A Randomized Trial of Intravenous Amino Acids for Kidney Protection.

BACKGROUND: Acute kidney injury (AKI) is a serious and common complication of cardiac surgery, for which reduced kidney perfusion is a key contributing factor. Intravenous amino acids increase kidney perfusion and recruit renal functional reserve. However, the efficacy of amino acids in reducing the occurrence of AKI after cardiac surgery is uncertain. METHODS: In a multinational, double-blind trial, we randomly assigned adult patients who were scheduled to undergo cardiac surgery with cardiopulmonary bypass to receive an intravenous infusion of either a balanced mixture of amino acids, at a dose of 2 g per kilogram of ideal body weight per day, or placebo (Ringer's solution) for up to 3 days. The primary outcome was the occurrence of AKI, defined according to the Kidney Disease: Improving Global Outcomes creatinine criteria. Secondary outcomes included the severity of AKI, the use and duration of kidney-replacement therapy, and all-cause 30-day mortality. RESULTS: We recruited 3511 patients at 22 centers in three countries and assigned 1759 patients to the amino acid group and 1752 to the placebo group. AKI occurred in 474 patients (26.9%) in the amino acid group and in 555 (31.7%) in the placebo group (relative risk, 0.85; 95% confidence interval [CI], 0.77 to 0.94; P = 0.002). Stage 3 AKI occurred in 29 patients (1.6%) and 52 patients (3.0%), respectively (relative risk, 0.56; 95% CI, 0.35 to 0.87). Kidney-replacement therapy was used in 24 patients (1.4%) in the amino acid group and in 33 patients (1.9%) in the placebo group. There were no substantial differences between the two groups in other secondary outcomes or in adverse events. CONCLUSIONS: Among adult patients undergoing cardiac surgery, infusion of amino acids reduced the occurrence of AKI. (Funded by the Italian Ministry of Health; PROTECTION ClinicalTrials.gov number, NCT03709264.).

Improved outcome with individualised antifibrinolytic therapy: what is the evidence?

Viscoelastic haemostatic testing (VHT) has been used to determine hyperfibrinolysis and hypofibrinolysis. When modified by addition of tissue plasminogen activator (tPA), VHT has been suggested to assess responses to antifibrinolytic therapy and to estimate the concentration of tranexamic acid in patients undergoing cardiac surgery. Despite some evidence that tPA-modified VHT might allow individualisation of antifibrinolytic therapy, further studies are warranted to prove its clinical benefit for postsurgical bleeding, transfusion of blood products, and thromboembolic events.

The Use of Pulmonary Artery Catheters and Echocardiography in the Cardiac Surgery Setting: A Nationwide Italian Survey.

OBJECTIVE: Wide variations exist in the use of pulmonary artery catheters (PACs) and echocardiography in the field of cardiac surgery. DESIGN: A national survey promoted by the Italian Association of Cardio-Thoracic Anesthesiologists and Intensive Care was conducted. SETTING: The study occurred in Italian cardiac surgery centers (n = 71). PARTICIPANTS: Anesthesiologists-intensivists were enrolled. INTERVENTIONS: Anonymous questionnaires were used to investigate the use of PACs and echocardiography in the operating room (OR) and intensive care unit (ICU). MEASUREMENTS AND MAIN RESULTS: A total of 257 respondents (32.2% response rate) from 59 centers (83.1% response rate) participated. Use of PACs seems less common in ORs (median insertion in 20% [5-70] of patients), with slightly higher use in ICUs; in about half of cases, it was the continuous cardiac output monitoring system of choice. Almost two-thirds of respondents recently inserted at least one PAC within a few hours of ICU admission, despite its need being largely preoperatively predictable. Protocols regulating PAC insertion were reported by 25.3% and 28% of respondents (OR and ICU, respectively). Transesophageal echocardiography (TEE) was performed intraoperatively in >75% of patients by 86.4% of respondents; only 23.7% stated that intraoperative TEE relied on anesthesiologists. Tissue Doppler and/or 3D imaging were widely available (87.4% and 82%, respectively), but only 37.8% and 24.3% of respondents self-declared skills in these modalities, respectively; 77.1% of respondents had no echocardiography certification, nor were pursuing certification (various reasons); 40.9% had not attended recent echocardiography courses. Lower PAC use was associated with university hospitals (OR: p = 0.014, ICU: p = 0.032) and with lower interventions/year (OR: p = 0.023). Higher independence in performing TEE was reported in university hospitals (OR: p < 0.001; ICU: p = 0.006), centers with higher interventions/year (OR: p = 0.019), and by respondents with less experience in cardiology (ICU: p = 0.046). CONCLUSION: Variability in the use of PACs and echocardiography was found. Protocols regulating the use of PACs seem infrequent. University centers use PACs less and have greater skills in TEE. Training and certifications in echocardiography should be encouraged.

