Gut Failure in the ICU

ABSTRACT

The role of dysfunction of the gastrointestinal tract in the pathogenesis of multiple organ failure (MOF) complicating the course of critically ill patients has been suspected for more than 40 years. However, several hypotheses have been proposed and sometimes refuted to establish a link. This review summarizes the current knowledge on gastrointestinal physiology and recapitulates existing evidence on the link between gastrointestinal dysfunction and MOF. The gastrointestinal tract has various functions apart from digestion. It produces hormones with local and systemic effects, plays a major role in immunological function, and serves as a barrier against antigens within its lumen. Gastrointestinal dysfunction or gut failure is frequently encountered in critical care patients and is associated with bacterial translocation, which can lead to the development of sepsis, initiation of a cytokine-mediated systemic inflammatory response syndrome (SIRS), multiple organ dysfunction syndrome (MODS), and death. The aim of this manuscript is to define gut failure, to review physiopathological mechanisms and clinical implications, and, finally, to suggest preventive measures.

Gut failure - bacterial translocation - sepsis - multiple organ failure - critical care

REFERENCES

• 1 Gatt M, Reddy B S, MacFie J. Review article: bacterial translocation in the critically ill—evidence and methods of prevention.  Aliment Pharmacol Ther. 2007;  25 (7) 741-757
• 2 Reintam A, Parm P, Kitus R, Kern H, Starkopf J. Gastrointestinal symptoms in intensive care patients.  Acta Anaesthesiol Scand. 2009;  53 (3) 318-324
• 3 Piton G, Manzon C, Cypriani B, Carbonnel F, Capellier G. Acute intestinal failure in critically ill patients: is plasma citrulline the right marker?.  Intensive Care Med. 2011;  37 (6) 911-917
• 4 Le Gall J R, Lemeshow S, Saulnier F. A new Simplified Acute Physiology Score (SAPS II) based on a European/North American multicenter study.  JAMA. 1993;  270 (24) 2957-2963
• 5 Vincent J L, Moreno R, Takala J et al.. The SOFA (sepsis-related organ failure assessment) score to describe organ dysfunction/failure. On behalf of the Working Group on Sepsis-Related Problems of the European Society of Intensive Care Medicine.  Intensive Care Med. 1996;  22 (7) 707-710
• 6 Fagon J Y, Chastre J, Novara A, Medioni P, Gibert C. Characterization of intensive care unit patients using a model based on the presence or absence of organ dysfunctions and/or infection: the ODIN model.  Intensive Care Med. 1993;  19 (3) 137-144
• 7 Crenn P, Messing B, Cynober L. Citrulline as a biomarker of intestinal failure due to enterocyte mass reduction.  Clin Nutr. 2008;  27 (3) 328-339
• 8 Cummings J H, Antoine J M, Azpiroz F et al.. PASSCLAIM—gut health and immunity.  Eur J Nutr. 2004;  43 (Suppl 2) II118-II173
• 9 Cheng H, Leblond C P. Origin, differentiation and renewal of the four main epithelial cell types in the mouse small intestine, V: Unitarian theory of the origin of the four epithelial cell types.  Am J Anat. 1974;  141 (4) 537-561
• 10 Hall P A, Coates P J, Ansari B, Hopwood D. Regulation of cell number in the mammalian gastrointestinal tract: the importance of apoptosis.  J Cell Sci. 1994;  107 (Pt 12) 3569-3577
• 11 Grootjans J, Hodin C M, de Haan J J et al.. Level of activation of the unfolded protein response correlates with Paneth cell apoptosis in human small intestine exposed to ischemia/reperfusion.  Gastroenterology. 2011;  140 (2) 529-539 e3
• 12 Utech M, Brüwer M, Nusrat A. Tight junctions and cell-cell interactions.  Methods Mol Biol. 2006;  341 185-195
