ICU-Acquired Weakness (ICU-AW)
🔹 Definition
ICU-acquired weakness (ICU-AW) is a diffuse, symmetric, generalized muscle weakness that develops during critical illness, in the absence of any other identifiable cause (e.g., stroke, Guillain-Barré syndrome).
It represents a spectrum of neuromuscular disorders affecting critically ill patients, commonly those with sepsis, multi-organ failure, or prolonged mechanical ventilation.
🔹 Types (Spectrum of ICU-AW)
|
Type |
Primary Site of Involvement |
Description |
|
Critical Illness Polyneuropathy (CIP) |
Peripheral nerves (axonal sensory-motor) |
Axonal degeneration of motor and sensory fibers → decreased CMAPs and SNAPs |
|
Critical Illness Myopathy (CIM) |
Skeletal muscle (myofiber dysfunction) |
Primary myopathic process with muscle fiber atrophy and myosin loss |
|
Critical Illness Neuromyopathy (CINM) |
Both nerve and muscle |
Mixed pattern of CIP + CIM (most common presentation) |
# Overall, these are collectively termed ICU-acquired weakness (ICU-AW).
🔹 Epidemiology
- Incidence: 25–50% of critically ill patients with sepsis, MODS, or prolonged ventilation.
- Seen typically after 7 days or more in the ICU.
- Up to 70% of long-stay (>2 weeks) ventilated patients may develop weakness.
🔹 Pathophysiology
ICU-AW results from multifactorial insults involving inflammation, metabolic stress, immobility, and medication effects.
1. Systemic Inflammation & Sepsis
- Cytokines (TNF-α, IL-1β, IL-6) cause microvascular dysfunction, mitochondrial injury, and oxidative stress.
- Leads to axonal degeneration and myofiber catabolism.
2. Mitochondrial Dysfunction
- Impaired ATP generation → reduced muscle contractility and repair.
- Increased ROS and apoptosis of muscle cells.
3. Disuse and Immobilization
- Even 48 hours of immobility can cause measurable muscle atrophy.
- Preferential loss of type II (fast-twitch) fibers.
4. Endocrine and Metabolic Factors
- Hyperglycemia → oxidative stress and microvascular injury.
- Corticosteroids → myosin loss (steroid myopathy).
- Neuromuscular blocking agents (especially prolonged infusion) → potentiate muscle injury.
5. Microcirculatory and Bioenergetic Failure
- Reduced perfusion of peripheral nerves and muscles.
- Decreased protein synthesis and increased proteolysis.
🔹 Risk Factors
|
Category |
Specific Factors |
|
Patient-related |
Older age, pre-existing frailty, malnutrition |
|
Critical illness-related |
Sepsis, multi-organ failure, ARDS, prolonged mechanical ventilation |
|
Iatrogenic |
Prolonged use of corticosteroids or neuromuscular blockers, deep sedation |
|
Metabolic |
Hyperglycemia, hypophosphatemia, electrolyte disturbances |
|
Environmental |
Prolonged immobility, inadequate physiotherapy, bed rest |
🔹 Clinical Features
- Symmetric, flaccid weakness (predominantly proximal > distal)
- Areflexia or hyporeflexia
- No sensory level or cranial nerve involvement
- Facial muscles usually spared
- Diaphragmatic weakness → difficulty weaning from ventilator
- Muscle atrophy becomes evident after several days
- Conscious patients: complain of limb heaviness or inability to move
Key Clinical Clue: Difficulty in weaning from ventilator in an otherwise stable patient should prompt evaluation for ICU-AW.
🔹 Diagnostic Evaluation
Diagnosis is clinical, supported by electrophysiologic and histopathologic tests.
1. Bedside/Clinical Assessment
- Manual muscle testing (MRC scale):
- Each muscle group graded 0–5.
- Total score (sum of 12 muscle groups, max 60).
- ICU-AW = MRC sum score < 48.
