Acute normovolemic hemodilution in cardiac surgery: Rationale and design of a multicenter randomized trial.

BACKGROUND: Minimizing the use of blood component can reduce known and unknown blood transfusion risks, preserve blood bank resources, and decrease healthcare costs. Red Blood Cell (RBC) transfusion is common after cardiac surgery and associated with adverse perioperative outcomes, including mortality. Acute normovolemic hemodilution (ANH) may reduce bleeding and the need for blood product transfusion after cardiac surgery. However, its blood-saving effect and impact on major outcomes remain uncertain. METHODS: This is a single-blinded, multinational, pragmatic, randomized controlled trial with a 1:1 allocation ratio conducted in Tertiary and University hospitals. The study is designed to enroll patients scheduled for elective cardiac surgery with planned cardiopulmonary bypass (CPB). Patients are randomized to receive ANH before CPB or the best available treatment without ANH. We identified an ANH volume of at least 650 mL as the critical threshold for clinically relevant benefits. Larger ANH volumes, however, are allowed and tailored to the patient's characteristics and clinical conditions. RESULTS: The primary outcome is the percentage of patients receiving RBCs transfusion from randomization until hospital discharge, which we hypothesize will be reduced from 35% to 28% with ANH. Secondary outcomes are all-cause 30-day mortality, acute kidney injury, bleeding complications, and ischemic complications. CONCLUSION: The trial is designed to determine whether ANH can safely reduce RBC transfusion after elective cardiac surgery with CPB. STUDY REGISTRATION: This trial was registered on ClinicalTrials.gov in April 2019 with the trial identification number NCT03913481.

Early-Staged Carotid Artery Stenting Prior to Coronary Artery Bypass Grafting: Analysis of the Early and Mid-Term Results in Comparison with a Consecutive Cohort of Isolated Coronary Artery Surgery Patients.

AIM: The aim of the present study was to analyze retrospectively the results of patients who underwent early-staged, i.e., within 24-48 h, carotid artery stenting (e-s CAS) before coronary artery bypass grafting (CABG). METHODS: Between December 2014 and December 2022, 1046 consecutive patients underwent CABG; 31 of these patients (3%) were subjected to e-s CAS prior to CABG (e-s CAS + CABG group). Preoperative and intraoperative variables and early and mid-term results of the e-s CAS + CABG group were compared with those of patients who underwent isolated CABG (CABG group). RESULTS: As compared with the CABG group, the e-s CAS + CABG group showed a worse clinical risk profile due to higher Euroscore-2 values and incidence of obstructive pulmonary disease and bilateral carotid artery and peripheral artery diseases (p < 0.05, for all comparisons). The combined end point of operative mortality, periprocedural myocardial infarction, and stroke was 3.2% (0%/0%/3.2%) in the e-s CAS + CABG group vs. 5.9% (2.2%/2.8%/0.9%) in the CABG group (p > 0.5, for all measurements). At 5 years, actuarial survival was 74% ± 16% in the e-s CAS + CABG group vs. 93% ± 4.0% in the CABG group, freedom from cardiac death was 100% vs. 98% ± 1.0% (p = 0.6), and freedom from MACCEs was 85% ± 15% vs. 97% ± 2.5% (p > 0.1, for all comparisons). Independent predictors of all-causes death were advanced age at the operation (p < 0.0001), a lower value for left ventricular ejection fraction (p = 0.05), and a high Euroscore-2 (p = 0.04). CONCLUSIONS: CABG preceded by e-s CAS appears to be associated with satisfactory early outcomes while limiting the risk of myocardial infarction to a very short time interval between the two procedures. Freedom from late all-causes death, cardiac death, and MACCEs were comparable and equally satisfactory, underscoring the positive protective effects of CAS and CABG on the carotid and coronary territories over time.

Co-ultramicronized palmitoylethanolamide/luteolin normalizes GABAB-ergic activity and cortical plasticity in long COVID-19 syndrome.

OBJECTIVE: Transcranial magnetic stimulation (TMS) studies showed that patients with cognitive dysfunction and fatigue after COVID-19 exhibit impaired cortical GABAB-ergic activity, as revealed by reduced long-interval intracortical inhibition (LICI). Aim of this study was to test the effects of co-ultramicronized palmitoylethanolamide/luteolin (PEA-LUT), an endocannabinoid-like mediator able to enhance GABA-ergic transmission and to reduce neuroinflammation, on LICI. METHODS: Thirty-nine patients (26 females, mean age 49.9 ± 11.4 years, mean time from infection 296.7 ± 112.3 days) suffering from persistent cognitive difficulties and fatigue after mild COVID-19 were randomly assigned to receive either PEA-LUT 700 mg + 70 mg or PLACEBO, administered orally bid for eight weeks. The day before (PRE) and at the end of the treatment (POST), they underwent TMS protocols to assess LICI. We further evaluate short-latency afferent inhibition (SAI) and long-term potentiation (LTP)-like cortical plasticity. RESULTS: Patients treated with PEA-LUT but not with PLACEBO showed a significant increase of LICI and LTP-like cortical plasticity. SAI remained unaffected. CONCLUSIONS: Eight weeks of treatment with PEA-LUT restore GABAB activity and cortical plasticity in long Covid patients. SIGNIFICANCE: This study confirms altered physiology of the motor cortex in long COVID-19 syndrome and indicates PEA-LUT as a candidate for the treatment of this post-viral condition.

