Ann Thorac Surg 2001;72:850-853
© 2001 The Society of Thoracic Surgeons
Original article: cardiovascular
Is the use of albumin in colloid prime solution of cardiopulmonary bypass circuit justified?
Ricardo H. Boks, BSa,
Lex A. van Herwerden, MD, PhDa,
Johanna J.M. Takkenberg, MDa,
Willem van Oeveren, PhDb,
Y. John Gu, PhDb,
Marianne J. Wijersa,
Ad J.J.C. Bogers, MD, PhDa
a Department of Cardiothoracic Surgery, Erasmus Medical Center Rotterdam, Rotterdam, The Netherlands
b Blood Interaction Research, Department of Cardiothoracic Surgery, University Hospital Groningen, Groningen, The Netherlands
Accepted for publication May 3, 2001.
Address reprint requests to Mr Boks, Department of Cardiothoracic Surgery, Division of Extracorporeal Circulation, Bd 467, Dr. Molewaterplein 40, 3015 GD Rotterdam, The Netherlands
e-mail: boks{at}thch.azr.nl
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Abstract
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Background. Albumin in the priming solution precoats the surface of the cardiopulmonary bypass circuit, supposedly causing delayed adsorption of fibrinogen and reduced activation and adhesion of platelets. This action may result in lower transoxygenator resistance. Because our institution uses a colloidal prime solution (Gelofusine), questions were raised about the value of albumin in the prime solution. We decided to focus on the clinical effects of transoxygenator resistance.
Methods. Sixty adults undergoing elective cardiac operations were randomly divided into three groups: a group with 20-g albumin (n = 20), a group with 2-g albumin (n = 20), and a group with no albumin (n = 20) in the 1,600-mL colloidal prime. Patients older than 75 years and patients with a preoperative serum albumin level of 30 g/L or less were excluded. The transoxygenator resistance was measured throughout cardiopulmonary bypass. ß-Thromboglobulin levels were used to study contact activation of platelets. Measures of prothrombin F1,2 fragments were used as a marker of thrombin generation. Body surface area, age, preoperative albumin, hematocrit, hemoglobin, fibrinogen, platelet count, and colloid osmotic pressure levels were compared between groups.
Results. Base line characteristics and chosen control measurements were similar for all three populations. When comparing the observed transoxygenator resistance among the three different groups, no significant differences were noted. Prothrombin F1.2 fragments remained low for all the groups without significant differences. In the no-albumin group the level of ß-thromboglobulin appeared to be higher, but the difference was not statistically significant.
Conclusions. Addition of albumin to prime solution in a cardiopulmonary bypass circuit that already contains colloids does not affect the transoxygenator resistance of the COBE Duo flat sheet oxygenator and does not affect prothrombin F1.2 and ß-thromboglobulin levels. Therefore additional costs for the albumin are not justified. Measurement of transoxygenator resistance is a reliable, simple method to determine the effects of a prime solution on the oxygenator surface in vivo.
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Introduction
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Adding albumin to the priming solution of the cardiopulmonary bypass (CPB) circuit is part of the standard protocol in many cardiac surgery centers. In addition to its main function, the maintenance of plasma oncotic pressure, albumin is also supposed to coat the surface of the CPB circuit.
The hypothetical effect of this protein layer is a delay in the adsorption of circulating fibrinogen and reduced surface activation of platelets during CPB [1–11]. Albumin diminishes the viscosity of blood and supports the maintenance of an acceptable colloid osmotic pressure (COP) [4–6] during CPB. This can result in a lower transoxygenator resistance. However, the effect of albumin in a priming solution on the transoxygenator resistance is not known. Recent studies have reported elevated pressure reductions when using hollow fiber oxygenators. We decided to examine a simple reproducible method to monitor the effects of the priming solution on the oxygenator resistance in a clinical set up.
Therefore, this study was designed to investigate in a randomized in vivo setting the effects of different concentrations of albumin in the CPB prime solution on the transoxygenator resistance in elective adult cardiac surgical patients.