The Appraisal of Adults with Congenital Heart Disease: Lesson from Comparison of Surgical Outcomes.

The population of adults with congenital heart disease (ACHD) is constantly growing. There seems to be a consensus that these patients are difficult to manage especially if compared to patients with acquired heart disease. The aim of this study is to compare outcomes and results of cardiac surgery in ACHD patients with a reference population of adults with acquired cardiac disease. Retrospective study of 5053 consecutive patients older than 18 years hospitalized for cardiac surgery during a 5-years period in our Institution. Two groups of patients were identified. Group I: 419 patients operated for congenital heart disease; Group II: 4634 patients operated for acquired heart disease. In each Group were identified low, medium, and high-risk patients, according to validated scores. Right ventricular outflow tract surgery was the most frequent procedure in Group I, while coronary artery by-pass grafting was the most common in Group II. Patients with ACHD were younger (37.8 vs. 67.7 years), with higher number of previous operations (32.1% vs. 6.9%), had longer post-ICU hospital stay (11 vs. 8 days) but had lower ICU stay (1 vs. 2 days), shorter assisted mechanical ventilation (12 vs. 14 h) and lower surgical mortality (1 vs. 3.7%) (all p < 0.001). No differences were found in term of post-operative complications (12.4 vs. 15%). The surgical treatment of ACHD patients can be done with excellent results and if compared with acquired cardiac disease patients they have better results with shorter ICU stay and lower mortality.

HCG18, LEF1AS1 and lncCEACAM21 as biomarkers of disease severity in the peripheral blood mononuclear cells of COVID-19 patients.

BACKGROUND: Even after 3 years from SARS-CoV-2 identification, COVID-19 is still a persistent and dangerous global infectious disease. Significant improvements in our understanding of the disease pathophysiology have now been achieved. Nonetheless, reliable and accurate biomarkers for the early stratification of COVID-19 severity are still lacking. Long noncoding RNAs (LncRNAs) are ncRNAs longer than 200 nucleotides, regulating the transcription and translation of protein-coding genes and they can be found in the peripheral blood, thus holding a promising biomarker potential. Specifically, peripheral blood mononuclear cells (PBMCs) have emerged as a source of indirect biomarkers mirroring the conditions of tissues: they include monocytes, B and T lymphocytes, and natural killer T cells (NKT), being highly informative for immune-related events. METHODS: We profiled by RNA-Sequencing a panel of 2906 lncRNAs to investigate their modulation in PBMCs of a pilot group of COVID-19 patients, followed by qPCR validation in 111 hospitalized COVID-19 patients. RESULTS: The levels of four lncRNAs were found to be decreased in association with COVID-19 mortality and disease severity: HLA Complex Group 18-242 and -244 (HCG18-242 and HCG18-244), Lymphoid Enhancer Binding Factor 1-antisense 1 (LEF1-AS1) and lncCEACAM21 (i.e. ENST00000601116.5, a lncRNA in the CEACAM21 locus). Interestingly, these deregulations were confirmed in an independent patient group of hospitalized patients and by the re-analysis of publicly available single-cell transcriptome datasets. The identified lncRNAs were expressed in all of the PBMC cell types and inversely correlated with the neutrophil/lymphocyte ratio (NLR), an inflammatory marker. In vitro, the expression of LEF1-AS1 and lncCEACAM21 was decreased upon THP-1 monocytes exposure to a relevant stimulus, hypoxia. CONCLUSION: The identified COVID-19-lncRNAs are proposed as potential innovative biomarkers of COVID-19 severity and mortality.

Incidence and predictors of 30-day and 6-month stroke after TAVR: Insights from the multicenter OBSERVANT II study.

