Risk Prediction Models for Renal Function Decline After Cardiac Surgery Within Different Preoperative Glomerular Filtration Rate Strata.

BACKGROUND: Our goal was to create a simple risk-prediction model for renal function decline after cardiac surgery to help focus renal follow-up efforts on patients most likely to benefit. METHODS AND RESULTS: This single-center retrospective cohort study enrolled 24 904 patients who underwent cardiac surgery from 2012 to 2019 at Fuwai Hospital, Beijing, China. An estimated glomerular filtration rate (eGFR) reduction of ≥30% 3 months after surgery was considered evidence of renal function decline. Relative to patients with eGFR 60 to 89 mL/min per 1.73 m2 (4.5% [531/11733]), those with eGFR ≥90 mL/min per 1.73 m2 (10.9% [1200/11042]) had a higher risk of renal function decline, whereas those with eGFR ≤59 mL/min per 1.73 m2 (5.8% [124/2129]) did not. Each eGFR stratum had a different strongest contributor to renal function decline: increased baseline eGFR levels for patients with eGFR ≥90 mL/min per 1.73 m2, transfusion of any blood type for patients with eGFR 60 to 89 mL/min per 1.73 m2, and no recovery of renal function at discharge for patients with eGFR ≤59 mL/min per 1.73 m2. Different nomograms were established for the different eGFR strata, which yielded a corrected C-index value of 0.752 for eGFR ≥90 mL/min per 1.73 m2, 0.725 for eGFR 60-89 mL/min per 1.73 m2 and 0.791 for eGFR ≤59 mL/min per 1.73 m2. CONCLUSIONS: Predictors of renal function decline over the follow-up showed marked differences across the eGFR strata. The nomograms incorporated a small number of variables that are readily available in the routine cardiac surgical setting and can be used to predict renal function decline in patients stratified by baseline eGFR.

A Comprehensive Patient Blood Management Program During Cardiopulmonary Bypass in Patients Over 60 Years of Age.

Purpose: There is currently no consensus on the most appropriate blood transfusion strategy for older adults undergoing cardiovascular surgery. We aimed to investigate the potential benefits of the patient blood management (PBM) program specifically for advanced age patients, and to evaluate the relationship of age and PBM in cardiovascular surgery. Patients and Methods: We collected data from patients over 60 years old who underwent on-pump cardiovascular surgery. We compared transfusion and clinical outcomes between the pre-PBM and post-PBM groups using a propensity score matching method. Then, we conducted a subgroup analysis within the original cohort, specifically focusing on patients aged of 75 and above with multivariable adjusted models. Results: Data of 9703 older adults were analyzed. Red blood cell (RBC) transfusion rates during cardiopulmonary bypass (CPB) (31.6% vs 13.1%, P<0.001), during the operation (50.8% vs 39.0%, P<0.001) and after the operation (5.6% vs 3.1%, P<0.001) were significantly reduced, and mortality and the risk of some adverse events were also reduced after the PBM. Subgroup analysis showed that there was no interaction between age and PBM, and advanced age (over age 75) did not modify the effect of PBM program in reducing RBC transfusion (Pinteraction=0.245), on mortality (Pinteration=0.829) and on certain complications. Conclusion: The comprehensive PBM program could reduce RBC transfusion without adverse outcomes in older patients undergoing CPB. Even patients over age 75 may benefit from a more stringent transfusion indication. Comprehensive blood conservation measures should be applied to optimize the blood management for older patients.

Effects of Extracorporeal Membrane Oxygenation on the Coagulation System.

This study aimed to investigate the effects of long-term awake extracorporeal membrane oxygenation (ECMO) on the coagulation system in a sheep model. A total of ten healthy sheep were included in the study, with 5 sheep in each group. In the veno-arterial ECMO (V-A ECMO) group, cannulation was performed in the right carotid artery and the right external jugular vein. In the veno-venous ECMO (V-V ECMO) group, a dual-lumen catheter was utilized to insert into the right external jugular vein. After initiating ECMO, the sheep were recovered from anesthesia and remained awake for 7 days. The target activated clotting time (ACT) goal was set at 220-250 s. In both groups, the actual ACT fluctuated around 250 s with the dose of heparin gradually increasing, reaching almost 60 IU/kg/min at the end of the experiments. Moreover, the activated partial thromboplastin time (APTT) and thrombin time (TT) values were significantly higher in the V-A ECMO group compared to the V-V ECMO group, despite receiving the same doses of heparin. Although laboratory test results fluctuated within a normal and reasonable range, infarct foci in the kidneys were observed in both groups at the end of the study.

