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Cell salvage of cardiotomy suction blood improves the balance between pro- and anti-inflammatory cytokines after cardiac surgery
Gabel J, Westerberg M, Bengtsson A, Jeppsson A
European Journal of Cardio-Thoracic Surgery. 2013;44((3):):506-11.
Abstract
OBJECTIVES The inflammatory response after cardiac surgery is characterized by a profound release of pro- and anti-inflammatory cytokines. Recent data suggest that the balance between pro- and anti-inflammatory cytokines is of greater importance than the absolute levels. Retransfusion of unwashed cardiotomy suction blood contributes to the inflammatory response, but the balance between pro- and anti-inflammatory cytokines in cardiotomy suction blood and whether cell salvage before retransfusion influences the systemic balance have not been investigated previously. METHODS Twenty-five coronary artery bypass grafting patients were randomized to either cell salvage of cardiotomy suction blood or no cell salvage before retransfusion. Plasma levels of three anti-inflammatory cytokines [interleukin (IL)-1 receptor antagonist, IL-4 and IL-10] and two proinflammatory cytokines (tumour necrosis factor-alpha and IL-6), and the IL-6-to-IL-10 ratio was measured in cardiotomy suction blood before and after cell salvage, and in the systemic circulation before, during and after surgery. RESULTS Plasma levels of all cytokines except IL-4 and IL-10 were significantly higher in cardiotomy suction blood than in the systemic circulation. The IL-6-to-IL-10 ratio was 6-fold higher in cardiotomy suction blood than in the systemic circulation [median 10.2 (range 1.1-75) vs 1.7 (0.2-24), P < 0.001]. Cell salvage reduced plasma levels of cytokines in cardiotomy suction blood and improved the systemic IL-6-to-IL-10 ratio 24 h after surgery [median 5.2 (3.6-17) vs 12.4 (4.9-31)] compared with no cell salvage (P = 0.032). CONCLUSIONS The balance of pro- and anti-inflammatory cytokines in cardiotomy suction blood is unfavourable. Cell salvage reduces the absolute levels of both pro- and anti-inflammatory cytokines in cardiotomy suction blood and improves the balance in the systemic circulation after surgery.
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2.
Complement split products and proinflammatory cytokines in intraoperatively salvaged unwashed blood during hip replacement: comparison between heparin-coated and non-heparin-coated autotransfusion systems
Kvarnström A, Schmidt A, Tylman M, Jacobsson M, Bengtsson A
Vox Sanguinis. 2008;95((1):):33-8.
Abstract
BACKGROUND AND OBJECTIVES The aim of the present study was to investigate the quality of shed blood collected in a new intraoperative autotransfusion system (Sangvia, AstraTech, Sweden) and to study whether heparin-coated surfaces in the device reduce the production of inflammatory mediators. MATERIAL AND METHODS The study was randomized and prospective. Twelve total hip arthroplasty patients whose blood was collected with a device having a heparin-coated surface and 12 patients whose blood was collected with a device having a non-heparin-coated surface were included. Venous blood was drawn from the patients preoperatively. Intraoperatively 200 ml salvaged blood was collected and samples were also withdrawn; samples were obtained from the blood bag. RESULTS Compared to venous blood, elevated concentrations of interleukin 6 (IL-6), IL-8, C3a and polymorphonuclear elastase were found in collected blood. No significant differences in inflammatory mediators were found between the heparin-coated and the non-heparin-coated groups. The median haemoglobin concentration in the salvaged blood was 74 g/l in both groups. Plasma haemoglobin and potassium concentrations were also elevated. There were no significant differences between the groups. CONCLUSION The present study indicates that the blood salvaged intraoperatively contains elevated levels of complement split product and proinflammatory cytokines and that heparin-coated surfaces of the salvage device do not significantly influence the formation of inflammatory mediators.
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3.
Hemodynamic effects of cardiotomy suction blood
Westerberg M, Gäbel J, Bengtsson A, Sellgren J, Eidem O, Jeppsson A
The Journal of Thoracic and Cardiovascular Surgery. 2006;131((6):):1352-7.
