Invasive mechanical ventilation in patients with acute respiratory distress syndrome receiving extracorporeal support: a narrative review of strategies to mitigate lung injury.

Veno-venous extracorporeal membrane oxygenation is indicated in patients with acute respiratory distress syndrome and severely impaired gas exchange despite evidence-based lung protective ventilation, prone positioning and other parts of the standard algorithm for treating such patients. Extracorporeal support can facilitate ultra-lung-protective ventilation, meaning even lower volumes and pressures than standard lung-protective ventilation, by directly removing carbon dioxide in patients needing injurious ventilator settings to maintain sufficient gas exchange. Injurious ventilation results in ventilator-induced lung injury, which is one of the main determinants of mortality in acute respiratory distress syndrome. Marked reductions in the intensity of ventilation to the lowest tolerable levels under extracorporeal support may be achieved and could thereby potentially mitigate ventilator-induced lung injury and theoretically patient self-inflicted lung injury in spontaneously breathing patients with high respiratory drive. However, the benefits of this strategy may be counterbalanced by the use of continuous deep sedation and even neuromuscular blocking drugs, which may impair physical rehabilitation and impact long-term outcomes. There are currently a lack of large-scale prospective data to inform optimal invasive ventilation practices and how to best apply a holistic approach to patients receiving veno-venous extracorporeal membrane oxygenation, while minimising ventilator-induced and patient self-inflicted lung injury. We aimed to review the literature relating to invasive ventilation strategies in patients with acute respiratory distress syndrome receiving extracorporeal support and discuss personalised ventilation approaches and the potential role of adjunctive therapies in facilitating lung protection.

Electric Cell-Substrate Impedance Sensing (ECIS) as a Platform for Evaluating Barrier-Function Susceptibility and Damage from Pulmonary Atelectrauma.

Biophysical insults that either reduce barrier function (COVID-19, smoke inhalation, aspiration, and inflammation) or increase mechanical stress (surfactant dysfunction) make the lung more susceptible to atelectrauma. We investigate the susceptibility and time-dependent disruption of barrier function associated with pulmonary atelectrauma of epithelial cells that occurs in acute respiratory distress syndrome (ARDS) and ventilator-induced lung injury (VILI). This in vitro study was performed using Electric Cell-substrate Impedance Sensing (ECIS) as a noninvasive evaluating technique for repetitive stress stimulus/response on monolayers of the human lung epithelial cell line NCI-H441. Atelectrauma was mimicked through recruitment/derecruitment (RD) of a semi-infinite air bubble to the fluid-occluded micro-channel. We show that a confluent monolayer with a high level of barrier function is nearly impervious to atelectrauma for hundreds of RD events. Nevertheless, barrier function is eventually diminished, and after a critical number of RD insults, the monolayer disintegrates exponentially. Confluent layers with lower initial barrier function are less resilient. These results indicate that the first line of defense from atelectrauma resides with intercellular binding. After disruption, the epithelial layer community protection is diminished and atelectrauma ensues. ECIS may provide a platform for identifying damaging stimuli, ventilation scenarios, or pharmaceuticals that can reduce susceptibility or enhance barrier-function recovery.

Validation of at-the-bedside formulae for estimating ventilator driving pressure during airway pressure release ventilation using computer simulation.

BACKGROUND: Airway pressure release ventilation (APRV) is widely available on mechanical ventilators and has been proposed as an early intervention to prevent lung injury or as a rescue therapy in the management of refractory hypoxemia. Driving pressure ([Formula: see text]) has been identified in numerous studies as a key indicator of ventilator-induced-lung-injury that needs to be carefully controlled. [Formula: see text] delivered by the ventilator in APRV is not directly measurable in dynamic conditions, and there is no "gold standard" method for its estimation. METHODS: We used a computational simulator matched to data from 90 patients with acute respiratory distress syndrome (ARDS) to evaluate the accuracy of three "at-the-bedside" methods for estimating ventilator [Formula: see text] during APRV. RESULTS: Levels of [Formula: see text] delivered by the ventilator in APRV were generally within safe limits, but in some cases exceeded levels specified by protective ventilation strategies. A formula based on estimating the intrinsic positive end expiratory pressure present at the end of the APRV release provided the most accurate estimates of [Formula: see text]. A second formula based on assuming that expiratory flow, volume and pressure decay mono-exponentially, and a third method that requires temporarily switching to volume-controlled ventilation, also provided accurate estimates of true [Formula: see text]. CONCLUSIONS: Levels of [Formula: see text] delivered by the ventilator during APRV can potentially exceed levels specified by standard protective ventilation strategies, highlighting the need for careful monitoring. Our results show that [Formula: see text] delivered by the ventilator during APRV can be accurately estimated at the bedside using simple formulae that are based on readily available measurements.