• 13 Coopersmith C M, Stromberg P E, Davis C G et al.. Sepsis from Pseudomonas aeruginosa pneumonia decreases intestinal proliferation and induces gut epithelial cell cycle arrest.  Crit Care Med. 2003;  31 (6) 1630-1637
• 14 Husain K D, Stromberg P E, Woolsey C A et al.. Mechanisms of decreased intestinal epithelial proliferation and increased apoptosis in murine acute lung injury.  Crit Care Med. 2005;  33 (10) 2350-2357
• 15 Potoka D A, Upperman J S, Zhang X R et al.. Peroxynitrite inhibits enterocyte proliferation and modulates Src kinase activity in vitro.  Am J Physiol Gastrointest Liver Physiol. 2003;  285 (5) G861-G869
• 16 Rafferty J F, Noguchi Y, Fischer J E, Hasselgren P O. Sepsis in rats stimulates cellular proliferation in the mucosa of the small intestine.  Gastroenterology. 1994;  107 (1) 121-127
• 17 Clark J A, Coopersmith C M. Intestinal crosstalk: a new paradigm for understanding the gut as the “motor” of critical illness.  Shock. 2007;  28 (4) 384-393
• 18 Fukatsu K, Sakamoto S, Hara E et al.. Gut ischemia-reperfusion affects gut mucosal immunity: a possible mechanism for infectious complications after severe surgical insults.  Crit Care Med. 2006;  34 (1) 182-187
• 19 Bäckhed F, Ley R E, Sonnenburg J L, Peterson D A, Gordon J I. Host-bacterial mutualism in the human intestine.  Science. 2005;  307 (5717) 1915-1920
• 20 Alverdy J C, Laughlin R S, Wu L. Influence of the critically ill state on host-pathogen interactions within the intestine: gut-derived sepsis redefined.  Crit Care Med. 2003;  31 (2) 598-607
• 21 Lazazzera B A. Quorum sensing and starvation: signals for entry into stationary phase.  Curr Opin Microbiol. 2000;  3 (2) 177-182
• 22 Kinney K S, Austin C E, Morton D S, Sonnenfeld G. Norepinephrine as a growth stimulating factor in bacteria—mechanistic studies.  Life Sci. 2000;  67 (25) 3075-3085
• 23 Deane A, Chapman M J, Fraser R JL, Horowitz M. Bench-to-bedside review: the gut as an endocrine organ in the critically ill.  Crit Care. 2010;  14 (5) 228-238
• 24 Nind G, Chen W H, Protheroe R et al.. Mechanisms of gastroesophageal reflux in critically ill mechanically ventilated patients.  Gastroenterology. 2005;  128 (3) 600-606
• 25 Nguyen N Q, Fraser R J, Chapman M et al.. Proximal gastric response to small intestinal nutrients is abnormal in mechanically ventilated critically ill patients.  World J Gastroenterol. 2006;  12 (27) 4383-4388
• 26 Chapman M, Fraser R, Vozzo R et al.. Antro-pyloro-duodenal motor responses to gastric and duodenal nutrient in critically ill patients.  Gut. 2005;  54 (10) 1384-1390
• 27 Deane A M, Fraser R J, Chapman M J. Prokinetic drugs for feed intolerance in critical illness: current and potential therapies.  Crit Care Resusc. 2009;  11 (2) 132-143
• 28 Chapman M J, Fraser R J, Bryant L K et al.. Gastric emptying and the organization of antro-duodenal pressures in the critically ill.  Neurogastroenterol Motil. 2008;  20 (1) 27-35
• 29 Johnston J D, Harvey C J, Menzies I S, Treacher D F. Gastrointestinal permeability and absorptive capacity in sepsis.  Crit Care Med. 1996;  24 (7) 1144-1149
• 30 Chapman M J, Fraser R J, Matthews G et al.. Glucose absorption and gastric emptying in critical illness.  Crit Care. 2009;  13 (4) R140
• 31 Wren A M, Seal L J, Cohen M A et al.. Ghrelin enhances appetite and increases food intake in humans.  J Clin Endocrinol Metab. 2001;  86 (12) 5992-5995
• 32 Parker B A, Doran S, Wishart J, Horowitz M, Chapman I M. Effects of small intestinal and gastric glucose administration on the suppression of plasma ghrelin concentrations in healthy older men and women.  Clin Endocrinol (Oxf). 2005;  62 (5) 539-546
