Venoarterial extracorporeal membrane oxygenation provides cardiorespiratory support to patients in cardiogenic shock. This comes at the cost of increased left ventricle (LV) afterload that can be partly ascribed to retrograde aortic flow, causing LV distension, and leads to complications including cardiac thrombi, arrhythmias, and pulmonary edema. LV unloading can be achieved by using an additional circulatory support device to mitigate the adverse effects of mechanical overload that may increase the likelihood of myocardial recovery. Observational data suggest that these strategies may improve outcomes, but in whom, when, and how LV unloading should be employed is unclear; all techniques require balancing presumed benefits against known risks of device-related complications. This review summarizes the current evidence related to LV unloading with venoarterial extracorporeal membrane oxygenation.

Mortality in acute respiratory distress syndrome (ARDS) remains unacceptably high at approximately 39%. One of the only treatments is supportive: mechanical ventilation. However, improperly set mechanical ventilation can further increase the risk of death in patients with ARDS. Recent studies suggest that ventilation-induced lung injury (VILI) is caused by exaggerated regional lung strain, particularly in areas of alveolar instability subject to tidal recruitment/derecruitment and stress-multiplication. Thus, it is reasonable to expect that if a ventilation strategy can maintain stable lung inflation and homogeneity, regional dynamic strain would be reduced and VILI attenuated. A time-controlled adaptive ventilation (TCAV) method was developed to minimize dynamic alveolar strain by adjusting the delivered breath according to the mechanical characteristics of the lung. The goal of this review is to describe how the TCAV method impacts pathophysiology and protects lungs with, or at high risk of, acute lung injury. We present work from our group and others that identifies novel mechanisms of VILI in the alveolar microenvironment and demonstrates that the TCAV method can reduce VILI in translational animal ARDS models and mortality in surgical/trauma patients. Our TCAV method utilizes the airway pressure release ventilation (APRV) mode and is based on opening and collapsing time constants, which reflect the viscoelastic properties of the terminal airspaces. Time-controlled adaptive ventilation uses inspiratory and expiratory time to (1) gradually “nudge” alveoli and alveolar ducts open with an extended inspiratory duration and (2) prevent alveolar collapse using a brief (sub-second) expiratory duration that does not allow time for alveolar collapse. The new paradigm in TCAV is configuring each breath guided by the previous one, which achieves real-time titration of ventilator settings and minimizes instability induced tissue damage. This novel methodology changes the current approach to mechanical ventilation, from arbitrary to personalized and adaptive. The outcome of this approach is an open and stable lung with reduced regional strain and greater lung protection.

Background: There are limited data on acute kidney injury (AKI) progression and long-term outcomes in critically ill patients with coronavirus disease-19 (COVID-19). We aimed to describe the prevalence and risk factors for development of AKI, its subsequent clinical course and AKI progression, as well as renal recovery or dialysis dependence and survival in this group of patients. Methods: This was a retrospective observational study in an expanded tertiary care intensive care unit in London, United Kingdom. Critically ill patients admitted to ICU between 1st March 2020 and 31st July 2020 with confirmed SARS-COV2 infection were included. Analysis of baseline characteristics, organ support, COVID-19 associated therapies and their association with mortality and outcomes at 90 days was performed. Results: Of 313 patients (70% male, mean age 54.5 ± 13.9 years), 240 (76.7%) developed AKI within 14 days after ICU admission: 63 (20.1%) stage 1, 41 (13.1%) stage 2, 136 (43.5%) stage 3. 113 (36.1%) patients presented with AKI on ICU admission. Progression to AKI stage 2/3 occurred in 36%. Risk factors for AKI progression were mechanical ventilation [HR (hazard ratio) 4.11; 95% confidence interval (CI) 1.61–10.49] and positive fluid balance [HR 1.21 (95% CI 1.11–1.31)], while steroid therapy was associated with a reduction in AKI progression (HR 0.73 [95% CI 0.55–0.97]). Kidney replacement therapy (KRT) was initiated in 31.9%. AKI patients had a higher 90-day mortality than non-AKI patients (34% vs. 14%; p < 0.001). Dialysis dependence was 5% at hospital discharge and 4% at 90 days. Renal recovery was identified in 81.6% of survivors at discharge and in 90.9% at 90 days. At 3 months, 16% of all AKI survivors had chronic kidney disease (CKD); among those without renal recovery, the CKD incidence was 44%. Conclusions: During the first COVID-19 wave, AKI was highly prevalent among severely ill COVID-19 patients with a third progressing to severe AKI requiring KRT. The risk of developing CKD was high. This study identifies factors modifying AKI progression, including a potentially protective effect of steroid therapy. Recognition of risk factors and monitoring of renal function post-discharge might help guide future practice and follow-up management strategies. Trial registration NCT04445259

