Arginine Enriched Nutrition in Trauma Patients

Abstract

Nutritional status is affected by traumatic injury that induces a stress response which is necessary for recovery of the patient. When the trauma patient develops complications, the patient may become “critically ill”; a condition that requires large quantities of nutrients. Different combinations of nutrients (e. g., arginine, glutamine, fish oils, and nucleotides) have been given to different groups of patients in order to enhance the immune system and to improve organ function. Immunonutrition containing arginine has proven to be successful in elective surgical patients. Interestingly, recent studies showed that immune-enhancing formulas with arginine adversely affected outcome in septic patients. Although the exact mechanism of this harm has not been elucidated, the function of arginine as precursor of nitric oxide (NO) might be of interest. Overproduction of NO may be disadvantageous by exerting cytotoxic effects and causing haemodynamic disturbances. Arginine enriched nutrition should not be routinely given to all critically ill patients until potential harmful effects of additional arginine in subgroups of ICU patients are elucidated. Noteworthy, trauma patients on the ICU might benefit from arginine supplementation during the first weeks of their illness because, in this period, they can be regarded as postoperative surgical patients. However, when their inflammatory response is exaggerated such as during sepsis or when arginine plasma levels are already increased such as in critically ill patients suffering from hepatic failure, nutritional support including arginine may not be indicated.