• 33 Tack J, Depoortere I, Bisschops R, Verbeke K, Janssens J, Peeters T. Influence of ghrelin on gastric emptying and meal-related symptoms in idiopathic gastroparesis.  Aliment Pharmacol Ther. 2005;  22 (9) 847-853
• 34 Murray C D, Martin N M, Patterson M et al.. Ghrelin enhances gastric emptying in diabetic gastroparesis: a double blind, placebo controlled, crossover study.  Gut. 2005;  54 (12) 1693-1698
• 35 De Winter B Y, De Man J G, Seerden T C et al.. Effect of ghrelin and growth hormone-releasing peptide 6 on septic ileus in mice.  Neurogastroenterol Motil. 2004;  16 (4) 439-446
• 36 Nematy M, O'Flynn J E, Wandrag L et al.. Changes in appetite related gut hormones in intensive care unit patients: a pilot cohort study.  Crit Care. 2006;  10 (1) R10
• 37 Vantrappen G, Janssens J, Peeters T L, Bloom S R, Christofides N D, Hellemans J. Motilin and the interdigestive migrating motor complex in man.  Dig Dis Sci. 1979;  24 (7) 497-500
• 38 Peeters T L, Muls E, Janssens J et al.. Effect of motilin on gastric emptying in patients with diabetic gastroparesis.  Gastroenterology. 1992;  102 (1) 97-101
• 39 Pilichiewicz A N, Chaikomin R, Brennan I M et al.. Load-dependent effects of duodenal glucose on glycemia, gastrointestinal hormones, antropyloroduodenal motility, and energy intake in healthy men.  Am J Physiol Endocrinol Metab. 2007;  293 (3) E743-E753
• 40 Fried M, Erlacher U, Schwizer W et al.. Role of cholecystokinin in the regulation of gastric emptying and pancreatic enzyme secretion in humans. Studies with the cholecystokinin-receptor antagonist loxiglumide.  Gastroenterology. 1991;  101 (2) 503-511
• 41 Schwizer W, Borovicka J, Kunz P et al.. Role of cholecystokinin in the regulation of liquid gastric emptying and gastric motility in humans: studies with the CCK antagonist loxiglumide.  Gut. 1997;  41 (4) 500-504
• 42 Hildebrand P, Beglinger C, Gyr K et al.. Effects of a cholecystokinin receptor antagonist on intestinal phase of pancreatic and biliary responses in man.  J Clin Invest. 1990;  85 (3) 640-646
• 43 Nguyen N Q, Fraser R J, Chapman M J et al.. Feed intolerance in critical illness is associated with increased basal and nutrient-stimulated plasma cholecystokinin concentrations.  Crit Care Med. 2007;  35 (1) 82-88
• 44 Adrian T E, Ferri G L, Bacarese-Hamilton A J, Fuessl H S, Polak J M, Bloom S R. Human distribution and release of a putative new gut hormone, peptide YY.  Gastroenterology. 1985;  89 (5) 1070-1077
• 45 Savage A P, Adrian T E, Carolan G, Chatterjee V K, Bloom S R. Effects of peptide YY (PYY) on mouth to caecum intestinal transit time and on the rate of gastric emptying in healthy volunteers.  Gut. 1987;  28 (2) 166-170
• 46 Nguyen N Q, Fraser R J, Bryant L K et al.. The relationship between gastric emptying, plasma cholecystokinin, and peptide YY in critically ill patients.  Crit Care. 2007;  11 (6) R132
• 47 Meier J J, Nauck M A. Glucagon-like peptide 1(GLP-1) in biology and pathology.  Diabetes Metab Res Rev. 2005;  21 (2) 91-117
• 48 Nauck M A, Heimesaat M M, Orskov C, Holst J J, Ebert R, Creutzfeldt W. Preserved incretin activity of glucagon-like peptide 1 [7-36 amide] but not of synthetic human gastric inhibitory polypeptide in patients with type-2 diabetes mellitus.  J Clin Invest. 1993;  91 (1) 301-307
• 49 Nauck M A. Is glucagon-like peptide 1 an incretin hormone?.  Diabetologia. 1999;  42 (3) 373-379
