Yavuz M. Bilgin

Double-Blind, Randomized Controlled Trial on the Effect of Leukocyte-Depleted Erythrocyte Transfusions in Cardiac Valve Surgery

Background—Leukocytes in allogeneic blood transfusions are believed to be the cause of immunomodulatory events. A few trials on leukocyte removal from transfusions in cardiac surgery have been conducted, and they showed inconclusive results. We found in a previous study a decrease in mortality rates and number of infections in a subgroup of more heavily transfused patients. Methods and Results—Patients (n= 496) undergoing valve surgery (with or without CABG) were randomly assigned in a double-blind fashion to receive standard buffy coat–depleted (PC) or prestorage, by filtration, leukocyte-depleted erythrocytes (LD). The primary end point was mortality at 90 days, and secondary end points were in-hospital mortality, multiple organ dysfunction syndrome, infections, intensive care unit stay, and hospital stay. The difference in mortality at 90 days was not significant (PC 12.7% versus LD 8.4%; odds ratio [OR], 1.52; 95% confidence interval [CI], 0.84 to 2.73). The in-hospital mortality rate was almost twice as high in the PC group (10.1% versus 5.5% in the LD group; OR, 1.99; 95% CI, 0.99 to 4.00). The incidence of multiple organ dysfunction syndrome in both groups was similar, although more patients with multiple organ dysfunction syndrome died in the PC group. LD was associated with a significantly reduced infection rate (PC 31.6% versus LD 21.6%; OR, 1.64; 95% CI, 1.08 to 2.49). In both groups, intensive care unit stay and hospital stay were similar, and postoperative complications increased with the number of transfused units. Conclusions—Mortality at 90 days was not significantly different; however, a beneficial effect of LD in valve surgery was found for the secondary end points of in-hospital mortality and infections.

Effects of allogeneic leukocytes in blood transfusions during cardiac surgery on inflammatory mediators and postoperative complications

Objective: To investigate whether the higher prevalence of postoperative complications in cardiac surgery after transfusion of leukocyte-containing red blood cells can be related to inflammatory mediators. Design: Analysis of inflammatory markers interleukin-6, interleukin-10, interleukin-12, and procalcitonin in patients participating in a randomized trial comparing leukocyte-depleted with leukocyte-containing, buffy-coat-depleted red blood cells. Setting: Two university-affiliated hospitals in the Netherlands. Subjects: A total of 346 patients undergoing cardiac valve surgery with a complete series of pre- and postoperative blood samples. Measurements and Main Results: There were no differences in the cytokines and procalcitonin concentrations between both study arms when the patients arrived in the intensive care unit. In subgroups, patients who received zero to three red blood cell transfusions showed similar cytokine concentrations in both study arms, whereas patients with ≥4 red blood cell transfusions had significantly higher interleukin-6 concentrations in the leukocyte-containing, buffy-coat-depleted red blood cell group. Patients who developed postoperative infections and multiple organ dysfunction syndrome showed, respectively, increased concentrations of interleukin-6 and interleukin-12 in the leukocyte-containing, buffy-coat-depleted, red blood cell group. The interaction tests in these subgroups showed significantly different reaction patterns in the leukocyte-containing, buffy-coat-depleted red blood cell group compared with leukocyte-depleted red blood cell group for interleukin-6 and interleukin-12. Multivariate analysis showed a high interleukin-6 concentration with multiple organ dysfunction syndrome and both high interleukin-6 and interleukin-10 concentrations with hospital mortality. Conclusions: Allogeneic leukocyte-containing blood transfusions compared with leukocyte-depleted blood transfusions induce dose-dependent significantly higher concentrations of proinflammatory mediators in the immediate postoperative period after cardiac surgery. High concentrations of interleukin-6 are strong predictors for development of multiple organ dysfunction syndrome, whereas both interleukin-6 and interleukin-10 are associated with hospital mortality. These findings suggest that leukocyte-containing red blood cells interfere with the balance between postoperative proinflammatory response, which may further affect the development of complications after cardiac surgery.

Postoperative complications associated with transfusion of platelets and plasma in cardiac surgery

BACKGROUND: Studies in cardiac surgery have reported increased postoperative morbidity and mortality after allogeneic red blood cell (RBC) transfusions. Whether platelet (PLT) and/or plasma transfusions are a marker for more concomitant RBC transfusions or are independently associated with complications after cardiac surgery is unknown.

Mannose-binding lectin is involved in multiple organ dysfunction syndrome after cardiac surgery: effects of blood transfusions.

BACKGROUND: Serum levels of mannose‐binding lectin (MBL), a recognition molecule of the lectin pathway of complement, are highly variable, based on genetic variation. After cardiac surgery, extracorporeal circulation and ischemia‐reperfusion injury initiate a systemic inflammatory response, which can evolve to multiple organ dysfunction syndrome (MODS). Preoperative transfusions of allogeneic white blood cells (WBCs) contribute to infectious and inflammatory complications. This study investigates the role of MBL in relation to blood transfusions and complications after cardiac surgery.

Allogeneic leukocytes in cardiac surgery: Good or bad?

Worldwide, cardiac surgery is a common procedure requiring a large quantity of allogeneic blood products, which are associated with postoperative complications. Leukocytes present in blood products may play a role in these complications, which are referred to as transfusion-related immunomodulation (TRIM). Several randomized controlled trials (RCTs) in different settings investigated the effects of allogeneic leukocytes in red blood cells (RBCs). Cardiac surgery studies reported a reduction in postoperative infections and mortality in patients that received leukocyte-reduced RBCs compared with leukocyte-containing RBCs; this was mainly due to more deaths due to infections and multiple organ dysfunction syndrome (MODS) in the group that received leukocyte-containing RBCs. Patients with postoperative complications had higher concentrations of inflammatory mediators. These findings suggest that leukocyte-containing transfusion during cardiac surgery induces a second insult to the systemic inflammatory response. In the present review we discuss the possible role of blood transfusions in cardiac surgery. Especially, we focus on the possible role of allogeneic leukocytes associated with postoperative complications after cardiac surgery.

HS2 COST-EFFECTIVENESS OF LEUKODEPLETION IN MAJOR CARDIAC SURGERY

rials, labour and surgical procedures) and are dependent on TTH. RESULTS: After 18,000 iterations the average TTH (cost) fell from 25.9 (€2136) to 22.0 weeks (€1987) for small ulcers (<10cm) and from 39.0 (€7047) to 33.0 weeks (€6362) for large ulcers (>=10cm) when UK-970005 Device was added. Corresponding coefficients of variation ranged between 99% and 125% for TTH and 86% and 120% for costs. The main cost driver was labour costs (75% and 84% for small and large ulcers, respectively). The remaining costs were split equally on materials and surgical procedures. Break-even was reached at a relative efficacy of UK-97-0005 Device of 7%. On the basis of an average prevalence of VLU of 0.2% in Sweden, the total cost of treating VLU-patients with UK-97-0005 Device was estimated to €59.7 million. CONCLUSION: At a relative efficacy above 7%, UK-970005 Device was shown to be a dominant alternative compared to conventional treatment of VLU in Sweden.