Preoperative anaemia and outcome after elective cardiac surgery: a Dutch national registry analysis.

BACKGROUND: Previous studies have shown that preoperative anaemia in patients undergoing cardiac surgery is associated with adverse outcomes. However, most of these studies were retrospective, had a relatively small sample size, and were from a single centre. The aim of this study was to analyse the relationship between the severity of preoperative anaemia and short- and long-term mortality and morbidity in a large multicentre national cohort of patients undergoing cardiac surgery. METHODS: A nationwide, prospective, multicentre registry (Netherlands Heart Registration) of patients undergoing elective cardiac surgery between January 2013 and January 2019 was used for this observational study. Anaemia was defined according to the WHO criteria, and the main study endpoint was 120-day mortality. The association was investigated using multivariable logistic regression analysis. RESULTS: In total, 35 484 patients were studied, of whom 6802 (19.2%) were anaemic. Preoperative anaemia was associated with an increased risk of 120-day mortality (adjusted odds ratio [aOR] 1.7; 95% confidence interval [CI]: 1.4-1.9; P<0.001). The risk of 120-day mortality increased with anaemia severity (mild anaemia aOR 1.6; 95% CI: 1.3-1.9; P<0.001; and moderate-to-severe anaemia aOR 1.8; 95% CI: 1.4-2.4; P<0.001). Preoperative anaemia was associated with red blood cell transfusion and postoperative morbidity, the causes of which included renal failure, pneumonia, and myocardial infarction. CONCLUSIONS: Preoperative anaemia was associated with mortality and morbidity after cardiac surgery. The risk of adverse outcomes increased with anaemia severity. Preoperative anaemia is a potential target for treatment to improve postoperative outcomes.

Does Intraoperative Cell Salvage Reduce Postoperative Infection Rates in Cardiac Surgery?

OBJECTIVE: Primary outcome was the risk for infections after cell salvage in cardiac surgery. DESIGN: Data of a randomized controlled trial on cell salvage and filter use (ISRCTN58333401). SETTING: Six cardiac surgery centers in the Netherlands. PARTICIPANTS: All 716 patients undergoing elective coronary artery bypass grafting, valve surgery, or combined procedures over a 4-year period who completed the trial. INTERVENTIONS: Postoperative infection data were assessed according to Centre of Disease Control and Prevention/National Healthcare Safety Network surveillance definitions. MEASUREMENTS AND MAIN RESULTS: Fifty-eight (15.9%) patients with cell salvage had infections, compared with 46 (13.1%) control patients. Mediation analysis was performed to estimate the direct effect of cell salvage on infections (OR 2.291 [1.177;4.460], p = 0.015) and the indirect effects of allogeneic transfusion and processed cell salvage blood on infections. Correction for confounders, including age, seks and body mass index was performed. Allogeneic transfusion had a direct effect on infections (OR = 2.082 [1.133;3.828], p = 0.018), but processed cell salvage blood did not (OR = 0.999 [0.999; 1.001], p = 0.089). There was a positive direct effect of cell salvage on allogeneic transfusion (OR = 0.275 [0.176;0.432], p < 0.001), but a negative direct effect of processed cell salvage blood (1.001 [1.001;1.002], p < 0.001) on allogeneic transfusion. Finally, there was a positive direct effect of cell salvage on the amount of processed blood. CONCLUSIONS: Cell salvage was directly associated with higher infection rates, but this direct effect was almost completely eliminated by its indirect protective effect through reduced allogeneic blood transfusion.

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.

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.

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.

First-in-man experience with a new embolic deflection device in transcatheter aortic valve interventions.

AIMS: To report our first-in-man experience with a new cerebral embolic deflection device (SMT Embolic Deflection Device) during transcatheter aortic valve implantation (TAVI). A significant number of strokes and brain infarcts are caused by embolisation of atherosclerotic material, clots and other debris during various phases of invasive cardiac procedures, especially TAVI. The application of a temporary filter in the aortic arch averting dislodged emboli from entering the cerebral circulation might prevent this. METHODS AND RESULTS: In 15 patients (mean age 79 years) with severe aortic stenosis undergoing percutaneous transfemoral or transapical aortic valve implantation, the SMT Embolic Deflection Device was advanced utilising the contralateral femoral artery access using a 9 Fr delivery sheath. Once deployed in the aortic arch, a porous membrane shields the supraaortic-cerebral trunks by deflecting emboli away from the cerebral circulation. Embolic material is not contained or removed by the device. A 6 Fr pigtail catheter can be used through the same sheath throughout the whole procedure. Brain diffusion weighted (DW)-MRI was obtained in 10 patients before and at 4 days after (± 2 days) the procedure and retrospectively compared to 20 patients previously undergoing TAVI without a protection device. Successful placement of the embolic protection device was achieved in all patients. Additional procedural time due to the use of the device was 7 min (± 2 min). There were no procedural complications. No patient developed new neurological symptoms or clinical findings of stroke except one patient who suffered from a transient ischaemic attack (TIA) two days after the procedure. DW-MRI showed 3.2 new cerebral lesions per patient, compared to 7.2 new lesions per patient in the group without SMT filter. CONCLUSIONS: In this first-in-man experience, the feasibility of a new embolic deflection device is demonstrated. Larger randomised, prospective studies are required to confirm these findings and prove safety and efficacy by reducing the incidence of cerebral embolism and stroke after TAVI.

