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J Thorac Cardiovasc Surg 1998;115:426-439
© 1998 Mosby, Inc.
CARDIOPULMONARY SUPPORT AND PHYSIOLOGY |
This work was supported in part from a grant from Miles (Bayer) Pharmaceuticals, New Haven, Conn., to T.K.R.
Read at the Twenty-third Annual Meeting of The Western Thoracic Surgical Association, Napa, Calif., June 25-28, 1997.
Received for publication Feb. 14, 1997; revisions requested May 7, 1997; revisions received June 6, 1997; accepted for publication June 9, 1997. Address for reprints: Todd K. Rosengart, MD, The New York Hospital–Cornell Medical Center, Department of Cardiothoracic Surgery, 525 East 68th St., F-2103, New York, NY 10021.
Abstract
Objectives: The obligatory hemodilution resulting from crystalloid priming of the cardiopulmonary bypass circuit represents a major risk factor for blood transfusion in cardiac operations. We therefore examined whether retrograde autologous priming of the bypass circuit would result in decreased hemodilution and red cell transfusion. Methods: Sixty patients having first-time coronary bypass were prospectively randomized to cardiopulmonary bypass with or without retrograde autologous priming. Retrograde autologous priming was performed at the start of bypass by draining crystalloid prime from the arterial and venous lines into a recirculation bag (mean volume withdrawal: 880 ± 150 ml). Perfusion and anesthetic techniques were otherwise identical for the two groups. The hematocrit value was maintained at a minimum of 16% and 23% during and after cardiopulmonary bypass, respectively, in all patients. Patients were well matched for all preoperative variables, including established transfusion risk factors. Subsequent hemodynamic parameters, pressor requirements, and fluid requirements were equivalent in the two groups.
Results: The lowest hematocrit value during cardiopulmonary bypass was 22% ± 3% versus 20% ± 3% in patients subjected to retrograde autologous priming and in control patients, respectively (p = 0.002). One (3%) of 30 patients subjected to retrograde autologous priming had intraoperative transfusion, and seven (23%) of 30 control patients required transfusion during the operation (p = 0.03). The number of patients receiving any homologous red cell transfusions in the two groups during the entire hospitalization was eight of 30 (27%; retrograde autologous priming) versus 16 of 30 (53%; control) (p = 0.03).
Conclusions: These data suggest that retrograde autologous priming is a safe and effective means of significantly decreasing hemodilution and the number of patients requiring red cell transfusion during cardiac operations.
Homologous blood transfusions remain a persistent risk of cardiac operations. Two to four donor exposures are required in up to 70% of patients, despite the recent introduction of many innovative blood conservation techniques.
1-4 In fact, coronary bypass grafting has been associated with about 10% of all blood transfusions in the United States. 5 Hemodilution, the direct result of the mixing of the patient's blood volume with the crystalloid cardiopulmonary bypass (CPB) circuit prime, is a unique and obligatory feature of cardiac surgery as currently practiced that imposes a significant risk for red blood cell transfusions. 6,7 In this regard, the decrease in hematocrit value associated with hemodilution may lead to obligatory red cell transfusions resulting from unacceptably lowered hematocrit values during or after cardiac operations. Incremental improvements have been made in decreasing the hemodilution associated with CPB, such as through the use of "low prime" oxygenators. 6,7 Nevertheless, we hypothesized that a significant margin for minimizing hemodilution and thereby decreasing homologous red cell transfusions could be achieved with the use of a technique called retrograde autologous priming (RAP). With this technique, the crystalloid CPB prime is evacuated from the pump circuit at the initiation of bypass in advance of the patient's blood column.
