Asian Cardiovasc Thorac Ann 2004;12:198-201
© 2004 Asia Publishing EXchange Ltd
Blood-Air Interface during Cardiopulmonary Bypass
Arndt-H Kiessling, MD,
Mahmud Khalil, MD,
Ohmed Assaf, MD,
Frank Isgro, MD,
Kai-U Kretz, CP,
Werner Saggau, MD
Heartcenter Ludwigshafen, Cardiac Surgery, Klinikum Ludwigshafen, Germany
For reprint information contact: Arndt-H Kiessling, Tel: 49 621 503 4050, Fax: 49 621 503 4060, Email: kiesslia{at}klilu.de Klinik für Herzchirurgie, Herzzentrum Ludwigshafen, Bremserstr. 79, 67063 Ludwigshafen, Germany.
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ABSTRACT
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The aim of this study was to compare the systemic blood activation with open and closed perfusion management during cardiopulmonary bypass. In 30 patients undergoing coronary artery bypass grafting, we prospectively studied systemic blood activation, blood loss and the need for donor blood. In 15 patients we used an open venous reservoir consisting of a hard shell venous reservoir with an integrated cardiotomy filter. In another 15 patients we used a totally closed venous reservoir consisting of a collapsible venous reservoir, no coronary suction, modified vent and cell saver. Venous blood samples were collected pre, post and 24 hours postoperatively. Sex, age and perfusion times were identical in both groups. There were no statistically significant differences in concentrations of FXIIa and C3a, amount of blood loss and need for donor blood. Interleukin-6 and Elastase levels showed trends toward a lesser inflammatory reaction in closed venous reservoir patients. Modification of perfusion management with optimized air management does not seem to be an effective strategy in reducing the inflammatory response and influencing the coagulation system in this small cohort.
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INTRODUCTION
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The prerequisite to the introduction of modern cardiac surgery was the successful development of cardiopulmonary bypass (CPB). CPB provides oxygenation and systemic perfusion in a nonphysiologic manner. Significant clinical morbidity is relatively unusual, although this owes more to the body’s ability to compensate for the damaging effects of CPB than to extracorporeal circulatory perfection.1 CPB poses significant pathophysiological effects, specifically from four aspects: hemodynamics and perfusion;2,3 gaseous exchange;4,5 hypothermia and acid-base regulation;6,7 and blood contact activation.1,8 Contact activation is caused when the formed elements of blood and plasma are exposed to nonendothelial extracorporeal surfaces and air. This results in a systemic inflammatory response, which is exacerbated by surgical trauma and reperfusion injury.9 Air contact as a foreign surface is less examined.10 The aim of this study was to evaluate the influence of the blood-air interface during CPB.
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PATIENTS AND METHODS
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We included in this prospective and randomized study of 30 patients undergoing elective isolated coronary artery bypass grafting. The inclusion criteria were: age between 18 and 75 years; LV ejection fraction > 40%; hemoglobin concentration > 12 mg•dL–1; preoperative leucocytes count < 12•nL–1; creatinine kinase < 1.3 mg•dL–1; platelets > 140•nL–1. Administration of platelet inhibitors was discontinued at least 6 days before operation. Patients with disease of the liver or coagulopathy were excluded and when postoperative intraaortic balloon pumping or rethoracotomy was indicated. All patients received before and during the operation 2 Mio KIU aprotinin.
Patients were assigned randomly to one of two groups: open venous reservoir (OVR) or closed venous reservoir (CVR). In the CVR group, patients (n = 15) underwent cardiopulmonary bypass with a circuit consisting of a closed soft shell collapsible venous reservoir and separate cardiotomy reservoir, no coronary suction, modified vent suction and cell saver. In the OVR group, patients (n = 15) underwent cardiopulmonary bypass including an open hard shell venous reservoir with integrated filter, coronary suction and standard vent. In all cases, the extracorporeal circuit was equipped with a membrane oxygenator (OptimaTM, Cobe Cardiovascular Inc., Arvada, CO, USA), arterial line filter (SentryTM Cobe Cardiovascular Inc., Arvada, CO, USA), polyvinyl chloride tubing and roller pump (S 900, 3M Sarns Inc., Ann Arbor, MI, USA) with silicone tubing. The extracorporeal circuit, in which an open or closed venous reservoir was applied, was primed with 1000 mL ringer lactate and 500 ml gelatin solution. In both groups 250 mL of 15% mannitol and 10,000 units heparin were added to the pump prime. Heparin, 300 units•kg–1 body weight, was given after preparation of internal mammary artery. Aortic cannulation was performed with a 24 Fr cannula (Jostra AG, Hirrlingen, Germany) and a 36/51 Fr two-stage cannula was used for the venous return. The perfusion flow rate was 3 L•qm–1•m–2 at normothermia and 2.5 L•qm–1•m–2 at moderate hypothermia of 32°C. After cross-clamping, cardioplegia was induced with 800 mL cold (4°C) St. Thomas’ Hospital solution. Shed blood accumulated in the pericardial and pleural space was removed by cell saver in the CVR group, and by coronary suction in the OVR group.