Abstract
OBJECTIVE Cardiac surgery induces a systemic inflammatory activation, which in severe cases is associated with peripheral vasodilation and hypotension. Cardiotomy suction blood contains high levels of inflammatory mediators, but the effect of cardiotomy suction blood on the vasculture is unknown. We investigated the effect of cardiotomy suction blood on systemic vascular resistance in vivo and whether cell-saver processing of suction blood affects the vascular response. METHODS Twenty-five patients undergoing coronary surgery (mean age, 68 +/- 2 years; 80% men) were included in a prospective randomized study. The patients were randomized to retransfusion of cell-saver processed (n = 13) or cell-saver unprocessed (n = 12) suction blood during full cardiopulmonary bypass. Mean arterial blood pressure was continuously registered during retransfusion, and systemic vascular resistance was calculated. Plasma concentrations of tumor necrosis factor alpha, interleukin 6, and complement factor C3a were measured in suction blood. RESULTS Retransfusion of cardiotomy suction blood induced a transient reduction in systemic vascular resistance in all patients. The peak reduction was significantly less pronounced in the group receiving cell-saver processed blood (-12% +/- 2% vs -28% +/- 3%, P = . 001). There was a significant correlation between tumor necrosis factor alpha concentration in retransfused cardiotomy suction blood and peak reduction of systemic vascular resistance (r = 0. 60, P = . 002). CONCLUSIONS The results suggest cardiotomy suction blood is vasoactive and might influence vascular resistance and blood pressure during cardiac surgery. The observed vasodilation is proportional to the inflammatory activation of suction blood and can be reduced by processing suction blood with a cell-saving device before retransfusion.
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IL-6 and IL-8 response to erythropoietin therapy in radical hysterectomy
Hyllner M, Avall A, Bengtson JP, Bengtsson A
Acta Anaesthesiologica Scandinavica. 2005;49((1):):47-51.
Abstract
BACKGROUND The use of recombinant human erythropoietin (rHuEPO) improves autologous blood donation before elective surgery. However, there are other studies indicating that rHuEPO may suppress postoperative endogenous production of erythropoietin and stimulate inflammatory mediator release. Weekly donations generate only a moderate increase in endogenous erythropoietin production. We scheduled patients with cancer to predeposit three units of blood in 2 weeks, with or without rHuEPO therapy. The aim was to determine whether rHuEPO therapy and/or an aggressive donation schedule alter perioperative erythropoietin concentrations and whether rHuEPO therapy leads to the release of the pro-inflammatory cytokines IL-6 and IL-8. METHODS Thirty women scheduled for radical hysterectomy and pelvic lymphadenectomy were randomly assigned to either a control group with no rHuEPO therapy or to receive rHuEPO. Three units of whole blood were collected from each patient before the operation. Concentrations of haemoglobin, erythropoietin (s-EPO) and cytokines (IL-6 and IL-8) were repeatedly analyzed before and after the operation. RESULTS During the preoperative donation period, median s-EPO levels in the control group increased from 7 to 14 IU l(-1). There was a great increase in s-EPO concentrations 1 h postoperatively in the rHuEPO group compared with the control group (P < 0. 001). IL-6 and IL-8 were not significantly changed after intravenous administration of rHuEPO. CONCLUSION The use of rHuEPO therapy to optimise autologous blood donation does not influence IL-6 and IL-8 release. 1 h postoperatively rHuEPO therapy resulted in elevated s-EPO concentrations. There was, however, no difference in s-EPO between the groups from day 1 postoperatively and until the end of the study.
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5.
Coronary surgery without cardiotomy suction and autotransfusion reduces the postoperative systemic inflammatory response
Westerberg M, Bengtsson A, Jeppsson A
The Annals of Thoracic Surgery. 2004;78((1):):54-9.
Abstract
BACKGROUND Cardiotomy suction and autotransfusion of mediastinal shed blood may contribute to the inflammatory response after cardiac surgery. We compared inflammatory activation, myocardial injury, bleeding, and hemoglobin levels in patients undergoing coronary surgery with or without retransfusion of cardiotomy suction blood and mediastinal shed blood. METHODS Twenty-nine patients were included in a prospective randomized study. Cardiotomy suction blood and mediastinal shed blood were either retransfused or discarded. Plasma concentrations of the cytokines tumor necrosis factor-alpha and interleukin-6 and complement factor C3a were measured preoperatively and 10 minutes, 2 hours, and 24 hours after cardiopulmonary bypass. C-reactive protein, erythrocyte sedimentation rate, troponin-T, and hemoglobin levels were analyzed preoperatively, and 24 and 48 hours after cardiopulmonary bypass. Postoperative bleeding the first 12 hours was registered. RESULTS Baseline data did not differ between the groups. Plasma concentrations of tumor necrosis factor-alpha, interleukin-6, and C3a increased after surgery in both groups but significantly less in the group without cardiotomy suction and autotransfusion. The peak delta values in the no-retransfusion group was 36% (tumor necrosis factor-alpha), 47% (interleukin-6), and 75% (C3a) of the values in the retransfusion group. C-reactive protein, erythrocyte sedimentation rate, and troponin-T increased after surgery in both groups without intergroup differences. Postoperative bleeding and hemoglobin levels did not differ between the groups. No patient received homologous blood transfusion. CONCLUSIONS Coronary surgery without retransfusion of cardiotomy suction blood and mediastinal shed blood reduces the postoperative systemic inflammatory response.