Our strategy would bring nearly full circle the technique of blood versus crystalloid priming. The CPB circuit had historically been primed with up to 8 units of whole blood. Subsequently, the virtues of moderate and even "extreme" hemodilution in terms of blood circulation, microcirculatory flow, and organ function were advanced, 8-12 and use of an asanguineous pump prime ultimately received widespread acceptance. In 1960, Panico and Neptune 13 described a technique to eliminate donor blood prime from the CPB circuit by instead substituting 1 L of physiologic saline solution. After arterial cannulation, the patient's blood was drained retrogradely into the CPB circuit. Panico and Neptune 13 demonstrated in a series of 25 patients that the use of a bloodless prime reduced homologous blood transfusions. Thirty-seven years later, we now report a modification of their technique in which we use currently available technologies that decreases the number of patients requiring homologous red cell transfusions associated with "excessive" hemodilution during CPB.
Patients and methods
Study design.
Sixty patients having first-time coronary bypass were prospectively randomized by envelope selection without replacement to CPB with (n = 30) or without (n = 30) RAP. Exclusion criteria were age less than 18 or greater than 85 years, left ventricular ejection fraction less than 30%, emergency procedure, history of stroke, hematocrit value less than 30%, and weight less than 55 or greater than 115 kg. Physicians ordering blood transfusions were blinded for randomization. Informed consent and was obtained from each patient and the study was approved by the Investigational Review Board of The New York Hospital–Cornell Medical Center.
Anesthesia and CPB setup.
Patients received lorazepam and morphine intramuscularly for premedication before arrival in the operating room. Anesthesia was induced with intravenous fentanyl, thiopental, and midazolam. Muscle relaxation was achieved with pancuronium. After intubation, anesthesia was maintained with a combination of fentanyl, midazolam, and isoflurane. Hemodynamic monitoring and blood sampling were obtained by means of radial and pulmonary artery catheters. A urinary catheter with indwelling temperature probe was used for urine output measurements and core temperature assessment.
The extracorporeal circuit consisted of a hollow-fiber membrane with integral cardiotomy (Terumo Medical Corporation, Somerset, N.J.), centrifugal arterial pump (Bio-Medicus, Medtronic Bio-Medicus, Eden Prairie, Minn.), 4:1 "coil in bucket" blood cardioplegia set (Gish Biomedical Incorporated, Irvine, Calif.), arterial line filter, and a polyvinylchloride tubing set. The total pump prime was 1400 ml, which consisted of 1100 ml of electrolyte solution (Plasma-Lyte 7.4, Abbott), 10,000 units U.S. Pharmacopeia porcine mucosa heparin, 100 ml normal serum albumin, and 200 ml 20% mannitol. A calculated volume of intraoperative autologous donation blood was withdrawn at the start of the operation to yield a CPB hematocrit value of at least 18%, as previously described. 14 Initial heparin dosing (300 units/kg) was followed by a standard cannulation of the ascending aorta and right atrium with 20F and 36/51F two-stage venous cannulas, respectively (Sarns/3M, Inc., Ann Arbor, Mich.).
RAP.
For the implementation of RAP, a 
-inch recirculation line was diverted off the arterial outlet line of the oxygenator. This line was attached to a 1000 ml blood transfer bag, which was hung on the pump mast 20 cm higher than the right atrium. In addition, a -inch line was "y'd" off the venous line just before its connection to the venous inlet of the oxygenator. During the entire RAP process, a minimum systolic blood pressure of 100 mm Hg was maintained with oxymetazoline HCl (Neo-Synephrine), as needed. RAP was implemented in three stages, beginning after the activated clotting time (International Technidyne Corporation, Edison, N.J.) reached 400 seconds, as follows (Fig. 1):
1. Arterial line drainage.
With the systolic arterial blood pressure maintained greater than 100 mm Hg, the recirculation line clamp was slowly released. This allowed for the patient's blood to travel through the pump arterial line from the aorta through the filter, into the recirculation line, and up into the 1000 ml transfer bag. Up to 400 ml was recovered from the pump circuit at this time.
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3. Venous line drainage.
As CPB was initiated, almost all of the 400 ml of pump prime from the venous line was drained into the recirculation bag. Once the venous line fluid became sanguineous, this -inch line was clamped. The bag was then rehung to allow for crystalloid transfusion as necessary. The targeted RAP volume to be withdrawn was 1100 ml.
Performance of CPB.
