Gut Peptides and Enteral Feeding in Critically Ill Patients: Implications for Gastric Dysmotility and Appetite

  • N. Q. Nguyen
  • R. H. Holloway


While enteral nutrition is the preferred mode of nutritional delivery in the critically ill, adequate delivery of enteral feeds to critically ill patients is frequently hampered by a variety of factors, the most frequent of which is gastric dysmotility. Impaired gastric motor function in these patients not only involves all regions of the stomach but is also associated with an enhanced enterogastric inhibitory feedback. The etiology of impaired gastric motility during critical illness remains unclear. In addition to mechanical ventilation, medication, hyperglycemia, shock, circulating inflammatory cytokines, and the admission diagnosis, a number of recent findings suggest that disturbances to the gastrointestinal hormones which mediate enterogastric feedback inhibition may be important. The motor abnormalities that have been identified in both proximal and distal regions of the stomach in response to small intestinal nutrient stimulation are consistent with enhanced enterogastric inhibitory effects. Plasma levels of the two major gastrointestinal hormones, cholecystokinin (CCK) and peptide YY (PYY), that mediate this enterogastric feedback are significantly elevated in critically ill patients. More importantly, both fasting and nutrient-stimulated plasma concentrations of CCK and PYY are higher in patients with delayed gastric emptying, and there is an inverse relationship between the rate of gastric emptying and both the plasma levels as well as the integrated changes in the plasma levels of CCK and PYY. These findings strongly support the potential role of plasma CCK and PYY in the pathogenesis of gastric dysmotility in critically ill patients.


Gastric Emptying Critical Illness Enteral Nutrition Delayed Gastric Emptying Migrate Motor Complex 
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.



