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Ann Thorac Surg 1996;61:27-32
© 1996 The Society of Thoracic Surgeons
Department of Surgery, Allegheny General Hospital, and Allegheny Campus, The Medical College of Pennsylvania, Pittsburgh, Pennsylvania
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Abstract |
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Methods. From January 1, 1992, to December 31, 1993, 2,033 patients having isolated coronary artery bypass grafting procedures were studied; 1,446 (71%) were male and 587 (29%), female. The mean age was 65.1 ± 9.9 years (range, 31 to 88 years). Emergency operation, urgent operation, and reoperations were done in 78 (4%), 188 (9%), and 189 (9%) patients, respectively. In the entire group, 1,245 (61%) received transfusion during hospitalization, and 788 (39%) did not. Logistic regression analysis was used to construct a model that predicted the need of transfusion of packed red blood cells after coronary artery bypass grafting. A transfusion risk score was constructed by assigning points to independent predictive factors on the basis of the logistic regression coefficient and the odds ratio. Preoperative predictors of transfusion were emergency operation, urgent operation, cardiogenic shock, catheterization-induced coronary occlusion, low body mass index, left ventricular ejection fraction lower than 0.30, age greater than 74 years, female sex, low red cell mass, peripheral vascular disease, insulin-dependent diabetes, creatinine level greater than 1.8 mg/dL, albumin value lower than 4 g/dL, and redo operation.
Results. The mean transfusion risk score for patients receiving 0, 1 to 4, and greater than 4 units of packed red blood cells was 2.3 ± 0.9, 5.2 ± 3.0, and 9.6 ± 3.5, respectively (p = 0.001). Patients with a score higher than 6 had a 95% transfusion incidence. The predictive model was validated on 422 patients having coronary artery bypass grafting from January 1 to May 31, 1994. The observed rates of the validation group fell within the 95% confidence intervals of the predicted rates.
Conclusions. These data demonstrate that readily available patient variables can predict patients at risk for transfusion. Routine use of aprotinin and other adjustments of cardiopulmonary bypass should be considered to reduce transfusion in high-risk patients.
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Introduction |
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-aminocaproic acid to reduce bleeding after cardiopulmonarybypass. Others [6–8] have emphasized the importance of autotransfusion using a variety of techniques, such as storage of autologous blood, reinfusion of shed mediastinal blood, or autotransfusion of platelets. Relatively little information exists on predicting the need of transfusion based on patient-related preoperative and postoperative variables. It is obvious that all patients are not at the same risk for needing blood during or after a cardiac operation, but identification of high-risk patients has been an imprecise science. Here we provide a framework for predicting which patients will need transfusion as a means to facilitate further research in blood conservation. For editorial comment, see page 8.
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Material and Methods |
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Techniques of Operation and Patient Management
All operations were done using cardiopulmonary bypass and mild systemic hypothermia (30°C) with a membrane oxygenator and a centrifugal pump. The prime volume of the circuit was approximately 1,500 mL, which consisted of Plasmalyte-A (Baxter Healthcare Corp, Deerfield, IL) and 25 g of mannitol. The hearts were arrested with a combination of antegrade and retrograde cold blood cardioplegia. Distal anastomoses were done first, and proximal anastomoses were done with a partial occluding clamp on the ascending aorta. The left internal mammary artery was routinely used to graft the left anterior descending coronary artery. Overall utilization rate for this mammary artery was 70% in the test group and 80% in the validation group. Bilateral internal mammary artery grafting was not routinely done except in young patients with favorable anatomy.
The decision to transfuse blood was made by individual clinicians, and a rigidly enforced protocol was not used. In general, however, blood was given when the hemoglobin level was lower than 7 g/dL while the patient was on cardiopulmonary bypass or lower than 7.5 g/dL 6 hours or more postoperatively. Blood was not ordered when the value was greater than 8.0 g/dL unless the patient was hemodynamically unstable or bleeding acutely. The majority of the patients were receiving aspirin and heparin sodium prior to operation, and operation was not delayed by their administration. No further aspirin was given once the patient was scheduled for operation, and heparin was discontinued when the patient was called to the operating room. Aprotinin was not used in any first-time procedures and was given in ten (5%) of 189 redo operations. A cell-saving device was routinely used during operation, and all blood remaining in the cardiopulmonary bypass circuit was reinfused postoperatively. Storage of autologous blood, reinfusion of postoperatively shed blood, and autologous platelet transfusion were not used.