CPB was otherwise conducted as per standard practice in all patients. Mean arterial pressure was maintained at or greater than 50 mm Hg, and the venous reservoir was maintained at a level greater than 400 ml. Standard level sensor and air emboli detectors were used for protection against air embolism. Left ventricular venting was accomplished by means of the aortic root cannula. Pericardial blood was aspirated and collected in the reservoir. The hematocrit value was maintained at a minimum of 16%. Moderate hypothermia (bladder temperature G28° C) was used. Nonpulsatile flow rates during CPB ranged from 1.6 L/min per square meter during hypothermia up to 2.4 L/min per square meter during normothermia. The protocol mandated that hematocrit values be maintained at a level of 28% or less at all times during hypothermia by adding crystalloid solution, as needed. After aortic crossclamping, cold blood cardioplegic solution (15 ml/kg) was given at 15- to 20-minute intervals. Blood gases were managed by the alpha-stat method. Patients were slowly weaned from CPB when a bladder temperature of 35.5° C was reached. Heparin was neutralized with equal doses of protamine sulfate. Total fluid administration was measured. The pump contents and any additional fluid in the Cell Saver System (Sarns, Haemonetics Corp., Braintree, Mass.) were immediately processed and transfused after the patient's condition was deemed stable, and the aortic cannula was removed. The hematocrit value was maintained at a minimum of 23% after CPB.
Postoperative care.
All patients were admitted to the intensive care unit and treated as per standard clinical practice. Platelets (6-unit pack) were transfused for chest tube drainage greater than 600 ml in the first 3 hours after the operation, followed by 2 units of fresh frozen plasma if subsequent drainage was greater than 100 ml/hr. Cardiac index was maintained greater than 2.0 L/min per square meter and mean arterial pressure was maintained at 60 mm Hg or higher by crystalloid infusion or vasoactive agents, as appropriate.
Data analysis.
Data were collected as indicated by a research nurse who was blinded to the randomization. All patients were followed up until the day of discharge. Safety data included continuous intraoperative hemodynamic and electrocardiographic monitoring and analysis of the postoperative electrocardiogram for myocardial infarction, blood urea nitrogen and creatinine for renal dysfunction, and survey for clinical evidence of cerebrovascular accidents. Data were collected and analyzed with the use of spreadsheet and analytical software (Excel, Microsoft Corporation, Redmond, Wash., and STATISTIX, Tallahassee, Fla.). By way of normalizing for red cell transfusions, a corrected hematocrit value was generated by subtracting the number of packed red cell transfusions times three from the measured hematocrit value obtained at all time points after these transfusions. Comparisons between groups of numeric values were made by means of a two-sample t test. The 
2 test was used for comparison of proportions.
Results
Definition of populations and performance of RAP.
Sixty adult patients scheduled for nonemergency primary coronary artery bypass were enrolled in this study over a 3-month period and randomized to CPB with or without RAP. All enrolled patients were included in the data analysis. The RAP and non-RAP groups were closely matched for established risk factors for transfusion, including age, sex, preoperative hematocrit value and red cell mass, aspirin ingestion, and other intraoperative variables (Table I). Patients were also closely matched for coexisting disease (Table II). No patients required any forms of ventricular assist, such as intraaortic balloon pumping. No complications or deaths occurred in either the RAP or control group.
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and hemodynamic parameters (Fig. 2)
were equivalent for the two groups. The CPB flow rates were also equivalent in RAP compared with control patients throughout CPB (data not shown). The mean arterial pressure was maintained well above minimal safety margins in both patient groups at all times, as defined in the clinical protocol (see Patients and methods). Intraoperative and postoperative vasopressor administration was also similar for the RAP and non-RAP groups (Table IV). By the end of CPB, RAP volumes had to be reinfused in 19 (63%) of the patients (volume reinfused 720 ± 100 ml). Postoperative weight gain, measured as an indicator of third-space fluid sequestration, nevertheless demonstrated a statistically significant trend toward a lesser increase 36 hours after the operation in the RAP group as compared with the control group (Table III). There were no deaths or clinical evidence of myocardial infarction, stroke, or renal dysfunction in either of the groups.