Trauma patients - critical illness - nutrition - arginine

References

• 1 Alberti K G, Johnston H H, Lauler D P, Jagger P I. Effect of arginine on electrolyte metabolism in man.  Clin Res. 1967;  15 476-(Abstract)
• 2 Alderton W K, Cooper C E, Knowles R G. Nitric oxide synthases: structure, function and inhibition.  Biochem J. 2001;  357 593-615
• 3 Atkinson S, Sieffert E, Bihari D. A prospective, randomized, double-blind, controlled clinical trial of enteral immunonutrition in the critically ill. Guy's Hospital Intensive Care Group.  Crit Care Med. 1998;  26 1164-1172
• 4 Avontuur J A, Biewenga M, Buijk S L, Kanhai K J, Bruining H A. Pulmonary hypertension and reduced cardiac output during inhibition of nitric oxide synthesis in human septic shock.  Shock. 1998;  9 451-454
• 5 Avontuur J A, Bruining H A, Ince C. Inhibition of nitric oxide synthesis causes myocardial ischemia in endotoxemic rats.  Circ Res. 1995;  76 418-425
• 6 Barbul A, Lazarou S A, Efron D T, Wasserkrug H L, Efron G. Arginine enhances wound healing and lymphocyte immune responses in humans.  Surgery. 1990;  108 331-336
• 7 Bertolini G, Iapichino G, Radrizzani D, Facchini R, Simini B, Bruzzone P, Zanforlin G, Tognoni G. Early enteral immunonutrition in patients with severe sepsis. Results of an interim analysis of a randomized multicentre clinical trial.  Intensive Care Med (in press).
• 8 Biffl W L, Moore E E, Haenel J B. Nutrition support of the trauma patient.  Nutrition. 2002;  18 960-965
• 9 Bone R C. Sir Isaac Newton, sepsis, SIRS, and CARS.  Crit Care Med. 1996;  24 1125-1128
• 10 Borsook H, Dubnoff J W. The conversion of citrulline to arginine in kidney.  J Biol Chem. 1941;  140 717-738
• 11 Bower R H, Cerra F B, Bershadsky B, Licari J J, Hoyt D B, Jensen G L, van Buren C T, Rothkopf M M, Daly J M, Adelsberg B R. Early enteral administration of a formula (Impact) supplemented with arginine, nucleotides, and fish oil in intensive care unit patients: results of a multicenter, prospective, randomized, clinical trial.  Crit Care Med. 1995;  23 436-449
• 12 Brusilow S W, Horwich A L. Urea cycle enzymes. In: Scriver CR, Beaudet AL, Sly WS, Valle D (eds). The metabolic basis of inherited disease. McGraw-Hill, St. Louis 1989; 629-663
• 13 Campisi R, Czernin J, Schoder H, Sayre J W, Schelbert H R. L-Arginine normalizes coronary vasomotion in long-term smokers.  Circulation. 1999;  99 491-497
• 14 Cerra F B. Hypermetabolism, organ failure, and metabolic support.  Surgery. 1987;  101 1-14
• 15 Cohen R I, Hassell A M, Marzouk K, Marini C, Liu S F, Scharf S M. Renal effects of nitric oxide in endotoxemia.  Am J Respir Crit Care Med. 2001;  164 1890-1895
• 16 Creager M A, Gallagher S J, Girerd X J, Coleman S M, Dzau V J, Cooke J P. L-Arginine improves endothelium-dependent vasodilation in hypercholesterolemic humans.  J Clin Invest. 1992;  90 1248-1253
• 17 Cui X L, Iwasa M, Iwasa Y, Ogoshi S. Arginine-supplemented diet decreases expression of inflammatory cytokines and improves survival in burned rats.  J Parenter Enteral Nutr. 2000;  24 89-96
• 18 Dent D L, Heyland D K, Levy H, Martindale R, Tayek J, Schloerb P, Kelley M J. Immunonutrition may increase mortality in critically ill patients with pneumonia: results of a randomized trial.  Crit Care Med. 2003;  30 A17-(abstract)
• 19 Doursout M F, Kilbourn R G, Hartley C J, Chelly J E. Effects of N-methyl-L-arginine on cardiac and regional blood flow in a dog endotoxin shock model.  J Crit Care. 2000;  15 22-29
• 20 Freund H R, Ryan J A, Fischer J E. Amino acid derangements in patients with sepsis: treatment with branched chain amino acid rich infusions.  Ann Surg. 1978;  188 423-430
• 21 Furchgott R F. The 1996 Albert Lasker Medical Research Awards. The discovery of endothelium-derived relaxing factor and its importance in the identification of nitric oxide.  JAMA. 1996;  276 1186-1188
• 22 Giugliano D, Marfella R, Verrazzo G, Acampora R, Coppola L, Cozzolino D, D'Onofrio F. The vascular effects of L-arginine in humans. The role of endogenous insulin.  J Clin Invest. 1997;  99 433-438
• 23 Hertz P, Richardson J A. Arginine-induced hyperkalemia in renal failure patients.  Arch Intern Med. 1972;  130 778-780
• 24 Heyland D K. Immunonutrition in the critically ill patient: putting the cart before the horse?.  Nutr Clin Pract. 2002;  17 267-272
• 25 Heyland D K, Novak F, Drover J W, Jain M, Su X, Suchner U. Should immunonutrition become routine in critically ill patients? A systematic review of the evidence.  JAMA. 2001;  286 944-953
• 26 Heyland D K, Samis A. Does immunonutrition in patients with sepsis do more harm than good?.  Intensive Care Med. 2003 (in press); 
