Summary
ICU-acquired weakness (ICU-AW) is generalized limb weakness that develops during critical illness without an alternative cause; it encompasses critical illness polyneuropathy (CIP), critical illness myopathy (CIM), and critical illness polyneuromyopathy. ICU-AW affects approximately half of all critically ill patients. Risk factors include severe illness (e.g., sepsis), iatrogenic factors (e.g., prolonged mechanical ventilation, early parenteral nutrition, certain medications including glucocorticoids), and hyperglycemia. Patients typically present with diffuse, symmetrical, flaccid limb weakness; weaning from mechanical ventilation may be prolonged if the respiratory muscles are affected. Clinical features often overlap, but CIP is characterized by distal sensory disturbances and reduced or absent deep tendon reflexes, whereas CIM is characterized by muscle atrophy and typically affects proximal muscles more than distal muscles. The diagnosis is based on clinical features and confirmed on electrodiagnostic studies. Additional diagnostic testing is required to rule out alternative causes. Management focuses on treating the underlying critical illness, addressing contributing iatrogenic factors, and ensuring early mobilization with physical and occupational therapy. Most patients make a full recovery, usually over weeks to months.
Definitions
ICU-AW is generalized limb weakness that develops during critical illness without an alternative cause; it encompasses: [1][2]
- Critical illness polyneuropathy (CIP): axonal sensorimotor polyneuropathy [3]
- Critical illness myopathy (CIM): primary myopathy [3]
- Critical illness polyneuromyopathy: combination of CIP and CIM [4]
Epidemiology
Epidemiological data refers to the US, unless otherwise specified.
Etiology
The exact etiology is unknown and likely multifactorial.
- Several risk factors for ICU-AW have been identified, including: [3]
- Severe illness
-
Iatrogenic factors
- Prolonged mechanical ventilation [1]
- Prolonged ICU stay and immobility
- Early parenteral nutrition [5]
- Medications (e.g., glucocorticoids, neuromuscular blockers)
- Laboratory findings
- Hyperglycemia
- Elevated serum lactate level [5]
- Premorbid comorbidity and frailty [2]
- Obesity may be associated with a decreased risk. [5]
Pathophysiology
The pathophysiology is not fully understood; a combination of factors may contribute to muscle atrophy and dysfunction, e.g.: [5]
- Microcirculatory disturbances → hypoperfusion and hypoxia
- Structural changes (e.g., axonal nerve degeneration, myosin loss)
- Channelopathies (e.g., sodium channel inactivation)
- Mitochondrial dysfunction
Clinical features
CIP and CIM often have overlapping clinical features, but characteristic features help distinguish them; features of both conditions may coexist in critical illness polyneuromyopathy. [3][6]
- General features of ICU-AW
-
Characteristic features of CIP
- Reduced or absent deep tendon reflexes
- Distal sensory disturbance (e.g., dysesthesia) [7]
- Typically affects distal muscles more than proximal muscles [7]
-
Characteristic features of CIM
- Normal or reduced deep tendon reflexes
- Muscle atrophy [7]
- Typically affects proximal muscles more than distal muscles [3][7]
ICU-AW is a common cause of prolonged weaning from mechanical ventilation in critically ill patients with sepsis. [6]
Diagnostics
To assess for ICU-AW, evaluate muscle strength using a validated scale (e.g., Medical Research Council sum score); Order confirmatory studies if significant strength deficits persist on serial evaluations.[5]
Confirmatory studies [3][5]
- Laboratory studies: Creatine kinase is normal in CIP and may be mildly elevated in CIM.
-
Electrodiagnostic studies: used to confirm the diagnosis and rule out alternative diagnoses
-
Electromyography
- Spontaneous activity (e.g., fibrillations, positive sharp waves)
- Can differentiate between CIM and CIP based on motor unit action potentials
-
Nerve conduction studies
- Normal nerve conduction velocity
- Reduced compound muscle action potential amplitude
- Can differentiate between CIM and CIP based on compound sensory nerve action potentials
-
Electromyography
-
Muscle biopsy
- May be considered for diagnostic confirmation if electrodiagnostic studies are inconclusive [6]
- Findings may include:
- Denervation atrophy in CIP
- Loss of thick myosin filaments and necrosis in CIM
Additional studies [8]
Indicated to rule out alternative causes; See "Diagnostics for neuromuscular weakness" for details.
-
Laboratory studies: Obtain targeted studies based on clinical evaluation for common systemic causes of weakness.
- BMP, including serum electrolytes
- Thyroid function tests
- Cortisol
- Acetylcholine receptor antibodies (See "Diagnostics for myasthenia gravis.")
- Studies for infectious etiologies (e.g., HIV, Lyme disease)
- Neuroimaging and spinal imaging: to exclude structural causes based on clinical suspicion
Differential diagnoses
See also "Causes of neuromuscular weakness."
-
Central causes
- Ischemic stroke
- Acute encephalopathy
- Spinal cord lesions (e.g., acute myelopathy)
- Polyneuropathies
-
Neuromuscular junction disorders
- Myasthenia gravis
- Lambert-Eaton myasthenic syndrome
- Prolonged neuromuscular blockade (see “Skeletal muscle relaxants”)
- Acute myopathies: rhabdomyolysis
The differential diagnoses listed here are not exhaustive.
Management
There is no specific treatment for ICU-AW; a multidisciplinary team approach is recommended. [3][6][7]
- Mobilize patients and consult physical therapy and occupational therapy as early as possible.
- Treat the underlying critical illness (e.g., sepsis, MODS).
- Address iatrogenic factors if present (e.g., prolonged mechanical ventilation).
- Provide supportive care for the critically ill patient.