Advertisement

Intensive Care Medicine

, Volume 29, Issue 10, pp 1710–1716 | Cite as

A prospective randomized trial of enteral glutamine in critical illness

  • John C. Hall
  • Geoffrey Dobb
  • Jane Hall
  • Ruth de Sousa
  • Lisa Brennan
  • Rosalie McCauley
Original

Abstract

Objective

To assess the influence of enteral glutamine on the incidence of severe sepsis and death in critically ill patients.

Design

This two-armed clinical trial was triple blind (patients, attending staff, research nurse).

Setting

The 10 bed general ICU at Royal Perth Hospital, Western Australia.

Patients

This trial evaluated 363 patients requiring mechanical ventilation (median APACHE II score=14); of these, 85 had trauma.

Intervention

The intervention solution contained 20 g/l glutamine and the control solution was isojoulic and isonitrogenous.

Measurements and results

The groups had similar characteristics at baseline, and they also received equivalent amounts of protein and energy. Patients in the glutamine group received a median of 19 g/glutamine per day and 91% (332 of 363) of the patients were fed via a nasogastric tube (median duration=10 days). The outcomes were similar in the two groups: (a) death within 6 months: glutamine group 15% (27 of 179) vs control group 16% (30 of 184); p=0.75; relative risk, 0.95 (95% confidence interval, 0.71–1.28); and (b) severe sepsis: glutamine group 21% (38 of 179) vs control group 23% (43 of 184); p=0.62; relative risk, 0.94 (95% confidence interval, 0.72–1.22). There was also no discernable difference in the secondary outcomes relating to infections, febrile period, antimicrobial therapy, and consumption of inotropes.

Conclusion

This clinical trial did not support the use of enteral glutamine supplements in similar cohorts of critically ill patients.

Keywords

Enteral nutrition Glutamine Critical illness Trauma Sepsis 

Notes

Acknowledgements. This study was funded by the National Health and Medical Research Council of Australia. The authors thank the ICU staff at Royal Perth Hospital for facilitating the performance of this study. We are particularly indebted to the staff of the Feed Preparation Room at Royal Perth Hospital for their generous support of this clinical trial.

