Adrianus J. de Vries

Influence of Mechanical Cell Salvage on Red Blood Cell Aggregation, Deformability, and 2,3-Diphosphoglycerate in Patients Undergoing Cardiac Surgery With Cardiopulmonary Bypass

BACKGROUND Mechanical cell salvage is increasingly used during cardiac surgery. Although this procedure is considered safe, it is unknown whether it affects the red blood cell (RBC) function, especially the RBC aggregation, deformability, and the contents of 2,3-diphosphoglycerate (2,3-DPG). This study examines the following: (1) whether the cell salvage procedure influences RBC function; and (2) whether retransfusion of the salvaged blood affects RBC function in patients. METHODS Forty patients undergoing cardiac surgery with cardiopulmonary bypass were randomly allocated to a cell saver group (n = 20) or a control group (n = 20). In the cell saver group, the blood aspirated from the wound area and the residual blood from the heart-lung machine were processed with a continuous-flow cell saver before retransfusion. In the control group this blood was retransfused without processing. The RBC aggregation and deformability were measured with a laser-assisted optical rotational cell analyzer and 2,3,-DPG by conventional laboratory test. RESULTS The cell saver procedure did not influence the RBC aggregation but significantly reduced the RBC deformability (p = 0.007) and the content of RBC 2,3-DPG (p = 0.032). However, in patients receiving the processed blood, their intraoperative and postoperative RBC aggregation, deformability, and 2,3-DPG content did not differ from those of the control patients. Both groups of patients had a postoperative drop of RBC function as a result of hemodilution. CONCLUSIONS The mechanical cell salvage procedure reduces the RBC deformability and the cell 2,3-DPG content. Retransfusion of the processed blood by cell saver does not further compromise the RBC function in patients undergoing cardiac surgery with cardiopulmonary bypass.

Do repeated runs of a cell saver device increase the pro-inflammatory properties of washed blood?

OBJECTIVE Intra-operative cell salvage is increasingly used, especially in longer cases with continuing blood loss. However it is unknown if the quality of processed blood is affected when larger quantities of blood are processed. We hypothesized that the quality of the washed blood decreases after multiple runs. METHODS Intra-operative cell salvage was performed in 42 consecutive patients undergoing cardiac surgery. When 1250 ml of blood was collected in the blood collection reservoir, this was processed and returned to the patient. In 21 patients more than 2500 ml of blood was collected during the whole procedure, thus allowing at least two subsequent runs with the auto-transfusion device. Blood samples were drawn from the blood collection reservoir of the cell saver device before, and from the processed blood after each run. RESULTS After the first run interleukin-6 concentrations were reduced with 85% (from 21+/-35 microg/l to 3.1+/-4.4 microg/l), whereas after the second run 72% was removed (63+/-69 microg/l to 17.6+/-25.3 microg/l). Leukocyte counts almost doubled after both processing runs (from 2.6+/-1.5 x 10(9)/l to 5+/-3.6 x 10(9)/l) and from 3.9+/-2.2 x 10(9)/l to 7.7+/-5.9 x 10(9)/l), hemoglobin concentration (14.8+/-1.6 mmol/l vs 15.0+/-1.1 mmol/l), free hemoglobin (2.3+/-1.6g/l vs 2.1+/-1.4 g/l) and platelet counts (18+/-9 x 10(9)/l vs 28+/-23 x 10(9)/l) were not different between the two runs. CONCLUSIONS Our results suggest, based on interleukin-6 and free hemoglobin washout that the quality of the processed blood remains constant with multiple runs of the cell saver device.

Effects of Cell-Saving Devices and Filters on Transfusion in Cardiac Surgery: A Multicenter Randomized Study

