Extracorporeal circuitry and components are major contributors to haemodilution during open heart surgery. Haemodilution, which is induced by a large fixed crystalloid prime volume, may reduce haematocrit (HCT) values to a level that necessitates the administration of homologous packed red blood cells (PRBCs). A HCT of less than 20% during cardiopulmonary bypass (CPB) and transfusion of PRBCs are each associated with an increased probability of adverse events in cardiac surgery [1–3]. Retrograde autologous priming (RAP) has been demonstrated to decrease the number of homologous RBC transfusions associated with ‘excessive’ haemodilution during CPB [4–7]. Although those studies [4–7] showed a decrease in blood requirements, patients with higher risk for perioperative transfusion [i.e. low body weight and low body surface area (BSA)] were excluded.
We conducted a prospective, randomized study with strict transfusion criteria to determine whether RAP in small adult patients (BSA < 1.5 m2) could reduce CPB-induced haemodilution and, therefore, requirements of allogeneic blood transfusions.
Patients and methods
The current prospective cohort study was approved by the ethics committee of the Beijing Anzhen Hospital. The sample size was 120 patients, based on demonstrating a reduction in transfusion from 60 to 40% , with a confidence level of 0.95 and a power of 0.8. Both medical and nursing staff in the ICU and the postoperative wards were blinded from the priming technique used for the purpose of this study. The primary endpoint of the study was to compare RAP of the CPB circuit with conventional priming in reducing the percentage of patients receiving homologous blood transfusion. Secondary endpoints included the trend of HCT and colloid osmotic pressure (COP) during the perioperative period, the volume of homologous blood transfused per patient who received transfusion and postoperative clinical outcomes.
One hundred and twenty consecutive adult patients with a BSA of less than 1.5 m2 scheduled for elective primary cardiac surgical procedures by the same surgical team were investigated. Exclusion criteria were age more than 70 years or less than 16 years, left ventricular ejection fraction less than 30%, haemodynamic instability or urgent/emergency operations, neurological deficits or a history of stroke, preoperative heparin or warfarin therapy, a preoperative HCT value less than 33% and estimated CPB time of at least 90 min.
After written informed consent was obtained, the patients were randomly allocated either to the standard priming group (n = 60) or to the retrograde priming group (RAP group, n = 60). Randomization was performed by a computer-generated random number sequence.
The patients were brought to the operating room, where a large-bore peripheral intravenous line was placed. A radial artery catheter and the continuous monitors were placed. General anaesthesia was induced with midazolam, propofol and either fentanyl or sufentanil. After intubation, anaesthesia was maintained with isoflurane and neuromuscular blockade. The target mean blood pressure (BP) was 70 mmHg before CPB and 60 mmHg after CPB. Anticoagulation was achieved with heparin 300 U kg−1 before CPB. After separation from CPB, 1 mg protamine sulphate for each 100 U total heparin dose was administered. At the conclusion of the procedure, the patients were transferred to the cardiac ICU.
The extracorporeal circuit consisted of roller pumps (Cobe Cardiovascular Inc., Arvada, Colorado, USA), a hollow fibre membrane oxygenator (Capiox SX18; Terumo Inc., Tokyo, Japan) in combination with the cardiotomy reservoir and an arterial filter (Quart arterial filter; Maquet Cardiopulmonary AG, Hirrlingen, Germany). The tubing diameter of the perfusion set was 5/16 in. (7.9 mm) for both the arterial side and the venous side (two tubes). The circuit (uncoated) was primed with approximately 1000 ml of sodium acetate Ringer's solution, 0.25 g kg−1 of mannitol (20%), 30 meq of bicarbonate and 5000 IU porcine heparin. For CPB, standard cannulation of the ascending aorta and venae cavae was performed.
Cardiopulmonary bypass management
Intermittent cold (4°C) blood cardioplegia was infused by means of a heat exchanger. Patients were actively cooled to 32°C during CPB. Management of CPB included alpha-stat pH management, targeted mean arterial BPs between 50 and 80 mmHg and pump flow rates of 2.0–2.4 l min−1 m−2. Patients were warmed to 37°C before separation from CPB. Perfusion equipment and techniques remained constant throughout the study period.
Shed mediastinal blood suction and left heart venting were actively performed with two separated roller pumps. The technique of separated suction was not used. The blood contained in the CPB circuit was always returned to the patient before leaving the operating room. The heart–lung machine was always kept as close as possible to the operating table in order to reduce tubing length. Ultrafiltration technique was not routine in adults undergoing open heart surgery.
