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.).

Two-months quality of life of COVID-19 invasively ventilated survivors; an Italian single-center study.

BACKGROUND: COVID-19 disease can lead to severe functional impairments after discharge. We assessed the quality of life of invasively ventilated COVID-19 ARDS survivors. METHODS: We carried out a prospective follow-up study of the patients admitted to the Intensive Care Units (ICUs) of a teaching hospital. Patients affected by COVID-19 ARDS who required invasive ventilation and were successfully discharged home were assessed through the telephone administration of validated tests. We explored survival, functional outcomes, return to work, quality of life, cognitive and psychological sequelae. The main variables of interest were the following: demographics, severity scores, laboratory values, comorbidities, schooling, working status, treatments received during ICU stay, complications, and psychological, cognitive, functional outcomes. RESULTS: Out of 116 consecutive invasively ventilated patients, overall survival was 65/116 (56%) with no death occurring after hospital discharge. Forty-two patients were already discharged home with a median follow-up time of 61 (51-71) days after ICU discharge and 39 of them accepted to be interviewed. Only one patient (1/39) experienced cognitive decline. The vast majority of patients reported no difficulty in walking (32/35:82%), self-care (33/39:85%), and usual activities (30/39:78%). All patients were either malnourished (15/39:38%) or at risk for malnutrition (24/39:62%). Exertional dyspnea was present in 20/39 (51%) patients. 19/39 (49%) reported alterations in senses of smell and/or taste either before or after hospitalization. CONCLUSIONS: Invasively ventilated COVID-19 ARDS survivors have an overall good recovery at a 2-months follow-up which is better than what was previously reported in non-COVID-19 ARDS patients.

Prevalence, Characteristics, Risk Factors, and Outcomes of Invasively Ventilated COVID-19 Patients with Acute Kidney Injury and Renal Replacement Therapy.

BACKGROUND: There is no information on acute kidney injury (AKI) and continuous renal replacement therapy (CRRT) among invasively ventilated coronavirus disease 2019 (COVID-19) patients in Western healthcare systems. OBJECTIVE: To study the prevalence, characteristics, risk factors and outcome of AKI and CRRT among invasively ventilated COVID-19 patients. METHODS: Observational study in a tertiary care hospital in Milan, Italy. RESULTS: Among 99 patients, 72 (75.0%) developed AKI and 17 (17.7%) received CRRT. Most of the patients developed stage 1 AKI (33 [45.8%]), while 15 (20.8%) developed stage 2 AKI and 24 (33.4%) a stage 3 AKI. Patients who developed AKI or needed CRRT at latest follow-up were older, and among CRRT treated patients a greater proportion had preexisting CKD. Hospital mortality was 38.9% for AKI and 52.9% for CRRT patients. CONCLUSIONS: Among invasively ventilated COVID-19 patients, AKI is very common and CRRT use is common. Both carry a high risk of in-hospital mortality.

Esmolol in Cardiac Surgery: A Randomized Controlled Trial.

OBJECTIVE: To assess whether the administration of the ultra-short-acting ß-blocker esmolol in cardiac surgery could have a cardioprotective effect that translates into improved postoperative outcomes. DESIGN: Single-center, double-blinded, parallel-group randomized controlled trial. SETTING: A tertiary care referral center. PARTICIPANTS: Patients undergoing elective cardiac surgery with preoperative evidence of left ventricular end-diastolic diameter >60 mm and/or left ventricular ejection fraction <50%. INTERVENTIONS: Patients were assigned randomly to receive either esmolol (1 mg/kg as a bolus before aortic cross-clamping and 2 mg/kg mixed in the cardioplegia solution) or placebo in a 1:1 allocation ratio. MEASUREMENTS AND MAIN RESULTS: The primary composite endpoint of prolonged intensive care unit stay and/or in-hospital mortality occurred in 36/98 patients (36%) in the placebo group versus 27/102 patients (27%) in the esmolol group (p = 0.13). In the esmolol group, a reduction in the maximum inotropic score during the first 24 postoperative hours was observed (10 [interquartile range 5-15] v 7 [interquartile range 5-10.5]; p = 0.04), as well as a trend toward a reduction in postoperative low-cardiac-output syndrome (13/98 v 6/102; p = 0.08) and the rate of hospital admission at one year (26/95 v 16/96; p = 0.08). A trend toward an increase in the number of patients with ejection fraction ≥60% at hospital discharge also was observed (4/95 v 11/92; p = 0.06). CONCLUSIONS: In the present trial, esmolol as a cardioplegia adjuvant enhanced postoperative cardiac performance but did not reduce a composite endpoint of prolonged intensive care unit stay and/or mortality.

