Descripción del proyecto
Morbilidades adquiridas en la unidad de cuidados intensivos
La unidad de cuidados intensivos (UCI) desempeña un papel fundamental en la prevención de la muerte por afecciones graves como sepsis, intervenciones quirúrgicas complicadas o traumatismos extensos, al proporcionar un soporte vital a los órganos. Sin embargo, las estancias prolongadas en la UCI suelen provocar enfermedades concomitantes como insuficiencia orgánica persistente, debilidad muscular y dependencia de respiradores. El equipo del proyecto AdrenalWeakness, financiado por el Consejo Europeo de Investigación, se centra en la posible asociación mecanicista entre la debilidad muscular adquirida en la UCI y la insuficiencia suprarrenal, una hipótesis de trabajo que no se había estudiado antes. El enfoque de investigación experimental y clínica de AdrenalWeakness pretende identificar y probar compuestos que aborden estas enfermedades concomitantes simultáneamente, lo que evitará efectos secundarios perjudiciales y mejorará los resultados de la recuperación.
Objetivo
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. We will test this hypothesis via an experimental and a clinical track. The proposal starts from a novel, controversial idea, developed via experiments in a unique, clinically relevant and validated mouse model of sepsis-induced critical illness and via the study of human patients, and aims to close the loop with a proof-of-concept randomized controlled trial. Our ambition is to identify and test a novel compound, or combination of compounds, to concomitantly reverse adrenal insufficiency and muscle weakness in prolonged critical illness, while avoiding deleterious side-effects and aiming for synergy. Reaching this ambitious goal would represent ground-breaking progress.
Palabras clave
Programa(s)
- HORIZON.1.1 - European Research Council (ERC) Main Programme
Régimen de financiación
HORIZON-ERC - HORIZON ERC GrantsInstitución de acogida
3000 Leuven
Bélgica