Sobre los usos, aplicaciones y beneficios de las soluciones parenterales de glutamina

Alfredo Matos Adames, Sergio Santana Porbén

Texto completo:

PDF

Resumen

El conocimiento de las propiedades farmacológicas de la glutamina (Gln) ha provisto el estímulo para el desarrollo de la Inmunonutrición como especialidad de la terapia nutricional y el apoyo nutricional mediante la inclusión de este aminoácido en productos enterales, o como soluciones de dipéptidos para la incorporación dentro de regímenes de nutrición parenteral. Varios cuerpos de expertos recomiendan el uso de los dipéptidos de Gln en situaciones clínico-quirúrgicas como el trauma y la cirugía de las vías digestivas. Varios estudios han sugerido beneficios tangibles tras el uso de los dipéptidos de Gln en en estas situaciones. Sin embargo, el empleo de la Gln como fármaconutriente, y hasta la propia existencia de la especialidad de la Inmunonutrición, fueron puestos en duda tras los resultados de los ensayos REDOXS (Heyland et al., 2013) y MetaPlus (van Zanten et al., 2014), los que concluyeron que la administración exógena de Gln (en cualquier forma de presentación farmacéutica) podría significar un mayor riesgo de mortalidad para los pacientes críticamente enfermos. Los análisis post-hoc de los ensayos antes citados revelaron importantes falencias del diseño metodológico de los mismos, y una pobre definición de los objetivos de la suplementación exógena con Gln. En la resaca de los resultados de los ensayos REDOXS y MetaPlus se han conducido nuevos meta-análisis y revisiones sistémicas que confirman la efectividad de las soluciones de la Gln como parte de los esquemas de repleción nutricional que se conducen en las unidades de cuidados críticos. También se han emitido nuevas recomendaciones y pautas sobre la mejor selección de los pacientes que se beneficiarían máximamente de la administración de Gln, las precauciones que se deben observar con estos preparados farmacológicos, y las contraindicaciones para el uso de la Gln. Se avizora una nueva era de (re)descubrimientos del lugar de la Gln en la terapia nutricional.

Palabras clave

Glutamina; Dipéptidos; Nutrición parenteral; Cuidados críticos

Referencias

Ehrensvärd G, Fischer A, Stjernholm R. Protein metabolism of tissue cells in vitro. 7. The chemical nature of some obligate factors of tissue cell nutrition. Acta Physiol Scand 1949;18: 218-30.

Eagle H, Oyama VI, Levy M, Horton CL, Fleischman R. The growth response of mammalian cells in tissue culture to L-glutamine and L-glutamic acid. J Biol Chem 1956;218:607-16.

Blaker GJ, Birch JR, Pirt SJ. The glucose, insulin and glutamine requirements of suspension cultures of HeLa cells in a defined culture medium. J Cell Sci 1971;9:529-37.

Newsholme P, Curi R, Curi TP, Murphy CJ, Garcia C, De Melo MP. Glutamine metabolism by lymphocytes, macrophages, and neutrophils: Its importance in health and disease. J Nutr Biochem 1999;10:316-24.

Wells SM, Kew S, Yaqoob P, Wallace FA, Calder PC. Dietary glutamine enhances cytokine production by murine macrophages. Nutrition 1999;15:881-4.

Calder PC, Yaqoob P. Glutamine and the immune system. Amino acids 1999;17:227-41.

Ashy AA, Ardawi MSM. Glucose, glutamine, and ketone-body metabolism in human enterocytes. Metabolism (Clin Exp) 1988;37:602-9.

Ardawi M, Salleh M. The transport of glutamine and alanine into rat colonocytes. Biochem J 1986;238:131-5.

Newsholme EA, Carrie AL. Quantitative aspects of glucose and glutamine metabolism by intestinal cells. Gut 1994;35(1 Suppl):S13-S17.

Sumbilla CM, Zielke CL, Reed WD, Ozand PT, Zielke HR. Comparison of the oxidation of glutamine, glucose, ketone bodies and fatty acids by human diploid fibroblasts. Biochim Biophys Acta 1981;675:301-4.

Karna E, Miltyk W, Wołczyński S, Pałka JA. The potential mechanism for glutamine-induced collagen biosynthesis in cultured human skin fibroblasts. Comp Biochem Physiol Part B Biochem Mol Biol 2001;130:23-32.

Smith RJ, Wilmore DW. Glutamine nutrition and requirements. JPEN J Parenter Enter Nutr 1990;14(Suppl):S94-S99.

Lacey JM, Wilmore DW. Is glutamine a conditionally essential amino acid? Nutr Rev 1990;48:297-309.

Wilmore DW, Shabert JK. Role of glutamine in immunologic responses. Nutrition 1998;14:618-26.

García de Lorenzo A, Zarazaga A, García Luna PP, Gonzalez Huix F, López Martínez J, Miján A; et al. Clinical evidence for enteral nutritional support with glutamine: A systematic review. Nutrition 2003;19:805-11.

Grant JP, Snyder PJ. Use of L-glutamine in total parenteral nutrition. J Surg Res 1988;44:506-13.

Fürst P, Albers S, Stehle P. Glutamine‐containing dipeptides in parenteral nutrition. JPEN J Parenter Enter Nutr 1990;14(Suppl):S118-S124.

Jiang ZM, Wang LJ, Qi Y, Liu TH, Qiu MR, Yang NF, Wilmore DW. Comparison of parenteral nutrition supplemented with L‐glutamine or glutamine dipeptides. JPEN J Parenter Enter Nutr 1993;17:134-41.