• 50 Meier J J, Gallwitz B, Schmidt W E, Nauck M A. Glucagon-like peptide 1 as a regulator of food intake and body weight: therapeutic perspectives.  Eur J Pharmacol. 2002;  440 (2-3) 269-279
• 51 Chaikomin R, Doran S, Jones K L et al.. Initially more rapid small intestinal glucose delivery increases plasma insulin, GIP, and GLP-1 but does not improve overall glycemia in healthy subjects.  Am J Physiol Endocrinol Metab. 2005;  289 (3) E504-E507
• 52 Meier J J, Weyhe D, Michaely M et al.. Intravenous glucagon-like peptide 1 normalizes blood glucose after major surgery in patients with type 2 diabetes.  Crit Care Med. 2004;  32 (3) 848-851
• 53 Müssig K, Oncü A, Lindauer P et al.. Effects of intravenous glucagon-like peptide-1 on glucose control and hemodynamics after coronary artery bypass surgery in patients with type 2 diabetes.  Am J Cardiol. 2008;  102 (5) 646-647
• 54 Deane A M, Chapman M J, Fraser R J, Burgstad C M, Besanko L K, Horowitz M. The effect of exogenous glucagon-like peptide-1 on the glycaemic response to small intestinal nutrient in the critically ill: a randomised double-blind placebo-controlled cross over study.  Crit Care. 2009;  13 (3) R67
• 55 Straub R H, Wiest R, Strauch U G, Härle P, Schölmerich J. The role of the sympathetic nervous system in intestinal inflammation.  Gut. 2006;  55 (11) 1640-1649
• 56 Miksa M, Wu R, Zhou M, Wang P. Sympathetic excitotoxicity in sepsis: pro-inflammatory priming of macrophages by norepinephrine.  Front Biosci. 2005;  10 2217-2229
• 57 Keita A V, Söderholm J D. The intestinal barrier and its regulation by neuroimmune factors.  Neurogastroenterol Motil. 2010;  22 (7) 718-733
• 58 Santos J, Saunders P R, Hanssen N P et al.. Corticotropin-releasing hormone mimics stress-induced colonic epithelial pathophysiology in the rat.  Am J Physiol. 1999;  277 (2 Pt 1) G391-G399
• 59 Santos J, Yates D, Guilarte M, Vicario M, Alonso C, Perdue M H. Stress neuropeptides evoke epithelial responses via mast cell activation in the rat colon.  Psychoneuroendocrinology. 2008;  33 (9) 1248-1256
• 60 Smith F, Clark J E, Overman B L et al.. Early weaning stress impairs development of mucosal barrier function in the porcine intestine.  Am J Physiol Gastrointest Liver Physiol. 2010;  298 (3) G352-G363
• 61 Wallon C, Yang P C, Keita A V et al.. Corticotropin-releasing hormone (CRH) regulates macromolecular permeability via mast cells in normal human colonic biopsies in vitro.  Gut. 2008;  57 (1) 50-58
• 62 Moeser A J, Klok C V, Ryan K A et al.. Stress signaling pathways activated by weaning mediate intestinal dysfunction in the pig.  Am J Physiol Gastrointest Liver Physiol. 2007;  292 (1) G173-G181
• 63 Crowe S E, Perdue M H. Anti-immunoglobin E-stimulated ion transport in human large and small intestine.  Gastroenterology. 1993;  105 (3) 764-772
• 64 Santos J, Saperas E, Nogueiras C et al.. Release of mast cell mediators into the jejunum by cold pain stress in humans.  Gastroenterology. 1998;  114 (4) 640-648
• 65 Berg R D, Garlington A W. Translocation of certain indigenous bacteria from the gastrointestinal tract to the mesenteric lymph nodes and other organs in a gnotobiotic mouse model.  Infect Immun. 1979;  23 (2) 403-411
• 66 Carrico C J, Meakins J L, Marshall J C, Fry D, Maier R V. Multiple-organ-failure syndrome.  Arch Surg. 1986;  121 (2) 196-208
• 67 Dominguez J A, Coopersmith C M. Can we protect the gut in critical illness? The role of growth factors and other novel approaches.  Crit Care Clin. 2010;  26 (3) 549-565 x
• 68 Alverdy J C, Laughlin R S, Wu L. Influence of the critically ill state on host-pathogen interactions within the intestine: gut-derived sepsis redefined.  Crit Care Med. 2003;  31 (2) 598-607
