Neuromuscular weakness related to critical illness
- David Lacomis, MD
David Lacomis, MD
- Professor of Neurology and Pathology
- University of Pittsburgh School of Medicine
Neuromuscular 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 or to critical illness polyneuropathy. This topic will review the peripheral neuromuscular disorders of critical illness.
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. Prolonged neuromuscular junction blockade is rare. Each of these disorders is discussed in detail below.
Other acute and subacute myopathies can occur in critically ill patients, including rhabdomyolysis and cachectic myopathy. In addition, rare acute neuropathies such as Guillain-Barré syndrome can also develop in the ICU.
Rhabdomyolysis — Some critically ill patients develop rhabdomyolysis due to their illness or medications . (See "Clinical manifestations and diagnosis of rhabdomyolysis".)
- De Jonghe B, Sharshar T, Lefaucheur JP, et al. Paresis acquired in the intensive care unit: a prospective multicenter study. JAMA 2002; 288:2859.
- Warren JD, Blumbergs PC, Thompson PD. Rhabdomyolysis: a review. Muscle Nerve 2002; 25:332.
- Al-Shekhlee A, Hachwi R, Jaberi MM, Katirji B. The electromyographic features of acute rhabdomyolysis. J Clin Neuromuscul Dis 2005; 6:114.
- Bolton CF. Neuromuscular manifestations of critical illness. Muscle Nerve 2005; 32:140.
- Puthucheary ZA, Rawal J, McPhail M, et al. Acute skeletal muscle wasting in critical illness. JAMA 2013; 310:1591.
- Koch S, Spuler S, Deja M, et al. Critical illness myopathy is frequent: accompanying neuropathy protracts ICU discharge. J Neurol Neurosurg Psychiatry 2011; 82:287.
- Latronico N, Bolton CF. Critical illness polyneuropathy and myopathy: a major cause of muscle weakness and paralysis. Lancet Neurol 2011; 10:931.
- Amaya-Villar R, Garnacho-Montero J, García-Garmendía JL, et al. Steroid-induced myopathy in patients intubated due to exacerbation of chronic obstructive pulmonary disease. Intensive Care Med 2005; 31:157.
- Douglass JA, Tuxen DV, Horne M, et al. Myopathy in severe asthma. Am Rev Respir Dis 1992; 146:517.
- Campellone JV, Lacomis D, Kramer DJ, et al. Acute myopathy after liver transplantation. Neurology 1998; 50:46.
- Shee CD. Risk factors for hydrocortisone myopathy in acute severe asthma. Respir Med 1990; 84:229.
- Lacomis D, Giuliani MJ, Van Cott A, Kramer DJ. Acute myopathy of intensive care: clinical, electromyographic, and pathological aspects. Ann Neurol 1996; 40:645.
- Panegyres PK, Squier M, Mills KR, Newsom-Davis J. Acute myopathy associated with large parenteral dose of corticosteroid in myasthenia gravis. J Neurol Neurosurg Psychiatry 1993; 56:702.
- Deconinck N, Van Parijs V, Beckers-Bleukx G, Van den Bergh P. Critical illness myopathy unrelated to corticosteroids or neuromuscular blocking agents. Neuromuscul Disord 1998; 8:186.
- Showalter CJ, Engel AG. Acute quadriplegic myopathy: analysis of myosin isoforms and evidence for calpain-mediated proteolysis. Muscle Nerve 1997; 20:316.
- Riggs JE, Pandey HK, Schochet SS Jr. Critical illness myopathy associated with hyperthyroidism. Mil Med 2004; 169:71.
- Bolton CF, Young GB, Zochodne DW. The neurological complications of sepsis. Ann Neurol 1993; 33:94.
- Hanson P, Dive A, Brucher JM, et al. Acute corticosteroid myopathy in intensive care patients. Muscle Nerve 1997; 20:1371.
- Zochodne DW, Ramsay DA, Saly V, et al. Acute necrotizing myopathy of intensive care: electrophysiological studies. Muscle Nerve 1994; 17:285.
