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Ann Thorac Surg 2004;77:626-634
© 2004 The Society of Thoracic Surgeons

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Original article: cardiovascular

Predictors of transfusion requirements for cardiac surgical procedures at a blood conservation center

^a Department of Anesthesiology and Critical Care Medicine, Englewood, New Jersey, USA
^b Department of Cardiothoracic Surgery, Englewood, New Jersey, USA
^c Division of Cardiology, Department of Internal Medicine, Englewood Hospital and Medical Center, Englewood, New Jersey, USA
^d Department of Biomathematical Sciences, Mount Sinai Medical Center, New York, New York, USA

Accepted for publication July 10, 2003.

^* Address reprint requests to Dr Moskowitz, Director, Cardiothoracic Anesthesia, Department of Anesthesiology and Critical Care Medicine, Englewood Hospital and Medical Center, Englewood, NJ 07631, USA.
e-mail: david.moskowitz{at}ehmc.com

	Abstract

Top Abstract Introduction Patients and methods Results Comment Appendix 1 Appendix 2 Appendix 3 References

 
BACKGROUND: Previous studies defining perioperative risk factors for allogeneic transfusion requirements in cardiac surgery were limited to highly selected cardiac surgery populations or were associated with high transfusion rates. The purpose of this study was to determine perioperative risk factors and create a formula to predict transfusion requirements for major cardiac surgical procedures in a center that practices a multimodality approach to blood conservation.

METHODS: We performed an observational study on 307 consecutive patients undergoing coronary artery bypass grafting, valve, and combined (coronary artery bypass grafting and valve) procedures. An equation was derived to estimate the risk of transfusion based on preoperative risk factors using multivariate analysis. In patients with a calculated probability of transfusion of at least 5%, intraoperative predictors of transfusion were identified by multivariate analysis.

RESULTS: Thirty-five patients (11%) required intraoperative or postoperative allogeneic transfusions. Preoperative factors as independent predictors for transfusions included red blood cell mass, type of operation, urgency of operation, number of diseased vessels, serum creatinine of at least 1.3 mg/dL, and preoperative prothrombin time. Intraoperative factors included cardiopulmonary bypass time, three or fewer bypass grafts, lesser volume of acute normovolemic hemodilution removed, and total crystalloid infusion of at least 2,500 mL. The derived formula was applied to a validation cohort of 246 patients, and the observed transfusion rates conformed well to the predicted risks.

CONCLUSIONS: A multimodality approach to blood conservation in cardiac surgery resulted in a low transfusion rate. Identifying patients' risks for transfusion should alter patient management perioperatively to decrease their transfusion rate and make more efficient use of blood resources.

	Introduction

Top Abstract Introduction Patients and methods Results Comment Appendix 1 Appendix 2 Appendix 3 References

 
Transfusion of allogeneic blood in cardiac surgery is a major health issue. Ten percent to 20% of the nation's blood supply is consumed during cardiac surgery [1]. Advances in perioperative techniques have called for a reevaluation of transfusion management during these procedures [2]. We have instituted a blood conservation program that has the potential to markedly alter the current paradigm concerning allogeneic blood use in cardiac surgery. In previous studies, perioperative risk factors for allogeneic transfusions have been identified [3–10]. Transfusion rates and types of cardiac surgical procedures have varied widely among these studies and may not apply to a program that practices blood conservation. By identifying a patient's risk for transfusion, perioperative management can be altered to minimize the risk for transfusions and assist in proper blood ordering practices. Therefore, we evaluated the preoper-ative and intraoperative risk factors and derived a formula to predict allogeneic blood transfusions in a prospective, sequential series of patients undergoing isolated coronary artery bypass grafting (CABG), isolated valve, or combined CABG and valve procedures in a center with a commitment to perioperative blood conservation.