• 69 Deitch E A. Bacterial translocation or lymphatic drainage of toxic products from the gut: what is important in human beings?.  Surgery. 2002;  131 (3) 241-244
• 70 Deitch E A, Xu D, Kaise V L. Role of the gut in the development of injury- and shock induced SIRS and MODS: the gut-lymph hypothesis, a review.  Front Biosci. 2006;  11 520-528
• 71 Deitch E A. Role of the gut lymphatic system in multiple organ failure.  Curr Opin Crit Care. 2001;  7 (2) 92-98
• 72 Senthil M, Brown M, Xu D Z, Lu Q, Feketeova E, Deitch E A. Gut-lymph hypothesis of systemic inflammatory response syndrome/multiple-organ dysfunction syndrome: validating studies in a porcine model.  J Trauma. 2006;  60 (5) 958-965 discussion 965-967
• 73 Deitch E A, Forsythe R, Anjaria D et al.. The role of lymph factors in lung injury, bone marrow suppression, and endothelial cell dysfunction in a primate model of trauma-hemorrhagic shock.  Shock. 2004;  22 (3) 221-228
• 74 Steinberg S M. Bacterial translocation: what it is and what it is not.  Am J Surg. 2003;  186 (3) 301-305
• 75 Spahn T W, Kucharzik T. Modulating the intestinal immune system: the role of lymphotoxin and GALT organs.  Gut. 2004;  53 (3) 456-465
• 76 Garside P, Millington O, Smith K M. The anatomy of mucosal immune responses.  Ann N Y Acad Sci. 2004;  1029 9-15
• 77 Song F, Whitacre C C. The role of the gut lymphoid tissue in induction of oral tolerance.  Curr Opin Investig Drugs. 2001;  2 (10) 1382-1386
• 78 O'Boyle C J, MacFie J, Mitchell C J, Johnstone D, Sagar P M, Sedman P C. Microbiology of bacterial translocation in humans.  Gut. 1998;  42 (1) 29-35
• 79 MacFie J, Reddy B S, Gatt M, Jain P K, Sowdi R, Mitchell C J. Bacterial translocation studied in 927 patients over 13 years.  Br J Surg. 2006;  93 (1) 87-93
• 80 Sedman P C, Macfie J, Sagar P et al.. The prevalence of gut translocation in humans.  Gastroenterology. 1994;  107 (3) 643-649
• 81 Reynolds J V, Murchan P, Leonard N, Clarke P, Keane F B, Tanner W A. Gut barrier failure in experimental obstructive jaundice.  J Surg Res. 1996;  62 (1) 11-16
• 82 Hua T C, Moochhala S M. Role of nitric oxide in hemorrhagic shock-induced bacterial translocation.  J Surg Res. 2000;  93 (2) 247-256
• 83 de Madaria E, Martínez J, Lozano B et al.. Detection and identification of bacterial DNA in serum from patients with acute pancreatitis.  Gut. 2005;  54 (9) 1293-1297
• 84 Küçükaydin M, Kocaoğlu C, Köksal F, Kontaş O. Detection of intestinal bacterial translocation in subclinical ischemia-reperfusion using the polymerase chain reaction technique.  J Pediatr Surg. 2000;  35 (1) 41-43
• 85 Galeev Y M, Lishmanov Y B, Grigorev E G, Popov M V, Aparcin K A, Salato O V. Scintigraphic visualization of bacterial translocation in experimental strangulated intestinal obstruction.  Eur J Nucl Med Mol Imaging. 2009;  36 (11) 1822-1828
• 86 Kabaroudis A, Papaziogas B, Koutelidakis I, Kyparissi-Kanellaki M, Kouzi-Koliakou K, Papaziogas T. Disruption of the small-intestine mucosal barrier after intestinal occlusion: a study with light and electron microscopy.  J Invest Surg. 2003;  16 (1) 23-28
• 87 Antequera R, Bretaña A, Cirac A, Brito A, Romera M A, Zapata R. Disruption of the intestinal barrier and bacterial translocation in an experimental model of intestinal obstruction.  Acta Cient Venez. 2000;  51 (1) 18-26
• 88 Samel S, Keese M, Kleczka M et al.. Microscopy of bacterial translocation during small bowel obstruction and ischemia in vivo—a new animal model.  BMC Surg. 2002;  2 6-13