BACKGROUND Cell-saving devices (CS) are frequently used in cardiac surgery to reduce transfusion requirements, but convincing evidence from randomized clinical trials is missing. Filtration of salvaged blood in combination with the CS is widely used to improve the quality of retransfused blood, but there are no data to justify this approach. METHODS To determine the contribution of CS and filters on transfusion requirements, we performed a multicenter factorial randomized clinical trial in two academic and four nonacademic hospitals. Patients undergoing elective coronary, valve, or combined surgical procedures were included. The primary end point was the number of allogeneic blood products transfused in each group during hospital admission. RESULTS From 738 included patients, 716 patients completed the study (CS+filter, 175; CS, 189; filter, 175; neither CS nor filter, 177). There was no significant effect of CS or filter on the total number of blood products (fraction [95% confidence interval]: CS, 0.96 [0.79, 1.18]; filter, 1.17 [0.96, 1.43]). Use of a CS significantly reduced red blood cell transfusions within 24 hours (0.75 [0.61,0.92]), but not during hospital stay (0.86 [0.71, 1.05]). Use of a CS was significantly associated with increased transfusions of fresh frozen plasma (1.39 [1.04, 1.86]), but not with platelets (1.25 [0.93, 1.68]). Use of a CS significantly reduced the percentage of patients who received any transfusion (odds ratio [95% confidence interval]: 0.67 [0.49, 0.91]), whereas filters did not (0.92 [0.68, 1.25]). CONCLUSIONS Use of a CS, with or without a filter, does not reduce the total number of allogeneic blood products, but reduces the percentage of patients who need blood products during cardiac surgery.

Angiopoietin/Tie2 Dysbalance Is Associated with Acute Kidney Injury after Cardiac Surgery Assisted by Cardiopulmonary Bypass

Introduction The pathophysiology of acute kidney injury (AKI) after cardiac surgery is not completely understood. Recent evidence suggests a pivotal role for the endothelium in AKI. In experimental models of AKI, the endothelial specific receptor Tie2 with its ligands Angiopoietin (Ang) 1 and Ang2 are deranged. This study investigates their status after cardiac surgery, and a possible relation between angiopoietins and AKI. Methods From a cohort of 541 patients that underwent cardiac surgery, blood and urine was collected at 5 predefined time points. From this cohort we identified 21 patients who had at least 50% post-operative serum creatinine increase (AKI). We constructed a control group (n = 21) using propensity matching. Systemic levels of Ang1, Ang2, and sTie2 were measured in plasma and the AKI markers albumin, kidney injury molecule-1 (KIM-1) and N-acetyl-beta-D-glucosaminidase (NAG) were measured in the urine. Results Ang2 plasma levels increased over time in AKI (from 4.2 to 11.6 ng/ml) and control patients (from 3.0 to 6.7 ng/ml). Ang2 levels increased 1.7-fold more in patients who developed AKI after cardiac surgery compared to matched control patients. Plasma levels of sTie2 decreased 1.6-fold and Ang1 decreased 3-fold over time in both groups, but were not different between AKI and controls (Ang1 P = 0.583 and sTie2 P = 0.679). Moreover, we found a positive correlation between plasma levels of Ang2 and urinary levels of NAG. Conclusions The endothelial Ang/Tie2 system is in dysbalance in patients that develop AKI after cardiac surgery compared to matched control patients.

Intraoperative cell salvage during cardiac surgery is associated with reduced postoperative lung injury

OBJECTIVES In addition to its blood-sparing effects, intraoperative cell salvage may reduce lung injury following cardiac surgery by removing cytokines, neutrophilic proteases and lipids that are present in cardiotomy suction blood. To test this hypothesis, we performed serial measurements of biomarkers of the integrity of the alveolar-capillary membrane, leucocyte activation and general inflammation. We assessed lung injury clinically by the duration of postoperative mechanical ventilation and the alveolar arterial oxygen gradient. METHODS Serial measurements of systemic plasma concentrations of interleukin-6 (IL-6), myeloperoxidase, elastase, surfactant protein D (SP-D), Clara cell 16 kD protein (CC16) and soluble receptor for advanced glycation endproducts (sRAGEs) were performed on blood samples from 195 patients who underwent cardiac surgery with the use of a cell salvage (CS) device (CS, n = 99) or without (CONTROL, n = 96). RESULTS Postoperative mechanical ventilation time was shorter in the CS group than in the CONTROL group [10 (8-15) vs 12 (9-18) h, respectively, P = 0.047]. The postoperative alveolar arterial oxygen gradient, however, was not different between groups. After surgery, the lung injury biomarkers CC16 and sRAGEs were lower in the CS group than in the CONTROL group. Biomarkers of systemic inflammation (IL-6, myeloperoxidase and elastase) were also lower in the CS group. Finally, mechanical ventilation time correlated with CC16 plasma concentrations. CONCLUSIONS The intraoperative use of a cell salvage device resulted in less lung injury in patients after cardiac surgery as assessed by lower concentrations of lung injury markers and shorter mechanical ventilation times.

