Contribution of electrical impedance tomography to personalize positive end-expiratory pressure under ECCO2R.

Extracorporeal Carbon Dioxide Removal (ECCO2R) is used in acute respiratory distress syndrome (ARDS) patients to facilitate lung-protective ventilatory strategies. Electrical Impedance Tomography (EIT) allows individual, non-invasive, real-time, bedside, radiation-free imaging of the lungs, providing global and regional dynamic lung analyses. To provide new insights for future ECCO2R research in ARDS, we propose a potential application of EIT to personalize End-Expiratory Pressure (PEEP) following each reduction in tidal volume (VT), as demonstrated in an illustrative case. A 72-year-old male with COVID-19 was admitted to the ICU for moderate ARDS. Monitoring with EIT was started to determine the optimal PEEP value (PEEPEIT), defined as the intersection of the collapse and overdistention curves, after each reduction in VT during ECCO2R. The identified PEEPEIT values were notably low (< 10 cmH2O). The decrease in VT associated with PEEPEIT levels resulted in improved lung compliance, reduced driving pressure and a more uniform ventilation pattern. Despite current Randomized Controlled Trials showing that ultra-protective ventilation with ECCO2R does not improve survival, the applicability of universal ultra-protective ventilation settings for all patients remains a subject of debate. Inappropriately set PEEP levels can lead to alveolar collapse or overdistension, potentially negating the benefits of VT reduction. EIT facilitates real-time monitoring of derecruitment associated with VT reduction, guiding physicians in determining the optimal PEEP value after each decrease in tidal volume. This original description of using EIT under ECCO2R to adjust PEEP at a level compromising between recruitability and overdistention could be a crucial element for future research on ECCO2R.

Albumin Infusion Reduces Fluid Loading for Postresuscitation Syndrome in a Pig Model of Refractory Cardiac Arrest Resuscitated With Venoarterial Extra Corporeal Membrane Oxygenation.

Hemodynamic instability in postresuscitation syndrome worsens survival and neurological outcomes. Venoarterial extracorporeal membrane oxygenation (VA ECMO) for refractory cardiac arrest might improve outcomes. Hemodynamical support under VA ECMO relies on norepinephrine and crystalloids. The present work aims to assess the effects of albumin (ALB) infusion in a swine model of ischemic refractory cardiac arrest implanted by VA ECMO. Cardiac arrest was performed in 18 pigs and VA ECMO was initiated after 30 minutes cardiopulmonary resuscitation (CPR). Pigs were randomly assigned to standard care (norepinephrine + crystalloids) versus ALB group (ALB + standard care). Hemodynamical assessments were performed over 6 hours. Severe hypoalbuminemia was observed in the control group and could be reversed with ALB infusion. Total crystalloid load was significantly reduced with ALB infusion (1,000 [1,000-2,278] ml vs. 17,000 [10,000-19,000] ml, ALB versus control group, respectively, p < 0.001). There was no significant impact with regard to lactate clearance (29.16% [12.5-39.32] and 10.09% [6.78-29.36] for control versus ALB groups, respectively, p = 0.185), sublingual capillary microvascular parameters, or cerebral near-infrared spectrometer (NIRS) values. Compared to standard care, ALB infusion was highly effective in reducing fluid loading in a porcine model of postresuscitation syndrome after refractory cardiac arrest treated with VA ECMO.

Predictors of acute ischemic cerebral lesions in immune-mediated thrombotic thrombocytopenic purpura and hemolytic uremic syndrome.

