Glutamine Supplementation in ICU Patients

  • A. Berg
  • O. Rooyackers
  • J. Wernerman


Glutamine is a non-essential amino acid with a special role in metabolism and nutrition. The depletion of glutamine is reported to be a predictor of a poor outcome in particular for intensive care unit (ICU) patients [1]. Consequently, supplementation of intravenous nutrition with glutamine improves outcome in terms of mortality and morbidity in ICU patients [2, 3, 4]. A number of questions have been raised concerning the handling of glutamine-supplemented nutrition in ICU patients, including the vascular and metabolic tolerance of the dipeptide infusions, the handling of glutamine during renal replacement therapy in ICU patients, and the safety of glutamine administration in head trauma patients. These issues will be dealt with in this short chapter.


Continuous Renal Replacement Therapy Glutamine Supplementation Plasma Glutamine Level Plasma Glutamine Concentration Head Trauma Patient 
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  1. 1.
    Oudemans-van Straaten HM, Bosman RJ, Treskes M, van der Spoel HJ, Zandstra DF (2001) Plasma glutamine depletion and patient outcome in acute ICU admissions. Intensive Care Med 27: 84–90CrossRefPubMedGoogle Scholar
  2. 2.
    Goeters C, Wenn A, Mertes N, et al (2002) Parenteral L-alanyl-L-glutamine improves 6-month outcome in critically ill patients. Crit Care Med 30: 2032–2037CrossRefPubMedGoogle Scholar
  3. 3.
    Griffiths RD, Jones C, Palmer TE (1997) Six-month outcome of critically ill patients given glutamine-supplemented parenteral nutrition. Nutrition 13: 295–302PubMedGoogle Scholar
  4. 4.
    Novak F, Heyland DK, Avenell A, Drover JW, Su X (2002) Glutamine supplementation in serious illness: a systematic review of the evidence. Crit Care Med 30: 2022–2029CrossRefPubMedGoogle Scholar
  5. 5.
    Newsholme P, Gordon S, Newsholme EA (1987) Rates of utilization and fates of glucose, glutamine, pyruvate, fatty acids and ketone bodies by mouse macrophages. Biochem J 242: 631–636PubMedGoogle Scholar
  6. 6.
    Ardawi MS, Newsholme EA (1990) Glutamine, the immune system, and the intestine. J Lab Clin Med 115: 654–655PubMedGoogle Scholar
  7. 7.
    Vesali RF, Klaude M, Rooyackers OE, TJäder I, Barle H, Wernerman J (2002) Longitudinal pattern of glutamine/glutamate balance across the leg in long-stay intensive care unit patients. Clin Nutr 21: 505–514CrossRefPubMedGoogle Scholar
  8. 8.
    van Acker BA, Hulsewe KW, Wagenmakers AJ, von Meyenfeldt MF, Soeters PB (2000) Response of glutamine metabolism to glutamine-supplemented parenteral nutrition. Am J Clin Nutr 72: 790–795PubMedGoogle Scholar
  9. 9.
    Van Acker BA, Hulsewe KW, Wagenmakers AJ, et al (1998) Absence of glutamine isotopic steady state: implications for the assessment of whole-body glutamine production rate. Clin Sci (Lond) 95: 339–346CrossRefGoogle Scholar
  10. 10.
    Clemmesen JO, Kondrup J, Ott P (2000) Splanchnic and leg exchange of amino acids and ammonia in acute liver failure. Gastroenterology 118: 1131–1139CrossRefPubMedGoogle Scholar
  11. 11.
    Gamrin L, Essen P, Forsberg AM, Hultman E, Wernerman J (1996) 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 24: 575–583CrossRefPubMedGoogle Scholar
  12. 12.
    Tjader I, Rooyackers O, Forsberg AM, Vesali RF, Garlick PJ, Wernerman J (2004). Effects on skeletal muscle of intravenous glutamine supplementation to ICU patients. Intensive Care Med 30: 266–275CrossRefPubMedGoogle Scholar
  13. 13.
    Boza JJ, Dangin M, Moennoz D, et al (2001) Free and protein-bound glutamine have identical splanchnic extraction in healthy human volunteers. Am J Physiol Gastrointest Liver Physiol 281:G267–274PubMedGoogle Scholar
  14. 14.
    Heyland DK, Dhaliwal R, Drover JW, Gramlich L, Dodek P (2003) Canadian clinical practice guidelines for nutrition support in mechanically ventilated, critically ill adult patients. JPEN J Parenter Enteral Nutr 27: 355–373CrossRefPubMedGoogle Scholar
  15. 15.
