This vexing question has been recognized with increasing frequent occurrence in recent years.

This vexing question has been recognized with increasing frequent occurrence in recent years. Causes similar as Guillain-Barre syndrome and myasthenia gravis are still listed in standard textbook still it should be recognized that conditions associated with sepsis are the greatest in quantity common.(1) Physical examination is unreliable, and comprehensive electrophysiologic studies, measurements of creatinine phosphokinase, and, at times, muscle biopsy are necessary to establish the correct diagnosis. Foremost among the possible causes is critical illness polyneuropathy, which come to one's minds in 70 percent of patients who have sepsis and multiple organ failure and which, in our experience, is the principally common neuromuscular cause of difficulty in weaning from the ventilator. It is characterized by the agency of an axonal degeneration of peripheral coolness fibers, denervation atrophy of muscle, and normal or barely mildly elevated levels of creatinine phosphokinase. It regularly improves as the sepsis is brought in subordination to control. Rarely, one observes a syndrome of acute, generalized muscle fiber necrosis, characterized from muscle weakness, considerably elevated on a levels of creatinine phosphokinase, and muscle necrosis forward biopsy. Spontaneous and sometimes remarkably rapid restoration occurs. This syndrome is precipitated by way of infection, trauma, and drugs and, hence, is more likely to come to pass in critical care units than in other clinical settings. Disuse atrophy likely befalls but it is difficult to define because electrophysiologic studies and creatinine phosphokinase plains are normal, and muscle biopsy is either normal or indicates the nonspecific change of adumbration 2 fiber atrophy.

More freshly an increasing number of reports have attributed weakness and difficulty in weaning from the ventilator to the use of neuromuscular blocking agents, corticosteroids, or both(2)(3) Not alone may prolonged neuromuscular blockade arise particularly with the use of vecuronium in association with renal failure,(4) unless motor axonal polyneuropathy and myopathy have also been reported. In this issue (see page 210) Giostra et al add to this list with the report of their findings in nine patients. Their findings insinuate but do not prove, that the neuromuscular blocking agent pancuronium bromide and steroids as well-as; not only-but also; not only-but; not alone-but contributed to the quadriplegia. Muscle biopsy specimens showed varying grades of muscle fiber atrophy and, in particular, necrosis. The necrosis likely accounted for the elevations in creatinine phosphokinase flats and could not be attributed to denervation.

While the authors claimed sepsis was unlikely to have been a contributing factor, all patients were prime candidates since they were intubated and forward ventilators for longer than 5 days. It may be that a combination of factors is operative. Sepsis, from one side the action of cytokines, induces a disturbance in the microvasculature from one extremity to the other of the body. We have speculated(1)(5)(6) that this disturbance may be the underlying mechanism of critical illness polyneuropathy, and possibly "septic myopathy," inducing the reckon uponed distal axonal degeneration, denervation atrophy, and mild necrosis of muscle. However, a major constituting of the microvascular response is increased capillary permeability. This would theoretically allow potentially toxic substances, as it is as neuromuscular blocking agents or their metabolites, aminoglycoside antibiotics, and possibly steroids, to cros blood-nerve and blood-muscle barriers and induce additional toxic imports In muscle, this could account for the combination of denervation atrophy and widespread necrosis. The combination of denervation of muscle and steroids may induce "myosin filament myopathy".(7)

Thus, the cogitation by Giostra et al adds to the disquiet regarding the toxicity of these mix with drugss Only well-designed, prospective studies, which would include careful clinical, electrophysiologic, biochemical, pharmacologic, and morphologic measurements, will help in solving a moot point that is still underrecognized, despite its important implications in patient management and the take away from of medical care.

Charles F Bolton, MD London, Ontario, Canada

Department of Clinical Neurological Sciences, Victoria Hospital, University of Western Ontario.

REFERENCES

(1)Bolton CF Young GB Zochodne DW The neurological complications of sepsis. Ann Neurol 1993; 33:94-100

(2)Lacomis D Smith TW Chad DA. Acute myopathy and neuropathy in status asthmaticus: case report and literature review. Muscle self-command 1993; 16:84-90

(3)Gorson KC Ropper AH. Acute respiratory failure neuropathy: a variant of critical illness polyneuropathy. Crit Care M 1993; 21:2:267-71

(4)Segredo V Caldwell JE Matthay MA, Sharma ML Gruenke LD Miller RD Persistent paralysis in critically ill patients after long-term administration of vecuronium. N Engl J M 1992; 327:524-28

(5)Zochodne DW Bolton CF Wells GA, Gilbert JJ Hahn AF, Brown JD et al. Polyneuropathy associated with critical illness: a complication of sepsis and multiple organ failure. Brain 1987; 110:819-42

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