Pathophysiology and management of critical illness polyneuropathy and myopathy

J Appl Physiol (1985). 2021 May 1;130(5):1479-1489. doi: 10.1152/japplphysiol.00019.2021. Epub 2021 Mar 18.


Critical illness-associated weakness (CIAW) is an umbrella term used to describe a group of neuromuscular disorders caused by severe illness. It can be subdivided into three major classifications based on the component of the neuromuscular system (i.e. peripheral nerves or skeletal muscle or both) that are affected. This includes critical illness polyneuropathy (CIP), critical illness myopathy (CIM), and an overlap syndrome, critical illness polyneuromyopathy (CIPNM). It is a common complication observed in people with critical illness requiring intensive care unit (ICU) admission. Given CIAW is found in individuals experiencing grave illness, it can be challenging to study from a practical standpoint. However, over the past 2 decades, many insights into the pathophysiology of this condition have been made. Results from studies in both humans and animal models have found that a profound systemic inflammatory response and factors related to bioenergetic failure as well as microvascular, metabolic, and electrophysiological alterations underlie the development of CIAW. Current management strategies focus on early mobilization, achieving euglycemia, and nutritional optimization. Other interventions lack sufficient evidence, mainly due to a dearth of large trials. The goal of this Physiology in Medicine article is to highlight important aspects of the pathophysiology of these enigmatic conditions. It is hoped that improved understanding of the mechanisms underlying these disorders will lead to further study and new investigations for novel pharmacologic, nutritional, and exercise-based interventions to optimize patient outcomes.

Keywords: COVID-19; ICU-related weakness; critical illness myopathy; critical illness neuropathy; critical illness polyneuromyopathy.

MeSH terms

  • Critical Care
  • Critical Illness
  • Humans
  • Intensive Care Units
  • Muscular Diseases* / therapy
  • Neuromuscular Diseases*
  • Polyneuropathies* / therapy