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ABSTRACTS & COMMENTARY
Sources: Lacomis D, et al. Acute myopathy of intensive care: Clinical, electromyographic, and pathological aspects. Ann Neurol 1996;40:645-654; Berek K, et al. Critical illness polyneuropathy in multiple organ dysfunction syndrome and weaning from the ventilator. Intensive Care Med 1996;22:849-855; Leijten FSS, et al. Critical illness polyneuropathy in multiple organ dysfunction syndrome and weaning from the ventilator. Intensive Care Med 1996;22:856-861.
Three recent articles bring new insight to the clinical and pathophysiologic aspects of neuromuscular conditions occurring in the intensive care unit. Lacomis et al describe 14 patients with either pulmonary disorders and sepsis (n = 6) or post organ transplantation (n = 8) who received high-dose intravenous corticosteroids, with or without neuromuscular junction (NMJ) blocking agents. Flaccid quadriparesis and failure to wean from mechanical ventilation was detected following discontinuation of NMJ blockers. Creatine kinase was elevated in only three, while electromyography demonstrated findings consistent with a destructive myopathy confirmed on muscle biopsy by the presence of necrosis in all and loss of thick myosin filaments in 11. Delayed diagnoses resulting from the difficulties encountered in examining pharmacologically paralyzed respirator-dependent patients explain why serum CK values, once drawn, are normal in most patients despite the presence of a destructive myopathy.
In the study from Berek et al, among all patients without evidence of pre-existing neurologic disease admitted to the Innsbruck University Hospital intensive care unit over a one-year period, 22 had multiple organ failure or sepsis. None received corticosteroids or NMJ blocking agents. Using clinical and electrophysiological criteria, an astonishing 18 (82%) developed an axonal (n = 16) or mixed axonal-demyelinating (n = 2) polyneuropathy during admission. At least in Austria critical illness polyneuropathy (CIP) is more prevalent than previously suspected.
In Leijten et al's study, among all ICU patients admitted for a variety of reasons but without evidence of pre-existing neuropathy, distal weakness, numbness, or paresthesiae, 38 required mechanical ventilation for longer than one week. Eighteen developed an axonal CIP. Although CIP patients were ventilated longer, this association did not reach statistical significance (P = 0.26). Rather, CIP was significantly associated with the number of organ systems involved (P = 0.009) and the severity of their dysfunction (P = 0.003), particularly cardiac, renal, and hematologic failure, suggesting a common pathogenesis.
Pharmacologic neuromuscular blockade is a powerful but not completely benign tool in the armamentarium for critically ill ICU patients. Atracurium and vecuronium are the preferred agents to facilitate mechanical ventilation, limit oxygen consumption, and calm severely agitated patients (Appadu BL, et al. Intensive Care Med 1996;22:862-866), but it is clear that success comes at a heavy cost. Despite the purported relative lack of side effects of these intermediary acting NMJ blockers, reports of prolonged muscle weakness following their use continue to appear (Hoey LL, et al. Pharmacotherapy 1995;15:254-259; Rubio ER, et al. South Med J 1996;18:937-942). Significantly, prolonged motor weakness encompassing critical illness polyneuropathy, junctionopathy, and myopathy complicating NMJ blockade in the ICU adds more than $66,000 (range, $23,485-$189,214) to the median cost of hospitalization (Rudis MI, et al. Crit Care Med 1996;24:1749-1756).
Etiology remains uncertain. Most patients have no previous neuromuscular disease. Although some believe that the combination of steroids and prolonged NMJ block is critical for the development of myopathy (Lacomis D, et al. Muscle Nerve 1993;1993:16:84-90), this is not universally so (Zochodne DW, et al. Muscle Nerve 1994;17:285-292). Further, following prolonged NMJ blockade, some patients develop a destructive myopathy, while others develop prolonged weakness that resolves in several days, the latter most likely due to metabolite accumulation.
In the presence of overwhelming sepsis, multiple organ failure may result from the toxic side effects of inflammation (Witt NJ, et al. Chest 1991;99:176-184). Its association with CIP, whose frequency correlates with increased organ dysfunction and increased number of organs involved, suggests that CIP may have a similar pathogenesis. Although intercostal muscle biopsy has demonstrated structural alterations of the end plate in CIP (Wokke JH, et al. J Neurol Sci 1988;88:95-106), this must be confirmed by others. CIP may thus simply represent another organ that fails in the face of critical illness. Non-septic acute conditions, however, are also associated with CIP (Gorson KC, et al. Crit Care Med 1993;21:267-271). Cytokines, histamines, complement, and cell adhesion systems may possibly play a role in the genesis of CIP associated with sepsis by disturbing microvascular circulation and capillary permeability (Witt NJ, et al. Chest 1991;99:176-184; Hund EF. J Neurol Sci 1996;136:10-16). Alternatively, or concomitantly, free radicals may play an additional role (Goode HF, et al. Crit Care Med 1993;21:1770-1776). Necrotic myopathy in the acutely ill may result from identical mechanisms but may also be seen in aseptic patients who have received either corticosteroids or neuromuscular blocking agents, and thus its etiology is least understood.