• 89 Sagar P M, MacFie J, Sedman P, May J, Mancey-Jones B, Johnstone D. Intestinal obstruction promotes gut translocation of bacteria.  Dis Colon Rectum. 1995;  38 (6) 640-644
• 90 Deitch E A, Sittig K, Li M, Berg R, Specian R D. Obstructive jaundice promotes bacterial translocation from the gut.  Am J Surg. 1990;  159 (1) 79-84
• 91 Karsten T M, van Gulik T M, Spanjaard L et al.. Bacterial translocation from the biliary tract to blood and lymph in rats with obstructive jaundice.  J Surg Res. 1998;  74 (2) 125-130
• 92 Ogata Y, Nishi M, Nakayama H, Kuwahara T, Ohnishi Y, Tashiro S. Role of bile in intestinal barrier function and its inhibitory effect on bacterial translocation in obstructive jaundice in rats.  J Surg Res. 2003;  115 (1) 18-23
• 93 Cakmakci M, Tirnaksiz B, Hayran M, Belek S, Gürbüz T, Sayek I. Effects of obstructive jaundice and external biliary diversion on bacterial translocation in rats.  Eur J Surg. 1996;  162 (7) 567-571
• 94 Ding J W, Andersson R, Soltesz V, Willén R, Bengmark S. Obstructive jaundice impairs reticuloendothelial function and promotes bacterial translocation in the rat.  J Surg Res. 1994;  57 (2) 238-245
• 95 Reynolds J V, Murchan P, Redmond H P et al.. Failure of macrophage activation in experimental obstructive jaundice: association with bacterial translocation.  Br J Surg. 1995;  82 (4) 534-538
• 96 Sheen-Chen S M, Chau P, Harris H W. Obstructive jaundice alters Kupffer cell function independent of bacterial translocation.  J Surg Res. 1998;  80 (2) 205-209
• 97 Parks R W, Stuart Cameron C H, Gannon C D, Pope C, Diamond T, Rowlands B J. Changes in gastrointestinal morphology associated with obstructive jaundice.  J Pathol. 2000;  192 (4) 526-532
• 98 Reynolds J V, Murchan P, Leonard N, Clarke P, Keane F B, Tanner W A. Gut barrier failure in experimental obstructive jaundice.  J Surg Res. 1996;  62 (1) 11-16
• 99 Wells C L, Jechorek R P, Erlandsen S L. Inhibitory effect of bile on bacterial invasion of enterocytes: possible mechanism for increased translocation associated with obstructive jaundice.  Crit Care Med. 1995;  23 (2) 301-307
• 100 Parks R W, Clements W D, Smye M G, Pope C, Rowlands B J, Diamond T. Intestinal barrier dysfunction in clinical and experimental obstructive jaundice and its reversal by internal biliary drainage.  Br J Surg. 1996;  83 (10) 1345-1349
• 101 Kuzu M A, Kale I T, Cöl C, Tekeli A, Tanik A, Köksoy C. Obstructive jaundice promotes bacterial translocation in humans.  Hepatogastroenterology. 1999;  46 (28) 2159-2164
• 102 Al-Bahrani A Z, Darwish A, Hamza N et al.. Gut barrier dysfunction in critically ill surgical patients with abdominal compartment syndrome.  Pancreas. 2010;  39 (7) 1064-1069
• 103 Byers R J, Eddleston J M, Pearson R C, Bigley G, McMahon R F. Dopexamine reduces the incidence of acute inflammation in the gut mucosa after abdominal surgery in high-risk patients.  Crit Care Med. 1999;  27 (9) 1787-1793
• 104 Lisbon A. Dopexamine, dobutamine, and dopamine increase splanchnic blood flow: what is the evidence?.  Chest. 2003;  123 (5, Suppl) 460S-463S
• 105 MacFie J, O'Boyle C, Mitchell C J, Buckley P M, Johnstone D, Sudworth P. Gut origin of sepsis: a prospective study investigating associations between bacterial translocation, gastric microflora, and septic morbidity.  Gut. 1999;  45 (2) 223-228
• 106 Cheung N W, Napier B, Zaccaria C, Fletcher J P. Hyperglycemia is associated with adverse outcomes in patients receiving total parenteral nutrition.  Diabetes Care. 2005;  28 (10) 2367-2371
• 107 Jeejeebhoy K N. Total parenteral nutrition: potion or poison?.  Am J Clin Nutr. 2001;  74 (2) 160-163
