Acute respiratory distress syndrome (ARDS) is a rapidly developing non-cardiogenic pulmonary edema caused by pulmonary and systemic infections or sterile tissue injuries that evoke a severe lung-damaging host inflammatory response. The lung loses its normal gas exchange efficiency with disruption of the tight permeability characteristics of the alveolar capillary barrier. Interstitial and subsequent alveolar edema lead to alveolar collapse/de-recruitment, reduced lung compliance and greater pulmonary vascular resistance, often with marked regional heterogeneity in severity. Regional heightened stress applied to surrounding normal or less injured lung from edematous and collapsed regions along with associated barotrauma, volutrauma and atelectrauma with mechanical or extreme spontaneous ventilatory efforts further propagate injury in a vicious cycle called ventilator induced lung injury. Resulting arterial hypoxemia and hypercapnia arise from the creation of regions of shunt and low ventilation-perfusion (V A /Q) ratios, in addition to creation of high V A /Q and dead space areas by blood flow obstruction with thrombosis and/or high ventilating pressures. The pathophysiology of ARDS is discussed in this article and focuses on changes in the lung parenchyma and vasculature that reduce compliance, increase vascular resistance and compromise maintenance of dry normally compliant alveolar space by active alveolar fluid clearance and passive lymphatic fluid clearance from the lung interstitium. The COVID-19 pandemic that has emerged with the novel coronavirus, SARS-CoV-2, has generated a new form of severe acute lung injury that resembles ARDS in many of its features, but has different characteristics in its earliest stages leading to more profound hypoxemia and loss of dyspnea perception with less radiologically evident lung injury, not described before in ARDS. Understanding the pathophysiological features of ARDS and COVID-19 lung injury is critical to the best use of supportive therapies such as low tidal volume ventilation, supplemental oxygen concentrations, positive end-expiratory pressure (PEEP), permissive hypercapnia, prone positioning and neuromuscular blockade.

The ongoing coronavirus disease (COVID-19) pandemic has been unprecedented on many levels, not least of which are the challenges in understanding the pathophysiology of these new critically ill patients. One widely reported phenomenon is that of a profoundly hypoxemic patient with minimal to no dyspnea out of proportion to the extent of radiographic abnormality and change in lung compliance. This apparently unique presentation, sometimes called “happy hypoxemia or hypoxia” but better described as “silent hypoxemia,” has led to the speculation of underlying pathophysiological differences between COVID-19 lung injury and acute respiratory distress syndrome (ARDS) from other causes. We explore three proposed distinctive features of COVID-19 that likely bear on the genesis of silent hypoxemia, including differences in lung compliance, pulmonary vascular responses to hypoxia, and nervous system sensing and response to hypoxemia. In the context of known principles of respiratory physiology and neurobiology, we discuss whether these particular findings are due to direct viral effects or, equally plausible, are within the spectrum of typical ARDS pathophysiology and the wide range of hypoxic ventilatory and pulmonary vascular responses and dyspnea perception in healthy people. Comparisons between lung injury patterns in COVID-19 and other causes of ARDS are clouded by the extent and severity of this pandemic, which may underlie the description of “new” phenotypes, although our ability to confirm these phenotypes by more invasive and longitudinal studies is limited. However, given the uncertainty about anything unique in the pathophysiology of COVID-19 lung injury, there are no compelling pathophysiological reasons at present to support a therapeutic approach for these patients that is different from the proven standards of care in ARDS.

IntroductionLactate clearance has been implicated as a predictor of mortality among emergency department (ED) patients with severe sepsis or septic shock. We aimed to validate prior studies showing that lactate clearance during the ED stay is associated with decreased mortality.MethodsRetrospective dual-centered cross-sectional study using patients identified in the Yale-New Haven Hospital Emergency Medicine sepsis registry with severe sepsis or septic shock who had initial lactate levels measured in the ED and upon arrival (<24 hours) to the hospital floor. Lactate clearance was calculated as percent of serum lactate change from ED to floor measurement. We compared mortality and hospital interventions between patients who cleared lactate and those who did not.Results207 patients (110 male; 63.17±17.9 years) were included. Two reviewers extracted data with 95% agreement. One hundred thirty-six patients (65.7%) had severe sepsis and 71 patients (34.3%) had septic shock. There were 171 patients in the clearance group and 36 patients in the non-clearance group. The 28-day mortality rates were 15.2% in the lactate clearance group and 36.1% in the non-clearance group (p<0.01). Vasopressor support was initiated more often in the non-clearance group (61.1%) than in the clearance group (36.8%, p<0.01) and mechanical ventilation was used in 66.7% of the non-clearance group and 36.3% of the clearance group (p=0.001).ConclusionPatients who do not clear their lactate in the ED have significantly higher mortality than those with decreasing lactate levels. Our results are confirmatory of other literature supporting that lactate clearance may be used to stratify mortality-risk among patients with severe sepsis or septic shock.