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Ann Thorac Surg 2004;78:1547-1554
© 2004 The Society of Thoracic Surgeons
a Division of Cardiac Surgery, Dalhousie University, Halifax, Nova Scotia, Canada
Accepted for publication April 27, 2004.
* Address reprint requests to Dr Hirsch, New Halifax Infirmary, QEII HSC, Division of Cardiac Surgery, 1796 Summer Room 2006, Halifax, Nova Scotia, B3H 3A7, Canada
ghirsch{at}dal.ca
| Abstract |
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METHODS: All 3,046 consecutive, isolated coronary artery bypass graft (CABG) procedures at a university hospital from 1995 to 1998 were included. A logistic regression model was created to identify independent predictors of allogeneic blood product transfusion. This model was validated using a prospective patient sample.
RESULTS: Overall use of allogeneic blood products was 23% with a crude operative mortality of 2.1%. In isolated, elective, first-time CABG cases, 16.9% received allogeneic blood products. Independent predictors of blood product usage in CABG patients were preoperative hemoglobin 12.0 or less, emergent operation, renal failure, female sex, age 70 years or older, left ventricular ejection fraction 0.40 or less, redo procedure, and low body surface area. Prospective validation of this model on 2,117 consecutive isolated CABG patients demonstrated an observed-to-expected allogeneic blood product transfusion rate ratio of 1.06.
CONCLUSIONS: This internally validated logistic regression risk model is a sensitive and specific predictor of allogeneic blood product use in patients undergoing isolated CABG. Utilization of this model allows for preoperative risk stratification and may allow for more rational resource allocation of costly blood conservation strategies and blood bank resources.
| Introduction |
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In efforts to reduce perioperative blood product use, several effective blood conservation techniques have been developed. These include the use of nonhemic prime for the cardiopulmonary bypass (CPB) machine [15], salvage of blood from the surgical field with cardiotomy suction [16], hemodilution during CPB, retransfusion of all contents of the oxygenator at the end of CPB, acceptance of perioperative normovolemic anemia [1719], and the routine use of antifibrinolytic medications. Additional techniques such as supplemental mechanical devices (ie, cell-saving systems), autotransfusion of shed mediastinal chest tube drainage, use of modified ultrafiltration, and autologous blood donation programs have also been demonstrated to reduce allogeneic blood product transfusion [2, 16, 2022]. However, the cost effectiveness of the indiscriminate application of these expensive strategies for patients undergoing isolated coronary artery bypass grafting (CABG) procedures has been questioned [7, 16, 23]. To allow for appropriate allocation of blood bank resources, a preoperative determination of which patients are at high risk of transfusion is desirable, and by inference would merit the expense associated with these conservation strategies.
In the present study, we have retrospectively reviewed the perioperative use of blood products in all patients undergoing an isolated CABG procedure from 1995 through 1998 in a single academic institution. On analysis of this retrospective data, we sought to develop a preoperative risk model capable of predicting the perioperative use of allogeneic blood products and subsequently validate this model on a separate group of patients to guide strategies of blood conservation.
| Material and Methods |
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Urgency status was determined using the Maritime Heart Centre Cardiac Surgery database definitions. An elective case was defined as any patient who remained clinically stable for more than 24 hours before the procedure. The term "in-house" elective referred to inpatients receiving medical treatment for more than 48 hours, pending surgery. Many of these patients were receiving intravenous heparin or nitrates until the time of operation. An urgent classification denoted patients who required a procedure to be performed within 24 hours to prevent further clinical deterioration, and an emergent/emergent salvage patient required an immediate operation. Body surface area (BSA) was calculated for each patient. Groupings for BSA were divided into approximate quartiles as follows: >2.04, >1.98 to
2.08, >1.86 to
1.90, and
1.80, as described previously [24]. All procedures were performed at a single tertiary care institution with university affiliation.
