Volatile Anesthetics versus Total Intravenous Anesthesia for Cardiac Surgery.

BACKGROUND: Volatile (inhaled) anesthetic agents have cardioprotective effects, which might improve clinical outcomes in patients undergoing coronary-artery bypass grafting (CABG). METHODS: We conducted a pragmatic, multicenter, single-blind, controlled trial at 36 centers in 13 countries. Patients scheduled to undergo elective CABG were randomly assigned to an intraoperative anesthetic regimen that included a volatile anesthetic (desflurane, isoflurane, or sevoflurane) or to total intravenous anesthesia. The primary outcome was death from any cause at 1 year. RESULTS: A total of 5400 patients were randomly assigned: 2709 to the volatile anesthetics group and 2691 to the total intravenous anesthesia group. On-pump CABG was performed in 64% of patients, with a mean duration of cardiopulmonary bypass of 79 minutes. The two groups were similar with respect to demographic and clinical characteristics at baseline, the duration of cardiopulmonary bypass, and the number of grafts. At the time of the second interim analysis, the data and safety monitoring board advised that the trial should be stopped for futility. No significant difference between the groups with respect to deaths from any cause was seen at 1 year (2.8% in the volatile anesthetics group and 3.0% in the total intravenous anesthesia group; relative risk, 0.94; 95% confidence interval [CI], 0.69 to 1.29; P = 0.71), with data available for 5353 patients (99.1%), or at 30 days (1.4% and 1.3%, respectively; relative risk, 1.11; 95% CI, 0.70 to 1.76), with data available for 5398 patients (99.9%). There were no significant differences between the groups in any of the secondary outcomes or in the incidence of prespecified adverse events, including myocardial infarction. CONCLUSIONS: Among patients undergoing elective CABG, anesthesia with a volatile agent did not result in significantly fewer deaths at 1 year than total intravenous anesthesia. (Funded by the Italian Ministry of Health; MYRIAD ClinicalTrials.gov number, NCT02105610.).

Long-term health-related quality of life after surgery in patients with chronic thromboembolic pulmonary hypertension.

PURPOSE: To assess the dynamic of various health-related quality of life (HRQoL) parameters 3 years after pulmonary thromboendarterectomy (PTE), and to identify factors affecting HRQoL parameters in patients with chronic thromboembolic pulmonary hypertension (CTEPH) in the long-term follow-up after surgery. METHODS: This prospective cohort study included 128 patients with CTEPH before and after the PTE (3 year follow-up). The HRQoL was examined using the Short-Form 36 Health Survey Questionnaire (SF-36). RESULTS: In patients with CTEPH 3 years after PTE, a significant improvement in all the HRQoL parameters. The summary indicators of the physical and mental components of health remained at the same level as 1 year after the PTE and did not exceed 50 points. The residual pulmonary hypertension was a leading factor limiting parameters of physical and mental health 3 years after a PTE. In addition, the parameters of physical activity were adversely affected by age and the age-adjusted Charlson Comorbidity Index. CONCLUSIONS: In the study group of patients with CTEPH, PTE contributes to a significant improvement in all HRQoL parameters, which observed both 1 year and 3 years after surgery. The leading factor adversely affecting the physical and emotional components of health in the long-term period after PTE was residual pulmonary hypertension recorded in the early postoperative period. In addition, some physical HRQoL parameters are affected by age and age-adjusted Charlson Comorbidity Index.

Brain Oxygen Supply in Older Adults During Coronary Artery Bypass Grafting.

OBJECTIVES: To evaluate the dynamics of the cerebral oxygen supply in patients aged ≥65 years, during coronary artery bypass grafting (CABG), and to test the hypothesis that lower intraoperative brain oxygen saturation is associated with postoperative neurological complications. DESIGN: Prospective cohort study. SETTING: The E. Meshalkin National Medical Research Center of the Ministry of Health of the Russian Federation, Novosibirsk, Russia. PARTICIPANTS: The study comprised 200 elderly patients who underwent CABG between April, 2018 and November, 2019. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The regional hemoglobin oxygen saturation (rSO2, %) of the right and left brain hemispheres were assessed during the intraoperative period using bilateral near-infrared spectroscopy. Furthermore, neurological complications during hospitalization were evaluated. At the anesthesia induction stage, the average levels of rSO2 for the right and left hemispheres were within 65% and did not differ significantly at any stage of CABG (p>0.05). The risk of neurological complications was associated with rSO2 decrease during cardiopulmonary bypass (CPB). An increased risk was associated with rSO2 decrease by 20% or more during CPB, relative to the stage of anesthesia induction, which was observed in 19% of patients. CONCLUSIONS: In elderly patients, the decrease in rSO2 during CPB is associated with an increased risk of neurological complications during hospitalization. This risk increases with a decrease in rSO2 by 20% or more during CPB relative to the stage of anesthesia induction, by a 5-fold and 7-fold for the left and right hemispheres, respectively.

