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.).

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.

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.

Endovascular treatment of chronic ilio-femoral vein obstruction with extension below the inguinal ligament in patients with post-thrombotic syndrome.

OBJECTIVE: This study aimed to evaluate postoperative outcomes of patients with chronic iliofemoral venous outflow obstruction and post-thrombotic syndrome (PTS) who underwent endovascular recanalization and stenting across the inguinal ligament. METHODS: All consecutive patients with chronic iliofemoral venous outflow obstruction and PTS were included in the analysis, from January 2018 and February 2022. Preoperative, intraoperative, and postoperative outcomes were assessed. Primary endpoints analyzed were major adverse events (MAEs) at 30 days and primary patency rate at 2 years of follow-up. Secondary endpoints assessed were secondary patency rate, target vessel revascularization, and clinical improvement evaluated with the Venous Clinical Severity Score (VCSS) classification, Villalta scale, and visual analog scale (VAS), respectively. RESULTS: A total of 63 patients (mean age, 48.1 ± 15.5 years; female, 61.9%) were evaluated. No intraoperative and 30-day postoperative complications were documented. The technical success rate was achieved at 100%. Overall, one in-stent occlusion and five in-stent restenosis were detected during follow-up. The primary patency rate was 93.7% (95% confidence interval [CI], 87.8%-99.9%) and 92.1% (95% CI, 85.6%-99%), at 1- and 2-year follow-up, respectively (Kaplan-Meier analysis). Target vessel revascularization was conducted in two cases, resulting in a secondary patency of 98.4% (95% CI, 95.4%-100%) at 2 years of follow-up. Stent fracture and/or migration were not observed during follow-up. A significant clinical improvement in the patient's quality of life was documented. The median improvement of VCSS and Villalta scores were 4 (interquartile range, 2-7; P = .001), and 3 (interquartile range, 1.5-5; P = .001) vs baseline at the last follow-up. Overall, pain reduction of 17 mm on the VAS scale was documented at 2 years of follow-up. At multivariate analysis, presence of trabeculation into the femoral vein and deep femoral vein (odds ratio, 1.89; 95% CI, 0.15-6.11; P = .043), and Villalta scale >15 points at admission (odds ratio, 1.89; 95% CI, 0.15-6.11; P = .043) were predictive for in-stent occlusion during the follow-up. CONCLUSIONS: The use of a dedicated venous stent across the inguinal ligament was safe and effective for the treatment of symptomatic iliofemoral venous disease with acceptable primary and secondary patency rates at 2 years of follow-up.

The Smokers Health Multiple ACtions (SMAC-1) Trial: Study Design and Results of the Baseline Round.