Technique for retrograde autologous priming
Heparin was administered (300 U kg−1) to obtain an activated clotting time of more than 400 s. Before RAP was started, mean arterial pressure was maintained to approximately 90–100 mmHg using small doses of intravenously administered phenylephrine. A recirculation bag was connected to the purge line of the arterial filter. First, after ascending aorta cannulation was completed, the arterial line was drained into the recirculation bag by displacing approximately 150 ml of priming solution with the patient's blood from the aorta. Then the arterial line connecting the patient to the arterial filter was clamped. Second, once the venous line had been connected to the venous cannula, the variable occlusion clamp on the venous line was slowly released allowing the venous blood to drain from the patient. At the same time, the arterial pump was slowly rotated at a sufficient flow (400–600 ml min−1) to maintain a constant level in the venous reservoir. The crystalloid priming fluid of the venous reservoir was driven at a minimal level into the bag. The venous side of the circuit was drained, slowly replacing the crystalloid priming volume by filling the circuit with the patient's blood. This fluid mixture of the venous reservoir was slowly pumped through the membrane oxygenator and arterial filter, displacing the priming fluid of the tubing, the oxygenator and the arterial filter into the recirculation bag. The recirculation bag was then connected to the venous reservoir, so that crystalloid fluid replacement could be performed during CPB upon haemodynamic requirements. The arterial line and venous clamps were then fully opened and the pump flow increased to establish full CPB. The procedure was performed while the patient's haemodynamic status was carefully monitored. The retrograde priming procedure required 3–5 min before the onset of CPB.
Arterial and mixed venous blood samples were obtained for gas analyses and measurement of plasma COP. Sample time points were as follows: after induction of anaesthesia, 10 min after aortic cross-clamp, 10 min after declamping, after CPB, at ICU arrival and 6 h after ICU arrival. Perioperative parameters were measured, including arteriovenous oxygen difference [P(av)O2], breathing index, oxygenation index, total bilirubin, direct bilirubin, serum glutamic-oxaloacetic transaminase, blood urea nitrogen and creatinine. The outcomes of patients were evaluated by awake time, duration of postoperative ventilation and length of ICU and hospital stay.
All patients followed strict transfusion criteria. PRBCs were transfused during CPB if the haemoglobin (Hb) concentration was below 8.0 g dl−1 or the HCT was less than 24%, and after CPB and during all the hospital stay if the Hb was below 9 g dl−1 or the HCT was less than 27%.
The data were maintained in an Access database. Normality for all variables was tested with the Shapiro Wilk's test. Normal distributed variables concerning both study and control circuits were compared using Student's t-test for independent samples. For other variables whose distributions were not normal, nonparametric statistical tests equivalent to the parametric Student's t-test were used (Mann–Whitney and Wilcoxon test). For all statistical analyses, a P value of less than 0.05 was considered significant. All statistical analyses were performed using SPSS 11.5 (SPSS Inc., Chicago, Illinois, USA) for Windows.
All patients completed the surgery without complications and were successfully discharged. The two groups were compared with respect to baseline characteristics, the type of surgical procedure and duration of aortic cross clamping and CPB (Table 1). There were no statistically significant differences.
The amount of fluids administered before CPB was 680.4 ± 235.1 ml in the RAP group and 759.8 ± 313.8 ml in the standard priming group (P > 0.05). The average priming volume was 1185.3 ± 98.9 ml in the standard priming group. The priming volume removed in the RAP group was 614.8 ± 138.8 ml, which represented 53.6 ± 11.0% of priming volume. This made the actual priming volume of the RAP group significantly less than that of the standard priming group (P < 0.01). The average of the RAP volumes returned was 264.5 ± 171.4 ml. Intraoperative urine output was similar for the standard priming and RAP groups (Table 2).
Sixteen (26.7%) of 60 patients in the RAP group received a transfusion on pump as compared with 50 (83.3%) of 60 patients in the standard priming group (P < 0.001). Perioperatively, fewer patients in the RAP group received PRBCs than did the standard priming group patients [30 (50%) vs. 54 (90%)] (P < 0.01). Amongst patients who received transfusion on pump, the number of homologous units of PRBCs was less in the RAP group than that in the standard priming group (0.94 ± 0.32 vs. 1.48 ± 0.68 units, P = 0.03). Total number of homologous units of PRBCs was less in the RAP group than that in the standard priming group amongst patients who received transfusion perioperatively with no statistically significant differences (1.24 ± 0.54 vs. 1.69 ± 0.69 units, P = 0.15) (Table 3). The transfusion of fresh frozen plasma and platelets intraoperatively and postoperatively was not significantly different between the two groups.