Calcium Administration During Weaning From Cardiopulmonary Bypass: A Narrative Literature Review.

The search for safe and effective patient management strategies during weaning from cardiopulmonary bypass is ongoing; intravenous calcium is occasionally used as a first-line drug. The physiologic role of calcium suggests that it can support the function of the cardiovascular system during this critical period. Patients may be mildly hypocalcemic after cardiopulmonary bypass; however, this degree of hypocalcemia does not significantly impair the cardiovascular system. The transient beneficial effects of calcium administration (increase in arterial blood pressure, systemic vascular resistance, cardiac index, stroke volume, and coronary perfusion pressure) might be helpful in cases of moderate contractility reduction or vasoplegia. Nonetheless, effects on clinically relevant endpoints are unknown, and possible systemic side effects, such as transient reduction in internal mammary artery graft flow, attenuation of the effects of ß-sympathomimetics, "stone heart" phenomenon, and pancreatic cellular injury, may limit the use of calcium salts. Further studies are needed to expand the understanding of the effects of calcium administration on patient outcomes.

Current Practice of Calcium Use During Cardiopulmonary Bypass Weaning: Results of an International Survey.

OBJECTIVES: To describe international practices on the use of calcium salts during cardiopulmonary bypass (CPB) weaning in adult cardiac surgery patients. DESIGN: Multiple-choice survey on current practice of CPB weaning. SETTING: Online survey using the SurveyMonkey platform. PARTICIPANTS: Departments of cardiac anesthesiology worldwide. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Out of 112 surveys sent, 100 centers from 32 countries replied. The majority of centers (88 of 100 = 88%) administer calcium salts intraoperatively: 71 of 100 (71%) are using these drugs for CPB weaning and 78 of 100 (78%) for correction of hypocalcemia. Among the 88 centers that use calcium salts intraoperatively, 66% (58 of 88) of respondents use calcium chloride, 22% (19 of 88) use calcium gluconate, and 12% (11 of 88) use both drugs. Calcium salts are routinely used during normal (47 of 71 centers = 66%) and difficult (59 of 71 centers = 83%) weaning from CPB. Doses of 5 to 15 mg/kg during termination of CPB were used by 55 of 71 centers (77%) either by bolus (39 of 71, 55%) or over a time period longer than 1 minute (32 of 71 = 45%). Norepinephrine is the most commonly used first line vasopressor or inotropic agent used to support hemodynamics during termination of CPB in 32 out of 100 centers (32%), and calcium is the second one, used by 23 out of 100 centers (23%). CONCLUSION: This survey demonstrates that the majority of cardiac centers use calcium in adult patients undergoing cardiac surgery, especially during weaning from CPB. There is variability on the type of drug, dose, and modality of drug administration.

Sustained High-dose Thiamine Supplementation in High-risk Cardiac Patients Undergoing Cardiopulmonary Bypass: A Pilot Feasibility Study (The APPLY trial).

OBJECTIVE: To test the feasibility and investigate possible cardiovascular effects of a sustained high-dose intravenous thiamine protocol in patients undergoing combined valvular and coronary artery bypass graft surgery. DESIGN: Randomized, placebo-controlled, pilot feasibility trial. SETTING: Cardiac surgery department of a tertiary hospital. PARTICIPANTS: Forty patients undergoing combined valvular and coronary artery bypass surgery. INTERVENTIONS: Intravenous thiamine (600 mg on the day of surgery, and 400 mg/day on postoperative days 1, 2, and 3) or placebo. MEASUREMENTS AND MAIN RESULTS: The primary feasibility endpoints were recruitment rate and protocol compliance. Secondary endpoints included markers of possible biological and physiological effects. The mean recruitment rate was 8 patients per month and protocol compliance was 97.5%. There were no differences in median peak postoperative lactate (2.7 mmol/L [interquartile range [IQR] 1.4-4.6] for thiamine v 2.5 mmol/L [IQR 1.4-3.6] for placebo; p = 0.53), median peak postoperative creatinine (104 µmol/L [IQR 92.5-129] for thiamine v 99 µmol/L [IQR 86.5-109.5] for placebo; p = 0.53), median nadir postoperative cardiac index (1.8 L/min/m2 [IQR 1.5-2.1] for thiamine v 2.2 L/min/m2 [IQR 1.5-2.5] for placebo; p = 0.25), or the number of patients on vasopressor/inotropic agents (thiamine, 12 [63%]; placebo, 12 [60%]; p = 0.80), or in the total inotrope/vasopressor dose 0.14 µg/kg for thiamine v 0.12 µg/kg for placebo; p = 0.88). CONCLUSIONS: A double-blind trial of sustained high-dose intravenous thiamine supplementation in higher-risk cardiac surgery patients was feasible and appeared to be safe. However, such treatment did not demonstrate evidence of biological or physiological effects.