Bivalirudin is inferior to heparin in preservation of intraoperative autologous blood

INTRODUCTION Bivalirudin is used as an alternative to heparin in cardiac surgery, and may be superior to heparin with regard to platelet function. Bivalirudin however, is prone to cleavage by thrombin resulting in coagulation in areas of stasis. MATERIAL AND METHODS We compared the preservation of platelet function and the quality of anticoagulation in autologous blood of 26 cardiac surgical patients collected intraoperatively and anticoagulated ex vivo with either bivalirudin or heparin, with supplementation of bivalirudin over time and prevention of stasis. RESULTS We found in both preservatives a reduction in ADP-induced platelet aggregation response over a period of 105 minutes (median, IQR: 73-141) as measured by Multiplate®. Supplementation of additional bivalirudin (23 ± 1.1 μg/ml/hr) and prevention of stasis was not able to prevent thrombin generation. We found a 5-fold increase in levels of prothrombin fragment 1+2 in bivalirudin preserved autologous blood as compared to heparin preserved blood (F(1+2) levels median 8.9 nM [quartile percentiles 4.2-12.4] vs 1.3 nM [0.6-2.1], P=0.001 Mann-Whitney, n=10). CONCLUSIONS Our study suggests that preservation of platelet function in autologous blood anticoagulated with bivalirudin is not a suitable alternative to heparin.

Platelet Function in Stored Heparinised Autologous Blood Is Not Superior to in Patient Platelet Function during Routine Cardiopulmonary Bypass

Background In cardiac surgery, cardiopulmonary bypass (CPB) and unfractionated heparin have negative effects on blood platelet function. In acute normovolemic haemodilution autologous unfractionated heparinised blood is stored ex-vivo and retransfused at the end of the procedure to reduce (allogeneic) transfusion requirements. In this observational study we assessed whether platelet function is better preserved in ex vivo stored autologous blood compared to platelet function in the patient during CPB. Methodology/Principal Finding We measured platelet aggregation responses pre-CPB, 5 min after the start of CPB, at the end of CPB, and after unfractionated heparin reversal, using multiple electrode aggregometry (Multiplate®) with adenosine diphosphate (ADP), thrombin receptor activating peptide (TRAP) and ristocetin activated test cells. We compared blood samples taken from the patient with samples taken from 100 ml ex-vivo stored blood, which we took to mimick blood storage during normovolemic haemodilution. Platelet function declined both in ex-vivo stored blood as well as in blood taken from the patient. At the end of CPB there were no differences in platelet aggregation responses between samples from the ex vivo stored blood and the patient. Conclusion/Significance Ex vivo preservation of autologous blood in unfractionated heparin does not seem to be profitable to preserve platelet function.

Leucocyte filtration of salvaged blood during cardiac surgery: effect on red blood cell function in concentrated blood compared with diluted blood

OBJECTIVE Leucocyte filtration of salvaged blood has been suggested to prevent patients from receiving activated leucocytes during auto-transfusion in cardiac surgery. This study examines whether leucocyte filtration of salvaged blood affects the red blood cell (RBC) function and whether there is a difference between filtration of the concentrated and diluted blood on RBC function. METHODS Forty patients undergoing cardiac surgery with cardiopulmonary bypass were randomly divided into a group receiving leucocyte filtration of concentrated blood (High-Hct, n=20) and another group receiving leucocyte filtration of the diluted blood (Low-Hct, n=20). During operation, all the salvaged blood, as well as the residual blood, from the heart-lung machine was filtered. In the High-Hct group, blood was concentrated with a cell saver prior to filtration, whereas in the Low-Hct group, blood was filtered without concentration. RBC function was represented by RBC aggregation and deformability measured by a laser-assisted optical rotational cell analyser and by the RBC 2,3-diphosphoglycerate (2,3-DPG) and adenosine triphosphate (ATP) contents with conventional biochemical tests. RESULTS Leucocyte filtration of diluted blood with a low haematocrit (14+/-4%) did not affect RBC function. However, when the concentrated blood with a high haematocrit (69+/-12%) was filtered, there was a reduction of ATP content in RBCs after passing through the filter (from 1.45+/-0.57 micromol g(-1) Hb to 0.92+/-0.75 micromol g(-1) Hb, p<0.05). For patients who received the concentrated blood, their in vivo RBC function did not differ from those who received diluted blood. CONCLUSIONS Leucocyte filtration of the diluted salvaged blood during cardiac surgery does not affect RBC function, but it tends to deplete the ATP content of RBCs as the salvaged blood has been concentrated prior to filtration.