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Correspondingly, the transfusion of fresh frozen plasma and platelets was not significantly different between the two groups (Table V).
Subset analysis.
Additional analysis was performed on patients with a body surface area (BSA) less than 1.9 m2(lowest 30th percentile of study population). The decrease in the number of patients receiving transfusions in the low BSA group was not significantly greater than that for patients with a BSA greater than 1.9 m2 (low BSA, 3 [30%] of 10 patients [RAP] vs 6 [67%] of 9 patients [control] receiving transfusions; high BSA, 5 [25%] of 20 patients [RAP] vs 10 [48%] of 21 patients [control] receiving transfusions).
Discussion
In the numerous recent trials, a variety of hemostatic agents have been demonstrated to result in dramatic reductions of postoperative blood loss and decreases in the number of transfusions associated with cardiac operations, but a significant number of patients in these studies have continued to require red cell transfusions. 4,15-17 These findings highlight the critical contribution of factors other than bleeding to the transfusion risk associated with cardiac operations. The hemodilution associated with the use of an asanguineous (crystalloid) CPB prime results in decreased intraoperative and postoperative hematocrit values in patients undergoing cardiac operations. 6,7,12 The current study demonstrated that RAP could safely be used to decrease the crystalloid pump prime and the hemodilution associated with this prime volume; in this way the number of patients requiring red blood cell transfusions could be reduced by avoiding the obligatory transfusions triggered by hematocrit values decreased below minimum safety triggers.
RAP and hemodilution.
Patients undergoing cardiac operations who will require transfusions can be predicted before the operation by a number of variables, including red cell mass. 14,18-20 This is consistent with the assumption that patients with a low red cell mass are more likely to have low hematocrit values and therefore require transfusions after CPB as a result of the proportionately greater hemodilution caused by CPB in these patients. For example, a 60 kg woman with a 30% hematocrit value at the start of CPB would be more likely than a 90 kg man with the same hematocrit value to require a transfusion on or shortly after CPB because of a profound degree of relative hemodilution. Our own experience has similarly confirmed that patients weighing less than 70 kg expended 60% of all the homologous blood products transfused, although they comprised only 40% of the caseload. 7
This was a pilot study designed to determine whether RAP would be of benefit in the general cardiac surgery population. Patients were not specifically preselected into high- or low-risk groups on the basis of BSA, although patients with extremely low hematocrit values or red cell mass (as determined by weight) were eliminated because transfusion probably could not be avoided in these patients even with maximal RAP. With these exceptions, it can be concluded from this study that RAP successfully reduces transfusions in the general coronary bypass population.
It is not intuitively obvious whether RAP would be of greater benefit to patients with low BSA compared with the general population. Successful implementation of RAP would likely be more difficult in patients with a low BSA because the red cell mass withdrawn would represent a proportionately greater amount of the patient's total intravascular volume and therefore would cause more hemodynamic compromise. On the other hand, the pump prime volume would equivalently represent a greater proportion of these patients' intravascular blood volumes and therefore would produce more profound hemodilution and greater likelihood of hematocrit values low enough to mandate obligatory transfusions. A limited analysis was performed on patients in the current study with a BSA of less than 1.9 m2(lowest 30th percentile). In fact, the transfusion risk in patients with a low BSA was improved to a somewhat greater extent than that in patients with a larger BSA, although greater numbers would be required to achieve statistical significance in this analysis.
The hematocrit value resulting from the hemodilution associated with CPB can be directly calculated as the product of the patient's hematocrit value and the patient's red cell mass (volume) as a fraction of the crystalloid CPB prime volume plus the red cell volume (appendix). Red cell mass, the product of blood volume times hematocrit value, can be determined with the use of a nomogram based on the initial hematocrit value, height, weight, and gender. Thus the patients in whom RAP may play a critical role in avoiding transfusion may be predictable before the operation.
RAP as a blood conservation modality.
