Abstract
Neuromuscular disorders increasingly are recognized as a complication in patients in the intensive care unit (ICU) and represent a common cause of prolonged ventilator dependency. The distinct syndromes of critical illness myopathy, prolonged neuromuscular blockade, and critical illness polyneuropathy (CIP) may arise as a consequence of sepsis, multi-organ failure, and exposure to various medications—notably, intravenous corticosteroids and neuromuscular blocking agents—but the pathophysiology of these disorders remains poorly understood. More than one syndrome may occur simultaneously, and the distinctions may be difficult in a particular patient, but a specific diagnosis usually can be established after careful clinical, electrodiagnostic, and, when necessary, histological evaluation. For example, asthmatics requiring treatment with corticosteroids and neuromuscular blocking agents may develop an acute myopathy characterized by generalized weakness, preserved eye movements, elevated creatine kinase levels, and myopathic motor units on electromyography (EMG). Muscle biopsy demonstrates distinctive features of thick (myosin) filament loss on ultrastructural studies. Conversely, those with a prolonged ICU course that is complicated by episodes of sepsis with failure to wean from the ventilator, distal or generalized flaccid limb weakness, and areflexia probably have CIP. EMG in these patients demonstrates reduced or absent motor and sensory potentials with neurogenic motor units. Prolonged neuromuscular blockade most commonly occurs in patients with renal failure who have received prolonged infusions of neuromuscular blockers. There is severe flaccid, areflexic paralysis with normal sensation, facial weakness, and ophthalmoparesis that persists for days or weeks after the neuromuscular blockers have been discontinued. Repetitive nerve stimulation shows a decrement of the compound muscle action potential and, in most cases, establishes a disorder of neuromuscular transmission. With the recent epidemic of West Nile virus infection, a clinical syndrome of acute flaccid paralysis with several features indistinguishable from poliomyelitis has emerged. This article critically examines the clinical, electrophysiological, and pathological features of these and other acute neuromuscular syndromes that arise in the context of ICU care and summarizes the current understanding of the pathophysiology and treatment of these disorders.
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Gorson KC, Ropper AH. Generalized paralysis in the intensive care unit: emphasis on the complications of neuromuscular blocking agents and corticosteroids. J Int Care Med 1996;11:219–231.
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 Med 1992;327:524–528.
De Jonghe B, Bastuji-Garin S, Sharshar T, Outin H, Brochard L. Does ICU-acquired paresis lengthen weaning from mechanical ventilation? Intensive Care Med 2004;6:1117–1121.
Hirano M, Ott BR, Raps EC, et al. Acute quadriplegic myopathy: a complication of treatment with steroids, non-depolarizing blocking agents, or both. Neurology 1992;42:2082–2087.
Zochodne DW, Ramsay DA, Saly, V, Shelley S, Moffatt S. Acute necrotizing myopathy of intensive care: electrophysiological studies. Muscle Nerve 1994;17:285–292.
Ramsay DA, Zochodne DW, Robertson DM, Nag S, Ludwin SK. A syndrome of acute severe muscle necrosis in intensive care unit patients. J Neuropath Exp Neurol 1993;52:387–398.
Barohn RJ, Jackson CE, Rogers SJ, Ridings LW, McVey AL. Prolonged paralysis due to non-depolarizing neuromuscular blocking agents and corticosteroids. Muscle Nerve 1994;17:647–654.
Waclawik AJ, Sufit RL, Beinlich BR, Schutta HS. Acute myopathy with selective degeneration of myosin filaments following status asthmaticus treated with methylprednisolone and vecuronium. Neuromusc Disord 1992;2:19–26.
Bolton CF, Gilbert JJ, Hahn AF, Sibbald WJ. Polyneuropathy in critically ill patients. J Neurol Neurosurg Psych 1984;47:1223–1231.
Zochodne DW, Bolton CF, Gilbert JJ. Polyneuropathy in critical illness: pathologic features. Ann Neurol 1985;18:160,161.
Witt NJ, Bolton CF, Sibbald WJ. The incidence and early features of the polyneuropathy of critical illness. Neurology 1985;35(Suppl 1):74.
Bolton CF, Laverty DA, Brown JD, Witt NJ, Hahn AF, Sibbald WJ. Critically ill polyneuropathy: electrophysiological studies and differentiation from Guillain-Barre syndrome. J Neur Neurosurg Psych 1986;49:563–573.
Zochodne DW, Bolton CF, Wells GA, et al. Critical illness polyneuropathy. A complication of sepsis and multi-organ failure. Brain 1987;110:819–842.
Bolton CF. Polyneuropathy as a cause of respiratory failure in critical illness. Int Crit Care Digest 1988;77:8.
Bolton CF. Electrophysiologic studies of critically ill patients. Muscle Nerve 1987;10:129–135.
Coronel B, Mercatello A, Couturier JC, et al. Polyneuropathy: potential causes of difficult weaning. Crit Care Med 1990;16:486–489.
Op de Coul AAW, Lambregts PCLA, Kleman J, van Puyenbroek MJE, Ter Laak HJ, Garbreels-Festen AAWM. Neuromuscular complications in patients given Pavulon (pancuronium bromide) during artificial ventilation. Clin Neurol Neurosurg 1985;87:17–22.
Op de Coul AAW, Verheul GAM, Leyten ACM, Schellens RLLA, Teepen JLJM. Critical illness polyneuromyopathy after artificial respiration. Clin Neurol Neurosurg 1991;93:27–33.
