|
|
||||||||
Ann Thorac Surg 1999;67:604-609
© 1999 The Society of Thoracic Surgeons
a Department of Cardiothoracic Surgery, University Hospital Groningen, Groningen, The Netherlands
b Department of Anaesthesiology, University Hospital Groningen, Groningen, the Netherlands
Accepted for publication July 13, 1998.
Address reprint requests to Dr van Oeveren, Blood Interaction Research, Department of Cardiothoracic Surgery, University Hospital Groningen, Bloemsingel 10, 9712 KZ Groningen, the Netherlands
| Abstract |
|---|
|
|
|---|
Methods. Forty cardiac surgical patients undergoing cardiopulmonary bypass were allocated randomly to a leukocyte depletion group (n = 20) and a control group (n = 20). In the depletion group, leukocyte filtration was achieved with two filter sets located between the venous drainage and the venous reservoir. Leukocyte filtration was commenced after the start of rewarming but before the release of the aortic cross-clamp, and it was driven by a spare roller pump of the heart-lung machine.
Results. All the episodes of filtration went smoothly within a period of 10 minutes and with a blood flow rate of 400 mL/min. The mean leukocyte removal rate calculated at the end of filtration was 69%. Circulating leukocytes were reduced by 38% in the depletion group compared with the control group at the moment of cross-clamp release (4.3 x 109/L versus 6.8 x 109/L, p < 0.05). The postoperative inflammatory response also was reduced as indicated by less production of interleukin-8 (p < 0.05). Clinically, there was no significant difference between the two groups in postoperative PaO2 or pulmonary hemodynamics.
Conclusions. It is technically feasible to deplete circulating leukocytes through the venous side of the cardiopulmonary bypass circuit with a low blood flow rate. Future studies should focus on the duration and timing of leukocyte depletion to optimize the methodology of leukocyte depletion for cardiac surgical patients.
| Introduction |
|---|
|
|
|---|
For systemic leukocyte depletion from the CPB circuit, an arterial line leukocyte-depleting filter is used, usually from the initiation of CPB [6, 8, 11, 14]. The advantage of this method is the combination of the leukocyte-depleting filter with the conventional arterial line filter. However, the filter is located on the arterial side of the circuit and thus is confronted with a high rate of blood flow, which may reduce its efficiency [3, 8].
We used a new clinical leukocyte depletion method in which systemic leukocyte depletion is achieved through the venous side of the CPB circuit. Using this approach, we started the process of leukocyte depletion during the middle period of CPB before the reperfusion phase and with a low rate of blood flow. We evaluated whether this method was technically feasible for depleting circulating leukocytes during CPB, and whether this temporary depletion method would affect patient outcome after cardiac operations.
| Patients and methods |
|---|
|
|
|---|
|
Cardiopulmonary bypass
The CPB circuit consisted of roller pumps (Stöckert Instrumentation, Munich, Germany) and a microporous polypropylene membrane oxygenator (CML Excel; Cobe Laboratories Inc, Lakewood, CO), and it was primed with 1,500 mL of Ringers lactate solution plus 500 mL of 10% hydroxyethyl starch solution (Fresenius, Bad Homburg, Germany). Myocardial preservation during aortic cross-clamping was achieved with 1 L of St. Thomas cardioplegia solution (4°C) infused into the aortic root. During CPB, moderate hypothermia was applied with a pump flow of 2.4 L · min-1 · m-2. Anticoagulation during CPB was monitored with the celite-activated clotting time (International Technidyne Co, Edison, NJ). After CPB, 3 mg/kg of protamine chloride was administered to neutralize the effect of heparin.
Leukocyte depletion method
Leukocyte depletion during CPB was achieved with the use of two Pall Duplex filter sets (J1647G; Pall Biomedical, Portsmouth, United Kingdom) equivalent to four transfusion leukocyte-depleting filters, as reported previously [13]. The filtration circuit was located between the venous drainage and the venous reservoir and was driven by a separate roller pump (Fig 1). Leukocyte depletion was performed during CPB after the start of rewarming but before the release of the aortic cross-clamp. For each filter set, 2,000 mL of the CPB perfusate was filtered at a flow rate of 400 mL/min. The total blood volume for filtration was 4,000 mL, and the entire filtration procedure was completed within 10 minutes.
