Cardiopulmonary bypass (CPB) has a known association with various postoperative morbidities which have resulted in an increased need for research to be performed to find sources of formation and methods of reduction of the incidence of complications. It has been suggested that coated circuits improve postoperative outcomes compared with the traditional uncoated ones [
It is known that CPB induces a systemic inflammatory reaction that results in increased postoperative morbidity and hospital stay [
Innovative CPB settings have been developed in order to integrate the concepts of “surface-coating,” “blood-filtration,” and “miniaturization.” Indeed, the integration of arterial line filters with oxygenators fulfill these principles. However, there are a few studies that compare these innovations with traditional CPB equipment. The aim of the present study was to compare integrated and nonintegrated arterial line filters in patients who underwent CPB surgery in terms of peri- and postoperative clinical variables, inflammatory response, and transfusion needs.
This study was approved by the local Institutional Review Board (09.2010.0095/B.30.2.MAR.0.01.02/AEK/55). Written informed consent was obtained from all subjects. Thirty-six consecutive patients, admitted to the Department of Cardiovascular Surgery of our university, between March 2011 and November 2011, were prospectively included in the study. Patients were divided into two groups by block randomization method using the sealed envelope technique. In the study, oxygenators with an integrated (
Patients who did not want to participate in the study, patients who required emergency surgery or additional surgical procedure due to any complications, the ones with known malignancies, hepatic and renal disorders, unstable angina, myocardial damage, and low cardiac reserve (left ventricular ejection fraction <40%), and the ones under 18 years old were excluded from the study. Patients were excluded from the study if they had systemic infections, urinary tract infections, concurrent use of antibiotics, or steroids as these conditions may affect serum levels of IL-6 and IL-2R.
Anesthesia was induced with 4–6 mg/kg pentothal, 0.1 mg/kg midazolam, 3
All procedures were performed using an S5 roller pump (Stöckert, Sorin Group Inc., Munich, Germany) in both groups. Polyvinyl chloride tube was the same for both groups. In
All operations were performed through a standard median sternotomy incision. For the revascularization of the left anterior descending artery, left internal mammarian artery, and for other vessels, appropriately longer segments of vena saphena magna excised either from the right or left extremity were used. Pericardium was opened and elevated with slings, and then 300 U/kg heparin sodium was delivered. During CPB surgery, additional doses of heparin were administered in case of need to keep activated clotting time above 400 secs. Arterial flow was maintained with an aortic cannula (CalMed Lab, CA, USA) implanted inside ascending aorta, while for venous return two-way irrigation-aspiration cannula (CalMed Lab, CA, USA) positioned inside right atrium was used. A cannula was implanted in ascending aorta for cardioplegia and vent, and then the operation was proceeded with CPB. Moderate degrees of systemic hypothermia (28°C–32°C) were used intraoperatively. Following cross-clamping of ascending aorta, a blood cardioplegic solution (10 mEq MgSO4, 20 mEq potassium) warmed to the temperature of the pump was delivered at a dose of 10 mL/kg through an antegrade route to achieve cardiac arrest. When cross-clamping time exceeded 20 minutes, additional dose of cardioplegic solution was prepared anew and delivered through antegrade route. In both groups, pulsatile-flow cardiopulmonary bypass was performed. Extracorporeal circulation was started with nonpulsatile mode, at the time of aortic cross-clamping procedure was switched to pulsatile mode. When cross-clamp was removed, and left ventricular ejection started, nonpulsatile mode was resumed again. Distal anastomoses were performed using 7/0-8/0 prolene sutures dependent on the vascular structure, and then cross-clamp was removed. Heart rate was resumed to normal sinus rhythm spontaneously or via defibrillation. Proximal anastomoses were approximated with 6/0 prolene sutures, while the ascending aorta was partially clamped. CPB was terminated when esophageal temperature reached 37°C, and optimal cardiac conditions were achieved. Heparin was neutralized with protamine at a ratio of 1 : 1. After hemostatic control, drains were inserted into mediastinum and thoracal cavity. For the closure of the sternum, steel wire, and for subcutaneous layer, skin vicryl sutures were used.
