1. Introduction

Rationale: ICU-acquired weakness (ICU-AW) is a common and debilitating multifactorial syndrome characterized by the rapid onset of muscle and nerve dysfunction during the course of critical illness. It represents a significant barrier to recovery and a major driver of long-term morbidity.

By definition, ICU-AW is a new-onset, generalized, and symmetrical muscle weakness that develops after the onset of critical illness and persists beyond the acute phase. It is an umbrella term that encompasses several overlapping conditions:

• Critical Illness Polyneuropathy (CIP): A primary disorder of the peripheral nerves.
• Critical Illness Myopathy (CIM): A primary disorder of the muscle tissue itself.
• Disuse Atrophy: Muscle wasting resulting from prolonged immobilization.

The clinical impact of ICU-AW is profound, leading to increased ventilator days, prolonged ICU and hospital lengths of stay, and higher short-term mortality. Survivors often face persistent functional deficits and a significantly reduced quality of life for months or even years following their discharge.

2. Epidemiology and Incidence

Rationale: Understanding the high prevalence and significant burden of ICU-AW underscores the urgency for systematic screening and prevention strategies in all critically ill patients.

Prevalence and Resource Impact

ICU-AW is not a rare complication; it is a frequent consequence of modern critical care. Its incidence varies depending on the patient population and diagnostic criteria used:

• General ICU Cohort: Affects 25–50% of all patients admitted to the ICU.
• Prolonged Ventilation: Incidence rises to approximately 43% in patients requiring mechanical ventilation for more than 7 days.
• Sepsis/Multiorgan Failure: The highest risk is seen in patients with sepsis or multiorgan failure, where the prevalence can exceed 60%.

The development of ICU-AW places a substantial strain on healthcare resources. Compared to unaffected patients, those with ICU-AW experience an average of 4–7 additional ventilator days and 6–10 additional ICU days. This also translates to an attributable increase in in-hospital mortality of approximately 15%.

Long-Term Burden

The consequences extend far beyond the hospital walls. Approximately 50% of ICU survivors report persistent weakness and impairment in their activities of daily living (ADLs) at 6 months post-discharge, highlighting a major public health challenge.

3. Pathophysiology of ICU-AW

Rationale: ICU-AW is not a single disease but a syndrome resulting from the convergence of neuropathic, myopathic, and disuse-related mechanisms. These processes are driven by the systemic inflammatory response, profound catabolism, and the effects of immobilization inherent to critical care.

• Critical Illness Polyneuropathy (CIP): Characterized by diffuse axonal degeneration of both motor and sensory nerve fibers. It is mediated by pro-inflammatory cytokines (e.g., TNF-α, IL-6), microvascular hypoperfusion of the nerves, and endoneurial edema, leading to Wallerian-like degeneration and slowed nerve conduction velocities.
• Critical Illness Myopathy (CIM): Involves direct muscle damage, including selective loss of the contractile protein myosin, muscle fiber necrosis, and severe mitochondrial dysfunction. This is driven by upregulated proteolysis via the ubiquitin–proteasome and autophagy pathways, which are activated by high levels of cortisol, catecholamines, and cytokines.
• Disuse Atrophy: Immobilization itself triggers a rapid decline in muscle mass. This occurs through a shutdown of anabolic signaling pathways (e.g., IGF-1/Akt/mTOR) and an upregulation of muscle-specific ubiquitin ligases (MuRF-1, Atrogin-1) that tag proteins for degradation.

4. Risk Factors Analysis

Rationale: A multitude of intrinsic patient factors and extrinsic iatrogenic exposures converge to amplify the risk for developing ICU-AW. Identifying and modifying these factors is a cornerstone of prevention.

