BACKGROUND: Prospective, single-center trials have shown that the implementation of the Kidney Disease: Improving Global Outcomes (KDIGO) recommendations in high-risk patients significantly reduced the development of acute kidney injury (AKI) after surgery. We sought to evaluate the feasibility of implementing a bundle of supportive measures based on the KDIGO guideline in high-risk patients undergoing cardiac surgery in a multicenter setting in preparation for a large definitive trial. METHODS: In this multicenter, multinational, randomized controlled trial, we examined the adherence to the KDIGO bundle consisting of optimization of volume status and hemodynamics, functional hemodynamic monitoring, avoidance of nephrotoxic drugs, and prevention of hyperglycemia in high-risk patients identified by the urinary biomarkers tissue inhibitor of metalloproteinases-2 [TIMP-2] and insulin growth factor-binding protein 7 [IGFBP7] after cardiac surgery. The primary end point was the adherence to the bundle protocol and was evaluated by the percentage of compliant patients with a 95% confidence interval (CI) according to Clopper-Pearson. Secondary end points included the development and severity of AKI. RESULTS: In total, 278 patients were included in the final analysis. In the intervention group, 65.4% of patients received the complete bundle as compared to 4.2% in the control group (absolute risk reduction [ARR] 61.2 [95% CI, 52.6-69.9]; P < .001). AKI rates were statistically not different in both groups (46.3% intervention versus 41.5% control group; ARR −4.8% [95% CI, −16.4 to 6.9]; P = .423). However, the occurrence of moderate and severe AKI was significantly lower in the intervention group as compared to the control group (14.0% vs 23.9%; ARR 10.0% [95% CI, 0.9-19.1]; P = .034). There were no significant effects on other specified secondary outcomes. CONCLUSIONS: Implementation of a KDIGO-derived treatment bundle is feasible in a multinational setting. Furthermore, moderate to severe AKI was significantly reduced in the intervention group. (Anesth Analg XXX;XXX:00-00) KEY POINTS• Question: Is it feasible to implement a bundle of supportive measures in high-risk patients undergoing cardiac surgery in a multinational setting? • Findings: In this multicenter randomized clinical trial, we found that the implementation of the Kidney Disease: Improving Global Outcomes (KDIGO) bundle is feasible in a multinational setting and that these supportive measures significantly reduced the occurrence of moderate and severe acute kidney injury (AKI). • Meaning: The findings underpin the need for a definitive trial to evaluate whether the KDIGO bundle reduces the occurrence of AKI in high-risk patients after cardiac surgery.

VPA provided neuroprotection and axonal regrowth after ONC. Alterations were observed in several pathways; however, the precise mechanism of VPA-mediated protection is not yet fully understood.

Upon RIPC, the level of cardioprotective RNase1 increased, while the concentration of damaging eRNA and TNF-α decreased. The present findings imply a significant contribution of the RIPC-dependent (endothelial) RNase1 for improving the outcome of cardiac surgery. However, the exact mechanism of RNase1-induced cardioprotection still remains to be explored.

Aims The antiplatelet treatment strategy providing optimal balance between thrombotic and bleeding risks in patients undergoing coronary artery bypass grafting (CABG) is unclear. We prospectively compared the efficacy of ticagrelor and aspirin after CABG. Methods and results We randomly assigned in double-blind fashion patients scheduled for CABG to either ticagrelor 90 mg twice daily or 100 mg aspirin (1:1) once daily. The primary outcome was the composite of cardiovascular death, myocardial infarction (MI), repeat revascularization, and stroke 12 months after CABG. The main safety endpoint was based on the Bleeding Academic Research Consortium classification, defined as BARC ≥4 for periprocedural and hospital stay-related bleedings and BARC ≥3 for post-discharge bleedings. The study was prematurely halted after recruitment of 1859 out of 3850 planned patients. Twelve months after CABG, the primary endpoint occurred in 86 out of 931 patients (9.7%) in the ticagrelor group and in 73 out of 928 patients (8.2%) in the aspirin group [hazard ratio 1.19; 95% confidence interval (CI) 0.87–1.62; P = 0.28]. All-cause mortality (ticagrelor 2.5% vs. aspirin 2.6%, hazard ratio 0.96, CI 0.53–1.72; P = 0.89), cardiovascular death (ticagrelor 1.2% vs. aspirin 1.4%, hazard ratio 0.85, CI 0.38–1.89; P = 0.68), MI (ticagrelor 2.1% vs. aspirin 3.4%, hazard ratio 0.63, CI 0.36–1.12, P = 0.12), and stroke (ticagrelor 3.1% vs. 2.6%, hazard ratio 1.21, CI 0.70–2.08; P = 0.49), showed no significant difference between the ticagrelor and aspirin group. The main safety endpoint was also not significantly different (ticagrelor 3.7% vs. aspirin 3.2%, hazard ratio 1.17, CI 0.71–1.92; P = 0.53). Conclusion In this prematurely terminated and thus underpowered randomized trial of ticagrelor vs. aspirin in patients after CABG no significant differences in major cardiovascular events or major bleeding could be demonstrated. ClinicalTrials.gov Identifier NCT01755520.

Mock circulatory loops (MCLs) are usually developed for assessment of ventricular assist devices and consist of abstracted anatomical structures represented by connecting tubing pipes and controllable actuators which could mimic oscillating flow processes. However, with increasing use of short-term peripheral mechanical support (extracorporeal life support [ECLS]) and the upcoming evidence of even counteracting flow processes between the failing native circulation and ECLS, MCLs incorporating the peripheral vascular system and preserved anatomical structures are becoming more important for systematic assessment of these processes. For reproducible and standardized fluid-mechanical studies using magnetic resonance imaging, Doppler ultrasound, and computational fluid dynamics measurements, we developed a MCL of the human circulation. Silicon-based life-sized dummies of the human aorta and vena cava (vascular module) were driven by paracorporeal pneumatic assist devices. The vascular module is placed in a housing with all arterial branches merging into peripheral resistance and compliances modules, and blood-mimicking fluid returns to the heart module through the venous dummy. Compliance and resistance chambers provide for an adequate simulation of the capillary system. Extracorporeal life support cannulation can be performed in the femoral and subclavian arteries and in the femoral and jugular veins. After adjusting vessel diameters using variable Hoffmann clamps, physiologic flow rates were achieved in the supraaortic branches, the renal and mesenteric arteries, and the limb arteries with physiologic blood pressure and cardiac output (4 L/min). This MCL provides a virtually physiologic platform beyond conventional abstracted MCLs for simulation of flow interactions between the human circulation and external circulation generated by ECLS.