Statistical Methods
Allegheny General Hospital prospectively maintains a computerized cardiothoracic database, which collects information on 320 variables including preoperative cardiovascular status, comorbid diseases, laboratory studies, operative events, and postoperative outcome. Data are retrieved from the database by query language, and computations are performed using SPSS (SPSS, Inc, Chicago, IL), BMDP (BMDP Statistical Software, Inc, Los Angeles, CA), and EPI Info (USD, Inc, Stone Mountain, GA) information statistical programs. Several statistical tests including 
2 analysis, Fisher's exact test, and analysis of variance were used to perform a univariate study of the relationship between preoperative variables and homologous blood transfusion. Dichotomous variables were scored 0 for absent and 1 for present. Cutoff points for continuous variables were established to determine the best relationship to transfusion incidence. Rates of transfusion were calculated for each interval, and intervals with similar rates were combined. Univariate variables with significance at the level of p less than 0.10 were entered into a forward stepwise regression analysis using the BMPD-LR program. The multivariate analysis was limited to variables that were known prior to operation. A subsequent analysis was done with intraoperative and postoperative variables to determine additional factors associated with transfusion.
Independent preoperative predictive variables from the regression analysis were then used to generate a transfusion risk score (TRS). The points for the scoring system were derived from the regression coefficient, odds ratio, and clinical relevance as judged by the surgeons. The patients were stratified from low to high risk for transfusion on the basis of their individual TRS. The transfusion rates at each risk level in the validation group were compared with the predicted rates of the test group. Ninety-five percent confidence intervals were calculated for each risk interval. The relationship between the TRS and the units of blood transfused was compared by linear regression and one-way analysis of variance. Receiver operating characteristic curves were used to analyze the accuracy of the TRS.
Definitions of Variables
Blood transfusion was analyzed for the incidence and the number of packed red blood cell transfusions but not for the administration of fresh frozen plasma or platelets. Less than 1% of the patients received plasma or platelets without also requiring packed red blood cells. Documentation of homologous blood product administration was determined by records of signed blood administration forms and by review of blood products issued.
Predictive factors were defined as follows: peripheral vascular disease = claudication resulting in functional disability, noninvasive test showing greater than 50% arterial obstruction, absent femoral pulses, prior peripheral vascular operation, inability to insert an intraaortic balloon pump because of obstructed arteries, or a combination of these; insulin-dependent diabetes = patients receiving insulin prior to operation; Anemia = hemoglobin level of 12.5 g/dL or less and 11 g/dL or less for male and female patients, respectively, blood transfusion within 7 days prior to operation, or both; low body mass index = 24 or less weight (kg)/height (m2); low red cell mass = 1,500 mL or less with red cell mass defined as blood volume x hematocrit, where blood volume was calculated with adjustment for height, weight, and sex; left ventricular ejection fraction = ejection fraction less than 0.30 on ventriculogram, echocardiogram, or radionuclide scan; redo operation = history of any prior heart operation; low serum albumin level = less than 4.0 g/dL; renal dysfunction = history of chronic renal disease, serum creatinine value greater than 1.8 mg/dL, or both; cardiogenic shock = systolic blood pressure lower than 90 mm Hg or mean systemic blood pressure lower than 50 mm Hg, and cardiac index of less than 2.0 L•min-1•m-2 with evidence of peripheral hypoperfusion; emergency operation = procedure performed on patient in unstable condition and refractory to all forms of therapy; urgent operation = operation done within 48 hours of an acute ischemic event requiring an intraaortic balloon pump and inotropic agents or intravenous nitroglycerin; catheterization-induced coronary occlusion = iatrogenic occlusion or dissection or both of a coronary artery secondary to an invasive cardiac procedure requiring CABG within 24 hours; cardiac collapse = intraoperative or postoperative acute myocardial infarction, intraaortic balloon pump support, ventricular assist device, arrest with resuscitation, inotropic cardiac support requiring two or more drugs for longer than 24 hours, or a combination of these; respiratory failure = postoperative ventilatory support for longer than 48 hours, tracheostomy, or both; respiratory insufficiency = postextubation desaturation, hypercapnia, labored respirations requiring prolonged oxygen therapy, or a combination of these; major wound infection = any surgical wound site manifesting clinical evidence of sepsis requiring additional hospital stay, invasive treatment for resolution, or both; gastrointestinal bleeding = gastrointestinal hemorrhage documented by heme-positive stool; atrial arrhythmia = fibrillation, flutter, or tachycardia sustained long enough to be documented, producing patient symptoms, or requiring treatment with pacing, conversion, or drugs; and systemic sepsis = respiratory, urinary tract, or blood infection documented by positive culture, clinical evidence, or both requiring additional treatment for resolution.