BACKGROUND: The incidence and predictors of 30-day stroke after transcatheter aortic valve replacement (TAVR) were derived from early studies investigating first-generation devices. The incidence of 6-month stroke and its related predictors are unknown. AIMS: To investigate the incidence and to identify procedural and patient-related predictors of 30-day and 6-month stroke after TAVR. METHODS: Data from 2753 consecutive patients with severe aortic stenosis undergoing TAVR were obtained from the OBSERVANT-II study, an observational, prospective, multicenter cohort study. The study endpoints were symptomatic 30-day and 6-month stroke after TAVR. RESULTS: The occurrence of a 30-day and 6-month stroke was low (1.3% and 2.4%, respectively) but with significant impact on survival. Aortic valve predilatation (odds ratio [OR]: 2.28, 95% confidence interval [CI]: 1.12-4.65, p = 0.023), diabetes (OR: 3.10, 95% CI: 1.56-6.18, p = 0.001), and left ventricle ejection fraction < 50% (OR: 2.15, 95% CI: 1.04-4.47, p = 0.04) were independent predictors of 30-day stroke, whereas diabetes (sub-distribution hazard ratio [SHR]: 2.07, 95% CI: 1.25-3.42, p = 0.004), pre-existing neurological dysfunction (SHR: 3.92, 95% CI: 1.54-10, p = 0.004), bicuspid valve (SHR: 4.75, 95% CI: 1.44-15.7, p = 0.011), and critical status (SHR: 3.05, 95% CI: 1.21-7.72, p = 0.018) were predictive of 6-month stroke. Conversely, antiplatelet therapy and anticoagulation were protective factors at both 30 days and 6 months. CONCLUSIONS: Stroke after TAVR was rare. Predilatation was the only procedural factor predictive of 30-day stroke, whereas the remaining were patient-related risk factors, suggesting appropriate risk stratification preoperatively.

The Rise and Fall of Antithrombin Supplementation in Cardiac Surgery.

Various cohort studies, both retrospective and prospective, showed that low antithrombin levels after cardiac surgery (at the arrival in the intensive care unit and during the next days) were associated with a number of adverse outcomes, including surgical reexploration and thromboembolic events, eventually leading to prolonged stay in the intensive care. Values lower than 58% to 64% of antithrombin activity were indicative of this higher morbidity with good sensitivity and specificity. The scenario generated the hypothesis that low antithrombin levels needed to be corrected by supplementation to improve postoperative outcome. However, randomized controlled studies run to test this idea failed to demonstrate any benefit of antithrombin supplementation, showing no effects on outcome, neither as preemptive preoperative strategy nor for treating postoperative low antithrombin values. In addition, randomized trials highlighted that those patients who received antithrombin experienced significantly higher incidence of acute kidney injury with a pooled odds ratio of 4.41 (95% CI, 1.90-10.23; P = .001). A strongly decreased thrombin activity after antithrombin correction may eventually affect the efficiency of the glomerular filtration and cause the deterioration of kidney function, but underlying biological mechanisms remain unclear. In conclusion, low levels of antithrombin activity after cardiac surgery should be considered as a marker of greater severity of the patient's conditions and/or of the complexity of the surgical procedure. There are no indications for antithrombin supplementation in cardiac surgery unless for correcting heparin resistance.

Clopidogrel Resistance and Ticagrelor Replacement in Dual Antiplatelet Therapy for Carotid Artery Stenting.

