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Critical illness myopathy: sepsis-mediated failure of the peripheral nervous system

Published online by Cambridge University Press:  01 February 2008

O. Friedrich
O. Friedrich*
Affiliation:
Ruprecht-Karls-University, Institute of Physiology & Pathophysiology, Department of System Physiology, Medical Biophysics, Heidelberg, Germany
*
Correspondence to: Oliver Friedrich, Medical Biophysics, Department of System Physiology, Institute of Physiology & Pathophysiology, Ruprecht-Karls-University, Im Neuenheimer Feld 326, 69120 Heidelberg, Germany. E-mail: oliver.friedrich@physiologie.uni-heidelberg.de; Tel: +49-6221-54-4143; Fax: +49-6221-54-4123
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Summary

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.

Keywords

POLYNEUROPATHYCRITICAL CAREMUCULAR DISEASESNEUROMUSCULAR DISEASESSEPSISMYOPATHY
Type
Original Article
Information
European Journal of Anaesthesiology , Volume 25 , Issue S42 , February 2008 , pp. 73 - 82
Copyright
Copyright © European Society of Anaesthesiology 2008

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References

1.Laupland, KB. Population-based epidemiology of intensive care: critical importance of ascertainment of residency status. Critical Care 2004; 8: R431–R436.Google Scholar
2.Martin, CM, Hill, AD, Burns, K, Chen, LM. Characteristics and outcomes for critically ill patients with prolonged intensive care unit stays. Crit Care Med 2005; 33: 1922–1927.Google Scholar
3.Angus, DC, Linde-Zwirble, WT, Lidicker, J, Clermont, G, Garcillo, J, Pinsky, MR. Epidemiology of severe sepsis in the United States: analysis of incidence, outcome and associated costs of care. Crit Care Med 2001; 29: 1303–1310.Google Scholar
4.Brunkhorst, FM, Engel, C, Reinhart, K et al. . Epidemiology of severe sepsis and septic shock in Germany: results from the German ‘Prevalence’ study. Critical Care 2005; 9: P196.Google Scholar
5.Hund, E. Neurological complications of sepsis: critical illness polyneuropathy and myopathy. J Neurol 2001; 248: 929–934.Google Scholar
6.Bolton, CF. Neuromuscular manifestations of critical illness. Muscle Nerve 2005; 32: 140–163.Google Scholar
7.Bolton, CF, Young, GB, Zochodne, DW. The neurological complications of sepsis. Ann Neurol 1993; 33: 94–100.Google Scholar
8.Pastores, SM. Critical illness polyneuropathy and myopathy in acute respiratory distress syndrome: more common than we realize! Crit Care Med 2005; 33: 895–896.CrossRefGoogle ScholarPubMed
9.Zochodne, DW, Bolton, CF, Wells, GA et al. . Critical illness polyneuropathy: a complication of sepsis and multiple organ failure. Brain 1987; 110: 819–841.Google Scholar
10.Latronico, N, Fenzi, F, Recupero, D et al. . Critical illness myopathy and neuropathy. Lancet 1996; 347: 1579–1582.Google Scholar
11.Latronico, N, Peli, E, Botteri, M. Critical illness myopathy and neuropathy. Curr Opin Crit Care 2005; 11: 126–132.CrossRefGoogle ScholarPubMed
12.Khan, J, Harrison, TB, Rich, MM, Moss, M. Early development of critical illness myopathy and neuropathy in patients with severe sepsis. Neurology 2006; 67: 1421–1425.CrossRefGoogle ScholarPubMed
13.Bednarik, J, Lukas, Z, Vondracek, P. Critical illness polyneuromyopathy: the electrophysiological components of a complex entity. Crit Care Med 2003; 29: 1505–1514.Google ScholarPubMed