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6.
Inflammatory mediators in autotransfusion drain blood after knee arthroplasty, with and without leucocyte reduction
Dalén T, Bengtsson A, Brorsson B, Engström KG
Vox Sanguinis. 2003;85((1):):31-39.
Abstract
BACKGROUND AND OBJECTIVES The aim of this study was to evaluate whether leucocyte-reducing filters influenced complement activation and the formation of pro-inflammatory cytokines in autotransfusion drain blood after knee arthroplasty. MATERIALS AND METHODS Twenty- three patients undergoing knee arthroplasty were divided into two groups. All patients were given salvage blood postoperatively. In Group A, a leucocyte filter was connected between the wound and the drain blood container. In Group B the drain blood was not leucocyte filtered. Complement split products and cytokines were analysed in circulating blood and in drain blood, together with blood-cellular differential counts. RESULTS Drain blood showed activation vs. venous blood, with elevated concentrations of C3a, SC5b-9, interleukin (IL)-6, IL-8, polymorphonuclear (PMN) elastase and tumour necrosis factor-alpha (TNF-alpha) (P<0. 05 to P<0. 001). The leucocyte filter reduced TNF-alpha (P<0. 01), but triggered complement activation (P<0. 05). Room-temperature incubation increased the concentration of IL-8 (P<0. 01), which was seen in both venous and drain blood. The leucocyte filter prevented formation of IL-8 (P<0. 01). In drain blood at 24 h the inflammatory reactions accelerated (P<0. 05-0. 001), although the filter reduced the leucocyte counts and TNF-alpha concentrations. CONCLUSIONS The leucocyte filter reduced IL-8 and TNF-alpha in drain blood, but at the same time triggered complement activation. Incubation affected the inflammatory spectrum of both drain blood and control venous blood, and the filtering reduced this activation
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Recombinant human erythropoietin in preoperative autologous blood donation did not influence the haemoglobin recovery after surgery
Avall A, Hyllner M, Bengtson JP, Carlsson L, Bengtsson A
Acta Anaesthesiologica Scandinavica. 2003;47((6):):687-92.
Abstract
BACKGROUND Recombinant human erythropoietin in combination with preoperative autologous blood donation is an established regime for avoiding allogenic blood transfusions. The aim of the study was to determine endogenous erythropoietin production and haemoglobin recovery after preoperative autologous blood donation and surgery, with or without recombinant human erythropoietin treatment. METHODS Thirty-eight patients having total hip joint replacement surgery were randomised to receive either autologous blood transfusion (control group) or autologous transfusion plus preoperative recombinant human erythropoietin treatment (EPO group). Haemoglobin, haematocrit, erythropoietin and reticulocyte concentrations were repeatedly analysed, before, during, and after surgery. RESULTS No significant differences were found between the groups regarding haemoglobin, haematocrit, and erythropoietin, but the reticulocyte count increased significantly more in the EPO group. There was no difference in the requirement for allogeneic blood transfusions between the groups. The baseline haemoglobin was >13 g dL-1 in all but four patients. CONCLUSIONS In patients with normal preoperative haemoglobin levels, recombinant human erythropoietin treatment did not improve haemoglobin levels, or reduce the need for allogenic blood transfusion. There were no differences in serum erythropoietin concentrations between the groups. We question whether recombinant human erythropoietin treatment facilitates preoperative autologous blood donation in patients with normal haemoglobin levels.