Intensive care unit




Peptide YY


Glucagons-like peptide 1


Isolated pyloric pressure wave


Migrating motor complex




  1. Adrian TE, Ferri GL, Bacarese-Hamilton AJ, Fuessl HS, Polak JM, Bloom SR. Human distribution and release of a putative new gut hormone, peptide YY. Gastroenterology. 1985;89:1070–7.PubMedGoogle Scholar
  2. Alpers DH. Enteral feeding and gut atrophy. Cur Op Clin Nutr Metab Care. 2002;5:679–83.CrossRefGoogle Scholar
  3. Artinian V, Krayem H, DiGiovine B. Effects of early enteral feeding on the outcome of critically ill mechanically ventilated medical patients. Chest. 2006;129:960–7.PubMedCrossRefGoogle Scholar
  4. Berger MM, Chiolero RL, Pannatier A, Cayeux MC, Tappy L. A 10-year survey of nutritional support in a surgical ICU: 1986–1995. Nutrition. 1997;13:870–7.PubMedCrossRefGoogle Scholar
  5. Bosscha K, Nieuwenhuijs V, Vos A, Samsom M, Roelof J, Akkermans L. Gastrointestinal motility and gastric tube feeding in mechanically ventilated patients. Crit Care Med. 1998;26:1510–17.PubMedCrossRefGoogle Scholar
  6. Brener W, Hendrix TR, McHugh PR. Regulation of the gastric emptying of glucose. Gastroenterology. 1983;85:76–82.PubMedGoogle Scholar
  7. Chapman M, Fraser R, Vozzo R, Bryant L, Tam W, Nguyen N, Zacharakis B, Butler R, Davidson G, Horowitz M. Antro-pyloro-duodenal motor responses to gastric and duodenal nutrient in critically ill patients. Gut. 2005;54:1384–90.PubMedCrossRefGoogle Scholar
  8. Chapman MJ, Fraser RJ, Bryant LK, Vozzo R, Nguyen NQ, Tam W, Zacharakis B, Davidson G, Butler R, Horowitz M. Gastric emptying and the organization of antro-duodenal pressures in the critically ill. Neurogastroenterol Motil. 2008;20:27–35.PubMedCrossRefGoogle Scholar
  9. Corazziari E, Ricci R, Biliotti D, Bontempo I, De Medici A, Pallotta N,Torsoli A. Oral administration of loxiglumide (CCK antagonist) inhibits postprandial gallbladder contraction without affecting gastric emptying. Dig Dis Sci. 1990;35:50–54.PubMedCrossRefGoogle Scholar
  10. Corvilain B, Abramonwicz M, Fery Y, Schoutens A, Verlinden M, Balase E, Horowitz M. Effect of short term starvation on gastric emptying in humans: relationship to oral glucose tolerance. Am J Physiol. 1995;269:G512–7.PubMedGoogle Scholar
  11. Dive A, Moulart M, Jonard P, Jamart J, Mahieu P. Gastroduodenal motility in mechanically ventilated critically ill patients: a manometric study. Crit Care Med. 1994;22:441–7.PubMedCrossRefGoogle Scholar
  12. Dive A, Michel I, Galanti L, Jamart J, Vander Borght T, Installe E. Gastric acidity and duodenogastric reflux during nasojejunal tube feeding in mechanically ventilated patients. Intensive Care Med. 1999;25:574–80.PubMedCrossRefGoogle Scholar
  13. Doig AK, Simpson F. Evidence-based guidelines for nutritional support of the critically ill: results of a bi-national guideline development conference.; 2005.
  14. Doig AK, Simpson F, Delaney A. A review of the true methodological quality of nutritional support trials conducted in the critically ill: time for improvement. Anaesth Analg. 2005;100:527–33.CrossRefGoogle Scholar
  15. Dubois A, Henry DP, Kopin IJ. Plasma catecholamines and postoperative gastric emptying and small intestinal propulsion in the rat. Gastroenterology. 1975;68:466–9.PubMedGoogle Scholar
  16. Fraser R, Fone D, Horowitz M, Dent J. Cholecystokinin octapeptide stimulates phasic and tonic pyloric motility in healthy humans. Gut. 1993;34:33–7.PubMedCrossRefGoogle Scholar
  17. Fried M, Erlacher U, Schwizer W, Lochner C, Koerfer J, Beglinger C, Jansen JB, Lamers CB, Harder F, Bischof-Delaloye A, 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;101:503–11.PubMedGoogle Scholar
  18. Greeley GH, Jr., Jeng YJ, Gomez G, Hashimoto T, Hill FL, Kern K, Kurosky T, Chuo HF, Thompson JC. Evidence for regulation of peptide-YY release by the proximal gut. Endocrinology. 1989;124:1438–43.PubMedCrossRefGoogle Scholar
