Enteral Glutamine During Active Shock Resuscitation Is Safe and Enhances Tolerance of Enteral Feeding

Abstract

Background: Feeding the hemodynamically unstable patient is increasingly practiced, yet few data exist on its safety. Because enteral glutamine is protective to the gut in experimental models of shock and improves clinical outcomes, it may benefit trauma patients undergoing shock resuscitation and improve tolerance if administered early. This pilot study aimed to evaluate gastrointestinal tolerance and safety of enteral feeding with glutamine, beginning during shock resuscitation in severely injured patients. Methods: In a prospective randomized trial, 20 patients were randomly assigned to either an enteral glutamine group (n = 10) or a control group (n = 10). Patients with severe trauma meeting standardized shock resuscitation criteria received enteral glutamine 0.5 g/kg/d during the first 24 hours of resuscitation and 10 days thereafter. Immune-enhancing diet began on postinjury day 1, with a target of 25 kcal/kg/d. Control patients received isonitrogenous whey powder plus immune-enhancing diet. Tolerance (vomiting, nasogastric output, diarrhea, and distention) was assessed throughout the study. Results: Glutamine was well tolerated and no adverse events occurred. Treated patients had significantly fewer instances of high nasogastric output (5 vs 23; p = .010), abdominal distention (3 vs 12; p = .021), and total instances of intolerance (8 vs 42; p = .011). Intensive care unit (ICU) and hospital length of stay were comparable. Control patients required supplemental parenteral nutrition (PN) to meet goals at day 7. Conclusions: Enteral glutamine administered during active shock resuscitation and through the early postinjury period is safe and enhances gastrointestinal tolerance. A large clinical trial is warranted to determine if enteral glutamine administered to the hemodynamically unstable patient can reduce infectious morbidity and mortality.

This pilot study in severely injured patients delivered high-dose enteral glutamine beginning during shock resuscitation and evaluated the impact on gastrointestinal tolerance.

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References

Moore FA, Moore EE, Jones TN, McCroskey BL, Petersen VM. TEN versus TPN following major abdominal trauma reduced septic morbidity. J Trauma. 1989;29:916– 922.

Kozar RA, Hu S, Hassoun HT, DeSoignie R, Moore FA. Specific intraluminal nutrients alter mucosal blood flow during gut ischemia/reperfusion. JPEN J Parenter Enteral Nutr. 2002 ;26:226– 229.

Kozar RA, Schultz SG, Bick RJ, Poindexter BJ, DeSoignie R, Moore FA. Enteral glutamine but not alanine maintains small bowel barrier function after ischemia/reperfusion injury in rats. Shock. 2004 ;21:433– 437.

Kozar RA, Verner-Cole E, Schultz SG, et al. The immune-enhancing enteral agents arginine and glutamine differentially modulate gut barrier function following mesenteric ischemia/reperfusion. J Trauma. 2004 ;57:1150– 1156.

A.S.P.E.N. Board of Directors and the Clinical Guidelines Task Force. Guidelines for the use of parenteral and enteral nutrition in adult and pediatric patients. JPEN J Parenter Enteral Nutr 2002 ;26(1 Suppl):1SA– 138SA. Errata 2002;26:144.

Zaloga GP, Roberts PR, Marik P. Feeding the hemodynamically unstable patient: a critical evaluation of the evidence. Nutr Clin Pract. 2003;18:285– 293.

Reeds PJ, Burrin DG. Glutamine and the bowel. J Nutr. 2001; 131(9 Suppl): 2505S–2508S.

Kles KA, Tappenden KA. Hypoxia differentially regulates nutrient transport in rat jejunum regardless of luminal nutrient present. Am J Physiol Gastrointest Liver Physiol. 2002 ;283:G1336– G1342.

Kazamias P, Kotzampassi K, Koufogiannis D, Eleftheriadis E. Influence of enteral nutrition-induced splanchnic hyperemia on the septic origin of splanchnic ischemia. World J Surg. 1998 ;22:6– 11.

10.

Matheson PJ, Spain DA, Harris PD, Garrison RN, Wilson MA. Glucose and glutamine gavage increase portal vein nitric oxide metabolite levels via adenosine A2b activation. J Surg Res. 1999 ; 84:57– 63.

11.

Thomas S, Prabhu R, Balasubramanian KA. Surgical manipulation of the intestine and distant organ damage: protection by oral glutamine supplementation. Surgery. 2005 ;137:48– 55.

12.

Coëffier M, Le Pessot F, Leplingard A, et al. Acute enteral glutamine infusion enhances hemo-oxygenase-1 expression in human duodenal mucosa. J Nutr. 2002;132:2570– 2573.

13.

Sato N, Moore FA, Kone BC, et al. Differential induction of PPAR-gamma by luminal glutamine and iNOS by luminal arginine in the rodent post ischemic small bowel. Am J Physiol Gastrointest Liver Physiol. 2006;290:G616– G623.

14.

Blikslager AT, Rhoads JM, Bristol DG, Roberts MC, Argenzio RA. Glutamine and transforming growth factor-alpha stimulate extracellular regulated kinases and enhance recovery of villous surface area in porcine ischemic-injured intestine. Surgery. 1999 ;125:186– 194.

15.

McQuiggan MM, Marvin RG, McKinley BA, Moore FA. Enteral feeding following major torso trauma: from theory to practice. New Horizons. 1999;7:131– 146.

16.

Kozar RA, McQuiggan MM, Moore EE, Kudsk K, Jurkovich G, Moore FA. Postinjury enteral tolerance is reliably achieved by a standardized protocol.J Surg Res. 2002;104:70– 75.

17.

McAnena OJ, Moore FA, Moore EE, Mattox KL, Marx JA, Pepe P. Invalidation of the APACHE II scoring system for patients with acute trauma.J Trauma. 1992;33:504– 507.