Andrade Hernández MB, Chaug Solórzano MA, Andino Rodríguez FX, Rodríguez Veintimilla D. Sobre las propiedades y los usos de la glutamina en la citorreducción tumoral. RCAN Rev Cubana Aliment Nutr 2017;27:430-64.

Heyland DK, Dhaliwal R, Day AG, Muscedere J, Drover J, Suchner U; et al; for the Canadian Critical Care Trials Group. REducing Deaths due to OXidative Stress (The REDOXS© Study): Rationale and study design for a randomized trial of glutamine and antioxidant supplementation in critically ill patients. Proc Nutr Soc 2006;65;250-63.

Heyland D, Muscedere J, Wischmeyer PE, Cook D, Jones G, Albert M; et al; for the Canadian Critical Care Trials Group. A randomized trial of glutamine and antioxidants in critically ill patients. N Engl J Med 2013;368:1489-97.

van Zanten AR, Sztark F, Kaisers UX, Zielmann S, Felbinger TW, Sablotzki AR; et al. High-protein enteral nutrition enriched with immune modulating nutrients vs. standard high protein enteral nutrition and nosocomial infections in the ICU: A randomized clinical trial. JAMA 2014;312:514-24.

van Zanten AR, Hofman Z, Heyland DK. Consequences of the REDOXS and METAPLUS trials: The end of an era of glutamine and antioxidant supplementation for critically ill patients? JPEN J Parenter Enter Nutr 2015;39:890-2.

Festen B, van Zanten AR. The end of an era of pharmaconutrition and immunonutrition trials for the critically-ill patient. Minerva Anestesiol 2016;82: 262-4.

Heyland DK, Elke G, Cook D, Berger MM, Wischmeyer PE, Albert M; et al; for the Canadian Critical Care Trials Group. Glutamine and antioxidants in the critically ill patient: A post hoc analysis of a large-scale randomized trial. JPEN J Parenter Enter Nutr 2015;39:401-9.

Hofman Z, Swinkels S, van Zanten AR. Glutamine, fish oil and antioxidants in critical illness: MetaPlus trial post hoc safety analysis. Ann Intensive Care 2016;6(1):119-131. Disponible en: https://doi.org/10.1186/s13613-016-0220-y. Fecha de última visita: 6 de Febrero del 2018.

Stehle P, Ellger B, Kojic D, Feuersenger A, Schneid C, Stover J; et al. Glutamine dipeptide-supplemented parenteral nutrition improves the clinical outcomes of critically ill patients: A systematic evaluation of randomised controlled trials. Clin Nutr 2017;17:75-85.

McClave SA, Taylor BE, Martindale RG, Warren MM, Johnson DR, Braunschweig C; et al. Guidelines for the provision and assessment of nutrition support therapy in the adult critically ill patient. JPEN J Parenter Enter Nutr 2016;40:159-211.

Santana Porbén S, Barreto Penié J. Metabolismo de los sustratos. En: Nutrición enteral y parenteral [Editores: Arenas Márquez H, Anaya Prado R]. McGraw Hill Interamericana. México: 2007.

Smith RJ. Glutamine metabolism and its physiologic importance. JPEN J Parenter Enter Nutr 1990;14(Suppl):S40-S44.

Xi P, Jiang Z, Zheng C, Lin Y, Wu G. Regulation of protein metabolism by glutamine: Implications for nutrition and health. Front Biosci 2011;16:578-97.

Biolo G, Zorat F, Antonione R, Ciocchi B. Muscle glutamine depletion in the intensive care unit. Int J Biochem Cell Biol 2005;37:2169-79.

Marliss EB, Aoki TT, Pozefsky T, Most AS, Cahill GF. Muscle and splanchnic glutamine and glutamate metabolism in postabsorptive and starved man. J Clin Invest 1971;50:814-7.

Curthoys NP, Watford M. Regulation of glutaminase activity and glutamine metabolism. Annu Rev Nutr 1995;15:133-59.

Häussinger D. Regulation of hepatic ammonia metabolism: The intercellular glutamine cycle. Adv Enzyme Regulat 1986;25:159-80.

Coster J, McCauley R, Hall J. Glutamine: Metabolism and application in nutrition support. Asia Pacific J Clin Nutr 2004;13:25-31.

Watford M. Glutamine and glutamate metabolism across the liver sinusoid. J Nutr 2000;130(Suppl):S983-S987.

Lenders CM, Liu S, Wilmore DW, Sampson L, Dougherty LW, Spiegelman D, Willett WC. Evaluation of a novel food composition database that includes glutamine and other amino acids derived from gene sequencing data. Eur J Clin Nutr 2009;63:1433-9.

Hammarqvist F, Ejesson B, Wernerman J. Stress hormones initiate prolonged changes in the muscle amino acid pattern. Clin Physiol 2001;21:44-50.

Roth E, Funovics J, Mühlbacher F, Schemper M, Mauritz W, Sporn P, Fritsch A. Metabolic disorders in severe abdominal sepsis: Glutamine deficiency in skeletal muscle. Clin Nutr 1982;1:25-41.

Oliveira GP, Dias CM, Pelosi P, Rocco PR. Understanding the mechanisms of glutamine action in critically ill patients. Anais Acad Bras Ciencias 2010; 82:417-30.