	Patients and methods

Top Abstract Introduction Patients and methods Results Comment Appendix 1 Appendix 2 Appendix 3 References

 
At Englewood Hospital and Medical Center, a broad-based blood conservation program is practiced in all patients. This program includes (1) preoperative optimization of hemoglobin, (2) intraoperative acute normovolemic hemodilution (ANH), (3) autotransfusion, (4) tolerance of anemia, (5) meticulous surgical technique, (6) endovascular vein harvesting, (7) on-site coagulation monitoring (thromboelastography and heparin concentration determination), and (8) targeted pharmacotherapy (antifibrinolytic agents and desmopressin acetate). Institutional review board approval was obtained. All consecutive patients undergoing CABG (on-pump and off-pump), valve replacement, or combined CABG and valve replacement procedures from July 1, 2000, to December 31, 2001, were included in the final analysis. A single surgical team performed all procedures. Risk factors, comorbidities, and complications were defined by the State of New Jersey.

All patients received -aminocaproic acid except for patients considered classically to be at high risk for transfusion (reoperations and patients who were of the Jehovah's Witness faith), who received aprotinin (Trasylol, Bayer Corp, West Haven, CT). Antifibrinolytic agents were not used in procedures in which cardiopulmonary bypass (CPB) was not used or when there was a specific contraindication for their use (ie, hypercoagulable medical condition). Heparin concentrations were measured to detect heparin resistance and to determine appropriate protamine dosing (Hepcon HMS Plus, Medtronic, Inc, Minneapolis, MN). Bovine lung heparin was administered for anticoagulation during CPB (300 IU/kg) to achieve a target activated clotting time level more than 400 seconds (celite activated) for patients receiving -aminocaproic acid and more than 550 seconds (kaolin activated) for those patients receiving aprotinin.

The CPB circuit consisted of a hollow-fiber, trillium-coated membrane oxygenator (Medtronic, Inc), non–heparin-coated tubing (Medtronic, Inc), arterial line filter (Medtronic, Inc), and a roller pump for perfusion. A leukocyte-depletion filter (Pall Biomedical Products, Co, East Hills, NY) was incorporated in the circuit in patients with a modified Parsonett Score more than 25 [11]. The tubing length was kept to a minimum, and the circuit was primed with a total of 1,250 mL of fluid. Hypothermic perfusion to 24°C was maintained during the period of myocardial ischemia. Myocardial protection consisted of intermittent antegrade crystalloid cardioplegia supplemented by topical hypothermia. Standard surgical techniques were used in patients undergoing coronary revascularization on the beating heart without CPB.

Patients were considered to have a transfusion if they received any allogeneic blood products intraoperatively or within 28 days postoperatively. Hematocrit levels of 20% during CPB and at least 24% after CPB and into the postoperative period were tolerated if the patient had no evidence of anemia-induced adverse physiology. Intraoperatively, if the hematocrit level fell below these values, all attempts were made to hemoconcentrate the patient during and after CPB. If intolerable anemia still persisted, then autologous blood was returned to the patient before allogeneic blood was used. Postoperatively, lower levels were tolerated if there was no clinical evidence of hemodynamic instability or ongoing bleeding. In general mediastinal blood was autotransfused if chest tube drainage was more than 400 mL within the first 4 hours of surgery.

Intraoperatively, a diagnosis of microvascular bleeding was made when there was no residual heparin, on the basis of blood-heparin concentrations (Hepcon), in the setting of an abnormal thromboelastography, and there was no other observed source for surgical bleeding. Allogeneic blood products were given only if there was ongoing bleeding in the setting of abnormal test results. Transfusion therapy was guided by thromboelastography results intraoperatively and postoperatively combined with standard postoperative laboratory tests. Algorithms for transfusion as set forth by previous studies were used as guidelines [12]. No specific triggers were used for transfusion of platelets, fresh-frozen plasma, or cryoprecipitate.

