What are the risk factors for Intensive Care Unit (ICU) acquired weakness?

From the Guidelines

ICU-acquired weakness (ICUAW) is primarily caused by critical illness polyneuropathy and myopathy, with several key risk factors contributing to its development, including prolonged mechanical ventilation, sepsis, systemic inflammatory response syndrome, multiple organ failure, hyperglycemia, and prolonged immobility, as supported by the most recent guideline on multimodal rehabilitation for patients with post-intensive care syndrome 1. The main risk factors for ICUAW include:

• Prolonged mechanical ventilation
• Sepsis
• Systemic inflammatory response syndrome
• Multiple organ failure
• Hyperglycemia
• Prolonged immobility Medications such as corticosteroids, neuromuscular blocking agents (especially when used for more than 48 hours), and aminoglycoside antibiotics significantly increase the risk, as noted in the guideline on positioning and early mobilisation in the critically ill by an expert panel 1. Patient-specific factors also play a role, including:
• Advanced age
• Female gender
• Pre-existing diabetes
• Poor nutritional status Electrolyte abnormalities (particularly hypophosphatemia, hypokalemia, and hypomagnesemia) further contribute to muscle weakness, as discussed in the American Thoracic Society clinical practice guideline 1. The pathophysiology involves microvascular injury, altered membrane excitability, bioenergetic failure, and proteolysis from inflammatory cytokines and oxidative stress. Prevention strategies include:
• Minimizing sedation
• Early mobilization protocols
• Tight glycemic control (maintaining blood glucose between 140-180 mg/dL)
• Judicious use of corticosteroids and neuromuscular blockers
• Proper nutritional support with attention to protein intake and electrolyte balance, as recommended in the guideline on multimodal rehabilitation for patients with post-intensive care syndrome 1.

From the Research

Risk Factors for ICU Acquired Weakness

The risk factors for ICU acquired weakness can be categorized into modifiable and non-modifiable factors.

• Non-modifiable factors include:
  • Advanced age 2
  • Female gender 2
  • Multiple organ failure 2
• Modifiable factors include:
  • Neuromuscular blocking agents 3, 4, 2
  • Hyperglycemia 3, 4, 2
  • Corticosteroids 3, 4, 2
  • Aminoglycosides 2
  • Renal replacement therapy 2
  • Norepinephrine 2
  • Immobility 4
  • Sepsis 4
  • Persistent systemic inflammation 4
  • Multiorgan system failure 4
  • Glucocorticoids 4
  • Parenteral nutrition 3
  • Hypoalbuminemia 3
  • Duration of the stay in the ICU and of mechanical ventilation 3
  • Severity and duration of the systemic inflammatory response 3

Pathophysiology and Clinical Features

The pathophysiology of ICU acquired weakness remains unknown 4. Clinical features may be neuropathic, myopathic, or a combination of both 3, 4.

• Muscle weakness may be the result of axonal polyneuropathy, myopathy or a combination of both 3
• Loss of thick filaments (myosin), atrophy of the myofibers, necrosis, and regeneration features has been consistently shown in muscle samples during critical illness 3
• A slow-to-fast fiber type shift, reduced muscle fiber cross-sectional area of the myofibers, alterations in muscle contractility, reduced aerobic capacity and protein synthesis, and the electromechanical properties of the nerve-muscle interface are also relevant features in skeletal muscles of critically ill patients and experimental models 3