Arterial blood samples for the assessments of complete hemogram (white blood cell (WBC) counts, hemoglobin (Hb), hematocrit (Htc), and platelet counts), creatinine, blood urea nitrogen (BUN), alanine aminotransferase (ALT), and aspartate aminotransferase (AST) were collected (1) before the operation, (2) at 24 hours, and (3) 2 and 4 days after the operation.
Serum samples for the analysis of interleukin-6 (IL-6) and interleukin-2R (IL-2R) were collected (1) preoperatively, (2) during immediate postoperative period and before heparin administration, and (3) at 6 and 24 hours after the operation. The serum samples were centrifuged at 5,000 g for 5 min and stored at −80°C until they were used. IL-6 and IL-2R levels were measured using the immulite automated chemiluminometer system (Immulite 2000 Analyzer, Siemens Healthcare Diagnostics Products Ltd. Llanberis, Gwynedd UK).
Arterial blood samples for the measurement of C-reactive protein (CRP) were collected (1) before the operation, (2) after the operation and before heparin administration, (3) at 6 and 24 hours, and (4) 2 and 4 days after the operation. CRP was measured by the CRP immunoturbidimetric method (CRPLX from Roche Diagnostics, Indianapolis, IN) on a COBAS INTEGRA 800 analyzer (Roche Diagnostics).
Need for postoperative dialysis, inotropic therapy and transfusion, in addition to extubation time, total amount of drainage (mL), length of intensive care unit, and hospital stay, and mortality rates were also recorded for each patient.
Data were analyzed using the Statistical Package for Social Sciences (SPSS) software (version 19.0 for Windows). All differences associated with a chance probability of 0.05 or less were considered statistically significant. Continuous variables are presented as mean ± SD. A normal distribution of the quantitative data was checked using Kolmogorov-Smirnov test. Parametric tests were applied to data of normal distribution and nonparametric tests were applied to data of questionably normal distribution. Independent-samples
Of the 36 patients (26 males, 10 females) whose charts were reviewed, the average age was 63.78 ± 10.37 (range 44 to 84) years. Baseline characteristics of both groups were comparable and shown in Table
Baseline characteristics of the study groups.
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Age (yr) |
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Female/male | 5/13 | 5/13 |
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Height (cm) |
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Weight (kg) |
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Diabetes mellitus | 8/18 | 8/18 |
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Hypertension | 13/18 | 14/18 |
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Hyperlipidemia | 6/18 | 9/18 |
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Tobacco use | 9/18 | 13/18 |
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Alcohol use | 1/18 | 1/18 |
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CCS grading | |||
I-II | 17/18 | 17/18 |
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III-IV | 1/18 | 1/18 |
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NYHA classification | |||
I-II | 15/18 | 17/18 |
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III-IV | 3/18 | 1/18 |
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Preoperative ejection fraction (%) |
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CCS: Canadian cardiovascular society; NYHA: New York heart association.
Perioperative and postoperative variables of the study groups.
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Perioperative variables | |||
Number of bypass grafts |
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Cross-clamp time (min) |
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CPB time (min) |
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Primary volume (mL) | 1650 | 1450 |
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Intraoperative Htc |
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Hypothermia (°C) |
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Red cell transfusion (units) |
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Postoperative variables | |||
Total drainage (mL) |
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Extubation time (hours) |
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Intensive care unit stay (days) |
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Hospital stay (days) |
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Inotropic therapy | 4/18 | 4/18 |
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Htc: hematocrit; CPB: cardiopulmonary bypass.
The mean value for WBC, Hb, Htc, platelet count, creatinine, BUN, ALT, and ASTwas not statistically different between the two groups. In both groups, CRP values increased statistically significantly starting from the 6th postoperative hour (
C-reactive protein levels of the study groups.
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C-reactive protein |
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T2 |
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T3 |
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T4 |
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T5 |
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T6 |
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T1: before the operation; T2: after the operation and before heparin administration; T3: 6 hours after the operation; T4: 24 hours after the operation; T5: 2 days after the operation; T6: 4 days after the operation.
