HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Abstract Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to Personal Folders Download to citation manager Author home page(s): Joe R. Utley Permission Requests Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Utley, J. R. Articles by Johnson, H. D. Search for Related Content PubMed PubMed Citation Articles by Utley, J. R. Articles by Johnson, H. D. Related Collections Related Article

Ann Thorac Surg 1995;60:570-574
© 1995 The Society of Thoracic Surgeons

---

Original Articles: Cardiovascular

Intraoperative Blood Transfusion Is a Major Risk Factor for Coronary Artery Bypass Grafting in Women

Division of Cardiac Surgery, Spartanburg Regional Medical Center, Spartanburg, South Carolina

Accepted for publication April 3, 1995.

	Abstract

Top Footnotes Abstract Introduction Material and Methods Results Comment Acknowledgments References

 
Background. Women have been found to have greater mortality from coronary artery bypass grafting than men. Uncertainty exists regarding the causes of the differences in outcomes between men and women after coronary artery bypass grafting.

Methods. From a database of 2,569 patients having coronary bypass grafting we have determined factors that contribute to poorer outcomes in women compared with men.

Results. Women were found to have greater mortality, postoperative bleeding, and postoperative pulmonary failure than men (p < 0.05). There was no significant difference between men and women in postoperative renal failure, postoperative infection, postoperative stroke, or intraaortic balloon pump (p = not significant). Patient factors other than sex accounted for all the significant predictors (stepwise logistic regression) of mortality, postoperative bleeding, postoperative renal failure, postoperative pulmonary failure, postoperative stroke, need for intraaortic balloon pump, and postoperative infection (p < 0.05). Poorer outcomes in women are associated with greater need for transfusion during operation. Diabetes is predictive of renal failure and stroke.

Conclusions. Mortality and morbidity is less in men despite their higher preoperative creatinine level, greater incidence of reoperation, lower ejection fraction, and more common atherosclerosis of the ascending aorta.

	Introduction

Top Footnotes Abstract Introduction Material and Methods Results Comment Acknowledgments References

 
See also page 574.

Many studies have shown an increased mortality for coronary artery bypass grafting in women [1–9]. Women having coronary artery bypass grafting have been shown to differ from men in several respects. These differences include older age, smaller body size [2], smaller coronary artery size [2], greater incidence of incomplete revascularization [3], and more frequent early graft occlusion [3]. Women having coronary artery bypass grafting also have a greater incidence of diabetes and hypertension than men [5]. Some authors have attributed the greater risk in women to selection of women for operation with further advanced disease [10, 11]. Women were found more commonly to have unstable angina, post–myocardial infarction angina, congestive heart failure, and New York Heart Association class IV symptoms [10]. Other studies have shown that men were more likely to be subjected to catheterization and coronary artery bypass grafting with early disease than women [12, 13]. We have analyzed the clinical data of patients having coronary artery bypass grafting to determine possible causes of poorer outcomes in women.

	Material and Methods

Top Footnotes Abstract Introduction Material and Methods Results Comment Acknowledgments References

 
We collected data on 2,569 patients having coronary artery bypass grafting between October 1983 and April 1994. Data were recorded prospectively on clinical database software (Patient Analysis and Tracking System, Dendrite, Inc, Portland, OR). Data were transferred to SPSS/PC+ software (Statistical Package for the Social Sciences; SPSS, Inc, Chicago, IL) for t test, ² test, and stepwise logistic regression analysis.

The data included patient factors, operative factors, and postoperative factors. Definitions and criteria are as follows: Body mass index as a measure of obesity was determined after the method described by Frankel [14, 15]. Ejection fraction was determined at cardiac catheterization. The criterion for diabetes was the need for treatment with either oral hypoglycemics or insulin. Recent myocardial infarction was myocardial infarction diagnosed by electrocardiogram and isoenzymes within 6 weeks of operation. Coronary artery size index was determined by the mean of the diameter of the largest coronary probe that could easily be introduced into the coronary arteries at the site of arteriotomy. We used 1-, 1.5-, and 2-mm probes. Thus if a patient had two bypass grafts and one vessel would admit a 1-mm probe and the second vessel would admit a 2-mm probe, the coronary artery size index would be 1.5 (mean of 1 and 2). A coronary artery size index was calculated for each patient. We determined the 1, 2, 3-vessel disease index by recording for each patient the presence of one-, two-, or three-vessel coronary artery disease. Atherosclerosis of ascending aorta was recorded when it was observed by the surgeon during the operation.