Blood Conservation Strategies
The techniques used at the study center included the use of nonhemic prime for the CPB machine [15], salvage of blood from the surgical field with cardiotomy suction [16], hemodilution during CPB, retransfusion of all contents of the oxygenator at the end of CPB, and acceptance of perioperative normovolemic anemia [1719]. The use of antifibrinolytic medications, either epsilon aminocaproic acid or tranexamic acid, was routine in all cases except for patients with a known sensitivity to the agent. Aprotinin was used in less than 1% of cases, typically reserved for Jehovah Witness patients and/or selected cases considered at an increased risk of perioperative bleeding (e.g., complicated redo procedures and/or known coagulopathy not including patients on warfarin). The decision to use aprotinin was usually a joint determination between the individual surgeon and cardiac anesthetist. Before the discontinuation of epsilon aminocaproic acid we infused an initial 100 to 150 mg/kg bolus followed by continuous infusion of 10 mg/kg per hour until the termination of the case. For tranexamic acid, our usual dose was a bolus of 10 mg/kg and then an infusion of 1 mg/kg per hour. Aprotinin was given as a full Hammersmith dose with 2 million units on induction with an additional 2 million units in the CPB prime, followed by 500,000 U per hour until the administration of protamine. An intraoperative cell-saving device was used only occasionally, again, in complicated reoperative and in OPCAB procedures. Postoperatively nonhemic volume expanders were used routinely (ie, crystalloid and pentastarch solutions).
Transfusion Triggers
The need for perioperative blood product transfusion was determined on an individual, patient-by-patient basis by 1 of the 7 attending cardiovascular surgeons or supporting resident house staff. Overall transfusion rates of allogeneic blood products were captured for blood products given during and after the operation. The principal blood product used was packed red blood cells (pRBCs). The decision to use blood products other than pRBCs (ie, platelets, fresh frozen plasma, and cryoprecipitate) was made on a case-by-case basis for patients with evidence of ongoing blood loss or a demonstrable coagulopathy. Preoperative transfusions were not included in this analysis.
Although no rigid criterion or single absolute hemoglobin (Hb) value was used as a trigger for transfusion, in general, allogeneic blood product transfusion was not considered until the serum Hb was less than 7 g/dL, unless evidence suggested ongoing blood loss or the patient was clinically considered at risk for inadequate oxygen delivery. This determination included patients with signs of insufficient tissue perfusion (lactate levels > 2, mixed venous oxygen saturation < 65%, urine output < 0.5 mL · kg1 · h1), significant hemodynamic instability, the need for two or more inotropic agents, utilization of a intraaortic balloon pump (IABP), or organ dysfunction in two or more systems.
The addition of pRBCs to the CPB machine prime was considered (although not routinely given) if the calculated dilutional hematocrit was less than 0.21. The decision to add pRBCs to the prime was made in collaboration among the surgeon, anesthetist, and perfusionist at the time of the surgical procedure.
Statistics
The primary outcome was the transfusion of any allogeneic blood product (pRBCs, plasma, platelets, or cryoprecipitate) during the intraoperative or postoperative period. Statistical analysis was performed using SAS 8.2 (SAS Institute Inc, Cary, NC). Continuous and discrete variables underwent univariate analysis by t test,
2, or Fisher exact test, as appropriate. Independent preoperative predictors of blood transfusion were identified by logistic regression, and variables were retained if their associated p < 0.05. A C-statistic was calculated as a measure of the sensitivity and specificity of the logistic regression model. The C-statistic is equivalent to the area under the receiver operating characteristic curve in which a C-value of 0.5 indicates no discriminatory power and a C-value of 1.0 indicates a perfect discrimination between patients requiring blood transfusion. Validation of this stepwise logistic model was performed using a bootstrapping procedure. C-statistic values were calculated for each of 200 bootstrap samples, and the 95% confidence interval (CI) was obtained from the 2.5 and 97.5 percentiles of the bootstrap distribution. In a second validation step, the original model (derivation group) was applied to a subsequent group of 2,117 isolated CABG cases (validation group) performed from January 1999 through September 2001.
| Results |
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The in-hospital mortality for the derivation group was 2.1% (n = 63). Of these 63 patients, 85.7% received at least one allogeneic blood product transfusion versus 21.8% in the remaining patients (p < 0.001). Twenty-three patients (0.76%) required reexploration for postoperative bleeding, and 100% of these patients received a blood product.
