1747–8. [21] Elmistekawy EM, Errett L, Fawzy HF. Predictors of packed red cell transfusion after isolated primary coronary artery bypass grafting — the experience of a single cardiac center: a prospective observational study. J Cardiothorac Surg 2009;4:20. [22] Covin R, O'Brien M, Grunwald G, et al. Factors affecting transfusion of fresh frozen plasma, platelets, and red blood cells during elective coronary artery bypass graft surgery. Arch Pathol Lab Med 2003;127(4):415–23. [23] Koch CG, Li L, Duncan AI, et al. Transfusion in coronary artery bypass grafting is associated with reduced long-term survival. Ann Thorac Surg 2006;81(5):1650–7. [24] Kuduvalli M, Oo AY, Newall N, et al. Effect of peri-operative red blood cell transfusion on 30-day and 1-year mortality following coronary artery bypass surgery. Eur J Cardiothorac Surg 2005;27(4):592–8. [25] Scott BH, Seifert FC, Grimson R. Blood transfusion is associated with increased resource utilisation, morbidity and mortality in cardiac surgery. Ann Card Anaesth 2008;11(1):15–9. [26] Society of Thoracic Surgeons. Society of Thoracic Surgeons Adult Cardiac Surgery Database data specifications, version 2.81. http://www.sts.org/sites/default/files/ documents/STSAdultCVDataSpecificationsV2_81.pdf. [Accessed May 21, 2015]. [27] Ad N, Massimiano PS, Burton NA, et al. Effect of patient age on blood product transfusion after cardiac surgery. J Thorac Cardiovasc Surg 2015;150:209–14. [28] Edwards FH, Carey JS, Grover FL, Bero JW, Hartz RS. Impact of gender on coronary bypass operative mortality. Ann Thorac Surg 1998;66(1):125–31. [29] Karkouti K, Cohen MM, McCluskey SA, Sher GD. A multivariable model for predicting the need for blood transfusion in patients undergoing first-time elective coronary bypass graft surgery. Transfusion 2001;41(10):1193–203.
Please cite this article as: Ad N, et al, Operative risk and preoperative hematocrit in bypass graft surgery: Role of gender and blood transfusion, Cardiovasc Revasc Med (2015), http://dx.doi.org/10.1016/j.carrev.2015.07.007