Our protocols call for transfusion during operation if the hematocrit is less than 20% during cardiopulmonary bypass. No patients were transfused before bypass. Transfusion needs during operation but after cardiopulmonary bypass are met with blood from the heart lung machine and the cell-saving device. First transfusion during operation was always given during cardiopulmonary bypass. Patients who received transfusions only postoperatively were not designated as having transfusion during operation.

Major postoperative complications were defined as follows: Mortality was death during hospitalization or within 30 days of operation. Intraaortic balloon pump is use of the balloon pump postoperatively. Postoperative bleeding is bleeding requiring reoperation. Postoperative stroke is any new neurologic deficit postoperatively. Postoperative renal failure is renal failure requiring hemodialysis or peritoneal dialysis postoperatively. Postoperative pulmonary failure is inability to extubate within 48 hours of operation. Postoperative infection is any infection proven by culturing pathogenic organisms from blood, sputum, urine, or wound requiring antibiotic therapy.

We performed t test and ² analysis of all patient, operative, and postoperative factors to determine which factors were significantly different between men and women (Tables 1–3). We made comparisons between men and women who died with respect to day of death after operation and associated postoperative complications (Table 4).

	Results

Top Footnotes Abstract Introduction Material and Methods Results Comment Acknowledgments References

Men had longer cross-clamp times and more often received internal mammary artery grafts. Women more often received transfusion during operation.

Mortality, postoperative bleeding, and postoperative pulmonary failure were more common in women than in men. No morbidity was more common in men. There was no significant difference between men and women who died with respect to intraaortic balloon pump, postoperative bleeding, postoperative renal failure, postoperative pulmonary failure, postoperative infection, and postoperative stroke (see Table 4).

Determining Whether Sex Is a Determinant of Mortality and Morbidity
We performed stepwise logistic regression analysis to determine which patient and operative factors contributed to the prediction of mortality and morbidity. The results of this analysis are shown in Table 5. Inspection of this table shows that many patient and operative factors are predictive of mortality and morbidity. Transfusion during operation was the most common and often the strongest predictor of mortality and morbidity. Other factors that were predictive of two or more poor outcomes were older age, lower ejection fraction, elevated preoperative creatinine level, emergency operation, atherosclerosis of ascending aorta, cross-clamp time, unstable angina, and reoperation. Factors that were not predictive of any poor outcome were sex, prior myocardial infarction, body mass index (obesity), average vessel size index, and hypertension.

	Comment

Top Footnotes Abstract Introduction Material and Methods Results Comment Acknowledgments References

 
We have previously shown that female sex is associated with greater incidence of leg complications; low preoperative hematocrit; shorter perfusion times and clamp times; and small blood volume, red cell volume, and plasma volume; as well as greater mortality and morbidity [16–18]. The present study shows that women are more likely to suffer mortality, bleeding, and pulmonary failure. This study shows, however, that poorer outcomes in women can be attributed to factors other than their sex.

Of the patient and operative factors that contribute to the prediction of mortality and morbidity, some are detrimental to men and others are more detrimental to women. Of the five factors predictive of mortality, ejection fraction was lower in men, abnormal ascending aorta was more common in men, and preoperative creatinine level is higher in men. The fraction requiring emergency operation was not significantly different between men and women. Transfusion during operation was significantly greater in women. Thus transfusion during operation is the only factor predictive of mortality that is detrimental to women. Ejection fraction, preoperative creatinine level, and abnormal ascending aorta, although predictors of mortality, are detrimental to men because they are less common or abnormal in women. Of the 11 predictors of need for intraaortic balloon pump, six are more detrimental to men and four detrimental to women.