Couturier JC, Robert D, Monier P. Polynevrites compliquant des sejours prolonges en reanimation. A Propos de 11 cas d’etiologie encore inconnue. Lyon Med 1984;252:274–279.
Williams AC, Sturman S, Kelsey S, et al. The neuropathy of the critically ill. Br Med J 1986;293:790,791.
Gorson KC, Ropper AH. Acute respiratory failure in neuropathy: a variant of critical illness polyneuropathy. Crit Care Med 1993;21:267–271.
Raps EC, Bird SJ, Hansen-Flaschen JH. Prolonged muscle weakness after neuromuscular blockade in the intensive care unit. Crit Care Clinics 1994;10:799–813.
van Mook WNKA, Hulsewe-Evers RPMG. Critical illness polyneuropathy. Opin Crit Care 2002;8:302–310.
Hund E. Neurological complications of sepsis:critical illness polyneuropathy and myopathy. J Neurol 2001;248:929–934.
Gazmuri RJ, Hanif S, Wagner B. Persistent paralysis after vecuronium administration. N Engl J Med 1992;327:1881,1882.
Hansen-Flaschen J, Cowen J, Raps EC. Neuromuscular blockade in the intensive care unit. More than we bargained for. Am Rev Respir Dis 1993;147:234–236.
Marinelli WA, Leatherman JW. Neuromuscular disorders in the intensive care unit. Crit Care Clin 2002;18:915–929.
Chad DA, Lacomis D. Critically ill patients with newly acquired weakness: the clinicopathological spectrum. Ann Neurol 1994;35:257–259.
Hund EF. Neuromuscular complications in the ICU: the spectrum of critical illness-related conditions causing muscular weakness and weaning failure. J Neurol Sci 1996;136:10–16.
Hund E. Myopathy in critically ill patients. Crit Care Med 1999;27:2544–2547.
Bolton CF. The polyneuropathy of critical illness. J Intensive Care Med 1994;9:132–138.
Leijten FSS, de Weerd AW. Critical illness polyneuropathy. A review of the literature, definition and pathophysiology. Clin Neurol Neurosurg 1994;96:10–19.
Bolton CF. Sepsis and the systemic inflammatory response syndrome: neuromuscular manifestations. Crit Care Med 1996;24:1408–1416.
Zochodne DW, Bolton CF. Neuromuscular disorders in critical illness. Bailliere’s Clinical Neurology 1996;5:645–671.
Maher J, Rutledge F, Remtulla H, Parkes A, Bernardi L, Bolton CF. Neuromuscular disorders associated with failure to wean from the ventilator. Intensive Care Med 1995;21:737–743.
MacFarlane IA, Rosenthal FD. Severe myopathy after status asthmaticus. Lancet 1977;2:615.
Van Marle W, Woods KL. Acute hydrocortisone myopathy. Br Med J 1980;281:271,272.
Williams VJ, O’Hehir RE, Czarny D, Horne M. Bowes G Acute myopathy in severe acute asthma treated with intravenously administered corticosteroids. Am Rev Respir Dis 1988;137:460–463.
Bachmann P., Gaussorgues P., Piperno D., et al. Acute myopathy after status asthmaticus. Presse Med 1987;16:1486.
Kaplan PW, Rocha W, Sanders DB, D’Souza B, Spock A. Acute steroid induced tetraplegia following status asthmaticus. Pediatrics 1986;78:121–123.
Shee CD. Risk factors for hydrocortisone myopathy in acute severe asthma. Resp Med 1990;84:229–233.
Helliwell TR, Coakley JH, Wagenmakers AJM, Griffiths RD, et al. Necrotizing myopathy in critically ill patients. J Path 1991;164:307–314.
Danon M.J., Carpenter S. Myopathy with thick filament (myosin) loss following prolonged paralysis with vecuronium during steroid treatment. Muscle Nerve 1991;14:1131–1139.
Al-Lozi MT, Pestronk A, Yee WC, Flairs N, Cooper J. Rapidly evolving myopathy with myosin deficient muscle fibers. Ann Neurol 1994;35:273–279.
Sher JH, Shafiq SA, Schutta HS. Acute myopathy with selective lysis of myosin filaments. Neurology 1979;29:100–106.
Subramony SH, Carpenter DE, Raju S, Pride M, Evans OB. Myopathy and prolonged neuromuscular blockade after a lung transplant. Crit Care Med 1991;19:1580–1582.
Spitzer AR, Giancarlo T, Maher L, Awerbuch G, Bowles A. Neuromuscular causes of prolonged ventilator dependency. Muscle Nerve 1992;15:682–686.
Zochodne DW, Ramsay DA. Acute quadriplegic myopathy (letter). Neurology 1994;44:988,989.
Wokke JHJ, Jennekens FGI, van den Oord, CJM, Veldman H, van Gijn J. Histological investigations of muscle atrophy and end plates in two critically ill patients with generalized weakness. J Neurol Sci 1988;88:95–106.
Apte-Kakade F. Rehabilitation of patients with quadriparesis after treatment of status asthmaticus with neuromuscular blocking agents and high dose corticosteroids. Arch Phys Med Rehabil 1991;72:1024–1028.
Sitwell LD, Weinshenker BG, Monpetit V, Reid D. Complete ophthalmoplegia as a complication of acute corticosteroid and pancuronium associated myopathy. Neurology 1991;41:921,922.
Banwell BL, Mildner RJ, Hassall AC, et al. Muscle weakness in critically ill children. Neurology 2003;61:1779–1782.
