Myocardial protection in cardiac surgery: a comprehensive review of current therapies and future cardioprotective strategies.

Cardiac surgery with cardiopulmonary bypass results in global myocardial ischemia-reperfusion injury, leading to significant postoperative morbidity and mortality. Although cardioplegia is the cornerstone of intraoperative cardioprotection, a number of additional strategies have been identified. The concept of preconditioning and postconditioning, despite its limited direct clinical application, provided an essential contribution to the understanding of myocardial injury and organ protection. Therefore, physicians can use different tools to limit perioperative myocardial injury. These include the choice of anesthetic agents, remote ischemic preconditioning, tight glycemic control, optimization of respiratory parameters during the aortic unclamping phase to limit reperfusion injury, appropriate choice of monitoring to optimize hemodynamic parameters and limit perioperative use of catecholamines, and early reintroduction of cardioprotective agents in the postoperative period. Appropriate management before, during, and after cardiopulmonary bypass will help to decrease myocardial damage. This review aimed to highlight the current advancements in cardioprotection and their potential applications during cardiac surgery.

Cefiderocol in Difficult-to-Treat Nf-GNB in ICU Settings.

BACKGROUND: The efficacy and safety of cefiderocol in ICU patients with difficult-to-treat resistance (DTR) non-fermenting Gram-negative bacteria (Nf-GNB) are not as well-established. Consequently, we conducted a cohort study to compare Cefiderocol with the Best Available Therapy (BAT) in ICU patients. METHODS: We included adult patients from 9 different ICUs, including a burn ICU unit, from 2019 to 2023 treated with Cefiderocol for DTR Nf-GNB isolated from the blood or lungs. We matched each patient at a 1:2 ratio based on the same DTR Nf-GBN isolated pathogen, and when possible, within the same type of ICU (burn unit or not). The primary endpoint of the study was the clinical cure at 15 days, with secondary endpoints including clinical cure at 30 days, relapse, and in-ICU mortality. For each outcome, adjusted odds ratios were estimated using bidirectional stepwise regression in a final model, which included 13 preselected confounders. RESULTS: We included 27 patients with cefiderocol, matched with 54 patients receiving the BAT. Four patients were not exactly matched on the type of ICU unit. Characteristics were comparable between groups, mostly male with a Charlson Comorbidity Index of 3 [1-5], and 28% had immunosuppression. Cefiderocol patients were most likely to have higher number of antibiotic lines. The main DTR Nf-GNB identified was Pseudomonas aeruginosa (81.5%), followed by Acinetobater baumanii (14.8%) and Stenotrophomonas maltophilia (3.7%). Pneumonia was the identified infection in 21 (78.8%) patients in the Cefiderocol group and in 51 (94.4%) patients in the BAT group (p = 0.054). Clinical cure at 15 and 30-day and the in-ICU mortality was comparable between groups, however relapse was higher in the cefiderocol group (8-29.6% vs. 4-7.4%;aOR 10.06[1.96;51.53]) CONCLUSION: Cefiderocol did not show an improvement in clinical cure or mortality rates compared to BAT in the treatment of DTR Nf-GNB, but it was associated with a higher relapse rate.

Oxygenation management during veno-arterial ECMO support for cardiogenic shock: a multicentric retrospective cohort study.