An Extracorporeal Membrane Oxygenation First Strategy in COVID-19 Acute Respiratory Distress Syndrome.

COVID-19 can be associated with acute respiratory distress syndrome, which increases the likelihood of morbidity and mortality. Ventilator-induced lung injury is a known complication of mechanical ventilation (MV) and can further compound lung injury and recovery. Escalation to extracorporeal membrane oxygenation can be required in patients who deteriorate on MV. We report our experience with complete avoidance of MV using an ECMO First strategy deployed in an awake nonintubated COVID-19 patient with severe pneumonia.

Targeted lateral positioning decreases lung collapse and overdistension in COVID-19-associated ARDS.

BACKGROUND: Among the challenges for personalizing the management of mechanically ventilated patients with coronavirus disease (COVID-19)-associated acute respiratory distress syndrome (ARDS) are the effects of different positive end-expiratory pressure (PEEP) levels and body positions in regional lung mechanics. Right-left lung aeration asymmetry and poorly recruitable lungs with increased recruitability with alternating body position between supine and prone have been reported. However, real-time effects of changing body position and PEEP on regional overdistension and collapse, in individual patients, remain largely unknown and not timely monitored. The aim of this study was to individualize PEEP and body positioning in order to reduce the mechanisms of ventilator-induced lung injury: collapse and overdistension. METHODS: We here report a series of five consecutive mechanically ventilated patients with COVID-19-associated ARDS in which sixteen decremental PEEP titrations were performed in the first days of mechanical ventilation (8 titration pairs: supine position immediately followed by 30° targeted lateral position). The choice of lateral tilt was based on X-Ray. This targeted lateral position strategy was defined by selecting the less aerated lung to be positioned up and the more aerated lung to be positioned down. For each PEEP level, global and regional collapse and overdistension maps and percentages were measured by electrical impedance tomography. Additionally, we present the incidence of lateral asymmetry in a cohort of forty-four patients. RESULTS: The targeted lateral position strategy resulted in significantly smaller amounts of overdistension and collapse when compared with the supine one: less collapse along the PEEP titration was found within the left lung in targeted lateral (P = 0.014); and less overdistension along the PEEP titration was found within the right lung in targeted lateral (P = 0.005). Regarding collapse within the right lung and overdistension within the left lung: no differences were found for position. In the cohort of forty-four patients, ventilation inequality of > 65/35% was observed in 15% of cases. CONCLUSIONS: Targeted lateral positioning with bedside personalized PEEP provided a selective attenuation of overdistension and collapse in mechanically ventilated patients with COVID-19-associated ARDS and right-left lung aeration/ventilation asymmetry. TRIAL REGISTRATION: Trial registration number: NCT04460859.

Challenges for the development of alternative low-cost ventilators during COVID-19 pandemic in Brazil. / Desafios para o desenvolvimento de ventiladores alternativos de baixo custo durante a pandemia de COVID-19 no Brasil.

The COVID-19 pandemic has brought concerns to managers, healthcare professionals, and the general population related to the potential mechanical ventilators' shortage for severely ill patients. In Brazil, there are several initiatives aimed at producing alternative ventilators to cover this gap. To assist the teams that work in these initiatives, we provide a discussion of some basic concepts on physiology and respiratory mechanics, commonly used mechanical ventilation terms, the differences between triggering and cycling, the basic ventilation modes and other relevant aspects, such as mechanisms of ventilator-induced lung injury, respiratory drive, airway heating and humidification, cross-contamination risks, and aerosol dissemination. After the prototype development phase, preclinical bench-tests and animal model trials are needed to determine the safety and performance of the ventilator, following the minimum technical requirements. Next, it is mandatory going through the regulatory procedures as required by the Brazilian Health Regulatory Agency (Agência Nacional de Vigilância Sanitária - ANVISA). The manufacturing company should be appropriately registered by ANVISA, which also must be notified about the conduction of clinical trials, following the research protocol approval by the Research Ethics Committee. The registration requisition of the ventilator with ANVISA should include a dossier containing the information described in this paper, which is not intended to cover all related matters but to provide guidance on the required procedures.