Douglass JA, Tuxen, DV, Horne M, et al. Myopathy and severe asthma. Am Rev Respir Dis 1992;146:517–519.
Giostra E, Magistris MR, Pizzolato G, Cox J, Chevrolet JC. Neuromuscular disorder in intensive care unit patients treated with pancuronium bromide. Chest 1994;106:210–220.
Zochodne DW, Bolton CF, Thompson RT, Driedger AA, Hahn AF, Gilbert JJ. Myopathy in critical illness. Muscle Nerve 1986;9:652.
Lacomis D, Smith TW, Chad DA. Acute myopathy and neuropathy in status asthmaticus: case report and literature review. Muscle Nerve 1993;16:84–90.
Kupfer Y, Okrent DG, Twersky RA, Tessler S. Disuse atrophy in a ventilated patient with status asthmaticus receiving neuromuscular blockade. Crit Care Med 1987;15:795,796.
Knox AJ, Mascie-Taylor BH, Meurs MF. Acute hydrocortisone myopathy in acute severe asthma. Thorax 1986;41:411,412.
Coakley JH, Nagendran K, Honavar M, Hinds CJ. Preliminary observations on the neuromuscular abnormalities in patients with organ failure and sepsis. Int Care Med 1993;19:323–328.
Coakley JH, Nagendran K, Ormerod IEC, Ferguson CN, Hinds CJ. Prolonged neurogenic weakness in patients requiring mechanical ventilation for acute airflow limitation. Chest 1992;101:1413–1416.
Margolis BD, Khachikian D, Friedman Y, Garrard C. Prolonged reversible quadriparesis in mechanically ventilated patients who received long term infusions of vecuronium. Chest 1991;100:877,878.
Brun-Buisson C, Gherardi R. Hydrocortisone and pancuronium bromide: acute myopathy during status asthmaticus. Crit Care Med 1988;16:731,732.
Picado C, Montserrat J, Agusti-Vidal A. Muscle atrophy in severe exacerbation of asthma requiring mechanical ventilation. Respiration 1988;53:201–203.
Mackie G, Road J, Stewart H, Eisen A. Reversible paralysis with status asthmaticus, steroids and pancuronium. Clinical electrophysiological correlates. Neurology 1993;43:A166.
Hunter JM. New neuromuscular blocking drugs. N Engl J Med 1995;332:1691–1699.
Meyer KC, Prielipp RC, Grossman JE, Coursin DB. Prolonged weakness after infusion of atracurium in two intensive care unit patients. Anesth Analg 1994;78:772–774.
Krendel DA, Reid C, Roeske L. Persistent weakness following atracurium and corticosteroid administration. Muscle Nerve 1994;17:1124.
Bella IR, Chad DA, Smith TW, et al. Ophthalmoplegia and quadriplegia in the wake of intensive therapy for status asthmaticus. Muscle Nerve 1994;17:1122.
De Smet Y, Jaminet M, Jaeger U, et al. Acute corticosteroid myopathy following status asthmaticus. Rev Neurol 1991;147:682–685.
Griffin D, Fairman N, Cousin D, Rawsthorne L, Grossman JE. Acute myopathy during treatment of status asthmaticus with corticosteroids and steroidal muscle relaxants. Chest 1992;102:510–514.
Lacomis D, Giuliani MJ, Van Cott A, Kramer DJ. Acute myopathy of intensive care: clinical, electromyographic, and pathological aspects. Ann Neurol 1996;40:645–654.
Campellone JV, Lacomis D, Kramer DJ, van Cott AC, Giuliani MJ. Acute myopathy after liver transplantation. Neurology 1998;50:46–53.
Lacomis D, Petrella JT, Giuliani MJ. Causes of neuromuscular weakness in the intensive care unit: a study of ninety-two patients. Muscle Nerve 1998;21:610–617.
Hanson P, Dive A, Brucher JM, Bisteau M, Dangoisse M, Deltombe T. Acute corticosteroid myopathy in intensive care patients. Muscle Nerve 1997;20:1371–1380.
Lacomis D, Zochodne DW, Bird SJ. Critical illness myopathy. Muscle Nerve 2000;23:1785–1788.
Tsai LK, Sung-Tsang H, Chi-Chao C, et al. Neuromuscular disorders in severe acute respiratory syndrome. Arch Neurol 2004;61:1669–1673.
Latronico N, Fenzi F, Recupero D, et al. Critical illness myopathy and neuropathy. Lancet 1996;347:1579–1582.
Faragher MW, Day BJ, Dennett X. Critical care myopathy: an electrophysiological and histological study. Muscle Nerve 1996; 19:516–518.
Sander HW, Golden M, Danon MJ. Quadriplegic areflexic ICU illness: selective thick filament loss and normal nerve histology. Muscle Nerve 2002;26:499–505.
Rich MM, Bird SJ, Raps EC, McCluskey LF, Teener JW. Direct muscle stimulation in acute quadriplegic myopathy. Muscle Nerve 1997;20:665–673.
Trojaborg W, Weimer LH, Hays AP. Electrophysiologic studies in critical illness associated weakness: myopathy or neuropathy—a reappraisal. Clin Neurophysiology 2001;112:1586–1593.
Bednarik J, Zdenek L, Vondracek P. Critical illness polyneuromyopathy: the electrophysiological components of a complex entity. Int Care Med 2003;1505–1514.
Bizzarri-Schmid ND, Desai SP. Prolonged neuromuscular blockade with atracurium. Can Anaesth Soc J 1986;33:209–212.
