Immunonutrition — A New Aspect in the Treatment of Critically Ill Patients

  • S. Bengmark
  • L. Gianotti


The mortality following extensive operations and trauma has decreased considerably during last two decades. The postoperative morbidity remains, however, unacceptably high, especially in burns, after extensive visceral operations, particularly after transplantation, but also in severe liver failure and pancreatitis. A similar development is seen in patients with HIV/AIDS, especially in advanced stages. Infections, sometimes leading to multiple organ failure (MOF), are the dominating cause of postoperative and posttrauma sepsis (POTS). These infections are mainly gram-negative aerobic bacterial, but sometimes of viral, fungal, or protozoal origin.


Nitric Oxide Enteral Nutrition Microbial Translocation Selective Decontamination Enteric Tube Feeding 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


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  1. 1.
    van Goor H, Rosman C, Grond J, Kooi K, Wubbels GH, Bleichrodt RP (1994) Translocation of bacteria and endotoxin in organ donors. Arch Surg 129:1063–1066.PubMedCrossRefGoogle Scholar
  2. 2.
    McDonald WS, Sharp CW, Deitch EA (1991) Immediate enteral feeding in bum patients is safe and effective. Ann Surg 214:177–183CrossRefGoogle Scholar
  3. 3.
    Dobke MK, Simoni J, Ninnemann TJ, Garrett J, Hamar TJ (1989) Endotoxin after burn injury: effects of early excision on circulating levels. J Bum Care Rehabil 10:107–111CrossRefGoogle Scholar
  4. 4.
    O’Dwyers ST, Michie HR, Ziegler TR, Revhaug A, Smith JR, Wilmore DW (1988) A single dose of endotoxin increases intestinal permeability in healthy humans. Arch Surg 123: 1459–1464CrossRefGoogle Scholar
  5. 5.
    Bengmark S. Econutrition and health maintenance — a new concept to prevent GI inflammation, ulceration and sepsis — an invited review. J Clin Nutr. Under publicationGoogle Scholar
  6. 6.
    Burd RS, Cody CS, Dunn DL (1992) Immunotherapy of gram-negative bacterial sepsis. Landes, AustinGoogle Scholar
  7. 7.
    Doglio GR, Pusajo JF, Egurrola MA, Bonfigli G, Parra C, Vetere LM, Hernandez MS, Fernandez S, Palizas F, Gutierrez G (1990) Gastric mucosal pH as a prognostic index of mortality in critically ill patients. Crit Care Med 19:1037–1040CrossRefGoogle Scholar
  8. 8.
    Carrico CJ, Meakins JL, Marshall JC, Fry D, Maier RV (1986) Multiple-organ failure syndrome. Arch Surg 121:196–208PubMedCrossRefGoogle Scholar
  9. 9.
    Levine GM, Deren JJ, Steiger E, Zinno R (1974) Role of oral intake in maintenance of gut mass and disaccharide activity. Gastroenterology 67:975–982PubMedGoogle Scholar
  10. 10.
    Sunzel H (1963) Effects of surgical trauma on the liver glycogen in fasting and in glucose fed patients. Acta Chir Scand 125:118–128PubMedGoogle Scholar
  11. 11.
    Bark T, Katouli M, Ljungquist O, Möllby R, Svenberg T (1995) Glutamine supplementation does not prevent bacterial translocation after non-lethal hemorrhage in rats. Eur J Surg 161: 3–8PubMedGoogle Scholar
  12. 12.
    Moore FA, Feliciano DV, Andrassy RJ, McArdle AH, McL Booth FV, Morgenstein-Wagner TB, Kellum Jr JM, Welling RE, Moore EE (1991) Early enteral feeding, compared with parenteral, reduces postoperative septic comphcations. Ann Surg 216(2): 172–182CrossRefGoogle Scholar
  13. 13.
    Ljungquist O, Thorell A, Gutniak M, Häggström T, Efencic S (1994) Glucose infusion instead of preoperative fasting reduces postoperative insulin resistance. Surg Gynecol Obstet 178: 329–335Google Scholar
  14. 14.
    Mandel ID (1987) The function of saliva. J Dent Res 66:623–627PubMedGoogle Scholar
  15. 15.
    Starkey RH, Orth D (1977) Radioimmunoassay of human epidermal growth factor (Urogastrone). Clin Endocrinol Metab 45:1144–1153CrossRefGoogle Scholar
  16. 16.