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Material and methods
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After obtaining approval of the Medical Ethical Commission of the University Hospital Rotterdam and the informed consent of the participants, 60 consecutive patients undergoing elective open-heart operations were randomly divided into three groups of 20 patients each. Group A received 20 g albumin (Human albumin, CLB Red Cross, Amsterdam, The Netherlands), group B received 2 g albumin, and group C received no albumin in the 1,600-mL priming solution.
The inclusion criteria were body surface area 1.5 m2 or more, age 75 years or younger, preoperative albumin level 30 g/L or higher, and hematocrit level 0.35 L/L or higher. Controlled cardiotomy suction was performed during CPB. Patient demographic data were collected for all patients: age, body surface area, sex, preoperative albumin, hemoglobin, platelets, hematocrit, cross-clamp time, CPB time, and type of operation.
Perfusion technique
The CPB circuit consisted of a hard shell venous reservoir (Avecor, Minneapolis, MN), an arterial line filter (Avecor Affinity arterial filter), a roller-pump (Stöckert Instrumente GmbH, Munich, Germany), and a membrane oxygenator (COBE Duo, Arvada, CO). The basic priming solution consisted of 1,400 mL Gelofusine (Gelatina modificata, B. Braun Medical SA, Emmenbrücke, Switzerland) and 200 mL mannitol 200 g/L (Baxter Healthcare BV, Utrecht, The Netherlands). Moderate hypothermia (from 28° to 30°C) was used. The initial heparin (Leo Pharmaceuticals Product BV, Weesp, The Netherlands) dosage was 300 IU/kg bodyweight with an additional 7,500 IU in the pump prime.
Anesthesia
Anesthesia was induced with fentanyl (Janssen-Cilag, Tilburg, The Netherlands), midazolam (Roche Consumer Health, Eindhoven, The Netherlands), and pancuronium (Organon Technica, Oss, The Netherlands) or propofol (Zeneca Farma, Ridderkerk, The Netherlands). Nitrates and inotropic agents were titrated intravenously to control the systemic and pulmonary arterial pressure.
Blood sampling and assay
Levels of hematocrit, hemoglobin, COP, fibrinogen, and platelet count were measured before bypass and after 15, 30, and 60 minutes of CPB. Prothrombin F1,2 and ß-thromboglobulin (ß-TG) levels were measured after 15, 30, and 60 minutes of CPB; prebypass samples were not collected because we decided to monitor only changes during CPB between and within the study groups.
Part of the blood was immediately mixed with a medium containing hirudin and aprotinin (Dade Behring Diagnostics, Deerfield, IL) and stored on ice until plasma was prepared and stored frozen at -70°C. Fragment F1,2 is a product from prothrombin during formation of thrombin and thus a measure of activation of the clotting system. From blood collected into medium containing the platelet inhibitor indomethacin and carbamazin (Dade Behring Diagnostics), the platelet release product ß-TG was determined in plasma as an indicator of platelet activation. The prothrombin F1.2 fragment and ß-TG were measured at the Blood Interaction Research Laboratories, University Hospital Groningen, The Netherlands.
The transoxygenator resistance was monitored by an operating room data integration system [7, 8] developed at the University Hospital Rotterdam. The pressures were monitored on the inlet and outlet of the oxygenator. The average fluid resistance was computed by averaging the computed momentary resistance (every 30 seconds) over the time of CPB. We divided the measurements into a hypothermia (from 28°C to 30°C) and a normothermia (35°C or higher) period. The protocol resulted in two average fluid resistances (AFR) for each CPB performed. The formula we used to calculate the AFR was:
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Statistical analysis
The statistical software package SPSS 9.0 for Windows (SPSS Inc, Chicago, IL) was used for all analyses. Data were expressed as a mean ± the standard error of the mean (SEM). Two-way analysis of variance for repeated measures was used for comparisons of variables measured over time between the groups. Data were further compared by unpaired t test. The results were considered significant if the p value was less than 0.05.