Danon MJ, Kumarasiri M, Giometti CS, Etlinger J, Zeman R. Steroid induced quadriplegic myopathy with thick filament (myosin) loss: biochemical studies and the 1st autopsy report. Neurology 1998;50:A205.
Showalter CJ, Engel AG. Acute quadriplegic myopathy: analysis of myosin isoforms and evidence of calpain-mediated proteolysis. Muscle Nerve 1997;20:316–322.
Hoke A, Rewcastle NB, Zochodne DW. Acute quadriplegic myopathy unrelated to steroids or paralyzing agents: quantitative EMG studies. Can J Neurol Sci 1999;26:325–329.
Deconinck N, van Parijs V, Beckers-Bleukx G, van den Bergh P. Critical illness myopathy unrelated to corticosteroids or neuromuscular blocking agents. Neuromusc Dis 1998;8:186–192.
Gutmann L, Blumenthal D, Gutmann L, Schochet SS. Acute type II myofiber atrophy in critical illness. Neurology 1996;46:819–821.
Bazzi P, Moggio M, Prelle A, et al. Critically ill patients: immunological evidence of inflammation of muscle biopsy. Clin Neuropathol 1999;18:23–30.
Matsumoto N, Nakamura T, Yasui Y, Torii J. Analysis of muscle proteins in acute quadriplegic myopathy. Muscle Nerve 2000;23:1270–1276.
de Letter MA, van Doorn PA, Savelkoul HF, et al. Critical illness polyneuropathy and myopathy (CIPNM): evidence for local immune activation by cytokine-expression in the muscle tissue. J Neuroimmunol 2000;106:206–213.
Larsson L, Li X, Edstrom L, et al. Acute quadriplegia and loss of muscle myosin in patients treated with nondepolarizing neuromuscular blocking agents and corticosteroids: mechanisms at the cellular and molecular level. Crit Care Med 2000;28:34–45.
Yarom R, Sphira Y. Myosin degeneration in a congenital myopathy. Arch Neurol 1977;34:114,115.
Carpenter S, Karpati G. Pathology of skeletal muscle. New York: Churchill and Livingstone. 1984.
Ruff RL. Acute illness myopathy. Neurology 1996;46:600,601.
DuBois DC, Almon RR. A possible role for glucocorticoids in denervation atrophy. Muscle Nerve 1981;4:370–373.
Rouleau G, Karpati G, Carpenter S, Soza M, Prescott S, Holland P. Glucocorticoid excess induces preferential depletion of myosin in denervated skeletal muscle fibers. Muscle Nerve 1987;10:428–438.
Carpenter S, Massa R, Karpati G. Depletion and reconstitution of thick myofilaments in steroid treated rat solei after denervation and reinnervation. J Neurol Sci 1990;98:377.
Massa R, Carpenter S, Holland P, Karpati G. Loss and renewal of thick myofilaments in glucocorticoid treated rat soleus after denervation and reinnervation. Muscle Nerve 1992;15:1290–1298.
Wing SS, Goldberg AL. Glucocorticoids activate the ATP-ubiquitin-dependent proteolytic system in skeletal muscle during fasting. Am J Physiol 1993;264:668–676.
Minetti C, Hirano M, Morreale G, et al. Ubiquitin expression in acute steroid myopathy with loss of myosin thick filaments. Muscle Nerve 1996;19:94–96.
Di Giovanni S, Molon A, Broccolini A, et al. Constitutive activation of MAPK cascade in acute quadriplegic myopathy. Ann Neurol 2004;55:195–206.
Panegyres PK, Squier M, Mills KR, Newsom-Davis J. Acute myopathy associated with large parenteral dose of corticosteroid in myasthenia gravis. J Neurol Neurosurg Psych 1993;56:702–704.
Rich MM, Pinter MJ, Kraner SD, Barchi RL. Loss of electrical excitability in an animal model of acute quadriplegic myopathy. Ann Neurol 1998;43:171–179.
Rich MM, Teener JW, Raps EC, Schotland DL, Bird SJ. Muscle is electrically inexcitable in acute quadriplegic myopathy. Neurology 1996;46:731–736.
van der Hoeven JH. Decline of muscle fiber conduction velocity during short-term high dose methylprednisolone therapy. Muscle Nerve 1996;19:100–102.
Rich MM, Pinter MJ. Sodium channel inactivation in an animal model of acute quadriplegic myopathy. Ann Neurol 2001;50:26–33.
Filatov GN, Rich MM. Hyperpolarized shifts in the voltage dependence of fast activation of Nav1.4 and Nav1.5 in a rat model of critical illness myopathy. J Physiol 2004;559:813–820.
Friedrich O, Hund E, Weber C, Hacke W, Fink RH. Critical illness myopathy serum fractions affect membrane excitability and intracellular calcium release in mammalian skeletal muscle. J Neurol 2004;251:53–65.
Clowes GHA, George BC, Villee CA. Muscle proteolysis induced by a circulating peptide in patients with sepsis or trauma. N Engl J Med 1983;308:545–552.
Ruff RL, Secrist D. Inhibitors of prostaglandin synthesis or Cathepsin B prevent muscle wasting due to sepsis in the rat. J Clin Invest 1984;73:1483–1486.
Arellano F, Krupp P. Muscular disorders associated with cyclosporin. Lancet 1991;:337–915.
Chassagne P, Mejjad O, Moore N, et al. Myopathy as possible side-effect of cyclosporin. Lancet 1989;2:1104.