Univariate analysis was performed on a large number of preoperative and intraoperative variables in our database using the Student's t test and ² test to identify those variables that might be associated with allogeneic blood transfusions (Appendix 1). Variables with a p value of 0.20 or less were retained for subsequent analysis. Preoperative factors were considered first. They were entered into a stepwise multiple logistic regression analysis to select the ones that were significant independent predictors of the need for transfusion. The factors identified were then used to derive a formula for estimating the probability of transfusion from information that is available preoperatively. The formula was then applied to each patient in this study, and used to distinguish a group of patients who were at low risk for transfusion from those who had a moderate to high risk. The latter group was labeled "high risk." Stepwise multiple logistic regression analysis of intraoperative variables only was applied to this subgroup of high-risk patients to further distinguish the risk of transfusion. The prognostic value of the derived formula was then prospectively evaluated in a subsequent validation cohort of 246 patients who presented for cardiac surgery from January 2002 to January 2003.

	Results

Top Abstract Introduction Patients and methods Results Comment Appendix 1 Appendix 2 Appendix 3 References

 
The study population consisted of 307 consecutive patients, including 199 patients who underwent CABG, 58 valve, and 50 combined CABG and valve procedures. The demographic and clinical characteristics of these patients are shown in (Table 1). Eleven patients died in the hospital for an overall mortality of 3.5% (11 of 307). Two patients (<1%) required reoperation for bleeding. Two patients (<1%) had perioperative myocardial infarction, 4 patients (1%) experienced permanent stroke, and 1 patient (<1%) had a sternal wound infection. Renal failure requiring temporary dialysis occurred in 9 patients (3%). The average 24-hour chest tube drainage was 428 mL ± 238 mL. Thirty-five patients (11%; 35 of 307) received allogeneic blood or blood products. Overall 0.5 U of packed red blood cells (RBC), 0.2 U of fresh-frozen plasma, 0.4 U of platelets, and 0.3 U of cryoprecipitate were transfused (Table 2).

Of 150 patients with a calculated transfusion probability of at least 5% (high-risk group), 21% (32 of 150) received a transfusion, whereas in those with a calculated transfusion probability of less than 5%, only 2% (3 of 157) received a transfusion (Fig 1). .

View larger version (9K): [in this window] [in a new window]   Fig 1. Percentage of patients transfused and probability of transfusion.

View this table: [in this window] [in a new window]   Table 4. Significant Intraoperative Predictors of Transfusion Based on Patients With a Preoperative Estimated Risk of Transfusion 5%a

View larger version (9K): [in this window] [in a new window]   Fig 2. Prospective evaluation of the probability of transfusion and the transfusion rate.

	Comment

Top Abstract Introduction Patients and methods Results Comment Appendix 1 Appendix 2 Appendix 3 References

Earlier studies have evaluated risk factors for allogeneic transfusions in highly selected cardiac surgery populations. In a study limited to patients undergoing first-time CABG procedures, with a mean age of 58 years and an overall preoperative hematocrit of 42%, Cosgrove and colleagues [13] reported a transfusion rate of 10%. Bilfinger and coworkers [9], in a retrospective study of 467 patients limited to primary CABG procedures, excluding reoperations and chronic renal failure, reported a 44% rate of transfusion. Magovern and associates [7] derived a transfusion risk scoring system in a series of patients (average age, 65 ± 9.9 years) undergoing isolated CABG procedures including emergency operations and reoperations. They reported a transfusion rate of 61% and using logistic regression analysis identified 14 factors as significant predictors for perioperative transfusion [7]. The current study reports a transfusion rate of 13% for cardiac surgery that includes the majority of surgical procedures (CABG, valve, and combined CABG and valve procedures) seen in clinical practice. This shows that an organized approach to blood conservation in cardiac surgery is effective in significantly reducing the perioperative use of allogeneic blood and blood products. Only 4 of 14 preoperative predictors of transfusion are common to the scoring system reported by Magovern and associates [7] and those that enter into the predictive equation derived from the current study. This variation in preoperative predictors of transfusion indicates that predictors, which may have been valid in the absence of a concerted effort for blood conservation, may not apply in the modern era of blood conservation in cardiac surgery.