Biolo G, Fleming RD, Maggi SP, Nguyen TT, Herndon DN, Wolfe RR. Inhibition of muscle glutamine formation in hypercatabolic patients. Clin Sci 2000; 99:189-94.

Mittendorfer B, Gore DC, Herndon DN, Wolfe RR. Accelerated glutamine synthesis in critically ill patients cannot maintain normal intramuscular free glutamine concentration. JPEN J Parenter Enter Nutr 1999;23:243-52.

Boelens PG, Nijveldt RJ, Houdijk AP, Reijner S, van Leevwen PAM. Glutamine metabolism: Nutritional and clinical significance. J Nutr 2001;131(Suppl):S2569-S2577.

Kotler DP, Tierney AR, Wang J, Pierson Jr RN. Magnitude of body-cell-mass depletion and the timing of death from wasting in AIDS. Am J Clin Nutr 1989;50:444-7.

Oudemans-van Straaten HM, Bosman RJ, Treskes M, van der Spoel HJI, Zandstra DF. Plasma glutamine depletion and patient outcome in acute ICU admissions. Intensive Care Med 2001;27:84-90.

Ziegler TR, Benfell K, Smith RJ, Young LS, Brown E, Ferrari‐Baliviera E; et al. Safety and metabolic effects of L‐glutamine administration in humans. JPEN J Parenter Enter Nutr 1990;14(Suppl):S137-S146.

Khan K, Hardy G, McElroy B, Elia M. The stability of L-glutamine in total parenteral nutrition solutions. Clin Nutr 1991;10:193-8.

Abumrad NN, Morse EL, Lochs H, Williams PE, Adibi SA. Possible sources of glutamine for parenteral nutrition: Impact on glutamine metabolism. Am J Physiol Endocrinol Metab 1989;257:E228-E234.

Albers S, Wernerman J, Stehle P, Vinnars E, Fürst P. Availability of amino acids supplied intravenously in healthy man as synthetic dipeptides: Kinetic evaluation of L-alanyl-L-glutamine and glycyl-L-tyrosine. Clin Sci [London] 1988;75:463-8.

Tjader I, Berg A, Wernerman J. Exogenous glutamine- Compensating a shortage? Crit Care Med 2007;35(9 Suppl):S553-S556.

Wischmeyer PE. Glutamine: Mode of action in critical illness. Crit Care Med 2007;35(9 Suppl):S541-S544.

Dupertuis YM, Raguso CA, Pichard C. Basics in clinical nutrition: Nutrients which influence immunity- Clinical and experimental data. e-SPEN 2009;1(4): e7-e9. Disponible en: http://doi:10.1016/j.eclnm.2008.07.017. Fecha de última visita: 8 de Febrero del 2018.

Miller AL. Therapeutic considerations of L-glutamine: A review of the literature. Alter Med Rev 1999;4:239-48.

Ziegler TR, Ogden LG, Singleton KD, Luo M, Fernandez-Estivariz C, Griffith DP, Galloway JR, Wischmeyer PE. Parenteral glutamine increases serum heat shock protein 70 in critically ill patients. Intensive Care Med 2005; 31:1079-86.

Harward TR, Coe D, Souba WW, Klingman N, Seeger JM. Glutamine preserves gut glutathione levels during intestinal ischemia/reperfusion. J Surg Res 1994;56:351-5.

Suh GJ, Youn YK, Song HG, Rhee JE, Jung SE. The effect of glutamine on inducible nitric oxide synthase gene expression in intestinal ischemia-reperfusion injury. Nutr Res 2003;23: 131-40.

Chen G, Shi J, Qi M, Yin H, Hang C. Glutamine decreases intestinal nuclear factor kappa B activity and pro-inflammatory cytokine expression after traumatic brain injury in rats. Inflammat Res 2008;57:57-64.

Singleton KD, Beckey VE, Wischmeyer PE. Glutamine prevents activation of NF-κB and stress kinase pathways, attenuates inflammatory cytokine release, and prevents acute respiratory distress syndrome (ARDS) following sepsis. Shock 2005;24:583-9.

Wernerman J. Clinical use of glutamine supplementation. J Nutr 2008;138(10 Suppl):S2040-S2044.

Wernerman J. Glutamine supplementation. Ann Intensive Care 2011;1(1):25-25. Disponible en: https:// doi:10.1186/2110-5820-1-25. Fecha de última visita: 8 de Febrero del 2018.

Bakalar B, Duska F, Pachl J, Fric M, Otahal M, Pazout J, Andel M. Parenterally administered dipeptide alanyl-glutamine prevents worsening of insulin sensitivity in multiple trauma patients. Crit Care Med 2006;34:381-6.

Déchelotte P, Hasselmann M, Cynober L, Allaouchiche B, Coëffier M, Hecketsweiler B; et al. L-alanyl-L-glutamine dipeptide-supplemented total parenteral nutrition reduces infectious complications and glucose intolerance in critically ill patients: The French controlled, randomized, double-blind, multicenter study. Crit Care Med 2006; 34:598-604.

Grintescu IM, Vasiliu IL, Badica IC, Mirea L, Pavelescu D, Balanescu A, Grintescu IC. The influence of parenteral glutamine supplementation on glucose homeostasis in critically ill polytrauma patients- A randomized-controlled clinical study. Clin Nutr 2015;34:377-82.

Ziegler TR, May AK, Hebbar G, Easley KA, Griffith DP, Dave N; et al. Efficacy and safety of glutamine-supplemented parenteral nutrition in surgical ICU patients: An American multicenter randomized controlled trial. Ann Surg 2016;263:646-55.