BACKGOUND: Hyperoxemia is common and associated with poor outcome during veno-arterial extracorporeal membrane oxygenation (VA ECMO) support for cardiogenic shock. However, little is known about practical daily management of oxygenation. Then, we aim to describe sweep gas oxygen fraction (FSO2), postoxygenator oxygen partial pressure (PPOSTO2), inspired oxygen fraction (FIO2), and right radial arterial oxygen partial pressure (PaO2) between day 1 and day 7 of peripheral VA ECMO support. We also aim to evaluate the association between oxygenation parameters and outcome. In this retrospective multicentric study, each participating center had to report data on the last 10 eligible patients for whom the ICU stay was terminated. Patients with extracorporeal cardiopulmonary resuscitation were excluded. Primary endpoint was individual mean FSO2 during the seven first days of ECMO support (FSO2 mean (day 1-7)). RESULTS: Between August 2019 and March 2022, 139 patients were enrolled in 14 ECMO centers in France, and one in Switzerland. Among them, the median value for FSO2 mean (day 1-7) was 70 [57; 79] % but varied according to center case volume. Compared to high volume centers, centers with less than 30 VA-ECMO runs per year were more likely to maintain FSO2 ≥ 70% (OR 5.04, CI 95% [1.39; 20.4], p = 0.017). Median value for right radial PaO2 mean (day 1-7) was 114 [92; 145] mmHg, and decreased from 125 [86; 207] mmHg at day 1, to 97 [81; 133] mmHg at day 3 (p < 0.01). Severe hyperoxemia (i.e. right radial PaO2 ≥ 300 mmHg) occurred in 16 patients (12%). PPOSTO2, a surrogate of the lower body oxygenation, was measured in only 39 patients (28%) among four centers. The median value of PPOSTO2 mean (day 1-7) value was 198 [169; 231] mmHg. By multivariate analysis, age (OR 1.07, CI95% [1.03-1.11], p < 0.001), FSO2 mean (day 1-3)(OR 1.03 [1.00-1.06], p = 0.039), and right radial PaO2 mean (day 1-3) (OR 1.03, CI95% [1.00-1.02], p = 0.023) were associated with in-ICU mortality. CONCLUSION: In a multicentric cohort of cardiogenic shock supported by VA ECMO, the median value for FSO2 mean (day 1-7) was 70 [57; 79] %. PPOSTO2 monitoring was infrequent and revealed significant hyperoxemia. Higher FSO2 mean (day 1-3) and right radial PaO2 mean (day 1-3) were independently associated with in-ICU mortality.

Comparison of mortality and outcomes of four respiratory viruses in the intensive care unit: a multicenter retrospective study.

This retrospective study aimed to compare the mortality and burden of respiratory syncytial virus (RSV group), SARS-CoV-2 (COVID-19 group), non-H1N1 (Seasonal influenza group) and H1N1 influenza (H1N1 group) in adult patients admitted to intensive care unit (ICU) with respiratory failure. A total of 807 patients were included. Mortality was compared between the four following groups: RSV, COVID-19, seasonal influenza, and H1N1 groups. Patients in the RSV group had significantly more comorbidities than the other patients. At admission, patients in the COVID-19 group were significantly less severe than the others according to the simplified acute physiology score-2 (SAPS-II) and sepsis-related organ failure assessment (SOFA) scores. Using competing risk regression, COVID-19 (sHR = 1.61; 95% CI 1.10; 2.36) and H1N1 (sHR = 1.87; 95% CI 1.20; 2.93) were associated with a statistically significant higher mortality while seasonal influenza was not (sHR = 0.93; 95% CI 0.65; 1.31), when compared to RSV. Despite occurring in more severe patients, RSV and seasonal influenza group appear to be associated with a more favorable outcome than COVID-19 and H1N1 groups.

Use of Aprotinin versus Tranexamic Acid in Cardiac Surgery Patients with High-Risk for Excessive Bleeding (APACHE) trial: a multicentre retrospective comparative non-randomized historical study.

OBJECTIVES: Following the reintroduction of aprotinin into the European market, the French Society of Cardiovascular and Thoracic Anaesthesiologists recommended its prophylactic use at half-dose for high-risk cardiac surgery patients. We examined whether the use of aprotinin instead of tranexamic acid could significantly reduce severe perioperative bleeding. METHODS: This multicentre, retrospective, historical study included cardiac surgery patients treated with aprotinin or tranexamic acid between December 2017 and September 2020. The primary efficacy end point was the severe or massive perioperative bleeding (class 3-4 of the universal definition of perioperative bleeding). The safety secondary end points included the occurrence of thromboembolic events and all-cause mortality within 30 days after surgery. RESULTS: Among the 693 patients included in the study, 347 received aprotinin and 346 took tranexamic acid. The percentage of patients with severe or massive bleeding was similar in the 2 groups (42.1% vs 43.6%, Adjusted odds ratio [ORadj] = 0.87, 95% confidence interval: 0.62-1.23, P = 0.44), as was the perioperative need for blood products (81.0% vs 83.2%, ORadj = 0.75, 95% confidence interval: 0.48-1.17, P = 0.20). However, the median (Interquartile range) 12 h postoperative blood loss was significantly lower in the aprotinin group (383 ml [241-625] vs 450 ml [290-730], P < 0.01). Compared to tranexamic acid, the intraoperative use of aprotinin was associated with increased risk for thromboembolic events (adjusted Hazard ratio 2.30 [95% Cl: 1.06-5.30]; P = 0.04). CONCLUSIONS: Given the modest reduction in blood loss at the expense of a significant increase in thromboembolic adverse events, aprotinin use in high-risk cardiac surgery patients should be based on a carefully considered benefit-risk assessment.