Similarly, the predictors of postoperative renal failure that are detrimental to women are transfusion during operation and diabetes. Preoperative creatinine level is higher in men. There is no difference in emergency operation between men and women.

The only predictor of postoperative bleeding was transfusion during operation. Transfusion during operation and unstable angina were the factors detrimental to women that predicted postoperative pulmonary failure. Ejection fraction, preoperative creatinine level, and reoperation were predictors of pulmonary failure but were detrimental to men. Of the predictors of stroke and infection, transfusion during operation was the only one detrimental to women; all others were detrimental to men.

A factor is detrimental if it is significantly different in men or women and is a predictor of mortality or morbidity. Factors detrimental to women include transfusion during operation, age, diabetes, and history of unstable angina. Vessel size index is smaller in women and hypertension is more common in women. They are not predictors of mortality or morbidity and therefore not detrimental. Factors detrimental to men include ejection fraction, preoperative creatinine level, atherosclerosis of ascending aorta, cross-clamp time, reoperation, and smoking history. The 1, 2, 3-vessel disease index is greater in men but is not detrimental because it is not a predictor of mortality or morbidity. Factors not detrimental to men or women because there is no difference between them include emergency operation, membrane oxygenator, recent infarction, prior stroke, and body mass index.

Other studies have shown that women have a higher incidence of emergency operation and carotid bruits [16]. Some prior studies of mortality and morbidity have included few female patients, as low as 0.8% [19, 20]. We found that female patients are significantly older than male patients and age contributes to the prediction of intraaortic balloon pump use and postoperative infection.

Unstable angina is more common in women (68.9%) than in men (63.4%). Unstable angina accounts for a significant portion of the prediction of intraaortic balloon pump use and postoperative pulmonary failure. The higher incidence of unstable angina in women and its association with morbidity is consistent with the view that women are typically sicker and at a more symptomatic stage of their disease than men when they are referred for coronary bypass grafting [6]. Unstable angina is the only factor indicative of more advanced or severe disease that is more common in women and is also a predictor of greater morbidity.

Several factors that are indicative of more advanced disease are not only more common and severe in men but are also predictors of mortality and morbidity. These include greater preoperative creatinine level, lower ejection fraction, and more common atherosclerosis of ascending aorta. This study does not indicate that more severe and far advanced disease accounts for the poorer results in women.

One of the most significant differences between men and women is the lower hematocrit values in women. Our previous study shows that preoperative hematocrit is significantly predicted by female sex, preoperative hospital stay, weight, left ventricular end-diastolic pressure, age, no smoking history, and recent myocardial infarction. Furthermore we found that lower red cell mass was significantly correlated with female sex, no smoking history, weight, emergency operation, and body mass index (obesity). Thus the smaller body size gives women a lower red cell mass. Their hematocrit falls more for every amount of blood lost during cardiac catheterization or for blood testing: 6.5% of patients have a hematocrit less than 35% with 4 or less days preoperative stay and 13.1% have a hematocrit less than 35% after more than 4 days preoperative hospital stay [18]. History of smoking is associated with higher hematocrit, which is one reason for men having higher hematocrit values [18]. This study suggests that the main reason small body size is associated with increased risk of coronary operation is because of the lower probability of avoiding blood transfusion during operation.

Transfusion during operation contributes significantly to the prediction of mortality and morbidity evaluated in this study. Our protocols call for transfusion during operation to increase oxygen carrying capacity rather than for volume replacement. Low bypass hematocrit is the usual indication. It has been suggested that a lower hematocrit that is safe while on cardiopulmonary bypass may need to be higher when cardiopulmonary bypass is being terminated [21]. Experimental investigations show that the addition of homologous blood during cardiopulmonary bypass greatly increases complement activation [22]. The need to transfuse women during cardiopulmonary bypass may begin the cascade of events that contributes to postoperative organ dysfunction and morbidity associated with complement activation [23].

The increased mortality and morbidity associated with transfusion during operation suggests that strategies should be developed to maintain or increase hematocrit preoperatively. Such strategies might include conservation of blood in the catheterization laboratory and limiting blood for testing by using micro (pediatric) techniques. Blood testing perhaps should be limited as one would in a Jehovah's Witness. It is possible that homologous transfusion during the preoperative period might be preferable to transfusion during cardiopulmonary bypass. We do not dismiss the possibility that transfusion during operation is one factor that is associated with a larger number of determininants of risk. Important therapeutic possibilities are presented by this observation, however.