Venoarterial Extracorporeal Membrane Oxygenation Implementation in Septic Shock Rat Model.

Septic shock, a global health concern, boasts high mortality rates. Research exploring the efficacy of venoarterial extracorporeal membrane oxygenation (VA-ECMO) in septic shock remains limited. Our study aimed to establish a rodent model employing VA-ECMO in septic shock rats, assessing the therapeutic impact of VA-ECMO on septic shock. Nineteen Sprague-Dawley rats were randomly assigned to sham, septic shock, and (septic shock + VA-ECMO; SSE) groups. Septic shock was induced by intravenous lipopolysaccharides, confirmed by a mean arterial pressure drop to 25-30% of baseline. Rats in the SSE group received 2 hours of VA-ECMO support and 60 minutes of post-weaning ventilation. Sham and septic shock groups underwent mechanical ventilation for equivalent durations. Invasive mean arterial pressure monitoring, echocardiographic examinations, and blood gas analysis revealed the efficacy of VA-ECMO in restoring circulation and ensuring adequate tissue oxygenation in septic shock rats. Post-experiment pathology exhibited the potential of VA-ECMO in mitigating major organ injury. In summary, our study successfully established a stable septic shock rat model with the implementation of VA-ECMO, offering a valuable platform to explore molecular mechanisms underlying VA-ECMO's impact on septic shock.

Effects of albumin and crystalloid priming strategies on red blood cell transfusions in on-pump cardiac surgery: a network meta-analysis.

BACKGROUND: In on-pump cardiac surgery, the albumin priming strategy could maintain colloid osmotic pressure better than crystalloid solutions and reduce excessive perioperative fluid balance. However, a high-quality meta-analysis is required to compare the safety of these approaches in perioperative red blood cell (RBC) transfusions. Owing to limited direct evidence, we conducted a network meta-analysis (NMA) to increase the pool of studies and provide indirect evidence. METHODS: The pre-defined primary outcomes were intraoperative and the first 24 h postoperative RBC transfusion volume in units. The pre-defined secondary outcome was postoperative blood loss (the first 24 h). We reviewed all randomized controlled trials comparing albumin, crystalloid, and artificial colloid priming strategies. Studies that only displayed pre-defined outcomes could be included. A pairwise meta-analysis was performed on studies that directly compared the pre-defined outcomes between albumin and crystalloids. Additionally, a random-effects network meta-analysis (NMA) model was employed to generate indirect evidence for the pre-defined outcomes between albumin and crystalloids. RESULTS: The literature search identified 830 studies,10 of which were included in the final analysis. Direct meta-analysis indicated that crystalloid priming significantly decreased total perioperative RBC transfusions (MD: -0.68U; 95%CI: -1.26, -0.09U; P = 0.02) and intraoperative RBC transfusions (MD: -0.20U; 95%CI: -0.39, -0.01U; P = 0.03) compared to albumin. Postoperative RBC transfusions showed a decreasing trend in the crystalloid group; however, the difference was not statistically significant. (MD: -0.16U; 95%CI: -0.45, 0.14U; P = 0.30). After including indirect evidence, the NMA results continued to demonstrate a higher RBC receiving with the albumin priming strategy compared to crystalloids, although the differences did not reach statistical significance. For postoperative blood loss, direct evidence showed no significant differences between albumin and crystalloid priming strategies. However, NMA evidence displayed that albumin exist higher probability of reducing postoperative blood loss than crystalloid. CONCLUSION: Both direct and NMA evidence indicated that the albumin priming strategy resulted in more perioperative RBC transfusions than crystalloids. Considering the additional blood management burden, the application of an albumin-priming strategy in on-pump cardiac surgery still needs more consideration.

Deoxyribonuclease I Alleviates Septic Liver Injury in a Rat Model Supported by Venoarterial Extracorporeal Membrane Oxygenation.

Sepsis is an unusual systemic reaction with high mortality and secondary septic liver injury is proposed to be the major cause of mortality. Extracorporeal membrane oxygenation (ECMO) can enhance terminal organ perfusion by elevating circulatory support which is used in severe sepsis patients. However, the interaction of blood components with the biomaterials of the extracorporeal membrane elicits a systemic inflammatory response. Besides, inflammation and apoptosis are the main mediators in the pathophysiology of septic liver injury. Therefore, we investigated the protective effect of Deoxyribonuclease I (DNase I) against septic liver injury supported by ECMO in rats. Sepsis was induced by lipopolysaccharide (LPS) and 24 hours after the administration, the rats were treated with ECMO. Then blood samples and liver tissues were collected. DNase I significantly attenuated the level of alanine aminotransferase (ALT), aspartate aminotransferase (AST) and significantly decreased hepatic levels of NOD-like receptor thermal protein domain associated protein 3 (NLRP3) inflammasome, myeloperoxidase (MPO), downstream inflammatory factor interleukin-1ß (IL-1ß) and interleukin-18 (IL-18), and improved neutrophil infiltration. Additionally, DNase I significantly reduced the expression of apoptosis key protein and terminal-deoxynucleotidyl transferase-mediated nick end labeling (TUNEL)-labeled apoptotic hepatocytes. In summary, our findings demonstrated that DNase I alleviates liver injury in ECMO-supported septic rats by reducing the inflammatory and apoptotic responses.