Prognostic value of capillary refill time in adult patients: a systematic review with meta-analysis.

PURPOSE: Acute circulatory failure leads to tissue hypoperfusion. Capillary refill time (CRT) has been widely studied, but its predictive value remains debated. We conducted a meta-analysis to assess the ability of CRT to predict death or adverse events in a context at risk or confirmed acute circulatory failure in adults. METHOD: MEDLINE, EMBASE, and Google scholar databases were screened for relevant studies. The pooled area under the ROC curve (AUC ROC), sensitivity, specificity, threshold, and diagnostic odds ratio using a random-effects model were determined. The primary analysis was the ability of abnormal CRT to predict death in patients with acute circulatory failure. Secondary analysis included the ability of CRT to predict death or adverse events in patients at risk or with confirmed acute circulatory failure, the comparison with lactate, and the identification of explanatory factors associated with better accuracy. RESULTS: A total of 60,656 patients in 23 studies were included. Concerning the primary analysis, the pooled AUC ROC of 13 studies was 0.66 (95%CI [0.59; 0.76]), and pooled sensitivity was 54% (95%CI [43; 64]). The pooled specificity was 72% (95%CI [55; 84]). The pooled diagnostic odds ratio was 3.4 (95%CI [1.4; 8.3]). Concerning the secondary analysis, the pooled AUC ROC of 23 studies was 0.69 (95%CI [0.65; 0.74]). The prognostic value of CRT compared to lactate was not significantly different. High-quality CRT was associated with a greater accuracy. CONCLUSION: CRT poorly predicted death and adverse events in patients at risk or established acute circulatory failure. Its accuracy is greater when high-quality CRT measurement is performed.

ESAIC focused guideline for the use of cardiac biomarkers in perioperative risk evaluation

In recent years, there has been increasing focus on the use of cardiac biomarkers in patients undergoing noncardiac surgery. The aim of this focused guideline was to provide updated guidance regarding the pre-, post- and combined pre-and postoperative use of cardiac troponin and B-type natriuretic peptides in adult patients undergoing noncardiac surgery. The guidelines were prepared using Grading of Recommendations Assessment Development and Evaluation (GRADE) methodology. This included the definition of critical outcomes, a systematic literature search, appraisal of certainty of evidence, evaluation of biomarker measurement in terms of the balance of desirable and undesirable effects including clinical outcomes, resource use, health inequality, stakeholder acceptance, and implementation. The panel differentiated between three different scopes of applications: cardiac biomarkers as prognostic factors, as tools for risk prediction, and for biomarker-enhanced management strategies. In a modified Delphi process, the task force defined 12 critical outcomes. The systematic literature search resulted in over 25,000 hits, of which 115 full-text articles formed the body of evidence for recommendations. The evidence appraisal indicated heterogeneity in the certainty of evidence across critical outcomes. Further, there was relevant gradient in the certainty of evidence across the three scopes of application. Recommendations were issued and if this was not possible due to limited evidence, clinical practice statements were produced. The ESAIC focused guidelines provide guidance on the perioperative use of cardiac troponin and B-type natriuretic peptides in patients undergoing noncardiac surgery, for three different scopes of application.

Lower Limb Ischemia in Surgical Femoral Veno-Arterial Extracorporeal Membrane Oxygenation.

OBJECTIVES: To analyze the incidence, clinical impact on survival, and risk factors of lower limb ischemia (LLI) of surgical peripheral femoral venoarterial extracorporeal membrane oxygenation (VA ECMO) in the current era. DESIGN: A retrospective analysis of the authors' institutional database of VA ECMO was performed. Patients were divided into 2 groups according to the occurrence of LLI. The primary endpoint was survival to hospital discharge. Risk factors of LLI were searched with multivariate analyses. SETTING: University hospital. PARTICIPANTS: Adult patients receiving peripheral VA ECMO for refractory cardiogenic shock and cardiac arrest. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: From January 2018 to December 2021, 188 patients (mean age: 52.0 ± 14.1 years; 63.8% male, 36.2% female) received peripheral VA ECMO. Male sex was more prevalent in the group without LLI (65.9% v 33.3%; p = 0.031). Twelve (6.4%) patients developed LLI during VA ECMO support (n = 6) or after VA ECMO removal (n = 6). Survival to hospital discharge was not statistically different between patients with and without LLI (50.0% v 48.3%; p = 0.571). Female sex patients were at increased risk for LLI (odds ratio 4.38, 95% CI 1.21-15.81; p = 0.024). CONCLUSIONS: Peripheral femoral VA ECMO through a surgical approach is associated with a low LLI rate, which does not increase the risk of in-hospital mortality. The female sex is an independent risk factor for LLI.