Effect of Intraoperative Dexamethasone on Major Complications and Mortality Among Infants Undergoing Cardiac Surgery: The DECISION Randomized Clinical Trial.

Importance: Corticosteroids are widely used in pediatric cardiac surgery to blunt systemic inflammatory response and to reduce complications; nevertheless, their clinical efficacy is uncertain. Objective: To determine whether intraoperative administration of dexamethasone is more effective than placebo for reducing major complications and mortality during pediatric cardiac surgery. Design, Setting, and Participants: The Intraoperative Dexamethasone in Pediatric Cardiac Surgery was an investigator-initiated, double-blind, multicenter randomized trial that involved 4 centers in China, Brazil, and Russia. A total of 394 infants younger than 12 months, undergoing cardiac surgery with cardiopulmonary bypass were enrolled from December 2015 to October 2018, with follow-up completed in November 2018. Interventions: The dexamethasone group (n = 194) received 1 mg/kg of dexamethasone; the control group (n = 200) received an equivolume of 0.9% sodium chloride intravenously after anesthesia induction. Main Outcomes and Measures: The primary end point was a composite of death, nonfatal myocardial infarction, need for extracorporeal membrane oxygenation, need for cardiopulmonary resuscitation, acute kidney injury, prolonged mechanical ventilation, or neurological complications within 30 days after surgery. There were 17 secondary end points, including the individual components of the primary end point, and duration of mechanical ventilation, inotropic index, intensive care unit stay, readmission to intensive care unit, and length of hospitalization. Results: All of the 394 patients randomized (median age, 6 months; 47.2% boys) completed the trial. The primary end point occurred in 74 patients (38.1%) in the dexamethasone group vs 91 patients (45.5%) in the control group (absolute risk reduction, 7.4%; 95% CI, -0.8% to 15.3%; hazard ratio, 0.82; 95% CI, 0.60 to 1.10; P = .20). Of the 17 prespecified secondary end points, none showed a statistically significant difference between groups. Infections occurred in 4 patients (2.0%) in the dexamethasone group vs 3 patients (1.5%) in the control group. Conclusions and Relevance: Among infants younger than 12 months undergoing cardiac surgery with cardiopulmonary bypass, intraoperative administration of dexamethasone, compared with placebo, did not significantly reduce major complications and mortality at 30 days. However, the study may have been underpowered to detect a clinically important difference. Trial Registration: ClinicalTrials.gov Identifier: NCT02615262.

Chronic Lung Disease and Mortality after Cardiac Surgery: A Prospective Cohort Study.

OBJECTIVE: To investigate the 1-year survival in cardiac surgical patients with lung disease, including previously undiagnosed cases. DESIGN: Prospective cohort study. SETTING: Tertiary hospital. PARTICIPANTS: Patients scheduled for elective coronary artery bypass graft (CABG) surgery. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Pulmonary function tests (PFTs) were performed in 454 patients before surgery. Abnormal respiratory patterns were defined as follows: obstructive (forced expiratory volume in 1 second/forced vital capacity <0.70), restrictive (forced expiratory volume in 1 second/forced vital capacity ≥0.70 and forced vital capacity <80% of predicted), and mixed. Overall 1-year mortality was 3.3%. Among 31 patients with documented chronic obstructive pulmonary disease (COPD), mortality was 9.6%, hazard ratio (HR) 1.28, 95% confidence interval (CI) 1.02-12.80, p = 0.04. Of 423 patients without history of COPD, 57 obstructive, 46 restrictive, and 4 mixed abnormal patterns were identified. Of a total of 72 with obstructive lung disease confirmed by PFT (ie, 15 of COPD patients and 57 newly identified cases), 6.9% died, HR 2.75, 95% CI 0.98-8.07, p = 0.06. When combined with cases of COPD where a respiratory abnormality was confirmed (26 patients), newly diagnosed obstructive lung disease (57 patients) was significantly associated with 1-year mortality, HR 4.13, 95% CI 1.50-11.42, p = 0.006. The adjustment for EuroSCORE II did not change the results. CONCLUSIONS: Combination of confirmed preexisting lung disease and newly diagnosed cases provides a clear link to mid-term mortality.

