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Ann Thorac Surg 2003;75:23-27
© 2003 The Society of Thoracic Surgeons


Original article: cardiovascular

Retrograde autologous priming: is it useful in elective on-pump coronary artery bypass surgery?

Gregory P. Eising, MDa*, Martin Pfaudera, Markus Niemeyera, Peter Tassani, MDb, Hubert Schad, MDa, Robert Bauernschmitt, MDa, Rüdiger Lange, MDa

a Department of Cardiovascular Surgery, German Heart Center Munich, Technical University, Munich, Germany
b Institute of Anesthesiology, German Heart Center Munich, Technical University, Munich, Germany

Accepted for publication July 23, 2002.

* Address reprint requests to Dr Eising, Klinik für Herz- und Gefäßchirurgie, Deutsches Herzzentrum München, Lazarettstrasse 36, D-80636 München, Germany.
e-mail: eising{at}dhm.mhn.de


    Abstract
 Top
 Abstract
 Introduction
 Material and methods
 Results
 Comment
 References
 
BACKGROUND: The effect of reduced cardiopulmonary bypass (CPB) prime volume by retrograde autologous priming (RAP) was studied.

METHODS: Twenty patients undergoing elective coronary artery bypass grafting were randomized to either standard prime (SP) volume (1,602 ± 202 mL crystalloid prime, n = 10) or RAP (395 ± 150 mL). RAP was performed by draining crystalloid prime from the arterial and venous lines into a recirculation bag before CPB. Cardiac index, pulmonary vascular resistance index, systemic vascular resistance index, alveolar-arterial oxygen tension difference, pulmonary shunt fraction, extravascular lung water (EVLW), plasma colloid osmotic pressure (COP), crystalloid fluid balance, body weight, and clinical parameters were evaluated perioperatively.

RESULTS: Demographic data and operative parameters were equal for patients in both groups. During CPB, COP was reduced by 55% in the SP group (9.8 ± 2.0 vs 21.4 ± 2.1 mm Hg) and by 41% in the RAP group (12.4 ± 1.1 vs 20.9 ± 1.8 mm Hg) (p = 0.008, SP vs RAP group). Compared with preoperatively, EVLW was unchanged in the RAP group 2 hours post-CPB, but it was elevated by 21% in the SP group (p = 0.002, SP vs RAP group). End-CPB crystalloid fluid balance was significantly reduced in the RAP group (1,857 ± 521 vs 2,831 ± 637 mL). Postoperative (day 2) weight gain in the SP group (1.5 ± 1.2 kg, p = 0.021) was absent in the RAP group (0.1 ± 0.9, NS). Postoperative time to full mobilization was shorter in the RAP group. Postpump cardio-respiratory function did not differ among groups.

CONCLUSIONS: This small-scale pilot study indicates that by reducing crystalloid fluid administration and fall of COP during CPB, RAP reduces postpump EVLW accumulation and weight gain in uncomplicated coronary artery bypass graft patients with no associated effects on cardio-respiratory function.


    Introduction
 Top
 Abstract
 Introduction
 Material and methods
 Results
 Comment
 References
 
Sudden crystalloid hemodilution and the rapid fall of colloid osmotic pressure (COP) with the onset of cardiopulmonary bypass (CPB) is associated with postpump organ dysfunction in cardiac surgery [15]. A decrease in COP increases effective filtration pressure and microvascular filtration. Consequently, a rise in extravascular lung water [1, 2] and myocardial edema formation [68] were shown to be present after weaning from CPB. Hyperoncotic CPB-prime using 10% hydroxyethyl starch (HES) has been shown to increase postpump cardiac index, and to prevent extravascular lung water (EVLW) accumulation and postoperative weight gain [9].

Retrograde autologous priming (RAP) has been demonstrated to decrease the number of homologous red cell transfusions associated with "excessive" hemodilution during CPB [10]. The following small-scale pilot study was undertaken to evaluate possible effects of RAP on COP, EVLW, pulmonary function, and cardiac index in patients undergoing elective coronary artery bypass surgery.