Wijdicks EFM. Neurology of critical illness. F. A. Davis Co. Philadelphia: 1995.
Rosenow EC, Engel AG. Acid maltase deficiency in adults presenting as respiratory failure. Am J Med 1978;64:485–491.
Barohn RJ, Clanton TL, Sahenk Z, Mendell JR. Recurrent respiratory insufficiency and depressed ventilatory drive complicating mitochondrial myopathies. Neurology 1990;40:103–106.
DeVere R, Bradley WG. Polymyositis: its presentation, morbidity and mortality. Brain 1975;98:637–666.
Jammes Y, Pouget J, Grimaud C, Serratrice G. Pulmonary function and electromyographic study of respiratory muscles in myotonic dystrophy. Muscle Nerve 1985;8:586–594.
Belafsky MA, Klawans HL. Prolonged neuromuscular blockade with pancuronium bromide in a young healthy woman. Anesthesiology 1974;40:295,296.
Shanks AB, Long T, Aitkenhead AR. Prolonged neuromuscular blockade following vecuronium. Br J Anaesth 1985;57:807–810.
Haas JL, Shaefer MS, Miwa J, Wood RP, Shaw BW. Prolonged paralysis associated with long-term pancuronium use. Pharmacotherapy 1989;9:154–157.
Partridge BL, Abrams JH, Bazemore C, Rubin R. Prolonged neuromuscular blockade after long term infusion of vecuronium bromide in the intensive care unit. Crit Care Med 1990;18:1177–1179.
Rossiter A, Souney PF, McGowan S, Carvajal P. Pancuronium-induced prolonged neuromuscular blockade. Crit Care Med 1991;19:1583–1587.
Lagasse RS, Katz RI, Petersen M, Jacobson MJ, Poppers PJ. Prolonged neuromuscular blockade following vecuronium infusion. J Clin Anesth 1990;2:269–271.
Gooch JL, Suchyta MR, Balbierz JM, Petajan JH, Clemmer TP. Prolonged paralysis after treatment with neuromuscular junction blocking agents. Crit Care Med 1991;19:1125–1131.
Segredo V, Matthay MA, Sharma ML, Gruenke LD, Caldwell JE, Miller RD. Prolonged neuromuscular blockade after long term administration of vecuronium in two critically ill patients. Anesthesiology 1990;72:566–570.
Vanderheyden BA, Reynolds HN, Gerold KB, Emanuel T. Prolonged paralysis after long term vecuronium infusion. Crit Care Med 1992;20:304–307.
Feldman SA, Levi JA. Prolonged paresis following gallamine. Brit J Anaesth 1963;35:804–806.
Vandenbrom RHG, Wierda JMKH. Pancuronium bromide in the intensive care unit: a case of overdose. Anesthesiology 1988;69:996,997.
Gooch JL, Moore MH, Ryser DK. Prolonged paralysis after neuromuscular junction blockade: case reports and electrodiagnostic findings. Arch Phys Med Rehabil 1993;74:1007–1011.
Torres CF, Maniscalco WM, Agostinelli T. Muscle weakness and atrophy following prolonged paralysis with pancuronium bromide in neonates. Ann Neurol 1985;18:403.
Smith CL, Hunter JM, Jones RS. Vecuronium infusions in patients with renal failure in an ITU. Anaesthesia 1987;42:387–393.
Sinclair JF, Malcolm GA, Stephenson JBP, Halworth D. Prolonged neuromuscular blockade in an infant. Anaesthesia 1987;42:1020.
Camp CE, Tessem J, Adenwala J, Joyce TH. Vecuronium and prolonged neuromuscular blockade in postpartum patients. Anesthesiology 1987;67:1006–1008.
Benzing G, Iannaccone ST, Bove KE, Keebler PJ, Shockley LI. Prolonged myasthenic syndrome after one week of muscle relaxants. Pediatr Neurol 1990;6:190–196.
Hansen-Flaschen JH, Brazinsky S, Basile C, Lanken PN. Use of sedating drugs and neuromuscular blocking agents in patients requiring mechanical ventilation for respiratory failure. JAMA 1991;266:2870–2875.
Klessig HT, Geiger HJ, Murray MJ, Coursin DB. A national survey on the practice patterns of anesthesiologists in the use of muscle relaxants. Crit Care Med 1992;20:1441–1445.
Murray MJ, Cowen J, DeBlock H, et al. Clinical practice guidelines for sustained neuromuscular blockade in the adult critically ill patient. Crit Care Med 2002;30:142–156.
Marshall IG, Gibb AJ, Durant NN. Neuromuscular and vagal blocking actions of pancuronium bromide, its metabolites, and vecuronium bromide (ORG NC 45) and its potential metabolites in the anaesthetized cat. Br J Anaesth 1983;55:703–714.
Bencini AF, Houwertjes MC, Agoston S. Effects of hepatic uptake of vecuronium bromide and its putative metabolites on the neuromuscular blocking actions in the cat. Br J Anaesth 1985;57:789–795.
Clarens DM, Kelly KJ, Gilliland SS, Kohls PK, Nahum A, Vance-Bryan K. A retrospective analysis of long-term use of non-depolarizing neuromuscular blocking agents in the intensive care unit, and guidelines for drug selection. Pharmacotherapy 1993;13:647–655.
Crosby E, Robblee JA. Cyclosporine-pancuronium interaction in a patient with a renal allograft. Can J Anaesth 1988;35:300–302.