Although erythropoietin can be used to minimize hemodilution by enhancing the total red cell mass, 21,23 RAP is a more expeditious, inexpensive technique, which minimizes hemodilution by modifying the inverse aspect of the hemodilution equation: that is, the CPB prime volume rather than the red cell mass. Despite this demonstrated efficacy, patients with exceedingly low red cell masses, such as severely anemic patients or those, such as elderly patients, women, or others with small BSAs, will experience excessive hemodilution, significantly decreased hematocrit values, and increased transfusion risk despite maximal RAP. These patients may therefore be viewed as remaining candidates for preoperative erythropoietin therapy, despite the potential application of RAP. Although hemoconcentration may also cause increased concentrations of platelets and clotting factors and thereby reduce postoperative bleeding, no direct evidence of this was provided by our results. RAP can thus not be viewed as a hemostatic modality.
Safety.
As described in this article, RAP is safe and extremely well tolerated. One potential risk of RAP, paradoxically, is related to the efficiency of RAP in minimizing hemodilution in patients undergoing CPB. Early investigators had demonstrated that an inverse linear relationship exists between temperature and blood viscosity; blood viscosities can increase 10% to 30% under the hypothermic conditions associated with CPB. 24-26 Therefore moderate hemodilution during CPB has been considered desirable in avoiding this increased viscosity and potential compromise of the microcirculation, and such a degree of hemodilution has generally been provided by a total crystalloid prime. 9-11 Because of these considerations, we maintained a hematocrit value less than 28% ("less than the blood temperature") during CPB by using intraoperative autologous donation before CPB or by adding crystalloid prime during CPB, as required. In fact, with the use of intraoperative autologous donation, "excessive" hematocrit values were not encountered during CPB.
A second theoretical risk of RAP is related to the potential of hemodynamic instability caused by the large volumes of crystalloid solution withdrawn during the RAP process. 6 It is somewhat unexpected in considering the relative hypovolemia induced by RAP that a significant volume or pressor requirement was not subsequently observed in patients subjected to RAP to "fill up" or "shrink" the intravascular space, respectively, and thereby avoid hypotension. In fact, withdrawal of RAP volumes was well tolerated, with hemodynamic parameters and pressor requirements that were equivalent to those in control patients. Although some patients did require reinfusion of RAP volumes, clinical experience suggested that correction of preoperative dehydration minimized the incidence of RAP reinfusion.
Increased vascular tone induced by neuroendocrine mechanisms and intravascular fluid shifts from the extravascular compartment are two of the normal adaptive responses to intravascular hypovolemia and may thus be regarded as potential physiologic responses to RAP. Because the mean arterial pressure and the systemic vascular resistance were demonstrated to be similar in the RAP and non-RAP groups in the current study, it would appear that fluid shifts, as opposed to an endogenous pressor response, may account for the lack of an exogenous volume or pressor requirement noted in patients undergoing RAP. Such fluid shifts from the extravascular into the intravascular compartment, compensating for the volume depletion occurring during the RAP process, may furthermore explain the relative postoperative fluid "loss" noted in RAP versus control groups, as denoted by the difference in weights noted in these patients 36 hours after the operation. A relatively greater colloid oncotic pressure, produced by substitution of the crystalloid prime with autologous blood, may also be responsible for a net extravascular fluid loss and relative weight decrease in the RAP compared with control patients. Either or both of these effects may result in decreased lung water accumulation and expedited ventilator weaning after cardiac operations, as has been previously suggested. 6,27 Thus RAP may generate additional clinical benefits apart from decreased homologous blood transfusions.
Limitations.
The study was designed to be a small-scale pilot study to assess the safety and efficacy of RAP in patients undergoing coronary bypass. Although a more rigorous randomization procedure would be appropriate for larger studies, the technique employed in this study provided the unbiased creation of equivalent study populations in this trial.
