Background: Altered concentrations of ghrelin, motilin, and cholecystokinin (CCK) may contribute to gastric hypomotility. The aims of this study were to evaluate the concentrations of these hormones in patients tolerant and intolerant to gastric nutrition, assess the influence of prokinetic therapy on these hormone concentrations, determine the associations between these mediators and gastric emptying, and evaluate whether inflammation influences their concentrations. Methods: Post hoc analyses of 2 prospective studies that enrolled 20 critically ill patients with an aspirated gastric residual (GR) >150 mL while receiving gastric enteral nutrition (intolerant group) and 10 critically ill patients with minimal GR (tolerant group). Patients with intolerance were also assessed 1 day after prokinetic therapy. Fasting serum concentrations of total ghrelin, acyl ghrelin (active), des-acyl ghrelin (inactive), motilin, CCK, and tumor necrosis factor (TNF)−α were determined. Gastric emptying was assessed concurrently using the acetaminophen absorption method. Results: Compared to the tolerant group, the intolerant group had higher total ghrelin (1324.8 ± 1204.6 vs 285.1 ± 132.5 pg/mL; P < .001), lower acyl ghrelin (70.5 ± 65.4 vs 208.5 ± 186.9 pg/mL; P < .05), and lower acyl ghrelin to des-acyl ghrelin ratio (1.11 ± 1.35 vs 3.47 ± 3.21 pg/mL; P < .05). Concentrations of other hormones and TNF-α were similar. Despite accelerated gastric emptying after prokinetic therapy, concentrations of all hormones and TNF-α were similar to baseline values. Hormone concentrations were not associated with gastric emptying or TNF-α. Conclusion: Patients intolerant to gastric nutrition generate less acyl ghrelin, which may contribute to gastric hypomotility. Intolerance is not associated with altered concentrations of other hormones. Hormone concentrations are not influenced by prokinetic therapy.
McClaveSADeMeoMTDeLegge. North American Summit on aspiration in the critically ill patient: consensus statement. JPEN J Parenter Enteral Nutr. 2002;26(6)(suppl):S80-S85.
StroudMDuncanHNightingaleJ; British Society of Gastroenterology. Guidelines for enteral feeding in adult hospital patients. Gut. 2003;52(suppl 7):vii7-vii12.
4.
HeylandDKDhaliwalRDroverJW; 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.
5.
KompanLKremzarBGadzijevEProsekM. 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.
6.
DoigGSHeighesPTSimpsonFSweetmanEADaviesAR. Early enteral nutrition, provided within 24 h of injury or intensive care unit admission, significantly reduces mortality in critically ill patients: a meta-analysis of randomised controlled trials. Intensive Care Med. 2009;35:2018-2027.
7.
MarikPEZalogaGP. Early enteral nutrition in acutely ill patients: a systematic review. Crit Care Med. 2001;26:2264-2270.
8.
ArtinianVKrayemHDiGiovineB. Effects of early enteral feeding on the outcomes of critically ill mechanically ventilated medical patients. Chest. 2006;129:960-967.
9.
ChapmanMJNguyenNQFraserRJ. Gastrointestinal motility and prokinetics in the critically ill. Curr Opin Crit Care. 2007;13:187-194.
10.
FruhwaldSHolzerPMetzlerH. Intestinal motility disturbances in intensive care patients: pathogenesis and clinical impact. Intensive Care Med. 2007;33:36-44.
11.
DeaneAChapmanMJFraserRJBryantLKBurgstadCNguyenNQ. Mechanisms underlying feed intolerance in the critically ill: implications for treatment. World J Gastroenterol. 2007;13:3909-3917.
12.
MutluGMMutluEAFactorP. GI complications in patients receiving mechanical ventilation. Chest. 2001;119:1222-1241.
13.
DiveAMoulartMJonardPJamartJMahieuP. Gastroduodenal motility in mechanically ventilated critically ill patients: a manometric study. Crit Care Med. 1994;22:441-447.
14.
HeylandDKTougasGKingDCookDJ. Impaired gastric emptying in mechanically ventilated, critically ill patients. Intensive Care Med. 1996;22:1339-1344.
15.
RitzMAFraserREdwardsN. Delayed gastric emptying in ventilated critically ill patients: measurement by 13 C-octanoic acid breath test. Crit Care Med. 2001;29:1744-1749.
16.
MontejoJC; for the Nutritional and Metabolic Working Group of the Spanish Society of Intensive Care Medicine and Coronary Units. Enteral nutrition-related gastrointestinal complications in critically ill patients: a multicenter study. Crit Care Med. 1999;27:1447-1453.
17.
ChangRWSJacobsSLeeB. Gastrointestinal dysfunction among intensive care unit patients. Crit Care Med. 1987;15:909-914.
18.
HeylandDCookDJWinderBBrylowskiLVan deMarkHGuyattG. Enteral nutrition in the critically ill patient: a prospective survey. Crit Care Med. 1995;23:1055-1060.