Anesthesiologic Management of Patients Undergoing Cardiac Transapical Procedures: Which Challenges in the Modern Era?

OBJECTIVE: Patients undergoing transapical cardiac procedure are a minority of cardiac surgery patients but represent a challenge for cardiac anesthesiologists because they generally are older and have more comorbidities than do open heart cardiac surgery patients. The aims of this study were to describe the anesthetic experience with transapical procedures in a single high-volume center and to analyze the most critical aspects for anesthetic management. DESIGN: Retrospective study. SETTING: IRCCS San Raffaele Scientific Institute, Milan, Italy. PARTICIPANTS: All patients undergoing a cardiac transapical procedure from January 2009 to April 2018 were included in this case series. INTERVENTIONS: Patients were managed by a multidisciplinary heart team. The perioperative anesthetic approach and hemodynamic management were consistent and performed by a group of trained cardiac anesthesiologists. MEASUREMENTS AND MAIN RESULTS: The study population comprised 143 patients: 81 (57%) underwent an aortic valve procedure, 60 (42%) a mitral valve intervention, 1 patient underwent a procedure involving both the aortic and mitral valves, and 1 patient underwent correction of a congenital heart defect. A major intraoperative complication occurred in 5 (3.5%) patients, the procedure was not technically feasible because of unsuitable anatomy in 3 patients, and conversion to open heart surgery was needed in 2 patients. All patients were admitted to the intensive care unit. Intensive care unit stay was 1 (1-3) days, and hospital stay was 6 (5-8) days. Hospital survival was 94%. CONCLUSIONS: Patients undergoing transapical cardiac procedures are a minority of cardiac surgery patients, but represent a high-risk population. A patient-tailored anesthetic approach, in the context of the therapeutic strategy shared by the heart team, is crucial to improve outcomes.

Protamine and Heparin Interactions: A Narrative Review.

ABSTRACT: Protamine, first isolated from salmon fish sperm and now produced through recombinant biotechnology, is an antidote that neutralizes the anticoagulant properties of heparin. Protamine function is based on the capacity to dissociate the heparin-antithrombin III (AT III) complex (an important link that promotes blood fluidification by inhibiting coagulation), forming the inactive heparin-protamine complex. Protamine has itself dose-dependent anticoagulant properties: It interferes with coagulation factors and platelet function; it stimulates fibrinolysis; it can lead to thrombocytopenia and reduction in thrombin-related platelet aggregation; it decreases platelet response to thrombin receptor agonist in a dose-dependent manner. In this review, we will focus on protamine and its interaction with heparin. Notably, protamine is able to antagonize not only unfractionated heparin (UFH) but also low molecular weight heparins to various degrees. Protamine-allergic and anaphylactoid systemic reactions may affect up to 1 in 10 people and should be prevented and treated early.

Characteristics, treatment, outcomes and cause of death of invasively ventilated patients with COVID-19 ARDS in Milan, Italy.

OBJECTIVE: Describe characteristics, daily care and outcomes of patients with coronavirus disease 2019 (COVID-19) acute respiratory distress syndrome (ARDS). DESIGN: Case series of 73 patients. SETTING: Large tertiary hospital in Milan. PARTICIPANTS: Mechanically ventilated patients with confirmed COVID-19 admitted to the intensive care unit (ICU) between 20 February and 2 April 2020. MAIN OUTCOME MEASURES: Demographic and daily clinical data were collected to identify predictors of early mortality. RESULTS: Of the 73 patients included in the study, most were male (83.6%), the median age was 61 years (interquartile range [IQR], 54-69 years), and hypertension affected 52.9% of patients. Lymphocytopenia (median, 0.77 x 103 per mm3; IQR, 0.58-1.00 x 103 per mm3), hyperinflammation with C-reactive protein (median, 184.5 mg/dL; IQR, 108.2-269.1 mg/dL) and pro-coagulant status with D-dimer (median, 10.1 µg/m; IQR, 5.0-23.8 µg/m) were present. Median tidal volume was 6.7 mL/kg (IQR, 6.0-7.5 mL/kg), and median positive end-expiratory pressure was 12 cmH2O (IQR, 10-14 cmH2O). In the first 3 days, prone positioning (12-16 h) was used in 63.8% of patients and extracorporeal membrane oxygenation in five patients (6.8%). After a median follow-up of 19.0 days (IQR, 15.0-27.0 days), 17 patients (23.3%) had died, 23 (31.5%) had been discharged from the ICU, and 33 (45.2%) were receiving invasive mechanical ventilation in the ICU. Older age (odds ratio [OR], 1.12; 95% CI, 1.04-1.22; P = 0.004) and hypertension (OR, 6.15; 95% CI, 1.75-29.11; P = 0.009) were associated with mortality, while early improvement in arterial partial pressure of oxygen (PaO2) to fraction of inspired oxygen (FiO2) ratio was associated with being discharged alive from the ICU (P = 0.002 for interaction). CONCLUSIONS: Despite multiple advanced critical care interventions, COVID-19 ARDS was associated with prolonged ventilation and high short term mortality. Older age and pre-admission hypertension were key mortality risk factors. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT04318366.