A transfusion risk stratification score to facilitate quality management in cardiopulmonary bypass.

BACKGROUND: Our previous showed that a blood management program in the cardiopulmonary bypass (CPB) department, reduced red blood cell (RBC) transfusion and complications, but assessing transfusion practice solely based on transfusion rates was insufficient. This study aimed to design a risk stratification score to predict perioperative RBC transfusion to guide targeted measures for on-pump cardiac surgery patients. STUDY DESIGN AND METHODS: We analyzed data from 42,435 adult cardiac patients. Eight predictors were entered into the final model including age, sex, anemia, New York Heart Association classification, body surface area, cardiac surgery history, emergency surgery, and surgery type. We then simplified the score to an integer-based system. The area under the receiver operating characteristic curve (AUC), Hosmer-Lemeshow goodness-of-fit test, and a calibration curve were used for its performance test. The score was compared to existing scores. RESULTS: The final score included eight predictors. The AUC for the model was 0.77 (95% CI, 0.76-0.77) and 0.77 (95% CI, 0.76-0.78) in the training and test set, respectively. The calibration curves showed a good fit. The risk score was finally grouped into low-risk (score of 0-13 points), medium-risk (14-19 points), and high-risk (more than 19 points). The score had better predictive power compared to the other two existing risk scores. DISCUSSION: We developed an effective risk stratification score with eight variables to predict perioperative RBC transfusion for on-pump cardiac surgery. It assists perfusionists in proactively preparing blood conservation measures for high-risk patients before surgery.

Dynamic predictive scores for cardiac surgery-associated agitated delirium: a single-center retrospective observational study.

BACKGROUND: Prevention, screening, and early treatment are the aims of postoperative delirium management. The scoring system is an objective and effective tool to stratify potential delirium risk for patients undergoing cardiac surgery. METHODS: Patients who underwent cardiac surgery between January 1, 2012, and January 1, 2019, were enrolled in our retrospective study. The patients were divided into a derivation cohort (n = 45,744) and a validation cohort (n = 11,436). The AD predictive systems were formulated using multivariate logistic regression analysis at three time points: preoperation, ICU admittance, and 24 h after ICU admittance. RESULTS: The prevalence of AD after cardiac surgery in the whole cohort was 3.6% (2,085/57,180). The dynamic scoring system included preoperative LVEF ≤ 45%, serum creatinine > 100 µmol/L, emergency surgery, coronary artery disease, hemorrhage volume > 600 mL, intraoperative platelet or plasma use, and postoperative LVEF ≤ 45%. The area under the receiver operating characteristic curve (AUC) values for AD prediction were 0.68 (preoperative), 0.74 (on the day of ICU admission), and 0.75 (postoperative). The Hosmer‒Lemeshow test indicated that the calibration of the preoperative prediction model was poor (P = 0.01), whereas that of the pre- and intraoperative prediction model (P = 0.49) and the pre, intra- and postoperative prediction model (P = 0.35) was good. CONCLUSIONS: Using perioperative data, we developed a dynamic scoring system for predicting the risk of AD following cardiac surgery. The dynamic scoring system may improve the early recognition of and the interventions for AD.

Comparative effects of off-pump and multiple cardiopulmonary bypass strategies in coronary artery bypass grafting surgery: protocol for a systematic review and network meta-analysis.