19.
BinnekadeJMTepaskeRBruynzeelPMathus-VliegenEMdeHannRJ. Daily enteral feeding practice on the ICU: attainment of goals and interfering factors. Crit Care. 2005;9:R218-R225.
20.
AdamSBatsonS. A study of problems associated with the delivery of enteral feed in critically ill patients in five ICUs in the UK. Intensive Care Med. 1997;23:261-266.
21.
McClaveSASextonLKSpainDA. Enteral tube feeding in the intensive care unit: factors impeding adequate delivery. Crit Care Med. 1999;27:1252-1256.
HeylandDKDhaliwalRDayAJainMDroverJ. Validation of the Canadian clinical practice guidelines for nutrition support in mechanically ventilated, critically ill adult patients: results of a prospective observational study. Crit Care Med. 2004;32:2260-2266.
24.
HeylandDKSchroter-NoppeDDroverJW. Nutrition support in the critical care setting: current practice in Canadian ICUs—opportunities for improvement?JPEN J Parenter Enteral Nutr. 2003;27:74-83.
25.
BosschaKNieuwenhuijsVBVosASamsomMRoelofsJMAkkermansLM. Gastrointestinal motility and gastric tube feeding in mechanically ventilated patients. Crit Care Med. 1998;26(9):1510-1517.
26.
MentecHDupontHBocchettiMCaniPPoncheFBleichnerG. Upper digestive intolerance during enteral nutrition in critically ill patients: frequency, risk factors, and complications. Crit Care Med. 2001;29:1955-1961.
27.
InglisTJSherrattMJSproatLJGibsonJSHawkeyPM. Gastroduodenal dysfunction and bacterial colonisation of the ventilated lung. Lancet. 1993;341:911-913.
28.
KaziNMobarhanS. Enteral feeding associated gastroesophageal reflux and aspiration pneumonia: a review. Nutr Rev. 1996;54:324-328.
29.
MacLarenR. Intolerance to intragastric enteral nutrition in critically ill patients: complications and management. Pharmacotherapy. 2000;20:1486-1498.
30.
MethenyNASchallomMEEdwardsSJ. Effect of gastrointestinal motility and feeding tube site on aspiration risk in critically ill patients: a review. Heart Lung. 2004;33:131-145.
31.
DodekPKeenanSCookD; Canadian Critical Care Trials Group; Canadian Critical Care Society. Evidence-based clinical practice guideline for the prevention of ventilator-associated pneumonia. Ann Intern Med. 2004;141:305-313.
32.
American Thoracic Society, Infectious Diseases Society of America. Guidelines for the management of adults with hospital-acquired, ventilator-associated, and healthcare-associated pneumonia. Am J Respir Crit Care Med. 2005;171:388-416.
33.
NguyenNQFraserRJChapmanM. Fasting and nutrient-stimulated plasma peptide-YY levels are elevated in critical illness, and associated with feed intolerance: an observational, controlled study. Crit Care. 2006;10:R175-R184.
34.
NguyenNQFraserRJBryantLK. The impact of delaying enteral feeding on gastric emptying, plasma cholecystokinin, and peptide YY concentrations in critically ill patients. Crit Care Med. 2008;26:1469-1474.
35.
NguyenNQFraserRJBryantLK. The relationship between gastric emptying, plasma cholecystokinin, and peptide YY in critically ill patients. Crit Care. 2007;11:R132-R140.
36.
NguyenNQFraserRJChapmanMJ. Feed intolerance in critical illness is associated with increased basal and nutrient-stimulated plasma cholecystokinin concentrations. Crit Care Med. 2007;35:82-88.
37.
De SmetBMitselosADepoortereI. Motilin and ghrelin as prokinetic drug targets. Pharmacol Ther. 2009;123:207-223.
38.
OhnoTMochikiEKuwanoH. The roles of motilin and ghrelin in gastrointestinal motility. Int J Pept. 2010;2010:1-6.
39.
CamilleriMPapathanasopoulosAOdunsiST. Actions and therapeutic pathways of ghrelin for gastrointestinal disorders. Nat Rev Gastroenterol Hepatol. 2009;6:343-352.
40.
ChenCYAsakawaAFujimiyaMLeeSDInuiA. Ghrelin gene products and the regulation of food intake and gut motility. Pharmacol Rev. 2009;61:430-481.
41.
KageyamaHTakenoyaFShibaKShiodaS. Neuronal circuits involving ghrelin in the hypothalamus-mediated regulation of feeding. Neuropeptides. 2010;44:133-138.
42.
UenoHShiiyaTNakazatoM. Translational research of ghrelin. Ann N Y Acad Sci. 2010;1200:120-127.
43.
LeeSHKimYDKongYH. The relevance of serum ghrelin concentration to severity of acute pancreatitis. Gut Liver. 2010;4:234-210.