BACKGROUND: Lung cancer screening with low-dose helical computed tomography (LDCT) reduces mortality in high-risk subjects. Cigarette smoking is linked to up to 90% of lung cancer deaths. Even more so, it is a key risk factor for many other cancers and cardiovascular and pulmonary diseases. The Smokers health Multiple ACtions (SMAC-1) trial aimed to demonstrate the feasibility and effectiveness of an integrated program based on the early detection of smoking-related thoraco-cardiovascular diseases in high-risk subjects, combined with primary prevention. A new multi-component screening design was utilized to strengthen the framework on conventional lung cancer screening programs. We report here the study design and the results from our baseline round, focusing on oncological findings. METHODS: High-risk subjects were defined as being >55 years of age and active smokers or formers who had quit within 15 years (>30 pack/y). A PLCOm2012 threshold >2% was chosen. Subject outreach was streamlined through media campaign and general practitioners' engagement. Eligible subjects, upon written informed consent, underwent a psychology consultation, blood sample collection, self-evaluation questionnaire, spirometry, and LDCT scan. Blood samples were analyzed for pentraxin-3 protein levels, interleukins, microRNA, and circulating tumor cells. Cardiovascular risk assessment and coronary artery calcium (CAC) scoring were performed. Direct and indirect costs were analyzed focusing on the incremental cost-effectiveness ratio per quality-adjusted life years gained in different scenarios. Personalized screening time-intervals were determined using the "Maisonneuve risk re-calculation model", and a threshold <0.6% was chosen for the biennial round. RESULTS: In total, 3228 subjects were willing to be enrolled. Out of 1654 eligible subjects, 1112 participated. The mean age was 64 years (M/F 62/38%), with a mean PLCOm2012 of 5.6%. Former and active smokers represented 23% and 77% of the subjects, respectively. At least one nodule was identified in 348 subjects. LDCTs showed no clinically significant findings in 762 subjects (69%); thus, they were referred for annual/biennial LDCTs based on the Maisonneuve risk (mean value = 0.44%). Lung nodule active surveillance was indicated for 122 subjects (11%). Forty-four subjects with baseline suspicious nodules underwent a PET-FDG and twenty-seven a CT-guided lung biopsy. Finally, a total of 32 cancers were diagnosed, of which 30 were lung cancers (2.7%) and 2 were extrapulmonary cancers (malignant pleural mesothelioma and thymoma). Finally, 25 subjects underwent lung surgery (2.25%). Importantly, there were zero false positives and two false negatives with CT-guided biopsy, of which the patients were operated on with no stage shift. The final pathology included lung adenocarcinomas (69%), squamous cell carcinomas (10%), and others (21%). Pathological staging showed 14 stage I (47%) and 16 stage II-IV (53%) cancers. CONCLUSIONS: LDCTs continue to confirm their efficacy in safely detecting early-stage lung cancer in high-risk subjects, with a negligible risk of false-positive results. Re-calculating the risk of developing lung cancer after baseline LDCTs with the Maisonneuve model allows us to optimize time intervals to subsequent screening. The Smokers health Multiple ACtions (SMAC-1) trial offers solid support for policy assessments by policymakers. We trust that this will help in developing guidelines for the large-scale implementation of lung cancer screening, paving the way for better outcomes for lung cancer patients.

Effect of volatile anesthetics on myocardial infarction after coronary artery surgery: a post hoc analysis of a randomized trial

OBJECTIVE: To investigate the effect of volatile anesthetics on the rates of postoperative myocardial infarction (MI) and cardiac death after coronary artery bypass graft (CABG). DESIGN: A post hoc analysis of a randomized trial. SETTING: Cardiac surgical operating rooms. PARTICIPANTS: Patients undergoing elective, isolated CABG. INTERVENTIONS: Patients were randomized to receive a volatile anesthetic (desflurane, isoflurane, or sevoflurane) or total intravenous anesthesia (TIVA). The primary outcome was hemodynamically relevant MI (MI requiring high-dose inotropic support or prolonged intensive care unit stay) occurring within 48 hours from surgery. The secondary outcome was 1-year death due to cardiac causes. Measurements and main Results: A total of 5,400 patients were enrolled between April 2014 and September 2017 (2,709 patients randomized to the volatile anesthetics group and 2,691 to TIVA). The mean age was 62 ± 8.4 years, and the median baseline ejection fraction was 57% (50-67), without differences between the 2 groups. Patients in the volatile group had a lower incidence of MI with hemodynamic complications both in the per-protocol (14 of 2,530 [0.6%] v 27 of 2,501 [1.1%] in the TIVA group; p = 0.038) and as-treated analyses (16 of 2,708 [0.6%] v 29 of 2,617 [1.1%] in the TIVA group; p = 0.039), but not in the intention-to-treat analysis (17 of 2,663 [0.6%] v 28 of 2,667 [1.0%] in the TIVA group; p = 0.10). Overall, deaths due to cardiac causes were lower in the volatile group (23 of 2,685 [0.9%] v 40 of 2,668 [1.5%] than in the TIVA group; p = 0.03). CONCLUSIONS: An anesthetic regimen, including volatile agents, may be associated with a lower rate of postoperative MI with hemodynamic complication in patients undergoing CABG. Furthermore, it may reduce long-term cardiac mortality.

Volatile versus Total Intravenous Anesthesia for Coronary Artery Bypass Graft Surgery: Analysis of 1586 MYRIAD Trial Patients Managed with the Same Perioperative Protocol.

