Kinetic profiling of in vivo lung cellular inflammatory responses to mechanical ventilation.

Mechanical ventilation, through overdistension of the lung, induces substantial inflammation that is thought to increase mortality among critically ill patients. The mechanotransduction processes involved in converting lung distension into inflammation during this ventilator-induced lung injury (VILI) remain unclear, although many cell types have been shown to be involved in its pathogenesis. This study aimed to identify the profile of in vivo lung cellular activation that occurs during the initiation of VILI. This was achieved using a flow cytometry-based method to quantify the phosphorylation of several markers (p38, ERK1/2, MAPK-activated protein kinase 2, and NF-κB) of inflammatory pathway activation within individual cell types. Anesthetized C57BL/6 mice were ventilated with low (7 ml/kg), intermediate (30 ml/kg), or high (40 ml/kg) tidal volumes for 1, 5, or 15 min followed by immediate fixing and processing of the lungs. Surprisingly, the pulmonary endothelium was the cell type most responsive to in vivo high-tidal-volume ventilation, demonstrating activation within just 1 min, followed by the alveolar epithelium. Alveolar macrophages were the slowest to respond, although they still demonstrated activation within 5 min. This order of activation was specific to VILI, since intratracheal lipopolysaccharide induced a very different pattern. These results suggest that alveolar macrophages may become activated via a secondary mechanism that occurs subsequent to activation of the parenchyma and that the lung cellular activation mechanism may be different between VILI and lipopolysaccharide. Our data also demonstrate that even very short periods of high stretch can promote inflammatory activation, and, importantly, this injury may be immediately manifested within the pulmonary vasculature.

PIM-COVID study: protocol for a multicentre, longitudinal study measuring the psychological impact of surviving an intensive care admission due to COVID-19 on patients in the UK.

INTRODUCTION: Psychological distress is common in intensive care unit (ICU) survivors and is anticipated in those who were treated for severe COVID-19 infection. This trainee-led, multicentre, observational, longitudinal study aims to assess the psychological outcomes of ICU survivors treated for COVID-19 infection in the UK at 3, 6 and/or 12 months after ICU discharge and explore whether there are demographic, psychosocial and clinical risk factors for psychological distress. METHODS AND ANALYSIS: Questionnaires will be provided to study participants 3, 6 and/or 12 months after discharge from intensive care, assessing for anxiety, depression, post-traumatic stress symptoms, health-related quality of life and physical symptoms. Demographic, psychosocial and clinical data will also be collected to explore risk factors for psychological distress using latent growth curve modelling. Study participants will be eligible to complete questionnaires at any of the three time points online, by telephone or by post. ETHICS AND DISSEMINATION: The PIM-COVID study was approved by the Health Research Authority (East Midlands - Derby Research and Ethics Committee, reference: 20/EM/0247). TRIAL REGISTRATION NUMBER: NCT05092529.

Hypercoagulopathy in Severe COVID-19: Implications for Acute Care.

COVID-19 was first described in late 2019 and has since developed into a pandemic affecting more than 21 million people worldwide. Of particular relevance for acute care is the occurrence of COVID-19-associated coagulopathy (CAC), which is characterised by hypercoagulability, immunothrombosis and venous thromboembolism, and contributes to hypoxia in a significant proportion of patients. This review describes diagnosis and treatment of CAC in the emergency department and in intensive care. We summarise the pathological mechanisms and common complications of CAC such as pulmonary thrombosis and venous thromboembolic events and discuss current strategies for thromboprophylaxis and therapeutic anti-coagulation in the acute care setting.