    Sarosiek J, Feng TT, McCallum RW (1991) The interrelationship between salivary epidermal growth factor and the functional integrity of the mucosal barrier in the rat. Am J Med Sci 302:359–363PubMedCrossRefGoogle Scholar
  17. 17.
    Tabak LA, Levine MJ, Mandel ID, Ellison SA (1982) Role of salivary mucins in the protection of the oral cavity. J Oral Pathol 11:1–17PubMedCrossRefGoogle Scholar
  18. 18.
    Vahouny GV, Le T, Ifrim I, Satchithanandam S, Cassidy MM (1985) Stimulation of intestinal cytokinetics and mucin turnover in rats fed wheat bran and cellulose. Am J Clin Nutr 41: 895–900.PubMedGoogle Scholar
  19. 19.
    Sreebny LM, Banoczy J, Baum BJ, Edgar WM, Epstein JB, Fox PC, Larmas M (1992) Saliva: its role in health and disease. Int Dent J 42;4 [Suppl 2]:291–304Google Scholar
  20. 20.
    Fox PC, van der Ven PF, Baum BJ, Mandel ID (1986) Pilocarpine for the treatment of xerostomia associated with salivary gland dysfunction. Oral Surg 61:243–248PubMedCrossRefGoogle Scholar
  21. 21.
    Wilder-Smith CH, Spirig C, Krech T, Merki HS (1992) Bactericidal factors in gastric juice. Eur J Gastroenterol Hepatol 4:885–891Google Scholar
  22. 22.
    Driks MR, Craven DE, Celli BR, Manning M, Burke RA, Garvin GM, Kunches LM, Färber HW, Wedel SA, McCabe WR (1987) Nosocomial pneumonia in intubated patients given sucralfate as compared with antacids or histamin type 2 blockers. N Engl J Med 317: 1376–1382PubMedCrossRefGoogle Scholar
  23. 23.
    Toung TJK, Rosenfeld BA, Yoshiki A, Grayson RF, Traystman RJ (1993) Sucralfate does not reduce the risk of acid aspiration pneumonitis. Crit Care Med 21:1359–1364PubMedCrossRefGoogle Scholar
  24. 24.
    Bengmark S, Jeppsson B (1995) Gastrointestinal surface protection and mucosa reconditioning. JPEN J Parenter Enteral Nutr (in press)Google Scholar
  25. 25.
    Bonten MJM, Gaillard CA, van Thiel FH, van der Geest S, Stobberingh EE (1994) Continuous enteral feeding counteracts preventive measures for gastric colonization in intensive care patients. Crit Care Med 22:939–944PubMedCrossRefGoogle Scholar
  26. 26.
    Preiser J-C, Lejeune P, Roman A, Carlier E, De Backer D, Leeman M, Kahn RJ, Vincent J (1995) Methylene blue administration in septic shock: a clinical trial. Crit Care Med 23(2): 259–264PubMedCrossRefGoogle Scholar
  27. 27.
    Wright CE, Rees DD, Moncada S (1992) Protective and pathological roles of nitric oxide in endotoxin shock. Cardiovasc Res 26:48–57PubMedCrossRefGoogle Scholar
  28. 28.
    Green SJ (1995) Nitric oxide in mucosal immunity. Nature Med 6:515–517Google Scholar
  29. 29.
    Malawista SE, Montgomery RR, van Blaricom GJ (1992) Evidence for reactive nitrogen intermediates in killing of staphylococci by human neutrophil cytoplasts. A new microbiocidal pathway for polymorphonuclear leukocytes. J Clin Invest 90:631–636PubMedCrossRefGoogle Scholar
  30. 30.
    Herndon DN, Ziegler ST (1993) Bacterial translocation after thermal injury. Crit Care Med 21:S50-S54PubMedCrossRefGoogle Scholar
  31. 31.
    Forman D, Al-Dabbagh S, Doll R (1985) Nitrates, nitrites and gastric cancer in Great Britain. Nature 313:620–625PubMedCrossRefGoogle Scholar
  32. 32.
    Knight TM et al (1990) Nitrate and nitrite exposure in Italian populations with different gastric cancer rates. Int J Epidemiol 19:510PubMedCrossRefGoogle Scholar
  33. 33.
    Benjamin N, O’Driscoll F, Dougall H, Duncan C, Smith S, Golden M (1994) Stomach NO synthesis. Nature 368:502PubMedCrossRefGoogle Scholar
  34. 34.