|
Efficiency of leukocyte removal in patients
Blood samples from patients were taken from the radial arterial catheter before operation, at several points during CPB, at the end of CPB, at the end of operation during skin closure, 1 hour and 3 hours after transfer to the intensive care unit, and at 6 AM the next morning in the intensive care unit. Circulating leukocytes were counted by the Cell-Dyn electronic counter. Further, levels of inflammatory mediators were determined mainly during the postoperative course in 10 patients in each group. For these tests, leukocyte activation was indicated by elastase activity determined by an enzyme immunoassay (Kordia, Leiden, the Netherlands) and the soluble form of L-selectin (R & D Systems Europe, Abingdon, United Kingdom). Cytokine release was indicated by levels of interleukin-8 (Amersham International Inc, Buckinghamshire, United Kingdom). Clinically, pulmonary gas exchange function was determined by the partial arterial oxygen pressure (PaO2) standardized at a 40% fraction of the inspired oxygen. Postoperative intubation time and blood loss were recorded from the intensive care data sheet. Length of stay in the intensive care unit and in the hospital were obtained from hospital registration records.
Statistics
Data for cell counts are expressed as means with the minimal and maximal counts in parentheses except where otherwise indicated. Data for the inflammatory markers and the postoperative observations are expressed as means plus or minus standard deviation. The Students t-test or the Mann-Whitney U test was used for comparing differences between the two groups. A p value of less than 0.05 was considered statistically significant.
| Results |
|---|
|
|
|---|
|
|
|
|
|
|
| Comment |
|---|
|
|
|---|
For adequate bodily perfusion during CPB for adult patients, a high rate of blood flow (as high as 4,000 mL/min or more) is required on the arterial side of the CPB circuit. Although the arterial line leukocyte-depleting filter is designed to accommodate such a high rate of flow, it has been described as relatively inefficient at the beginning of CPB [3]. Using the current method through the venous side of the CPB circuit, the rate of blood flow for leukocyte depletion can be reduced considerably. It is conceivable that a high rate of blood flow exerts a greater hemodynamic force that is likely to propel leukocytes through the filter, whereas a lower rate of blood flow allows a longer contact time between the leukocytes and the filter medium, a mechanism that is known to promote leukocyte adhesion to the filter medium [19].
In this study, the mean leukocyte removal rate was 69% as calculated across the filter at the end of filtration. This filter efficiency was lower than expected; we previously obtained a much higher filter efficiency by filtering the residual blood in the heart-lung machine using a similar rate of blood flow [13]. However, a major difference between the two studies was the method of blood sampling used. In the previous study, a blood sample was taken at the end of filtration from a retention bag containing a mixture of all the filtered blood. The result reflected the average efficiency over the entire period of filtration. In the current study, however, the blood sample was taken at the end of filtration from the outlet of the filtration circuit. This represents the lowest removal rate, because it is known that filtration efficiency can decrease as the volume of blood filtered increases. Therefore, the overall leukocyte removal rate would be higher than estimated.
In this study, an interesting phenomenon was noted with regard to the efficiency of leukocyte filters during CPB. Although the leukocyte removal rates were variable between patients, in any individual patient, the leukocyte removal rate of the first filter set bore a close relation to that of the second filter set (Fig 2). This suggests that patient-related factors, rather than varying capacity of the filters, may influence the efficiency of leukocyte depletion during CPB. Several possible factors were investigated. First, temperature may influence leukocyte depletion during CPB, because temperature is known to influence leukocyte adhesion [20, 21]. In this study, a positive correlation was found between the nasopharyngeal temperature before the start of filtration and the efficiency of leukocyte removal, suggesting that hypothermia tends to reduce the efficiency of leukocyte depletion during CPB. Second, medication given before operation may affect leukocyte adhesion (eg, the use of the cyclooxygenase inhibitor, aspirin). However, we could not find a relation between the efficiency of leukocyte depletion and the preoperative use of aspirin or the preoperative concentration of the leukocyte activation marker, soluble L-selectin. Finally, the systemic leukocyte count before filtration seems less likely to play a role in the efficiency of leukocyte removal, because no relation was found between these two variables.