BACKGROUNDS: Resistance to the pharmacological effect of clopidogrel in patients undergoing dual antiplatelet therapy for carotid stenting may increase the risk of periprocedural neurological events. The purpose of the study was to describe the phenomenon of clopidogrel resistance in a series of patients undergoing carotid stenting. METHODS: Data of patients who consecutively underwent carotid stenting from November 2016 to December 2020 for a significant stenosis and who underwent a dual antiplatelet therapy using acetyl-salicylic acid and clopidogrel were prospectively collected. Patients who were already taking a different thienopyridine were excluded. The effectiveness of antiplatelet drugs was assessed by the impedance aggregometry test. Primary endpoint was to evaluate the incidence of clopidogrel resistance and the effectiveness of ticagrelor as alternative therapy. P values < 0.05 were considered statistically significant. RESULTS: Two-hundred patients (80 females, 40%) underwent stenting for carotid stenosis (94% asymptomatic). The phenomenon of clopidogrel resistance was observed in 38 patients (19%), in whom clopidogrel was replaced by ticagrelor (90 mg/bis in die) with 100% effectiveness at aggregometry test. Platelet counts was associated to clopidogrel resistance (P = 0.001). There was no stent thrombosis at 30 days, neither major hemorrhagic events; a total of 12/200 major adverse cardiovascular events occurred (6%), including 1 in the group of patients who took ticagrelor and 11 in group of patients under clopidogrel (2.6% versus 6.7%, P = 0.55). CONCLUSIONS: Clopidogrel was ineffective in 19% of patients undergoing carotid stenting. Platelet count seemed to affect this phenomenon. In these patients, clopidogrel was effectively replaced by ticagrelor.

Cardiac surgery-Associated acute kidney injury - A narrative review.

Cardiac Surgery-Associated Acute Kidney Injury (CSA-AKI) is a serious complication seen in approximately 20-30% of cardiac surgery patients. The underlying pathophysiology is complex, often involving both patient- and procedure related risk factors. In contrast to AKI occurring after other types of major surgery, the use of cardiopulmonary bypass comprises both additional advantages and challenges, including non-pulsatile flow, targeted blood flow and pressure as well as the ability to manipulate central venous pressure (congestion). With an increasing focus on the impact of CSA-AKI on both short and long-term mortality, early identification and management of high-risk patients for CSA-AKI has evolved. The present narrative review gives an up-to-date summary on definition, diagnosis, underlying pathophysiology, monitoring and implications of CSA-AKI, including potential preventive interventions. The review will provide the reader with an in-depth understanding of how to identify, support and provide a more personalized and tailored perioperative management to avoid development of CSA-AKI.

2021 MiECTiS focused update on the 2016 position paper for the use of minimal invasive extracorporeal circulation in cardiac surgery.

The landmark 2016 Minimal Invasive Extracorporeal Technologies International Society (MiECTiS) position paper promoted the creation of a common language between cardiac surgeons, anesthesiologists and perfusionists which led to the development of a stable framework that paved the way for the advancement of minimal invasive perfusion and related technologies. The current expert consensus document offers an update in areas for which new evidence has emerged. In the light of published literature, modular minimal invasive extracorporeal circulation (MiECC) has been established as a safe and effective perfusion technique that increases biocompatibility and ultimately ensures perfusion safety in all adult cardiac surgical procedures, including re-operations, aortic arch and emergency surgery. Moreover, it was recognized that incorporation of MiECC strategies advances minimal invasive cardiac surgery (MICS) by combining reduced surgical trauma with minimal physiologic derangements. Minimal Invasive Extracorporeal Technologies International Society considers MiECC as a physiologically-based multidisciplinary strategy for performing cardiac surgery that is associated with significant evidence-based clinical benefit that has accrued over the years. Widespread adoption of this technology is thus strongly advocated to obtain additional healthcare benefit while advancing patient care.

The Long Term Residual Effects of COVID-Associated Coagulopathy.

During the acute phase of COVID-19, many patients experience a complex coagulopathy characterized by a procoagulant pattern. The present study investigates the persistence of hemostatic changes in post-COVID patients at a long-term follow up, and the link with the persistence of physical and neuropsychological symptoms. We completed a prospective cohort study on 102 post-COVID patients. Standard coagulation and viscoelastic tests were performed, along with an assessment of persistent symptoms and recording of acute phase details. A procoagulant state was adjudicated in the presence of fibrinogen > 400 mg/dL, or D-dimer > 500 ng/mL, or platelet count > 450,000 cells/µL, or a maxim clot lysis at viscoelastic test < 2%. A procoagulant state was identified in 75% of the patients at 3 months follow up, 50% at 6 months, and 30% at 12-18 months. Factors associated with the persistence of a procoagulant state were age, severity of the acute phase, and persistence of symptoms. Patients with major physical symptoms carry a procoagulant state relative risk of 2.8 (95% confidence interval 1.17-6.7, p = 0.019). The association between persistent symptoms and a procoagulant state raises the hypothesis that an ongoing process of thrombi formation and/or persistent microthrombosis may be responsible for the main physical symptoms in long-COVID patients.

