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Ann Thorac Surg 2005;80:1394-1400
© 2005 The Society of Thoracic Surgeons

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Original article: Cardiovascular

Effects of a Leukocyte Depleting Arterial Line Filter on Perioperative Morbidity in Patients Undergoing Cardiac Surgery: A Controlled Randomized Trial

^a Division of Critical Care, Hospital Universitario "Virgen del Rocío," Sevilla, Spain
^b Division of Cardiac Surgery, Hospital Universitario "Virgen del Rocío," Sevilla, Spain
^c Division of Hematology, Hospital Universitario "Virgen del Rocío," Sevilla, Spain

Accepted for publication April 14, 2005.

^_* Address reprint requests to Dr Leal-Noval, Servicio de Cuidados Críticos y Urgencias, Hospital Universitario "Virgen del Rocío" Avda/Manuel Siurot, s/n°, Seville 41013, Spain (Email: sramon{at}cica.es).

	Abstract

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BACKGROUND: Activated leukocytes may increase morbidity in cardiac surgery. The objective of this study is to investigate the influence on morbidity of leukocyte-depleting blood filters placed into the arterial line of cardiopulmonary bypass circuits.

METHODS: Simple, blind, prospective, randomized and controlled clinical trial carried out in a cardiac surgery ICU at a university center. We included 159 consecutive low-risk patients (ie, Parsonnet score < 10) undergoing cardiac surgery who were initially stratified in three risk levels according to the Parsonnet score at admission into the hospital (ie, low, < 4; middle, 4 to 7; and high, 8 to 10). Once stratified, all patients were randomized to undergo cardiopulmonary bypass either with a conventional blood filter or with a leukocyte filter (randomization ratio, 2:1). The outcome variable was morbidity. Patients were considered to have a high morbidity if any of the following clinical situations were present (ie, pulmonary dysfunction, cardiac dysfunction, perioperative infections, postoperative hyperthermia, and hyperdynamic states).

RESULTS: The leukocyte filter was used in 52 patients and the conventional filter in 107 patients. The morbidity rate was similar in both groups, but patients with leukocyte filter had a lower incidence of perioperative infections, fever, and hyperdynamic states as compared with patients with the conventional filter.

CONCLUSIONS: Leukocyte filtration in patients undergoing cardiac surgery with extracorporeal perfusion showed no measurable effects on postoperative morbidity. However, although not statistically significant, a decrease was observed in the rates of perioperative infection, fever, and hyperdynamic states.

	Introduction

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The contact of blood with foreign surfaces into the cardiopulmonary bypass (CPB) circuit induces an inflammatory response with a potentially harmful effect from the occurrence of several dysfunctions in patients undergoing cardiac surgery [1]. Leukocytes play a central role in this inflammatory response and the evolving view of leukocyte-mediated morbidity consequent to bypass surgery suggests that neutrophil activation is a prerequisite for parenchymal cell destruction [2]. Activated leukocytes have been implicated in nonsurgical bleeding, postoperative infection, and pulmonary and cardiac dysfunction [1]. Some studies have demonstrated the value of leukocyte reduction, whereas others fail to demonstrate any apparent effect on the circulating leukocyte level, physiological response or clinical end points [1]. Leukocyte depletion has been shown to improve postoperative respiratory function in CPB patients [3], decrease myocardial cell injury [4], and reduce blood transfusion requirements [5], length of hospital stay, and costs in low-risk patients [6]. Conversely, other studies have failed to demonstrate an improvement in postoperative lung function [7, 8], hemostatic dysfunction [8], and clinical outcome [9], including hospital stay.

Only a few randomized, controlled trials have investigated the influence of leukocyte depletion on morbidity in low-risk cardiac surgery patients, and the need for new studies has already been recognized [6]. The purpose of this prospective, controlled and randomized clinical trial was to determine whether leukocyte depletion by means of an arterial leukocyte filter improves postoperative morbidity in low-risk cardiac surgery patients.

	Material and Methods

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Patients
The study was conducted between June 2003 and December 2003 at the Hospital Universitario "Virgen del Rocío" in Seville, Spain, a 2,000-bed, public teaching hospital. The study was approved by the Institutional Ethical Committee and informed consent was obtained from all patients. We included low-risk patients (ie, Parsonnet level 10) undergoing elective cardiac surgery. Exclusion criteria were comprised of urgent surgery, high-risk surgery (ie, Parsonnet score >10) [10], abnormal preoperative pulmonary function (ie, chronic obstructive pulmonary disease, severe pulmonary hypertension), severe preoperative cardiac dysfunction (ie, heart ejection fraction < 40%, left main coronary artery disease, or the need for intraaortic balloon pump before surgery), preoperative anemia (ie, hemoglobin < 110 g/L), hemostatic dysfunction (ie, platelet count < 200 x 10⁹, thrombin or partial thromboplastin time > 1.5 control), and presence of fever or any symptom of infection before surgery.