Clinically, this temporary filtration protocol did not improve lung function, although a reduced interleukin-8 concentration was observed in patients who underwent leukocyte depletion. The timing of leukocyte filtration in this study may have influenced the overall outcome of systemic leukocyte depletion. Initiating leukocyte depletion before the release of the aortic cross-clamp is theoretically attractive for reducing leukocyte-mediated lung injury during the reperfusion period. However, this attempt is counteracted by concomitant rewarming of the systemic blood, which is known to contribute to systemic leukocytosis. Further, the duration of leukocyte depletion must be considered. The 10-minute filtration protocol used in the current study was chosen based on calculations of filter efficiency from our previous study [13]. A protocol of such short duration apparently is insufficient for targeting the circulating leukocytes during rewarming. However, a longer period of filtration may deplete sufficient leukocytes but be complicated by the potential release of elastase from trapped leukocytes [8].
One possible disadvantage of this method is that a separate filter circuit with a roller pump is required to allow low-flow filtration. However, this is not a practical problem, because most heart-lung machines contain at least one spare pump head and most perfusionists are familiar with the installation of and perfusion with a parallel circuit (eg, a hemofiltration circuit). This method may have an advantage in that the filter and its circuit, like the hemofiltration circuit, can be installed by the perfusionist at any time during CPB without the preinstallation required by the custom packs.
We conclude that it is technically feasible to install a leukocyte filter device on the venous side of the CPB circuit that is driven by a separate roller pump using a low rate of blood flow. Ten minutes of leukocyte depletion before the reperfusion phase using this method achieved a 38% reduction in circulating leukocytes. Postoperatively, this temporary leukocyte depletion method resulted in a reduction in interleukin-8 production but not an improvement in lung function. This study poses additional questions about systemic leukocyte depletion during CPB, such as the optimal duration and timing of leukocyte depletion, that need to be explored further to optimize the overall methodology of leukocyte depletion for cardiac surgical patients.
| Acknowledgments |
|---|
|
|
|---|
| References |
|---|
|
|
|---|
This article has been cited by other articles:
![]() |
E. M. Carvalho, E. A Gabriel, and T. A Salerno Pulmonary Protection During Cardiac Surgery: Systematic Literature Review Asian Cardiovasc Thorac Ann, December 1, 2008; 16(6): 503 - 507. [Abstract] [Full Text] [PDF] |
||||
![]() |
J. W. Hammon Extracorporeal Circulation: Perfusion System Card. Surg. Adult, January 1, 2008; 3(2008): 350 - 370. [Full Text] |
||||
![]() |
J. W. Hammon Extracorporeal Circulation: The Response of Humoral and Cellular Elements of Blood to Extracorporeal Circulation Card. Surg. Adult, January 1, 2008; 3(2008): 370 - 389. [Full Text] |
||||
![]() |
O. Warren, C. Alexiou, R. Massey, D. Leff, S. Purkayastha, J. Kinross, A. Darzi, and T. Athanasiou The effects of various leukocyte filtration strategies in cardiac surgery Eur. J. Cardiothorac. Surg., April 1, 2007; 31(4): 665 - 676. [Abstract] [Full Text] [PDF] |
||||
![]() |
W. J Vermeijden, H. de Vries, J. Kieboom, and T. Waterbolk Leucocyte depletion in a drowning victim during rewarming with extracorporeal circulation may limit pulmonary oedema Perfusion, September 1, 2006; 21(5): 305 - 308. [Abstract] [PDF] |
||||
![]() |
H. B. Bittner, M. Richter, T. Kuntze, A. Rahmel, P. Dahlberg, M. Hertz, and F. W. Mohr Aprotinin decreases reperfusion injury and allograft dysfunction in clinical lung transplantation Eur. J. Cardiothorac. Surg., February 1, 2006; 29(2): 210 - 215. [Abstract] [Full Text] [PDF] |
||||
![]() |