Diminished RBC mass, combined CABG and valve procedures, urgent or emergent operation, more than one diseased vessel, Cr of at least 1.3 mg/dL, and elevated preoperative prothrombin time were independent preoperative predictors for transfusion. Other factors (age, reoperation, renal insufficiency or failure, congestive heart failure, albumin < 3 g/dL, international normalized ratio > 1.4, body surface area, hemoglobin or hematocrit, estimated blood volume, and platelet count) that were significant in univariate analyses were found in the multivariate analysis not to add significant additional predictive information. These along with other preoperative factors (sex, low body mass index, serum albumin, and other significant medical conditions including diabetes or insulin dependency, peripheral vascular disease, heart failure, and low ejection fraction) did not reach statistical significance in contrast to other studies [3, 5, 7, 9, 13, 14]. Diminished RBC mass appears to be one of the strongest predictors of transfusion common to most of these studies including the current one (Fig 3). . The inevitable hemodilution from the CPB circuit and surgical blood loss have a proportionally greater effect on patients with a small initial RBC mass. Among the laboratory values, Cr of at least 1.3 mg/dL was a significant preoperative independent predictor of allogeneic transfusion. This is consistent with the findings of three previous studies [5, 7, 9]. Twenty-eight percent of patients with Cr of at least 1.3 mg/dL were transfused compared with only 5% of patients with Cr of less than 1.3 mg/dL (Appendix 2).

View larger version (9K): [in this window] [in a new window]   Fig 3. Red blood cell (RBC) mass versus transfusion rate.

Medications that affect the coagulation system have been shown to increase bleeding and transfusion rates perioperatively [15–18]. Other studies have not established this to be a consistent finding [3, 19]. Within the constraints of the patient's medical presentation, we made a concerted effort to discontinue or eliminate all drugs that are known or presumed to affect the coagulation system before surgery. Although a substantial number of patients remained at risk for bleeding perioperatively with recent use of these agents preoperatively, exposure to antiplatelet or anticoagulant medications was not found to have a significant association with transfusions in this study.

Intraoperative factors predictive of transfusion in patients for whom the estimated probability of transfusion based on preoperative factors was at least 5% included longer CPB times, three or fewer bypass grafts, lesser volume of ANH removed, and total crystalloid infusion of at least 2,500 mL. Longer CPB times are encountered in more complex cases and are associated with increased damage to cellular components of the blood and coagulopathy as a result of altered homeostasis of the coagulation cascade. In past studies the postoperative bleeding and rate of allogeneic transfusions were found to be associated with use of the internal mammary artery and increasing number of bypass grafts [4, 9, 20, 21]. Contrary to past experience, three or more bypass grafts was found to be a negative predictor for transfusion in the current study. The risk of receiving a blood transfusion was higher in patients who had three or fewer bypass grafts. The initial thought, to ascribe this effect to the fact that patients undergoing isolated CABG usually receive more bypass grafts than those undergoing complex combined procedures, does not completely explain this observation as this relation remains significant even after controlling for type of operation (ie, CABG versus valve versus CABG and valve) in the multivariate model. The notion that increasing number of vessels bypassed leads to increased allogeneic transfusions because of additional suture lines, increased CPB time, and tissue dissection does not appear to be valid in the current study.

Antifibrinolytic agents, regardless of type, did not have an impact on transfusion requirements. Aprotinin has been perceived to be more effective than other antifibrinolytic agents at minimizing the negative effects of CPB on coagulation and perioperative bleeding. We reserve the use of aprotinin, because of its cost, only for cases that have been classically labeled as high risk [22, 23]. This selective usage may have offset any statistical advantage that aprotinin might have had in previous studies. Moreover, antifibrinolytic agents, especially aprotinin, may have been unnecessary in a majority of cases that were not at high risk based on our formula. Future studies will be required to answer this question and the possibility of other cost-saving maneuvers.

Blood conservation strategies are well tolerated in patients undergoing cardiac surgery with comorbid medical conditions [24–29]. Although there is some controversy regarding the effectiveness of ANH in cardiac surgery, ANH is an important component of most of these strategies as it is a vital part of our approach to blood conservation [24, 25, 30–32]. In this study the amount of ANH removed was a negative predictor of perioperative transfusions; the higher the ANH volume removed the less was the probability of transfusion. Undoubtedly the permissible volume of ANH is closely related to RBC mass. In spite of this, the amount of ANH removed remained an independent predictor. Therefore, we are justified in strongly believing that protecting a substantial volume of blood against exposure to the CPB circuit and diluting the blood to decrease the amount of RBC loss during surgery can only have beneficial effects without adversely altering the patient outcomes.