• 27 Houdijk A P, Rijnsburger E R, Jansen J, Wesdorp R I, Weiss J K, McCamish M A, Teerlink T, Meuwissen S G, Haarman H J, Thijs L G, van Leeuwen P A. Randomised trial of glutamine-enriched enteral nutrition on infectious morbidity in patients with multiple trauma.  Lancet. 1998;  352 772-776
• 28 Kirk S J, Hurson M, Regan M C, Holt D R, Wasserkrug H L, Barbul A. Arginine stimulates wound healing and immune function in elderly human beings.  Surgery. 1993;  114 155-159
• 29 Kox W J, Volk T, Kox S N, Volk H D. Immunomodulatory therapies in sepsis.  Intensive Care Med. 2000;  26 (Suppl 1) S124-S128
• 30 Lorente J A, Delgado M A, Tejedor C, Mon E, Hervas M, Pascual T, Fernandez-Segoviano P, Rieppi G, Soler A, Ayuso D, Esteban A. Modulation of systemic hemodynamics by exogenous L-arginine in normal and bacteremic sheep.  Crit Care Med. 1999;  27 2474-2479
• 31 Massara F, Martelli S, Cagliero E, Camanni F, Molinatti G M. The hypophosphatemic and hyperkalemic effect of arginine in man.  J Endocrinol Invest. 1980;  3 177-180
• 32 Mudge G H. Agents affecting volume and composition of body fluids. In: Goodman LS, Gilman AG (eds). The Pharmacologic Basis of Therapeutics. Macmillan, New York 1980; 892-915
• 33 Naini A B, Dickerson J W, Brown M M. Preoperative and postoperative levels of plasma protein and amino acid in esophageal and lung cancer patients.  Cancer. 1988;  62 355-360
• 34 Nakaki T, Hishikawa K, Suzuki H, Saruta T, Kato R. L-Arginine-induced hypotension.  Lancet. 1990;  336 696
• 35 Nijveldt R J, Prins H A, Siroen M P, Rauwerda J A, Teerlink T, van Leeuwen P A. Low arginine plasma levels in patients after thoracoabdominal aortic surgery.  Eur J Clin Nutr. 2000;  54 615-617
• 36 Nijveldt R J, Siroen M P, van der Hoven B, Teerlink T, Prins H A, van Leeuwen P A. High plasma arginine concentrations in critically ill patients suffering from hepatic failure.  Eur J Clin Nutr. in press; 
• 37 Palmer R M, Ashton D S, Moncada S. Vascular endothelial cells synthesize nitric oxide from L-arginine.  Nature. 1988;  333 664-666
• 38 Petros A, Lamb G, Leone A, Moncada S, Bennett D, Vallance P. Effects of a nitric oxide synthase inhibitor in humans with septic shock.  Cardiovasc Res. 1994;  28 34-39
• 39 Prins H A, Houdijk A P, Wiezer M J, Teerlink T, van Lambalgen A A, Thijs L G, van Leeuwen P A. Reduced arginine plasma levels are the drive for arginine production by the kidney in the rat.  Shock. 1999;  11 199-204
• 40 Prins H A, Houdijk A P, Wiezer M J, Teerlink T, van Lambalgen A A, Thijs L G, van Leeuwen P A. The effect of mild endotoxemia during low arginine plasma levels on organ blood flow in rats.  Crit Care Med. 2000;  28 1991-1997
• 41 Rector T S, Bank A J, Mullen K A, Tschumperlin L K, Sih R, Pillai K, Kubo S H. Randomized, double-blind, placebo-controlled study of supplemental oral L-arginine in patients with heart failure.  Circulation. 1996;  93 2135-2141
• 42 Ren J, Wang S, Li J, Li A. Effects of early enteral feeding and L-arginine supplementation on liver albumin synthesis in burned rats.  Zhonghua Shao Shang Za Zhi. 2000;  16 206-209
• 43 Reynolds J V, Daly J M, Zhang S, Evantash E, Shou J, Sigal R, Ziegler M M. Immunomodulatory mechanisms of arginine.  Surgery. 1988;  104 142-151
• 44 Sato H, Zhao Z Q, McGee D S, Williams M W, Hammon J W, Vinten-Johansen J. Supplemental L-arginine during cardioplegic arrest and reperfusion avoids regional postischemic injury.  J Thorac Cardiovasc Surg. 1995;  110 302-314
• 45 Stinnett J D, Alexander J W, Watanabe C, MacMillan B G, Fischer J E, Morris M J, Trocki O, Miskell P, Edwards L, James H. Plasma and skeletal muscle amino acids following severe burn injury in patients and experimental animals.  Ann Surg. 1982;  195 75-89
• 46 Takala J, Ruokonen E, Webster N R, Nielsen M S, Zandstra D F, Vundelinckx G, Hinds C J. Increased mortality associated with growth hormone treatment in critically ill adults.  N Engl J Med. 1999;  341 785-792
• 47 Wiebke E A, Grieshop N A, Sidner R A, Howard T J, Yang S. Effects of L-arginine supplementation on human lymphocyte proliferation in response to nonspecific and alloantigenic stimulation.  J Surg Res. 1997;  70 89-94
• 48 Yu Y M, Ryan C M, Burke J F, Tompkins R G, Young V R. Relations among arginine, citrulline, ornithine, and leucine kinetics in adult burn patients.  Am J Clin Nutr. 1995;  62 960-968
• 49 Yu Y M, Sheridan R L, Burke J F, Chapman T E, Tompkins R G, Young V R. Kinetics of plasma arginine and leucine in pediatric burn patients.  Am J Clin Nutr. 1996;  64 60-66
• 50 Yu Y M, Young V R, Castillo L, Chapman T E, Tompkins R G, Ryan C M, Burke J F. Plasma arginine and leucine kinetics and urea production rates in burn patients.  Metabolism. 1995;  44 659-666