Mechanical methods of reducing blood transfusion in cardiac surgery: randomised controlled trial

Management of patients before cardiopulmonary bypass

All patients received standard premedication and anaesthesia. In all groups intravenous fluids and intravenous boluses of phenylephrine (50-100 μg) were used to maintain invasively monitored arterial blood pressure to within 20% of preoperative values. In the operating room antifibrinolytic treatment and choice of myocardial preservation remained at the discretion of the surgeon. All patients received anticoagulation treatment of 3 mg/kg of intravenous heparin to achieve an activated clotting time of >400 s, with an additional 1 mg/kg intravenous bolus to treat an activated clotting time of <400 s.

Fig 1.

Flow of patients through the trial

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Intraoperative cell salvage group A cell saver (Dideco Compact, Dideco, Mirandola, Italy) was used from incision until the end of surgery.

Combined treatment group After induction of anaesthesia 10 ml/kg of blood was removed from the central venous line while being replaced at the same time with an equivalent volume of modified gelatin (Gelofusine). The Harvest Blood Stream Recovery System, an autologous recovery system, was used to remove blood. The recovered blood was stored at room temperature.

Management of patients during cardiopulmonary bypass

All groups were managed identically during cardiopulmonary bypass. The cardiopulmonary bypass circuit was primed with 2 l of crystalloid solution. Cardiopulmonary bypass flows were 2.4 l/min/m². If a patient's haematocrit fell below 0.2, blood was added to the circuit. Moderate hypothermia was used to lower the patient's temperature to 32°C. Mean arterial pressures were maintained at 50-80 mm Hg.

Management after cardiopulmonary bypass

After the termination of the bypass all patients received intravenous protamine to neutralise circulating heparin. The dose of protamine matched that of the pre-bypass dose of heparin weight for weight.

Control group The residual cardiopulmonary bypass circuit volume was retransfused into the patient after protamine administration.

Intraoperative cell salvage group After protamine administration any shed blood and the residual cardiopulmonary bypass circuit volume were washed and centrifuged by the intraoperative cell salvage machine then retransfused.

Combined treatment group After protamine administration the autologous blood collected after induction of anaesthesia was retransfused. The cell saver was used in the same manner as in the intraoperative cell salvage group.

Intensive care

All patients were under the care of cardiac intensivists, who were blind to the allocation of patients to study group. The surgical team was involved only when further surgical issues arose. The threshold for transfusion of allogeneic red blood cells was the same in all groups: haemoglobin concentration <90 g/l and haematocrit <0.27. Administration of allogeneic blood coagulation products (fresh frozen plasma and platelets) was at the discretion of the cardiac intensivists.

Statistical analysis

Percentages of patients receiving the various blood products were compared in logistic regression models, controlled for surgeon. Differences between groups in these percentages were deemed significant if they achieved significance of P<0.025 in the Wald test. The Kruskal-Wallis one way analysis of variance was used to compare the differences between the groups in the amounts of blood products used and in the secondary outcomes.

Baseline characteristics

The distributions of sex, age, weight, left ventricular function, and aspirin administration were similar across the three groups (table 1). Parsonnet scores, which reflect a number of patient variables and allow preoperative risk stratification, were also similar across the groups.

Primary outcomes

Table 2 describes the differences in primary outcomes between the groups.

Comparison of intraoperative cell salvage and combined treatment

The combination of acute perioperative normovolaemic haemodilution and intraoperative cell salvage did not show any additional benefit over intraoperative cell salvage alone in relation to the number of patients needing allogeneic red blood cell transfusion, the mean number of units of allogeneic red blood transfused per patient, or the number of patients who were given any allogeneic blood product.

Most patients were not given allogeneic blood (fig 2). Fifty one patients received one unit of blood, and 25 received two. Nine patients needed a markedly higher amount of transfused blood (≥3 units). These patients were returned to the operating theatre for re-exploration of the mediastinum. A surgical cause of bleeding was found in seven of these patients (three in the control group and two each in the intraoperative cell salvage group and the combined treatment group).

Fig 2.

No of units of allogeneic blood transfused into patients

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The variations in haemoglobin concentration from before the operation to day 3 after the operation were similar in the three groups (table 3). No patient was given a transfusion of allogeneic blood after leaving the intensive care unit.

Table 3.

Haemoglobin concentrations (g/l) at different stages of patients' stay in hospital (n=84 in each group)

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Secondary outcomes

Table 4 shows the differences between the groups in the secondary outcomes. There were no differences between the groups in mediastinal drainage, time in intensive care, or length of stay in hospital. Table 5 shows perioperative variables in the three groups. Patients in the combination treatment group spent the longest time in the anaesthetic room. The median duration of acute perioperative normovolaemic haemodilution was 13 minutes. Groups were similar with respect to total anaesthesia and surgery times, and times on cardiopulmonary bypass and with the aorta cross-clamped. Perioperative complications were evenly distributed across the groups (table 6).

Intraoperative cell salvage

Our results are consistent with other published work. A recent meta-analysis of cell salvage in cardiac and orthopaedic surgery found that in cardiac surgery cell salvage marginally reduced use of allogeneic blood products (relative risk 0.85 (0.79 to 0.92)).10 However, none of the trials washed the salvaged blood before returning it to the patient, and the intraoperative cell salvage devices were used only postoperatively. Trials in which intraoperative cell salvage machines were used intraoperatively failed to meet standard eligibility criteria for the meta-analysis. Our method of intraoperative cell salvage maximised surgical salvage of red blood cells, and our washing of the residual cardiopulmonary bypass volume allowed optimal haemoconcentration, accounting for the greater efficacy of intraoperative cell salvage. Our study is the first to compare intraoperative use of intraoperative cell salvage with control treatment.

Acute perioperative normovolaemic haemodilution

Acute perioperative normovolaemic haemodilution is not well established in cardiac surgery. A meta-analysis of the treatment across surgical specialties concluded that it reduces the need for allogeneic red blood cells (odds ratio 0.31 (0.15 to 0.62)), but that the evidence in cardiac surgery was less compelling (0.51 (0.26 to 0.99)).11 This meta-analysis included 11 randomised controlled trials in cardiac surgery.12^–22 However, the quality of the evidence from these trials varied, only four of the trials having a transfusion protocol. 17 18 21 22 Overall the evidence for the benefit of acute perioperative normovolaemic haemodilution in reducing use of allogeneic red blood cells during cardiac surgery was equivocal.

Our study was designed to look at the additional benefit that acute perioperative normovolaemic haemodilution might give over intraoperative cell salvage alone. Our results indicate that acute perioperative normovolaemic haemodilution does not confer additional benefits in terms of reduced use of allogeneic transfusion (odds ratio 1.05 (0.56 to 1.98)). This may be because not enough blood was removed at the start of the procedure. Given the patients' severe coronary artery disease, we decided not to exceed a predonated volume of 10 ml/kg. Removing a greater volume of blood preoperatively may expose patients to ischaemic events and decreased myocardial contractility.23

Limitations

Just over half (43/84) the patients in the control group were given a transfusion—a considerably lower proportion than that reported for our institution in a previous study.4 We believe the main reason for this was that the transfusion threshold was reduced between the two studies from a haemoglobin concentration of 100 g/l to 90 g/l.

The lack of a protocol on the use of allogeneic blood coagulation products means that caution is needed in interpreting differences between the groups in the use of fresh frozen plasma and platelets. Our trial involved patients undergoing elective coronary artery bypass grafting. Although intraoperative cell salvage may be useful in more complex cardiac surgery or for patients with pre-existing coagulopathy, our findings cannot necessarily be extrapolated to such patients.

Intraoperative masking of mechanical conservation technique was not possible. This might have led to transfusion practice being driven by knowledge of allocation to group. This effect would be pronounced if no transfusion protocol were used. Our finding of a decrease in the number of patients who received a transfusion of allogeneic red blood cells may be related to the haemoglobin concentration that is used as the transfusion threshold, the efficacy of intraoperative cell salvage, or transfusion practices. Because the intensive care staff were blinded to allocation to group, and no protocol violations occurred, we can assume that the reduction in allogeneic red blood cell transfusion is related to the efficacy of intraoperative cell salvage.

Conclusions

The need for allogeneic red blood cell transfusion in elective coronary artery bypass grafting can be reduced by using intraoperative cell salvage. Acute perioperative normovolaemic haemodilution with intraoperative cell salvage confers no additional benefit. We believe a transfusion rate of 31% of patients undergoing elective coronary artery bypass grafting is still unacceptable. The lower safe limit of haemoglobin concentration in patients undergoing cardiac surgery—either while they are on bypass or postoperatively—is unknown. If this limit was known, and made use of, the combination of optimal pharmacological strategies with intraoperative cell salvage could achieve yet further reductions in the numbers of patients who need to be given transfusions of allogeneic red blood cells and blood coagulation products.