The impact of heparin-coated circuits on hemodynamics during and after cardiopulmonary bypass.

This study was performed to investigate if heparin-coated extracorporeal circuits can reduce the systemic inflammatory reaction with the subsequent release of vasoactive substances during and after cardiopulmonary bypass. Fifty-one patients scheduled for coronary artery bypass grafting were perfused with either a heparin-coated or an uncoated circuit. During bypass the mean arterial pressure was maintained as near as possible to 60 mm Hg. Mediators for inflammation, hemodynamic, and oxygen parameters were determined during and after bypass. To reach the target mean arterial pressure in the first hour of bypass the pump flow in the uncoated group had to be increased (P<0.05), consequently the systemic vascular resistance index decreased (P<0.05). After bypass more inotropic support was necessary in this group to reach this pressure. In the coated group less bradykinin, complement activation, and elastase was generated during bypass (P<0.05). The results of this study suggest that heparin coating not only improves biocompatibility, but also ameliorates the hemodynamic instability during and after bypass.

The impact of heparin coated circuits upon metabolism in vital organs: effect upon cerebral and renal function during and after cardiopulmonary bypass.

During cardiopulmonary bypass (CPB), the brain and the kidneys may be damaged because of microemboli, ischemia, and inflammation. The latter has been reduced by the use of heparin coated circuits. We questioned whether heparin coated circuits could also reduce cerebral and renal damage and whether inflammatory markers correlate with damage to the brain and the kidneys. Fifty-one patients scheduled for coronary artery bypass grafting were perfused with either a heparin coated or an uncoated circuit. To compare the effect of a heparin coated circuit with an uncoated circuit upon cerebral and renal function in relation to inflammation, we assessed markers of cerebral (S100beta) and renal (N-acetyl-beta-D-glucosaminidase [NAG], creatinine, and urea) function, inflammation, and oxygen metabolism. S100beta levels and NAG levels increased during CPB in both groups as compared with baseline levels (p < 0.01), without differences between the groups. After 15 minutes on CPB, C4b/c levels were significantly higher in the coated group compared with the uncoated group (p < 0.02). C4b/c correlated with S100beta (p < 0.01). Total body oxygen delivery (DO2) and consumption (VO2) decreased significantly in both groups during CPB (p < 0.01), but recovery was better in the coated group. After protamine infusion, total body oxygen delivery and consumption correlated negatively with S100beta levels (both p < 0.05) and with NAG levels (both p < 0.01). This study suggests that, if adequate tissue perfusion is not maintained, the use of a heparin coated circuit gives no additional benefit beyond that of the uncoated circuit. The inverse relationship of both cerebral and renal markers with DO2 and VO2 suggests that increased levels of S100beta and NAG during CPB may primarily be caused by an oxygen deficit and secondary to the inflammatory response.

Negative and positive inotropic effects of propofol via L-type calcium channels and the sodium-calcium exchanger in rat cardiac trabeculae.

BACKGROUND: Conflicting opinions are present in the literature regarding the origin of the negative inotropic effect of propofol on the myocardium. This study aims to resolve these discrepancies by investigating the inotropic effects of propofol the L-type calcium channels and the sodium-calcium exchanger (NCX). METHODS: The effect of 20 microg/ml propofol on force development was determined in rat cardiac trabeculae at different pacing frequencies and different extracellular calcium concentrations. Postrest potentiation, sodium withdrawal during quiescence, and the NCX inhibitor KB-R7943 were used to study changes in the activity of the reverse mode of the NCX by propofol. RESULTS: The effect of propofol on steady state peak force depended on pacing frequency and calcium concentration. A negative inotropic effect was observed at pacing frequencies greater than 0.5 Hz, but a positive inotropic effect was observed at 0.1 Hz and low calcium, which cannot be explained by an effect on the L-type calcium channel. Propofol enhanced postrest potentiation in a calcium-dependent manner. Sodium withdrawal during quiescence and the use of the specific NCX inhibitor KB-R7943 provided evidence for an enhancement of calcium influx by propofol the reverse mode of the NCX. CONCLUSIONS: The effects of propofol on the myocardium depend on pacing frequency and calcium concentration. The positive inotropic effect of propofol is associated with increased calcium influx the reverse mode of the NCX. The authors conclude that the net inotropic effect of propofol is the result of its counteracting influence on the functioning of the L-type calcium channel and the NCX.