IL-6 and IL-8 response to erythropoietin therapy in radical hysterectomy.

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.

Recombinant human erythropoietin in preoperative autologous blood donation did not influence the haemoglobin recovery after surgery.

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.

Increased serum erythropoietin concentration after allogeneic compared with autologous blood transfusion.

Serum erythropoietin (sEPO) level is known to increase as hemoglobin (Hb) concentration decreases during and after preoperative autologous blood donation (PAD). The endogenous erythropoietin (EPO) production after allogeneic blood transfusion has not to our knowledge, been studied. The aim of the present study was to determine whether there is, after surgery, any change in sEPO concentration after allogeneic blood transfusion, and whether there is any difference in EPO response after autologous or allogeneic blood transfusion. Thirty-one patients approaching total hip-joint replacement surgery, were randomized to receive either allogeneic red blood cells (n = 15) or predeposited autologous whole blood transfusion (n = 16). The relationship between Hb, sEPO, and reticulocytes in the recipients were repeatedly analyzed before, during and after surgery. The Hb followed an expected pattern, with a decreased concentration after PAD in the autologous group, then in both groups after surgery. The sEPO concentration was significantly higher in the allogeneic than in the autologous group on day one and day 4-5 postoperatively. The reticulocyte level, on the contrary, was higher in the autologous patients before, one hour after, and one day after surgery. The study showed a greater increase in sEPO concentration after allogeneic blood transfusion than after autologous blood transfusion. There may be an inverse relationship between sEPO and the reticulocyte level.

Release of interleukin-10 by reinfusion of salvaged blood after knee arthroplasty.

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.

Greater increase in cytokine concentration after salvage with filtered whole blood than with washed red cells, but no difference in postoperative hemoglobin recovery.

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.

Formation of complement split products and proinflammatory cytokines by reinfusion of shed autologous blood.

1. The purpose of this study was to determine whether shed autologous blood collected postoperatively contains complement split products (C3a and SC5b-9) and proinflammatory cytokines (TNF-alpha, IL-1beta, IL-6 and IL-8) and whether transfusion of shed blood increases the concentrations of inflammatory mediators in the circulation. 2. Twenty consecutive patients undergoing total hip replacement surgery under spinal anaesthesia were studied. The patients were transfused with whole blood collected postoperatively. 3. The median volume shed blood returned to the patients was 350 ml (25-75% range = 300-450). Before transfusion of shed blood was filtered using a 40 microm filter (Solcotrans). Samples for complement and cytokine determinations were drawn from the collected blood. 4. Venous blood samples were drawn 1 min before transfusion, 1 and 60 min after completed transfusion. High concentrations of C3a, SC5b-9, TNF-alpha, IL-1beta, IL-6 and IL-8 were found in shed blood. The concentrations were higher than the circulating levels (P < 0.05). The filtration procedure did not significantly reduce the concentrations. 5. Transfusion of the shed blood did not significantly alter the circulating concentrations of C3a, SC5b-9, TNF-alpha, IL-1beta, and IL-8. The plasma concentrations of IL-6 were increased both 1 and 60 min after completed transfusion compared to before (P < 0.05). 6. This study shows that whole blood collected from a surgical wound contains large concentrations of complement split products and proinflammatory cytokines. Transfusion of shed blood leads to elevated plasma levels of IL-6.

Postoperative inflammatory response after autologous and allogeneic blood transfusion.

BACKGROUND: Allogeneic blood transfusions cause immunosuppression. The aim of this study was to determine whether complement anaphylatoxins, cytokines, or both are released in the recipient, after blood transfusions in general, and after autologous blood transfusions in particular. METHODS: Thirty-one patients having total hip joint replacement surgery were randomized to receive either allogeneic red blood cells (n = 15) or predeposited autologous whole blood transfusion (n = 16). Plasma concentrations of the anaphylatoxins C3a and C5a, the terminal C5b-9 complement complex, and cytokines IL-6 and IL-8 in the recipients were repeatedly analyzed before, during, and after surgery. RESULTS: Significantly increased concentrations of IL-6 and IL-8 appeared in both groups, with a significantly greater increase in the autologous blood group. Patients in both groups developed a moderate but significant increase of C3a without a significant difference between them. C5a and terminal C5b-9 complement complex were not greatly changed. CONCLUSIONS: The study showed a greater increase in cytokine concentration after autologous blood transfusion than after allogeneic blood transfusion. The lower response in the latter may result from transfusion-induced suppression of cellular immunity.

Effects on complement activation of a new continuous autotransfusion system.

Allogeneic blood transfusions may subject patients to risks of infection and allergic reactions. Various techniques for transfusion of shed blood have been developed. The aim of this study was to evaluate a new continuous autotransfusion system (Fresenius CATS) as regards its impact on the complement system, and on erythrocytes and leucocytes. Eighteen consecutive patients undergoing hip replacement surgery were studied. Complement variables (C4d, factor Bb, C3a and terminal complement complex, SC5b-9) and free haemoglobin, haemoglobin, leucocytes, platelets, albumin and protein were determined in the patient's blood preoperatively, 1 min before the start of transfusion, 15 and 60 min after transfusion; and in the reservoir, in the waste bag and in the retransfusion blood. Increased concentrations of C3a and SC5b-9 were found in the collected reservoir blood (P < 0.05). The washing and centrifugation procedure reduced these concentrations (< 0.001). High levels of free haemoglobin were found in the collected blood as well as in the processed product. The median haemoglobin level in the processed blood was 260gL-1 (range 104-289gL-1). Inflammatory mediators from the complement cascade are removed by continuous autotransfusion technique. The processed blood contains high levels of free haemoglobin.