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Results
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When comparing the observed transoxygenator resistance among the groups, there were no significant differences noted during hypothermia (from 28°C to 30°C) and normothermia (35°C or higher). The results during hypothermia were: group A, 46 ± 3 mm Hg/L per minute; group B, 48 ± 4 mm Hg/L per minute; and group C, 47 ± 4 mm Hg/L per minute. The results during normothermia were: group A, 42 ± 3 mm Hg/L per minute; group B, 43 ± 3 mm Hg/L per minute; and group C, 43 ± 4 mm Hg/L per minute. These data show no significant difference between the study groups. Because of the constant values of hematocrit and hemoglobin throughout CPB in all groups, making corrections for these values was not necessary. Figure 1 shows an example of the resistance measurement throughout CPB from 1 patient. Figure 2 shows the AFR for the three groups at normothermia and hypothermia period during CPB.
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Fig 1. Example of oxygenator resistance monitored in patient 1A by the operating room data integration system. (CPB = cardiopulmonary bypass.)
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Fig 2. Average resistance during cardiopulmonary bypass of the study groups in the normothermia and hypothermia periods. Values are expressed as mean ± standard deviation.
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Patient characteristics were similar for all groups (Table 1). The mean levels for preoperative albumin, pre-CPB hemoglobin, hematocrit, and platelet counts were similar for the study groups (Table 2). There were no significant differences or changes during CPB between the groups for hematocrit, hemoglobin, platelet count, COP, and fibrinogen. There was a 10% increase of ß-TG and a 30% increase of prothrombin F1.2 during CPB for all groups (Fig 3 and Fig 4).
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Fig 3. Beta-thromboglobulin levels during cardiopulmonary bypass for the study groups. Values are expressed as mean ± standard error of the mean computed by repeated measurement for multiple groups.
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Fig 4. Prothrombin F1.2 levels during cardiopulmonary bypass for the study groups. Values are expressed as mean ± standard error of the mean computed by repeated measurement for multiple groups.
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Comment
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Albumin is the most common colloidal additive to the priming solution [5] for the CPB circuit. In our hospital, we use albumin in a colloidal priming solution. Addition of albumin to the CPB circuit is questionable when the priming solution is already colloidal [4–6]. Additionally, albumin is supposed to improve the biocompatibility of the CPB surface. Because of lack evidence in the literature, we decided to investigate the value of albumin in our colloidal priming solution. We studied the resistance of the oxygenator and the results showed no difference between the investigated groups. We looked at the normothermia and hypothermia period because temperature influences the fluid viscosity. The activation of platelets, shown by ß-TG release, can result in adhesion on the surface area and influence the resistance of the oxygenator. Although the ß-TG concentrations were on average low, large individual differences were found that persisted throughout CPB. Although not significant, after 15 minutes CPB time the ß-TG concentrations appeared higher in group C than in groups A or B. This difference remained throughout CPB. These data suggest an immediate activation of platelets during first contact with the nonalbumin CPB circuit [2]. After this first contact no further substantial platelet activation occurred. No significant differences were observed between the groups over time. Adequate heparin anticoagulation was important for this study to eliminate any coagulation effects on the oxygenator resistance. We used the prothrombin F1.2 test as measurement to exclude inadequate heparin anticoagulation. The results of the prothrombin F1.2 show an increase of 30% in all three groups during CPB. The prothrombin F1,2 concentrations in all samples were less than 3 nmol/L and must be considered low. This finding indicated that heparin anticoagulation was adequate and prevented activation of the clotting system.
In conclusion, the addition of albumin to our colloid priming solution did not result in lower oxygenator resistance and diminished platelet activation. This conclusion is valid for the investigated oxygenator; the effects on noncoated and coated hollow fiber membrane oxygenators needs further study. Because albumin is expensive and may even put patients at risk with regard to anaphylactic reaction and transmitted diseases [6–10], its routine use in colloid prime is not justified. In addition, not using albumin saves our department US $70 per patient. Whether albumin may be still justified in our prime of the CPB circuit for older patients (75 years of age or older) and infants or patients with a pathologic preoperative albumin, remains to be investigated.
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Acknowledgments
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The authors acknowledge the financial support of the companies involved in the Foundation Biomedical Engineering.
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References
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Abstract
Introduction