    Material and methods
 Top
 Abstract
 Introduction
 Material and methods
 Results
 Comment
 References
 
The study was approved by the ethical committee of the Technical University of Munich (January 27, 2001). Twenty consecutive patients scheduled for elective coronary artery bypass grafting (CABG) were investigated. Exclusion criteria were age >75 years; body weight ± 30% of ideal body weight; left ventricular ejection fraction <40%; hemodynamic instability or emergency operations; valvular diseases; complete bundle branch block; third-degree atrioventricular block; impaired renal function (creatinine >1.3 mg%); and hematocrit <30%.

After written informed consent was obtained, the patient was randomly allocated either to the standard priming group (SP group) or to the retrograde priming group (RAP group). Randomization was performed by drawing lots out of a case, containing 20 envelopes (10 including the note SP, 10 including the note RAP).

The patients’ body weight was determined with calibrated scales before premedication and 36 hours postoperatively. At the second postoperative day, all patients were readily mobilized and able to sit on the scale.

Anesthesia
Patients received flunitrazepam, morphine, and atropine intramuscularily for premedication. Induction of anesthesia was performed with sufentanil, midazolam, and pancuronium. After orotracheal intubation, mechanical ventilation with 100% oxygen was provided. Anesthesia was maintained by sufentanil and midazolam. Aprotinin (Trasylol) was given according to the Hammersmith protocol [11].

A radial and pulmonary artery catheter and two large-bore intravenous catheters were placed for hemodynamic monitoring and blood sampling. A combined fiberoptic-thermistor catheter (4 F) was inserted into the femoral artery and advanced 40 cm up to the thoracic aorta for measurement of EVLW by the double indicator technique [12].

Cardiopulmonary bypass
The extracorporeal circuit consisted of roller pumps (Stöckert, München, Germany), a membrane oxygenator (Compactflow Module 7500; Dideco, Mirandola, Italy) in combination with the cardiotomy reservoir (D772 Venocard; Dideco), and a tubing set (Dideco) including an arterial filter (D734 Micro 40; Dideco). For CPB, standard cannulation of the ascending aorta and the right atrium (two-stage venous cannula) was performed.

The priming fluid of the extracorporeal circulation circuit consisted of Ringer’s lactate (1,100 mL), Mannitol (3 mL/kg), and NaHCO3 (5 mL/kg) Potassium (5 mval) and Heparin 5,000 IU were added.

Technique for retrograde autologous priming
The original technique for retrograde autologous priming described by Rosengart and associates [10] was modified as follows (Fig 1). Before RAP was started, mean arterial pressure was elevated to approximately 100 mm Hg using small doses of intravenously administered phenylephrine. A recirculation bag was connected to the venous line. The crystalloid priming fluid of the venous reservoir was drained to a minimal level into the bag [1]. The venous side of the circuit was than drained, slowly replacing the crystalloid priming volume by filling the circuit with patient’s blood [1]. The recirculation bag was then disconnected from the venous line and connected with the purge line of the arterial filter. The retrograde priming was then continued until the blood volume in the venous reservoir reached approximately 200 mL. This fluid mixture of the venous reservoir was slowly pumped through the membrane oxygenator and the arterial filter, displacing the priming fluid of the tubing, the oxygenator, and the arterial filter into the recirculation bag [2]. The arterial line connecting the patient with the arterial filter was clamped at that time. Finally, the arterial line was drained into the recirculation bag by replacing the crystalloid fluid with the patient’s blood [3]. The procedure was performed while the patient’s hemodynamics were carefully monitored. The recirculation bag was then reconnected with the venous reservoir so that crystalloid fluid replacement could be performed during CPB upon hemodynamic requirements [4]. The retrograde priming procedure requires 4 to 5 minutes before the onset of CPB.