- Goodman BP, Harper CM, Boon AJ. Prolonged compound muscle action potential duration in critical illness myopathy. Muscle Nerve 2009; 40:1040.
- Lacomis D. Electrophysiology of neuromuscular disorders in critical illness. Muscle Nerve 2013; 47:452.
- Barohn RJ, Jackson CE, Rogers SJ, et al. Prolonged paralysis due to nondepolarizing neuromuscular blocking agents and corticosteroids. Muscle Nerve 1994; 17:647.
- Road J, Mackie G, Jiang TX, et al. Reversible paralysis with status asthmaticus, steroids, and pancuronium: clinical electrophysiological correlates. Muscle Nerve 1997; 20:1587.
- Rich MM, Bird SJ, Raps EC, et al. Direct muscle stimulation in acute quadriplegic myopathy. Muscle Nerve 1997; 20:665.
- Allen DC, Arunachalam R, Mills KR. Critical illness myopathy: further evidence from muscle-fiber excitability studies of an acquired channelopathy. Muscle Nerve 2008; 37:14.
- Lacomis D, Zochodne DW, Bird SJ. Critical illness myopathy. Muscle Nerve 2000; 23:1785.
- Trojaborg W. Electrophysiologic techniques in critical illness-associated weakness. J Neurol Sci 2006; 242:83.
- Rouleau G, Karpati G, Carpenter S, et al. Glucocorticoid excess induces preferential depletion of myosin in denervated skeletal muscle fibers. Muscle Nerve 1987; 10:428.
- Di Giovanni S, Mirabella M, D'Amico A, et al. Apoptotic features accompany acute quadriplegic myopathy. Neurology 2000; 55:854.
- Di Giovanni S, Molon A, Broccolini A, et al. Constitutive activation of MAPK cascade in acute quadriplegic myopathy. Ann Neurol 2004; 55:195.
- Capasso M, Di Muzio A, Pandolfi A, et al. Possible role for nitric oxide dysregulation in critical illness myopathy. Muscle Nerve 2008; 37:196.
- 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.
- Mozaffar T, Haddad F, Zeng M, et al. Molecular and cellular defects of skeletal muscle in an animal model of acute quadriplegic myopathy. Muscle Nerve 2007; 35:55.
- Rossignol B, Gueret G, Pennec JP, et al. Effects of chronic sepsis on the voltage-gated sodium channel in isolated rat muscle fibers. Crit Care Med 2007; 35:351.
- Latronico N, Shehu I, Seghelini E. Neuromuscular sequelae of critical illness. Curr Opin Crit Care 2005; 11:381.
- Lacomis, D. Management of generalized weakness in medical and surgical intensive care units. In: Neurological Therapeutics, Principles and Practice, Noseworthy, J (Ed), Martin Dunitz Ltd 2003.
- Mehrholz J, Pohl M, Kugler J, et al. Physical rehabilitation for critical illness myopathy and neuropathy. Cochrane Database Syst Rev 2015; :CD010942.
- Van den Berghe G, Schoonheydt K, Becx P, et al. Insulin therapy protects the central and peripheral nervous system of intensive care patients. Neurology 2005; 64:1348.
- Hermans G, Wilmer A, Meersseman W, et al. Impact of intensive insulin therapy on neuromuscular complications and ventilator dependency in the medical intensive care unit. Am J Respir Crit Care Med 2007; 175:480.
- Hermans G, De Jonghe B, Bruyninckx F, Van den Berghe G. Interventions for preventing critical illness polyneuropathy and critical illness myopathy. Cochrane Database Syst Rev 2014; :CD006832.
- Zochodne DW, Bolton CF, Wells GA, et al. Critical illness polyneuropathy. A complication of sepsis and multiple organ failure. Brain 1987; 110 ( Pt 4):819.
- Witt NJ, Zochodne DW, Bolton CF, et al. Peripheral nerve function in sepsis and multiple organ failure. Chest 1991; 99:176.
- Bolton CF, Gilbert JJ, Hahn AF, Sibbald WJ. Polyneuropathy in critically ill patients. J Neurol Neurosurg Psychiatry 1984; 47:1223.