Study Design
At admission to the hospital, patients were initially stratified into three levels of surgical risk according to their Parsonnet score (ie, low, < 4; middle, 4 to 7; high, 8 to 10). Once stratified, patients in each of these levels were subsequently randomized to belong to either a control group with a conventional filter or to a study group with a leukocyte filter. Randomization (ratio, 2:1) was performed in blocks of patients by means of sequentially numbered, identical-appearing containers; 107 patients were assigned to the conventional filter group in which 22 patients (12.9%) were low risk, 50 (46.7%) were middle risk, and 35 (32.7%) were high-risk. Fifty-two patients were assigned to the leukocyte filter group in which 8 patients (15.3%) were low risk, 25 (48%) were middle risk, and 19 (15.3%) were high risk. The aim of stratification according to the Parsonnet score within both randomization groups was to avoid the confounding effect that factors such as the performance status might have on the conclusions of the study.

The CPB circuit and perfusion conducts were the same for all the patients, except for the filter inserted into the arterial line of the circuits; a conventional filter alone for patients in the control group and a leukocyte-depleting filter in the study group. Intraoperative and postoperative data were collected from all patients and were compared with both groups for statistically significant differences.

Anesthesia, Surgical Intervention and Postoperative Procedures
Anesthetics (ie, midazolam, remifentanyl, and vecuronium), operative and postoperative monitoring, and support therapy were the same in both groups of patients. Arterial blood pressure, central venous pressure, body temperature, and arterial blood gases were monitored in all the patients. One hundred, seven patients (71 from the conventional filter group and 36 from the leukocyte filter group) required continuous recording of pulmonary arterial pressure, pulmonary capillary wedge pressure, cardiac output, and mixed venous saturation of oxygen, which were performed by means of a catheter inserted into the pulmonary arteria (Swan-Ganz catheter CCOmbo CCO/SvO₂ [Edwards Lifesciences, Irving, CA]). The management of myocardial protection, mechanical ventilation, and drug infusions was the same for all the patients. In most cases, mechanical ventilation was not required for longer than 8 hours, and extubation was possible when hemodynamic stability was achieved (Ramsay score of 2 to 3, SaO₂ > 95% with FiO₂ < 0.4 and no significant bleeding).

The cardiopulmonary bypass circuit was composed of a disposable membrane oxygenator (AFFINITY NT Oxygenator [Medtronic, Inc, Minneapolis, MN]) and a roller pump (Heart Lung Machine Sarns Modular Perfusion System 8000 [3M, Ann Arbor, MI]) primed with crystalloid solution containing 2 million KIU of aprotinin (only in valve replacement patients). The leukocyte-depleting arterial blood filter (Leuko-Guard-6 [Pall Biomedical Products Corp, East Hills, NY]) was incorporated instead of a standard arterial filter in patients from the leukocyte filter group. Systemic leukofiltration started at the onset of CPB and lasted throughout the entire procedure.

Variables
The outcome variable was morbidity. It was assessed and both groups were compared with several surrogated variables such as: (1) length of stay in the intensive care unit (ICU); (2) pulmonary functions (ie, PaO ₂/PIO ₂ ratio, dynamic pulmonary compliance [these variables were measured first during the surgical intervention and then at hours 1 and 4 of ICU stay], and mechanical ventilation time; (3)cardiac function (ie, perioperative ischemia (assessed by cardiac enzymes, electrocardiographic recording, and new segmental hypokinesia at the echocardiography), ejection fraction (assessed by echocardiography), cardiac output (only in patients with a pulmonary thermodilution catheter), postoperative heart failure, and cardiac enzymes (troponin T and CK-MB), which were being quantified every 4 hours, with the highest value during the first 24 hours, which was included in the statistical analysis; and (4) perioperative infections (ie, pneumonia, mediastinitis, sepsis), fever (T > 38°C), and incidence of hyperdynamic circulatory states.