BACKGROUND: The immune form of thrombotic thrombocytopenic purpura (iTTP) and the hemolytic and uremic syndrome (HUS) are two major forms of thrombotic microangiopathy (TMA). Their treatment has been recently greatly improved. In this new era, both the prevalence and predictors of cerebral lesions occurring during the acute phase of these severe conditions remain poorly known. AIM: The prevalence and predictors of cerebral lesions appearing during the acute phase of iTTP and Shiga toxin-producing Escherichia coli-HUS or atypical HUS were evaluated in a prospective multicenter study. METHODS: Univariate analysis was performed to report the main differences between patients with iTTP and those with HUS or between patients with acute cerebral lesions and the others. Multivariable logistic regression analysis was used to identify the potential predictors of these lesions. RESULTS: Among 73 TMA cases (mean age 46.9 ± 16 years (range 21-87 years) with iTTP (n = 57) or HUS (n = 16), one-third presented with acute ischemic cerebral lesions on magnetic resonance imagery (MRI); two individuals also had hemorrhagic lesions. One in ten patients had acute ischemic lesions without any neurological symptom. The neurological manifestations did not differ between iTTP and HUS. In multivariable analysis, three factors predicted the occurrence of acute ischemic lesions on cerebral MRI: (1) the presence of old infarcts on cerebral MRI, (2) the level of blood pulse pressure, (3) the diagnosis of iTTP. CONCLUSION: At the acute phase of iTTP or HUS, both symptomatic and covert ischemic lesions are detected in one third of cases on MRI. Diagnosis of iTTP and the presence of old infarcts on MRI are associated with the occurrence of such acute lesions as well as increased blood pulse pressure, that may represent a potential target to further improve the therapeutic management of these conditions.

The medical treatment of cardiogenic shock.

Cardiogenic shock (CS) is a leading cause of mortality worldwide. CS presentation and management in the current era have been widely depicted in epidemiological studies. Its treatment is codified and relies on medical care and extracorporeal life support (ECLS) in the bridge to recovery, chronic mechanical device therapy, or transplantation. Recent improvements have changed the landscape of CS. The present analysis aims to review current medical treatments of CS in light of recent literature, including addressing excitation-contraction coupling and specific physiology on applied hemodynamics. Inotropism, vasopressor use, and immunomodulation are discussed as pre-clinical and clinical studies have focused on new therapeutic options to improve patient outcomes. Certain underlying conditions of CS, such as hypertrophic or Takotsubo cardiomyopathy, warrant specifically tailored management that will be overviewed in this review.

Association between vasoactive-inotropic score, morbidity and mortality after heart transplantation.

OBJECTIVES: The aim of this study was to evaluate the association between vasoactive-inotropic score (VIS), calculated in the 24 h after heart transplantation, and post-transplant mortality and morbidity. METHODS: This was an observational single-centre retrospective study. Patients admitted to surgical intensive care unit after transplantation, between January 2015 and December 2018, were reviewed consecutively. VISmax was calculated as dopamine+ dobutamine+ 100 × epinephrine + 100 × norepinephrine + 50 × levosimendan + 10 × milrinone (all in µg/kg/min) + 10 000 × vasopressin (units/kg/min), using the maximum dosing rates of vasoactive and inotropic medications in the 24 h after intensive care unit admission. The primary outcome was mortality at 1 year post-transplant. The secondary outcomes included length of stay, duration of mechanical ventilation and inotropic support and the occurrence of septic shock, ventilator-associated pneumonia, bloodstream infection or renal replacement therapy. RESULTS: A total of 151 patients underwent heart transplantation and admitted to intensive care unit. The median VISmax was 39.2 (interquartile range = 19.4-83.0). VISmax was independently associated with 1-year post-transplant mortality, as well as recipient age [hazard ratio (HR) = 1.004, P-value = 0.013], recipient gender (female to male: hazard ratio = 2.23, P-value = 0.047) and combined transplantation (hazard ratio = 2.85, P-value = 0.048). There was a significant association between VISmax and duration of mechanical ventilation (P-value < 0.001), length of stay (P-value = 0.002), duration of infused inotropes (P-value < 0.001), occurrence of bloodstream infections, septic shocks, ventilation-acquired pneumonia and renal replacement therapy. CONCLUSIONS: VISmax calculated during the first 24 h after postoperative intensive care unit admission in transplanted patients is independently associated with 1-year mortality. In addition, length of stay, duration of mechanical ventilation and infused inotropes increased with increasing VISmax.

Practical application of the French two-score heart allocation scheme: Insights from a high-volume heart transplantation centre.