Overview of the current use of levosimendan in France: a prospective observational cohort study.

BACKGROUND: Following the results of randomized controlled trials on levosimendan, French health authorities requested an update of the current use and side-effects of this medication on a national scale. METHOD: The France-LEVO registry was a prospective observational cohort study reflecting the indications, dosing regimens, and side-effects of levosimendan, as well as patient outcomes over a year. RESULTS: The patients included (n = 602) represented 29.6% of the national yearly use of levosimendan in France. They were treated for cardiogenic shock (n = 250, 41.5%), decompensated heart failure (n = 127, 21.1%), cardiac surgery-related low cardiac output prophylaxis and/or treatment (n = 86, 14.3%), and weaning from veno-arterial extracorporeal membrane oxygenation (n = 82, 13.6%). They received 0.18 ± 0.07 µg/kg/min levosimendan over 26 ± 8 h. An initial bolus was administered in 45 patients (7.5%), 103 (17.1%) received repeated infusions, and 461 (76.6%) received inotropes and or vasoactive agents concomitantly. Hypotension was reported in 218 patients (36.2%), atrial fibrillation in 85 (14.1%), and serious adverse events in 17 (2.8%). 136 patients (22.6%) died in hospital, and 26 (4.3%) during the 90-day follow-up. CONCLUSIONS: We observed that levosimendan was used in accordance with recent recommendations by French physicians. Hypotension and atrial fibrillation remained the most frequent side-effects, while serious adverse event potentially attributable to levosimendan were infrequent. The results suggest that this medication was safe and potentially associated with some benefit in the population studied.

ESAIC focused guideline for the use of cardiac biomarkers in perioperative risk evaluation.

BACKGROUND: In recent years, there has been increasing focus on the use of cardiac biomarkers in patients undergoing noncardiac surgery. AIMS: The aim of this focused guideline was to provide updated guidance regarding the pre-, post- and combined pre-and postoperative use of cardiac troponin and B-type natriuretic peptides in adult patients undergoing noncardiac surgery. METHODS: The guidelines were prepared using Grading of Recommendations Assessment Development and Evaluation (GRADE) methodology. This included the definition of critical outcomes, a systematic literature search, appraisal of certainty of evidence, evaluation of biomarker measurement in terms of the balance of desirable and undesirable effects including clinical outcomes, resource use, health inequality, stakeholder acceptance, and implementation. The panel differentiated between three different scopes of applications: cardiac biomarkers as prognostic factors, as tools for risk prediction, and for biomarker-enhanced management strategies. RESULTS: In a modified Delphi process, the task force defined 12 critical outcomes. The systematic literature search resulted in over 25,000 hits, of which 115 full-text articles formed the body of evidence for recommendations. The evidence appraisal indicated heterogeneity in the certainty of evidence across critical outcomes. Further, there was relevant gradient in the certainty of evidence across the three scopes of application. Recommendations were issued and if this was not possible due to limited evidence, clinical practice statements were produced. CONCLUSION: The ESAIC focused guidelines provide guidance on the perioperative use of cardiac troponin and B-type natriuretic peptides in patients undergoing noncardiac surgery, for three different scopes of application.

Hemodynamic Effects of Awake Prone Positioning With COVID-19 Acute Respiratory Failure.