Pneumonia was diagnosed by the presence of new pulmonary infiltrate on chest roentgenogram, fever, leukocytosis, and positive quantitative culture of secretions obtained by tracheal aspirate of more than 10⁶ colony forming units (cfu)/mL, or by protected specimen brush 10³ cfu/mL, or by both [11]. Mediastinitis was diagnosed if the surgical wound was infected and required reintervention for its treatment, with positive cultures obtained at the sternotomy level [12]. Catheter-related bloodstream infection was diagnosed when the same strain was isolated in both blood cultures and the semi-quantitative culture of a catheter segment (yielding > 15 colonies), or if withdrawing the catheter was followed by a clear clinical response and no primary site other than the intravascular catheter that could be identified. Patients without evidence of pneumonia, mediastinitis, or catheter-infection, but with criteria for sepsis or septic syndrome were classified as patients with sepsis [13]. A hyperdynamic circulatory state (only in patients with pulmonary thermodilution catheters) was diagnosed when the following criteria were fulfilled: cardiac index > 3.8 L/m/m², oxygen mixed venous saturation (SvO₂) > 68%, systemic vascular resistance < 800 dyne/sec/cm⁵, temperature > 38°C (early), and mean arterial pressure < 60 mm Hg (providing that all of the cases yielded negative cultures). Leukocyte counts, platelet counts, and hemoglobin levels were measured at different intervals (ie, before surgery, after unclamping the aorta, after completing cardiopulmonary bypass, and at hours 1 and 12 of ICU stay).

Statistical Analysis
Comparisons with the conventional filter group and the leukocyte filter group were accomplished by using two-sample unpaired t-tests for parametric continuous variables, the Mann Whitney U test for nonparametric continuous variables, and Pearson's chi² test or Fisher's exact test for categorical variables. Statistical significance was considered when p was < 0.05. Data were collected and analyzed with the SPSS 10.0 software package (SPSS Inc, Chicago, IL).

	Results

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A total of 304 patients were assessed for eligibility (Fig 1). Among them, only 159 patients were actually enrolled in the study; fifty-two patients in the leukocyte filter group and 107 in the conventional filter group (Fig 1). No differences were found regarding preoperative and intraoperative variables between both groups (Table 1).

View larger version (34K): [in this window] [in a new window]   Fig 1. Number of patients assessed and enrolled in this trial.

View larger version (15K): [in this window] [in a new window]   Fig 2. Total white blood cell counts. Time number 1 (T1): before cardiopulmonary bypass (CPB); time number 2 (T2): aortic cross-clamp release; time number 3 (T3): end of CPB; time number 4 (T4): 1 hour in the intensive care unit (ICU); time number 5 (T5): 12 hours in the ICU. (C = conventional filter group; L = leukoguard filter group.)

View larger version (17K): [in this window] [in a new window]   Fig 3. Granulocytes polymorphonuclear (PMN) neutrophilic leukocyte counts. Time number 1 (T1): before cardiopulmonary bypass (CPB); time number 2 (T2): aortic cross-clamp release; time number 3 (T3): end of CPB; time number 4 (T4): 1 hour in the intensive care unit (ICU); time number 5 (T5): 12 hours in the ICU. (C = conventional filter group; L = leukoguard filter group.)

View larger version (16K): [in this window] [in a new window]   Fig 4. Lymphocyte counts. Time number 1 (T1): before cardiopulmonary bypass (CPB); time number 2 (T2): aortic cross-clamp release; time number 3 (T3): end of CPB; time number 4 (T4): 1 hour in the intensive care unit (ICU); time number 5 (T5): 12 hours in the ICU. (C = conventional filter group; L = leukoguard filter group.)

Cardiopulmonary Function
No statistically significant differences were found between the groups regarding compliance and PaO ₂/PIO ₂ ratio measured during the surgical intervention and at hours 1 and 4 of ICU stay (Table 2). With respect to the time of mechanical ventilation, all of the patients in both groups presented similar times, except for 1 patient in the control group who was extubated on post surgery day 4 due to cerebral dysfunction, who was therefore excluded from the analysis of mechanical ventilation time. Also those variables evaluating cardiac function yielded equivalent results in both groups (Table 2).