The HCT values during CPB were significantly higher in the RAP group (22.8 ± 1.2 vs. 27.0 ± 1.9% at 15 min after cross-clamp, P < 0.01; 22.8 ± 1.8 vs. 26.3 ± 1.6% at 15 min after declamping, P < 0.05, respectively) (Fig. 1). Lowest COP values were seen at 10 min after cross-clamp in both groups. COP values were significantly higher in the RAP group (14.6 ± 2.0 vs. 12.5 ± 1.7, P < 0.05) (Fig. 2).
The mean total dose of phenylephrine used during CPB was 2.6 ± 2.1 mg in the standard priming group and 2.7 ± 2.8 mg in the RAP group to achieve the mean target BP (P > 0.05). Postoperative respiratory, hepatic and renal functions were not significantly different in RAP patients as compared with standard priming patients. There were no significant differences in postoperative clinical outcomes (Table 4).
A minority of patients having cardiac procedures (15–20%) consume more than 80% of the blood products transfused at operation . Blood must be viewed as a scarce resource that carries risks and benefits. Many preoperative and perioperative interventions are likely to reduce bleeding and blood transfusion.
Multivariables, including patient and procedure-related factors, are associated with blood transfusion during CPB . Review of published reports identified that small body size (low preoperative RBC volume) is associated with increased intraoperative blood transfusion. A recent evidence-based review  of the practice of CPB in adults, focusing on the topic of haemodilution, concluded that ‘efforts should be made to reduce haemodilution, including reduction of prime volume, to avoid subsequent allogeneic blood transfusion’.
RAP has been reported to reduce allogeneic blood transfusion, as well as providing a synergistic effect with other prime reduction techniques . However, most reports focused on RAP in patients having a BSA of more than 1.7 m2. In the present prospective cohort study of 60 no-RAP and 60 RAP small adult patients (BSA < 1.5 m2), the authors observed a lower transfusion ratio and transfusion volume in the RAP group. These findings suggest that RAP, as a blood conservation method, is an efficient, well tolerated and inexpensive technique in small adult patients.
RAP has been recently introduced into clinical practice as a technique to limit the severity of haemodilution on CPB. RAP of the CPB circuit is not a new technique. In 1960, Panico and Neptune  first described a method of autologously priming the CPB circuit to reduce the requirements for homologous blood, which was used to prime the CPB circuit at that time. This technique did not prove popular until the late 1990s when numerous authors published modifications of this technique of priming of the CPB circuit. Although the technique of RAP varies depending upon the pump configuration and the CPB circuit design, the majority of authors described the technique of RAP in which the majority of prime displacement occurs in a retrograde direction through the aortic cannula. In the present study, the majority of prime displacement occurred in an antegrade direction for safety.
The current CPB circuit prime volume is still large for small adults. At the beginning of CPB, the deleterious nature of profound haemodilution will lead HCT values to drop. The lower HCT makes the patient more likely to reach a transfusion threshold and, therefore, receive a homologous blood product . Several large observational studies [14–16] have identified that a nadir HCT of less than 20% during CPB and transfusion of PRBCs are each associated with an increased probability of adverse events in adults. DeFoe et al.  reported that patients with intraoperative HCT values less than 19% are at significantly greater risk than those with a HCT more than or equal to 25%. Transfusion practices may vary because neither an optimal HCT nor a uniform transfusion trigger has been established. Nowadays, there is a pressing need to keep the optimal management of HCT and transfusion during CPB at a higher level . In our study, PRBCs were given on bypass when the HCT fell to 24% or less and in the postoperative period when the HCT fell to 27% or less.
Cormack et al.  used a low-prime CPB circuit and autologous circuit priming techniques in small adult patients. The priming volume was reduced from 1700 to 600 ml, the incidence of low HCT (<20%) during CPB was reduced from 70 to 15%, and there was a reduction in the incidence of renal complications, but the volume of blood transfusion was not different. In this trial, the priming volume of the CPB circuit was reduced from 1200 to 400 ml. The nadir HCT during CPB was significantly higher in the study group. Only 26.7% of patients received transfusion. The overall transfusion rate and intraoperative number of homologous units of PRBCs amongst patients who received transfusion were significantly less in the RAP group than in the standard priming group.
The current study showed a significantly higher COP during CPB, in addition to a higher HCT. However, the benefit for patients concerning pulmonary, renal or hepatic function could not be confirmed in the present study.
The results of our study show that reducing CPB priming volume by the RAP technique reduces homologous blood transfusion in small adult patients. A higher COP during CPB could be gained in addition to a higher HCT. However, the positive effect of RAP on postoperative performance of these patients was not shown in this study. Many techniques have been proven to reduce allogeneic blood transfusions such as acute normovolaemic haemodilution, mini-bypass circuit and coated circuit . It is believed that a better effect of blood conservation and even a better clinical outcome will be achieved when more than one technique is used.
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