Intensive Care Unit-Acquired Weakness: Not just Another Muscle Atrophying Condition

• Main Authors: Heta Lad, Tyler M. Saumur, Margaret S. Herridge, Claudia C. dos Santos, Sunita Mathur, Jane Batt, Penney M. Gilbert
• Format: Article
• Language: English
• Published: MDPI AG 2020-10-01
• Series: International Journal of Molecular Sciences
• Subjects: muscle atrophy; critical illness; intensive care unit-acquired weakness; critical illness myopathy; critical illness polyneuropathy; COVID-19
• Online Access: https://www.mdpi.com/1422-0067/21/21/7840
• ISSN: 1661-6596; 1422-0067

Intensive care unit-acquired weakness (ICUAW) occurs in critically ill patients stemming from the critical illness itself, and results in sustained disability long after the ICU stay. Weakness can be attributed to muscle wasting, impaired contractility, neuropathy, and major pathways associated with muscle protein degradation such as the ubiquitin proteasome system and dysregulated autophagy. Furthermore, it is characterized by the preferential loss of myosin, a distinct feature of the condition. While many risk factors for ICUAW have been identified, effective interventions to offset these changes remain elusive. In addition, our understanding of the mechanisms underlying the long-term, sustained weakness observed in a subset of patients after discharge is minimal. Herein, we discuss the various proposed pathways involved in the pathophysiology of ICUAW, with a focus on the mechanisms underpinning skeletal muscle wasting and impaired contractility, and the animal models used to study them. Furthermore, we will explore the contributions of inflammation, steroid use, and paralysis to the development of ICUAW and how it pertains to those with the corona virus disease of 2019 (COVID-19). We then elaborate on interventions tested as a means to offset these decrements in muscle function that occur as a result of critical illness, and we propose new strategies to explore the molecular mechanisms of ICUAW, including serum-related biomarkers and 3D human skeletal muscle culture models.