Neuromuscular Weakness Related to Critical Illness

Abstract

SUMMARY N euromuscular weakness is a common occurrence in patients who are critically ill, developing in ≥25 percent of patients who are in the intensive care unit (ICU) and ventilated for at least seven days . Weakness is partly a consequence of improved survival in patients with multiorgan failure and sepsis, but is also a consequence of treatments administered in the ICU, including intravenous glucocorticoids and sometimes paralytic agents. Neuromuscular weakness in the ICU is most often due to critical illness myopathy (CIM) or to critical illness polyneuropathy (CIP). In a critically ill patient who develops flaccid generalized weakness, the major considerations in the differential diagnosis are critical illness myopathy and critical illness polyneuropathy, or a combination of the two. Other considerations in the differential include rhabdomyolysis, cachectic myopathy, and Guillain-Barré syndrome. Myopathy is a general term for every potential muscle problem (primary structural or functional impairment). Myopathy may be hereditary or acquired. One of the most important causes of myopathy in critically ill patients is critical illness myopathy (CIM) which causes failure of weaning from ventilator. The strongest risk factor for CIM is the use of intravenous (IV) glucocorticoids in the ICU setting. CIM usually begins several days or so after IV glucocorticoid treatment is initiated. Many other risk factors are accused of precipitating CIM such as systemic inflammation, hyperglycemia, medications as (NMBAs, aminoglycosides and sedatives), electrolyte disturbances and immobility. The mechanism of CIM may be through either muscle membrane inexcitability, altered calcium homeostasis and consequently disturbing the excitation-contraction coupling, rapid decrease in muscle protein content due to up-regulation of proteolytic enzymes including the ubiquitin proteasome pathway and calpains, nitric oxide (NO) overproduction, antioxidant depletion, mitochondrial dysfunction and decreased ATP production and increase in reactive oxygen species (ROS), what is so called oxidative stress and bioenergetic failure.The most common presenting features are flaccid quadriparesis and failure to wean from mechanical ventilation. Major electrophysiologic findings of CIM include normal to low-amplitude, often broad (long duration) motor responses and short-duration motor unit potentials coupled with normal or near-normal sensory potentials. Needle electromyography shows early or normal full recruitment. Some muscles exhibit electrical inexcitability to direct muscle stimulation. The major histopathologic findings are myopathy and myosin loss. Serum CK elevation is seen in approximately one-half of patients. CIM is usually reversible over weeks to months but it leads to prolonged ICU stays and increased length of hospital stay overall. Treatment is directed toward discontinuation or reduction of glucocorticoids as soon as possible. Critical illness polyneuropathy (CIP) is another common cause of neuromuscular weakness that is acquired in the ICU, most often as a complication of severe sepsis . CIP is thought to represent a neurologic manifestation of the systemic inflammatory response syndrome. CIP is characterized clinically by limb muscle weakness and atrophy, reduced or absent deep tendon reflexes, loss of distal peripheral sensation, and relative preservation of cranial nerve function. It is hypothesized that microvascular endothelial alterations in the endoneurium surrounding the individual nerve fibers are crucial in the development of CIN. Compression neuropathies are common in ICU. Several nerves are particularly at risk, compression of which may increase morbidity as ulnar and peroneal nerves