    Garrel D, Patenaude J, Nedelec B, et al (2003) Decreased mortality and infectious morbidity in adult burn patients given enteral glutamine supplements: a prospective, controlled, randomized clinical trial. Crit Care Med 31: 2444–2449CrossRefPubMedGoogle Scholar
  16. 16.
    Hall JC, Dobb G, Hall J, de Sousa R, Brennan L, McCauley R (2003) A prospective randomized trial of enteral glutamine in critical illness. Intensive Care Med 29: 1710–1716CrossRefPubMedGoogle Scholar
  17. 17.
    Jones C, Palmer TE, Griffiths RD (1999) Randomized clinical outcome study of critically ill patients given glutamine-supplemented enteral nutrition. Nutrition 15: 108–115CrossRefPubMedGoogle Scholar
  18. 18.
    Fuentes-Orozco C, Cervantes-Guevara G, Mucino-Hernandez I, et al (2008). L-alanyl-L-glutamine-supplemented parenteral nutrition decreases infectious morbidity rate in patients with severe acute pancreatitis. JPEN J Parenter Enteral Nutr 32: 403–411CrossRefPubMedGoogle Scholar
  19. 19.
    Estivariz CF, Griffith DP, Luo M, et al (2008) Efficacy of parenteral nutrition supplemented with glutamine dipeptide to decrease hospital infections in critically ill surgical patients. JPEN J Parenter Enteral Nutr 32: 389–402CrossRefPubMedGoogle Scholar
  20. 20.
    Dechelotte P, Hasselmann M, Cynober L, et al (2006) 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 34: 598–604CrossRefPubMedGoogle Scholar
  21. 21.
    Powell-Tuck J, Jamieson CP, Bettany GE, et al (1999) A double blind, randomised, controlled trial of glutamine supplementation in parenteral nutrition. Gut 45: 82–88PubMedCrossRefGoogle Scholar
  22. 22.
    Wischmeyer PE, Lynch J, Liedel J, et al (2001) Glutamine administration reduces Gram-negative bacteremia in severely burned patients: a prospective, randomized, double-blind trial versus isonitrogenous control. Crit Care Med 29: 2075–2080CrossRefPubMedGoogle Scholar
  23. 23.
    van der Hulst RR, von Meyenfeldt MF, Deutz NE, Stockbrugger RW, Soeters PB (1996) The effect of glutamine administration on intestinal glutamine content. J Surg Res 61: 30–34CrossRefPubMedGoogle Scholar
  24. 24.
    Tremel H, Kienle B, Weilemann LS, Stehle P, Furst P (1994) Glutamine dipeptide-supplemented parenteral nutrition maintains intestinal function in the critically ill. Gastroenterology 107: 1595–1601PubMedGoogle Scholar
  25. 25.
    Houdijk AP, Rijnsburger ER, Jansen J, et al (1998) Randomised trial of glutamine-enriched enteral nutrition on infectious morbidity in patients with multiple trauma. Lancet 352: 772–776CrossRefPubMedGoogle Scholar
  26. 26.
    Ziegler TR, Young LS, Benfell K, et al (1992) Clinical and metabolic efficacy of glutaminesupplemented parenteral nutrition after bone marrow transplantation. A randomized, double-blind, controlled study. Ann Intern Med 116: 821–828PubMedGoogle Scholar
  27. 27.
    Schloerb PR, Amare M (1993) Total parenteral nutrition with glutamine in bone marrow transplantation and other clinical applications (a randomized, double-blind study). JPEN J Parenter Enteral Nutr 17: 407–413CrossRefPubMedGoogle Scholar
  28. 28.
    Mertes N, Schulzki C, Goeters C, et al (2000) Cost containment through L-alanyl-L-glutamine supplemented total parenteral nutrition after major abdominal surgery: a prospective randomized double-blind controlled study. Clin Nutr 19: 395–401CrossRefPubMedGoogle Scholar
  29. 29.
    Cerchietti LC, Navigante AH, Lutteral MA, et al (2006) Double-blinded, placebo-controlled trial on intravenous L-alanyl-L-glutamine in the incidence of oral mucositis following chemoradiotherapy in patients with head-and-neck cancer. Int J Radiat Oncol Biol Phys 65: 1330–1337PubMedGoogle Scholar
  30. 30.
    Neu J, Roig JC, Meetze WH, et al (1997) Enteral glutamine supplementation for very low birth weight infants decreases morbidity. J Pediatr 131: 691–699CrossRefPubMedGoogle Scholar
  31. 31.
    van der Hulst RR, von Meyenfeldt MF, Soeters PB (1996) Glutamine: an essential amino acid for the gut. Nutrition 12:S78–81CrossRefGoogle Scholar
  32. 32.
    Berg A, Rooyackers O, Norberg A, Wernerman J (2005) Elimination kinetics of L-alanyl-Lglutamine in ICU patients. Amino Acids 29: 221–228CrossRefPubMedGoogle Scholar