Intracortical GABAergic dysfunction in patients with fatigue and dysexecutive syndrome after COVID-19.

OBJECTIVE: A high proportion of patients experience fatigue and impairment of cognitive functions after coronavirus disease 2019 (COVID-19). Here we applied transcranial magnetic stimulation (TMS) to explore the activity of the main inhibitory intracortical circuits within the primary motor cortex (M1) in a sample of patients complaining of fatigue and presenting executive dysfunction after resolution of COVID-19 with neurological manifestations. METHODS: Twelve patients who recovered from typical COVID-19 pneumonia with neurological complications and complained of profound physical and mental fatigue underwent, 9 to 13 weeks from disease onset, a psychometric evaluation including a self-reported fatigue numeric-rating scale (FRS, Fatigue Rating Scale) and the Frontal Assessment Battery (FAB). Intracortical activity was evaluated by means of well-established TMS protocols including short-interval intracortical inhibition (SICI), reflecting GABAA-mediated inhibition, long-interval intracortical inhibition (LICI), a marker of GABAB receptor activity, and short-latency afferent inhibition (SAI) that indexes central cholinergic transmission. TMS data were compared to those obtained in a control group of ten healthy subjects (HS) matched by age, sex and education level. RESULTS: Post-COVID-19 patients reported marked fatigue according to FRS score (8.1 ± 1.7) and presented pathological scores at the FAB based on Italian normative data (12.2 ± 0.7). TMS revealed marked reduction of SICI, and disruption of LICI as compared to HS. SAI was also slightly diminished. CONCLUSIONS: The present study documents for the first time reduced GABAergic inhibition in the M1 in patients who recovered from COVID-19 with neurological complications and manifested fatigue and dysexecutive syndrome. SIGNIFICANCE: TMS may serve as diagnostic tool in cognitive disturbances and fatigue in post-COVID-19 patients.

Imaging and monitoring in minimally invasive valve surgery using an intra-aortic occlusion device: a single center experience.

BACKGROUND: Minimally invasive approach through a right mini-thoracotomy is a world-wide used procedure for mitral valve surgery. We performed a retrospective analysis based on our center experience in order to propose an effective, safe and reproducible method using an intra-aortic occlusion device. METHODS: This is a retrospective analysis on 48 consecutive patients undergoing mitral valve surgery through a right anterolateral mini-thoracotomy in our center. An intra-aortic occlusion device was used for aortic clamping and cardioplegia delivery. Simultaneous multi-plane three-dimensional echocardiography imaging was acquired to detect the venous cannulas position, the intra-aortic device location in the ascending aorta, the balloon inflation, the complete occlusion of the aorta, the cardioplegia delivery, the origin and the blood flow in the right coronary artery. Aortic root pressure was measured by the tip of the intra-aortic occlusion device. A bilateral upper extremity invasive arterial pressure monitoring was detected. Neuromonitoring was performed through bilateral cerebral oximetry. RESULTS: The analysis has shown no aortic dissection, neurological damage type 1 and myocardial ischemia in the study population. In 3 cases a distal displacement of the intra-aortic occlusion device was promptly detected by the combined use of echocardiographic imaging and by a drop of the right cerebral oximetry saturation and of the right radial artery pressure. CONCLUSIONS: The combined use of transesophageal simultaneous multi-plane three- dimensional echocardiography imaging, bilateral upper extremity invasive arterial pressure monitoring, aortic root pressure and cerebral oximetry is an effective, safe and reproducible method in patients undergoing minimally invasive valve surgery using an intra-aortic occlusion device.

Dopamine Optimizes Venous Return During Cardiopulmonary Bypass and Reduces the Need for Postoperative Blood Transfusion.

Venodilation occurs shortly after the institution of cardiopulmonary bypass (CPB), necessitating fluid or vasoconstrictor administration to maintain adequate oxygen delivery. The vasoconstrictor effects of dopamine are not well studied in this context. Therefore, we conducted a single-center, double-blind case-control study to determine the role and utility of dopamine as a vasoconstrictor during CPB. The study included 60 adults who were scheduled for isolated elective/urgent coronary artery bypass grafting. Patients in group A (n = 30) received a dopamine bolus (2 mg) 20 min after cross-clamping, whereas patients in group B (n = 30) did not receive any intervention at a specific time point. Both groups received standard care as needed (fluid replacement or norepinephrine bolus). Venous return was measured directly in the reservoir and indirectly by Doppler measurement at the level of the inferior vena cava with transesophageal echocardiography. Both open and closed circuits were used for CPB. A single dopamine bolus (2 mg) increased volume in the venous reservoir in group A. Group A patients also received significantly fewer units of red blood cells in the intensive care unit (ICU) than did patients in group B. There were no significant between-group differences in postoperative bleeding, mechanical ventilation, or length of stay in the ICU. These findings suggest that use of a dopamine bolus can increase venous return and reduce the need for fluid replacement during and after CPB in patients undergoing coronary artery bypass grafting.