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Autologous blood transfusion in radical hysterectomy with and without erythropoietin therapy
Hyllner M, Avall A, Swolin B, Bengtson JP, Bengtsson A
Obstetrics & Gynecology. 2002;99((5, Pt 1):):757-62.
Abstract
OBJECTIVE To investigate whether preoperative treatment with erythropoietin facilitates the collection of a sufficient amount of autologous blood in a short period of time. METHODS Forty-one women scheduled for radical hysterectomy were randomized to preoperative autologous blood donation with or without preoperative recombinant human erythropoietin therapy. All patients were scheduled to deposit three units of blood within 2 weeks before surgery. Hemoglobin, erythrocyte volume fraction, blood cells, iron status, and hemolysis were analyzed before and after surgery. RESULTS Hemoglobin levels decreased continuously in both groups after the first autologous donation until day 1 postoperatively. With erythropoietin therapy, the erythrocyte volume fraction and hemoglobin levels were significantly higher during precollection and day 1 after surgery. Preoperatively, the drop was 12 g/L less in the erythropoietin-treated group. The additional use of erythropoietin therapy reduced the inability of patients to predeposit blood from 17.8% to 3.4%. CONCLUSION Most women can predeposit three units of whole blood in only 2 weeks without obtaining severe anemia. By treating women with erythropoietin, one out of seven can be prevented from a hemoglobin level below the 100 g/L limit for donation.
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Release of interleukin-10 by reinfusion of salvaged blood after knee arthroplasty
Tylman M, Bengtson JP, Avall A, Hyllner M, Bengtsson A
Intensive Care Medicine. 2001;27((8):):1379-84.
Abstract
OBJECTIVES To determine whether the method of the autotransfusion in association with knee arthroplasty leads to differences in anti-inflammatory cytokines in the patient's circulation. DESIGN AND SETTING Prospective study in a university hospital. PATIENTS Twenty-one patients undergoing knee arthroplasty were randomized into two groups assigned to postoperative blood salvage. Seven patients received postoperatively filtered salvaged blood, and seven received centrifuged and washed salvaged blood. Patients with postoperative blood loss less than 400 ml (n=7) did not receive any transfusion. MEASUREMENTS AND RESULTS Plasma levels of interleukin (IL) 1beta, IL-4, and IL-10 and of polymorphonuclear leukocyte elastase were measured by enzyme-linked immunosorbent assay. The plasma concentration of IL-10 was elevated after reinfusion of salvaged blood in all groups 1 day after surgery (p<0.05). Plasma IL-6, IL-10, and PMN elastase was higher (p<0.01) in all groups 1 day after surgery than preoperatively. There were significantly higher plasma levels 1 min after retransfusion of IL-6 (p<0.01) and IL-10 (p<0.05) in patients receiving filtered blood than in those receiving centrifuged and washed salvaged blood. CONCLUSION Total knee arthroplasty results in the release of interleukin-10. Transfusion of filtered salvaged blood leads to higher levels of cytokines IL-6 and IL-10 than after transfusion of washed and centrifuged salvaged blood.
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10.
Greater increase in cytokine concentration after salvage with filtered whole blood than with washed red cells, but no difference in postoperative hemoglobin recovery
Avall A, Hyllner M, Bengtson JP, Carlsson L, Bengtsson A
Transfusion. 1999;39((3):):271-6.
Abstract
BACKGROUND Inflammatory mediators are released in association with intraoperative and postoperative salvage of blood. Whether these mediators (cytokines) participate in the modulation of erythropoiesis or not has been investigated. STUDY DESIGN AND METHODS Twenty-seven patients who were to undergo total knee replacement surgery were randomly assigned to postoperative blood salvage with either filtered whole blood or washed red cells. Patients with postoperative blood loss <400 mL were considered a control group. The control group did not receive any transfusions. Plasma concentrations of the anaphylatoxin C3a, the C5b-9 terminal complement complex, and the cytokines interleukins 6 and 8, hemoglobin, reticulocytes, and red cell volume fraction in the patients were repeatedly analyzed before and after surgery. RESULTS Significantly increased concentrations of interleukin 6 appeared in all three groups, which was interpreted as a response to the surgical trauma. The increase was significantly greater in the group that received filtered whole blood after return of shed blood. The recovery of hemoglobin levels did not differ in the groups. CONCLUSION The transfusion of filtered whole blood leads to the formation of interleukin 6 in the circulation, but postoperative hemoglobin recovery was similar in all groups.