Intensive care unit-acquired weakness Pathophysiology and diagnosis

Many patients on the intensive care unit (ICU) develop generalized muscle weakness. This condition, called intensive care unit- acquired weakness (ICU-AW), is caused by dysfunction or damage of muscles, nerves, or both. ICU-AW is associated with increased short- and long-term morbidity and mortality. The pathophysiology of ICU-AW is complex and remains to be elucidated. The first aim of this thesis was to investigate the role of inflammation in ICU-AW. We reviewed the literature and we investigated markers of systemic inflammation in patients with and without ICU-AW. The next aim of this thesis was to develop a new animal model for ICU-AW. Currently used animal models for ICU-AW have several limitations. We investigated if existing animal models for sepsis could serve as ICU-AW model. In the last part of this thesis we investigated new methods to diagnose and predict ICU-AW. ICU-AW is currently diagnosed by manual muscle strength testing. Consequently, the diagnosis of ICU-AW is often delayed, because sedation and reduced attentiveness hamper muscle strength testing, especially in the first days after ICU admission. An early diagnosis of ICU-AW, however, could lead to earlier initiation of supportive interventions. We examined the use of neuromuscular ultrasound, a non-invasive and harmless procedure, to diagnose ICU-AW. Furthermore, we investigated the external validity of a previously developed prediction model to predict ICU-AW at two days after ICU admission, in a multicenter prospective observational cohort study.