Cui Y, Hu L, Liu YJ, Wu YM, Jing L. Intravenous alanyl-L-glutamine balances glucose-insulin homeostasis and facilitates recovery in patients undergoing colonic resection: A randomised controlled trial. Eur J Anaesthesiol 2014;31:212-8.

Hammarqvist F, Wernerman J, von der Decken A, Vinnars E. Alanyl-glutamine counteracts the depletion of free glutamine and the postoperative decline in protein synthesis in skeletal muscle. Ann Surg 1990;212:637-44.

Karwowska KA, Szulc R, Dworacki G, Keromski J. Influence of glutamine enriched parenteral nutrition on nitrogen balance and immunological status in patients undergoing elective aortic aneurysms repair. Nutrition 2001;17:475-8.

Alves WF, Aguiar EE, Guimarães SB, da Silva Filho AR, Pinheiro PMA, Soares GDSD, de Vasconcelos PRL. L-alanyl-glutamine preoperative infusion in patients with critical limb ischemia subjected to distal revascularization reduces tissue damage and protects from oxidative stress. Ann Vasc Surg 2010; 24:461-7.

Paun BC, Cassie S, MacLean AR, Dixon E, Buie WD. Postoperative complications following surgery for rectal cancer. Ann Surg 2010;251:807-18.

Vonlanthen R, Slankamenac K, Breitenstein S, Puhan MA, Muller MK, Hahnloser D, Hauri D, Graf R, Clavien PA. The impact of complications on costs of major surgical procedures: A cost analysis of 1200 patients. Ann Surg 2011;254:907-13.

Brown SR, Mathew R, Keding A, Marshall HC, Brown JM, Jayne DG. The impact of postoperative complications on long-term quality of life after curative colorectal cancer surgery. Ann Surg 2014;259:916-23.

Stehle P, Zander J, Mertes N, Albers S, Puchstein C, Lawin P, Fürst P. Effect of parenteral glutamine peptide supplements on muscle glutamine loss and nitrogen balance after major surgery. The Lancet 1989;1:231-3

O’Riordain MG, Fearon KC, Ross JA, Rogers P, Falconer JS, Bartolo DC, Garden OJ, Carter DC. Glutamine-supplemented total parenteral nutrition enhances T-lymphocyte response in surgical patients undergoing colorectal resection. Ann Surg 1994;220:212-21.

Morlion BJ, Stehle P, Wachtler P, Siedhoff HP, Köller M, König W, Fürst P, Puchstein C. Total parenteral nutrition with glutamine dipeptide after major abdominal surgery: A randomized, double-blind, controlled study. Ann Surg 1998;227:302-8.

Jiang ZM, Cao JD, Zhu XG, Zhao WX, Yu JC, Ma EL; et al. The impact of alanyl-glutamine on clinical safety, nitrogen balance, intestinal permeability, and clinical outcome in postoperative patients: A randomized, double-blind, controlled study of 120 patients. JPEN J Parenter Enter Nutr 1999;23:62-6.

Mertes N, Schulzki C, Goeters C, Winde G, Benzing S, Kuhn KS; et al. Cost containment through L-alanyl-L-glutamine supplemented total parenteral nutrition after major abdominal surgery: A prospective randomized double-blind controlled study. Clin Nutr 2000;19: 395-401.

Neri A, Mariani F, Piccolomini A, Testa M, Vuolo G, Di Cosmo L. Glutamine-supplemented total parenteral nutrition in major abdominal surgery. Nutrition 2001;17:968-9.

Spittler A, Sautner T, Gornikiewicz A, Manhart N, Oehler R, Bergmann M; et al. Postoperative glycyl-glutamine infusion reduces immunosuppression: Partial prevention of the surgery induced decrease in HLA-DR expression on monocytes. Clin Nutr 2001;20:37-42.

Exner R, Tamandl D, Goetzinger P, Mittlboeck M, Fuegger R, Sautner T; et al. Perioperative Gly-Gln infusion diminishes the surgery-induced period of immunosuppression: Accelerated restoration of the lipopolysaccharide-stimulated tumor necrosis factor-alpha response. Ann Surg 2003;237:110-5.

Alivizatos V, Athanasopoulos P, Makris N, Karageorgos N. Early postoperative glutamine-supplemented parenteral nutrition versus enteral immunonutrition in cancer patients undergoing major gastrointestinal surgery. J BUON 2005; 10:119-22.

Yao GX, Xue XB, Jiang ZM, Yang NF, Wilmore DW. Effects of perioperative parenteral glutamine-dipeptide supplementation on plasma endotoxin level, plasma endotoxin inactivation capacity and clinical outcome. Clin. Nutr 2005;24:510-5.

Jo S, Choi SH, Heo JS, Kim EM, Min MS, Choi DW; et al. Missing effect of glutamine supplementation on the surgical outcome after pancreaticoduodenectomy for periampullary tumors: A prospective, randomized, double-blind, controlled clinical trial. World J Surg 2006;30: 1974-82.

Oguz M, Kerem M, Bedirli A, Mentes BB, Sakrak O, Salman B, Bostanci H. L-alanine–L-glutamine supplementation improves the outcome after colorectal surgery for cancer. Colorectal Dis 2007; 9:515-20.

Yeh CN, Lee HL, Liu YY, Chiang KC, Hwang TL, Jan YY, Chen MF. The role of parenteral glutamine supplement for surgical patient perioperatively: Result of a single center, prospective and controlled study. Langenbecks Arch Surg 2008;393:849-55.