Are Viscoelastic Tests Clinically Useful to Identify Platelet-Dependent Bleeding in High-Risk Cardiac Surgery Patients?

BACKGROUND: Postoperative use of platelet function testing to rule out microvascular bleeding due to platelet dysfunction after cardiac surgery still lacks strong reference data and reliable cutoff values, yielding a clinically adequate sensitivity and specificity. The present study aims to investigate the performance of two different point-of-care viscoelastic devices and platelet aggregometry in expressing surgery-dependent platelet dysfunction and anticipating postoperative major bleeding in a cohort of high-risk patients. METHODS: Prospective cohort study of 50 adult patients who were on antiplatelet drugs discontinued for no more than 7 days (clopidogrel and prasugrel) or 5 days (ticagrelor) undergoing cardiac surgery with cardiopulmonary bypass (CPB). Coagulation and platelet function testing, including QUANTRA, ROTEM, and Multiplate, were assessed preoperatively and postoperatively. Chest drain blood loss was measured in the first 12 postoperative hours. Perioperative bleeding was assessed using a modified version of the Universal Definition of Perioperative Bleeding (UDPB) in cardiac surgery, modified to not consider anemia-correcting packed red cells transfusions in the absence of bleeding >600 mL/12 h. Major bleeding was identified as UDPB class II or higher. RESULTS: Multiplate adenosine diphosphate (ADPtest) was significantly ( P = .001) reduced after CPB, whereas TRAPtest was not. The platelet component (PC) as extrapolated by ROTEM data (EXTEM MCF-FIBTEM MCF) was unchanged after CPB, while the A10 PC (PC at 10 minutes) was significantly ( P = .001) reduced. The QUANTRA platelet contribution to clot stiffness (PCS) was significantly ( P = .001) reduced, as well. At the ROC analysis for the predictive ability of the post-CPB platelet function testing, the best discrimination was obtained by the QUANTRA PCS, with an area under the curve (AUC) (95% confidence interval [CI]) of 0.80 (0.66-0.91), P = .001, followed by the ROTEM A10 PC with AUC (95% CI) of 0.75 (0.51-0.99), P = .004, and PC with AUC (95% CI) of 0.74 (0.50-0.99), P = .009. The Multiplate ADPtest had an AUC (95% CI) of 0.67 (0.42-0.91), and the TRAPtest had an AUC (95% CI) of 0.62 (0.37-0.86). The cutoff values identified were 13 hPa for the QUANTRA PCS, 40 mm for the ROTEM A10, and 48.5 mm for the ROTEM PC, with negative predictive values of 84%, 81%, and 86%, respectively, and positive predictive values of 55%, 53%, and 69%, respectively. CONCLUSIONS: QUANTRA PCS, ROTEM A10 PC, and Multiplate ADPtest showed a significant decrease after CPB, whereas ROTEM PC and Multiplate TRAPtest did not. Major bleeding was predicted with a moderate to good discrimination by the post-CPB viscoelastic tests (PCS, PC, and A10 PC).

A Multicenter, Randomized, Double-Blind, Placebo-Controlled Trial of Preoperative Antithrombin Supplementation in Patients at Risk for Antithrombin Deficiency After Cardiac Surgery.