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Results |
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. The two groups were similar in age, sex distribution, preoperative red blood cell mass, and incidence of comorbid diseases. The operative mortality rate for the two groups was 2.5% and 2.6%, respectively. There was no relationship between postoperative transfusion and preoperative aspirin, preoperative heparin, or percutaneous transluminal coronary angioplasty within 30 days of CABG. The mean pack number of packed red blood cells transfused per patient was 2.5 ± 0.3 in the prospective group and 2.9 ± 0.4 in the retrospective group. The incidence of blood transfusion for the combined groups is illustrated in Figure 1. Approximately 40% of the patients did not require any transfusion.
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lists the predictive factors with the coefficients, odds ratios, incidences, and 95% confidence intervals. Table 3 shows the variables scored for their predictive value.
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). Most patients with a low risk score (0 or 1) did not receive transfusion, whereas nearly all of the patients with a TRS of higher than 7 received blood. In addition, there was a high correlation (r = 0.96) between the TRS and the number of transfusions required (Fig 3), that is, the patients with a high risk score received more transfusions in addition to having the highest overall incidence of transfusion. Patients were also retrospectively sorted by the amount of blood used. The mean TRS for patients receiving 0, 1 through 4, and greater than 4 units of packed red blood cells was 2.3 ± 0.9, 5.2 ± 3.0, and 9.6 ± 3.5, respectively (p = 0.001).
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). In general, these factors were postoperative complications, such as cardiac arrest in the intensive care unit, respiratory failure, wound infection, and gastrointestinal bleeding. A cardiopulmonary bypass time longer than 105 minutes was a minor predictor of transfusion.
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Comment |
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This analysis is a large and detailed study of the factors that influence transfusion after CABG. All patients undergoing CABG during the study were analyzed, including those having emergency operations and redo procedures and those sustaining catheterization-induced coronary occlusion. Consequently, this series is a representative sample of the situation commonly found in clinical practice, and the incidence of patients requiring transfusion is higher than in some recent reports.
This analysis shows that the need of blood transfusion can be readily predicted from preoperative patient-related variables. We have not studied transfusion of platelets or fresh frozen plasma. The variables fall into three general categories: (1) emergency and unstable preoperative patient status; (2) factors associated with low preoperative red cell volume; and (3) comorbid conditions and diseases. Surgical factors such as the length of cardiopulmonary bypass and redo sternotomy were only minor contributors. Now that aprotinin can be used routinely for redo procedures, this factor should become even less significant than it was in this study.