We used a lower limit on-CPB and post-CPB hematocrit value of 16% and 23%, respectively, based on previous consensus findings regarding minimum safe hematocrit values with hypothermia and our own review of neurologic sequelae correlated with hematocrit values during CPB. 28-30 On the basis of these data, we did not think that hematocrit values lower than those adopted in this study were acceptable. We therefore do not believe that our control transfusion rate was "excessively" increased as a result of inappropriate transfusion triggers or that our RAP results were consequently significant only in reference to inappropriately increased control transfusion rates. Although the transfusion rate in our non-RAP group would nevertheless appear to be excessive, it is consistent with the results from a number of other trials. 1-5
One potential modification of the RAP technique as described in this study might have included slower RAP withdrawal, which might have improved the volume of RAP withdrawn and/or pressor requirements. However, the RAP technique performed as described in this study, with withdrawal over 1 to 5 minutes and with incremental administration of usually one to three boluses of 100 µgm of oxymetazoline, appeared to be both effective and well tolerated.
RAP can be viewed as one of a number of synergistic techniques that can be used to avoid transfusions during cardiac operations. Either alone or as component of a multimodality blood conservation protocol, RAP would appear to be a safe and inexpensive technique of minimizing hemodilution and red cell transfusions that are associated with cardiac operations.
Appendix: Discussion
Dr. Bradley J. Harlan (San Francisco, Calif.). This is a well-designed prospective randomized study. The surgical results were very good, there being no deaths in the 60 patients. This interesting technique, which Dr. Rosengart describes as having been rediscovered, is essentially a method of priming with autologous blood, as the crystalloid volume is deprimed before and right at the beginning of CPB. Despite this technique, by the time the patients left the operating room, the amount of crystalloid solution that each group had received was exactly the same. The authors conclude from their data that RAP is a safe and effective means of decreasing red blood cell transfusion in cardiac operations, and this is certainly the case at New York Hospital. However, would it be the case for most patients undergoing coronary artery bypass, in whom intraoperative autologous blood donation is not used? The reason I ask is that the control group had an unusually high incidence of blood transfusion during hospital stay, 53%, and a remarkably high incidence of intraoperative transfusion, 23%, despite the fact that the average preoperative hematocrit value of this group was 40%. I suspect that the use of intraoperative autologous blood donation may explain this. Dr. Rosengart, during CPB in the control group, when the hematocrit value reached your trigger level for transfusion, why didn't you reinfuse the autologously donated blood rather than expose the patient to a homologous transfusion?
Dr. Rosengart. We did reinfuse the patient's intraoperative autologous donation blood before transfusing homologous units of blood.
Dr. Harlan. That was not clear from the manuscript. At Sutter Memorial, we use a standard crystalloid prime and autotransfusion in the operating room after CPB, and most patients receive autotransfusion from the chest tube drainage in the postoperative period. We tried to find a similar group of patients, but obviously ours are not exactly the same as your control group. A very small proportion of these patients received aprotinin. In 470 patients in whom these techniques were used, our incidence of blood transfusion during hospitalization was 38% and the incidence of intraoperative transfusion was extremely low. In the postoperative period, did you use the patient's chest drainage for autotransfusion?
Dr. Rosengart. We do use mediastinal blood autotransfusion as a technique at New York Hospital; we did not in the completion of this cohort.
Dr. Harlan. You have shown that the technique is effective, but I am not sure you have shown that it is safe yet, because your study comprised a relatively small, highly selected group of good-risk patients. I wonder whether you have expanded your indications or the use of the technique since this study and whether, despite this expansion, the patients seem to tolerate this hypovolemia well.
Dr. Rosengart. We first started using RAP several years ago. We now perform RAP on essentially every patient that we operate on, with the caveat that if the patient is high risk or we are concerned about hypovolemia or hypotension, we will not perform RAP.
We probably attempt to perform RAP on 95% of the patients, and we are probably successful in delivering a significant amount of RAP volume in the majority of patients, at least 75% or 80%. About half of the patients require retransfusion of some of the RAP volume, and on average about half of the RAP volume is retransfused or readministered at some time. It is impressive, however, that the hematocrit values during CPB are higher than they would be without the technique. I think RAP is allowing the patients to avoid being in the operating room with hematocrit values of 15% or 16%, in which case we would be compelled to transfuse. Whether we really need to transfuse at a hematocrit value of 15% or 16% is an unresolved issue.