• 108 Miura S, Tanaka S, Yoshioka M et al.. Changes in intestinal absorption of nutrients and brush border glycoproteins after total parenteral nutrition in rats.  Gut. 1992;  33 (4) 484-489
• 109 Guedon C, Schmitz J, Lerebours E et al.. Decreased brush border hydrolase activities without gross morphologic changes in human intestinal mucosa after prolonged total parenteral nutrition of adults.  Gastroenterology. 1986;  90 (2) 373-378
• 110 Rossi T M, Lee P C, Young C, Tjota A. Small intestinal mucosa changes, including epithelial cell proliferative activity, of children receiving total parenteral nutrition (TPN).  Dig Dis Sci. 1993;  38 (9) 1608-1613
• 111 Pironi L, Paganelli G M, Miglioli M et al.. Morphologic and cytoproliferative patterns of duodenal mucosa in two patients after long-term total parenteral nutrition: changes with oral refeeding and relation to intestinal resection.  JPEN J Parenter Enteral Nutr. 1994;  18 (4) 351-354
• 112 Sedman P C, MacFie J, Palmer M D, Mitchell C J, Sagar P M. Preoperative total parenteral nutrition is not associated with mucosal atrophy or bacterial translocation in humans.  Br J Surg. 1995;  82 (12) 1663-1667
• 113 Groos S, Hunefeld G, Luciano L. Parenteral versus enteral nutrition: morphological changes in human adult intestinal mucosa.  J Submicrosc Cytol Pathol. 1996;  28 (1) 61-74
• 114 Moore F A, Moore E E, Jones T N, McCroskey B L, Peterson V M. TEN versus TPN following major abdominal trauma—reduced septic morbidity.  J Trauma. 1989;  29 (7) 916-922 discussion 922-923
• 115 Kudsk K A, Croce M A, Fabian T C et al.. Enteral versus parenteral feeding: effects on septic morbidity after blunt and penetrating abdominal trauma.  Ann Surg. 1992;  215 (5) 503-511 discussion 511-513
• 116 Lipman T O. Bacterial translocation and enteral nutrition in humans: an outsider looks in.  JPEN J Parenter Enteral Nutr. 1995;  19 (2) 156-165
• 117 Alpers D H. Enteral feeding and gut atrophy.  Curr Opin Clin Nutr Metab Care. 2002;  5 (6) 679-683
• 118 Thibault R, Pichard C. Parenteral nutrition in critical illness: can it safely improve outcomes?.  Crit Care Clin. 2010;  26 (3) 467-480 viii
• 119 Al-Omran M, Albalawi Z H, Tashkandi M F, Al-Ansary L A. Enteral versus parenteral nutrition for acute pancreatitis.  Cochrane Database Syst Rev. 2010;  (1) CD002837
• 120 van Saene H K, Petros A J, Ramsay G, Baxby D. All great truths are iconoclastic: selective decontamination of the digestive tract moves from heresy to level 1 truth.  Intensive Care Med. 2003;  29 (5) 677-690
• 121 Silvestri L, van Saene H K, Zandstra D F, Marshall J C, Gregori D, Gullo A. Impact of selective decontamination of the digestive tract on multiple organ dysfunction syndrome: systematic review of randomized controlled trials.  Crit Care Med. 2010;  38 (5) 1370-1376
• 122 de Smet A M, Kluytmans J A, Cooper B S et al.. Decontamination of the digestive tract and oropharynx in ICU patients.  N Engl J Med. 2009;  360 (1) 20-31
• 123 Chan E Y, Ruest A, Meade M O, Cook D J. Oral decontamination for prevention of pneumonia in mechanically ventilated adults: systematic review and meta-analysis.  BMJ. 2007;  334 (7599) 889-900
• 124 Fedorak R N. Probiotics in the management of ulcerative colitis.  Gastroenterol Hepatol (N Y). 2010;  6 (11) 688-690
• 125 O'Flaherty S, Saulnier D M, Pot B, Versalovic J. How can probiotics and prebiotics impact mucosal immunity?.  Gut Microbes. 2010;  1 (5) 293-300
• 126 Alberda C, Gramlich L, Meddings J et al.. Effects of probiotic therapy in critically ill patients: a randomized, double-blind, placebo-controlled trial.  Am J Clin Nutr. 2007;  85 (3) 816-823