BACKGROUND: Antithrombin (AT) activity is reduced during cardiac operations with cardiopulmonary bypass (CPB), which is associated with adverse outcomes. Preoperative AT supplementation, to achieve >58% and <100% AT activity, may potentially reduce postoperative morbidity and mortality in cardiac operations with CPB. This prospective, multicenter, randomized, double-blind, placebo-controlled study was designed to evaluate the safety and efficacy of preoperative treatment with AT supplementation in patients at risk for low AT activity after undergoing cardiac surgery with CPB. METHODS: A total of 425 adult patients were randomized (1:1) to receive either a single dose of AT (n = 213) to achieve an absolute increase of 20% above pretreatment AT activity or placebo (n = 212) before surgery. The study duration was approximately 7 weeks. The primary efficacy end point was the percentage of patients with any component of a major morbidity composite (postoperative mortality, stroke, acute kidney injury [AKI], surgical reexploration, arterial or venous thromboembolic events, prolonged mechanical ventilation, and infection) in the 2 groups. Secondary end points included AT activity, blood loss, transfusion requirements, duration of intensive care unit (ICU), and hospital stays. Safety was also assessed. RESULTS: Overall, 399 patients (men, n = 300, 75.2%) with a mean (standard deviation [SD]) age of 66.1 (11.7) years, with the majority undergoing complex surgical procedures (n = 266, 67.9%), were analyzed. No differences in the percentage of patients experiencing morbidity composite outcomes between groups were observed (AT-treated 68/198 [34.3%] versus placebo 58/194 [29.9%]; P = .332; relative risk, 1.15). After AT infusion, AT activity was significantly higher in the AT group (108% [42-143]) versus placebo group (76% [40-110]), and lasted up to postoperative day 2. At ICU, the frequency of patients with AT activity ≥58% in the AT group (81.5%) was significantly higher ( P < .001) versus placebo group (43.2%). Secondary end point analysis did not show any advantage of AT over placebo group. There were significantly more patients with AKI ( P < .001) in the AT group (23/198; 11.6%) than in the placebo group (5/194, 2.6%). Safety results showed no differences in treatment-emergent adverse events nor bleeding events between groups. CONCLUSIONS: AT supplementation did not attenuate adverse postoperative outcomes in our cohort of patients undergoing cardiac surgery with CPB.

A Comparative Study of Multiple Electrode Aggregometry Technologies in Cardiac Surgery: Different Values, Same Clinical Relevance.

OBJECTIVES: The assessment of platelet function in cardiac surgery patients who recently received dual-antiplatelet therapy is considered in the existing guidelines. Among available devices, Multiplate (MP) and ROTEM Platelet (RP) are both based on electrical impedance. This study aimed to determine the agreement between MP and RP in cardiac surgery patients under dual-antiplatelet therapy discontinued before surgery. Secondarily, it compared the ability of the MP and RP in predicting postoperative bleeding and the need for platelet transfusion. DESIGN: A prospective cohort study. SETTING: A hospital in Milan, Italy. PARTICIPANTS: Fifty adult patients preoperatively and postoperatively tested. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Patients were studied with adenosine diphosphate (ADP) and thrombin receptor-activating peptide (TRAP) testing on both of the devices. The mean preoperative ADP tests were below the respective lower limit of the reference value, thus reflecting a good ability of these tests to detect the residual or ongoing effects of antiplatelet drugs acting on the P2Y12 receptor. The agreement between the 2 methodologies was very poor for both the ADP and TRAP tests, with a percentage error of 80%. The preoperative ADP tests were predictive for the need of platelet concentrate transfusion, with cut-off values at 35 U for the ADP-MP and 60 Ω/min for the ADP-RP. No correlation was found for postoperative bleeding. CONCLUSION: Both technologies seemed to offer potential benefits in the surgical approach to patients who preoperatively received antiplatelet drugs. However, the results of these tests are not interchangeable, and different cut-off values should be applied.

Acute Respiratory Distress Syndrome in the Perioperative Period of Cardiac Surgery: Predictors, Diagnosis, Prognosis, Management Options, and Future Directions.

Acute respiratory distress syndrome (ARDS) after cardiac surgery is reported with a widely variable incidence (from 0.4%-8.1%). Cardiac surgery patients usually are affected by several comorbidities, and the development of ARDS significantly affects their prognosis. Herein, evidence regarding the current knowledge in the field of ARDS in cardiac surgery is summarized and is followed by a discussion on therapeutic strategies, with consideration of the peculiar aspects of ARDS after cardiac surgery. Prevention of lung injury during and after cardiac surgery remains pivotal. Blood product transfusions should be limited to minimize the risk, among others, of lung injury. Open lung ventilation strategy (ventilation during cardiopulmonary bypass, recruitment maneuvers, and the use of moderate positive end-expiratory pressure) has not shown clear benefits on clinical outcomes. Clinicians in the intraoperative and postoperative ventilatory settings carefully should consider the effect of mechanical ventilation on cardiac function (in particular the right ventricle). Driving pressure should be kept as low as possible, with low tidal volumes (on predicted body weight) and optimal positive end-expiratory pressure. Regarding the therapeutic options, management of ARDS after cardiac surgery challenges the common approach. For instance, prone positioning may not be easily applicable after cardiac surgery. In patients who develop ARDS after cardiac surgery, extracorporeal techniques may be a valid choice in experienced hands. The use of neuromuscular blockade and inhaled nitric oxide can be considered on a case-by-case basis, whereas the use of aggressive lung recruitment and oscillatory ventilation should be discouraged.

