İlkin ÇANKAYALI, Mehmet UYAR, Kubilay DEMİRAĞ, Özden BOYACILAR, Ali Reşat MORAL

Neuromuscular Dysfunction in Experimental Sepsis and Glutamine

Background: Electrophysiological studies show thatcritical illness polyneuromyopathy appears in the earlystage of sepsis before the manifestation of clinical findings.The metabolic response observed during sepsiscauses glutamine to become a relative essential aminoacid.Aims: We aimed to assess the changes in neuromusculartransmission in the early stage of sepsis after glutaminesupplementation.Study Design: Animal experimentation.Methods: Twenty male Sprague-Dawley rats wererandomized into two groups. Rats in both groups weregiven normal feeding for one week. In the study group,1 g/kg/day glutamine was added to normal feeding byfeeding tube for one week. Cecal ligation and perforation(CLP) surgery was performed at the end of oneweek. Before and 24 hours after CLP, compound muscleaction potentials were recorded from the gastrocnemiusmuscle.Results: Latency measurements before and 24 hoursafter CLP were 0.68±0.05 ms and 0.80±0.09 ms in thecontrol group and 0.69±0.07 ms and 0.73±0.07 ms inthe study group (p

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1. Ahlbeck K, Fredriksson K, Rooyackers O, Måbäck G, Remahl S, Ansved T, et al. Signs of critical illness polyneuropathy and myopathy can be seen early in the ICU course. Acta Anaesthesiol Scand 2009;53:717-23. [CrossRef]
2. Cankayali I, Dogan YH, Solak I, Demirag K, Eris O, Demirgoren S, et al. Neuromuscular deterioration in the early stage of sepsis in rats. Critical Care 2007;11:R1. [CrossRef]
3. Cankayali I, Dogan YH, Solak I, Eris O, Demirgoren S, Moral AR. Effects of IgM-enriched immunoglobulin and fluid replacement on nerve conduction velocity in experimental sepsis. Turkish Journal of Trauma & Emergency Surgery 2010; Ulus Travma Acil Cerrahi Derg 2010;16:9-14.
4. Brough W, Horne G, Blount A, Irving MH, Jeejeebhoy KN. Effects of nutrient intake. surgery. sepsis. and long term administration of steroids on muscle function. Br Med J 1986;293:983-8. [CrossRef]
5. Boczkowski J, Dureuil B, Branger C, Pavlovic D, Murciano D, Pariente R, et al. Effects of sepsis on diaphragmatic function in rats. Am Rev Respir Dis 1988;138:260-5. [CrossRef]
6. Ricks E. Critical illness polyneuropathy and myopathy: a review of evidence and the implications for weaning from mechanical ventilation and rehabilitation. Physiotherapy 2007;93:151-6. [CrossRef]
7. Burnham EL, Moss M, Ziegler TR. Myopathies in critical illness: Characterization and nutritional aspects. J Nutr 2005; 1818S-23S.
8. Latronico N, Shehu I, Seghelini E. Neuromuscular sequelae of critical illness. Curr Opin in Crit Care 2005;11:381-90. [CrossRef]
9. Vermeulen MA, van de Poll MC, Ligthart-Melis GC, Dejong CH, van den Tol MP, Boelens PG, et al. Spesific amino acids in critically ill patient-Exogenous glutamine/arginine: A common denominator. Crit Care Med 2007;35:S568-S76. [CrossRef]
10. Vesali RF, Klaude M, Rooyackers O, Wernerman J. Amino acid metabolism in leg muscle after an endotoxin injection in healthy volunteers. Am J Physiol Endocrinol Metab 2005;E360-E4. [CrossRef]
11. Häussinger D, Lang F, Gerok W. Regulation of cell function by the cellular hydration state. Am J Physiol 1994;67:E343-55.
