In 1892 Osler described ‘rapid loss of flesh’ in prolonged sepsis. Thereafter, for years, limb weakness was attributed to cachectic myopathy, and difficulty weaning from mechanical ventilation was attributed to diaphragmatic fatigue. In 1961 Mertens described ‘coma-polyneuropathies’, and in 1971 Henderson and colleagues described polyneuropathy in patients with burns. In 1984 Bolton and colleagues, in a series of reports, defined the clinical, electrophysiological and morphological features of septic encephalopathy and critical illness polyneuropathy. Evidence suggested that polyneuropathy was due to the ‘toxic’ effects of sepsis. Polyneuropathy was a common cause of difficulty in weaning when lung and cardiac cause had been excluded. Since 1984, cases of critical illness polyneuropathy have been reported from several countries. Moreover, a number of investigators reported instances of critical illness myopathy. Comprehensive studies by Latronico and colleagues indicated that polyneuropathy and myopathy often occurred together in the same patient. With successful treatment of sepsis, improvement often occurred in encephalopathy, polyneuropathy and myopathy, except in very severe cases.

With better survival of critically ill patients, ‘de novo’ arising neuromuscular complications like critical illness myopathy or polyneuropathy have been increasingly observed. Prolonged hospitalization not only imposes risks like pneumonia or thrombosis on patients but also represents a real budget threat to modern intensive-care medicine. Clinical symptoms like muscle weakness and weaning failure are common to critical illness myopathy and critical illness polyneuropathy and do not allow for distinction. Specific therapies are not yet available, and the quest for the pathomechanisms has proved more complicated than anticipated. Especially for critical illness myopathy, multiple sites of disturbances to the excitation–contraction coupling cascade are possible causes of muscle weakness. The present review summarizes the epidemiological, clinical and diagnostic features of critical illness myopathy and then focuses on current concepts of the presumed pathomechanisms of critical illness myopathy. Sepsis was shown to be a major cause of critical illness myopathy and special emphasis will be placed on how sepsis and inflammatory mediators influence (i) the membrane excitability at the level of voltage-gated ion channels and (ii) the intracellular protein signalling that results in selective loss of myosin protein content and muscle wasting. For (i), critical illness myopathy represents a new type of acquired channelopathy affecting the inactivation properties of Na+ channels. For (ii), both protein proteolysis and protein build up at the transcriptional level seem to be involved. Findings from different studies are put into a common context to propose a model for cytokine-mediated failure of muscle in severe sepsis. This can open a series of new possible trials to test specific therapeutic strategies in the future.

Neuromuscular complications encountered in intensive care can be due to peripheral nerves (polyneuropathies), muscles (myopathies), neuromuscular end-plate (transmission deficit) or a combination of these. Neurophysiopathological tests that enable us to diagnose and maybe differentiate between these causes are essentially electroneurographs and electromyographs. These assess, either directly or indirectly, the integrity of the peripheral system, both sensory (centripetal afferent pathways) and motor (lower motor neurones, neuromuscular junction, muscle membrane and contractile substrate). Electrical activity in the muscle is measured using a special device (an electromyograph) comprising preamplifiers, a computer with special programmes and algorithms for analysing, digitalizing, amplifying and filtering the recorded signal and a monitor on which to visualize the on-line trace. The machine also has speakers. These serve to recognize and identify the physiological events being recorded as they make such unusual, individual sounds. An electric stimulator with constant current can be used to stimulate branches of superficial nerves (motor, sensory or mixed) so that electric conduction speed can be studied and the sensory or motor response analysed. The results can be saved on a hard disc or on any magnetic or digital support, viewed off-line or even printed.

Direct muscular stimulation is quick, simple, non-invasive and can be carried out at the patient’s bedside. More importantly, it is reliable even when the patients cannot cooperate or are comatose. From the small amount of data available, it seems to be as accurate as neuromuscular biopsy in diagnosing critical illness myopathy. It would therefore be advisable to use it in everyday clinical practice.