Prevalence and Implications of Abnormal Respiratory Patterns in Cardiac Surgery: A Prospective Cohort Study.

OBJECTIVE: To investigate the prevalence and impact of abnormal respiratory patterns in cardiac surgery patients. DESIGN: Prospective cohort study. SETTING: Tertiary hospital. PARTICIPANTS: Patients scheduled for elective coronary artery bypass graft surgery. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Pulmonary function tests were performed in 454 patients before surgery. Abnormal respiratory patterns were defined as follows: obstructive (forced expiratory volume in 1 s [FEV1]/forced vital capacity [FVC]<0.70), restrictive (FEV1/FVC≥0.70 and FVC<80% of predicted), and mixed (FEV1/FVC<0.70 and both FEV1 and FVC<80% of predicted). Of the 31 patients with a history of chronic obstructive pulmonary disease, no abnormal respiratory pattern was confirmed in 5. Of the 423 patients without a history of lung disease, the authors newly identified 57 obstructive, 46 restrictive, and 4 mixed patterns. Therefore, lung disease was reclassified in 24.7% of cases. Independent predictors of obstructive pattern were age, male sex, history of smoking, and chronic obstructive pulmonary disease. Obstructive lung disease was associated with 16 hours or longer ventilation. A reduced FEV1 was associated with a likelihood of atrial fibrillation (1-L decrement, odds ratio: 1.38, 95% confidence interval: 1.01-to-1.90, p = 0.04) and hospitalization time (regression coefficient: 1.23, 95% confidence interval: 0.54-to-1.91, p<0.001). CONCLUSIONS: Abnormal respiratory patterns are common and often underdiagnosed in the cardiac surgery setting. Pulmonary function tests help reveal patients at risk of complications and may provide an opportunity for intervention.

Minimally invasive mitral valve repair and ablation of concomitant atrial fibrillation in a patient with severe hemophilia A.

Minimally invasive mitral valve repair and ablation of atrial fibrillation, combined with FVIII level-controlled replacement therapy, can be safely performed in patients with severe hemophilia.

Common Inflammatory Mechanisms in COVID-19 and Parkinson's Diseases: The Role of Microbiome, Pharmabiotics and Postbiotics in Their Prevention.

In the last decade, metagenomic studies have shown the key role of the gut microbiome in maintaining immune and neuroendocrine systems. Malfunction of the gut microbiome can induce inflammatory processes, oxidative stress, and cytokine storm. Dysfunction of the gut microbiome can be caused by short-term (virus infection and other infectious diseases) or long-term (environment, nutrition, and stress) factors. Here, we reviewed the inflammation and oxidative stress in neurodegenerative diseases and coronavirus infection (COVID-19). Here, we reviewed the renin-angiotensin-aldosterone system (RAAS) involved in the processes of formation of oxidative stress and inflammation in viral and neurodegenerative diseases. Moreover, the coronavirus uses ACE2 receptors of the RAAS to penetrate human cells. The coronavirus infection can be the trigger for neurodegenerative diseases by dysfunction of the RAAS. Pharmabiotics, postbiotics, and next-generation probiotics, are considered as a means to prevent oxidative stress, inflammatory processes, neurodegenerative and viral diseases through gut microbiome regulation.

Calcium administration In patients undergoing CardiAc suRgery under cardiopulmonary bypasS (ICARUS trial): Rationale and design of a randomized controlled trial.

INTRODUCTION: Weaning from cardiopulmonary bypass (CPB) is a critical step of any cardiac surgical procedure and often requires pharmacologic intervention. Calcium ions are pivotal elements for the excitation-contraction coupling process of cardiac myocytes. Thus, calcium administration might be helpful during weaning from CPB. METHODS: We describe a multicenter, placebo-controlled, double blind randomized clinical trial to assess the effect of calcium chloride on the need for inotropic support among adult patients during weaning from CPB. The experimental group (409 patients) will receive 15 mg/kg of calcium chloride. The control group (409 patients) will receive an equivalent volume of 0.9% sodium chloride. Both drugs will be administered intravenously as a bolus at the beginning of weaning from CPB. RESULTS: The primary outcome will be the need for inotropic support between termination of CPB and completion of surgery. Secondary outcomes will be: duration of inotropic support, vasoactive-inotropic score 30 min after transfer to intensive care unit and on postoperative day 1, plasma alpha-amylase on postoperative day 1, plasma Ca2+ concentration immediately before and 10-15 min after calcium chloride administration, non-fatal myocardial infarction, blood loss on postoperative day 1, need for transfusion of red blood cells, signs of myocardial ischemia on electrocardiogram after arrival to intensive care unit, all-cause mortality at 30 days or during hospital stay if this is longer than 30 days. DISCUSSION: This trial is designed to assess whether intravenous calcium chloride administration could reduce the need for inotropic support after cardiopulmonary bypass weaning among adults undergoing cardiac surgery.