The multifactorial dynamic perfusion index: A predictive tool of cardiac surgery associated acute kidney injury.

INTRODUCTION: cardiac surgery associated acute kidney injury (CSA-AKI) has a number of preoperative and intraoperative risk factors. Cardiopulmonary bypass (CPB) factors have not yet been elucidated in a single multivariate model. The aim of this study is to develop a dynamic predictive model for CSA-AKI. METHODS: retrospective study on 910 consecutive adult cardiac surgery patients. Baseline data were used to settle a preoperative CSA-AKI risk model (static risk model, SRM); CPB related data were assessed for association with CSA-AKI. CPB duration, nadir oxygen delivery, time of exposure to a low oxygen delivery, nadir mean arterial pressure, peak lactates and red blood cell transfusion were included in a multivariate dynamic perfusion risk (DPR). SRM and DPR were merged into a final logistic regression model (multifactorial dynamic perfusion index, MDPI). The three risk models were assessed for discrimination and calibration. RESULTS: the SRM model had an AUC of 0.696 (95% CI 0.663-0.727), the DPR model of 0.723 (95% CI 0.691-0.753), and the MDPI model an AUC of 0.769 (95% CI 0.739-0.798). The difference in AUC between SRM and DPR was not significant (p = 0.495) whereas the AUC of MDPI was significantly larger than that of SRM (p = 0.004) and DPR (p = 0.015). CONCLUSIONS: inclusion of dynamic indices of the quality of CPB improves the discrimination and calibration of the preoperative risk scores. The MDPI has better predictive ability than the existing static risk models and is a promising tool to integrate different factors into an advanced concept of goal-directed perfusion.

Monitoring the Evolution of Asynchrony between Mean Arterial Pressure and Mean Cerebral Blood Flow via Cross-Entropy Methods.

Cerebrovascular control is carried out by multiple nonlinear mechanisms imposing a certain degree of coupling between mean arterial pressure (MAP) and mean cerebral blood flow (MCBF). We explored the ability of two nonlinear tools in the information domain, namely cross-approximate entropy (CApEn) and cross-sample entropy (CSampEn), to assess the degree of asynchrony between the spontaneous fluctuations of MAP and MCBF. CApEn and CSampEn were computed as a function of the translation time. The analysis was carried out in 23 subjects undergoing recordings at rest in supine position (REST) and during active standing (STAND), before and after surgical aortic valve replacement (SAVR). We found that at REST the degree of asynchrony raised, and the rate of increase in asynchrony with the translation time decreased after SAVR. These results are likely the consequence of the limited variability of MAP observed after surgery at REST, more than the consequence of a modified cerebrovascular control, given that the observed differences disappeared during STAND. CApEn and CSampEn can be utilized fruitfully in the context of the evaluation of cerebrovascular control via the noninvasive acquisition of the spontaneous MAP and MCBF variability.

Anti-Factor Xa-Based Anticoagulation during Extracorporeal Membrane Oxygenation: Potential Problems and Possible Solutions.

Choices for monitoring of unfractionated heparin (UFH) anticoagulation in extracorporeal membrane oxygenation (ECMO) patients include activated clotting time, activated partial thromboplastin time, reaction times of viscoelastic tests, and anti-factor Xa activity (between 0.3 and 0.7 IU/mL). Recent studies propose the anti-factor Xa to be the gold standard for monitoring UFH anticoagulation in ECMO. However, many extraneous factors combined question the utility of anti-factor Xa as the sole method of monitoring of UFH effects in ECMO. Anti-factor Xa is a chromogenic assay, which may be biased by the frequently elevated values of bilirubin and free hemoglobin in ECMO patients. The test may alternatively underestimate UFH effects in cases of low antithrombin values. More importantly, the anti-factor Xa assay is a plasma-based test which does not take into account the role of platelets and fibrinogen in forming a stable clot. Thrombocytopenia and platelet dysfunction are common features in ECMO patients, and underestimating their role may lead to over-anticoagulation, should only anti-factor Xa guiding be used to adjust the UFH dose. Conversely, fibrinogen is an acute phase protein, and some patients may experience high levels of fibrinogen during the ECMO course. In this case, an UFH monitoring based on anti-factor Xa is insensitive to this condition, although it may potentially be associated with thrombotic complications. Finally, the generally suggested range of 0.3 to 0.7 IU/mL is a somewhat arbitrary estimate, based on the desired range for treating and preventing thrombotic events in non-ECMO patients. In conclusion, anti-factor Xa may offer useful information on the real effects of UFH only when combined with a whole blood test capable of assessing the relative contribution of platelets and fibrinogen to clot formation.