18.

Graves C, Saffle J, Morris S. Comparison of urine urea nitrogen collection times in critically ill patients. Nutr Clin Pract. 2005 ; 20:271– 275.

19.

Houdijk AP, Rijnsburger ER, Jansen J, et al. Randomized trial of glutamine-enriched enteral nutrition on infectious morbidity in patients with multiple trauma. Lancet. 1998 ;352:772– 776.

20.

Zhou YP, Jiang ZM, Sun YH, Wang XR, Ma EL, Wilmore D. The effect of supplemental enteral glutamine on plasma levels, gut function, and outcome in severe burns: a randomized, double-blind, controlled clinical trial.JPEN J Parenter Enteral Nutr. 2003 ;27:241– 245.

21.

Garrel D, Patenaude J, Nedelec B, et al. Decreased mortality and infectious morbidity in adult burn patients given enteral glutamine supplements: a prospective, controlled, randomized trial. Crit Care Med. 2003;31:2444– 2449.

22.

Brantley S, Pierce J. Effects of enteral glutamine on trauma patients [abstract]. Nutr Clin Pract. 2000 ;15: S13. Abstract P0095.

23.

Peng X, Yan H, You Z, Wang P, Wang S. Effects of enteral supplementation with glutamine granules on intestinal mucosal barrier function in severe burned patients. Burns. 2004 ;30:135– 139.

24.

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– 2029.

25.

Heyland DK, Dhaliwal R, Drover JW, Gramlich L, Dodek P; Canadian Critical Care Clinical Practice Guidelines Committee. Canadian clinical practice guidelines for nutrition support in mechanically ventilated, critically ill adult patients. JPEN J Parenter Enteral Nutr 2003 ;27:355– 373.

26.

Hall JC, Dobb G, Hall J, de Sousa R, Brennan L, McCauley R. A prospective randomized trial of enteral glutamine in critical illness.Intensive Care Med. 2003 ;29:1710– 1716.

27.

Moore FA, Cocanour CS, McKinley BA, et al. Migrating motility complexes persist after severe traumatic shock in patients who tolerate enteral nutrition. J Trauma. 2001 ;51:1075– 1082.

28.

Hassoun HH, Kone BC, Mercer DW, Moody FG, Weisbrodt NW, Moore FA. Post-injury multiple organ failure: the role of the gut. Shock. 2001 ;15:1– 10.

29.

Hassoun HT, Weisbrodt NW, Mercer DW, Kozar RA, Moody FG, Moore FA. Inducible nitric oxide synthase mediates gut ischemia/reperfusion induced ileus only after severe insults. J Surg Res. 2001 ;97:150– 154.

30.

Hassoun HT, Zou L, Moore FA, Kozar RA, Weisbrodt NW, Kone BC. Alpha-melanocyte-stimulating hormone protects against mesenteric ischemia-reperfusion injury. Am J Physiol Gastrointest Liver Physiol. 2002;282:G1059– G1068.

31.

Grossie VB, Weisbrodt NW, Moore FA, Moody F. Ischemia/reperfusion-induced disruption of small rat small intestine transit is reversed by total enteral nutrition. Nutrition. 2001 ;17:939– 943.

32.

American Dietetic Association. Enteral versus parenteral nutrition and critical illness. Available at: http://www.adaevidencelibrary.com/template.cfm?template=guide_summary&key=641. Accessed August 31, 2007.

33.

Ash JL, Gervasio JM, Zaloga GP, Rodman GH. Does the quantity of enteral nutrition affect outcomes in critically ill trauma patients [abstract]? JPEN J Parenter Enteral Nutr. 2005 ;29:S10– S11. Abstract 021.

34.

Marvin RG, McKinley BA, McQuiggan M, Cocanour CS, Moore FA. Nonocclusive bowel necrosis occurring in critically ill trauma patients receiving enteral nutrition manifests no reliable clinical signs for early detection. Am J Surg. 2000 ;179:7– 12.

35.

McClave SA, Chang WK. Feeding the hypotensive patient: does enteral feeding precipitate or protect against ischemic bowel? Nutr Clin Pract. 2003;18:279– 284.

36.

McAnena OJ, Moore FA, Moore EE, Jones TN, Parsons P. Selective uptake of glutamine in the gastrointestinal tract: confirmation in a human study. Br J Surg. 1991;78:480– 482.

37.

Cocanour CS, Weisbrodt N, Kozar RA, Messick C, Moore F. Gastric emptying following traumatic shock. Shock. 2003 ;19:18 .

38.

Kompan L, Kremzar B, Gadzijev E, Prosek M. Effects of early enteral nutrition on intestinal permeability and the development of multiple organ failure after multiple injury. Intensive Care Med. 1999 ;25:157– 161.

39.

Berger MM, Revelly JP, Cayeux MC, Chiolero RL. Enteral nutrition in critically ill patients with severe hemodynamic failure after cardiopulmonary bypass. Clin Nutr. 2005;24:124– 132.

40.

Consensus recommendations from the U.S.: summit on immune-enhancing enteral therapy. JPEN J Parenter Enteral Nutr. 2001 :25(Suppl 2):S61– S63.

41.

Moore FA, Moore EE, Kudsk KA, et al. Clinical benefits of an immune-enhancing diet for early postinjury enteral feeding. J Trauma. 1994:37;607– 615.

42.

Moore FA. Effects of immune enhancing diets on infectious morbidity and multiple organ failure. JPEN J Parenter Enteral Nutr. 2001 ;25(Suppl 2):S36– S43.

43.

Bistrian BR. Practical recommendations for immune-enhancing diets.J Nutr. 2004 ;134(Suppl 10):2868S– 2872S.