Gianotti L, Braga M, Biffi R, Bozzetti F, Mariani L. Perioperative intravenous glutamine supplemetation in major abdominal surgery for cancer: A randomized multicenter trial. Ann Surg 2009;250:684-90.

Fan YP, Yu JC, Kang WM, Zhang Q. Effects of glutamine supplementation on patients undergoing abdominal surgery. Chinese Med Sci J 2009;24:55-9.

Marton S, Ghosh S, Papp A, Bogar L, Koszegi T, Juhasz V; et al. Effect of glutamine in patients with esophagus resection. Diseases Esophagus 2010;23:106-11.

Lu CY, Shih YL, Sun LC, Chuang JF, Ma CJ, Chen FM; et al. The inflammatory modulation effect of glutamine-enriched total parenteral nutrition in postoperative gastrointestinal cancer patients. Am Surgeon 2011;77:59-64.

Wilmore DW. The effect of glutamine supplementation in patients following elective surgery and accidental injury. J Nutr 2001131(9 Suppl):S2543S-S2549. Disponible en: http://doi:10.1093/jn/131.9.2543S. Fecha de última visita: 9 de Febrero del 2018.

Jiang Z-M, Jiang H, Furst P. The impact of glutamine dipeptides on outcome of surgical patients: Systematic review of randomized controlled trials for Europe and Asia. Clin Nutr 2004;1(Suppl 1):S17-S23.

Zheng YM, Li F, Zhang MM, Wu XT. Glutamine dipeptide for parenteral nutrition in abdominal surgery: A meta-analysis of randomized controlled trials. World J Gastroenterol. 2006;12:7537-41.

Wang Y, Jiang ZM, Nolan MT, Jiang H, Han HR, Yu K; et al. The impact of glutamine dipeptide-supplemented parenteral nutrition on outcomes of surgical patients: A meta-analysis of randomized clinical trials. JPEN J Parenter Enter Nutr 2010;34:521-9.

Yue C, Tian W, Wang W, Huang Q, Zhao R, Zhao Y, Li Q, Li J. The impact of perioperative glutamine-supplemented parenteral nutrition on outcomes of patients undergoing abdominal surgery: A meta-analysis of randomized clinical trials. Am Surg 2013;79:506-13.

Kang K, Shu XL, Zhang YS, Liu XL, Zhao J. Effect of glutamine enriched nutrition support on surgical patients with gastrointestinal tumor: A metaanalysis of randomized controlled trials. Chinese Med J 2015;128:245-51.

Sandini M, Nespoli L, Oldani M, Bernasconi DP, Gianotti L. Effect of glutamine dipeptide supplementation on primary outcomes for elective major surgery: Systematic review and metaanalysis. Nutrients 2015;7:481-99.

Kelly D, Wischmeyer PE. Role of L-glutamine in critical illness: New insights. Curr Opin Clin Nutr Metab Care 2003;6:217-222.

Gottschalk A, Wempe C, Goeters C. Glutamine in the ICU: Who needs supply? Clin Nutr 2013;32:668-9.

Souba WW, Klimberg VS, Plumley DA, Salloum RM, Flynn TC, Bland KI, Copeland EM. The role of glutamine in maintaining a healthy gut and supporting the metabolic response to injury and infection. J Surg Res 1990;48:383-91.

Griffiths RD, Jones C, Palmer TE. Six-month outcome of critically ill patients given glutamine-supplemented parenteral nutrition. Nutrition 1997;13:295-302.

Powell-Tuck J, Jamieson CP, Bettany GEA, Obeid O, Fawcett HV, Archer C, Murphy DL. A double blind, randomised, controlled trial of glutamine supplementation in parenteral nutrition. Gut 1999;45:82-8.

Griffiths RD, Jones C, Palmer T. Six-month outcome of critically ill patients given glutamine-supplemented parenteral nutrition. Nutrition 2002;18:553-560.

Griffiths RD, Allen KD, Andrews FJ, Jones C. Infection, multiple organ failure, and survival in the intensive care unit: influence of glutamine-supplemented parenteral nutrition on acquired infection. Nutrition 2002;18: 546-52.

Goeters C, Wenn A, Mertes N, Wempe C, van Aken H, Stehle P, Bone HG. Parenteral L-alanyl-L-glutamine improves 6-month outcome in critically ill patients. Crit Care Med 2002;30: 2032-7.

Fuentes Orozco C, Anaya Prado R, González Ojeda A, Arenas Márquez H, Cabrera Pivaral C, Cervantes Guevara G, Barrera Zepeda LM. L-alanyl-L-glutamine-supplemented parenteral nutrition improves infectious morbidity in secondary peritonitis. Clin Nutr 2004; 23:13-21.

Estivariz CF, Griffith DP, Luo M, Szeszycki EE, Bazargan N, Dave N; et al Efficacy of parenteral nutrition supplemented with glutamine dipeptide to decrease hospital infections in critically ill surgical patients. JPEN J Parenter Enter Nutr 2008;32:389-402. http://doi.10.1177/0148607108317880. Fecha de última visita: 9 de Febrero del 2018.

Cetinbas F, Yelken B, Gulbas Z. Role of glutamine administration on cellular immunity after total parenteral nutrition enriched with glutamine in patients with systemic inflammatory response syndrome. J Crit Care 2010;25: 661.e1-e6. Disponible en: http://doi:10.1016/j.jcrc.2010.03.011. Fecha de última visita: 9 de Febrero del 2018.