Long-term outcome of perioperative low cardiac output syndrome in cardiac surgery: 1-year results of a multicenter randomized trial.

PURPOSE: Perioperative myocardial dysfunction occurs frequently in cardiac surgery, and is a risk factor for morbidity and mortality. Levosimendan has been suggested to reduce mortality of patients with perioperative myocardial dysfunction. However, long-term outcome data on its efficacy in cardiac surgery are lacking. MATERIALS AND METHODS: Cardiac surgery patients with perioperative myocardial dysfunction were randomized to levosimendan or placebo, in addition to standard inotropic care. One-year mortality data were collected. RESULTS: We randomized 506 patients (248 to levosimendan 258 to placebo). At 1-year follow-up, 41 patients (16.5%) died in the levosimendan group, while 47 (18.3%) died in the placebo group (absolute risk difference -1.8; 95% CI -8.4 to 4.9; P = .60). Female sex, history of chronic obstructive pulmonary disease, previous myocardial infarction, serum creatinine, hematocrit, mean arterial pressure, and duration of cardiopulmonary bypass were independently associated with 1-year mortality. CONCLUSIONS: Levosimendan administration does not improve 1-year survival in cardiac surgery patients with perioperative myocardial dysfunction. One-year mortality in these patients is 17%. Six predictive factors for long-term mortality were identified. STUDY REGISTRATION NUMBER: NCT00994825 (ClinicalTrials.gov).

Femoro-jugular cannulation in veno-venous extracorporeal membrane oxygenation PRO/CON.

Veno-venous (VV) extracorporeal membrane oxygenation (ECMO) is the most efficient technique for respiratory support. It is based on a patient adequate circulation and cardiac function and it is indicated for isolated lung failure after optimization of the ventilatory support and the medical treatment. We describe PRO and CONs of the Femoro-jugular (F>J) approach, as an ideal setting for patients which require high flow (>5 L/min), such as those with extreme hypoxemia and/or septic shock. This technique can be accomplished very quickly at the bedside also in an unstable patient.

Systolic anterior motion after mitral valve repair: a predictive computational model.

OBJECTIVES: Systolic anterior motion (SAM) can be an insidious complication after mitral repair. Predicting SAM represents a challenge, even for very experienced mitral valve surgeons. The goal of this pilot work was to illustrate for the first time, a computational software able to calculate and prevent SAM during mitral repair. METHODS: Using MATLAB graphical user interface, a clinical software to predict SAM, we tested the performances of the software on 136 patients with degenerative mitral valves undergoing repair with standard techniques. A combination of 6 key echocardiographic parameters was used to calculate the SAM risk score. The discriminative performance of the model was assessed by the area under the receiver-operating characteristic curve. The receiver-operating characteristic was used to divide patients into low, medium and high risk for SAM. Simulation of virtual mitral repair (posterior leaflet resection and mitral ring annuloplasty) was also tested to reduce the risk of SAM. RESULTS: The incidence of SAM was 8.1%; 73% were detected as high risk by the software. The area under the receiver-operating characteristic model discriminant performance was 0.87 (95% confidence interval: 0.78-0.95). Simulating a posterior leaflet resection with the leaflet length fixed at 15 mm, the estimated SAM risk was updated, and all patients were then classified at low risk. CONCLUSIONS: This software is the first computational model designed to predict SAM during mitral repair to show excellent discrimination. This software has the potential to predict SAM risk preoperatively and, after a virtual step-by-step mitral repair simulation, depending on the technique adopted, to always achieve a low-risk SAM profile.