Background: This study investigated the influence of volatile anesthesia (VA) on major complications and mortality in patients undergoing coronary artery bypass graft surgery (CABG). Methods: This post-hoc analysis included 1586 patients from the MYRIAD trial managed using the same perioperative protocol at a single institution. Patients were randomized to receive either volatile anesthesia (sevoflurane, isoflurane, or desflurane) or total intravenous anesthesia (TIVA). The assessed study outcomes were the rate of complications, including: myocardial infarction, stroke, acute kidney injury, prolonged ventilation ( > 24 h), receipt of high-dose inotropic support (inotropic score > 10), and need for mechanical circulatory support. The duration of intensive care unit (ICU) stay, length of hospitalization, hospital readmission during follow-up, 30-days and 1-year mortality were also analyzed. Results: 1586 patients were enrolled between September 2014-September 2017 and randomly assigned to the volatile anesthesia group (n = 794) and the TIVA group (n = 792). The median patient age was 63 years, with a median ejection fraction of 60%. There were no significant differences in the rates of major complications, duration of ICU stay, and hospitalization between the groups. The median total dose of fentanyl was 12.0 mcg/kg in volatile group and 14.4 mcg/kg in TIVA group (p < 0.001). One-year mortality rates were 2.5% (n = 20) and 3.2% (n = 25) in the volatile and TIVA groups, respectively. Two patients were lost at the 30-day and 1-year follow-ups in the volatile group compared to four patients in TIVA group. Regression analysis showed that cardiopulmonary bypass (CPB) duration, fentanyl dose, and baseline serum creatinine level were associated with 30-days mortality, while ejection fraction was associated with 1-year mortality. Conclusions: The use of VA in patients undergoing CABG did not result in a reduction in major complications or mortality compared with TIVA. A higher dose of fentanyl was used in the TIVA group and was associated with an increase in the 30-days mortality. These findings warrant further investigation. Clinical Trial Registration: ClinicalTrials.gov (NCT02105610).

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.). (AU)

Nonsurgical Strategies to Reduce Mortality in Patients Undergoing Cardiac Surgery: An Updated Consensus Process

OBJECTIVE:A careful choice of perioperative care strategies is pivotal to improve survival in cardiac surgery. However, there is no general agreement or particular attention to which nonsurgical interventions can reduce mortality in this setting. The authors sought to address this issue with a consensus-based approach.DESIGN:A systematic review of the literature followed by a consensus-based voting process.SETTING:A web-based international consensus conference.PARTICIPANTS:More than 400 physicians from 52 countries participated in this web-based consensus conference.INTERVENTIONS:The authors identified all studies published in peer-reviewed journals that reported on interventions with a statistically significant effect on mortality in the setting of cardiac surgery through a systematic Medline/PubMed search and contacts with experts. These studies were discussed during a consensus meeting and those considered eligible for inclusion in this study were voted on by clinicians worldwide.MEASUREMENTS AND MAIN RESULTS:Eleven interventions finally were selected: 10 were shown to reduce mortality (aspirin, glycemic control, high-volume surgeons, prophylactic intra-aortic balloon pump, levosimendan, leuko-depleted red blood cells transfusion, noninvasive ventilation, tranexamic acid, vacuum-assisted closure, and volatile agents), whereas 1 (aprotinin) increased mortality. A significant difference in the percentages of agreement among different countries and a variable gap between agreement and clinical practice were found for most of the interventions.CONCLUSIONS:This updated consensus process identified 11 nonsurgical interventions with possible survival implications for patients undergoing cardiac surgery. This list of interventions may help cardiac anesthesiologists and intensivists worldwide in their daily clinical practice and can contribute to direct future research in the field.

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, whethervolatile 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.

Randomized evidence for reduction of perioperative mortality: an updated consensus process

Objective: Out of the 230 million patients undergoing major surgical procedure every year, morethan 1 million will die within 30 days. Thus, any nonsurgical interventions that help reduce perioperative mortality might save thousands of lives. We decided to update a previous consensus process to identify all the nonsurgical interventions, supported by randomized evidence, that may help reduce perioperative mortality. Design and Setting: A web-based international consensus conference. Participants: 500 hundred clinicians from 61 countries. Interventions: A systematic literature search was performed to identify published literature aboutnonsurgical interventions, supported by randomized evidence showing a statistically significant impact on mortality. Eligible papers were discussed by a Consensus Conference of experts. The interventions identified by the conference were then submitted to colleagues worldwide through aweb-based survey...