Bleeding and Blood Transfusion
Both groups had similar incidences of bleeding during the first 24 hours (738 ± 791 cc conventional filter vs 688 ± 583 cc leukocyte filter; p = 0.703) and transfusion requirements (ie, erythrocyte concentrates [4.36 ± 3.09 in the conventional filter group vs 4.4 ± 2.2 in the leukocyte filter group; p = 0.891], fresh frozen plasma [3.55 ± 2.3 conventional filter patients vs 2.7 ± 2.1 leukocyte filter patients; p = 0.400], and platelet units [5.1 ± 1.9 conventional filter vs 4.6 ± 2.4 leukocyte filter; p = 0.701]).

Stay in the ICU
No significant differences were detected between the groups (5.0 ± 4.0 days for the conventional filter vs 4.2 ± 2.7 days for the leukocyte filter; p = 0.299).

	Comment

Top Abstract Introduction Material and Methods Results Comment The Society of Thoracic... Acknowledgments References

 
The major finding of this randomized and controlled study suggests that the use of a leukocyte-depleting blood filter placed at the arterial line of the CPB circuit in low-risk patients undergoing cardiac surgery has no measurable effect on postoperative morbidity. This outcome variable, assessed by means of cardiopulmonary function, perioperative infection rate, fever, incidence of hyperdynamic states, transfusional requirements, and length of stay in the ICU, was similar in both groups of patients (ie, leukocyte and conventional filters). However, those patients randomized to the leukocyte-depleting filter group showed a lower incidence of perioperative infections, fever, and hyperdynamic states when compared with the conventional filter group; however, the differences were not significant.

Plenty of reports are currently available suggesting a role of activated neutrophils in the pathogenesis and related morbidity that is associated with CPB. Therefore, reducing the neutrophil population by means of a leukocyte-depleting filter during the CPB procedure would be expected to result in a decreased neutrophil-mediated tissue injury and subsequent morbidity. However, the expected decline in the leukocyte count in the leukocyte-depleting filter group when compared with the conventional filter group did not occur either after CPB or during the ICU stay (Fig 2). Similar results have been published by other authors [14, 15]. Nevertheless, when using a leukocyte filter, the reduction of the leukocyte count may not be as apparent as expected, because its effect is somewhat selectively exerted on the activated neutrophil population, and it has less of an effect on other leukocyte subsets [16].

In regard to the benefits of leukocyte filters on the improvement of post-surgery cardiopulmonary function, incidence of bleeding, allogeneic blood transfusion requirements, and length of stay in the ICU, several reports have been published with conflicting results. We assessed the pulmonary function by means of lung compliance, oxygenation index, and mechanical ventilation time, with no statistically significant differences between the groups of patients. In a randomized controlled study, Mihaljevic and colleagues [7] evaluated post-surgical pulmonary function in a group of 14 patients with leukocyte-depleting filter during CPB, and compared the results with those obtained from a control group in which CPB was performed without leukofiltration. They found no differences between the groups, as assessed by oxygenation index, pulmonary vascular resistance, and intubation time. Another study, similar to ours, could not demonstrate any beneficial effects of leukocyte filtration on post-bypass pulmonary or myocardial function in elective CABG patients compared with patients undergoing CPB with a standard arterial line filter (15). A recent controlled, randomized trial did not find any benefit regarding extubation time in patients scheduled to be included in a leukocyte filtration group [14]. Conversely, leukodepletion has demonstrated an improvement in postoperative respiratory function in low-risk patients [6] and in patients with a low preoperative oxygenation capacity or long CPB time [17]. The use of a leukocyte filter during CPB was associated with transient reductions in intrapulmonary shunts and with increased systemic oxygenation, but these effects were no longer significant after 24 hours [3].

Increased hemodynamic instability during cardiac surgery may result from a spillover of cytokines [1]. Leukocyte depletion during extracorporeal circulation should reduce the release of these toxic compounds, thereby improving post-bypass myocardial and pulmonary function. One of the first works reported on the matter, carried out in an in vivo porcine model, showed that leukocyte depletion during initial reperfusion resulted in a sustained improvement in post-ischemic left ventricular function [18]. However, a controlled study designed to evaluate the influence of leukocyte-depleting arterial filter on post-bypass pulmonary and myocardial function showed no differences regarding the need for inotropic support and perioperative CK-MB and troponin between patients randomized to belong to the leukocyte-depleting filter group versus the standard filter group [15]. Our results show that cardiac index, cardiac enzymes, and the rate of cardiac dysfunction were similar in both groups, therefore suggesting that perioperative cardiopulmonary function in low risk patients does not improve with the use of leukocyte-depleting filters.