    Duncan C, Dougall H, Johnston P, Green S, Brogan R, Leifert C, Smith L, Golden M, Benjamin N (1995) Chemical generation of nitric oxide in the mouth from the enterosalivary circulation of dietary nitrate. Nature Med 1:546–551PubMedCrossRefGoogle Scholar
  35. 35.
    Lundberg JON, Weitzberg E, Lundberg JM, Alving K (1994) Intragastric nitric oxide production in humans: measurements in expelled air. Gut 35:1543–1546PubMedCrossRefGoogle Scholar
  36. 36.
    Brown JF, Hanson PJ, Whittle BJR (1992) Nitric oxide donors increase mucus gel thickness in rat stomach. Eur J Pharmacol 223:103–104PubMedCrossRefGoogle Scholar
  37. 37.
    Odum L, Andersson L-P (1995) Investigation of Helicobacter pylori ascorbic oxidation activity. FEMS Immunol Med Microbiol 10(3–4):289–294PubMedGoogle Scholar
  38. 38.
    Fujisaki H, Oketani K, Murakami M, Fujimote M, Wakabayashi T, Yamatsu I, Yamaguchi M, Sakzi H, Takeguchi M (1991) Inhibitions of acid secretion by E 3810 and omeprazole, and their reversal by glutathione. Biochem Pharmacol 42(2):321–328PubMedCrossRefGoogle Scholar
  39. 39.
    Verdu E, Viani F, Armstrong D, Eraser R, Siegrist HH, Pignatelli B, Idstrom J-P, Cederberg C, Blum AL, Fried M (1994) Effects of omeprazole on intragastric bacterial counts, nitrates, nitrites and N-nitrose compounds. Gut 35:455–460PubMedCrossRefGoogle Scholar
  40. 40.
    Streat SJ, Beddoe AH, Hill GL (1987) Aggressive nutritional support does not prevent protein loss despite fat gain in septic intensive care patients. J Trauma 27:262–266PubMedCrossRefGoogle Scholar
  41. 41.
    Detsky AS, Baker JP, O’Rourke K, Goel V (1987) Perioperative parenteral nutrition: a metaanalysis. Ann Intern Med 107(2): 195–203PubMedGoogle Scholar
  42. 42.
    Olivares L, Segovia A, Revuelta R (1974) Tube feeding and lethal aspiration in neurological patients: a review of 720 autopsy cases. Stroke 5:654–657PubMedCrossRefGoogle Scholar
  43. 43.
    Bengmark S, Larsson K, Molin G (1995) Gut mucosa reconditioning with species-specific lactobacilli, surfactants, pseudomucus and fiber — an invited review. Biotechnol Ther (in press)Google Scholar
  44. 44.
    Mulholland JH, Tui C, Wright AM, Vinci VJ (1943) Nitrogen metabolism, caloric intake and weight loss in postoperative convalescence. Ann Surg 117:512–534PubMedCrossRefGoogle Scholar
  45. 45.
    Riegel C, Koop CE, Drew J, Stevens LW, Rhoads JE (1947) The nutritional requirements for nitrogen balance in surgical patients during the early postoperative period. J Clin Invest 26: 18–23CrossRefGoogle Scholar
  46. 46.
    Shephard AP (1980) Intestinal blood flow autoregulation during foodstuff absorption. Am J Physiol 239:H156-H162Google Scholar
  47. 47.
    Roediger WEW (1980) Role of anaerobic bacteria in the metabolic welfare of the colonic mucosa in man. Gut 21:793–798PubMedCrossRefGoogle Scholar
  48. 48.
    Hoover HC, Ryan JA, Anderson EJ, Fischer JE (1980) Nutritional benefits of immediate postoperative jejunal feeding of an elemental diet. Am J Surg 139:153–159PubMedCrossRefGoogle Scholar
  49. 49.
    Alexander JW, MacMillan BG, Stinnett JD et al (1980) Beneficial effects of aggressive protein feeding in severely burned children. Ann Surg 192:505PubMedCrossRefGoogle Scholar
  50. 50.
    Vandenbroucke-Grauls CMJE, Vandenbroucke JP (1991) Effect of selective decontamination of the digestive tract on respiratory tract infections and mortality in the intensive care unit. Lancet 338:859–862PubMedCrossRefGoogle Scholar
  51. 51.
    Rees RPG, Payne-James JJ, King C, Silk DBA (1988) Spontaneous transpyloric passage and performance of “Fine Bore” polyurethane feeding tubes: a controlled trial. JPEN J Parenter Enteral Nutr 12(5):469–472PubMedCrossRefGoogle Scholar
  52. 52.