INTRODUCTION: Multiple revascularisation strategies with or without cardiac arrest have been developed to minimise the negative effects of cardiopulmonary bypass interventions during coronary artery bypass grafting (CABG) surgery. Several observational and randomised studies have evaluated the efficacy of these interventions. This study aims to compare the efficacy and safety of four prevalent revascularisation strategies with/without cardiopulmonary bypass interventions in CABG surgery. METHODS AND ANALYSIS: We will search on PubMed, Embase, Cochrane Library, Web of Science and ClinicalTrials.gov for randomised controlled trials and observational cohort studies comparing outcomes of CABG surgery under conventional on-pump, off-pump, on-pump beating heart and minimal extracorporeal circulation technology. All English articles published before 30 November 2022 will be considered. The primary outcome will be 30-day mortality. The secondary outcomes will be various early and late adverse events after CABG surgery. The Revised Cochrane Risk of Bias Tool and Newcastle-Ottawa Scale will be used to assess the quality of included articles. A random-effects pairwise meta-analysis will be performed to report the head-to-head comparison. Then, the network meta-analysis will be performed using a Bayesian framework with random-effects models. ETHICS AND DISSEMINATION: This research does not require the approval of an ethics committee as it relies on reviewing literature and does not involve dealing with humans or animals. The findings of this review will be published in a peer-reviewed journal. PROSPERO REGISTRATION NUMBER: CRD42023381279.

Transcriptomic Profiling of circRNAs in rat Hippocampus after Deep Hypothermic Circulatory Arrest.

Neurologic abnormalities occurring after deep hypothermic circulatory arrest (DHCA) remain a significant concern. However, molecular mechanisms leading to DHCA-related cerebral injury are still ill-defined. Circular RNAs (circRNAs) are a class of covalently closed non-coding RNAs and can play important roles in different types of cerebral injury. This study aimed to investigate circRNAs expression profiles in rat hippocampus after DHCA and explore the potential functions of circRNAs in DHCA-related cerebral injury. Hence, the DHCA procedure in rats was established and a transcriptomic profiling of circRNAs in rat hippocampus was done. As a result, a total of 35192 circRNAs were identified. Among them, 339 circRNAs were dysregulated, including 194 down-regulated and 145 up-regulated between DHCA and sham group. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses were performed based on the host genes of all dysregulated circRNAs. Also, 4 circRNAs were validated by RT-qPCR (rno_circ_0028462, rno_circ_0037165, rno_circ_0045161 and rno_circ_0019047). Then a circRNA-microRNA (miRNA) interaction network involving 4 candidate circRNAs was constructed. Furthermore, functional enrichment analysis of the miRNA-targeting mRNAs of every candidate circRNA was conducted to gain insight into each of the 4 circRNAs. Our study provided a better understanding of circRNAs in the mechanisms of DHCA-related cerebral injury and some potential targets for neuroprotection.

Does methylprednisolone provide protective effect in total aortic arch replacement requiring hypothermia circulatory arrest and selective cerebral perfusion?

BACKGROUND: Glucocorticoids (GC)were applied in total aortic arch replacement (TAAR) at various dosages in many centers, but with limited evidence. METHODS: The retrospective study was aimed to evaluate whether methylprednisolone was associated with better postoperative outcomes in patients undergoing TAAR. Patients undergoing TAAR with moderate hypothermia and selective cerebral perfusion between 2017.1 to 2018.12 in Fuwai hospital were classified into three groups according to doses of methylprednisolone given in the surgery: large-GC group (1500-3000 mg); medium-GC group (500-1000 mg) and no-GC group (0 mg). Postoperative outcomes were compared among three groups. Multivariable analysis was performed to identify the association of methylprednisolone with outcomes. RESULTS: Three hundred twenty-eight patients were enrolled. Two hundred twenty-eight were in the large-GC group, 34 were in the medium-GC group, and 66 were in the no-GC group. The incidences of major adverse outcomes in large-GC, medium-GC and no-GC groups were 22.8%, 17.6% and 18.2%, respectively, with no statistical difference. A significant difference was observed in post-cardiopulmonary bypass (CPB) fresh frozen plasma (FFP) transfusion (p < .001) and chest drainage volume (p < .001). Multivariable analysis demonstrated that methylprednisolone was not associated with better outcomes (p = .455), while large doses of methylprednisolone were significantly associated with excessive chest drainage (over 2000 mL) [OR (99% CI) 4.282 (1.66-11.044), p < .001] and excessive post-CPB FFP transfusion (over 400 mL) [OR (99% CI) 2.208 (1.027-4.747), p = .008]. CONCLUSIONS: Large doses of methylprednisolone (1500-3000 mg) did not show a protective effect in TAAR with moderate hypothermia arrest plus selective cerebral perfusion and might increase postoperative bleeding and FFP transfusion.

Dose-dependent influence of red blood cell transfusion volume on adverse outcomes in cardiac surgery.