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Fig 1. Scheme of the modified retrograde autologous priming (RAP) technique. Before RAP is started, mean arterial pressure is elevated to approximately 100 mm Hg using small doses of intravenously administered phenylephrine. (1) A recirculation bag is connected to the venous line and the crystalloid priming fluid of the venous reservoir is drained to a minimal level. The venous line is then drained, slowly replacing the crystalloid priming volume by filling the circuit with the patient’s blood. (2) The recirculation bag is disconnected from the venous line and connected with the purge line of the arterial filter. The draining of the venous line is then continued until the blood volume in the reservoir reaches approximately 200 mL. This fluid mixture of the reservoir is slowly pumped through the membrane oxygenator and the arterial filter, displacing the priming fluid of the tubing, the oxygenator, and the arterial filter into the recirculation bag. The arterial line connecting the patient with the arterial filter is clamped at that time. (3) The arterial line is drained into the recirculation bag by replacing the crystalloid fluid with the patient’s blood. (4) The recirculation bag is then reconnected with the venous reservoir for subsequent fluid replacement.

 
After starting the CPB at a flow rate of 2.4 L/min per m2 body surface area, the body was cooled to 32°C in all patients. For cardioplegia, 1,000 to 1,500 mL of ice-cold Custodiol (Köhler Chemie, Alsbach-Haehnlein, Germany) was used.

Postoperative care
All patients were admitted to the intensive care unit and treated as per standard clinical practice. The physicians responsible for postoperative care of the patients were blinded with respect to the study group. Mean arterial pressure was maintained at 60 mm Hg or higher by colloidal fluids (HES 6% 200, 0.5), crystalloid infusions, or vasoactive agents, as appropriate.

Blood analyses
Arterial and mixed venous blood samples were obtained for gas analyses and measurement of the colloid osmotic pressure. Alveolar-arterial oxygen tension difference (AaDO2) and pulmonary shunt (Qs/QT) were calculated using standard formulas, as described previously [13]. Extravascular lung water (EVLW) was measured in triplicate by using the Pulsion-COLD system (Pulsion, Munich, Germany) [12].

Fluid balances from preoperative to the end of CPB, to the morning of the first postoperative day (18 hours postoperatively), and 24 hours later (to the morning of the second postoperative day) were calculated. Volume of administered crystalloid and noncrystalloid fluids, priming volume, cardioplegia, urine output, and postoperative blood loss were recorded. Blood loss in surgical sponges, suction traps, and insensible fluid losses were not measured but can be assumed to be equal for the two groups and are not included in the fluid balance.

The length of postoperative ventilation, the length of stay on the intensive care unit (ICU), the incidence of atrial fibrillation, the time to full mobilization (ie, walking on the ward level), the time until the patient’s body weight was equal or below the preoperative value, and the number of postoperative days until hospital discharge were recorded. Patients were discharged if they were on oral medication only, were able to walk stairs, showed no signs of significant pericardial or pleural effusions (chest rhoentgenogram, echocardiography), and showed no signs for infection or renal failure.

Statistical analysis
After CPB in adult patients, EVLW was found to be elevated about 40% to 60% in different studies [1, 2]. A power calculation for a 40% difference in EVLW with the probability of type {alpha} error of 5% and a probability of type ß error of 20% yielded a sample size of 10 patients for each group. Data are presented as means ± standard deviation (SD). A nonparametric analysis for the vector of variables (the Friedman nonparametric analysis of variance for repeated measures) was conducted for both groups seperately. Posthoc comparisons were performed with the Wicoxon matched-pairs test; and significance values were corrected for repeated measures by using the Bonferroni correction. Comparisons between groups were conducted with the Mann-Whitney U test or with the Pearson {chi}2 test, if appropriate, using the statistic software SPSS 10.1 for Windows. Significant differences were accepted for a two-tailed p value of < 0.05 before correction.


    Results
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 Abstract
 Introduction
 Material and methods
 Results
 Comment
 References
 
Demographic data, operative parameters, pulmonary function data, and cardiac index are summarized in Tables 1 and 2, respectively. There was no statistically significant difference among the two groups. The perioperative fluid balances and body weight gain are summarized in Table 3. Postoperative creatinine and urea blood levels, and administration of diuretics (furosemide), were not different in the two groups. Renal complications were not seen. In none of the patients was reexploration for bleeding nessessary in the postoperative period.