In our series, the patients randomized to the conventional group had a higher rate of perioperative infections, fever, and hyperdynamic states than patients randomized to the leukocyte filter group (Table 2), although the differences were not significant. Both donor and receptor leukocytes have been involved, in different ways, in the incidence of perioperative infections. The role of donor allogeneic leukocytes present in erythrocyte concentrates in the occurrence of perioperative infections in patients undergoing cardiac surgery has already been demonstrated, and leukocyte depletion of transfused blood decreased the rate of infection in these patients [19]. More recently, Silliman and colleagues [20] proposed that allogeneic blood may exert a neutrophil-priming effect mediated by bioactive lipids that accumulate during storage on the receptor's leukocytes. Therefore these authors have demonstrated a relationship between multiorgan failure and transfusion of stored blood in trauma patients [21]. Recently, our group found an association between transfusion and nosocomial pneumonia [22] and also between transfusion of red blood cells stored for longer than 28 days and the development of nosocomial pneumonia [23]. In theory, it is possible that these neutrophils that were activated during the CPB procedure have deleterious effects similar to those of the neutrophils primed by transfused stored blood.

Nonsurgical postoperative bleeding has been correlated with the leukocyte count [24], activation of the complement cascade, and production of cytokines [1]. Therefore, in theory, removing the leukocytes from transfused blood could decrease the incidence of bleeding as well as the requirements of allogeneic blood transfusion. However, our results, and similarly the results from other authors [8, 14], do not support this hypothesis.

Finally, we used the stay at the ICU as a surrogated marker of morbidity. If leukocyte depletion had a beneficial effect, not detected by the variables used in this study, the length of stay at the ICU could decrease [6]. However, this and other trials could not demonstrate any beneficial effects of leukocyte-depletion on the length of ICU stay in low-risk cardiac surgery patients [9, 14].

This study may have limitations inherent to the sample size. It is possible that some significant differences would have been found in some of the variables studied (ie, infections) if the sample size was larger. However, the size of our sample can be considered large enough when compared with other studies published. Many other factors related to morbidity (such as the difficulty of surgery, staff, and equipment manipulation) may have been involuntarily discarded; nevertheless, we have evaluated morbidity by means of many different variables, and we believe this is a relevant contribution of our study.

In summary, in this randomized and controlled study, we failed to demonstrate a beneficial effect of leukocyte depletion by means of a leukocyte filter in low-risk patients undergoing cardiac surgery. Although a decrease in the rate of perioperative infections, hyperdynamic states, and postoperative fever has been observed in the leukocyte filter group with respect to the conventional filter group, the differences did not achieve statistical significance. Nevertheless, we strongly believe that further research would be worthwhile in order to support the possible deleterious effects that activated leukocytes may have in patients undergoing cardiac surgery.

	The Society of Thoracic Surgeons: Forty-Second Annual Meeting—New Location

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The city of New Orleans and part of the Gulf region have been devastated by the effects of Hurricane Katrina. Relief efforts have begun, but the clean-up and recovery processes will be slow. For this reason, The Society of Thoracic Surgeons will host its 42nd Annual Meeting in Chicago, Illinois. Please note: the meeting dates have not changed . The Annual Meeting will be held at McCormick Place, January 30–February 1, 2006, and STS/AATS Tech-Con 2006 will be held in the same location, January 28–29.

The Workforce on Annual Meeting's Program Task Force is meeting to discuss program details, and to organize an outstanding educational event. Chicago also offers a wide array of exciting social activities. The Advance Program Book will be mailed as usual in mid-to-late October and will include extensive information on ancillary activities for members and their families. Housing and meeting registration will be available online later in September.

Please continue to visit www.sts.org for important program information as it develops!

	Acknowledgments

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Supported by Spanish Government funds (FIS PI 030356).