BACKGROUND: In 2018, a cardiac allocation scheme based on an individual score considering the risk of death both on the waitlist and after heart transplantation was implemented in France. AIMS: To analyse the practical application of the pre- and post-transplant risk score in a French high-volume heart transplantation centre. METHODS: All consecutive adult patients listed for a first non-combined heart transplantation between 02 January 2018 and 30 June 2022 at our centre were included. Baseline characteristics of candidates and recipients were retrieved from the national CRISTAL registry. Both scores were calculated at listing and at transplant. RESULTS: Overall, 364 patients were included. During follow-up, 257 patients (70.6%) were transplanted, and 57 (15.6%) died or were removed from the waitlist. Post-transplant 3-month survival was 84.8%. Total bilirubin and natriuretic peptides had the most important weight in the pretransplant risk score. This score had a major impact on waitlist outcomes: quartile 1 was characterized by low access to heart transplantation (58.2%) and risk of death on the waitlist (9.9%) compared with quartile 4 (heart transplantation rate 74.1%, mortality on the waiting list>20%). According to the post-transplant risk score, a minimal number of candidates were considered ineligible for heart transplantation (<1%), but 12.4% were contraindicated to at least one donor category. The number of contraindicated donor categories had a significant impact on waitlist outcomes. Although adequately calibrated, the post-transplant score had a limited discrimination (area under the curve 0.65, 95% confidence interval 0.59-0.71). CONCLUSION: Our results highlight the major impact of pre- and post-transplantation risk scores on waitlist outcomes following the allocation scheme update.

Impact of the 2018 French two-score allocation scheme on the profile of heart transplantation candidates and recipients: Insights from a high-volume centre.

BACKGROUND: In 2018, a new cardiac allograft allocation scheme, based on an individual scoring system, considering the risk of death both on the waiting list and after heart transplantation, was implemented in France. AIM: To assess the impact of this new scheme on the profile of transplantation candidates and recipients. METHODS: In this single-centre retrospective study, we included consecutive patients listed and/or transplanted between 01 January 2012 and 30 September 2021 at La Pitié-Salpêtrière Hospital. Baseline characteristics of patients were retrieved from the national CRISTAL registry and were compared according to the type of allocation scheme (before or after 2018). RESULTS: A total of 1098 newly listed transplantation candidates and 855 transplant recipients were included. One-year mortality rates after listing and after transplantation were 12.4% and 20%, respectively. At listing, the proportion of candidates on inotropes significantly declined following the scheme update (26.3 versus 20.9%; P=0.038), reflecting a change in medical practice. At transplantation, recipients had worse kidney function (estimated glomerular filtration rate<60mL/min/1.73 m2: old scheme, 29.7%; new scheme, 46.4%; P<0.001) and were more likely to be on extracorporeal membrane oxygenation support (33.5% versus 28.1%; P=0.080) under the new scheme, reflecting the prioritization of more severe patients. Outcomes after transplantation were not significantly influenced by the allocation system. CONCLUSIONS: The implementation of the 2018 French allocation scheme had a limited impact on the profile of transplantation candidates, but selected more severe patients for transplantation without significant impact on outcomes after transplantation.

Measurement of airborne particle emission during surgical and percutaneous dilatational tracheostomy COVID-19 adapted procedures in a swine model: Experimental report and review of literature.

INTRODUCTION: Surgical tracheostomy (ST) and Percutaneous dilatational tracheostomy (PDT) are classified as high-risk aerosol-generating procedures and might lead to healthcare workers (HCW) infection. Albeit the COVID-19 strain slightly released since the vaccination era, preventing HCW from infection remains a major economical and medical concern. To date, there is no study monitoring particle emissions during ST and PDT in a clinical setting. The aim of this study was to monitor particle emissions during ST and PDT in a swine model. METHODS: A randomized animal study on swine model with induced acute respiratory distress syndrome (ARDS) was conducted. A dedicated room with controlled airflow was used to standardize the measurements obtained using an airborne optical particle counter. 6 ST and 6 PDT were performed in 12 pigs. Airborne particles (diameter of 0.5 to 3 µm) were continuously measured; video and audio data were recorded. The emission of particles was considered as significant if the number of particles increased beyond the normal variations of baseline particle contamination determinations in the room. These significant emissions were interpreted in the light of video and audio recordings. Duration of procedures, number of expiratory pauses, technical errors and adverse events were also analyzed. RESULTS: 10 procedures (5 ST and 5 PDT) were fully analyzable. There was no systematic aerosolization during procedures. However, in 1/5 ST and 4/5 PDT, minor leaks and some adverse events (cuff perforation in 1 ST and 1 PDT) occurred. Human factors were responsible for 1 aerosolization during 1 PDT procedure. ST duration was significantly shorter than PDT (8.6 ± 1.3 vs 15.6 ± 1.9 minutes) and required less expiratory pauses (1 vs 6.8 ± 1.2). CONCLUSIONS: COVID-19 adaptations allow preventing for major aerosol leaks for both ST and PDT, contributing to preserving healthcare workers during COVID-19 outbreak, but failed to achieve a perfectly airtight procedure. However, with COVID-19 adaptations, PDT required more expiratory pauses and more time than ST. Human factors and adverse events may lead to aerosolization and might be more frequent in PDT.

