The Role of Local and Systemic Inflammation in the Pathogenesis of Intensive Care Unit-acquired Weakness

A previously healthy 47-year old woman was admitted to the intensive care unit (ICU) with severe pneumosepsis. She received antimicrobial therapy and supportive care consisting of fluid resuscitation, inotropes and vasopressors, and lung-protective ventilation. She developed kidney failure for which continuous venovenous hemofiltration was initiated. She recovered within several days, but after cessation of sedatives it became apparent that she was very weak and could hardly move her limbs. She was clinically diagnosed with ICU-acquired weakness. After a period of intense rehabilitation she was discharged home, but a year later she still complained of severe impairments in physical functioning. She wondered how a pulmonary infection could have led to extreme weakness of the limbs. You realize that the pathophysiology of ICU-acquired weakness is far from understood, but there are suggestions that ICU-acquired weakness develops in response to a strong and uncontrolled inflammatory response, as seen with sepsis. In this chapter, building on a recently published translational review [1], we aim to provide an overview of studies on local and systemic inflammation in animal models of ICU-acquired weakness and in critically ill patients with ICU-acquired weakness, and discuss immune-modulating strategies that could benefit patients at risk for or with ICU-acquired weakness