14.Latronico, N. Neuromuscular alterations in critically ill patients: critical illness myopathy, critical illness neuropathy, or both? Intensive Care Med 2003; 29: 1411–1413.Google Scholar
15.Friedrich, O. Critical illness myopathy: what is happening? Curr Opin Clin Nutr Metab Care 2006; 9: 403–409.Google Scholar
16.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; 30: 1117–1121.CrossRefGoogle ScholarPubMed
17.Zarzhevsky, N, Menashe, O, Carmeli, E, Stein, H, Reznick, AZ. Capacity for recovery and possible mechanism in immobilisation atrophy of young and old animals. Ann NY Acad Sci 2001; 928: 212–225.Google Scholar
18.Widrick, JJ, Norenberg, KM, Romantowski, JG et al. . Force velocity power and force-pCa relationships of human soleus fibres after 17 days of bed rest. J Appl Physiol 1998; 85: 1949–1956.CrossRefGoogle ScholarPubMed
19.Ginz, HF, Iaizzo, PA, Girard, T, Urwyler, A, Parrger, H. Decreased isometric skeletal muscle force in critically ill patients. Swiss Med Wkly 2005; 135: 555–561.Google ScholarPubMed
20.Eikermann, M, Koch, G, Gerwig, M et al. . Muscle force and fatigue in patients with sepsis and multiorgan failure. Intensive Care Med 2006; 32: 251–259.Google Scholar
21.Diaz, NL, Finol, HJ, Torres, SH, Zambrano, CI, Adjounian, H. Histochemical and ultrastructural study of skeletal muscle in patients with sepsis and multiple organ failure syndrome (MOFS). Histol Histopathol 1998; 13: 121–128.Google Scholar
22.Reardon, KA, Davis, J, Kapsa, RM, Choong, P, Byrne, E. Myostatin, insulin-like growth factor-1 and leukimia inhibitory factor mRNAs are upregulated in chronic human disuse muscle atrophy. Muscle Nerve 2001; 24: 893–899.CrossRefGoogle Scholar
23.Machida, S, Booth, FW. Changes in signalling molecule levels in 10-day hindlimb immobilized rat muscles. Acta Physiol Scand 2005; 183: 171–179.Google Scholar
24.Caruso, P, Denari, SD, Ruiz, SA et al. . Inspiratory muscle training is ineffective in mechanically ventilated critically ill patients. Clinics 2005; 60: 479–484.CrossRefGoogle ScholarPubMed
25.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.Google Scholar
26.Rich, MM, Bird, SJ, Raps, EC, McCluskey, LF, Teener, JW. Direct muscle stimulation in acute quadriplegic myopathy. Muscle Nerve 1997; 20: 665–673.Google Scholar
27.Bolton, CF. Sepsis and the systemic inflammatory response syndrome: neuromuscular manifestations. Crit Care Med 1996; 24: 1408–1416.Google Scholar
28.Danon, MJ, Carpenter, S. Myopathy with thick filament (myosin) loss following prolonged paralysis with veuronium during steroid treatment. Muscle Nerve 1991; 14: 1131–1139.CrossRefGoogle ScholarPubMed
29.Hasselgren, PO, Fischer, JE. Sepsis: stimulation of energy-dependent protein breakdown resulting in protein loss in skeletal muscle. World J Surg 1998; 22: 203–208.CrossRefGoogle ScholarPubMed
30.Norman, H, Kandala, K, Kolluri, R et al. . A porcine model of acute quadriplegic myopathy: a feasibility study. Acta Anaesthesiol Scand 2006; 50: 1058–1067.Google Scholar
31.De Jonghe, B, Sharshar, T, Lefaucheur, JP et al. . Paresis acquired in the intensive care unit: a prospective multicenter study. JAMA 2002; 288: 2859–2867.CrossRefGoogle ScholarPubMed