  19. Grossman MI. Candidate hormones of the gut. Gastroenterology. 1974;67:730–55.PubMedGoogle Scholar
  20. Harrington L. Nutrition in critically ill adults: key processes and outcomes. Crit Care Nurs Clin N Am. 2004;16:459–65.Google Scholar
  21. Hernandez G, Velasco N, Wainstein C, Castillo L, Bugedo G, Maiz A, Lopez F, Guzman S, Vargas C. Gut mucosal atrophy after a short enteral fasting period in critically ill patients. J Crit Care. 1999;14:73–7.PubMedCrossRefGoogle Scholar
  22. Heyland D. Nutritional support in the critically ill patients. A critical review of the evidence. Crit Care Clin. 1998;14:423–40.PubMedCrossRefGoogle Scholar
  23. Heyland D, Cook DJ, Winder B, Brylowski L, Van demark H, Guyatt G. Enteral nutrition in the critically ill patient: a prospective survey. Crit Care Med. 1995;23:1055–60.PubMedCrossRefGoogle Scholar
  24. Heyland D, Dhaliwal R, Drover JW, Gramlich L, Dodek P. Canadian Critical Care Clinical Practice Guidelines. Canadian clinical practice guidelines for nutrition support in mechanically ventilated, critically ill adult patients. JPEN J Parenter Enteral Nutr. 2003;27:355–73.PubMedCrossRefGoogle Scholar
  25. Heyland DK, Tougas G, King D, Cook DJ. Impaired gastric emptying in mechanically ventilated, critically ill patients. Intensive Care Med. 1996;22:1339–44.PubMedCrossRefGoogle Scholar
  26. Heyland DK, MacDonald S, Keefe L, Drover JW. Total parenteral nutrition in the critically ill patient: a meta-analysis. JAMA. 1998;280:2013–9.PubMedCrossRefGoogle Scholar
  27. Horowitz M, Dent J, Fraser R, Sun W, Hebbard G. Role and integration of mechanisms controlling gastric emptying. Dig Dis Sci. 1994;39:7S–13S.PubMedCrossRefGoogle Scholar
  28. Kao C, Changlai S, Chieng P, Yen T. Gastric emptying in head-injury patients. Am J Gastroenterol. 1998;93:1108–12.PubMedCrossRefGoogle Scholar
  29. Kelly KA. Gastric emptying of liquids and solids: roles of proximal and distal stomach. Am J Physiol. 1980;239:G71–6.PubMedGoogle Scholar
  30. King PM, Heading RC, Pryde A. Coordinated motor activity of the human gastroduodenal region. Dig Dis Sci. 1985;30:219–24.PubMedCrossRefGoogle Scholar
  31. Kreiss C, Schwizer W, Borovicka J, Jansen JB, Bouloux C, Pignol R, Bischof Delaloye A, Fried M. Effect of lintitript, a new CCK-A receptor antagonist, on gastric emptying of a solid-liquid meal in humans. Regul Pept. 1998;74:143–9.PubMedCrossRefGoogle Scholar
  32. Kudsk K, Croce MA, Fabian TC. Enteral versus parenteral feeding: effects on septic morbidity after blunt and penetrating abdominal trauma. Ann Surg. 1992;215:503–11.PubMedCrossRefGoogle Scholar
  33. le Roux CW, Ghatei MA, Gibbs JS, Bloom SR. The putative satiety hormone PYY is raised in cardiac cachexia associated with primary pulmonary hypertension. Heart. 2005;91:241–2.PubMedCrossRefGoogle Scholar
  34. Ledeboer M, Masclee AA, Coenraad M, Vecht J, Biemond I, Lamers CB. Antroduodenal motility and small bowel transit during continuous intraduodenal or intragastric administration of enteral nutrition. Eur J Clin Invest. 1999;29:615–23.PubMedCrossRefGoogle Scholar
  35. Liddle RA, Gertz BJ, Kanayama S, Beccaria L, Coker LD, Turnbull TA, Morita ET. Effects of a novel cholecystokinin (CCK) receptor antagonist, MK-329, on gallbladder contraction and gastric emptying in humans. Implications for the physiology of CCK. J Clin Invest. 1989;84:1220–5.PubMedCrossRefGoogle Scholar
  36. Liddle RA, Morita ET, Conrad CK, Williams JA. Regulation of gastric emptying in humans by cholecystokinin. J Clin Invest. 1986;77:992–6.PubMedCrossRefGoogle Scholar
  37. Lin HC, Doty JE, Reedy TJ, Meyer JH. Inhibition of gastric emptying by glucose depends on length of intestine exposed to nutrient. Am J Physiol. 1989;256:G404–11.PubMedGoogle Scholar
  38. Lin HC, Chey WY, Zhao X. Release of distal gut peptide YY (PYY) by fat in proximal gut depends on CCK. Peptides. 2000;21:1561–3.PubMedCrossRefGoogle Scholar