Kupfer Y, Namba T, Kaldawi E, Tessler S. Prolonged weakness after long term infusion of vecuronium bromide. Ann Int Med 1992;117:484–486.
Lien CA, Matteo RS, Ornstein E, Schwartz AE, Diaz J. Distribution, elimination and action of vecuronium in the elderly. Anesth Analg 1991;73:39–42.
Dundee JW, Gray TC. Resistance to D-tubocurarine chloride in the presence of liver damage. Lancet 1953;2:16,17.
Erkola O. Complications of neuromuscular blockers: interaction with concurrent medications and other neuromuscular blockers. Anaesth Clin North Am 1993;11:427–444.
Durbin CG. Neuromuscular blocking agents and sedative drugs. Crit Care Clin 1991;7:489–506.
de Lemos JM, Carr RR, Shalansky KF, Bevan DR, Ronco JJ. Paralysis in the critically ill: intermittent bolus pancuronium compared with continuous infusion. Crit Care Med 1999;27:2648–2655.
Aggarwal A, Gutmann L, Gutierrez A. Electrophysiological features of vecuronium induced prolonged neuromuscular blockade. Muscle Nerve 1994;2:251–252.
Oh SJ, Kim DE, Kuruoglu R, Bradley RJ, Dwyer D. Diagnostic sensitivity of the laboratory tests in myasthenia gravis. Muscle Nerve 1992;15:720–724.
Baumann MH, McAlpin BW, Brown K, et al. A prospective randomized comparison of train-of-four monitoring and clinical assessment during continuous ICU cisatracurium paralysis. Chest 2004;126:1267–1273.
Wilson RW, Ward D, Johns TR. Corticosteroids: a direct effect at the neuromuscular junction. Neurology 1974;24:1091–1095.
Van Wilgenburg H. The effect of prednisolone on neuromuscular transmission in the rat diaphragm. Eur J Pharm 1979;55:355–361.
Miller RG, Milner-Brown HS, Mirka A. Prednisone-induced worsening of neuromuscular function in myasthenia gravis. Neurology 1986;36:729–732.
Segura RP, Tsairis P. Physiological effect of intravenous corticosteroids on the human neuromuscular junction. Electroenceph Clin Neurophsyiol 1978;45:19P.
Schwartz AE, Matteo RS, Ornstein E, Silverberg PA. Acute steroid therapy does not alter non-depolarizing muscle relaxant effects in humans. Anesthesiology 1986;65:326–327.
Arts WF, Oosterhuis HJ. Effects of prednisolone on neuromuscular blocking in mice in vivo. Neurology 1975;25:1088–1090.
Leeuwin RS, Wolters ECMJ. Effects of corticosteroids on sciatic nerve-tibialis anterior muscle of rats treated with hemicholinium-3. Neurology 1977;27:171–177.
Leeuwin RS, Veldsema-Currie RD, VanWilgenburg H, Ottenhof M. Effects of corticosteroids on neuromuscular blocking actions of D-tubocurarine. Eur J Pharm 1981;69:165–173.
Durant NN, Briscoe JR, Katz RL. The effects of acute and chronic hydrocortisone treatment on neuromuscular blockade in the anesthetized cat. Anesthesiology 1984;61:144–150.
Kindler CM, Verotta D, Gray AT, Gropper MA, Yost CS. Additive inhibition of nicotinic acetylcholine receptors by corticosteroids and the neuromuscular blocking drug vecuronium. Anesthesiology 2000;92:821–832.
Dodson B, Kelly BJ, Braswell LM, Cohen NH. Changes in acetylcholine receptor number in muscle from critically ill patients receiving muscle relaxants: an investigation of the molecular mechanism of prolonged paralysis. Crit Care Med 1995;23:815–821.
Pauker SG, Kopelman RI. Weak reasoning: diagnosis by drug reaction. N Eng J Med 1993;328:336–339.
Maher J, Bolton CF, Parkes T. Isolated respiratory denervation in myasthenia gravis. Can J Neurol Sci 1992;19:297.
Nagappan R, Kletcho S. Myasthenia gravis presenting as respiratory failure. New Zealand Med J 1992;105:152.
Nicolle MW, Stewart JD, Remtulla H, Chen R, Bolton CF. Lambert-Eaton myasthenic syndrome presenting with severe respiratory failure. Muscle Nerve 1996;19:1238–1333.
Argov Z, Mastaglia FL. Disorders of neuromuscular transmission caused by drugs. N Eng J Med 1979;301:409–413.
Warner WA, Sanders E. Neuromuscular blockade associated with gentamycin. JAMA 1971;215:1153,1154.
Witt NJ, Zochodne DW, Bolton CF, et al. Peripheral nerve function in sepsis and multi-organ failure. Chest 1991;99:176–184.
Berek K, Margreiter J, Willeit J, Berek A, Schmutzhard E, Mutz NJ. Polyneuropathies in critically ill patients: a prospective evaluation. Intensive Care Med 1996;22:849–855.
Tepper M, Rakic S, Haas JA, Woittiez AJ. Incidence and onset of critical illness polyneuropathy in patients with septic shock. Neth J Med 2000;56:211–214.
Leijten FS, Harinck-de Weerd JE, Poortvliet DCJ, de Weerd AW. The role of polyneuropathy in motor convalescence after prolonged mechanical ventilation. JAMA 1995;274:1221–1225.
Zifko UA. Long-term outcome of critical illness polyneuropathy. Muscle Nerve Suppl. 2000;9:S49-S52.
de Seze M, Petit H, Wiart L, et al. Critical illness polyneuropathy. A 2-year followup study in 19 severe cases. Eur Neurol 2000;43:61–69.