  33. 33.
    Albers S, Wernerman J, Stehle P, Vinnars E, Furst P (1988) Availability of amino acids supplied intravenously in healthy man as synthetic dipeptides: kinetic evaluation of L-alanyl-Lglutamine and glycyl-L-tyrosine. Clin Sci (Lond) 75: 463–468Google Scholar
  34. 34.
    Berg A, Norberg A, Martling CR, Gamrin L, Rooyackers O, Wernerman J (2007) Glutamine kinetics during intravenous glutamine supplementation in ICU patients on continuous renal replacement therapy. Intensive Care Med 33: 660–666CrossRefPubMedGoogle Scholar
  35. 35.
    Berg A, Bellander BM, Wanecek M, et al (2006). Intravenous glutamine supplementation to head trauma patients leaves cerebral glutamate concentration unaffected. Intensive Care Med 32: 1741–1746CrossRefPubMedGoogle Scholar
  36. 36.
    Lofberg E, Essen P, McNurlan M, et al (2000) Effect of hemodialysis on protein synthesis. Clin Nephrol 54: 284–294PubMedGoogle Scholar
  37. 37.
    Berg A, Bellander BM, Wanecek M, et al (2008) The pattern of amino acid exchange across the brain is unaffected by intravenous glutamine supplementation in head trauma patients. Clin Nutr 27: 816–821CrossRefPubMedGoogle Scholar
  38. 38.
    Jackson NC, Carroll PV, Russell-Jones DL, et al (2000) Effects of glutamine supplementation, GH, and IGF-I on glutamine metabolism in critically ill patients. Am J Physiol Endocrinol Metab 278:E226–233PubMedGoogle Scholar
  39. 39.
    Darmaun D, Matthews DE, Bier DM (1986) Glutamine and glutamate kinetics in humans. Am J Physiol 251:E117–126PubMedGoogle Scholar
  40. 40.
    Kreider ME, Stumvoll M, Meyer C, Overkamp D, Welle S, Gerich J (1997) Steady-state and non-steady-state measurements of plasma glutamine turnover in humans. Am J Physiol 272:E621–627PubMedGoogle Scholar
  41. 41.
    Biolo G, Zorat F, Antonione R, Ciocchi B (2005) Muscle glutamine depletion in the intensive care unit. Int J Biochem Cell Biol 37: 2169–2179CrossRefPubMedGoogle Scholar
  42. 42.
    Roth E, Funovics J, Muhlbacher F, et al (1982) Metabolic disorders in severe abdominal sepsis: Glutamine deficiency in skeletal muscle. Clin Nutr 1: 25–41CrossRefPubMedGoogle Scholar
  43. 43.
    Boza JJ, Turini M, Moennoz D, et al (2001) Effect of glutamine supplementation of the diet on tissue protein synthesis rate of glucocorticoid-treated rats. Nutrition 17: 35–40CrossRefPubMedGoogle Scholar
  44. 44.
    Svedjeholm R, Svensson S, Ekroth R, et al (1990) Trauma metabolism and the heart: studies of heart and leg amino acid flux after cardiac surgery. Thorac Cardiovasc Surg 38: 1–5CrossRefPubMedGoogle Scholar
  45. 45.
    Bruins MJ, Deutz NE, Soeters PB (2003) Aspects of organ protein, amino acid and glucose metabolism in a porcine model of hypermetabolic sepsis. Clin Sci (Lond) 104: 127–141CrossRefGoogle Scholar
  46. 46.
    Hammarqvist F, Wernerman J, von der Decken A, Vinnars E (1990) Alanyl-glutamine counteracts the depletion of free glutamine and the postoperative decline in protein synthesis in skeletal muscle. Ann Surg 212: 637–644CrossRefPubMedGoogle Scholar
  47. 47.
    Vesali RF, Klaude M, Rooyackers O, Wernerman J (2005) Amino acid metabolism in leg muscle after an endotoxin injection in healthy volunteers. Am J Physiol Endocrinol Metab 288: E360–364CrossRefPubMedGoogle Scholar
  48. 48.
    Wernerman J (2003) Glutamine to intensive care unit patients. JPEN J Parenter Enteral Nutr 27: 302–303CrossRefPubMedGoogle Scholar
  49. 49.
    Fish J, Sporay G, Beyer K, et al (1997) A prospective randomized study of glutamine-enriched parenteral compared with enteral feeding in postoperative patients. Am J Clin Nutr 65: 977–983PubMedGoogle Scholar
  50. 50.
    Haisch M, Fukagawa NK, Matthews DE (2000) Oxidation of glutamine by the splanchnic bed in humans. Am J Physiol Endocrinol Metab 278: E593–602PubMedGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2009

Authors and Affiliations

  • A. Berg
    • 1
  • O. Rooyackers
    • 1
  • J. Wernerman
    • 1
  1. 1.Department of Anesthesia and Intensive Care Karolinska InstituteHuddinge UniversityStockholmSweden

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