Time-Controlled Adaptive Ventilation Does Not Induce Hemodynamic Impairment in a Swine ARDS Model.

Background: The current standard of care during severe acute respiratory distress syndrome (ARDS) is based on low tidal volume (VT) ventilation, at 6 mL/kg of predicted body weight. The time-controlled adaptive ventilation (TCAV) is an alternative strategy, based on specific settings of the airway pressure release ventilation (APRV) mode. Briefly, TCAV reduces lung injury, including: (1) an improvement in alveolar recruitment and homogeneity; (2) reduction in alveolar and alveolar duct micro-strain and stress-risers. TCAV can result in higher intra-thoracic pressures and thus impair hemodynamics resulting from heart-lung interactions. The objective of our study was to compare hemodynamics between TCAV and conventional protective ventilation in a porcine ARDS model. Methods: In 10 pigs (63-73 kg), lung injury was induced by repeated bronchial saline lavages followed by 2 h of injurious ventilation. The animals were then randomized into two groups: (1) Conventional protective ventilation with a VT of 6 mL/kg and PEEP adjusted to a plateau pressure set between 28 and 30 cmH2O; (2) TCAV group with P-high set between 27 and 29 cmH2O, P-low at 0 cmH2O, T-low adjusted to terminate at 75% of the expiratory flow peak, and T-high at 3-4 s, with I:E > 6:1. Results: Both lung elastance and PaO2:FiO2 were consistent with severe ARDS after 2 h of injurious mechanical ventilation. There was no significant difference in systemic arterial blood pressure, pulmonary blood pressure or cardiac output between Conventional protective ventilation and TCAV. Levels of total PEEP were significantly higher in the TCAV group (p < 0.05). Driving pressure and lung elastance were significantly lower in the TCAV group (p < 0.05). Conclusion: No hemodynamic adverse events were observed in the TCAV group compared as to the standard protective ventilation group in this swine ARDS model, and TCAV appeared to be beneficial to the respiratory system.

Methylene Blue Reduces Fluid Loading and Norepinephrine Requirements for Post-Resuscitation Syndrome in a Pig Model of Refractory Cardiac Arrest Resuscitated with Veno-Arterial ECMO.

BACKGROUND: Refractory cardiac arrest management relies on extracorporeal cardiopulmonary resuscitation (ECPR), requiring the use of veno-arterial extracorporeal membrane oxygenation (VA-ECMO). Circulatory flow recovery can be associated with an ischemia-reperfusion injury, leading to vasoplegia and vasopressor requirement. The aim of this work was to evaluate the impact on hemodynamics of a methylene blue bolus infusion in a porcine model of ischemic refractory cardiac arrest. METHODS: Ischemic refractory cardiac arrest was induced in 20 pigs. After a low flow period of 30 min, VA-ECMO was initiated and the pigs were randomly assigned to the standard care group (norepinephrine + crystalloids) or methylene blue group (IV 2 mg·kg-1 bolus of methylene blue over 30 min + norepinephrine and crystalloids). Macrocirculatory parameters and lactate clearance were measured. Sublingual microcirculation was evaluated with sidestream dark field (SDF) imaging. The severity of the ischemic digestive lesions was assessed according to the histologic Chiu/Park scale. RESULTS: Eighteen pigs were included. The total crystalloid load (5000 (6000-8000) mL vs. 17,000 (10,000-19,000) mL, p = 0.007, methylene blue vs. standard care group) and catecholamine requirements (0.31 (0.14-0.44) µg·kg-1·min-1 vs. 2.32 (1.17-5.55) µg·kg-1·min-1, methylene blue vs. standard care group, p = 0.004) were significantly reduced in the methylene blue group. There were no significant between-group differences in lactate clearance, sublingual capillary microvascular parameters assessed by SDF or histologic Chiu/Park scale. CONCLUSIONS: In our refractory cardiac arrest porcine model treated with ECPR, methylene blue markedly reduced fluid loading and norepinephrine requirements in comparison to standard care during the first 6 h of VA-ECMO.