S. G Raja and G. D Dreyfus Modulation of Systemic Inflammatory Response after Cardiac Surgery Asian Cardiovasc Thorac Ann, December 1, 2005; 13(4): 382 - 395. [Abstract] [Full Text] [PDF] |
||||
![]() |
A. J de Vries, Y J. Gu, W. J Post, P. Vos, I. Stokroos, H. Lip, and W. van Oeveren Leucocyte depletion during cardiac surgery: a comparison of different filtration strategies Perfusion, January 1, 2003; 18(1): 31 - 38. [Abstract] [PDF] |
||||
![]() |
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] |
||||
![]() |
P. Menasche and L. H. Edmunds Jr. Extracorporeal Circulation: The Inflammatory Response Card. Surg. Adult, January 1, 2003; 2(2003): 349 - 360. [Full Text] |
||||
![]() |
N Nitescu, A Bengtsson, and J P Bengtson Blood salvage with a continuous autotransfusion system compared with a haemofiltration system Perfusion, September 1, 2002; 17(5): 357 - 362. [Abstract] [PDF] |
||||
![]() |
A. T.M. Tang, C. Alexiou, J. Hsu, S. V. Sheppard, M. P. Haw, and S. K. Ohri Leukodepletion reduces renal injury in coronary revascularization: a prospective randomized study Ann. Thorac. Surg., August 1, 2002; 74(2): 372 - 377. [Abstract] [Full Text] [PDF] |
||||
![]() |
C. S.H. Ng, S. Wan, A. P.C. Yim, and A. A. Arifi Pulmonary Dysfunction After Cardiac Surgery* Chest, April 1, 2002; 121(4): 1269 - 1277. [Abstract] [Full Text] [PDF] |
||||
![]() |
G. Asimakopoulos The inflammatory response to CPB: the role of leukocyte filtration Perfusion, March 1, 2002; 17(2_suppl): 7 - 10. [Abstract] [PDF] |
||||
![]() |
G. A Ortolano, G. S Aldea, K. Lilly, P. O'Gara, J. D Alkon, F. Madera, T. Murad, C. P Altenbern, C. S Tritt, A. Capetandes, et al. A review of leukofiltration in cardiac surgery: the time course of reperfusion injury may facilitate study design of anti-inflammatory effects Perfusion, March 1, 2002; 17(2_suppl): 53 - 62. [Abstract] [PDF] |
||||
![]() |
D. Paparella, T.M. Yau, and E. Young Cardiopulmonary bypass induced inflammation: pathophysiology and treatment. An update Eur. J. Cardiothorac. Surg., February 1, 2002; 21(2): 232 - 244. [Abstract] [Full Text] [PDF] |
||||
![]() |
H. A. Hennein Inflammation After Cardiopulmonary Bypass: Therapy for the Postpump Syndrome Seminars in Cardiothoracic and Vascular Anesthesia, September 1, 2001; 5(3): 236 - 255. [Abstract] [PDF] |
||||
![]() |
G Matheis, M Scholz, A Simon, O. Dzemali, and A Moritz Leukocyte filtration in cardiac surgery: a review Perfusion, September 1, 2001; 16(5): 361 - 370. [Abstract] [PDF] |
||||
![]() |
S J Morris Leukocyte reduction in cardiovascular surgery Perfusion, September 1, 2001; 16(5): 371 - 380. [PDF] |
||||
![]() |
A. M. Miller, A. R. McPhaden, R. M. Wadsworth, and C. L. Wainwright Inhibition by leukocyte depletion of neointima formation after balloon angioplasty in a rabbit model of restenosis Cardiovasc Res, March 1, 2001; 49(4): 838 - 850. [Abstract] [Full Text] [PDF] |
||||
![]() |
A. Fabbri, J. Manfredi, C. Piccin, G. Soffiati, M. R. Carta, E. Gasparotto, and G. Nardon Systemic leukocyte filtration during cardiopulmonary bypass Perfusion, January 1, 2001; 16(1_suppl): 11 - 18. [Abstract] [PDF] |
||||
![]() |
G Matheis, M Scholz, A Simon, D Henrich, G Wimmer-Greinecker, and A Moritz Timing of leukocyte filtration during cardiopulmonary bypass Perfusion, January 1, 2001; 16(1_suppl): 31 - 37. [Abstract] [PDF] |
||||
![]() |
A. Rahman, B. Ustunda, O. Burma, I. H. Ozercan, A. Cekirdekci, and M. K. Bayar Does aprotinin reduce lung reperfusion damage after cardiopulmonary bypass? Eur. J. Cardiothorac. Surg., November 1, 2000; 18(5): 583 - 588. [Abstract] [Full Text] [PDF] |
||||
![]() |
A. J. Levine, K. Parkes, S. Rooney, and R. S. Bonser Reduction of endothelial injury after hypothermic lung preservation by initial leukocyte-depleted reperfusion J. Thorac. Cardiovasc. Surg., July 1, 2000; 120(1): 47 - 54. [Abstract] [Full Text] [PDF] |
||||
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| ANN THORAC SURG | ASIAN CARDIOVASC THORAC ANN | EUR J CARDIOTHORAC SURG |
| J THORAC CARDIOVASC SURG | ICVTS | ALL CTSNet JOURNALS |