The most powerful predictors were those related to an unstable condition before operation. This includes patients in cardiogenic shock secondary to myocardial infarction, patients with unstable postinfarction angina, and patients with failure of angioplasty, including arrest in the catheterization laboratory. The reasons are multifactorial. Many of these patients are anticoagulated at the time of operation, as they had received heparin, thrombolysis, aspirin, or a combination of these before or during cardiac catheterization. In addition, survival is the overwhelming issue in this situation, and blood conservation is pushed into the background. Avoiding transfusion is probably not a realistic goal in these patients, as most have compromised cardiac function, which makes anemia and hemodilution undesirable. Nonetheless, this is the group with the largest transfusion requirement, which makes it an important area for reducing overall blood use in CABG. Perhaps routine use of aprotinin would reduce the transfusion requirement in this group of patients in unstable condition.
Factors associated with a reduced red cell volume have previously been shown to correlate with the need of transfusion [9–11]. These factors include anemia, female sex, older age, and small size. Our study confirms that patients who start with a lower initial hematocrit or red cell mass often require transfusion because hemodilution and blood loss have a proportionally greater effect on these patients than those with a higher red cell mass. It is likely that red cell mass is inversely related to the need of transfusion as a continuous function. We have analyzed this factor to find a cutoff level that is most strongly associated with transfusion, which occurs when the red cell mass is less than 1,500 mL. Preoperative anemia is a condition that is becoming more prevalent in patients referred for CABG, probably because of the change in the patient population since the advent of angioplasty [12]. Another factor that may also be contributing to this trend is a more aggressive medical approach to myocardial infarction, which includes thrombolysis, early catheterization, angioplasty, or a combination of these, all of which result in some blood loss.
This study suggests that preoperative comorbid conditions and diseases independently increase the need of transfusion. Factors included in this category are left ventricular ejection fraction lower than 0.30, peripheral vascular disease, insulin-dependent diabetes, creatinine value greater than 1.8 mg/dL, and albumin value lower than 4.0 g/dL. The mechanism of this is not entirely certain, but it is likely because these preoperative conditions result in increased postoperative morbidity and length of hospital stay, which in turn are associated with an increased need of transfusion [13, 14].
The occurrence of postoperative complications clearly increases the need of transfusion. We have identified cardiac arrest in the intensive care unit, respiratory failure, sternal wound infection, and postoperative gastrointestinal bleeding as the problems most likely to result in transfusion. These factors are markers of transfusion rather than predictors, as they reflect postoperative events. In this situation, the need of transfusion can be considered a consequence of the specific complication rather than the result of the preoperative condition of the patient. These problems occur in a small percentage of patients, but their consequences are devastating. Transfusion often occurs days or weeks after the initial operation and therefore is a separate issue from perioperative transfusion. Preventing transfusion in this group is not possible except by avoiding a specific complication, which is a more difficult task.
We have not analyzed the contribution of postoperative blood loss to the need of transfusion because this is by definition a postoperative event. In addition, it is evident that patients with excessive bleeding after operation will require transfusion. Our analysis shows that patients with a very high TRS are the ones who require massive transfusion. An occasional patient with a low risk score will have massive bleeding from a technical problem, but this is a rare event that cannot be predicted.
The information generated from this model has several practical applications. Patients with a low TRS should have less blood typed and crossed prior to operation. Most of these patients will not require blood, and if they do, it will be only 1 unit to 2 units. The number of low-risk patients who require massive transfusion is exceedingly small. Another finding is that many patients with a medium TRS receive 1 to 2 units of blood. Accepting a low transfusion trigger (6 g/dL of hemoglobin) during cardiopulmonary bypass will reduce the transfusion incidence, but this is not advisable for all patients [14]. Finally, patients with a high TRS will require blood transfusion, and many of them will require massive transfusion. Reducing the amount of transfused blood in this high-risk group may be aided by pharmacologic means, such as aprotinin, -aminocaproic acid, or tranexamic acid, which reduce bleeding caused by coagulopathy. Finally, in patients who are nearly certain to receive transfused blood, consideration should be given to adding blood to the cardiopulmonary bypass circuit prior to the start of the operation.
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Footnotes |
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Address reprint requests to Dr James Magovern, Department of Surgery, Allegheny General Hospital, 320 E North Ave, Pittsburgh, PA 15212.
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