Standard vs. Calorie-Dense Immune Nutrition in Haemodynamically Compromised Cardiac Patients: A Prospective Randomized Controlled Pilot Study.

BACKGROUND: The aim of study was to test the hypothesis that early enteral nutrition (EN) with calorie-dense and protein rich enteral formula improves enteral energy and protein delivery in critically ill cardiac patients. METHODS: Prospective randomized pilot study of 40 ventilated adult patients undergoing elective cardiac surgery with use of cardiopulmonary bypass receiving inotropic support postoperatively. Patients were to receive either standard isocaloric (1000 Kcal/L and 38 g/L protein) early EN (n = 20) or calorie-dense and protein-rich (1300 Kcal/L and 66.7 g/L protein) early EN (n = 20). RESULTS: The mean time to EN initiation was 27 ± 11 h. Early EN with the calorie-dense formula provided significantly more energy and protein enteral delivery on the 2nd, (p < 0.0001), 5th (p = 0.036), and 7th days (p = 0.024), and was associated with higher levels of prealbumin concentration on the 14th day (0.13 ± 0.01 g/L and 0.21 ± 0.1 g/L; p = 0.04) and significantly increased levels of transferrin on the 3rd, 5th, and 7th day (p < 0.05) after surgery. CONCLUSION: Present findings support hypothesis that early EN using a calorie-dense and protein rich formula leads to better enteral energy and protein delivery and higher levels of short-lived serum proteins.

MortalitY in caRdIAc surgery (MYRIAD): A randomizeD controlled trial of volatile anesthetics. Rationale and design.

OBJECTIVE: There is initial evidence that the use of volatile anesthetics can reduce the postoperative release of cardiac troponin I, the need for inotropic support, and the number of patients requiring prolonged hospitalization following coronary artery bypass graft (CABG) surgery. Nevertheless, small randomized controlled trials have failed to demonstrate a survival advantage. Thus, whether volatile anesthetics improve the postoperative outcome of cardiac surgical patients remains uncertain. An adequately powered randomized controlled trial appears desirable. DESIGN: Single blinded, international, multicenter randomized controlled trial with 1:1 allocation ratio. SETTING: Tertiary and University hospitals. INTERVENTIONS: Patients (n=10,600) undergoing coronary artery bypass graft will be randomized to receive either volatile anesthetic as part of the anesthetic plan, or total intravenous anesthesia. MEASUREMENTS AND MAIN RESULTS: The primary end point of the study will be one-year mortality (any cause). Secondary endpoints will be 30-day mortality; 30-day death or non-fatal myocardial infarction (composite endpoint); cardiac mortality at 30day and at one year; incidence of hospital re-admission during the one year follow-up period and duration of intensive care unit, and hospital stay. The sample size is based on the hypothesis that volatile anesthetics will reduce 1-year unadjusted mortality from 3% to 2%, using a two-sided alpha error of 0.05, and a power of 0.9. CONCLUSIONS: The trial will determine whether the simple intervention of adding a volatile anesthetic, an intervention that can be implemented by all anesthesiologists, can improve one-year survival in patients undergoing coronary artery bypass graft surgery.

Remote ischaemic preconditioning does not protect the heart in patients undergoing coronary artery bypass grafting.

Remote ischaemic preconditioning (RIPC) gained attention as a possibility to reduce myocardial injury after a subsequent sustained episode of myocardial ischaemia. This prospective randomized study was carried out to assess whether RIPC reduces myocardial injury in coronary artery bypass grafting patients. Eighty patients were assigned to remote preconditioning or control treatment. Ischaemic preconditioning was induced by three 5-min cycles of upper limb ischaemia and reperfusion after anaesthesia induction. Haemodynamic and markers of myocardial damage were analysed preoperatively and over 48 h postoperatively. The cardiac index was higher immediately after remote preconditioning in the main group. There were no differences in other haemodynamic, troponin I and creatine kinase-MB concentrations at any time point between groups. Thus, short-term remote preconditioning improves haemodynamics and does not reduce myocardial injury after coronary artery bypass surgery. Further study of high-risk patients may be needed to fully evaluate the clinical effect of RIPC.