References

  1. 1.
    Parry-Billings M, Baigrie RJ, Lamont PM, Morris PJ, Newsholme EA (1992) Effects of major and minor surgery on plasma glutamine and cytokine levels. Arch Surg 127:1237–1240PubMedGoogle Scholar
  2. 2.
    Hall JC, Heel KA, McCauley R (1996) Glutamine. Br J Surg 83:305–312PubMedGoogle Scholar
  3. 3.
    Karinch AM, Pan M, Lin CM, Strange R, Souba WW (2001) Glutamine metabolism in sepsis and infection. J Nutr 131 (Suppl):2535–2538Google Scholar
  4. 4.
    McCauley R, Kong S-E, Hall JC (1998) Glutamine and nucleotide metabolism within enterocytes. JPEN 22:105–111Google Scholar
  5. 5.
    Wilmore DW (2001) The effect of glutamine supplementation in patients following elective surgery and accidental injury. J Nutr 131 (Suppl):2543–2549Google Scholar
  6. 6.
    Ardawi MS (1991) Effect of glutamine-enriched total parenteral nutrition on septic rats. Clin Sci 81:215–222PubMedGoogle Scholar
  7. 7.
    Platell C, McCauley R, McCulloch R, Hall JC (1993) The influence of parenteral glutamine and branched-chain amino acids on total parenteral nutrition-induced atrophy of the gut. JPEN 17:348–354Google Scholar
  8. 8.
    Wilmore DW, Shabert JK (1998) Role of glutamine in immunologic responses. Nutrition 14:618–626PubMedGoogle Scholar
  9. 9.
    Gianotti L, Alexander JW, Gennari R, Pyles T, Babcock GF (1995) Oral glutamine decreases bacterial translocation and improves survival in experimental gut-origin sepsis. JPEN 19:69–74Google Scholar
  10. 10.
    Kudsk KA (2002) Current aspects of mucosal immunology and its influence by nutrition. Am J Surg 183:390–398CrossRefPubMedGoogle Scholar
  11. 11.
    Deitch EA (2002) Bacterial translocation or lymphatic drainage of toxic products from the gut: What is important in human beings? Surgery 131:241–244CrossRefPubMedGoogle Scholar
  12. 12.
    Buchman AL (2001) Glutamine: commercially essential or conditionally essential? A critical appraisal of the human data. Am J Clin Nutr 74:25–32PubMedGoogle Scholar
  13. 13.
    Griffiths RD, Jones C, Palmer TE (1997) Six-month outcome of critically ill patients given glutamine-supplemented parenteral nutrition. Nutrition 13:295–302PubMedGoogle Scholar
  14. 14.
    Griffiths RD (1997) Outcome of critically ill patients after supplementation with glutamine. Nutrition 13:752–754CrossRefPubMedGoogle Scholar
  15. 15.
    Baker SP, O'Neill B, Haddon W Jr, Long WB (1974) The Injury Severity Score: a method for describing patients with multiple injuries and evaluating emergency care. J Trauma 14:187–196PubMedGoogle Scholar
  16. 16.
    Knaus WA, Draper EA, Wagner DP, Zimmerman JE (1985) APACHE II: a severity of disease classification system. Crit Care Med 13:818–829PubMedGoogle Scholar
  17. 17.
    Barton RG (1994) Nutritional support in critical illness. NCP 9:127–139CrossRefGoogle Scholar
  18. 18.
    Bidlingmeyer B, Cohen S, Tarvin T (1984) Rapid analysis of amino acids using pre-column derivitization. J Chromatogr 336:93–104CrossRefPubMedGoogle Scholar
  19. 19.
    The American College of Chest Physicians/Society of Critical Care Medicine (1992) Definitions for sepsis and organ failure. Crit Care Med 20:864–874PubMedGoogle Scholar
  20. 20.
    Bernard GR, Artigas A, Brigham KL, Carlet J, Falke K, Hudson L, Lamy M, Legall JR, Morris A, Spragg R (1994) The American–European Consensus Conference on ARDS: definitions, mechanisms, relevant outcomes, and clinical trial coordination. Am J Respir Crit Care Med 149:818–824PubMedGoogle Scholar
  21. 21.
    Schwartz D, Lellouch J (1967) Explanatory and pragmatic attitudes in trials. J Chron Dis 210:637–648Google Scholar
  22. 22.
    Powell-Tuck J, Jamieson CP, Bettany GE, Obeid O, Fawcett HV, Archer C, Murphy DL (1999) A double-blind, randomised, controlled trial of glutamine supplementation in parenteral nutrition. Gut 45:82–88PubMedGoogle Scholar
  23. 23.
    Andrews FJ, Griffiths RD (2002) Glutamine: essential for immune nutrition in the critically ill. Br J Nutr 87 (Suppl):3–8CrossRefPubMedGoogle Scholar
  24. 24.