Fletcher SN, Kennedy DD, Ghosh IR, et al. Persistent neuromuscular and neurophysiological abnormalities in long-term survivors of prolonged critical illness. Crit Care Med 2003;31: 1012–1016.
Leijten FSS, De Weerd AW, Poortvliet DCJ, Ulrich C, Harinck-De Weerd JE. Critical illness polyneuropathy in multiple organ dysfunction syndrome and weaning from the ventilator. Intensive Care Med 1996;22:856–861.
Zifko UA, Zipko HT, Bolton CF. Clinical and electrophysiological findings in critical illness polyneuropathy. J Neurol Sci 1998;159:186–193.
Garnacho-Montero J, Madrazo-Osuna J, Garcia-Garmendia JL, et al. Critical illness polyneuropathy: risk factors and clinical consequences. A cohort study in septic patients. Intensive Care Med 2001;27:1288–1296.
De Letter MAC, Schmitz PIM, Visser LH, et al. Risk factors for the development of polyneuropathy and myopathy in critically ill patients. Crit Care Med 2001;29:2281–2286.
van den Berghe G, Wouters P, Weekers F, et al. Intensive insulin therapy in critically ill patients. N Engl J Med 2001;345: 1359–1367.
Hund E, Genzwurker H, Bohrer H, Jakob H, Thiele R, Hacke W. Predominant involvement of motor fibers in patients with critical illness polyneuropathy. Br J Anaesth 1997;78:274–278.
Schwarz J, Planck J, Briegel J, Straube A. Single fiber electromyography, nerve conduction studies, and conventional electromyography in patients with critical illness polyneuropathy: evidence for a lesion of terminal axons. Muscle Nerve 1997;20:696–701.
Coakley JH, Nagendran K, Yarwood GD, Honavar M, Hinds CJ. Patterns of neurophysiological abnormality in prolonged critical illness. Intensive Care Med 1998;24:801–807.
Bolton CF. Assessment of respiratory function in the intensive care unit. Can J Neurol Sci 1994;21:S28-S34.
Fenzi F, Latronico N, Refatti N, Rizzuto N. Enhanced expression of E-selectin on the vascular endothelium of peripheral nerve in critically ill patients with neuromuscular disorders. Acta Neuropathol (Berl) 2003;106:75–82.
Waldhausen E, Mingers B, Lippers P, Keser G. Critical illness polyneuropathy due to parenteral nutrition. Int Care Med 1997;23:922,923.
Marino PI, Millili JJ. Possible role of dietary lipids in critical illness polyneuropathy. Int Care Med 1998;24:87.
Fong Y. Cachectin/TNF or II-1a induces cachexia with redistribution of body proteins. Am J Physiol 1989;256:659–665.
Verheul GAM, de Jongh-Leuvenink J, Op de Coul AAW, van Landeghem AAJ, van Puyenbroek MJE. Tumor necrosis factor and interleukin-6 in critical illness polyneuropathy. Clin Neurol Neurosurg 1994;96:300–304.
Druschky A, Herkert M, Radespiel-Troger M, et al. Critical illness polyneuropathy: clinical findings and cell culture assay of neurotoxicity assessed by a prospective study. Intensive Care Med 2001;27:686–693.
Hund F Herbert M, Becker CM, Hacke W. A humoral neurotoxic factor in sera of patients with critical illness polyneuropathy. Ann Neurol 1996;40:539.
Van den Berge G, Schoonheydt K, Becx P, Bruyninckx F, Wouters PJ. Insulin therapy protects the central and peripheral nervous system of intensive care patients. Neurology 2005;64:1348–1353.
Wijdicks EFM, Fulgham JR. Failure of high dose intravenous immunoglobulins to alter the clinical course of critical illness polyneuropathy. Muscle Nerve 1994;17:1494,1495.
Mohr M, Englisch L, Roth A, Burchardi H, Zielmann S. Effects of early treatment with immunoglobulin on critical illness polyneuropathy following multiple organ failure and gram-negative sepsis. Intensive Care Med 1997;23:1144–1149.
Wiederholt WC, Mulder DW, Lambert EH. The Landry-Guillain-Barre-Strohl syndrome or polyradiculopathy. Historical review, report on 97 patients and present concepts. Mayo Clin Proc 1964;39:427–451.
Arnason BGW, Soliven B. Acute inflammatory demyelinating polyneuropathy. In: Dyck PJ, Thomas PK, Griffin JW, Low PA, Podulso JF, eds. Peripheral Neuropathy. Philadelphia: WB Saunders, 1993, pp. 1437–1497.
Millar AB, Clarke SW, Davis SN, Gross MLP. Prolonged ventilation in acute severe asthma caused by the Guillain-Barre’-Strohl syndrome. J Royal Soc Med 1984;77:965,966.
Hamilton RJ, Puckett R, Bazemore WC. Ventilator dependence in acute severe asthma due to a variant presentation of Guillain-Barre syndrome. Chest 1989;96:1205,1206.
Preston DC, Logigian EL. Guillain-Barre syndrome during high dose methylprednisolone therapy. Muscle Nerve 1991;14:378,379.
Terasako K, Seo N, Murayama T, Kai T, Hirata S, Fujiwara T. Are immune mechanisms involved in critical illness polyneuropathy? Int Care Med 1995;21:96,97.
