Background: Acute kidney injury (AKI) is a common complication following cardiopulmonary bypass (CPB) which can affect morbidity and mortality. Goal-directed perfusion (GDP) intended to avoid the nadir oxygen delivery index below the critical value is associated with reduced postoperative AKI. However, current studies suggested that GDP can only decrease the incidence of AKI stage 1 but showed no effects on AKI stages 2–3 and mortality. The objective of the present meta-analysis is to deter the effects of GDP on postoperative AKI in any stage and mortality following cardiac surgery. Methods: MEDLINE, Embase, and the Cochrane Library were searched to identify all clinical trials comparing GDP with control (standard care) during cardiopulmonary bypass conducting in adults undergoing cardiac surgery. The primary outcome was postoperative acute kidney injury. Secondary outcomes included postoperative mortality and length of ICU stay. Data synthesis was obtained by using risk ratio with 95% confidence interval by a random-effects model. Result: From 1094 potential studies, 3 trials enrolling 777 patients were included. Meta-analysis suggested the GDP strategy based on DO₂i reduced postoperative AKI compared with standard CPB management (RR = 0.52; 95% CI: 0.38–0.70; p < .0001), especially in AKI stage I (RR = 0.47; 95% CI: 0.33–0.66; p < .0001). But the GDP strategy did not reduce the incidence of severe AKI (stages 2–3) and postoperative mortality. Conclusion: The GDP strategy based on DO₂i during CPB obviously reduces AKI stage 1 and thus reduces overall AKI incidence. But it shows no effects on severe AKI (stages 2–3) and mortality.

Objective: Although fresh frozen plasma (FFP) is one of the most commonly used hemostatic agents in clinical specialties today, there is little evidence available supporting its administration. Our present study observed the effects of a priming strategy without FFP during cardiopulmonary bypass (CPB) on postoperative coagulation and clinical recovery in pediatric patients, aiming to supply new evidence for evidence-based use of FFP. Method: Eighty pediatric patients with congenital heart disease undergoing cardiac surgery with CPB were randomized to receive either 10-20 ml/kg 4% succinylated gelatin (Gelofusine, GEL group, n = 40) or 1-2 units FFP (FFP group, n = 40) in the pump prime. Rapid-thromboelastography (r-TEG) and functional fibrinogen level were measured before skin incision and 15 minutes after heparin reversal. We recorded the volume of chest tube drainage, transfusion requirements and the dosage of pharmacological agents. The ventilation time, ICU length of stay and hospitalization time after surgery were also collected. Results: After heparin neutralization, there were significantly elevated levels of fibrinogen in the FFP group, which were manifested by r-TEG parameters MAf and FLEV. No significant differences were observed between the two groups in postoperative bleeding, transfusion requirements and the usage of pharmacological agents. Recovery time was also comparable between the two groups. Conclusion: In conclusion, prophylactic use of FFP in the priming solution does not provide clinical benefits as presumed. Artificial colloids, such as Gelofusine, can be used safely and effectively as a substitute for FFP in the pump prime. TEG is an effective assessment tool to evaluate postoperative coagulation function in pediatric patients.

Background: The ischemia–reperfusion (IR) environment during deep hypothermic circulatory arrest (DHCA) cardiovascular surgery is a major cause of acute kidney injury (AKI), which lacks preventive measure and treatment. It was reported that cold inducible RNA-binding protein (CIRP) can be induced under hypoxic and hypothermic stress and may have a protective effect on multiple organs. The purpose of this study was to investigate whether CIRP could exert renoprotective effect during hypothermic IR and the potential mechanisms. Methods: Utilizing RNA-sequencing, we compared the differences in gene expression between Cirp knockout rats and wild-type rats after DHCA and screened the possible mechanisms. Then, we established the hypothermic oxygen–glucose deprivation (OGD) model using HK-2 cells transfected with siRNA to verify the downstream pathways and explore potential pharmacological approach. The effects of CIRP and enarodustat (JTZ-951) on renal IR injury (IRI) were investigated in vivo and in vitro using multiple levels of pathological and molecular biological experiments. Results: We discovered that Cirp knockout significantly upregulated rat Phd3 expression, which is the key regulator of HIF-1α, thereby inhibiting HIF-1α after DHCA. In addition, deletion of Cirp in rat model promoted apoptosis and aggravated renal injury by reactive oxygen species (ROS) accumulation and significant activation of the TGF-β1/p38 MAPK inflammatory pathway. Then, based on the HK-2 cell model of hypothermic OGD, we found that CIRP silencing significantly stimulated the expression of the TGF-β1/p38 MAPK inflammatory pathway by activating the PHD3/HIF-1α axis, and induced more severe apoptosis through the mitochondrial cytochrome c-Apaf-1-caspase 9 and FADD-caspase 8 death receptor pathways compared with untransfected cells. However, silencing PHD3 remarkably activated the expression of HIF-1α and alleviated the apoptosis of HK-2 cells in hypothermic OGD. On this basis, by pretreating HK-2 and rats with enarodustat, a novel HIF-1α stabilizer, we found that enarodustat significantly mitigated renal cellular apoptosis under hypothermic IR and reversed the aggravated IRI induced by CIRP defect, both in vitro and in vivo. Conclusion: Our findings indicated that CIRP may confer renoprotection against hypothermic IRI by suppressing PHD3/HIF-1α-mediated apoptosis. PHD3 inhibitors and HIF-1α stabilizers may have clinical value in renal IRI.