INTRODUCTION: Awake prone positioning (PP) reduces need for intubation for patients with COVID-19 with acute respiratory failure. We investigated the hemodynamic effects of awake PP in non-ventilated subjects with COVID-19 acute respiratory failure. METHODS: We conducted a single-center prospective cohort study. Adult hypoxemic subjects with COVID-19 not requiring invasive mechanical ventilation receiving at least one PP session were included. Hemodynamic assessment was done with transthoracic echocardiography before, during, and after a PP session. RESULTS: Twenty-six subjects were included. We observed a significant and reversible increase in cardiac index (CI) during PP compared to supine position (SP): 3.0 ± 0.8 L/min/m2 in PP, 2.5 ± 0.6 L/min/m2 before PP (SP1), and 2.6 ± 0.5 L/min/m2 after PP (SP2, P < .001). A significant improvement in right ventricular (RV) systolic function was also evidenced during PP: The RV fractional area change was 36 ± 10% in SP1, 46 ± 10% during PP, and 35 ± 8% in SP2 (P < .001). There was no significant difference in PaO2 /FIO2 and breathing frequency. CONCLUSION: CI and RV systolic function are improved by awake PP in non-ventilated subjects with COVID-19 with acute respiratory failure.

Comparison of landiolol and amiodarone for the treatment of new-onset atrial fibrillation after cardiac surgery (FAAC) trial: study protocol for a randomized controlled trial.

BACKGROUND: Postoperative atrial fibrillation (PoAF) after cardiac surgery has a high incidence of 30%, but its management is controversial. Two strategies are recommended without evidence of a superiority of one against the other: rate control with beta-blocker or rhythm control with amiodarone. Landiolol is a new-generation beta-blocker with fast onset and short half-life. One retrospective, single-center study compared landiolol to amiodarone for PoAF after cardiac surgery with a better hemodynamic stability and a higher rate of reduction to sinus rhythm with landiolol, justifying the need for a multicenter randomized controlled trial. Our aim is to compare landiolol to amiodarone in the setting of PoAF after cardiac surgery with the hypothesis of a higher rate of reduction to sinus rhythm with landiolol during the 48 h after the first episode of POAF. METHODS: The FAAC trial is a multicenter single-blind two parallel-arm randomized study, which planned to include 350 patients with a first episode of PoAF following cardiac surgery. The duration of the study is 2 years. The patients are randomized in two arms: a landiolol group and an amiodarone group. Randomization (Ennov Clinical®) is performed by the anesthesiologist in charge of the patient if PoAF is persistent for at least 30 min after correction of hypovolemia, dyskalemia, and absence of pericardial effusion on a transthoracic echocardiography done at bedside. Our hypothesis is an increase of the percentage of patients in sinus rhythm from 70 to 85% with landiolol in less than 48 h after onset of PoAF (alpha risk = 5%, power = 90%, bilateral test). DISCUSSION: The FAAC trial was approved by the Ethics Committee of EST III with approval number 19.05.08. The FAAC trial is the first randomized controlled trial comparing landiolol to amiodarone for PoAF after cardiac surgery. In case of higher rate of reduction with landiolol, this beta-blocker could be the drug of choice used in this context as to reduce the need for anticoagulant therapy and reduce the risk of complications of anticoagulant therapy for patients with a first episode of postoperative atrial fibrillation after cardiac surgery. TRIAL REGISTRATION: ClinicalTrials.gov NCT04223739. Registered on January 10, 2020.

Reliability and reproducibility of the DICART device to assess capillary refill time: a bench and in-silico study.

Capillary refill time (CRT) is an important indicator of peripheral perfusion with a strong prognostic value, but it is sensitive to environmental factors and numerous measurement methods are reported in the litterature. DiCARTECH has developed a device that assesses CRT. We sought to investigate the robustness of the device and the reproducibility of the algorithm in a bench and in-silico study. We used the video acquired from a previous clinical study on healthy volunteers. For the bench study, the measurement process was performed by a robotic system piloted by a computer that analyzed 250 times nine previously acquired videos. For the in-silico study, we used 222 videos to test the algorithm's robustness. We created 30 videos from each video with a large blind spot and used the "color jitter" function to create a hundred videos from each video. In the bench study, the coefficient of variation was 11% (95%CI: 9-13). The correlation with human-measured CRT was good (R2 = 0.91, P < 0.001). In the in-silico study, for the blind spotted video, the coefficient of variation was 13% (95%CI: 10-17). For the color-jitter modified video the coefficient of variation was 62% (95%CI: 55-70). We confirmed the ability of the DiCART™ II device to perform multiple measurements without mechanical or electronic dysfunction. The precision and reproducibility of the algorithm are compatible with the assessment of clinical small changes in CRT.