    Levenson R, Furner Jr WW, Dyson A, Zike L, Reisch J (1988) Do weighted nasoenteric feeding tubes facilitate duodenal intubations? JPEN J Parenter Enteral Nutr 12(2): 135–137PubMedCrossRefGoogle Scholar
  53. 53.
    Bengmark S Swedish patent 8700582, US patent 4 887 996, EU patent PTC/0278937Google Scholar
  54. 54.
    Jeppsson B, Tranberg K-G, Bengmark S (1992) Technical developments. A new self-propelling feeding tube. Clin Nutr 11:373–375PubMedCrossRefGoogle Scholar
  55. 55.
    Kudsk KA, Croce MA, Fabian TC, Minard G, Tolley EA, Poret HA, Kuhl MR, Brown RO (1992) Enteral versus parenteral feeding: effects on septic morbidity after blunt and penetrating abdominal trauma. Ann Surg 215:503PubMedCrossRefGoogle Scholar
  56. 56.
    Chandra RK, Baker M, Whang S, Au B (1991) Effect of two feeding formulas on immune responses and mortality in mice challenged with Listeria monocytogenes. Immunol Lett 27:45–48PubMedCrossRefGoogle Scholar
  57. 57.
    Klasing KC (1989) Nutritional aspects of leukocytic cytokines. J Nutr 118:1436–1446Google Scholar
  58. 58.
    Merimee TJ, Lillecrap DA, Rabinowitz D (1965) Effect of arginine on serum levels of human growth hormone. Lancet 2:668–670PubMedCrossRefGoogle Scholar
  59. 59.
    Scull CW, Rose WJC (1930) Arginine metabohsm: the relation of arginine content of the diet on the increments in tissue arginine during growth. J Biol Chem 39:109–121Google Scholar
  60. 60.
    Elsair J, Poey J, Issad H (1978) Effect of arginine chlorate on nitrogen balance during the three days following routine surgery in healthy human beings. Biomed Expr 29:312–317Google Scholar
  61. 61.
    Seifter E, Rettura G, Barbul A, Levenson SM (1978) Arginine: an essential amino acid for injured rats. Surgery 84:224–230PubMedGoogle Scholar
  62. 62.
    Barbul A, Sisto DA, Wasserkrug HL, Efron G (1981) Arginine stimulates lymphocyte immune response in healthy human beings. Surgery 90:244–251PubMedGoogle Scholar
  63. 63.
    Reynolds JV, Daly JM, Zhang S, Evantash E, Shou J, Sigal R, Ziegler MM (1988) Immunomodulary mechanisms of arginine. Surgery 104:142–151PubMedGoogle Scholar
  64. 64.
    Lieberman MD, Nishioka K, Redmond P, Daly JM (1992) Enhancement of interleukin-2 immunotherapy with 1-arginine. Ann Surg 215:157PubMedCrossRefGoogle Scholar
  65. 65.
    McGhee JR, Mestecky J, Elson CO, Kijono H (1989) Regulation of IgA synthesis and immune response by T cells and interleukins. J Clin Immunol 9:175PubMedCrossRefGoogle Scholar
  66. 66.
    Moncada S, Higgs EA (1991) Endogenous nitric oxide: physiology, pathology and clinical relevance. Eur J Clin Invest 21:361PubMedCrossRefGoogle Scholar
  67. 67.
    Nava E, Palmer RM, Moncada S (1991) Inhibition of nitric oxide synthesis in septic shock: how much is beneficial. Lancet 338:1555–1557PubMedCrossRefGoogle Scholar
  68. 68.
    Billiar TR, Curran RD, Harbrecht BG, Stuehr DJ, Demetris AJ, simmons RL (1990) Modulation of nitrogen oxide synthesis in vivo: NG-monethyl-l-arginine inhibits endo toxin-induced nitrate/nitrite biosynthesis while promoting hepatic damage. J Leukoc Biol 48:565PubMedGoogle Scholar
  69. 69.
    Gianotti L, Alexander JW, Pyles T, Fukushima R (1993) Arginine-supplemented diets improve survival in gut-derived sepsis and peritonitis by modulating bacterial clearance. The role of nitric oxide. Ann Surg 217:644–654PubMedCrossRefGoogle Scholar
  70. 70.