- Roelofs, R, Cerra, F, Bilka, N, et al. Prolonged respiratory insufficiency due to acute motor neuropathy: A new syndrome?. Neurology 1983; 33:s240.
- Sander HW, Golden M, Danon MJ. Quadriplegic areflexic ICU illness: selective thick filament loss and normal nerve histology. Muscle Nerve 2002; 26:499.
- Garnacho-Montero J, Amaya-Villar R, García-Garmendía JL, et al. Effect of critical illness polyneuropathy on the withdrawal from mechanical ventilation and the length of stay in septic patients. Crit Care Med 2005; 33:349.
- Latronico N, Peli E, Botteri M. Critical illness myopathy and neuropathy. Curr Opin Crit Care 2005; 11:126.
- Bolton, C. The polyneuropathy of critical illness. Intensive Care Med 1994; 9:132.
- Fletcher SN, Kennedy DD, Ghosh IR, et al. Persistent neuromuscular and neurophysiologic abnormalities in long-term survivors of prolonged critical illness. Crit Care Med 2003; 31:1012.
- Op de Coul AA, Verheul GA, Leyten AC, et al. Critical illness polyneuromyopathy after artificial respiration. Clin Neurol Neurosurg 1991; 93:27.
- Bednarik J, Lukas Z, Vondracek P. Critical illness polyneuromyopathy: the electrophysiological components of a complex entity. Intensive Care Med 2003; 29:1505.
- Khan J, Harrison TB, Rich MM, Moss M. Early development of critical illness myopathy and neuropathy in patients with severe sepsis. Neurology 2006; 67:1421.
- Novak KR, Nardelli P, Cope TC, et al. Inactivation of sodium channels underlies reversible neuropathy during critical illness in rats. J Clin Invest 2009; 119:1150.
- Latronico N, Bertolini G, Guarneri B, et al. Simplified electrophysiological evaluation of peripheral nerves in critically ill patients: the Italian multi-centre CRIMYNE study. Crit Care 2007; 11:R11.
- Latronico, N. Axonal inexcitability and axonal degeneration: two sides of the same coin [ELetter]. J Clin Invest 2009; April 27.
- Intiso D, Amoruso L, Zarrelli M, et al. Long-term functional outcome and health status of patients with critical illness polyneuromyopathy. Acta Neurol Scand 2011; 123:211.
- Guarneri B, Bertolini G, Latronico N. Long-term outcome in patients with critical illness myopathy or neuropathy: the Italian multicentre CRIMYNE study. J Neurol Neurosurg Psychiatry 2008; 79:838.
- Hunter JM. New neuromuscular blocking drugs. N Engl J Med 1995; 332:1691.
- Segredo V, Caldwell JE, Matthay MA, et al. Persistent paralysis in critically ill patients after long-term administration of vecuronium. N Engl J Med 1992; 327:524.
- Deem S, Lee CM, Curtis JR. Acquired neuromuscular disorders in the intensive care unit. Am J Respir Crit Care Med 2003; 168:735.
- Agoston S, Vandenbrom RH, Wierda JM. Clinical pharmacokinetics of neuromuscular blocking drugs. Clin Pharmacokinet 1992; 22:94.
- DIFFERENTIAL DIAGNOSIS
- Cachectic myopathy
- Guillain-Barré syndrome
- CRITICAL ILLNESS MYOPATHY
- Epidemiology and risk factors
- Clinical features of CIM
- Laboratory and electrodiagnostic findings in CIM
- - Direct muscle stimulation
- Pathology and pathogenesis of CIM
- Diagnosis of CIM
- Treatment and prognosis of CIM
- CRITICAL ILLNESS POLYNEUROPATHY
- Association with sepsis
- Clinical features of CIP
- Laboratory and electrodiagnostic findings in CIP
- Diagnosis of CIP
- Treatment and prognosis of CIP
- COMBINED CRITICAL ILLNESS MYOPATHY AND POLYNEUROPATHY
- Outcome and prognosis of combined CIM/CIP
- PROLONGED NEUROMUSCULAR JUNCTION BLOCKADE
- SUMMARY AND RECOMMENDATIONS