Critical Illness Myopathy: Mechanisms, Symptoms & Care Options

Muscle weakness is a common complication in critically ill patients, often leading to prolonged recovery and increased healthcare needs. Critical illness myopathy (CIM) primarily affects those requiring extended intensive care, significantly impacting mobility and complicating rehabilitation.

Understanding CIM is essential for early diagnosis and effective management.

Pathophysiological Mechanisms

CIM results from a complex interplay of metabolic, structural, and functional disruptions within skeletal muscle. A primary driver of muscle dysfunction is myosin depletion, particularly in fast-twitch muscle fibers, which are more susceptible to degradation under catabolic stress. This selective loss impairs contractile force generation, leading to profound weakness. Histological analyses frequently reveal myosin-deficient fibers, a hallmark of CIM.

Beyond myosin depletion, intracellular signaling disruptions contribute to muscle atrophy. The ubiquitin-proteasome system (UPS) and autophagy-lysosome pathway become hyperactive, accelerating protein breakdown. Concurrently, suppression of the insulin-like growth factor-1 (IGF-1)/Akt/mTOR pathway further shifts the balance toward catabolism. Research in The Lancet Neurology highlights increased expression of muscle-specific E3 ubiquitin ligases, such as atrogin-1 and MuRF1, as key drivers of proteolysis.

Mitochondrial dysfunction exacerbates muscle impairment by disrupting energy metabolism. Electron transport chain abnormalities and oxidative stress reduce ATP production, impairing contractility and endurance. Muscle biopsies from CIM patients show mitochondrial swelling and cristae disorganization, indicating structural damage. A study in Nature Reviews Neurology reported elevated reactive oxygen species (ROS) levels in CIM patients, which damage mitochondria and activate proteolytic pathways, perpetuating muscle degradation. This oxidative imbalance, compounded by reduced antioxidant defenses, sustains muscle dysfunction.

Clinical Manifestations

Muscle weakness in CIM often emerges as patients recover from their primary illness. It primarily affects the proximal limb muscles, making tasks like lifting the arms or standing difficult. The lower limbs tend to be more severely impacted, hindering ambulation and increasing dependence on mobility assistance. Facial and ocular muscles are typically spared, distinguishing CIM from disorders like Guillain-Barré syndrome or myasthenia gravis.

Severity varies from mild weakness to profound quadriparesis. In severe cases, patients may be unable to move against gravity, exhibiting flaccid paralysis with preserved deep tendon reflexes. This contrasts with critical illness polyneuropathy (CIP), where reflexes are diminished or absent. Electromyographic studies confirm that muscle excitability remains intact, emphasizing that dysfunction originates within the muscle fibers rather than the nerves. Clinicians may observe muscle wasting, particularly in the thighs and shoulders.

Respiratory muscle involvement can prolong mechanical ventilation. Diaphragm weakness leads to shallow breathing and impaired cough reflex, increasing infection risk and delaying ventilator weaning. A study in Chest found that CIM patients with significant diaphragm weakness required 40% longer ventilator support.

Influencing Factors In Critical Care

Several factors in intensive care contribute to CIM development. Prolonged immobility leads to rapid muscle deconditioning, with reductions in fiber cross-sectional area and a shift toward a more fatigue-prone phenotype. Early mobilization protocols help mitigate this decline, though sedation, hemodynamic instability, and ventilatory support often limit implementation.

Pharmacologic interventions also play a role. Corticosteroids, commonly used for inflammation and respiratory distress, exacerbate muscle catabolism by suppressing protein synthesis and enhancing proteolysis. Neuromuscular blocking agents, used to reduce oxygen demand in ventilated patients, impair muscle excitation-contraction coupling. Prolonged exposure to these agents, especially alongside corticosteroids, increases CIM risk.

Nutritional deficits further compound muscle wasting. Critically ill patients frequently experience inadequate protein intake due to feeding interruptions, gastrointestinal dysfunction, or metabolic alterations. While protein supplementation strategies aim to counteract catabolism, optimal dosing and timing remain under investigation. Micronutrient imbalances, such as deficiencies in vitamin D, selenium, and zinc, may further impair muscle metabolism and recovery.

Electrophysiological And Laboratory Tests

Diagnosing CIM involves electrophysiological studies and laboratory markers. Electromyography (EMG) reveals low-amplitude motor unit potentials with normal or near-normal nerve conduction velocities. Unlike polyneuropathies, where conduction slowing is prominent, CIM patients typically exhibit preserved sensory nerve function, reinforcing primary muscle involvement. Direct muscle stimulation studies further clarify the diagnosis, showing reduced muscle excitability without nerve dysfunction.

Muscle biopsy findings often align with electrophysiological abnormalities, but less invasive biomarkers are also being explored. Elevated serum creatine kinase (CK) levels can indicate muscle fiber breakdown, though this marker is not consistently elevated in prolonged illness. More specific to CIM, reductions in myosin-to-actin ratios in muscle tissue reflect selective myosin degradation. Emerging research suggests serum myosin light chain fragments may serve as an early CIM biomarker, though clinical validation is ongoing.

Differentiating From Polyneuropathy

Distinguishing CIM from CIP is crucial for tailored management, as both conditions present with profound muscle weakness but have distinct causes. While CIM results from muscle fiber dysfunction and myosin depletion, CIP stems from peripheral nerve axonal degeneration, impairing nerve conduction and causing sensory deficits.

A detailed neurological examination aids differentiation. CIM patients typically retain normal or near-normal deep tendon reflexes, while CIP patients often have diminished or absent reflexes due to nerve involvement. Sensory deficits, such as reduced vibratory perception or impaired pain sensation, are hallmarks of CIP but absent in CIM. Additionally, muscle atrophy is more pronounced in CIM due to direct myofiber degradation, whereas CIP-related weakness results from denervation-induced wasting.

Electrophysiological studies provide further clarity. Nerve conduction studies in CIP show reduced compound muscle action potentials (CMAPs) and sensory nerve action potentials (SNAPs), indicative of axonal loss. In contrast, CIM features normal or minimally affected sensory nerve conduction with reduced muscle membrane excitability and low-amplitude motor unit potentials on EMG. Direct muscle stimulation tests confirm diminished muscle excitability in CIM but remain normal in CIP. Some patients exhibit a mixed phenotype, necessitating comprehensive electrophysiological assessment.