44.
KadoglouNPLampropoulosSKapelouzouA. Serum levels of apelin and ghrelin in patients with acute coronary syndromes and established coronary artery disease—KOZANI STUDY. Transl Res. 2010;155:238-246.
45.
KochASansonEHelmAVoigtSTrautweinCTackeF. Regulation and prognostic relevance of serum ghrelin concentrations in critical illness and sepsis. Crit Care. 2010;14:R94-R103.
46.
LandzinskiJKiserTHFishDNWischmeyerPEMacLarenR. Gastric motility function in critically ill patients tolerant versus intolerant to gastric nutrition. JPEN J Parenter Enteral Nutr. 2008;32:45-50.
47.
MacLarenRKiserTHFishDNWischmeyerPE. Erythromycin versus metoclopramide for facilitating gastric emptying and tolerance to intragastric nutrition. JPEN J Parenter Enteral Nutr. 2008;32:412-419.
48.
RomeroAKirchnerHHeppnerKPflugerPTTschöpMHNogueirasR. GOAT: the master switch for the ghrelin system?Eur J Endocrinol. 2010;163:1-8.
49.
SchmidtAFabriziiVMaierC. Normal regulation of elevated plasma ghrelin concentrations in dialysis patients. Wien Klin Wochenschr. 2004;116:235-239.
50.
GoodyearSJMottersheadMSungEZ. Dysregulation of plasma ghrelin in alcoholic cirrhosis. Clin Endocrinol. 2010;73:323-329.
51.
El-ShehabyAMObaiaEMAlwakilSSHiekalAA. Total and acylated ghrelin in liver cirrhosis: correlation with clinical and nutritional status. Scand J Clin Lab Invest. 2010;70:252-258.
52.
TackeFBrabantGKruckE. Ghrelin in chronic liver disease. J Hepatol. 2003;38:447-454.
53.
YalnizMBahceciogluIHAtasevenH. Serum adipokine and ghrelin levels in nonalcoholic steatohepatitis. Mediators Inflamm. 2006;2006:78360.
54.
CohenRITsangDKoenigSWilsonDMcCloskeyTChandraS. Plasma ghrelin and leptin in adult cystic fibrosis patients. J Cyst Fibros. 2008;7:298-402.
55.
NematyMBrynesAEHornickPI. Postprandial ghrelin suppression is exaggerated following major surgery: implications for nutritional recovery. Nutr Metab. 2007;4:20.
56.
NematyMO’FlynnJEWandragL. Changes in appetite related gut hormones in intensive care unit patients: a pilot cohort study. Crit Care. 2006;10:R10-R19.
57.
NguyenNQFraserRJBryantLKChapmanMHollowayRH. Diminished functional association between proximal and distal gastric motility in critically ill patients. Intensive Care Med. 2008;34:1246-1255.
58.
ChenZWangSYuBLiA. A comparison study between early enteral nutrition and parenteral nutrition in severe burn patients. Burns. 2007;33:708-712.
59.
McClaveSASniderHL. Clinical use of gastric residual volumes as a monitor for patients on enteral tube feeding. JPEN J Parenter Enteral Nutr. 2002;26(suppl):S43-S50.
60.
MethenyNA. Preventing respiratory complications of tube feedings: evidence-based practice. Am J Crit Care. 2006;15:360-369.
61.
MallampalliAMcClaveSASniderHL. Defining tolerance to enteral feeding in the intensive care unit. Clin Nutr. 2000;19:213-215.
62.
McClaveSALukanJKStefaterJA. Poor validity of residual volumes as a marker for risk of aspiration in critically ill patients. Crit Care Med. 2005;33:324-330.
63.
MethenyNAClouseREChangYHStewartBJOliverDAKollefMH. Tracheobronchial aspiration of gastric contents in critically ill tube-fed patients: frequency, outcomes, and risk factors. Crit Care Med. 2006;34:1007-1015.
64.
MontejoJCMinambresEBordejeL. Gastric residual volume during enteral nutrition in ICU patients: the REGANE study. Intensive Care Med. 2010;36:1386-1393.
65.
TaylorSJFettesSBJewkesCNelsonRJ. Prospective, randomized, controlled trial to determine the effect of early enhanced enteral nutrition on clinical outcome in mechanically ventilated patients suffering head injury. Crit Care Med. 1999;27:2525-2531.
66.
PinillaJCSamphireJArnoldCLiuLThiessenB. Comparison of gastrointestinal tolerance to two enteral feeding protocols in critically ill patients: a prospective, randomized controlled trial. JPEN J Parenter Enteral Nutr. 2001;25:81-86.
67.
PoulardFDimetJMartin-LefevreL. Impact of not measuring residual gastric volume in mechanically ventilated patients receiving early enteral feeding: a prospective before-after study. JPEN J Parenter Enteral Nutr. 2010;34:125-130.
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