  39. Lundberg JM, Tatemoto K, Terenius L, Hellstrom PM, Mutt V, Hokfelt T, Hamberger B. Localization of peptide YY (PYY) in gastrointestinal endocrine cells and effects on intestinal blood flow and motility. Proc Nat Acad Scie USA. 1982;79:4471–5.CrossRefGoogle Scholar
  40. MacIntosh CG, Andrews JM, Jones KL, Wishart JM, Morris HA, Jansen JB, Morley JE, Horowitz M, Chapman IM. Effects of age on concentrations of plasma cholecystokinin, glucagon-like peptide 1, and peptide YY and their relation to appetite and pyloric motility. Am J Clin Nutr. 1999;69:999–1006.PubMedGoogle Scholar
  41. McClave SA, Sexton LK, Spain DA, Adams JL, Owens NA, Sullins MB, Blandford BS, Snider HL. Enteral tube feeding in the intensive care unit: factors impeding adequate delivery. Crit Care Med. 1999;27:1252–6.PubMedCrossRefGoogle Scholar
  42. McDermott JR, Leslie FC, D’Amato M, Thompson DG, Grencis RK, McLaughlin JT. Immune control of food intake: enteroendocrine cells are regulated by CD4+ T lymphocytes during small intestinal inflammation. Gut. 2006;55:492–7.PubMedCrossRefGoogle Scholar
  43. McWhirter JP, Pennington CR. Incidence and recognition of malnutrition in hospital. BMJ. 1994;308:945–8.PubMedCrossRefGoogle Scholar
  44. Mentec H, Dupont H, Bocchetti M, Cani P, Ponche F, Bleichner G. Upper digestive intolerance during enteral nutrition in critically ill patients: frequency, risk factors, and complications. Crit Care Med. 2001;29:1955–61.PubMedCrossRefGoogle Scholar
  45. Mesquita MA, Thompson DG, Troncon LE, D’Amato M, Rovati LC, Barlow J. Effect of cholecystokinin-A receptor blockade on lipid-induced gastric relaxation in humans. Am J Physiol. 1997;273:G118–23.PubMedGoogle Scholar
  46. Minard G, Kudsk KA, Melton S, Patton JH, Tolley EA. Early versus delayed feeding with an immune-enhancing diet in patients with severe head injuries. JPEN J Parenter Enteral Nutr. 2000;24:145–9.PubMedCrossRefGoogle Scholar
  47. Montejo JC. Enteral nutrition-related gastrointestinal complications in critically ill patients: a multicenter study. The Nutritional and Metabolic Working Group of the Spanish Society of Intensive Care Medicine and Coronary Units. Crit Care Med. 1999;27:1447–53.PubMedCrossRefGoogle Scholar
  48. Moran TH, McHugh PR. Cholecystokinin suppresses food intake by inhibiting gastric emptying. Am J Physiol. 1982;242:R491–7.PubMedGoogle Scholar
  49. Murray CD, Martin NM, Patterson M, Taylor SA, Ghatei MA, Kamm MA, Johnston C, Bloom SR, Emmanuel AV. Ghrelin enhances gastric emptying in diabetic gastroparesis: a double blind, placebo controlled, crossover study. Gut. 2005;54:1693–8.PubMedCrossRefGoogle Scholar
  50. Mutlu GM, Mutlu EA, Factor P. GI complications in patients receiving mechanical ventilation. Chest. 2001;119:1222–41.PubMedCrossRefGoogle Scholar
  51. Naslund E, Gryback P, Backman L, Jacobsson H, Holst JJ, Theodorsson JJ, Hellstrom PM. Distal small bowel hormones: correlation with fasting antroduodenal motility and gastric emptying. Dig Dis Sci. 1998;43:945–52.PubMedCrossRefGoogle Scholar
  52. Nematy M, O’Flynn J, Wandrag L, Brynes A, Brett S, Patterson M, Ghateir M, Bloom S, Frost G. Changes in appetite related gut hormones in intensive care unit patients: a pilot cohort study. Crit Care. 2005;10:R1–10.CrossRefGoogle Scholar
  53. Nguyen NQ, Fraser RJ, Chapman M, Bryant LK, Holloway RH, Vozzo R, Feinle-Bisset C. Proximal gastric response to small intestinal nutrients is abnormal in mechanically ventilated critically ill patients. World J Gastroenterol. 2006a;12:4383–8.PubMedGoogle Scholar
  54. Nguyen NQ, Fraser RJ, Chapman M, Bryant LK, Wishart J, Holloway RH, Horowitz M. Fasting and nutrient-stimulated plasma peptide-YY levels are elevated in critical illness and associated with feed intolerance: an observational, controlled study. Crit Care. 2006b;10:R175.PubMedCrossRefGoogle Scholar