Factors influencing the choice between transcatheter and surgical treatment of severe aortic stenosis in patients younger than 80 years: Results from the OBSERVANT study.

OBJECTIVES: We aimed to analyze the baseline features and clinical outcomes of patients younger than 80 years undergoing transfemoral transcatheter aortic valve implantation (TAVI) or surgical aortic valve replacement (SAVR) enrolled in the OBservational Study of Effectiveness of SAVR-TAVR procedures for severe Aortic steNosis Treatment (OBSERVANT) real-world study, focusing on variables guiding Heart Team decision toward TAVI. BACKGROUND: Patients treated with TAVI, independently of surgical risk score, are mostly older than 80 years. METHODS: OBSERVANT is a multicenter, observational, prospective cohort study that enrolled patients with symptomatic severe aortic stenosis (AS) who underwent SAVR or TAVI from December 2010 to June 2012 in 93 Italian participating hospitals. For this analysis, baseline characteristics, therapeutic approach and outcomes up to 5 years of follow-up of 4,801 patients under 80 years of age were collected. Patients were stratified by age classes (<65, 65-74, and 75-79 years). RESULTS: Patients <80 years of age with severe symptomatic AS undergoing TAVI (n = 483) had significantly higher Logistic EuroSCORE (10.84% vs. 5.22%, p < .001) and prevalence of comorbidities compared to subjects undergoing SAVR (n = 4,318). The decision to perform TAVI over SAVR was driven by anatomical factors, mainly previous cardiac surgery (odds ratio [OR] 24.73, confidence interval [CI] 12.71-48.10, p < .001) and the presence of porcelain aorta (OR 17.44, CI 6.67-45.55, p < .001), and clinical factors, mainly moderate-severe frailty score (OR 5.49, CI 3.33-9.07, p < .001), oxygen dependency (OR 7.42, CI 2.75-20.04, p < .001) and need for dialytic treatment (OR 5.24, CI 1.54-17.80, p < .008). Among patients undergoing TAVI, those under 65 years had the highest baseline risk profile (despite a low Logistic EuroSCORE) and the highest 5-year mortality compared to those 65-74 and 75-79-year-old (65.22% vs. 48.54% vs. 55.24%, log-rank p = .061). CONCLUSION: Among patients under 80 years of age with symptomatic severe AS, only 10% underwent TAVI. These patients were at higher baseline risk compared to those undergoing SAVR. The decision to perform TAVI was driven by the presence of both anatomical and clinical factors beyond surgical risk scores. Patients under 65 years of age, despite the low Logistic EuroSCORE, had the highest preoperative risk profile and carried the worse outcome.

COVID-19 and ECMO: the interplay between coagulation and inflammation-a narrative review.

Infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has presently become a rapidly spreading and devastating global pandemic. Veno-venous extracorporeal membrane oxygenation (V-V ECMO) may serve as life-saving rescue therapy for refractory respiratory failure in the setting of acute respiratory compromise such as that induced by SARS-CoV-2. While still little is known on the true efficacy of ECMO in this setting, the natural resemblance of seasonal influenza's characteristics with respect to acute onset, initial symptoms, and some complications prompt to ECMO implantation in most severe, pulmonary decompensated patients. The present review summarizes the evidence on ECMO management of severe ARDS in light of recent COVID-19 pandemic, at the same time focusing on differences and similarities between SARS-CoV-2 and ECMO in terms of hematological and inflammatory interplay when these two settings merge.