Grau T, Bonet A, Miñambres E, Piñeiro L, Irles JA, Robles A, Acosta J, Herrero I, Palacios V, Lopez J, et al. The effect of L-alanyl-L-glutamine dipeptide supplemented total parenteral nutrition on infectious morbidity and insulin sensitivity in critically ill patients. Crit Care Med 2011;39:1263-8.

Andrews PJ, Avenell A, Noble DW, Campbell MK, Croal BL, Simpson WG, Vale LD, Battison CG, Jenkinson DJ, Cook JA. Randomised trial of glutamine, selenium, or both, to supplement parenteral nutrition for critically ill patients. BMJ 2011;342:d1542:d1542. Disponible en: http://doi.10.1136/bmj.d1542. Fecha de última visita: 10 de Febrero del 2018.

Cekmen N, Aydin A, Erdemli O. The impact of L-alanyl-L-glutamine dipeptide supplemented total parenteral nutrition on clinical outcome in critically patients. E-SPEN Euro e-J Clin Nutr Metab 2011;6:64-7. Disponible en: http://doi.10.1016/j.eclnm.2011.02.001. Fecha de última visita: 10 de Febrero del 2018.

Novak F, Heyland DK, Avenell A, Drover JW, Su X. Glutamine supplementation in serious illness: A systematic review of the evidence. Crit Care Med 2002;30:2022-9.

Avenell A. Glutamine in critical care: Current evidence from systematic reviews. Proc Nutr Soc 2005;65:236-41.

Avenell A. Current evidence and ongoing trials on the use of glutamine in critically-ill patients and patients undergoing surgery. Proc Nut Soc 2009;68:261-8.

Pérez Bárcena J, Marsé P, Cervera M, Frontera G, Llompart Pou JA, Raurich J, García de Lorenzo A. Eficacia del dipéptido N (2)-L-Alanil-L-glutamina en los pacientes traumáticos ingresados en la UCI: Estudio prospectivo, multicéntrico, aleatorizado y doble ciego; hipótesis y protocolo. Nutrición Hospitalaria [España] 2012; 27:116-22.

Bollhalder L, Pfeil AM, Tomonaga Y, Schwenkglenks M. A systematic literature review and meta-analysis of randomized clinical trials of parenteral glutamine supplementation. Clin Nutr 2013;32:213-23.

Tao KM, Li XQ, Yang LQ; et al. Glutamine supplementation for critically ill adults. Cochrane Database Syst Rev 2014;9:CD010050. Disponible en: https://doi.org/10.1002/14651858.CD10050.pub2. Fecha de última visita: 10 de Febrero del 2018.

Wischmeyer PE, Dhaliwal R, McCall M, Ziegler TR, Heyland DK. Parenteral glutamine supplementation in critical illness: A systematic review. Crit Care 2014;18:R76:1-17. Disponible en: http://doi:10.1186/cc13836. Fecha de última visita: 10 de Febrero del 2018.

Oldani M, Sandini M, Nespoli L, Coppola S, Bernasconi DP, Gianotti L. Glutamine supplementation in intensive care patients: A meta-analysis of randomized clinical trials. Medicine 2015;94(31):e1319-e1319. Disponible en: http://doi:10.1097/MD.0000000000001319. Fecha de última visita: 11 de Febrero del 2018.

Beger HG, Rau B, Mayer J, Pralle U. Natural course of acute pancreatitis. World J Surg 1997;21:130-5.

Tenner S, Sica G, Hughes M, Noordhoek E, Feng S, Zinner M, Banks PA. Relationship of necrosis to organ failure in severe acute pancreatitis. Gastroenterology 1997;113:899-903.

Petrov MS, Pylypchuk RD, Emelyanov NV. Systematic review: Nutritional support in acute pancreatitis. Aliment Pharmacol Ther 2008;28:704-12.

Beger HG, Rau BM. Severe acute pancreatitis: Clinical course and management. World J Gastroenterol 2007;13:5043.

Karner J, Roth E. Alanyl-glutamine infusions to patients with acute pancreatitis. Clin Nutr 1990;9:43-4.

Ockenga J, Borchert K, Rifai K, Manns MP, Bischoff SC. Effect of glutamine-enriched total parenteral nutrition in patients with acute pancreatitis. Clin Nutr 2002;21:409-16.

Xian-Li H, Qing-Jiu M, Jian-Guo L, Yan-Kui C, Xi-Lin D. Effect of total parenteral nutrition (TPN) with and without glutamine dipeptide supplementation on outcome in severe acute pancreatitis (SAP). Clin Nutr 2004 (Suppl);1:43-7.

Sahin H, Mercanligil SM, Inanc N, Ok E. Effects of glutamine-enriched total parenteral nutrition on acute pancreatitis. Eur J Clin Nutr 2007;61:1429-34.

Fuentes Orozco C, Cervantes Guevara G, Mucino Hernández I, López Ortega A, Ambriz González G, Gutiérrez de la Rosa JL; et al. L-alanyl-L-glutamine-supplemented parenteral nutrition decreases infectious morbidity rate in patients with severe acute pancreatitis. JPEN J Parenter Enter Nutr 2008;32:403-11.

Zhan W, Huang S-W, Pei L. Significance of application of total parenteral nutrition associated with alanyl-glutamine on patients with acute severe pancreatitis. Pract Prev Med 2009;16:844-6.