Procedure Urgency, Redo Operations, and Intraaortic Balloon Pump Use
Procedure urgency was associated with increased rates of transfusion. Isolated elective ("true elective" and "in-house" elective) CABG procedures were associated with a transfusion rate of 18% versus 40% and 56% for urgent and emergent/emergent salvage procedures, respectively (p < 0.001) (Fig 1). Redo operations accounted for 7.7% of all isolated CABG cases, and elective redo operations (n = 162) had a higher transfusion rate (34%) than elective first-time CABG (17%) (p < 0.001). Approximately 10% of OPCAB procedures (n = 8) were done on an urgent basis, and 6% (n = 5) of OPCAB cases were redo operations.
Only 6.3% (n = 191) of patients required perioperative IABP assistance. Of these patients, 60.2% (n = 115) received an allogeneic transfusion compared with 20.6% transfusion rate in all other patients not requiring IABP use (p < 0.001). The timing of insertion of an IABP also appeared to be related to the risk of transfusion. Patients who required an IABP preoperatively (n = 153) had a transfusion rate of 54.2%, those receiving an IABP intraoperatively (n = 19) required a blood transfusion 73.7% of the time, and nearly all patients (94.7%) requiring a postoperative IABP (n = 19) received a blood transfusion.
Univariate Predictors
Several univariate risk factors were associated significantly with increased rate of blood transfusion; the strongest risk factor was the presence of a low preoperative Hb (
12.0 g/dL) with a univariate odds ratio of 13.1 (Table 3). The mean ± SD preoperative Hb level of patients receiving blood transfusions was 12.0 ± 1.8 g/dL, compared with 14.0 ± 1.4 g/dL for patients not requiring blood transfusions (p < 0.001). In addition, low BSA (< 1.80), female sex, and renal failure were also associated with an increased rate of allogeneic transfusion. However, preoperative Hb was significantly lower in patients with preoperative renal failure (11.3 ± 1.8 g/dL versus 13.7 ± 1.6 g/dL with normal renal function, p < 0.001) and between sexes (12.5 ± 1.5 g/dL and 13.9 ± 1.6 g/dL in female versus male, p < 0.001). Additionally, a greater proportion of women had a preoperative Hb less than 12.0 g/dL (36.3% versus 12.9%, female versus male, p < 0.001). Furthermore, more women were in the lowest quartile of BSA (< 1.80) than men (71.5 versus 15.7 respectively; p < 0.001).
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As a second validation step, the model was subsequently applied to a separate validation group of 2,117 consecutive patients (validation group) (January 1999 through September 2001). The validation group was similar to the derivation group except for a higher proportion of patients with diabetes mellitus, hypertension, and hypercholesterolemia (Table 1) and a lower proportion of patients undergoing a redo procedure or urgent status (Table 2). The predicted allogeneic blood product transfusion rate in the validation group was 22.2% while the actual observed transfusion rate was 23.6%, with an observed-to-expected ratio of 1.06. Using the coefficients from the original model, the C-statistic for the validation group was 0.79, with a 95% CI of 0.77 to 0.81 obtained by bootstrap procedure.
Risk Stratification
In using the generated risk model, we were able to subdivide the original cohort (derivation group) of patients into four groups based on the predicted risk of allogeneic transfusion: very low (
10% risk), low (> 10% to 20% risk), intermediate (> 20% to 50% risk), and high (> 50% risk) (Fig 3). When using these cut-off points, most patients in our original series of patients were allocated to the very low risk (39%) or low-risk group (29%), followed by an equal distribution in both the intermediate and high-risk groups (16% in each group). A small percentage of allogeneic transfusion occurred in the very low and low-risk groups, whereas substantially larger percentages of patients were transfused in both the remaining two groups (p < 0.0001).
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| Comment |
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The lowest transfusion rates were achieved for elective, first-time isolated CABG procedures, with a rate of 17.3% when using CPB and 2.7% for OPCAB cases (Fig 1) Costly supplemental methods of blood conservation, such as the use of preoperative donation of autologous blood and postoperative autotransfusion of shed mediastinal blood [21], were not used at our institution and therefore not included in this study. These data suggest that indiscriminate implementation of these conservation techniques is not necessary to achieve relatively low overall transfusion rates.
A risk model generated from a retrospective analysis of 3,046 consecutive, isolated CABG patients reliably predicted allogeneic blood product transfusion rates based on eight, easily identifiable, preoperative risk factors. Independent risk factors identified for blood transfusion in isolated CABG patients in this study included preoperative Hb less than 12.07 g/dL, emergent operation, renal failure, female sex, age older than 70 years, EF less than 0.40, redo procedure, and low BSA, are similar to those reported by others [1]. Validation of this model in a separate group of 2,117 CABG patients confirmed its predictive value.