Women have a higher incidence of diabetes (25.5%) than men (20.4%). Diabetes does not contribute to increased mortality in this study. Diabetes is a predictor only of postoperative renal failure.

Small coronary arteries have been implicated as a cause of greater risk of coronary artery bypass grafting among women [1, 2, 24]. Coronary artery size index does not correlate with mortality or morbidity. We have had the impression that the use of finer suture (8-0) on small coronary arteries has improved the flow of blood cardioplegia injected through the vein grafts. We have routinely used acetylsalicylic acid and dipyridamole postoperatively to improve early graft patency [25]. Small coronary arteries does not explain the greater risk with female patients.

The aggressive use of internal mammary artery grafts in women is supported by this study. Failure to use internal mammary artery grafts is associated with greater use of the intraaortic balloon pump.

This study shows that mortality and morbidity can be explained by factors other than sex, either male or female. Factors that indicate very advanced disease may be more common in women than in men.

Despite many factors that are detrimental to men, outcomes were worse in women and none were worse in men. Undoubtedly there are other factors not part of our database that contribute to worse outcomes in women. The elucidation of these factors in future studies may contribute to diminishing the risk of coronary artery bypass grafting in women.

	Acknowledgments

Top Footnotes Abstract Introduction Material and Methods Results Comment Acknowledgments References

 
This work was supported by the Cardiothoracic Research and Education Foundation.

	Footnotes

Top Footnotes Abstract Introduction Material and Methods Results Comment Acknowledgments References

 
Address reprint requests to Dr Utley, 100 E Wood St, Suite 300, Spartanburg, SC 29303.

	References

Top Footnotes Abstract Introduction Material and Methods Results Comment Acknowledgments References

 