At the end of cardiopulmonary bypass, heparin was neutralized by protamine chloride at a dose of 1.0 times the total dose of heparin, aiming at the baseline value of the activated clotting time. During CPB the hematocrit was not allowed to decrease to less than 20%. After completion of the CPB, any residual volume in the extracorporeal circuit was washed out by cell saver and reinfused to the patient. Postoperatively, homologous packed cells were transfused when the hematocrit fell to less than 25%.
Blood samples were collected at three timepoints – at the beginning (T1), at the end (T2), and 24 hours after the operation (T3) – for determination of hemoglobin (Hb), hematocrit (Hkt), platelet and leukocyte counts, and elastase levels (homogenous immunoassay Ecoline PMN elastase, Merck, Darmstadt, Germany). The levels of complement split product (C3a) were assessed by enzyme immunoassay (C3a-desArg ELISA) and of activated factor XII by enzyme immunoassay (activated factor XII ELISA, Diagnostic International, Karlsdorf, Germany). The levels of interleukin-6 (IL-6) were assessed by chemiluminescency-enzyme immunoassay (DPC Biermann, Bad Nauheim, Germany), serum hemoglobin by S HEM-Testpack (DUPONT, Bad Homburg, Germany), and procalcitonin (PCT) by immunoassay (LUMItest, B•R•A•H•M•S DIAGNOSTICA, Berlin, Germany). All blood samples except those for platelet and leukocyte counts were centrifuged immediately at 3,000 rpm and for FXIIa at 2,000 rpm to obtain poor plasma, which was stored at –70°C until the assays were performed. Requirements of homologous blood products were documented. Postoperatively, shed blood was collected in a chest tube system and registered during 24 hours. Patients received colloid and crystalloid solution based on the need for intravascular volume expansion. All values are expressed as mean and standard error of the mean. The Chi-quadrat-test, Fisher’s two tail test and student t test were used for the statistical analysis. Level of significance was p < 0.05.
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RESULTS
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Preoperative and intraoperative patient data were alike in the two groups (Table 1
). One patient was excluded from the study because he required reoperation for surgical bleeding. None of the patients had a perioperative myocardial infarction or died during hospitalization. The perioperative courses of hemoglobin concentration, platelet and leukocyte count, activated clotting time, antithrombin (AT) III, d-dimere and serum Hb were similar in both groups. We observed a minimal increase of activated Factor XII after CPB and a decrease below the baseline level 24 hours after the CPB in both groups (Figure 1). A significant increase in levels of C3a was noted at the end of the operation and declined 24 hours postoperatively to baseline level in all patients (Figure 2). Compared with baseline levels, we noticed an elevation in the concentration of IL-6 directly after operation and further rises 24 hours later in the circulating blood of all patients, which was higher in OVR patients but statistically not significant ( p = 0.61) (Figure 3). An increase in elastase levels at the end of bypass was noticed in the circulating blood of all patients and declined 24 hours postoperatively but remained higher compared with the baseline levels, becoming higher in the OVR group than in CVR patients, but statistically not significant ( p = 0.14) (Figure 4). The intraoperative shed blood in the pericardial and pleural space was removed by coronary suction in the OVR group, and by cell saver suction without coronary suction in the CVR group. The amount of postoperative blood loss was similar in the OVR and CVR groups: 602 ± 58 mL and 668 ± 60 mL, respectively. 20% of OVR and 7% of CVR patients required donor blood. The need for intravascular filling was similar in both groups.
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Figure 1. Pre, post and 24 hours postoperative serum concentration of Factor XIIa described as mean, median, 25th, 75th percentiles and standard deviation.
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Figure 2. Pre, post and 24 hours postoperative serum concentration of C3a described as mean, median, 25th, 75th percentiles and standard deviation.
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Figure 3. Pre, post and 24 hours postoperative serum concentration of Interleukin-6 described as mean, median, 25th, 75th percentiles and standard deviation.
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Figure 4. Pre, post and 24 hours postoperative serum concentration of Elastase described as mean, median, 25th, 75th percentiles and standard deviation.