32.Berchtold, MW, Brinkmeier, H, Müntener, M. Calcium ions in skeletal muscle: its crucial role for muscle function, plasticity and disease. Physiol Rev 2000; 80: 1215–1265.CrossRefGoogle Scholar
33.Gordon, AM, Homsher, E, Regnier, M. Regulation of contraction in striated muscle. Physiol Rev 2000; 80: 853–924.CrossRefGoogle ScholarPubMed
34.Murray, MJ, Brull, SJ, Bolton, CF. Brief review: nondepolarizing neuromuscular blocking drugs and critical illness myopathy. Can J Anesth 2006; 53: 1148–1156.CrossRefGoogle ScholarPubMed
35.De Letter, MA, Schmitz, PI, Visser, LH et al. . Risk factors for the development of polyneuropathy and myopathy in critically ill patients. Crit Care Med 2001; 29: 2281–2286.Google Scholar
36.Hughes, BJ, Krieg, M. Increased glucocorticoid/androgen receptor ratios in denervated striated muscle. J Steroid Biochem 1986; 25: 695–699.CrossRefGoogle ScholarPubMed
37.Rich, MM, Kraner, SD, Barchi, SL. Altered gene expression in steroid-treated denervated muscle. Neurobiol Dis 1999; 6: 515–522.Google Scholar
38.Prigent, H, Maxime, V, Annane, D. Clinical review: corticotherapy in sepsis. Crit Care 2004; 8: 122–129.Google Scholar
39.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.CrossRefGoogle Scholar
40.Rich, MM, Pinter, MJ. Sodium channel inactivation in an animal model of acute quadriplegic myopathy. Ann Neurol 2001; 50: 26–33.Google Scholar
41.Rich, MM, Pinter, MJ. Crucial role of sodium channel fast inactivation in muscle fibre inexcitability in a rat model of critical illness myopathy. J Physiol 2003; 547.2: 555–566.Google Scholar
42.Filatov, GN, Rich, MM. Hyperpolarized shifts in the voltage dependence of fast inactivation of Nav1.4 and Nav1.5 in a rat model of critical illness myopathy. J Physiol 2004; 559.3: 813–820.Google Scholar
43.Trunkey, DD, Illner, H, Wagner, IY, Shires, GT. The effect of septic shock on skeletal muscle action potentials in the primate. Surgery 1979; 85: 638–643.Google ScholarPubMed
44.Gibson, WH, Cook, JJ, Gatipon, G, Moses, ME. Effect of endotoxin shock on skeletal muscle cell membrane potential. Surgery 1977; 81: 571–577.Google Scholar
45.Tracey, KJ, Lowry, SF, Beutler, B, Cerami, A, Albert, JD, Shires, GT. Cachectin/tumor necrosis factor mediates changes of skeletal muscle plasma membrane potential. J Exp Med 1986; 164: 1368–1373.Google Scholar
46.Friedrich, O, Hund, E, Weber, C, Hacke, W, Fink, RHA. Critical illness myopathy serum fractions affect membrane excitability and intracellular calcium release in mammalian skeletal muscle. J Neurol 2004; 251: 53–65.Google Scholar
47.Niiya, T, Narimatsu, E, Namiki, A. Acute late sepsis attenuates effects of a non-depolarizing neuromuscular blocker, Rocuronium, by facilitation of endplate potential and enhancement of membrane excitability in vitro. Anesthesiology 2006; 105: 968–975.Google Scholar
48.Reid, CL, Campbell, IT, Little, RA. Muscle wasting and energy balance in critical illness. Clin Nutr 2004; 23: 273–280.CrossRefGoogle ScholarPubMed
49.Williams, AB, Decourten-Myers, GM, Fischer, JE, Luo, G, Sun, X, Hasselgren, PO. Sepsis stimulates release of myofilaments in skeletal muscle by a calcium-dependent mechanism. FASEB J 1999; 13: 1435–1443.Google Scholar