Practical Implementation of the Predictive Model
The safety and cost efficacy of autologous blood donation programs remain controversial [36]. Data derived from a prospective study examining a preoperative autologous donation program for CABG patients demonstrated significant associated cost implications in the order of $508,000 to $909,000 (US dollars) per quality-adjusted year of life saved [31]. Similarly, whereas autotransfusion of shed mediastinal blood may reduce the risk of infection and administrative errors associated with stored blood, several studies, including two prospective, randomized trials, failed to show any significant reduction in the amount of allogeneic transfusion requirements in postoperative cardiac patients [22, 37, 38].
One conclusion to be drawn from these studies is that the cost of implementing these techniques is not justified. An alternate conclusion may be that widespread utilization of these strategies may not be rational; however, selected use in patients most likely to benefit may demonstrate a cost-effective savings. For efficacious delivery, patients who are most likely to benefit from these interventions would need to be identified preoperatively.
Our findings suggest that, based on easily identifiable preoperative patient characteristics, subgroups of patients have a very low, low, intermediate, or high risk of receiving allogeneic blood products (Figs 2, 3). Utilizing the predictive model in this manner, the efficacy of costly blood conservation strategies could be evaluated in a subset of patients, and cost-effectiveness determined.
An example, proposed by others in both limited cardiac and noncardiac patient populations, are potential cost savings by eliminating the need for an obligatory preoperative allogeneic blood cross-match (at an additional cost of Canadian $72.00/patient at our center) in patients identified as "low risk" for transfusion. If we set the criteria for a "low-risk patient" at a predicted risk of transfusion of 20% or less (as suggested by others in noncardiac operation patients [39] (n = 2,058 or 68% of isolated CABG cases in our center), the cost saving per annum of performing a group and screen only (ABO typing and basic antibodies) versus a full cross-match is approximately $148,000 ($Cdn) at our institution. We have, since the close of this study, initiated a "no cross-match" policy in a limited manner for elective low risk patients at our institution. At 6 months (n = 300 patients), we have experienced no morbidity or mortality related to this procedural change.
This model, in contrast to previous studies [1, 34, 35], examined the transfusion rates of all postoperative blood products for a large group of consecutive patients and included both on-pump and off-pump cases, first-time and redo CABG, as well as elective, urgent, and emergent cases. In addition, this robust predictive model was further validated on a separate large group of consecutive patients. Others [25] have suggested that, due to baseline differences, ubiquitously applying a predictive model to all isolated CABG patients may not be appropriate and use of the model should therefore be limited to elective, first-time CABG cases. In contrast, our model included 1,011 patients (33% of the derivation group) who were, as stated "in-house" elective receiving medical treatment (including intravenous nitrates) for more than 48 hours before operation. Inclusion of these patients and subsequent application of our model to a large validation group, using only "basic" blood conservation strategies, demonstrated its generalizability to a more diverse group than purely elective, first-time isolated CABG cases. These results broaden the application of such data to a more representative group of patients in most surgeons' practices. An example of an easy-to-use preoperative "risk-score" card based on our model that could be used to predict the risk of transfusion is illustrated in Figure 4.
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Although utilizing the predictive model allows for stratification of risk based on preoperative risk factors, an overlap exists in groups of patients with two or more risk factors (Fig 2). Nevertheless, patients at either extreme of the model have predictable rates of transfusion and therefore are amenable to both further study and cost-saving strategies.
In summary, we evaluated blood transfusion practices after CABG operation. The patient population was representative of a tertiary referral center and the findings are likely applicable to other similar populations found in North American centers [32, 33]. A stable predictive model was generated from a large CABG population in which we could predict preoperatively, on an individual basis, the risk of receiving any blood products after operation. The strategy of introducing a no-cross-match policy is one example of the utility of the model presented in this study. The model provides the framework for a rational approach of appropriately targeting more costly strategies such as autologous blood donation, cell-saving systems, and the use of more expensive fibrinolytics (ie, aprotinin). By eliminating unnecessary expense among low-risk patients and identifying high-risk patients in whom more costly blood conservation strategies could be effective, this predictive model could have a substantial effect on both quality and cost of care.
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