Hypoxemic respiratory failure is one of the leading causes of mortality in intensive care. Frequent assessment of individual physiological characteristics and delivery of personalized mechanical ventilation (MV) settings is a constant challenge for clinicians caring for these patients. Electrical impedance tomography (EIT) is a radiation-free bedside monitoring device that is able to assess regional lung ventilation and changes in aeration. With real-time tomographic functional images of the lungs obtained through a thoracic belt, clinicians can visualize and estimate the distribution of ventilation at different ventilation settings or following procedures such as prone positioning. Several studies have evaluated the performance of EIT to monitor the effects of different MV settings in patients with acute respiratory distress syndrome, allowing more personalized MV. For instance, EIT could help clinicians find the positive end-expiratory pressure that represents a compromise between recruitment and overdistension and assess the effect of prone positioning on ventilation distribution. The clinical impact of the personalization of MV remains to be explored. Despite inherent limitations such as limited spatial resolution, EIT also offers a unique noninvasive bedside assessment of regional ventilation changes in the ICU. This technology offers the possibility of a continuous, operator-free diagnosis and real-time detection of common problems during MV. This review provides an overview of the functioning of EIT, its main indices, and its performance in monitoring patients with acute respiratory failure. Future perspectives for use in intensive care are also addressed.

Purpose of review: More than 230 million people have tested positive for severe acute respiratory syndrome-coronavirus-2 infection globally by September 2021. The infection affects primarily the function of the respiratory system, where ∼20% of infected individuals develop coronavirus-19 disease (COVID-19) pneumonia. This review provides an update on the pathophysiology of the COVID-19 acute lung injury. Recent findings: In patients with COVID-19 pneumonia admitted to the intensive care unit, the PaO₂/FiO₂ ratio is typically <26.7 kPa (200 mmHg), whereas lung volume appears relatively unchanged. This hypoxaemia is likely determined by a heterogeneous mismatch of pulmonary ventilation and perfusion, mainly associated with immunothrombosis, endothelialitis and neovascularisation. During the disease, lung weight, elastance and dead space can increase, affecting respiratory drive, effort and dyspnoea. In some severe cases, COVID-19 pneumonia may lead to irreversible pulmonary fibrosis. Summary: This review summarises the fundamental pathophysiological features of COVID-19 in the context of the respiratory system. It provides an overview of the key clinical manifestations of COVID-19 pneumonia, including gas exchange impairment, altered pulmonary mechanics and implications of abnormal chemical and mechanical stimuli. It also critically discusses the clinical implications for mechanical ventilation therapy.

Background: There is on-going controversy regarding the potential for increased respiratory effort to generate patient self-inflicted lung injury (P-SILI) in spontaneously breathing patients with COVID-19 acute hypoxaemic respiratory failure. However, direct clinical evidence linking increased inspiratory effort to lung injury is scarce. We adapted a computational simulator of cardiopulmonary pathophysiology to quantify the mechanical forces that could lead to P-SILI at different levels of respiratory effort. In accordance with recent data, the simulator parameters were manually adjusted to generate a population of 10 patients that recapitulate clinical features exhibited by certain COVID-19 patients, i.e., severe hypoxaemia combined with relatively well-preserved lung mechanics, being treated with supplemental oxygen. Results: Simulations were conducted at tidal volumes (VT) and respiratory rates (RR) of 7 ml/kg and 14 breaths/min (representing normal respiratory effort) and at VT/RR of 7/20, 7/30, 10/14, 10/20 and 10/30 ml/kg / breaths/min. While oxygenation improved with higher respiratory efforts, significant increases in multiple indicators of the potential for lung injury were observed at all higher VT/RR combinations tested. Pleural pressure swing increased from 12.0 ± 0.3 cmH ₂ O at baseline to 33.8 ± 0.4 cmH ₂ O at VT/RR of 7 ml/kg/30 breaths/min and to 46.2 ± 0.5 cmH ₂ O at 10 ml/kg/30 breaths/min. Transpulmonary pressure swing increased from 4.7 ± 0.1 cmH ₂ O at baseline to 17.9 ± 0.3 cmH ₂ O at VT/RR of 7 ml/kg/30 breaths/min and to 24.2 ± 0.3 cmH ₂ O at 10 ml/kg/30 breaths/min. Total lung strain increased from 0.29 ± 0.006 at baseline to 0.65 ± 0.016 at 10 ml/kg/30 breaths/min. Mechanical power increased from 1.6 ± 0.1 J/min at baseline to 12.9 ± 0.2 J/min at VT/RR of 7 ml/kg/30 breaths/min, and to 24.9 ± 0.3 J/min at 10 ml/kg/30 breaths/min. Driving pressure increased from 7.7 ± 0.2 cmH ₂ O at baseline to 19.6 ± 0.2 cmH ₂ O at VT/RR of 7 ml/kg/30 breaths/min, and to 26.9 ± 0.3 cmH ₂ O at 10 ml/kg/30 breaths/min. Conclusions: Our results suggest that the forces generated by increased inspiratory effort commonly seen in COVID-19 acute hypoxaemic respiratory failure are comparable with those that have been associated with ventilator-induced lung injury during mechanical ventilation. Respiratory efforts in these patients should be carefully monitored and controlled to minimise the risk of lung injury.