2. Electrophysiological Studies
|
Test |
Findings in CIP |
Findings in CIM |
|
Nerve conduction |
↓ CMAPs and ↓ SNAPs (axonal loss) |
↓ CMAPs, normal SNAPs |
|
EMG |
Denervation potentials |
Short-duration, low-amplitude MUAPs |
|
Direct muscle stimulation |
Normal (nerve lesion) |
↓ response (muscle lesion) |
CMAP = Compound Muscle Action Potential
SNAP = Sensory Nerve Action Potential
MUAPs = Motor Unit Action Potentials
|
Pattern of MUAPs |
What it indicates |
Typical condition |
|
Short-duration, low-amplitude MUAPs |
Fewer functioning muscle fibers per motor unit |
Myopathy (e.g., CIM) |
|
Long-duration, high-amplitude MUAPs |
Reinnervation after axonal loss |
Neuropathy (chronic CIP |
Distinguishes CIP (nerve lesion) from CIM (muscle lesion).
3. Muscle Biopsy (if uncertain)
- CIM: Myosin loss, muscle fiber necrosis, vacuolation
- CIP: Axonal degeneration, normal muscle fibers
4. Ancillary Investigations
- CK: Mildly elevated in CIM
- Exclude other causes: hypothyroidism, electrolyte disorders, myasthenia gravis, GBS, etc.
🔹 Differential Diagnosis
|
Condition |
Distinguishing Features |
|
Guillain-Barré syndrome |
Ascending weakness, autonomic dysfunction, albuminocytologic dissociation in CSF |
|
Myasthenia gravis |
Fluctuating weakness, ocular involvement, preserved reflexes |
|
Prolonged neuromuscular blockade |
Recent NMBA use, rapid recovery with discontinuation |
|
CNS lesion (stroke, cord) |
Asymmetry, spasticity, sensory level |
🔹 Complications
- Prolonged ventilator dependence
- Increased ICU and hospital length of stay
- Long-term physical disability
- Decreased quality of life
- Increased mortality
🔹 Management
1. Prevention
|
Measure |
Rationale |
|
Early mobilization and physiotherapy |
Reduces muscle atrophy and improves outcomes |
|
Tight glycemic control (target 140–180 mg/dL) |
Prevents hyperglycemia-induced nerve injury |
|
Minimize corticosteroid and NMBA use |
Avoid or shorten duration if possible |
|
Optimize nutrition |
Adequate protein and energy intake |
|
Limit deep sedation |
Facilitates early mobilization |
2. Supportive Management
- Early weaning trials and respiratory physiotherapy
- Nutritional support (high-protein feeding, avoid catabolic states)
- Rehabilitation (passive → active mobilization)
- Treatment of underlying sepsis and organ failure
3. Pharmacologic Approaches (Experimental / Not Established)
- No proven drug therapy reverses ICU-AW.
- Trials with antioxidants, anabolic steroids, or electrical stimulation are ongoing but inconclusive.
🔹 Prognosis
|
Feature |
Outcome |
|
Mild cases |
Recover in weeks |
|
Moderate to severe cases |
Recovery over months |
|
Persistent severe weakness |
May last >1 year |
|
Mortality |
Increased with prolonged weaning, sepsis, or MODS |
Early recognition and prevention are key to improving outcomes.
🔹 Summary Table
|
Feature |
CIP |
CIM |
|
Site |
Nerve (axonal) |
Muscle |
|
SNAPs |
↓ |
Normal |
|
CMAPs |
↓ |
↓ |
|
EMG |
Denervation |
Myopathic MUAPs |
|
Reflexes |
↓ |
↓ |
|
CK |
Normal |
Mildly ↑ |
|
Muscle biopsy |
Normal fibers |
Myosin loss |
|
Prognosis |
Slower recovery |
Better recovery |
🔹 Key Points
- ICU-AW = Weakness without other cause in critically ill patients.
- Most common cause of ICU-acquired weakness → Critical illness polyneuromyopathy.
- MRC score <48 → diagnostic threshold.
- Facial muscles spared, symmetrical weakness, difficulty in weaning → hallmark features.
- Prevention > Treatment — early mobilization and glycemic control are the best strategies.
References
- Harrison’s Principles of Internal Medicine, 21st Ed. – Chapter on Neuromuscular Complications of Critical Illness
- Marino’s ICU Book, 5th Ed. – ICU Myopathy and Polyneuropathy
- Critical Care Medicine (Hall & Schmidt, 2024)
- Stevens RD et al., Lancet Neurology 2009;8:877–889.
- Fan E. NEJM 2020;382:437–447 – “ICU-acquired weakness review.”