1. Kennedy JW, Kaiser GC, Fisher LD, et al. Multivariate discriminant analysis of the clinical and angiographic predictors of operative mortality from the Collaborative Study in Coronary Artery Surgery (CASS). J Thorac Cardiovasc Surg 1980;80:876–87.[Abstract]
2. Fisher LD, Kennedy JW, Davis KB, et al. Association of sex, physical size, and operative mortality after coronary artery bypass in the Coronary Artery Surgery Study (CASS). J Thorac Cardiovasc Surg 1982;84:334–41.[Abstract]
3. Becker RC, Corrao JM, Alpert JS. Coronary artery bypass surgery in women. Clin Cardiol 1988;11:443–8.[Medline]
4. Ivert T, Welti R, Ekestrom S, Björk VO. Early mortality after 2,902 coronary artery bypass operations. Scand J Thorac Cardiovasc Surg 1989;23:3–8.[Medline]
5. Douglas JS, King SB, Jones EL, Craver JM, Bradford JM, Hatcher CR. Reduced efficacy of coronary bypass surgery in women. Circulation 1981;64(Suppl 2):11–6.
6. Wenger NK, Speroff L, Packard B. Cardiovascular health and disease in women. N Engl J Med 1993;329:247–56.[Free Full Text]
7. Bolooki H, Vargas, Green R, et al. Results of direct coronary artery surgery in women. J Thorac Cardiovasc Surg 1975;69:271–7.[Abstract]
8. Tyras DH, Barner HB, Kaiser GC, Codd JR, Laks H, Willman VL. Myocardial revascularization in women. Ann Thorac Surg 1978;25:449–53.[Abstract]
9. Loop FD, Golding LR, Macmillan JP, Cosgrove DM, Lytle BW, Wheldon WC. Coronary artery surgery in women compared with men: analyses of risks and long-term results. J Am Coll Cardiol 1983;1:383–90.[Abstract]
10. Khan SS, Nessim S, Gray R, Czer LS, Chaux A, Matloff J. Increased mortality of women in coronary artery bypass surgery: evidence for referral bias. Ann Intern Med 1990;112:561–7.[Abstract/Free Full Text]
11. Gardner TJ, Horneffer PJ, Gott VL, et al. Coronary artery bypass grafting in women. A ten-year perspective. Ann Surg 1985;201:780–4.[Medline]
12. Ayanian JZ, Epstein AM. Differences in the use of procedures between women and men hospitalized for coronary artery bypass. N Engl J Med 1991;325:221–5.[Abstract]
13. Tobin JN, Wassertheil-Smoller S, Wexler JP, et al. Sex bias in considering coronary artery bypass surgery. Ann Intern Med 1987;107:19–25.[Abstract/Free Full Text]
14. National Institutes of Health Consensus Development Panel. Health implications of obesity: National Institutes of Health Consensus Development Conference statement. Ann Intern Med 1985;103:147–51.[Abstract/Free Full Text]
15. Frankel HM. Determination of body mass index. JAMA 1986;255:125.
16. Utley JR, Thomason ME, Wallace DJ, et al. Preoperative correlates of impaired wound healing after saphenous vein excision. J Thorac Cardiovasc Surg 1989;98:147–9.[Abstract]
17. Utley JR, Leyland SA, Johnson HD, et al. Correlation of preoperative factors, severity of disease, type of oxygenator and perfusion times with mortality and morbidity of coronary bypass. Perfusion 1991;6:15–22.[Abstract/Free Full Text]
18. Utley JR, Wallace DJ, Thomason ME, et al. Correlates of preoperative hematocrit value in patients undergoing coronary artery bypass. J Thorac Cardiovasc Surg 1989;98:451–3.[Abstract]
19. Golding LR, Groves LK. Results of coronary artery surgery in women. Cleve Clin Q 1976;43:113–5.[Medline]
20. Hammermeister KE, Burchfiel C, Johnson R, Grover FL. Identification of patients at greatest risk for developing major complications at cardiac surgery. Circulation 1990;82(Suppl 4):380–9.
21. Cooper JR, Slogoff S. Hemodilution and priming solutions for cardiopulmonary bypass. In: Gravlee GP, Davis RF, Utley JR, eds. Cardiopulmonary bypass: principles and practice. Baltimore: Williams and Wilkins, 1993:124–37.
22. Tamiya T, Yamasaki M, Yoshinobu M, Yamashiro T, Ogoshi S, Fujimoto S. Complement activation in cardiopulmonary bypass, with special reference to anaphylatoxin production in membrane and bubble oxygenators. Ann Thorac Surg 1988;46:47–57.[Abstract]
23. Kirklin JK, Westaby S, Blackstone EH, et al. Complement and the damaging effects of cardiopulmonary bypass. J Thorac Cardiovasc Surg 1983;86:845–57.[Abstract]
24. Spray TL, Roberts WC. Status of the grafts and the native coronary arteries proximal and distal to coronary anastomotic sizes of aortocoronary bypass grafts. Circulation 1977;55:741–9.[Abstract/Free Full Text]
25. Chesebro JH, Clements IP, Fuster V, et al. A platelet-inhibitor-drug trial in coronary-artery bypass operations: benefit of perioperative dipyridamole and aspirin therapy on early postoperative vein-graft patency. N Engl J Med 1982;307:73–8.[Abstract]

This article has been cited by other articles:

				H. K. Song, J. D. Grab, S. M. O'Brien, K. F. Welke, F. Edwards, and R. M. Ungerleider Gender Differences in Mortality After Mitral Valve Operation: Evidence for Higher Mortality in Perimenopausal Women Ann. Thorac. Surg., June 1, 2008; 85(6): 2040 - 2045. [Abstract] [Full Text] [PDF]

				J. Shuhaiber Long-term Mortality Associated With Aprotinin Following Coronary Artery Bypass Graft Surgery JAMA, June 13, 2007; 297(22): 2476 - 2476. [Full Text] [PDF]

				F. H. Edwards, V. A. Ferraris, D. M. Shahian, E. Peterson, A. P. Furnary, C. K. Haan, and C. R. Bridges Gender-Specific Practice Guidelines for Coronary Artery Bypass Surgery: Perioperative Management Ann. Thorac. Surg., June 1, 2005; 79(6): 2189 - 2194. [Abstract] [Full Text] [PDF]