Extracorporeal Life Support as a Bridge to Lung Transplantation: A Single-Center Experience With an Emphasis on Health-Related Quality of Life

BACKGROUND: Extracorporeal life support (ECLS) as a bridge to lung transplantation is increasingly used, but information on long-term outcome is scarce. We aim to summarize our experience with an emphasis on health-related quality of life. Secondary outcomes include ICU and hospital stay and pre- and post-transplant mortality. METHODS: A retrospective cohort study of all adult subjects receiving ECLS as a bridge to lung transplantation from 2010 to 2014 was reviewed and compared with all adult subjects who underwent bilateral lung transplantation in the same period. For the ECLS group, the general health status was assessed with the use of the EuroQol Group 5-Dimension Self-Report Questionnaire. RESULTS: A total of 130 bilateral transplants were performed, 9 transplants were performed after ECLS therapy. Another 11 subjects died on the waiting list while receiving ECLS. Quality of life, at 12 months after surgery, from a subjects perspective was comparable in both groups with a median score of 80 on the visual analog scale. The median (interquartile range [IQR]) EuroQol Group 5-Dimension Self-Report Questionnaire 3L score from the societal perspective in the ECLS group was 0.73 (0.5–0.9). Median (IQR) ICU stay was 25 d (9–68 d) for the ECLS group versus 7 d (4–18 d) for the control group (P = .001), and in-hospital stay was 66 d (40–114 d) versus 42 d (29–62 d) (P = .004). CONCLUSIONS: ECLS can be used as a bridge to lung transplantation. A significant number of subjects were not bridged successfully due to different reasons. Outcomes after successful transplantation after ECLS might be comparable with the general population undergoing lung transplantation in terms of quality of life, lung function, performance tests, and mortality, although ICU and hospital stay are longer.

Additional postoperative cell salvage of shed mediastinal blood in cardiac surgery does not reduce allogeneic blood transfusions: a cohort study.

Objectives: Does additional postoperative collection and processing of mediastinal shed blood with a cell salvage device reduce the number of allogeneic blood transfusions compared to intraoperative cell salvage alone? Methods: A single-centre cohort study in which adult patients with coronary artery bypass grafting or aortic valve replacement were allocated to either a C.A.T.S® group with intraoperative blood processing only or a CardioPat® group with both intra- and postoperative blood processing. The primary endpoint was the number of allogeneic blood transfusions during hospital admission. Results: The study included 99 patients; 50 in the C.A.T.S® and 49 in the CardioPat® group. There was no difference in the number of red blood cells (RBC) (C.A.T.S® group 43 units versus CardioPat® 50 units, p=0.74), fresh frozen plasma (C.A.T.S® 8 units versus CardioPat® 8 units, p=1.00) or platelets (C.A.T.S® 5 units versus CardioPat® 4 units, p=1.00) transfused during the hospital stay. Cardiac creatinine kinase (CK-MB) and troponin levels did not differ between the groups although a significant time effect (p<0.001) was present. Creatinine kinase (CK) levels were not different between the groups three hours after arrival in the intensive care unit (ICU) (CardioPat® group versus C.A.T.S® group, p=0.17). But, compared to the C.A.T.S® group on the first (350 [232-469] IU/L) and second postoperative days (325 [201-480] IU/L), the increase in CK levels was more in the CardioPat® group on the first (431 [286-642] IU/L, p=0.02) and second postoperative days (406 [239-760] IU/L, p=0.05), resulting in a difference between the groups (p=0.04) Conclusions: Postoperative cell salvage does not reduce transfusion requirements compared to intraoperative cell salvage alone, but results in elevated total CK levels that suggest haemolysis.