Pathophysiology and management of critical illness polyneuropathy and myopathy

Abstract

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.

Figure 1.

Conceptual depiction of the pathophysiological factors underlying critical illness-associated weakness (CIAW). Please note, the evidence for these factors is derived from heterogeneous studies including investigations in both humans and animal models. This figure is meant to graphically illustrate 1) the inherent complexity of CIAW and 2) how various potential pathophysiologic mechanisms relate to one another and how they may lead to either, or both of, polyneuropathy and myopathy. ROS, reactive oxygen species. GH, growth hormone.

Figure 2.

Common risk factors associated with the development of critical illness-associated weakness (CIAW). ICU, intensive care unit.

Figure 3.

Summary of prevention and management strategies for critical illness-associated weakness (CIAW). Interventions within solid lines are well supported by available evidence; interventions within hatched lines are theoretically supported but require further study.