Protein C zymogen in severe sepsis: a double-blinded, placebo-controlled, randomized study.

PURPOSE: To determine whether protein C zymogen (protein C concentrates or human protein C) improves clinically relevant outcomes in adult patients with severe sepsis and septic shock. METHODS: This is a randomized, double-blind, placebo-controlled, parallel-group trial that from September 2012 to June 2014 enrolled adult patients with severe sepsis or septic shock and high risk of death and of bleeding (e.g., APACHE II greater than 25, extracorporeal membrane oxygenation or disseminated intravascular coagulopathy). All patients completed their follow-up 90 days after randomization and data were analyzed according to the intention-to-treat principle. Follow-up was performed at 30 and 90 days after randomization. The primary endpoint was a composite outcome of prolonged intensive care unit (ICU) stay and/or 30-day mortality. Secondary endpoints included mortality. RESULTS: The study was stopped early in a situation of futility for the composite outcome of prolonged ICU stay and/or 30-day mortality that was 79 % (15 patients) in the protein C zymogen group and 67 % (12 patients) in the placebo group (p = 0.40) and for a concomitant safety issue: ICU mortality was 79 % (15 patients) in the protein C zymogen group vs 39 % (7 patients) in the placebo group (p = 0.020), and 30-day mortality was 68 vs 39 % (p = 0.072). CONCLUSION: Protein C zymogen did not improve clinically relevant outcomes in severe sepsis and septic shock adult patients. Given its high cost and the potential increase in mortality, the use of this drug in adult patients should be discouraged.

Methylene blue as a vasopressor: a meta-analysis of randomised trials.

OBJECTIVE: To evaluate the efficacy of methylene blue in raising mean arterial pressure in hypotensive patients. DESIGN: A meta-analysis of randomised controlled trials. DATA SOURCES: We searched BioMedCentral, PubMed, Embase and the Cochrane Central Register of clinical trials. DATA EXTRACTION: Inclusion criteria were random allocation to treatment and comparison of methylene blue versus any comparator. Exclusion criteria were duplicate publications, non-adult studies and no data on main outcomes. The primary end point was mean arterial blood pressure value 1 hour after the study drug administration; the secondary end points were mortality at the longest follow-up available, and cardiac index. DATA SYNTHESIS: Data from 174 patients in five randomised controlled studies were analysed. Mean arterial pressure rose in patients receiving methylene blue (weighted mean difference = 6.93 mmHg; 95% CI, 1.67 to 12.18; P for effect = 0.01; P for heterogeneity = 0.17; I2 = 41%). Only two studies reported the values of cardiac index with a non-statistically significant improvement in the methylene blue group (mean difference = 0.76 L/min/m2; 95% CI, ? 0.32 to 1.84; P for effect = 0.2). The overall mortality rate was 16% (14/88) among methylene blue treated patients and 23% (20/86) in the control group (odds ratio = 0.65; 95% CI, 0.21 to 2.08; P for effect = 0.5). CONCLUSIONS: Methylene blue increases arterial blood pressure and systemic vascular resistances in vasoplegic patients without a detrimental effect on survival.

Miniaturized cardiopulmonary bypass improves short-term outcome in cardiac surgery: a meta-analysis of randomized controlled studies.

OBJECTIVE: To investigate whether the use of miniaturized cardiopulmonary bypass translates into decreased morbidity and mortality in patients having cardiac surgery. METHODS: We independently conducted a systematic review and meta-analysis of data pooled from existing trials listed in PubMed and conference proceedings. Sixteen studies were identified, including 1619 patients having cardiac surgery. Inclusion criteria were random allocation to treatment and comparison of a miniaturized cardiopulmonary bypass system versus conventional cardiac surgery. Exclusion criteria were duplicate publications, nonhuman experimental studies, and no outcome data. The end points were the rate of neurologic and myocardial damage and the number of patients transfused. RESULTS: Miniaturized cardiopulmonary bypass was associated with significant reductions of neurologic damage (4/548 [0.7%] vs 19/555 [3.4%], odds ratio = 0.30 [0.12-0.73], P = .008), reduction in peak cardiac troponin (weighted mean difference = -0.15 ng/dL [-0.18, -0.11], P < .001), and in the number of transfused patients (55/552 [9.9%] vs 101/563 [17.9%], odds ratio = 0.42 [0.28-0.63], P < .001). No difference in mortality was noted (8/758 [1.0%] vs 14/771 [1.8%], odds ratio = 0.60 [0.26-1.39]). CONCLUSIONS: Miniaturized cardiopulmonary bypass has beneficial effects resulting in decreased transfusion rate and cardiac and neurologic damage.