Dr. Harlan. This study should stimulate us to review our methods of perfusion.
Dr. Neal W. Salomon (Lutherville, Md.). We have been doing the same procedure exactly as you described it for the past year and have had the same results. However, we have not done a randomized study. At the meeting of The American Association for Thoracic Surgery in April 1997, Richard Engelman's group from Bay State in Massachusetts reported similar results with a resurrection of an old technique. It is extremely simple, and they have had no problems. Neither of our groups has done a randomized trial because we use the technique on almost every patient and there is no need for an institutional review board protocol. We found that we have saved blood in the operating room, and the perfusionists and operating room personnel are very enthusiastic about the technique. However, a significant number of patients will require blood later during their hospital stay. You do get to an irreducible minimum. The patients who need transfusion the least are the ones in whom this technique provides the best results, and the patients with a small body mass who are already anemic have less red cell mass, and they are going to need a blood transfusion regardless. They do require less blood, however, and I think this simple procedure should generate considerable enthusiasm. I do not know whether is more effective than 40 or 80 mg of furosemide (Lasix) or a hemoconcentrator, but it is free. You also have to make sure that your anesthesiologist does not try to compensate for a reduced prime by infusing 2 L of saline solution.
Dr. Rosengart. I would add that RAP is just one of a number of techniques that can be used in combination to decrease blood transfusion. If RAP is successfully accomplished and the patient subsequently loses 2 L of blood because of a coagulopathy, the technique has accomplished nothing. One thing that we therefore try to accomplish with our program is to combine different synergistic and complementary aspects of blood conservation to help prevent such a scenario. We therefore focus on coagulopathy and use aprotinin, aminocaproic acid (Amicar), and so on, which all play important roles.
Dr. Salomon. And you have to make sure that your anesthesiologist does not compensate by adding 2 L of saline solution.
Dr. Thomas A. Pfeffer (Los Angeles, Calif.). You mentioned that one of your exclusion criteria was the history of stroke. Is that still considered?
Dr. Rosengart. No, it is not. That was initially an exclusion criteria because we initiated this protocol so that we could implement it as cautiously as possible.
Dr. Pfeffer. You also did not accept patients with asymptomatic carotid stenosis. Was the reason for originally excluding those patients concern about hypotension during the period of RCP?
Dr. Rosengart. Yes. Neurologic complications are of the gravest concern, and because this was a preliminary trial, we wanted to err on the side of caution. At this point, we try to perform RAP on essentially every patient.
Dr. Pfeffer. One of your slides indicated that there was no significant difference in the mean arterial pressure in the immediate prebypass period. Yet you also described the use of oxymetazoline. Were the pressures the same because those patients automatically received phenylephrine while the blood was being withdrawn?
Dr. Rosengart. About half of the patients received 100 µg boluses of phenylephrine as we started the RAP process. The total amount of pressor requirements was the same, however, and the hemodynamics were essentially the same. Whatever compensatory mechanism ensues that allows compensation for the net blood withdrawal associated with RAP is unknown. I presume it is either an extravascular fluid shift or a change in the venous capacitance that compensates for this net volume loss.
Dr. Pfeffer. Finally, what time frame is involved in withdrawing the blood and priming the circuit this way? Have there been any patients in whom the procedure was abandoned because of hemodynamic instability?
Dr. Rosengart. The entire RAP process requires from 1 to 5 minutes (maximum). The procedure is quickly done.
Appendix
The following equations were used to determine on-CPB hematocrit levels with intraoperative autologous donation (IAD) and retrograde autologous primine (RAP). The estimated blood volume was determined from a previously published nomogram* (abbreviations: CPB = cardiopulmonary bypass; HCT = hematocrit; CPV = (circuit prime volume – RAP volume); EBV = estimated blood volume; HCTinitial = HCT before IAD; HCTpre-CPB = HCT after IAD.