• 127 McNabb B, Isakow W. Probiotics for the prevention of nosocomial pneumonia: current evidence and opinions.  Curr Opin Pulm Med. 2008;  14 (3) 168-175
• 128 Jacobi C A, Schulz C, Malfertheiner P. Treating critically ill patients with probiotics: Beneficial or dangerous?.  Gut Pathog. 2011;  3 (1) 2-7
• 129 Besselink M G, van Santvoort H C, Buskens E Dutch Acute Pancreatitis Study Group et al. Probiotic prophylaxis in predicted severe acute pancreatitis: a randomised, double-blind, placebo-controlled trial.  Lancet. 2008;  371 (9613) 651-659
• 130 Duggan C, Gannon J, Walker W A. Protective nutrients and functional foods for the gastrointestinal tract.  Am J Clin Nutr. 2002;  75 (5) 789-808
• 131 Lardy H, Mouillé B, Thomas M et al.. Enterocyte metabolism during early adaptation after extensive intestinal resection in a rat model.  Surgery. 2004;  135 (6) 649-656
• 132 Hayashi Y, Sawa Y, Fukuyama N, Nakazawa H, Matsuda H. Preoperative glutamine administration induces heat-shock protein 70 expression and attenuates cardiopulmonary bypass-induced inflammatory response by regulating nitric oxide synthase activity.  Circulation. 2002;  106 (20) 2601-2607
• 133 Wischmeyer P E, Kahana M, Wolfson R, Ren H, Musch M M, Chang E B. Glutamine reduces cytokine release, organ damage, and mortality in a rat model of endotoxemia.  Shock. 2001;  16 (5) 398-402
• 134 Tremel H, Kienle B, Weilemann L S, Stehle P, Fürst P. Glutamine dipeptide-supplemented parenteral nutrition maintains intestinal function in the critically ill.  Gastroenterology. 1994;  107 (6) 1595-1601
• 135 Klimberg V S, Souba W W, Dolson D J et al.. Prophylactic glutamine protects the intestinal mucosa from radiation injury.  Cancer. 1990;  66 (1) 62-68
• 136 Alverdy J C. Effects of glutamine-supplemented diets on immunology of the gut.  JPEN J Parenter Enteral Nutr. 1990;  14 (4, Suppl) 109S-113S
• 137 Ziegler T R, Young L S, Benfell K et al.. Clinical and metabolic efficacy of glutamine-supplemented parenteral nutrition after bone marrow transplantation. A randomized, double-blind, controlled study.  Ann Intern Med. 1992;  116 (10) 821-828
• 138 Wischmeyer P E. Glutamine: mode of action in critical illness.  Crit Care Med. 2007;  35 (9, Suppl) S541-S544
• 139 Novak F, Heyland D K, Avenell A, Drover J W, Su X. Glutamine supplementation in serious illness: a systematic review of the evidence.  Crit Care Med. 2002;  30 (9) 2022-2029
• 140 Gianotti L, Alexander J W, Gennari R, Pyles T, Babcock G F. Oral glutamine decreases bacterial translocation and improves survival in experimental gut-origin sepsis.  JPEN J Parenter Enteral Nutr. 1995;  19 (1) 69-74
• 141 Mizock B A. Immunonutrition and critical illness: an update.  Nutrition. 2010;  26 (7-8) 701-707
• 142 Berthe M C, Darquy S, Breuillard C et al.. High plasma citrulline and arginine levels ensured by sustained-release citrulline supplementation in rats.  Nutrition. 2011 April 8. [Epub ahead of print]
• 143 Bertolini G, Iapichino G, Radrizzani D et al.. Early enteral immunonutrition in patients with severe sepsis: results of an interim analysis of a randomized multicentre clinical trial.  Intensive Care Med. 2003;  29 (5) 834-840
• 144 Marik P E, Zaloga G P. Immunonutrition in critically ill patients: a systematic review and analysis of the literature.  Intensive Care Med. 2008;  34 (11) 1980-1990
• 145 Gopal S, Jayakumar D, Nelson P N. Meta-analysis on the effect of dopexamine on in-hospital mortality.  Anaesthesia. 2009;  64 (6) 589-594