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DISCUSSION
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Treatment of patients with OVR versus CVR increased systemic blood activation. The repeated passage of patient’s blood through the extracorporeal circuit results in contact activation of blood components.11 This event triggers the complement,12 coagulation, fibrinolytic and kallikrein-kinin system mainly through the alternative pathway, which is dominated by activated factor XII (Hageman factor).13 Surprisingly, we did not observe the expected activation of FXIIa after the use of cardiopulmonary bypass, probably caused by the use of aprotinin, being an effective antifibrinolytic agent and inhibitor of the kallikrein system.14 Indeed, we noticed in all our patients a significant activation of the complement C3a after CPB, but equivalent in both groups, perhaps because of short perfusion times, and leukocytosis (elastase, IL-6). The highest values of elastase and IL-6 were found in OVR patients, being responsible for augmented permeability and playing a potential role in postperfusion myocardial injury.15 We also observed similar shed blood loss in both groups, and the need for homologous blood was not significantly more in the OVR patients. We believe that the application of aprotinin, with short cross-clamping and perfusion times, might reduce the differences between OVR and CVR.10,14
In conclusion, we noted no more systemic blood activation after cardiopulmonary bypass in patients treated with OVR than in those treated with CVR. This observation corroborates with the report of Schoenberger and colleagues.10
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REFERENCES
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- Hornick PH, GeorgeA. Blood contact activation: pathophysiological effects and therapeutic approaches. Perfusion
1996;11:3–19.[Free Full Text]
- Taylor KM, Casals JG, Mittra SM, Brannan JJ, Morton JJ. Haemodynamic effects of angiotensin converting enzyme inhibition after cardiopulmonary bypass in dogs. Cardiovasc Res
1980;14:199–205.[Medline]
- Taylor KM, Wright GS, Reid JM, Bain WH, Caves PK, Walker MS, et al. Comparative studies of pulsatile and nonpulsatile flow during cardiopulmonary bypass. II. The effects on adrenal secretion of cortisol. J Thorac Cardiovasc Surg
1978;75:574–8.[Abstract]
- Masters RG. The superiority of the membrane oxygenator. J Cardiothoracic Anesth
1989;3:235–7.[Medline]
- Gu YJ, Wang YS, Chiang BY, Gao XD, Ye CX, Wildevuur CR. Membrane oxygenator prevents lung reperfusion injury in canine cardiopulmonary bypass. Ann Thorac Surg
1991;51:513–7.
- Reeves RB. The interaction of body temperature and acid-base balance in ectothermic vertebrates. Ann Rev Physiol
1977;39:559–86.[Medline]
- White FN. A comparative physiological approach to hypothermia. J Thorac Cardiovasc Surg
1981;82:821–8.[Medline]
- Jansen N, Van Oeveren W, Gu YJ, Van Vliet MH, Eÿsman L, Wildevuur CR. Endotoxin release and tumor necrosis factor formation during cardiopulmonary bypass. Ann Thorac Surg
1992;54:744–8.[Abstract]
- Robicsek F, Schaper J. Reperfusion injury: fact or myth? J Card Surg
1997;12:133–7.[Medline]
- Schoenberger J, Everts PM, Hoffmann JJ. Systemic blood activation with open and closed venous reservoirs. Ann Thorac Surg
1995;59:1549–55.[Abstract/Free Full Text]
- Utley JR. Pathophysiology of cardiopulmonary bypass: current issues. J Card Surg
1990;5:177–89.[Medline]
- Chenoweth DE, Cooper SW, Hugli TE, Stewart RW, Blackstone EH, Kirklin JW. Complement activation during cardiopulmonary bypass: evidence for generation of C3a and C5a anaphylatoxins. N Engl J Med
1981;304:497–503.[Abstract]
- Silverberg M, Dunn JT, Garen L, Kaplan AP. Autoactivation of human Hageman factor. Demonstration utilizing a synthetic substrate. J Biol Chem
1980;225:7281–96.
- Van Oeveren W, Jansen NJ, Bidstrup BP, Royston D, Westaby S, Neuhof H, et al. Effects of aprotinin on hemostatic mechanisms during cardiopulmonary bypass. Ann Thorac Surg
1987;44:640–5.[Abstract]
- Gwechenberger M, Mendoza LH, Youker KA, Frangogiannis NG, Smith W, Michael LH, et al. Cardiac myocytes produce interleukin-6 in culture and in viable border zone of reperfused infarctions. Circulation
1999;99:546–51.[Abstract/Free Full Text]
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ABSTRACT
INTRODUCTION