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Table 1. Demographic Data and Operative Parameters of the Patients

 

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Table 2. Data on Hemodynamics and Pulmonary Function

 

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Table 3. Data on Perioperative Fluid Balance, Blood Loss, and Patients’ Gain of Body Weight After Cardiopulmonary Bypass

 
The fall of COP during CPB was significantly more pronounced in the SP group than in the RAP group. Lowest COP values were seen after infusion of cardioplegia, 15 minutes after the initiation of CPB. After this, COP continuously increased in either group, and 4 hours after weaning from CPB, COP levels were back to baseline (Fig 2). Compared with baseline levels, EVLW was unchanged after weaning from CPB in the RAP group, but was elevated by 21% in the SP group. Differences amoung groups were significant at 2 and at 4 hours post-CPB (Fig 3). The postoperative performance of the patients is summarized in Table 4.



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Fig 2. Change of plasma colloid osmotic pressure (COP) as percent of the preoperative level (pre–cardiopulmonary bypass [CPB] = 100%), during CPB, and in the intensive care unit in patients treated with retrograde autologous priming (closed circles) or with standard prime (control, open circles). Included are the exact percent values. *p= between the two groups.

 


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Fig 3. Change of extravascular lung water (EVLW) as percent of the preoperative level (pre–cardiopulmonary bypass [CPB] = 100%) at 2, 4, and 18 hours after CPB in patients treated with retrograde autologous priming (closed circles) or with standard prime (control, open circles). Included are the exact percent values. *p= between the two groups; #p= postoperative versus preoperative.

 

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Table 4. Postoperative Clinical Parameters of the Patients

 

    Comment
 Top
 Abstract
 Introduction
 Material and methods
 Results
 Comment
 References
 
The data of the present study demonstrate that RAP reduces the amount of crystalloid fluid administered during CPB (Table 3) and, consequently, the fall of plasma colloid osmotic pressure upon the onset of CPB in patients undergoing elective CABG is less pronounced (Fig 2). Profound hemodilution with crystalloid fluids leads to tissue water accumulation, caused by an imbalance of microvascular net filtration and removal of interstitial fluid by the lymphatics [6, 14].

In principle, we could prevent postoperative accumulation of EVLW in the early postpump period. The pulmonary function, however, was surely not affected in the two groups because both the reduced EVLW levels in the RAP group as well as the elevated EVLW levels in the standard priming group still stayed within the normal range, which is 5 to 7 mL/kg body weight [12]. Therefore, it is quite plausible that no change in AaDO2 and pulmonary shunt fraction occurred in either group (Table 2). And it is also not surprising that the time of postoperative ventilation did not differ among the two groups (Table 4).

A benefit for the patients concerning renal function and transfusion requirements after RAP, which was reported recently [10], could not be confirmed in the present study.

Our results show a highly statistical significant difference between the two groups concerning incidence of atrial fibrillation (AF). A 60% occurrance of AF in the control group, however, is not representative, neither compared with the literature (21%) [15] nor with our own experience. When looking at all CABG patients operated on in our institution in the year 2001 matching with our study inclusion criteria, we found an incidence of AF of about 12% (30/265). This is, in fact, not different compared with the results of the RAP group. Furthermore, a significantly reduced length of hospital stay was observed in the RAP group compared with the control group. Taking into account that the average length of hospital stay of the above-mentioned CABG patients is 9.3 ± 1.9 days, which is very close to the results of the control group (Table 4), the difference in hospital stay between the two study groups may not be explained by the higher incidence of AF in the control group. It might, if at all, be related to early mobilization of the RAP patients, who reach there preoperative body weight earlier than the patients of the control group (Table 4), possibly due, in part, to a less positive perioperative fluid balance (Table 3).

This study was designed to be a small-scale pilot study to evaluate a possible positive effect of RAP on postpump EVLW accumulation, which could be demonstrated. However, associated effects on cardiorespiratory function could not be shown. A favorable effect of RAP on post-operative performance of the patients, as shown in the present study, may be biased by the small size of the groups and influenced by the effects of the inflammatory response to CPB [16], which were not analyzed. RAP should be further investigated in a larger cohort, preferrably in high-risk patients with congestive heart failure, lung disease, or renal failure.


