Patients in the intensive care unit (ICU) may develop generalized weakness due to critical illness polyneuropathy or prolonged neuromuscular blockade, or secondary to a myopathic process. Approximately 30-50% of patients admitted to the ICU develop CIM, CIP, or both. Their clinical features often overlap. Clinical manifestations include difficulty weaning from the respirator and diffuse muscle weakness with immobilization. CIP is often monophasic and self-limiting; it can remit spontaneously once the eliciting condition is under control. Among the CIMs, three main types have been identified: a non-necrotizing “cachectic” myopathy, a myopathy with selective loss of myosin filaments (“thick filament myopathy”), which is most common, and an acute necrotizing myopathy of intensive care.
High dose intravenous corticosteroids along with nondepolarizing neuromuscular blockers, but it also occurs in patients with sepsis or multiorgan failure who never received either corticosteroids or nondepolarizing neuromuscular blocking agents.
Severe generalized weakness of the trunk, extremities, and respiratory muscles that can rarely involve the extraocular muscles are the presenting features. The myopathy is usually initially recognized by the inability to wean the patient from the ventilator. Sensory examination is usually normal but difficult to determine in an intubated patient with altered mental status. Sensation is usually spared, and is an important finding which differentiates it from CIP. and AIDP. Deep tendon reflexes are decreased or absent. The mortality is high secondary to frequent occurrence of multiple organ failure and sepsis. Muscle strength recovers slowly over several months.
Serum CK levels are normal or moderately elevated.
Risk factors: Typical risk factors for ICU-acquired weakness include sepsis, prolonged mechanical ventilation, prolonged ICU length of stay, hyperglycemia, systemic inflammatory response syndrome, and prolonged immobilization. Prolonged pharmacologic paralysis and high-dose steroids have been associated with ICU–acquired weakness.
Evaluation of ICU–acquired weakness has been traditionally performed by using the Medical Research Council sum score evaluated by manual muscle testing of three muscle groups in each extremity when a patient is able to participate in examination. A score less than 48 of 60 is consistent with the diagnosis. Patients may show a variable degree of muscle atrophy.
EMG and nerve conduction studies show variable combinations of neurogenic and myogenic abnormalities, which may be characterized as critical illness neuropathy, myopathy, or neuromyopathy. When present, the neuropathy is typically axonal in pattern. Electrodiagnostic studies are also valuable in cases of possible underlying demyelinating polyneuropathies, such as Guillain-Barré syndrome or chronic inflammatory demyelinating polyneuropathy, that could be amenable to immunomodulatory therapy.
Laboratory tests such as creatine kinase and interleukin 6 have been studied but have not been found to be useful in the diagnosis or prognosis of this syndrome.
Most current guidelines on the prevention and management of ICU–acquired weakness recommend aggressive high-protein enteral therapy and, when feasible, resistance exercise therapy. Intensive insulin therapy to prevent hyperglycemia and minimizing sedation to improve early mobility have been shown to be effective in reducing the incidence and impact of ICU–acquired weakness. Several clinical trials have investigated the use of functional electrical stimulation and specific nutritional strategies but have provided mixed results. Overall consensus favors early mobilization and exercise-based interventions as having positive outcomes in preventing ICU–acquired weakness. Specific syndromes such as acute lung injury–related muscle weakness, sepsis-induced myopathy, and steroid myopathy have been described in critically ill patients, as well. Emerging research in critical care has implicated proinflammatory mechanisms causing muscle weakness in addition to other factors such as muscle wasting resulting from disuse atrophy, insufficient nutrition, pharmacologic exposures, and imbalance between protein catabolism and synthesis. A syndrome of ventilator-induced diaphragm dysfunction has been described with controlled modes and higher levels of mechanical ventilatory support.
EDx: CIM and CIP can be difficult to differentiate clinically, but they often have distinctive pathological and electrophysiological features. CIM in the absence of polyneuropathy demonstrates relative preservation of sensory nerve action potentials (SNAPs), with low amplitude or absent compound muscle action potentials (CMAPs), and normal conduction velocities. Fibrillation potentials may be prominent early in the course of CIM, while voluntary contraction reveals rapid recruitment of small, polyphasic motor unit potentials (MUPs). These electrodiagnostic features can help to differentiate CIP and CIM. However, because these disorders can occur concurrently, and MUP analysis is often difficult to perform in paretic, sedated, and often encephalopathic patients, additional electrophysiological markers are needed to help establish an accurate diagnosis.
CMAP duration may be prolonged CIM.
Mean CMAP duration in msec from healthy controls:
Peroneal – tibialis anterior: 13.6* (12.1-15.9)
Peroneal – extensor digitorum brevis: 5.5 (3.5-7.8)
Tibial – abductor hallucis: 5.4 (3.8-6.8)
Median – thenar: 5.4 (3.0-7.8)
Ulnar – hypothenar: 6.0 (5.0-7.7)
Mean CMAP duration in msec from CIM patients:
Peroneal – tibialis anterior: 28.3 (23.5-38.8)
Peroneal – extensor digitorum brevis: 17.7 (8.8-21.5)
Tibial – abductor hallucis: 20.3 (17.9-19.9)
Median – thenar:11.9 (7.4-22.0)
Ulnar – hypothenar: 12.8 (9.8-15.1)
In CIM, muscle fibers often are inexcitable to direct stimulation. In contrast in CIP, muscle fibers can be activated by direct stimulation. Thus it is possible to differentiate between CIM from CIP using direct stimulation. The ratio of nerve stimulation CMAP (neCMAP)/Direct muscle CMAP (dmCMAP) for CIP is low or zero as there is disproportionate lower neCMAP compared to dmCMAP. For CIM the ratio is close to one, as both the amplitudes are proportionately affected.
Muscle biopsies reveal a wide spectrum of histological abnormalities, including type 2 muscle fiber atrophy with or without type 1 fiber atrophy, scattered necrotic muscle fibers, and importantly, focal or diffuse loss of reactivity for myosin ATPase activity. EM reveals loss of thick filaments (myosin).
Intensive hyperglycemia treatment with insulin reduces the risk of development of critical illness neuropathy (CIN) in the ICU. Sepsis, hypoalbuminemia, and nutritional factors are risk factors for CIN. Systemic inflammatory response syndrome-associated inflammatory cytokines and microvascular damage leads to axonal degeneration in CIN.