  55. Nguyen NQ, Fraser RJ, Bryant LK, Chapman M, Holloway RH. Proximal gastric motility in critically ill patients with type 2 diabetes mellitus. World J Gastroenterol. 2007a;13:270–5.PubMedGoogle Scholar
  56. Nguyen NQ, Fraser RJ, Bryant LK, Chapman MJ, Wishart J, Holloway RH, Butler R, Horowitz M. The relationship between gastric emptying, plasma cholecystokinin, and peptide YY in critically ill patients. Crit Care. 2007b;11:R132.PubMedCrossRefGoogle Scholar
  57. Nguyen NQ, Fraser RJ, Chapman MJ, Bryant LK, Holloway RH, Vozzo R, Wishart J, Feinle-Bisset C, Horowitz M. Feed intolerance in critical illness is associated with increased basal and nutrient-stimulated plasma cholecystokinin concentrations. Crit Care Med. 2007c;35:82–8.PubMedCrossRefGoogle Scholar
  58. Nguyen NQ, Ng MP, Chapman M, Fraser RJ, Holloway RH. The impact of admission diagnosis on gastric emptying in critically ill patients. Crit Care. 2007d;11:R16.PubMedCrossRefGoogle Scholar
  59. Nguyen NQ, Chapman MJ, Fraser RJ, Bryant LK, Burgstad C, Ching K, Bellon M, Holloway RH. The effects of sedation on gastric emptying and intra-gastric meal distribution in critical illness. Intensive Care Med. 2008a;34:454–60.PubMedCrossRefGoogle Scholar
  60. Nguyen NQ, Fraser RJ, Bryant LK, Burgstad C, Chapman MJ, Bellon M, Wishart J, Holloway RH, Horowitz M. The impact of delaying enteral feeding on gastric emptying, plasma cholecystokinin, and peptide YY concentrations in critically ill patients. Crit Care Med. 2008b;36:1469–74.PubMedCrossRefGoogle Scholar
  61. Nguyen NQ, Fraser RJ, Bryant LK, Chapman M, Holloway RH. Diminished functional association between proximal and distal gastric motility in critically ill patients. Intensive Care Med. 2008c;34:1246–55.PubMedCrossRefGoogle Scholar
  62. Pironi L, Stanghellini V, Miglioli M, Corinaldesi R, De Giorgio R, Ruggeri E, Tosetti C, Poggioli G, Morselli Labate AM, Monetti N, et al. Fat-induced ileal brake in humans: a dose-dependent phenomenon correlated to the plasma levels of peptide YY. Gastroenterology. 1993;105:733–9.PubMedGoogle Scholar
  63. Quirk J. Malnutrition in critically ill patients in intensive care units. Br J Nursing. 2000;9:537–41.Google Scholar
  64. Ritz MA, Fraser R, Edwards N, Di Matteo AC, Chapman M, Butler R, Cmielewski P, Tournadre JP, Davidson G, Dent J. Delayed gastric emptying in ventilated critically ill patients: measurement by 13 C-octanoic acid breath test. Crit Care Med. 2001;29:1744–9.PubMedCrossRefGoogle Scholar
  65. Souba WW. Cytokine control of nutrition and metabolism in critical illness. Curr Prob Surg. 1994;31:577–643.CrossRefGoogle Scholar
  66. Straathof JW, Mearadji B, Lamers CB, Masclee AA. Effect of CCK on proximal gastric motor function in humans. Am J Physiol. 1998;274:G939–44.PubMedGoogle Scholar
  67. Tarling MM, Toner CC, Withington PS, Baxter MK, Whelpton R, Goldhill DR. A model of gastric emptying using paracetamol absorption in intensive care patients. Intensive Care Med. 1997;23:256–60.PubMedCrossRefGoogle Scholar
  68. Thomas L., Robert D. Nutritional status and body composition in critically ill patients. Relationship between results and mortality. Am J Clin Nutr. 1979;32:510–11.PubMedGoogle Scholar
  69. White CM, Poxon V, Alexander-Williams J. A study of motility of normal human gastroduodenal region. Dig Dis Sci. 1981;26:609–17.PubMedCrossRefGoogle Scholar
  70. Yuan C, Foss J, O’Connor M, Roizen M, Moss J. Effects of low-dose morphine on gastric emptying in healthy volunteers. J Clin Pharmacol. 1998;38:1017–20.PubMedCrossRefGoogle Scholar

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© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  1. 1.Department of Gastroenterology and HepatologyRoyal Adelaide HospitalAdelaideAustralia

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