Hypothermia has been demonstrated to have negative effects on the coagulation system and transfusion requirements [3, 14]. Unlike these studies, the lowest temperature during CPB and the last temperature before coming off of CPB did not have a statistically significant impact on transfusions. This may lend credence to the fact that temporary hypothermia has a reversible effect, and meticulous surgical technique coupled with blood conservation maneuvers may overcome its negative effect.

The volume of crystalloid infusion (2,500 mL) significantly increased the risk of allogeneic transfusion. It is important to avoid excessive use of crystalloid during cardiac surgery as it can induce iatrogenic hemodilution and anemia. In most situations this leads to inappropriate transfusion. We primarily used colloids for volume replacement during ANH to minimize this effect. Despite its questionable effects on bleeding, hydroxyethyl starch in a balanced salt solution (Hextend, Abbott Laboratories, North Chicago, IL) was used in the majority of cardiac procedures [33]. There was no statistically significant relationship found between the volume of Hextend infused and the rate of transfusion perioperatively.

The derived formula, which predicts the probability of transfusion on the basis of preoperative characteristics of an individual patient, is valid only at a center devoted to blood conservation and cannot be generalized to other centers without such a commitment. Postoperative risk factors, especially the presence of specific complications, were not evaluated in this study. Many of these complications cannot be predicted preoperatively.

Many factors that were found to be predictors of perioperative transfusion are common to most studies on the subject. However, other variables reported to be significant predictors in the past have proven unimportant in the current era in a center that practices blood conservation successfully. The low incidence (13%) of perioperative allogeneic blood use in a heterogeneous, unselected group of patients undergoing a wide spectrum of cardiac surgical procedures is unprecedented in the literature. These results define a universally achievable new goal for blood conservation during cardiac surgery. By applying a multidisciplinary and multimodality approach to blood conservation, significant reductions in transfusion requirements are possible in cardiac surgery. The formula has become a useful tool in our hands for discussing risk of transfusion with individual patients in general and risk of surgery in patients with religious objection to transfusions in particular. Whether these results can be reproduced in other centers remains to be seen.

	Appendix 1

Top Abstract Introduction Patients and methods Results Comment Appendix 1 Appendix 2 Appendix 3 References

 
List of Variables That Were Screened for Possible Association With Transfusion

Dependent variable Transfused any allogeneic blood product Hematology RBC mass EBV Independent variables Hct Demographics Age Hgb Sex PT BSA INR BMI PTT Weight Platelets Pre-operative risk factors Urgency Medications Any antiplatelet or anticoagulant preoperatively HTN Antiplatelet medication Smoking NSAID Diabetes Heparin Insulin Coumadin Renal insufficiency/failure ASA Creatinine Anesthesia Total ANH volume Albumin Total crystalloid CVD Total colloid PVD Aprotinin COPD Amicar CHF Desmopressin acetate NYHA classification Baseline, post-ANH, and end of case TEG (r, k angle, MA, and EPL) Parsonnet Reoperation Operative factors On/off CPB Magovern transfusion risk score CPB time X-clamp time Cardiac EF Lowest T on bypass No. diseased vessels Last T on CPB CABG only Ultrafiltration volume Valve only Time to closure CABG + valve Total grafts bypassed Total heparin Total protamine

ANH = acute normovolemic hemodilution;

ASA = acetylsalicylic acid;

BMI = body mass index;

BSA = body surface area;

CABG = coronary artery bypass grafting;

CHF = congestive heart failure;

COPD = chronic obstructive pulmonary disease;

CPB = cardiopulmonary bypass;

CVD = cerebrovascular disease;

EBV = estimated blood volume;

EF = ejection fraction;

EPL = estimated percent fibrinolysis;

Hct = hematocrit;

Hgb = hemoglobin;

HTN = hypertension;

INR = international normalized ratio;

MA = maximum amplitude;

NSAID = nonsteroidal antiinflammatory drug;

NYHA = New York Heart Association;

PT = prothrombin time;

PTT = partial thromboplastin time;

PVD = peripheral vascular disease;

RBC = red blood cell;

T = temperature;

TEG = thromboelastography.