Interleukin-6 and interleukin-2R levels of the study groups.
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Interleukin-6 (pg/mL) | T1 |
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T2 |
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T3 |
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T4 |
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Interleukin-2R (U/mL) | T1 |
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T2 |
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T3 |
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T4 |
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T1: before the operation; T2: after the operation and before heparin administration; T3: 6 hours after the operation; T4: 24 hours after the operation.
C-reactive protein levels of the study groups (T1: before the operation; T2: after the operation and before heparin administration; T3: 6 hours after the operation; T4: 24 hours after the operation; T5: 2 days after the operation; T6: 4 days after the operation).
Interleukin-6 levels of the study groups (T1: before the operation; T2: after the operation and before heparin administration; T3: 6 hours after the operation; T4: 24 hours after the operation).
Interleukin-2R levels of the study groups (T1 = before the operation; T2 = after the operation and before heparin administration; T3 = 6 hours after the operation; T4 = 24 hours after the operation).
Mean release of CRP, IL-6, and IL-2R over the entire time of observation by repeated measures ANOVA did not reveal any statistical significance. Mean CRP values were 159.44 ± 56.70 in
Area under the curve values of C-reactive protein, interleukin-6, and interleukin-2R.
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C-reactive protein |
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0.757 |
Interleukin-6 |
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0.874 |
Interleukin-2R |
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0.706 |
Area under the curve values of C-reactive protein.
Area under the curve values of interleukin-6.
Area under the curve values of interleukin-2R.
In our study, we evaluated the impact of integrated arterial filtration systems on systemic inflammatory response and postoperative requirement for transfusion. Employment of integrated filtration systems decreased prime volume for an amount of 200 cc which led to higher intraoperative hematocrit levels and lower postoperative requirement for the infusion of erythrocyte suspensions. In the group of patients in whom integrated arterial filters were used, detection of partially lower mean postoperative IL-6, IL-2R, and CRP values at all time points of blood collection promises potential gains in the future.
During extracorporeal circulation, when blood comes in contact with nonendothelial surfaces, complement, and proinflammatory mediators such as cytokines are activated leading to emergence of a systemic inflammatory response. Systemic inflammatory response developing post-CPB can be restricted to an extent of only a subclinical increase in the levels of inflammatory mediators or it can be severe enough to cause multiorgan dysfunction or even death [
During CPB, the total white blood cell count and the number of circulating neutrophils increase [
Hemodilutional anemia occurring during CPB is an important cause of morbidity and mortality [
In separate studies where Formes et al. evaluated post-CPB development of inflammatory response and Ak et al. investigated lipoprotein lipase polymorphism and its effects on atherosclerosis, the authors detected peak levels of IL-6 at post-CPB 6th hours [
Our study has several limitations. Firstly, retrograde autologous prime volumes could be used to further decrease prime volumes which we already lowered using integrated arterial filters. Within this context, combination of integrated arterial filter systems with retrograde autologous prime method might be beneficial both in the alleviation of systemic inflammatory response and further decline in the requirement for transfusion. Secondly, the study was a single-centered investigation conducted with a small group of patients. Even though in a single-centered study all patients were operated by the same surgical and anesthesia team which provides concordance among interventions, and scarce number of patients appears to be the weak point of the study. Third limitation is the enrolment of a patient group with a relatively lower risk. Starting from the fact that open heart surgery can be performed in a patient with a lower risk using standard methods with decreased morbidity and mortality rates, it can be conceived that more valuable gains can be obtained in patients with a higher risk.
Since lesser amounts of prime volumes were required for the patient in whom integrated arterial filter oxygenators were used, their intraoperative hematocrit levels were found to be relatively higher. Besides, the need for postoperative erythrocyte transfusion was also decreased. It has been detected that using integrated arterial filter has no significant effect on postoperative systemic inflammatory response.
This paper has not been published or submitted for publication in any other journal.
The authors declare that there is no conflict of interests.
This study was supported by Marmara University Scientific Project Research Comity (BAPKO).