    Osborne DL, Seidel IR (1989) Microflora-derived polyamines modulate obstruction-induced colonic mucosal hypertrophy. Am J Physiol (Gastrointest Liver Physiol) 19:G 1049–1057Google Scholar
  71. 71.
    Montel MC, Champomier M-C (1987) Arginine catabohsm in Lactobacillus sake isolated from meat. Appl Environ Microbiol 53:2683–2685PubMedGoogle Scholar
  72. 72.
    Jónsson S, Clausen E, Raa J (1983) Amino acid degradation by a Lactobacillus plantarum strain from fish. System Appi Microbiol 4:148–154CrossRefGoogle Scholar
  73. 73.
    Alexander JW (1993) Immunoenhancement in enteral nutrition. Arch Surg 128:1242PubMedCrossRefGoogle Scholar
  74. 74.
    van Buren CT, Rudolph FB, Kuokarni A, Pizzini R, Fanslow WC, Kumar S (1990) Reversal of immunosuppression induced by protein-free diet: a comparison of nucleotides, fish oil and arginine. Crit Care Med 18:S2114Google Scholar
  75. 75.
    Gottschlick MM, Jenkins M, Warden GD, Baumer T, Havens P, Snook JT, Alexander JW (1990) Differential effects of three enteral dietary regimens on selected outcome variables in burn patients. JPEN J Parenter Enteral Nutr 14:225–236CrossRefGoogle Scholar
  76. 76.
    Daly JM, Lieberman MD, Goldfìne J, Shou J, Weintraub F, Rosato EF, Lavin Ph (1992) Enteral nutrition with supplemented arginine, RNA, and omega-3 fatty acids in patients after operation: immunologic, metabolic and clinical outcome. Surgery 112:56–67PubMedGoogle Scholar
  77. 77.
    Braga M, Vignali A, Gianotti L et al (1995) Immune and nutritional effects of early enteral nutrition after major abdominal operations. Eur J Surg 221:327–338Google Scholar
  78. 78.
    Bowers RB, Cerra FB, Bershadsky B, Licari JJ, Hoyt DB, Jensen GL, Van Buren CT, Rothkopf MM, Daly JM (1995) 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 23:436–449CrossRefGoogle Scholar
  79. 79.
    Kemen M, Senkal M, Homann HH et al (1995) Early postoperative enteral nutrition with arginine, omega 3-fatty acids and ribonucleic acid-supplemented diet versus placebo in cancer patients: an immunological evaluation of Impact R. Crit Care Med 23:652–659PubMedCrossRefGoogle Scholar
  80. 80.
    Senkal M, Kemen M, Homann HH et al (1995) Modulation of postoperative response by enteral nutrition with a diet enriched with arginine, RNA, and omega-3 fatty acids in patients with upper gastrointestinal cancer. Eur J Surg 161:115–122PubMedGoogle Scholar
  81. 81.
    Cummings JH (1995) Anatomy and physiology of human colon. Workshop on colonic microflora. Barcelona Spain. Nutr Rev (in press)Google Scholar
  82. 82.
    Croft DN, Cotton PB Gastro-intestinal cell loss in man. Its measurements and significance. Digestion 8:144–166Google Scholar
  83. 83.
    Bengmark S (1995) Eco-nutrition and health maintenance. J Clin Nutr (in press)Google Scholar
  84. 84.
    Bengmark S, Gianotti L (1995) Nutritional support to prevent and treat MOF. World J Surg (in press)Google Scholar
  85. 85.
    Eiseman B, Silen W, Bascom GS, Kauvar AJ (1958) Fecal enema as an adjunct in the treatment of pseudomembranous enterocolitis. Surgery 44:854–859PubMedGoogle Scholar
  86. 86.
    Wilmore DW (1993) The surgeon and intestinal bacteria — reconsideration of our relationship. After Baue A. The role of the gut in the development of multiple organ dysfunction in cardiothoracic patients. Ann Thorac Surg 55:822–829CrossRefGoogle Scholar
  87. 87.
    Lencner AA, Lencner ChP, Mikelsaar DR, Thuri ME, Toom MA, Väljaots MW, Silov VM, Liz’ko NN, Legenkov VI, Reznikov IM (1984) Die quantitative Zusammensetzung der Laktoflora des Verdauungstrakts vor und nach kosmischen Flügen unterschiedlicher Dauer. Nahrung 28:607–613PubMedCrossRefGoogle Scholar

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© Springer-Verlag Italia, Milano 1996

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  • S. Bengmark
  • L. Gianotti

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