From the Guidelines
Intensive Care Unit-Acquired Weakness (ICUAW) develops through multiple interrelated pathophysiological mechanisms, primarily involving systemic inflammation, mitochondrial dysfunction, and microvascular changes, as supported by the most recent evidence 1. The pathophysiology of ICUAW is complex and multifactorial, involving various mechanisms that contribute to muscle weakness and functional impairment. Some of the key mechanisms include:
- Systemic inflammation, where cytokines like TNF-α, IL-1, and IL-6 trigger muscle protein breakdown and inhibit protein synthesis, as seen in critically ill patients 1
- Mitochondrial dysfunction, which reduces ATP production and increases reactive oxygen species that damage muscle fibers, leading to impaired muscle function 1
- Microvascular changes, which lead to reduced perfusion and tissue hypoxia in muscle beds, exacerbating muscle damage and weakness 1
- Immobility and disuse atrophy, which accelerate muscle loss and contribute to functional impairment 1
- Critical illness polyneuropathy, which causes axonal degeneration through microvascular injury to nerve fibers, leading to muscle weakness and paralysis 1
- Hyperglycemia, which exacerbates nerve damage through increased oxidative stress, further contributing to muscle weakness 1
- Neuromuscular junction abnormalities, which impair muscle activation and contribute to functional weakness 1
- Nutritional deficiencies, particularly inadequate protein intake, which prevent muscle repair and contribute to ongoing muscle weakness 1
- Medications commonly used in ICU settings, especially corticosteroids and neuromuscular blocking agents, which directly contribute to muscle weakness through various mechanisms, including inhibition of protein synthesis and receptor desensitization 1
These mechanisms are interconnected and can exacerbate each other, leading to a complex and challenging clinical presentation. Understanding the pathophysiology of ICUAW is essential for developing effective prevention and treatment strategies, as highlighted in recent guidelines 1.
From the Research
Pathophysiology of ICUAW
The pathophysiology of Intensive Care Unit-Acquired Weakness (ICUAW) is complex and multifactorial. Key features include:
- Loss of muscle mass resulting from a shift in the dynamic balance of muscle protein synthesis and breakdown 2
- Reduction in force-generating capacity secondary to neuropathy, disruption of the myofilament structure and function, a disrupted sarcoplasmic reticulum, electrical inexcitability, and bioenergetic failure 2
- Metabolic, inflammatory, and bioenergetic alterations play a crucial role in the development of ICUAW 3
- Triggers for ICUAW include sepsis, mechanical ventilation, muscle unloading, steroid treatment, or denervation 4
- ICUAW can be caused by distinct neuromuscular disorders, namely critical illness polyneuropathy (CIP) and critical illness myopathy (CIM) 4, 3
Molecular Mechanisms
The molecular mechanisms of ICUAW involve:
- A shift in the dynamic balance of muscle protein synthesis and breakdown, resulting in loss of muscle mass 2
- Disruption of the myofilament structure and function, leading to reduced force-generating capacity 2
- Electrical inexcitability and bioenergetic failure, contributing to muscle weakness 2
- Altered inflammatory and metabolic pathways, deteriorating muscle function 4
- Ubiquitin proteasome and calpain activation, triggering muscle proteolysis and atrophy 4
Risk Factors
Risk factors for ICUAW include: