Intensive Care Unit-Acquired Weakness: A Review of Recent Progress With a Look Toward the Future

Abstract

Intensive care unit-acquired weakness (ICU-AW), a common neuromuscular complication associated with patients in the ICU, is a type of skeletal muscle dysfunction that commonly occurs following sepsis, mobility restriction, hyperglycemia, and the use of glucocorticoids or neuromuscular blocking agents. ICU-AW can lead to delayed withdrawal of mechanical ventilation and extended hospitalization. Patients often have poor prognosis, limited mobility, and severely affected quality of life. Currently, its pathogenesis is uncertain, with unavailability of specific drugs or targeted therapies. ICU-AW has gained attention in recent years. This manuscript reviews the current research status of the epidemiology, pathogenesis, diagnosis, and treatment methods for ICU-AW and speculates the novel perspectives for future research.

Keywords: diagnosis; intensive care unit-acquired weakness; neuromuscular junction; pathogenesis; treatment.

Figure 1

Possible mechanism of intensive care unit-acquired weakness (ICU-AW). Muscle atrophy is caused by an imbalance between protein synthesis and degradation. The ubiquitin–proteasome pathway and autophagy–lysosome system are activated during this period, leading to massive degradation of muscle proteins. ROS released after mitochondrial damage also induce proteolysis. The agrin-MuSK-Lrp4 signaling pathway is impaired during abnormal NMJ function, leading to muscle atrophy. Finally, inflammatory factors can cause axonal swelling in motor neurons, resulting in neurapraxia.

Figure 2

Modified Sihler's staining technique. The technique allows a clear three-dimensional visualization of terminal nerves (i.e., the site where an α-motor nerve ending attaches to the muscular fiber, namely, the motor end-plate), which cannot be observed by the naked eye. The relationship between the intramuscular terminal nerves and the muscle fibers (the NMJ) in the flexor hallucis longus is shown. The red arrowhead shows the terminal nerve, and the blue arrowhead shows the muscle fiber (right, superficial).