A pandemia por COVID-19 tem deixado os gestores, os profissionais de saúde e a população preocupados com a potencial escassez de ventiladores pulmonares para suporte de pacientes graves. No Brasil, há diversas iniciativas com o intuito de produzir ventiladores alternativos para ajudar a suprir essa demanda. Para auxiliar as equipes que atuam nessas iniciativas, são expostos alguns conceitos básicos sobre fisiologia e mecânica respiratória, os termos comumente utilizados no contexto da ventilação mecânica, as fases do ciclo ventilatório, as diferenças entre disparo e ciclagem, os modos ventilatórios básicos e outros aspectos relevantes, como mecanismos de lesão pulmonar induzida pela ventilação mecânica, pacientes com drive respiratório, necessidade de umidificação de vias aéreas, risco de contaminação cruzada e disseminação de aerossóis. Após a fase de desenvolvimento de protótipo, são necessários testes pré-clínicos de bancada e em modelos animais, a fim de determinar a segurança e o desempenho dos equipamentos, seguindo requisitos técnicos mínimos exigidos. Então, é imprescindível passar pelo processo regulatório exigido pela Agência Nacional de Vigilância Sanitária (ANVISA). A empresa responsável pela fabricação do equipamento deve estar regularizada junto à ANVISA, que também deve ser notificada da condução dos testes clínicos em humanos, seguindo protocolo de pesquisa aprovado pelo Comitê de Ética em Pesquisa. O registro do ventilador junto à ANVISA deve ser acompanhado de um dossiê, composto por documentos e informações detalhadas neste artigo, que não tem o propósito de esgotar o assunto, mas de nortear os procedimentos necessários.

Case Report of Patients with Acute Respiratory Distress Syndrome Caused by COVID-19: Successfully Treated by Venovenous Extracorporeal Membrane Oxygenation and an Ultra-Protective Ventilation.

Coronavirus disease (COVID-19) started in Wuhan (China) at the end of 2019, and then increased rapidly. In patients with severe acute respiratory distress syndrome (ARDS) caused by COVID-19, venovenous extracorporeal membrane oxygenation (VV-ECMO) is considered a rescue therapy that provides adequate gas exchange. The way in which mechanical ventilation is applied during VV-ECMO is not clear, however it is associated with prognosis. Currently, the mortality rate of COVID-19 patients that receive VV-ECMO stands at approximately 50%. Here, we report three patients that successfully recovered from COVID-19-induced ARDS after VV-ECMO and implementation of an ultra-protective ventilation. This ventilation strategy involved maintaining a peak inspiratory pressure of ≤20 cmH2O and a positive end-expiratory pressure (PEEP) of ≤ 10 cmH2O, which are lower values than have been previously reported. Thus, we suggest that this ultra-protective ventilation be considered during VV-ECMO as it minimizes the ventilator-induced lung injury.

Optimising Ventilator Use during the COVID-19 Pandemic.

Hypoxemia is the most common cause for hospitalization in COVID-19 patients. Acute hypoxemic respiratory failure or acute respiratory distress syndrome (ARDS) is the most common complication in COVID-19 patients. Close monitoring of respiratory decompensation is essential. Supplemental oxygen, high flow nasal canula, non-invasive ventilation and endotracheal intubation are the most commonly suggested methods to improve oxygenation. Early intubation with pre-oxygenation, modified rapid sequence intubation and intubation using a video laryngoscope has been advised as a strategy including lung protective ventilation, prone position ventilation, adequate sedation and extracorporeal membrane oxygenation. Strict personal precautions and challenges related to airway management has been currently studied. The authors summarize here the issues of mechanical ventilation and some strategies to resolve them. Key Words: Mechanical ventilation, COVID-19, Hypoxemia.

Initial emergency department mechanical ventilation strategies for COVID-19 hypoxemic respiratory failure and ARDS.

INTRODUCTION: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an emerging viral pathogen that causes the novel coronavirus disease of 2019 (COVID-19) and may result in hypoxemic respiratory failure necessitating invasive mechanical ventilation in the most severe cases. OBJECTIVE: This narrative review provides evidence-based recommendations for the treatment of COVID-19 related respiratory failure requiring invasive mechanical ventilation. DISCUSSION: In severe cases, COVID-19 leads to hypoxemic respiratory failure that may meet criteria for acute respiratory distress syndrome (ARDS). The mainstay of treatment for ARDS includes a lung protective ventilation strategy with low tidal volumes (4-8 mL/kg predicted body weight), adequate positive end-expiratory pressure (PEEP), and maintaining a plateau pressure of < 30 cm H2O. While further COVID-19 specific studies are needed, current management should focus on supportive care, preventing further lung injury from mechanical ventilation, and treating the underlying cause. CONCLUSIONS: This review provides evidence-based recommendations for the treatment of COVID-19 related respiratory failure requiring invasive mechanical ventilation.