Huang X-D, Hui H. Application of alany-glutamine dipeptide in patients with serious acute pancreatitis. Mod Diagn Treat 2010;21:342-3.

Liu X, Sun XF, Ge QX. The role of glutamine supplemented total parenteral nutrition (TPN) in severe acute pancreatitis. Eur Rev Med Pharmacol Sci 2016;20:4176-80.

Asrani V, Chang WK, Dong Z, Hardy G, Windsor JA, Petrov MS. Glutamine supplementation in acute pancreatitis: A meta-analysis of randomized controlled trials. Pancreatology 2013;13:468-474.

Yong L, Lu QP, Liu SH, Fan H. Efficacy of glutamine-enriched nutrition support for patients with severe acute pancreatitis: A meta-analysis. JPEN J Parenter Enter Nutr 2016;40:83-94.

Castro Gutiérrez V, Rada G. ¿Tiene algún rol la suplementación con glutamina en el manejo de la pancreatitis aguda? Medwave [Chile] 2016;16 (Suppl3):6512-6512. Disponible en: http://doi:10.5867/medwave.2016.6512. Fecha de última visita: 11 de Febrero del 2018.

Zhong X, Liang CP, Gong S. Intravenous glutamine for severe acute pancreatitis: A meta-analysis. World J Crit Care Med 2013;2:4-8.

Nielson CB, Duethman NC, Howard JM, Moncure M, Wood JG. Burns: Pathophysiology of systemic complications and current management. J Burn Care Res 2017;38(1):e469-e481. Disponible en: http://doi:10.1097/BCR.0000000000000355. Fecha de última visita: 19 de Febrero del 2018.

Kaddoura I, Abu-Sittah G, Ibrahim A, Karamanoukian R, Papazian N. Burn injury: Review of pathophysiology and therapeutic modalities in major burns. Ann Burns Fire Disast 2017;30:95-102.

Tancheva D, Hadjiiski O. Effect of early nutritional support on clinical course and septic complications in patients with severe burns. Ann Burns Fire Disast 2005;18:74-8.

Demling RH, Seigne P. Metabolic management of patients with severe burns. World J Surg 2000;24:673-80.

Wischmeyer PE, Lynch J, Liedel J, Wolfson R, Riehm J, Gottlieb L, Kahana M. Glutamine administration reduces Gram-negative bacteremia in severely burned patients: A prospective, randomized, double-blind trial versus isonitrogenous control. Crit Care Med 2001;29:2075-80.

Zhou YP, Jiang ZM, Sun YH, He GZ, Shu H. The effects of supplemental glutamine dipeptide on gut integrity and clinical outcome after major escharectomy in severe burns: A randomized, double-blind, controlled clinical trial. Clin Nutr 2004;1(Suppl): S55-S60.

Lin JJ, Chung XJ, Yang CY, Lau HL. A meta-analysis of trials using the intention to treat principle for glutamine supplementation in critically ill patients with burn. Burns 2013;39:565-70.

Pradelli L, Iannazzo S, Zaniolo O, Muscaritoli M, Eandi M. Effectiveness and cost-effectiveness of supplemental glutamine dipeptide in total parenteral nutrition therapy for critically ill patients: a discrete event simulation model based on Italian data. Int J Technol Assessm Health Care 2012;28: 22-8.

Pradelli L, Povero M, Muscaritoli M, Eandi M. Updated cost-effectiveness analysis of supplemental glutamine for parenteral nutrition of intensive-care patients. Eur J Clin Nutr 2015;69:546-51.

Vanek VW, Matarese LE, Robinson M, Sacks GS, Young LS, Kochevar M; for the Novel Nutrient Task Force, Parenteral Glutamine Workgroup and the American Society for Parenteral and Enteral Nutrition (ASPEN) Board of Directors. ASPEN position paper: Parenteral nutrition glutamine supplementation. Nutr Clin Pract 2011;26:479-94.

Canadian Critical Care Nutrition Clinical Guidelines. Summary of topics and recommendations. Disponible en: http://www.criticalcarenutrition.com/docs/cpg/srrev.pdf. Canadá: 2009. Fecha de última visita: 14 de Febrero del 2018.

Wernerman J. Glutamine supplementation. Ann Intensive Care 2011;1(1):25-25. Disponible en: https://doi.org/10.1186/2110-5820-1-25. Fecha de última visita: 13 de Febrero del 2018.

Álvarez CS, de Aguirre MZM, Laguna LB. Recomendaciones para el soporte nutricional y metabólico especializado del paciente crítico. Actualización. Consenso SEMICYUC-SENPE: Cirugía del aparato digestivo. Medicina Intensiva [España] 2011;35:42-7.

Malpica AB, García de Lorenzo Mateos A, González AR. Recomendaciones para el soporte nutricional y metabólico especializado del paciente crítico. Actualización. Consenso SEMICYUC-SENPE: Paciente politraumatizado. Medicina Intensiva [España] 2011;35:68-71.

García de Lorenzo Mateos A, Leyba CO, Sánchez SS. Recomendaciones para el soporte nutricional y metabólico especializado del paciente crítico. Actualización. Consenso SEMICYUC-SENPE: Paciente quemado crítico. Medicina Intensiva [España] 2011;35:63-7.

Toledo D, Castro M. Terapia nutricional em UTI. Editora Rubio. Sao Paulo: 2015.