	Appendix 2

Top Abstract Introduction Patients and methods Results Comment Appendix 1 Appendix 2 Appendix 3 References

 
Preoperative Factors Studied for Association With Chance of Transfusion

Factor n % Tx Univariate p Value Multivariate p Value OR CI Procedure 0.001 0.0087 Combined 50 26.0 3.9 1.4–11.0 CABG or valve alone 257 8.6 Urgency 0.007 0.0167 Elective 145 6.2 Urgent/emergent 162 16.1 3.5 1.3–9.8 Reoperation 0.0007 Yes 25 32.0 No 282 9.6 Renal insufficiency/failure 0.0007 Yes 30 30 No 277 9.4 CHF 0.0053 Yes 118 17.8 No 189 7.4 DM 0.2129 Yes 108 8.3 No 199 13.1 CVD 0.0807 Yes 55 18.2 No 252 9.9 PVD 0.1776 Yes 69 15.9 No 238 10.1 Drugs affectingcoagulation 0.1378 Yes 232 12.9 No 75 6.7 Albumin (g/dL) 0.0013 <3 31 29.0 3 273 9.5 Preoperative INR 0.0001 1.4 275 9.1 >1.4 24 41.7 Body mass index (kg/m2) 0.1175 <30 230 13.0 30 77 6.5 Number of diseased vessels 0.16 0.0296 0–1 52 5.8 >1 239 13.0 5.8 1.2–28.5 Creatinine (mg/dL) <0.0001 <0.0001 <1.3 231 5.63 1.3 76 29.0 6.1 2.6–14.5 Age 0.0068 EF 0.1095 RBC mass 0.0012 0.0012 0.998 0.997–0.999 Body surface area 0.0024 EBV 0.0117 Preoperative PT <0.0001 0.0136 1.5 1.1–2.0 Preoperative platelets 0.0025 Preoperative Hgb <0.0001 Preoperative Hct 0.0008

CABG = coronary artery bypass grafting;

CHF = congestive heart failure;

CI = confidence interval;

CVD = cerebrovascular disease;

DM = diabetes mellitus;

EBV = estimated blood volume;

EF = ejection fraction;

Hct = hematocrit;

Hgb = hemoglobin;

INR = international normalized ratio;

OR = odds ratio;

PT = prothrombin time;

PVD = peripheral vascular disease;

RBC = red blood cell;

Tx = transfusion.

	Appendix 3

Top Abstract Introduction Patients and methods Results Comment Appendix 1 Appendix 2 Appendix 3 References

 
Intraoperative Factors Studied for Association With Chance of Transfusion^a

Factor n % Tx Univariate p Value Multivariate p Value OR CI Aprotinin 0.0066 Yes 27 40.7 No 123 17.1 Total grafts bypassed 0.0344 0.0626 3 88 27.3 0.4 0.1–1.1 >3 62 12.9 Total crystalloid 0.0002 0.0282 <2,500 mL 132 17.4 2,500 mL 13 61.5 4.7 1.2–19.0 CPB time 0.0048 0.0010 1.013b 1.005–1.020 Aortic cross-clamp time 0.0974 Total amount of ANH removed 0.0034 0.0049 0.999c 0.998–0.999

ANH = acute normovolemic hemodilution;

CI = confidence interval;

CPB = cardiopulmonary bypass;

OR = odds ratio;

Tx = transfusion.

^a These analyses refer to patients whose risk of transfusion owing to preoperative factors was 0.05;

^b Per minute;

^c Per milliliter.

	References

Top Abstract Introduction Patients and methods Results Comment Appendix 1 Appendix 2 Appendix 3 References

 

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