INTRODUCTION: Red blood cell (RBC) transfusion is associated with adverse outcomes, but there are few studies on the RBC volume. This study aimed to evaluate the relationship between intraoperative RBC volume and postoperative adverse outcomes for on-pump cardiac surgery. METHODS: Adult patients undergoing on-pump cardiac surgery from 1 January 2017 to 31 December 2018 were included. Those transfused with more than 6 units of RBC were excluded. The clinical characteristics of four groups with various RBC volume were compared. We analyzed the relationship between RBC volume and adverse outcomes through multivariable logistic regression. RESULTS: 12,143 patients were analyzed, of which 3353 (27.6%) were transfused with 1-6U RBC intraoperatively. The incidence of death, overall morbidity, acute kidney injury and prolonged mechanical ventilation were increased stepwise along with incremental RBC volume. After adjusting for possible confounders, patients transfused with 1-2U were associated with a 1.42-fold risk of death (99% CI, 1.21-2.34, p = 0.01) compared with patients without RBC, patients with 3-4U were associated with a 1.57-fold risk (99% CI, 1.32-2.80, p = 0.005) and patients with 5-6U had a 2.26-fold risk of death (99% CI, 1.65-3.88, p < 0.001). Similarly, the incidence of overall morbidity, acute kidney injury and prolonged mechanical ventilation increased several folds as the RBC numbers increased. CONCLUSIONS: There was a significant dose-dependent influence of incremental intraoperative RBC volume on increased risk of adverse outcomes for on-pump cardiac surgery patients. Patient blood management practice should aim to reduce not only transfusion rate but also the volume of blood use.

Hemostatic alterations during extracorporeal membrane oxygenation in ovine veno-venous and veno-arterial models.

BACKGROUND: Extracorporeal membrane oxygenation (ECMO) has salvaged many people's life during global pandemics. However, ECMO is associated with a high incidence of hemostatic complications. This study aims to explore the effects of the ECMO system on the coagulation system in the healthy ovine ECMO model. METHODS: Ten healthy male sheep were included. Five received the veno-arterial ECMO and five received the veno-venous ECMO. Heparin was infused for systemic anticoagulation and was adjusted according to the activated clotting time. Blood routine tests, coagulation factors, anticoagulation proteins, and fibrinolysis markers were tested at the baseline and every 24 h. After weaning, the pump heads were dissected to explore thrombosis. RESULTS: Platelets decreased in the first 72 h and returned to the baseline at the 120th hour. The neutrophils increased in the first 24 h and returned to the baseline at the 48th hour. Factors II, VII, and X decreased in the first 24 h and gradually increased, while factors VIII, IX, XI, and XII decreased in the first 24 h and remained at a low level. The baseline antithrombin was 73.2 ± 14.4% and reduced to 42.6 ± 9.9% at the 168th hour. Pathology showed seven sheep developed thrombus, but no clinically relevant bleeding or thrombosis events occurred. CONCLUSIONS: The study explored hemostatic alterations during ECMO in healthy animal models, which eliminated the confounding under critically ill conditions. The study may provide insights into ECMO hemostatic disorders and aid the design of optimal therapeutic strategies.

Neutrophil extracellular traps are increased after extracorporeal membrane oxygenation support initiation and present in thrombus: A preclinical study using sheep as an animal model.

BACKGROUND: The balance between thrombosis and hemostasis is a difficult issue during extracorporeal membrane oxygenation (ECMO) support. The pathogenesis leading to thrombotic complications during ECMO support is not well understood. Neutrophil extracellular traps (NETs) were reported to participate in thrombosis and have a key role in inflammation. This study aimed to explore the role of NETs in thrombosis during ECMO support and investigate NETs as a predictive biomarker for thrombotic complications during ECMO assistance. METHODS: Ten ovine models of ECMO support were established. Animals were then randomly divided into 2 groups (5 sheep/group): venoarterial (VA) ECMO group and venovenous (VV) ECMO group. The venous blood samples were collected at different time points. Markers of NETs were detected in plasma, neutrophils, and thrombi from the vessels and membrane. Moreover, circulating NETs levels in 8 adults treated in the intensive care unit (ICU) who received VA-ECMO and 8 healthy controls were detected; patient survival was also recorded. RESULTS: In vivo study showed that neutrophils and NETs markers (dsDNA and citH3) levels were significantly elevated 6 h after ECMO compared to baseline. Isolated neutrophils from fresh blood at 6 h could release more NETs. dsDNA and citH3 levels were significantly higher in the VA mode than in the VV mode. NETs were found in thrombi from the vessel and membrane. Clinical data further revealed that dsDNA, citH3, and nucleosomes were higher in patients who received ECMO than in healthy controls. CONCLUSIONS: These data suggest NETs might be associated with thrombus during ECMO support, especially in the VA mode. These findings provide new insight into preventing thrombotic complications by targeting NETs. Also, NETs may potentially become an early warning biomarker for thrombosis under ECMO assistance.