Exploring a novel, shared upstream pathway as potential driver of ICU-acquired muscle weakness and central adrenal insufficiency in prolonged critical illness

Sepsis, complicated surgery or extensive trauma cause hyperinflammation-induced critical illness which requires vital organ support in an intensive care unit (ICU) in order to avoid imminent death. Although modern intensive care has reduced mortality, a large number of survivors continue to require such supportive care in the ICU sometimes for weeks or months. Once in this prolonged phase, typical ICU-acquired morbidities such as lingering organ failure, muscle wasting and weakness and vasopressor- and ventilator-dependency become the main drivers of poor short- and long-term outcome irrespective of the initial diagnosis upon admission. Research from our group has focused on two of these unresolved problems, namely ICU-acquired muscle weakness and ICU-acquired adrenal insufficiency, for which there is either no treatment or treatment has deleterious off-target effects that may fuel a vicious circle impairing short- and long-term recovery. Today, intensivists see these conditions as two separate pathophysiological entities, an assumption we think is false. We hypothesize that ICU-acquired adrenal insufficiency shares upstream underlying mechanisms with ICU-acquired muscle weakness, pathways that are currently unexplored and that can be manipulated with the potential to reverse both problems together. This hypothesis will be tested by an experimental and a clinical track.