Windebank, AJ, Bonkovsky HL. Porphyric neuropathy. In: Dyck PJ, Thomas PK, Griffin JW, Low PA, Poduslo JF, eds. Peripheral Neuropathy. Philadelphia: WB Saunders, 1993, pp. 1161–1169.
Zochodne DW, Semmler RT, Ludwin SK, Auer R. Acute fulminant symmetrical vasculitic polyneuropathy: need for early biopsy. Clin Neuropathol 1996;15:113–115.
Chen R, Grand’Maison F, Strong MJ, et al. Motor neuron disease presenting as acute respiratory failure: a clinical and pathological study. J Neurol Neurosurgery Psychiatry 1996;60:455–458.
Martin AA, Gubler DJ. West Nile Encephalitis: an emerging disease in the United States. Clin Inf Dis 2001;33:1713–1719.
Huhn GD, Sejvar JJ, Montgomery SP, Dworkin MS. West Nile virus in the United States: An update on an emerging infectious disease. Am Fam Physician 2003;68:653–660.
Solomon T, Ooi MH, Beasley DWC, Mallewa M. West Nile encephalitis. BMJ 2003;326:865–869.
Update: investigations of West Nile virus infections in recipients of organ transplantation and blood transfusion—Michigan, 2002. MMWR 2002;51:879.
Laboratory-acquired West Nile virus infections—United States 2002. MMWR 2002;51:877–878.
Mostashari F, Bunning ML, Kitsutani PT, et al. Epidemic West Nile encephalitis, New York, 1999: results of a household-based seroepidemiological survey. Lancet 2001;358:261–264.
Nash D, Mostashari F, Fine A, et al. The outbreak of West Nile virus infection in the New York City area in 1999. N Engl J Med 2001;344:1807–1814.
Jeha LE, Sila CA, Lederman RJ, et al. West Nile virus infection. A new acute paralytic illness. Neurology 2003;61:55–59.
Leis AA, Stokic DS. Neuromuscular manifestations of human West Nile virus infection. Curr Treat Options Neurol 2005;7:15–22.
Leis AA, Stokic DS, Polk JL, Dostrow V, Winkelmann M. A poliomyelitis-like syndrome from West Nile virus infection. N Eng J Med 2002;347:1279–1280.
Agamanolis DP, Leslie MJ, Caveny EA, Guarner J, Shieh WJ, Zaki SR. Neuropathological findings in West Nile virus encephalitis: a case report. Ann Neurol 2003;54:547–551.
Leis AA, Stokic DS, Webb RM, Slavinski SA, Fratkin J. Clinical spectrum of muscle weakness in human West Nile virus infection. Muscle Nerve 2003;28:302–308.
Doron SI, Dashe JF, Adelman LS, Brown WF, Werner BG, Hadley S. Histologically proven poliomyelitis with quadriplegiaand loss of brainstem function due to West Nile virus infection. Clin Inf Dis 2003;37:74–77.
Sampathkumar P. West Nile virus: epidemiology, clinical presentation, diagnosis, and prevention. Mayo Clin Proc 2003;78: 1137–1144.
Peterson LR, Marfin AA. West Nile virus: a primer for the clinician. Ann Intern Med 2002;137:173–179.
Li J, Loeb JA, Shy ME, et al. Asymmetric flaccid paralysis: a neuromuscular presentation of West Nile virus infection. Ann Neurol 2003;53:703–710.
Burton JM, Kern RZ, Halliday W, et al. Neurological manifestations of West Nile virus infection. Can J Neurol Sci 2004;31:185–193.
Gorson KC, Ropper AH. Nonpoliovirus poliomyelitis simulating Guillain-Barre syndrome. Arch Neurol 2001;58:1460–1464.
Kelley TW, Prayson RA, Ruiz AI, Isada CM, Gordon SM. The neuropathology of West Nile virus meningoencephalitis. A report of two cases and review of the literature. Am J Clin Pathol 2003;119:749–753.
Sayao AL, Suchowersky O, Al-Khathaami A, et al. Calgary experience with West Nile virus neurological syndrome during late summer of 2003. Can J Neurol Sci 2004;31:194–203.
Roos K. Fever and asymmetrical weakness in the Summer: evidence of a West Nile virus-associated poliomyelitis-like illness. Mayo Clin Proc 2003;78:1205–1206.
Ben-Nathan D, Lustig S, Tam G, Robinson S, Segal S, Rager-Zisman B. Prophylactic and therapeutic efficacy of human intravenous immunoglobulin in treating West Nile virus infection in mice. J Inf Dis 2003;188:5–12.
Pyrgos V, Younus F. High-dose steroids in the management of acute flaccid paralysis due to West Nile virus infection. Scan J Infect Dis 2004;36:509–512.
Gorson KC, Ropper AH. Acute respiratory failure in neuropathy: a variant of critical illness polyneuropathy. Crit Care Med (letter) 1993;21:1986–1987.
Young GB, Hammond RR. A stronger approach to weakness in the intensive care unit. Crit Care 2004;6:416–418.
Bolton CF, Breuer AC. Critical illness polyneuropathy. Muscle Nerve 1999;22:419–424.
Prielipp RC, Coursin DB. Applied pharmacology of common neuromuscular blocking agents in critical care. New Horizons 1994;2:34–47.
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Gorson, K.C. Approach to neuromuscular disorders in the intensive care unit. Neurocrit Care 3, 195–212 (2005). https://doi.org/10.1385/NCC:3:3:195
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DOI: https://doi.org/10.1385/NCC:3:3:195