HCTon bypass = HCTpreCPB(EBV)/(EBV + CPV) IAD volume = EBV(HCTinitial - HCTpre CPB)/HCTinitial
*Albert SN, editor. Blood volume and extracellular fluid volumes. Springfield [IL]: Charles C Thomas; 1972. p. 281-2.
Acknowledgments
We thank Genia Podwojski, Marie Kilcullen, Pat Esposito, Barbara Elmer, Youram Sukhram, James McVey, and Laura Deffeo, for their able assistance in completing this trial, and Leah Dinozo for her constant attention to detail.
Footnotes
References
This article has been cited by other articles:
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 G. S. Murphy, J. W. Szokol, M. Nitsun, D. A. Alspach, M. J. Avram, J. S. Vender, T. V. Votapka, and T. K. Rosengart The Failure of Retrograde Autologous Priming of the Cardiopulmonary Bypass Circuit to Reduce Blood Use After Cardiac Surgical Procedures Anesth. Analg., May 1, 2004; 98(5): 1201 - 1207. [Abstract] [Full Text] [PDF]
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M. Kurusz and B. D Butler Bubbles and bypass: an update Perfusion, January 1, 2004; 19(1_suppl): S49 - S55. [Abstract] [PDF]
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M. K. Banbury, J. A. White, E. H. Blackstone, and D. M. Cosgrove III Vacuum-assisted venous return reduces blood usage J. Thorac. Cardiovasc. Surg., September 1, 2003; 126(3): 680 - 687. [Abstract] [Full Text] [PDF]
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R. H. Habib, A. Zacharias, T. A. Schwann, C. J. Riordan, S. J. Durham, and A. Shah Adverse effects of low hematocrit during cardiopulmonary bypass in the adult: Should current practice be changed? J. Thorac. Cardiovasc. Surg., June 1, 2003; 125(6): 1438 - 1450. [Abstract] [Full Text] [PDF]
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 G. P. Eising, M. Pfauder, M. Niemeyer, P. Tassani, H. Schad, R. Bauernschmitt, and R. Lange Retrograde autologous priming: is it useful in elective on-pump coronary artery bypass surgery? Ann. Thorac. Surg., January 1, 2003; 75(1): 23 - 27. [Abstract] [Full Text] [PDF]
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E. A. Hessel II and L. H. Edmunds Jr. Extracorporeal Circulation: Perfusion Systems Card. Surg. Adult, January 1, 2003; 2(2003): 317 - 338. [Full Text]
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L. Y. Lee, W. J. DeBois, K. H. Krieger, and O. W. Isom Transfusion Therapy and Blood Conservation Card. Surg. Adult, January 1, 2003; 2(2003): 389 - 400. [Full Text]
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S. Balachandran, M. H. Cross, S. Karthikeyan, A. Mulpur, S. D. Hansbro, and P. Hobson Retrograde autologous priming of the cardiopulmonary bypass circuit reduces blood transfusion after coronary artery surgery Ann. Thorac. Surg., June 1, 2002; 73(6): 1912 - 1918. [Abstract] [Full Text] [PDF]
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R A B. van Kempen, J M Gasiorek, K Bloemendaal, R P. S. van Leeuwen, and E R Bulder Low-prime perfusion circuit and autologous priming in CABG surgery on a Jehova's Witness: a case report Perfusion, January 1, 2002; 17(1): 69 - 72. [Abstract] [PDF]
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K McCusker, V Vijay, W DeBois, R Helm, and D Sisto MAST system: a new condensed cardiopulmonary bypass circuit for adult cardiac surgery Perfusion, December 1, 2001; 16(6): 447 - 452. [Abstract] [PDF]
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M H Cross Autotransfusion in cardiac surgery Perfusion, September 1, 2001; 16(5): 391 - 400. [Abstract] [PDF]
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W. J. DeBois and T. K. Rosengart Retrograde autologous priming reduces blood use Ann. Thorac. Surg., September 1, 1998; 66(3): 987 - 987. [Full Text] [PDF]
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