    Wischmeyer PE, Wischmeyer PE, Lynch J, Liedel J, Wolfson R, Riehm J, Gottlieb L, Kahana M (2001) Glutamine administration reduces Gram-negative bacteremia in severely burned patients: a prospective, randomized, double-blind trial versus isonitrogenous control. Crit Care Med 29:2075–2080PubMedGoogle Scholar
  25. 25.
    Houdijk AP, Rijnsburger ER, Jansen J, Wesdorp RI, Weiss JK, McCamish MA, Teerlink T, Meuwissen SG, Haarman HJ, Thijs LG, van Leeuwen PA (1998) Randomised trial of glutamine-enriched enteral nutrition on infectious morbidity in patients with multiple trauma. Lancet 352:772–776PubMedGoogle Scholar
  26. 26.
    Jones C, Palmer TE, Griffiths RD (1999) Randomized clinical outcome study of critically ill patients given glutamine-supplemented enteral nutrition. Nutrition 15:108–115PubMedGoogle Scholar
  27. 27.
    Conejero R, Bonet A, Grau T et al. (2002) Effect of a glutamine-enriched enteral diet on intestinal permeability and infectious morbidity at 28 days in critically ill patients with systemic inflammatory response syndrome: a randomized, single-blind, prospective, multicenter study. Nutrition 18:716–721CrossRefPubMedGoogle Scholar
  28. 28.
    Sacks G (1999) Glutamine supplementation in catabolic patients. Ann Pharmacother 33:348–354PubMedGoogle Scholar
  29. 29.
    Labow BI, Souba WW (2000) Glutamine. World J Surg 24:1503–1513CrossRefPubMedGoogle Scholar
  30. 30.
    Petersson B, Decken A von der, Vinnars E, Wernerman J (1994) Long-term effects of postoperative total parenteral nutrition supplemented with glycylglutamine on subjective fatigue and muscle protein synthesis. Br J Surg 81:1520–1523PubMedGoogle Scholar
  31. 31.
    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 30:2022–2029PubMedGoogle Scholar
  32. 32.
    Salloum RM, Copeland EM, Souba WW (1991) Brush border transport of glutamine and other substrates during sepsis and endotoxaemia. Ann Surg 213:401–410PubMedGoogle Scholar
  33. 33.
    Whitworth PW, Cryer HM, Garrison RN, Baumgarten TE, Harris PD (1989) Hypoperfusion of the intestinal microcirculation without decreased cardiac output during live Escherichia coli sepsis in rats. Circ Shock 27:111–122PubMedGoogle Scholar
  34. 34.
    Cremaschi D, James PS, Meyer G, Rossetti C, Smith MW (1984) Developmental changes in intra-enterocyte cation activities in hamster terminal ileum. J Physiol 354:363–373PubMedGoogle Scholar
  35. 35.
    Austgen TR, Chen MK, Dudrick PS, Copeland EM, Souba WW (1992) Cytokine regulation of intestinal glutamine utilisation. Am J Surg 163:174–180PubMedGoogle Scholar
  36. 36.
    Parry-Billings M, Baigrie RJ, Lamont PM, Morris PJ, Newsholme EA (1992) Effects of major and minor surgery on plasma glutamine and cytokine levels. Arch Surg 127:1237–1240PubMedGoogle Scholar
  37. 37.
    Takala J, Ruokonen E, Webster NR, Nielsen MS, Zandstra DF, Vundelinckx G, Hinds CJ (1999) Increased mortality associated with growth hormone treatment in critically ill adults. N Engl J Med 341:785–792Google Scholar
  38. 38.
    Umpleby AM, Carroll PV, Russell-Jones DL, Treacher DF, Jackson NC (2002) Glutamine supplementation and GH/IGF-1 treatment in critically ill patients: effects on glutamine metabolism and protein balance. Nutrition 18:127–129CrossRefPubMedGoogle Scholar
  39. 39.
    Hall JC (1998) Glycine. JPEN 22:393–398Google Scholar
  40. 40.
    Lee MA, McCauley RD, Kong S-E, Hall JC (2001) Pretreatment with glycine reduces the severity of warm intestinal ischaemia-reperfusion injury in the rat. Ann Plast Surg 46:320–326PubMedGoogle Scholar
  41. 41.
    Lee MA, McCauley RD, Kong SE, Hall JC (2002) Influence of glycine on intestinal ischemia-reperfusion injury. JPEN 26:130–135Google Scholar

Copyright information

© Springer-Verlag 2003

Authors and Affiliations

  • John C. Hall
    • 1
  • Geoffrey Dobb
    • 2
  • Jane Hall
    • 1
  • Ruth de Sousa
    • 2
  • Lisa Brennan
    • 2
  • Rosalie McCauley
    • 1
  1. 1.Department of SurgeryThe University of Western AustraliaPerth WAAustralia
  2. 2.Intensive Care UnitRoyal Perth HospitalPerthWestern Australia

Personalised recommendations