				M. Kuduvalli, A. Y. Oo, N. Newall, A. D. Grayson, M. Jackson, M. J. Desmond, B. M. Fabri, and A. Rashid Effect of peri-operative red blood cell transfusion on 30-day and 1-year mortality following coronary artery bypass surgery Eur. J. Cardiothorac. Surg., April 1, 2005; 27(4): 592 - 598. [Abstract] [Full Text] [PDF]

				R. Wynne and M. Botti Postoperative Pulmonary Dysfunction in Adults After Cardiac Surgery With Cardiopulmonary Bypass: Clinical Significance and Implications for Practice Am. J. Crit. Care., September 1, 2004; 13(5): 384 - 393. [Abstract] [Full Text] [PDF]

				J. H. Shuhaiber Intraoperative hematocrit and cardiopulmonary bypass J. Thorac. Cardiovasc. Surg., April 1, 2004; 127(4): 1226 - 1227. [Full Text] [PDF]

				R. H. Habib, A. Zacharias, T. A. Schwann, C. J. Riordan, S. J. Durham, and A. Shah Reply to the Editor J. Thorac. Cardiovasc. Surg., April 1, 2004; 127(4): 1227 - 1228. [Full Text] [PDF]

				J. S. Hochman and J. E. Tamis-Holland Acute Coronary Syndromes: Does Sex Matter? JAMA, December 25, 2002; 288(24): 3161 - 3164. [Full Text] [PDF]

				M. C. Engoren, R. H. Habib, A. Zacharias, T. A. Schwann, C. J. Riordan, and S. J. Durham Effect of blood transfusion on long-term survival after cardiac operation Ann. Thorac. Surg., October 1, 2002; 74(4): 1180 - 1186. [Abstract] [Full Text] [PDF]

				Y. Zitser-Gurevich, E. Simchen, N. Galai, and M. Mandel Effect of perioperative complications on excess mortality among women after coronary artery bypass: The Israeli Coronary Artery Bypass Graft study (ISCAB) J. Thorac. Cardiovasc. Surg., March 1, 2002; 123(3): 517 - 524. [Abstract] [Full Text] [PDF]

				S. B. Chelemer, B. S. Prato, P. M. Cox Jr, G. T. O'Connor, and J. R. Morton Association of bacterial infection and red blood cell transfusion after coronary artery bypass surgery Ann. Thorac. Surg., January 1, 2002; 73(1): 138 - 142. [Abstract] [Full Text] [PDF]

				J. E Cormack, R. J Forest, R. C Groom, and J. Morton Size makes a difference: use of a low-prime cardiopulmonary bypass circuit and autologous priming in small adults Perfusion, March 1, 2000; 15(2): 129 - 135. [Abstract] [PDF]

				C. L. DAVIS, A. T. KAUSZ, R. A. ZAGER, E. D. KHARASCH, and R. P. COCHRAN Acute Renal Failure after Cardiopulmonary Bypass Is Related to Decreased Serum Ferritin Levels J. Am. Soc. Nephrol., November 1, 1999; 10(11): 2396 - 2402. [Abstract] [Full Text]

				G. S. Aldea, J. M. Gaudiani, O. M. Shapira, A. K. Jacobs, J. Weinberg, A. L. Cupples, H. L. Lazar, and R. J. Shemin Effect of gender on postoperative outcomes and hospital stays after coronary artery bypass grafting Ann. Thorac. Surg., April 1, 1999; 67(4): 1097 - 1103. [Abstract] [Full Text] [PDF]

				J. R. Utley Coronary Bypass in Women Ann. Thorac. Surg., March 1, 1996; 61 (3): 1042 - 1043. [Full Text]

This Article Abstract Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to Personal Folders Download to citation manager Author home page(s): Joe R. Utley Permission Requests Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Utley, J. R. Articles by Johnson, H. D. Search for Related Content PubMed PubMed Citation Articles by Utley, J. R. Articles by Johnson, H. D. Related Collections Related Article