12. Roth E, Oehler R. Hypothesis: Muscular glutamine deficiency in sepsis- a necessary step for a hibernation-like state. Nutrition 2010;26:571-4. [CrossRef]
13. Otero-Anton E, Gonzalez-Quintela A, Lopez-Soto A, LopezBen S, Llovo J, Perez LF. Cecal ligation and puncture as a model of sepsis in the rat: influence of the puncture size on mortality, bacteremia, endotoxemia and tumor necrosis factor alpha levels. Eur Surg Res 2001;33:77-9. [CrossRef]
14. Ritter C, Andrades M, Frota Junior ML, Bonatto F, Pinho RA, Polydoro M, et al. Oxidative parameters and mortality in sepsis induced by cecal ligation and perforation. Intensive Care Med 2003;29:1782-9. [CrossRef]
15. Bolton CF. Evidence of neuromuscular dysfunction in the early stage of the systemic inflammatory responce syndrome. Intensive Care Med 2000;26:1179-80. [CrossRef]
16. Bolton CF. Neuromuscular manifestations of critical illness. Muscle Nerve 2005;32:140-63. [CrossRef]
17. Tennilä A, Salmi T, Pettilä V, Roine RO, Varpula T, Takkunen O. Early signs of critical illness polyneuropathy in ICU patients with systemic inflammatory response syndrome or sepsis. Intensive Care Med 2000;26:1360-3. [CrossRef]
18. Cuddon PA, Murray M, Kraus K. Electrodiagnosis. In: Saltter DH, editor. Textbook of Small Animal Surgery Volume II, 3rd ed. Philadelphia; Saunders 2003:1108-17.
19. Bolton CF. Gilbert JJ. Hahn AF, Sibbald WJ. Polyneuropathy in critically ill patients. J Neurol Neurosurg Psychiatry 1984; 47:1223-31. [CrossRef]
20. Zochodne DW, Bolton CF, Wells GA, Gilbert JJ, Hahn AF, Brown JD et al. Critical illness polyneuropathy. A complication of sepsis and multiple organ failure. Brain 1987;110:819-41. [CrossRef]
21. Bolton CF. Sepsis and the systemic inflammatory response syndrome: neuromuscular manifestations. Crit Care Med 1996;24:1408-16. [CrossRef]
22. Routsi C, Gerovasili V, Vasileiadis I, Karatzanos E, Pitsolis T, Tripodaki E, et al. Electrical muscle stimulation prevents critical illness polyneuromyopathy: a randomized parallel intervention trial. Crit Care 2010;14:R74. [CrossRef]
23. Moss M, Yang M, Macht M, Sottile P, Gray L, McNulty M, et al. Screening for critical illness polyneuromyopathy with single nerve conduction studies. Intensive Care Med 2014;40:683-90. [CrossRef]
24. Plank LD, Connoly AB, Hill AG. Sequential changes in the metabolic response in severely septic patients during the first 23 days after onset of peritonitis. Ann Surg 1998;228:146-58. [CrossRef]
25. Vary TC, Lynch CJ. Biochemical approaches for nutritional support of skeleteal muscle protein metabolism during sepsis. Nutr Res Rev 2004;17:77-88. [CrossRef]
26. Askanazi J, Carpentier YA, Michelsen CB, Elwyn DH, Furst P, Kantrowitz LR, et al. Muscle and Plasma Amino Acids Following Injury Influence of Intercurrent Infection. Ann Surg 1980;192:1;78-85. [CrossRef]