50.Mitch, WE, Goldberg, AL. Mechanisms of muscle wasting: the role of the ubiquitin-proteasome pathway. N Engl J Med 1996; 335: 1897–1905.Google Scholar
51.Laghi, F, Tobin, J. Disorders of the respiratory muscle. Am J Respir Crit Care Med 2003; 168: 10–48.Google Scholar
52.Solomon, V, Goldberg, AL. Importance of the ATP-ubiquitin-proteasome pathway in the degradation of soluble and myofibrillar proteins in rabbit muscle extracts. J Biol Chem 1996; 271: 26690–26697.Google Scholar
53.Li, YP, Schwartz, RJ, Waddell, ID, Holloway, BR, Reid, MB. Skeletal muscle myocytes undergo protein loss and reactive oxygen-mediated NF-κB activation in response to tumor necrosis factor α. FASEB J 1998; 12: 871–880.Google ScholarPubMed
54.Li, YP, Reid, MB. NF-κB mediates the protein loss induced by TNF-α in differentiated skeletal muscle myotubes. Am J Physiol Regul Integr Comp Physiol 2000; 279: R1165–R1170.Google Scholar
55.Acharrya, S, Ladner, KJ, Nelson, LL et al. . Cancer cachexia is regulated by selective targeting of skeletal muscle gene products. J Clin Invest 2004; 114: 70–378.Google Scholar
56.Martin, C, Boisson, C, Haccoun, M, Thomachot, L, Mege, JL. Patterns of cytokine evolution (tumor necrosis factor-alpha and interleukin-6) after septic shock, hemorrhagic shock and severe trauma. Crit Care Med 1997; 25: 1813–1819.CrossRefGoogle ScholarPubMed
57.Price, SR, England, BK, Bailey, JL, Van Vreede, K, Mitch, WE. Acidosis and glucocorticoids concomitantly increase ubiquitin and proteasome subunit mRNAs in rat muscle. Am J Physiol 1994; 267: C955–C960.Google Scholar
58.Horinouchi, H, Kumamoto, T, Kimura, N, Ueyama, H, Tsuda, T. Myosin loss in denervated rat soleus muscle after dexamethasone treatment. Pathobiology 2005; 72: 108–116.Google Scholar
59.Fischer, DR, Sun, X, Prittis, TA, Hasselgren, PO. The amount of the glucocorticoid receptor (GR) and its hormone binding activity are increased in skeletal muscle during sepsis. Surg Forum 1999; 51: 214–216.Google Scholar
60.Combaret, L, Taillandier, D, Dardevet, D et al. . Glucocorticoids regulate mRNA levels for subunits of the 19S regulatory complex of the 26S proteasome in fast-twitch skeletal muscle. Biochem J 2004; 378: 239–246.Google Scholar
61.Lee, MC, Wee, GR, Kim, JH. Apoptosis of skeletal muscle on steroid-induced myopathy in rats. J Nutr 2005; 135: 1806S–1808S.CrossRefGoogle ScholarPubMed
62.Vanhorebeek, I, Langouche, L, van den Berghe, G. Endocrine aspects of acute and prolonged critical illness. Nat Clin Pract Endocrinol Metab 2006; 2: 20–31.CrossRefGoogle ScholarPubMed
63.Vanhorebeek, I, van den Berghe, G. The neuroendocrine response to critical illness is a dynamic process. Crit Care Clin 2006; 22: 1–15.CrossRefGoogle ScholarPubMed
64.Riedemann, NC, Guo, RF, Ward, PA. Novel strategies fort he treatment of sepsis. Nat Med 2003; 9: 517–524.Google Scholar
65.Brunkhorst, FM, Kuhnt, E, Engel, C et al. . Intensive insulin therapy in patients with severe sepsis and septic shock is associated with an increased rate of hypoglycemia – results from a randomized multicenter study (VISEP). Infection 2005; 33: 19–20.Google Scholar
66.Aghajani, E, Nordhaug, D, Korvald, C et al. . Mechanoenergetic inefficiency in the septic left ventricle is due to enhanced oxygen requirements for excitation–contraction coupling. Cardiovas Res 2004; 63: 256–263.Google Scholar