	References

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1. Laffey JG, Boylan JF, Cheng DC. The systemic inflammatory response to cardiac surgery Anesthesiology 2002;97:215-252.[Medline]
2. Edmuns LH. Inflammatory response to cardiopulmonary bypass Ann Thorac Surg 1998;66:S12-S16.[Abstract/Free Full Text]
3. Johnson D, Thomson D, Mycyk T, et al. Depletion of neutrophils by filter during aortocoronary bypass surgery transiently improves postoperative cardiorespiratory status Chest 1995;107:1253-1259.[Abstract/Free Full Text]
4. Di Salvo C, Louca LL, Pattichis K, et al. Does activated neutrophil depletion on bypass by leukocyte filtration reduce myocardial damage? A preliminary report J Cardiovasc Surg (Torino) 1996;37(6 Suppl 1):93-100.[Medline]
5. Stefanou DC, Gourlay T, Asimakopoulos G, et al. Leukodepletion during cardiopulmonary bypass reduces blood transfusion and crystalloid requirements Perfusion 2001;16:51-58.[Abstract/Free Full Text]
6. Gott JP, Cooper WA, Schmidt FEJ, et al. Modifying risk for extracorporeal circulationtrial of four antiinflammatory strategies. Ann Thorac Surg 1998;66:747-753.[Abstract/Free Full Text]
7. Mihaljevic T, Tonz M, Segesser LK, et al. The influence of leukocyte filtration during cardiopulmonary bypass on postoperative lung function J Thorac Cardiovasc Surg 1995;109:1138-1145.
8. Baksaas ST, Flom-Halvorsen HI, Ovrum E, et al. Leukocyte filtration during cardiopulmonary reperfusion in coronary artery bypass surgery Perfusion 1999;14:107-117.[Abstract/Free Full Text]
9. Hurst T, Johnson D, Cujec B, et al. Depletion of activated neutrophils by a filter during cardiac valve surgery Can J Anesth 1997;44:131-139.[Medline]
10. Parsonnet V, Dean D, Bernstein AD. A method of uniform stratification of risk for evaluating the results of surgery in acquired adult heart disease Circulation 1989;79:3-12.
11. Grossman RF, Fein A. ACCP evidence-based assessment of diagnostic tests for ventilator-associated pneumonia Chest 2000;117(Suppl 2):177S-218S.[Free Full Text]
12. El Oakley RM, Wright JE. Postoperative mediastinitisclassification and management. Ann Thorac Surg 1996;61:1030-1036.[Abstract/Free Full Text]
13. Bone RC. The pathogenesis of sepsis Ann Intern Med 1991;115:457-469.
14. Sahlman A, Ahonen J, Salo JA, et al. No impact of a leukocyte depleting arterial line filter on patient recovery after cardiopulmonary bypass Acta Anesthesiolol Scand 2001;45:558-563.
15. Mair P, Hoermann C, Mair J, et al. Effects of a leukocyte depleting arterial line filter on perioperative proteolytic enzyme and oxygen free radical release in patients undergoing aortocoronary bypass surgery Acta Anesthesiol Scand 1999;43:452-457.[Medline]
16. Ortolano G, Aldea GS, Lilly K, et al. A review of leukofiltration in cardiac surgerythe time course of reperfusion injury may facilitate study design of anti-inflammatory effects. Perfusion 2002;17:53-62.[Abstract/Free Full Text]
17. Marioka K, Muraoka R, Chiba Y, et al. Leukocyte and platelet depletion with a blood cell separatoreffects on lung injury after cardiac surgery with cardiopulmonary bypass. J Thorac Cardiovasc Surg 1996;111:45-54.[Abstract/Free Full Text]
18. Wilson IC, Gadner TJ, DiNatale JM, et al. Temporary leukocyte depletion reduces ventricular dysfunction during prolonged postischemic reperfusion J Thorac Cardiovasc Surg 1993;106:805-810.[Abstract]
19. Van de Watering LM, Hermans J, Houbiers JG, et al. Beneficial effects of leukocyte depletion of transfused blood on postoperative complications in patients undergoing cardiac surgerya randomized clinical trial. Circulation 1998;97:562-568.[Abstract/Free Full Text]
20. Silliman CC, Moore EE, Johnson JL, et al. Transfusion of the injured patient. Proceed with caution Shock 2004;21:291-299.[Medline]
21. Offner PJ, Moore EE, Biffl WL, et al. Increased rate of infection associated with transfusion of old blood after severe injury Arch Surg 2002;137:711-717.[Abstract/Free Full Text]
22. Leal-Noval SR, Márquez JA, García-Curiel A, et al. Nosocomial pneumonia in patients undergoing heart surgery Crit Care Med 2000;28:935-940.[Medline]
23. Leal-Noval SR, Jara I, García-Garmendía JL, et al. Influence of erythrocyte concentrate storage time on post surgical morbidity in cardiac surgery patients Anesthesiology 2003;98:815-822.[Medline]
24. Despostis GI, Levine V, Goodnough LT. Relationship between leukocyte count and patient risk for excessive blood loss after cardiac surgery Crit Care Med 1997;25:1338-1346.[Medline]

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