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Pulmonary arterial hypertension (PAH) is characterized by a progressive increase in pulmonary vascular resistance (PVR) due to vascular remodeling of the small pulmonary arteries. In advanced RV failure or severe hypoxemia, extra corporeal life support (ECLS) is now to be considered, with the objective to bridge patients back to their baseline clinical state while waiting or right after lung transplantation, or bridge to pharmacological optimization of PAH (i.e., bridge to recovery). We describe herein a case of a 30-year-old woman (gravida 6, para 6) with an incident case of heritable PAH revealed by refractory hypoxemia. Despite the use of mechanical ventilation and fluid optimization, the patient remained profoundly hypoxemic. ECLS was then initiated to avoid tissue hypoxia. The mechanical option chosen was peripheral femoro-femoral venoarterial extracorporeal membrane oxygen (VA-ECMO), percutaneously implanted. Due to the absence of evidence of chronic respiratory disease or chronic thromboembolic pulmonary hypertension, this severe pre-capillary pulmonary hypertension was attributed to PAH. Therefore, epoprostenol infusion and an association of oral treatments (bosentan and tadalafil) were administered. A dramatic improvement was observed, allowing decannulation 7 days after the initiation of pharmacological treatment. After 29 days, the patient was discharged from the hospital with epoprostenol, bosentan, and tadalafil. The assessment has been completed by positive research on mutations (c.741C > G, p.Tyr247) corresponding to a loss of function of the bone morphogenetic protein receptor 2 (BMPR2) gene. The final diagnosis was heritable PAH. The use of ECLS has been well demonstrated in patients with PAH complicated by acute RV failure or refractory hypoxemia in the “bridge-to-transplantation” strategy. Only a few reports have described the use of ECLS as a “bridge-to-recovery” with PAH drugs in untreated or undertreated PAH patients, but none has described such a rapid improvement with resolution of refractory hypoxemia. More studies are needed to assess the benefits and limitations of the “bridge-to-recovery” strategy and to identify the patients most likely to benefit from it.

Abstract Background COVID-19-associated acute respiratory distress syndrome (ARDS) supported by veno-venous extra-corporal membrane oxygenation (vv-ECMO) results in a high in-hospital mortality rate of more than 35%. However, after cannulation, no prognostic factor has been described to guide the management of these patients. The objective was to assess the association between static respiratory compliance over the first 10 days post-vv-ECMO implantation on 180-day mortality. Results In this multicentric retrospective study in three ECMO referral centers, all patients with COVID-19-associated ARDS supported by vv-ECMO were included from 03/01/2020 to 12/31/2021. Patients were ventilated with ultra-protective settings targeting a driving pressure lower than 15 cmH2O. 122 patients were included. Median age was 59 IQR (52–64), 83 (68%) were male, with a median body mass index of 33 (28–37) kg/m2. Delay between first symptoms to vv-ECMO implantation was 16 (10–21) days. Six-month death was 48%. Over the first ten days, compliance increased in 180 day survivors [from 18 (12–25) to 20 (15–27) mL/cmH2O] compared to non-survivors [from 12 (9–20) to 10 (8–14) mL/cmH2O, p interaction

The use of beta(β)-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 β-blockers alter hemodynamics in septic shock is debated; however, preclinical and clinical data show that β-blockers are safe when started at a low dose. Recent publications (2019–2021) on adrenergic β1 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.

BackgroundThe 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.MethodsIn 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.ResultsBoth 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).ConclusionNo 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.

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.

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.