Persisting muscle weakness after prolonged intensive care stay: incidence, risk factors, pathomysiology and contribution to long-term physical disabilities.

As ICU survival has markedly increased during the past decades, devastating sequellae of critical illness are becoming clear. ICU survivors manifest long-term physical disability and decreased quality of life. Several factors may contribute to this ‘legacy’ of critical illness. One of the main suggested contributors is delayed recovery from neuromuscular weakness acquired in the ICU (ICUAW). In this project we focus on the gap in knowledge on epidemiology, risk factors and pathophysiological mechanisms involved in prolonged ICUAW by performing long-term follow-up of a cohort of ICU survivors who were included in a large randomised controlled trial (n=4640) and therefore constitute an extensively documented sample. This translational research includes functional and neuromuscular evaluations years following ICU admission. We will describe independent risk factors for prolonged weakness and functional disabilities by performing multivariate regression analysis on potential risk factors involved. Unraveling pathophysiological mechanisms of persisting weakness will give insight into potential therapeutic strategies. For this purpose, muscle biopsies will be collected during the follow-up visits to study muscle structure, degeneration and regeneration. All data will be compared with those obtained during ICU stay in this cohort. This project will provide crucial information for developing interventions to reduce the burden of long-term morbidity.