Impaired Pharmacokinetics of Amiodarone under Veno-Venous Extracorporeal Membrane Oxygenation: From Bench to Bedside.

BACKGROUND: Adjusting drug therapy under veno-venous extracorporeal membrane oxygenation (VV ECMO) is challenging. Although impaired pharmacokinetics (PK) under VV ECMO have been reported for sedative drugs and antibiotics, data about amiodarone are lacking. We evaluated the pharmacokinetics of amiodarone under VV ECMO both in vitro and in vivo. METHODS: In vitro: Amiodarone concentration decays were compared between closed-loop ECMO and control stirring containers over a 24 h period. In vivo: Potassium-induced cardiac arrest in 10 pigs with ARDS, assigned to either control or VV ECMO groups, was treated with 300 mg amiodarone injection under continuous cardiopulmonary resuscitation. Pharmacokinetic parameters Cmax, Tmax AUC and F were determined from both direct amiodarone plasma concentrations observation and non-linear mixed effects modeling estimation. RESULTS: An in vitro study revealed a rapid and significant decrease in amiodarone concentrations in the closed-loop ECMO circuitry whereas it remained stable in control experiment. In vivo study revealed a 32% decrease in the AUC and a significant 42% drop of Cmax in the VV ECMO group as compared to controls. No difference in Tmax was observed. VV ECMO significantly modified both central distribution volume and amiodarone clearance. Monte Carlo simulations predicted that a 600 mg bolus of amiodarone under VV ECMO would achieve the amiodarone bioavailability observed in the control group. CONCLUSIONS: This is the first study to report decreased amiodarone bioavailability under VV ECMO. Higher doses of amiodarone should be considered for effective amiodarone exposure under VV ECMO.

Beta-blockers in septic shock: What is new?

The use of beta(ß)-blockers during septic shock aimed at countering peripheral adrenergic stress may be justified by the early reduction in deleterious effects resulting from sympathetic overactivation, and could improve the prognosis of patients in septic shock. Animal studies have demonstrated either a maintenance or increase in cardiac output (CO) despite the decrease in heart rate (HR) associated with improved myocardial performance. The mechanism by which ß-blockers alter hemodynamics in septic shock is debated; however, preclinical and clinical data show that ß-blockers are safe when started at a low dose. Recent publications (2019-2021) on adrenergic ß1 receptor antagonists used in septic shock indicate that esmolol and landiolol should not be used in the early phase. While there is no optimal timing for their administration, a minimum of 12 h after the initiation of vasopressor therapy in stabilized euvolemic patients is a reasonable option. Patients should have a normal cardiac function, although a slight depression is compatible with landiolol use under hemodynamic monitoring. Slow titration in patients who remain tachycardic is preferable to rapid titration. When used to decrease HR, landiolol is also effective in reducing the incidence of new arrhythmias. Results of a well-performed and well-powered randomized controlled trial (RCT) demonstrating a positive effect on survival - or at least on hard surrogates such as the incidence/duration of organ failure - are pending.

Pulsatility in ventricular assistance devices: A translational review focused on applied haemodynamics.

Heart failure affects more than 30 million people worldwide and its prevalence is constantly rising. In 2020, heart transplantation is the only curative treatment, but left ventricular assistance devices (LVADs) are fully integrated into the decision algorithm for management of patients with advanced heart failure, with more than 20,000 devices implanted worldwide in the last decade. Intended to support cardiac output, LVADs remove the blood from the left ventricle and eject it into the proximal aorta. Whereas first-generation LVADs were pulsatile, second- and third-generation LVADs are more reliable, but create a laminar flow, with reduced (or absent) blood flow pulsatility. Concomitantly, several new adverse events, some of them lethal, appeared when continuous-flow LVADs started to be implanted, including acquired von Willebrand disease, gastrointestinal bleeding and aortic valve fusion or regurgitation. This review aims to apply models describing pulsatility (such as the Windkessel effect applied by Frank, Guyton's continuity model of venous return and Sunagawa's left ventricular-arterial coupling) to LVADs, to better understand the physiopathology in patients using continuous-flow devices. This review also covers the means of exploring pulsatility and adverse events associated with a reduction in pulsatility, as well as the possible ways for restoring pulsatility in patients implanted with an LVAD.