27. Shou J. Glutamine. In: Zaloga GP. Ed. Nutrition in Critical Care. St. Louis. Missouri. USA: Mosby 1994;123-41.
28. Haussinger D, Roth E, Lang F, Gerok W. Cellular hydration state: an important determinant of protein catabolism in health and disease. Lancet 1993;341:1330-2. [CrossRef]
29. Wischmeyer PE. Glutamine: role in critical illness and ongoing clinical trials. Curr Opin Gastroenterol 2008;24:190-7. [CrossRef]
30. Gamrin L, Essén P, Forsberg AM, Hultman E, Wernerman J. A descriptive study of skeletal muscle metabolism in critically ill patients: free amino acids. energy-rich phosphates protein. nucleic acids. fat. water and electrolytes. Crit Care Med 1996;24:575-83. [CrossRef]
31. Wischmeyer PE, Kahana M, Wolfson R, Ren H, Musch MM, Chang EB. Glutamine reduces cytokine release, organ damage and mortality in a rat model of endotoxemia. Shock 2001;16:398-402. [CrossRef]
32. Singleton KD, Serkova N, Beckey WE, Wischmeyer PE. Glutamine attenuates lung injury and improves survival after sepsis. Role of enhanced heat shock protein expression. Crit Care Med 2005;33:1206-13. [CrossRef]
33. Morrison AL, Dinges M, Singleton KD, Odoms K, Wong HR, Wischmeyer PE. Glutamine's protection against celluler injury is dependent on heat shock factor. Am J Physiol Cell Physiol 2006;290:C1625-32. [CrossRef]
34. Wang WS, Lin JK, Lin TC, Chen WS, Jiang JK, Wang HS, et al. Oral glutamine is effective for preventing oxaplatininduced neuropathy in colorectal cancer patients. Oncologist 2007;12:312-9. [CrossRef]
35. Wernerman J. Glutamine supplementation. Ann Intensive Care 2011;18;1:25.
36. Vanek VW, Matarese LE, Robinson M, Sacks GS, Young LS, Kochevar M, et al. ASPEN position paper: parenteral nutrition glutamine supplementation. Nutr Clin Pract 2011;26:479-94. [CrossRef]
37. Apfel SC, Lipton RB, Arezzo JC, Kessler JA. Nerve growth factor prevents toxic neuropathy in mice. Ann Neurol 1991;29:87-90. [CrossRef]
38. Gwag BJ, Sessler FM, Robine V, Springer JE. Endogenous glutamate levels regulate nerve nerve growth factor mRNA expression in the rat dentate gyrus. Mol Cells 1997;7:425-30.
39. Cao Y, Kennedy R, Klimberg VS. Glutamine protects against doxorubicin-induced cardiotoxicity. J Surg Res 1999;85:178-82. [CrossRef]
40. Boyle FM, Wheeler HR, Shenfield GM. Glutamate ameliorates experimental vincristine neuropathy. J Pharmacol Exp Ther 1996;279:410-5.
41. Cascinu S, Catalano V, Cordella L, Labianca R, Giordani P, Baldelli AM, et al. Neuroprotective effect of reduced glutathione on oxaliplatin-base chemotherapy in advanced colorectal cancer: A randomized double-blind placebo-controlled trial. J Clin Oncol 2002;20:3478-83. [CrossRef]
42. Peltier AC, Russell JW. Recent advances in drug-induced neuropathies. Curr Opin Neurol 2002;15:633-8. [CrossRef]
43. Mori M, Rooyackers O, Smedberg M, Tjader I, Norberg A, Wernermann J. Endogenous glutamine production in critically ill patients: the effect of exogenous glutamine supplementation. Crit Care 2014;18:R72. [CrossRef]
44. Oudemans-van Straaten HM, van Zanten ARH. Glutamine supplementation in the critically ill : friend or foe? Crit Care 2014;18:143. [CrossRef]
45. Lin JJ, Chung XJ, Yang CY, Lau HL. A metaanalysis of trials using intention t oto treat pirinciple for glutamine supplemantation in critically ill patients with burn. Burns 2013;39:565-70. [CrossRef]
46. Ziegler TR, Young LS, Benfell K, Scheltinga M, Hortos K, Bye R, et al. Ann Intern Med 1992;116:821-8. [CrossRef]
47. Heyland D, Muscedere J, Wischmeyer PE, Cook D, Jones G, Albert Met, al. A randomized trial of glutamine and antioxidans in critically ill patients. N Eng J Med 2013;368:1489-97. [CrossRef]
48. Mulherin DW, Sacks SS. Uncertainty about the safety of supplemantalglutamine: an editorial on "A randomized trial of glutamine and antioxidans in critically ill patients." Hepatobiliary Surg Nutr 2015;76-9.
49. Doruk N, Buyukakilli B, Atici S, Cinel I, Cinel L, Tamer L, et al. The Effect of Preventive Use of Alanyl-Glutamine on Diaphragm Muscle Function in Cecal Ligation and Puncture-Induced Sepsis Model. JPEN J Parenter Enteral Nutr 2005;29:36-43. [CrossRef]