Human protein C zymogen concentrate in patients with severe sepsis and multiple organ failure after adult cardiac surgery.

PURPOSE: To describe outcome and changes in clotting and inflammatory parameters in an uncontrolled case series of consecutive patients with severe sepsis who received protein C concentrate soon after cardiac surgery. METHODS: From January 2007 to January 2008 nine consecutive adult patients with severe sepsis or septic shock and two or more organ failure after cardiac surgery received protein C concentrate, 50 IU/kg as a bolus followed by continuous infusion of 3 IU/kg per hour for 72 h. RESULTS: The increase in protein C levels was accompanied by an early drop in interleukins and near-normalization of prothrombin time, activated partial thromboplastin time, antithrombin and thrombin-antithrombin complex levels (p < or = 0.03). No patient experienced drug-related side effects. Thirty-day mortality was 11% (1 patient) compared to the expected mortality of 68%. CONCLUSIONS: In this pilot, uncontrolled study of nine patients with sepsis-induced double organ failure following cardiac surgery, treatment with protein C concentrate was associated with significant improvement in clinical, inflammatory and clotting parameters, no bleeding and low 30-day mortality.

Bispectral index evaluation of the sedative effect of acupuncture in healthy volunteers.

OBJECTIVE: To evaluate the sedative effect of acupuncture in healthy volunteers by means of the BIS monitor. Secondary end-points were the evaluation of subjective sedative sensation induced by acupuncture and possible lasting of the sedative effect post needles removal. METHODS: We performed a cross-over, single-blinded study on 10 healthy volunteers to evaluate objective and subjective sedative effect of acupuncture compared to sham acupuncture. We recorded heart rate, pulse-oxymetry, BIS at baseline, during a 20-min. stimulation period, and for the following 20 minutes after needles removal. Besides, we asked volunteers to score their subjective state by VAS at baseline, after the stimulation period (20th minute) and 20 minutes after needles removal. RESULTS: BIS values were not significantly different between true and sham acupuncture. A suggestive but not statistically significant difference was evident in VAS score, with true- better than sham acupuncture. There was no difference in the incidence of sleep during the experimental phases, nor in the incidence of insomnia or somnolence in the following 24 hours. HR and SpO2 remained always in a normal range. CONCLUSIONS: The sedative effect of true acupuncture was not different from that of sham acupuncture in healthy volunteers. We suggest that acupuncture could have a mild sedative action that can be demonstrated only treating anxious patients and not calm volunteers. In our opinion, the low potency of this technique can be an advantage allowing acupuncture safe application in a wide range of settings.

The effect of concomitant radiofrequency ablation and surgical technique (repair versus replacement) on release of cardiac biomarkers during mitral valve surgery.

All patients undergoing heart surgery experience a certain amount of nonspecific myocardial injury documented by the release of cardiac biomarkers and associated with poor outcome. We investigated the role of unipolar radiofrequency ablation of atrial fibrillation on the release of cardiac biomarkers in 71 patients undergoing mitral valve surgery and concomitant left atrial ablation case-matched with 71 patients undergoing isolated mitral surgery. The study was powered to detect a 3 ng/mL difference. There was no difference between the 2 groups in terms of cardiac troponin I (10 +/- 5.3 versus 12 + 10.4 ng/mL; P = 0.7) or creatine kinase-MB (50 +/- 21.8 versus 57 +/- 62.0 ng/mL; P = 0.5) release. Postoperative peak cardiac troponin I levels had univariate associations with the duration of cardiopulmonary bypass (P = 0.002) and aortic cross-clamping (P = 0.001) and with the surgical technique (15 +/- 12 ng/mL for mitral valve replacement versus 9 +/- 4.8 for mitral valve repair; P = 0.0007) at univariate analysis. Mitral valve replacement was the only independent predictor of postoperative peak release of cardiac troponin I identified with multivariate analysis (P = 0.005). Radiofrequency ablation of atrial fibrillation does not significantly increase cardiac biomarker release compared with isolated mitral surgery; mitral valve repair is associated with less release of cardiac biomarkers compared with mitral valve replacement.