Other Contributing Factors

• Prolonged Mechanical Ventilation & Sepsis: The duration of ventilation and the severity of sepsis directly correlate with ICU-AW severity, driven by the inflammatory storm and multiorgan failure.
• Metabolic Derangements: Electrolyte imbalances like hypophosphatemia (impairs ATP synthesis) and hypokalemia (affects membrane excitability) can exacerbate weakness. Prompt repletion is crucial.
• Pre-Existing Conditions: Patients with baseline frailty, sarcopenia, or chronic diseases (diabetes, COPD, CKD) have less physiological reserve and are more susceptible to rapid functional decline.
• Social Determinants of Health: Factors such as low health literacy, limited access to rehabilitation services, and socioeconomic constraints can create barriers to both in-ICU mobilization and post-discharge recovery.

5. Clinical Presentation and Detection

Rationale: Early and reliable detection of ICU-AW is crucial for prognostication and initiating targeted rehabilitation. This requires moving beyond subjective impressions to objective, standardized measures of strength.

Standardized Strength Testing

The diagnosis is confirmed at the bedside when a patient is awake and able to cooperate with an exam. The most widely used tools include:

• Medical Research Council (MRC) Sum Score: This is the gold standard for diagnosis. It involves testing three muscle groups in each limb bilaterally (shoulder abduction, elbow flexion, wrist extension, hip flexion, knee extension, ankle dorsiflexion). Each group is scored 0-5, for a total possible score of 60. A score <48 confirms a diagnosis of ICU-AW.
• Handgrip Dynamometry: A simpler, quicker tool that provides a quantitative measure of grip strength. It correlates well with overall muscle strength and functional outcomes. Thresholds of <11 kg for men and <7 kg for women are highly suggestive of ICU-AW.

Indirect Clinical Signs

Even before a patient can fully cooperate, certain clinical patterns may suggest underlying ICU-AW, particularly persistent and unexplained difficulty in weaning from mechanical ventilation. Signs include a weak cough, poor airway clearance, and low endurance during spontaneous breathing trials.

6. Systemic Impact of Immobility

Rationale: Beyond muscle weakness, prolonged immobility in the ICU has deleterious effects on nearly every organ system, compounding patient morbidity and creating a vicious cycle of deconditioning and complications.

• Pressure Ulcers: Sustained pressure on bony prominences, combined with poor tissue perfusion and malnutrition, leads to skin breakdown and the development of pressure injuries. Prevention relies on frequent repositioning, use of pressure-redistributing surfaces, and early mobilization to relieve pressure points.
• Venous Thromboembolism (VTE): Immobility causes venous stasis, a key component of Virchow’s triad, dramatically increasing the risk of deep vein thrombosis (DVT) and pulmonary embolism (PE). Standard prevention includes pharmacological prophylaxis (e.g., LMWH) combined with mechanical compression devices.
• Pulmonary Complications: The diaphragm, a skeletal muscle, atrophies rapidly with controlled mechanical ventilation. This, combined with atelectasis from shallow breathing and an inability to clear secretions, leads to hypoxemia and difficulty weaning.

7. Key Clinical Decision Points & Summary

Rationale: Mitigating ICU-AW and the hazards of immobility requires a proactive, systematic approach that integrates screening, prevention, and multidisciplinary coordination from the earliest days of an ICU stay.

Early Screening and Intervention Triggers

A high index of suspicion is essential. Consider a patient at high risk and activate early mobility protocols if they meet any of the following criteria, typically by ICU day 3:

• Mechanical ventilation > 48 hours
• Presence of sepsis or septic shock
• Requirement for deep sedation (RASS ≤–3) for a prolonged period
• Treatment with high-dose corticosteroids

Multidisciplinary Team Integration

No single discipline can manage this problem alone. A coordinated “ABCDEF Bundle” approach is most effective, with each team member playing a crucial role:

• Nurses: Lead sedation management, delirium screening, positional changes, and skin care.
• Physical & Occupational Therapists: Design and implement tailored rehabilitation plans, from passive range of motion to active mobilization.
• Respiratory Therapists: Manage ventilator settings to facilitate patient-ventilator synchrony and conduct spontaneous breathing trials.
• Pharmacists: Optimize sedation, analgesia, and glycemic control to remove pharmacological barriers to mobilization and participation.