    References
 Top
 Abstract
 Introduction
 Material and methods
 Results
 Comment
 References
 

  1. Hoeft A., Korb H., Mehlhorn U., Sonntag H. Priming of cardiopulmonary bypass with human albumin or Ringer’s lactate: effect on colloid osmotic pressure and extravascular lung water. Br J Anaesth 1991;66:73-80.[Abstract/Free Full Text]
  2. Boldt J., von Bormann B., Kling D., Scheld H.H., Hempelmann G. The influence of extracorporeal circulation on extravascular lung water in coronary surgery patients. J Thorac Cardiovasc Surg 1986;345:110-115.
  3. Foglia R.P., Lazar H.L., Steed D.L., et al. Iatrogenic myocardial edema with crytalloid primes: effects on left-ventricular compliance, performance and perfusion. Surg Forum 1978;29:312-315.[Medline]
  4. Goto R., Tearle H., Steward D.J., Ashmore P.G. Myocardial edema and ventricular function after cardioplegia with added mannitol. Can J Anaesth 1991;38:7-14.[Abstract/Free Full Text]
  5. Schüpbach R, Pappova E, Schilt W, Lundsgaard-Hansen P. Influence of oncotic pressure during cardiopulmonary bypass on tissue edema, metabolic acidosis and renal function. In: Hagl S, Klövekorn WP, Mayr N, Sebening F, eds. Thirty years of extracorporeal circulation. Carl Gerber: Munich, Germany, 1984:247–53
  6. Mehlhorn U., Allen S.J., Davis K.L., Geissler H.J., Warters R.D., de Vivie E.R. Increasing the colloid osmotic pressure of cardiopulmonary bypass prime and normothermic blood cardioplegia minimizes myocardial oedema and prevents cardiac dysfunction. Cardiovasc Surg 1998;6:274-281.[Medline]
  7. Geissler H.J., Allen S.J. Myocardial fluid balance: pathophysiology and clinical Implications. Thorac Cardiovasc Surg 1998;46(Suppl):242-247.
  8. Schad H. Bau und Funktion des kardialen Lymphsystems. Lymph Forsch 1999;3:65-71.
  9. Eising G.P., Niemeyer M., Günther Th., et al. Does a hyperoncotic cardiopulmonary bypass prime affect extravascular lung water and cardiopulmonary function in patients undergoing CABG?. Eur J Cardio-Thorac Surg 2001;20:282-289.[Abstract/Free Full Text]
  10. Rosengart T.K., DeBois W., O’Hara M., et al. Retrograde autologous priming for cardipulmonary bypass: a safe and effective means of decreasing hemodilution and transfusion requirements. J Thorac Cardiovasc Surg 1998;115:426-438.[Abstract/Free Full Text]
  11. Royston D. The serine antiprotease aprotinin (Trasylol): a novel approch to reducing postoperative bleeding. Blood-coagul-Fibrinolysis 1990;1:55-69.[Medline]
  12. Pfeiffer U.J., Backus G., Blümel G., et al. A fiberoptics based system for integrated monitoring of cardiac output, intrathoracic blood volume, extravascular lung water, O2 saturation, and a-v differences. In: Lewis F.R., Pfeiffer U.J., eds. Practical applications of fiberoptics in critical care monitoring. New York: Springer Verlag, 1990:114-125.
  13. Tassani P., Richter J.A., Barankay A., et al. Does high-dose methylprednisolone in aprotinin-treated patients attenuate the systemic inflammatory response during coronary artery bypass grafting procedures?. Cardiothorac Vasc Anesth 1999;13:165-172.
  14. Schad H. Physiologie der Lymphbildung und der Lymphströmung. Phlebol 1996;25:213-221.
  15. Hernandez F., Cohn W.E., Baribeau Y.R., et al. In-hospital outcomes of off-pump versus on-pump coronary artery bypass procedures: a multicenter experience. Ann Thorac Surg 2001;72:1528-1533.[Abstract/Free Full Text]
  16. Edmunds L.H., Jr Inflammatory response to cardiopulmonary bypass. Ann Thorac Surg 1998;66(Suppl 5):12-16.[Abstract/Free Full Text]



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