Abstract
Impaired tissue oxygenation is a landmark feature of critical illness. Studies performed at high altitude have been suggested as a model to study the mechanisms underlying the physiological adaptation to hypoxemia, contributing to our understanding of these processes. However, it has remained unclear whether critical illness modifies the response to hypoxemia or whether the adaptation processes may be available to critically ill patients, potentially limiting the translational utility of high-altitude studies. Recently, advances in the investigation of microcirculatory function have enabled microcirculatory adaptation mechanisms to be observed during the ascent to a Himalayan peak, revealing the functional recruitment of capillaries as the main mechanism by the systemic microcirculation to increase red blood cell (RBC) availability and oxygen delivery in the tissues. A similar mechanism has now been observed in critically ill patients with coronavirus disease (COVID-19), where it may serve to respond to the hypoxemia caused by severe pulmonary dysfunction, showing a direct link between high-altitude research and critical care medicine. These findings emphasize the role of RBC availability in determining oxygen availability in the tissue in both homeostasis and disease, and confirm previous physiological and methodological studies. Enabled by newly developed parameters, such as tissue RBC perfusion, automatically measured via handheld vital microscopy in the sublingual microcirculation, future studies may determine the optimal targets for tissue RBC perfusion and oxygenation, providing a promising approach to improving morbidity and mortality in critically ill patients.