Sales AEDSS, Batista FOC, Martins TDCL, de Carvalho Cunha AL. O papel da arginina e glutamina na imunomodulação em pacientes queimados-revisão de literatura. Rev Bras Queimaduras 2015;14:295-9.

Gomes RR, Logrado MHG. Atualidades em terapia nutricional na pancreatite aguda. Comun Ciênc Saúde 2012;149-159. Disponible en: http://bvsms.saude.gov.br/bvs/periodicos/revista_ESCS_v23_n2_a06_atualidades_terapia_nutricional_pancreatite_aguda.pdf. Fecha de última visita: 12 de Febrero del 2018.

García de Lorenzo A, Zarazaga A, García Luna PP, Gonzalez Huix F, López Martínez J, Miján A; et al. Clinical evidence for enteral nutritional support with glutamine: A systematic review. Nutrition 2003;19:805-11.

Jiang H, Chen W, Hu W, Cai B, Liao RJ. The impact of glutamine-enhanced enteral nutrition on clinical outcome of patients with critical illness: a systematic review of randomized controlled trials. Chinese J Burns 2009;25:325-30. Disponible en: http://wprim.whocc.org.cn/admin/article/articleDetail?WPRIMID=305657&articleId=305657. Fecha de última visita: 15 de Febrero del 2018.

van Zanten AR, Dhaliwal R, Garrel D, Heyland DK. Enteral glutamine supplementation in critically ill patients: A systematic review and meta-analysis. Crit Care 2015;19(1):294-294. Disponible en: http://doi:10.1186/s13054-015-1002-x. Fecha de última visita: 18 de Febrero del 2018.

Wernerman J, Kirketeig T, Andersson B, Berthelson H, Ersson A, Friberg H; et al; for the Scandinavian Critical Care Trials Group. Scandinavian Glutamine Trial: A pragmatic multicentre randomised clinical trial of intensive care unit patients. Acta Anaesthesiol Scand 2011;55:812-8.

McClave SA, Taylor BE, Martindale RG, Warren MM, Johnson DR, Braunschweig C; et al. Guidelines for the provision and assessment of nutrition support therapy in the adult critically ill patient. JPEN J Parenter Enter Nutr 2016;40:159-211.

Wischmeyer P. Glutamine supplementation in parenteral nutrition and intensive care unit patients: Are we throwing the baby out with the bathwater? JPEN J Parenter Enter Nutr 2015;39:893-7.

Chen QH, Yang Y, He HL, Xie JF, Cai SX, Liu AR; et al. The effect of glutamine therapy on outcomes in critically ill patients: A meta-analysis of randomized controlled trials. Crit Care 2014;18(1):R8-R8. Disponible en: https://ccforum.biomedcentral.com/articles/10.1186/cc13185. Fecha de última visita: 19 de Febrero del 2018.

Ledgard K, Mann B, Hind D, Lee MJ. What is the evidence for the use of parenteral nutrition (PN) in critically ill surgical patients: A systematic review and meta-analysis. Tech Coloproctol 2018;22:755-66. Disponible en: http://doi:10.1007/s10151-018-1875-1. Fecha de última visita: 24 de Febrero del 2018.

McRae MP. Therapeutic benefits of glutamine: An umbrella review of meta-analyses. Biomed Rep 2017;6:576-84. Disponible en: https://www.spandidos-publications.com/10.3892/br.2017.885. Fecha de última visita: 16 de Febrero del 2018.

McClave SA, Taylor BE, Martindale RG, Warren MM, Johnson DR, Braunschweig C; et al. Guidelines for the provision and assessment of nutrition support therapy in the adult critically ill patient: Society of Critical Care Medicine (SCCM) and American Society for Parenteral and Enteral Nutrition (ASPEN). JPEN J Parenter Enter Nutr 2016;40:159-211.

Singer P, Blaser AR, Berger MM, Alhazzani W, Calder PC, Casaer MP; et al. ESPEN guideline on clinical nutrition in the intensive care unit. Clin Nutr 2019;38:48-79. Disponible en: https://doi.org/10.1016/j.clnu.2018.08.037. Fecha de última visita: 20 de Febrero del 2018.

Grupo de Trabajo de Abordaje Nutricional en el Paciente Crítico. AANEP Asociación Argentina de Nutrición Enteral y Parenteral. Comité de Soporte Nutricional y Metabolismo. SATI Sociedad Argentina de Terapia Intensiva. Soporte nutricional en el paciente adulto críticamente enfermo. Un consenso de práctica clínica. RCAN Rev Cubana Aliment Nutr 2016;26(1 Supl 1):S1-S82.

Wernerman J. Glutamine- From conditionally essential to totally dispensable? Crit Care 2014;18(4):162-162. Disponible en: http://doi:10.1186/cc13964. Fecha de última visita: 20 de Febrero del 2018.

Smedberg M, Wernerman, J. Is the glutamine story over? Crit Care 2016;20:361-6. Disponible en: http://doi:10.1186/s13054-016-1531-y. Fecha de última visita: 20 de Febrero del 2018

Stehle P, Kuhn KS. Glutamine: An obligatory parenteral nutrition substrate in critical care therapy. BioMed Res Int 2015;2015:1-7. Disponible en: https://www.hindawi.com/journals/bmri/2015/545467/. Fecha de última visita: 21 de Febrero del 2018.

Enlaces refback

  • No hay ningún enlace refback.




Licencia de Creative Commons
Este obra está bajo una licencia de Creative Commons Reconocimiento-NoComercial 4.0 Internacional.