Critically ill patients often suffer from gastrointestinal problems including high gastric residual volumes as well as diarrhoea and constipation.1–4 The presence of gastrointestinal complications is associated with poor clinical outcomes and poor nutritional intake.
“Intolerance occurs frequently during Enteral Nutrition in critically ill patients and is associated with poorer nutrition and clinical outcomes.”
Original communication by Gungabissoon et all JPEN 20155
The unique protein blend P4 reduces gastric residual volumes
The third most important guideline on how to feed critically ill patients according the 2016 nutritional guidelines developed by the Society of Critical Care Medicine and American Society of Parenteral and Enteral Nutrition (SCCM/ASPEN), indicates the steps that should be taken to improve tolerance to gastric feeding. Danone Nutricia Research has developed the new unique protein blend not only to improve the amino acid quality but also to improve tolerance to gastric feeding .
Patient insights have shown that casein coagulates in the stomach due to its precipitation by gastric acid, while whey protein does not6. As a result, gastric emptying of casein is slower compared to whey. Due to the casein clots, gastric emptying of casein is similar to solids, while gastric emptying of whey is similar to liquids and therefore faster. Following the principles of coagulation by gastric acid, at Danone Nutricia Research we performed different in-vitro digestion tests showing that the vegetable proteins pea and soy are non-coagulating like whey and we confirmed in these models that casein is coagulating. The unique P4 protein blend was also shown to be non-coagulating7. After the initial experiments, tube feeding formulas containing the P4 protein blend have been developed and also tested in different in-vitro digestion models, showing that the P4 containing tube feeding formulas do not coagulate while casein dominant enteral nutrition formulas do coagulate.7
TIM model with outcome picture
The coagulation seen in the in-vitro models have been confirmed by an in-vivo study using MRI technique to measure gastric content8. Furthermore, we tested a high energy tube feed containing the intact whey dominant P4 protein blend by comparing it with two casein dominant tube feeds in a cross-over, randomised intervention trial showing faster gastric emptying measured by MRI techniques.9
The non-coagulating intact whey dominant P4 protein blend with better balanced amino acid pattern (compared to individual protein sources) has been incorporated in most of our tube feeding products.
The unique fibre blend (MF6™) to reduce risk of diarrhoea
Different types of fibres have different effects in the gastrointestinal tract. The soluble and fermentable fibres have important roles in short-chain fatty acid production, maintaining a healthy micro-flora in the gut, fluid and electrolyte absorption and gut integrity. The insoluble fibres play an important role in stool bulking, colon motor activity and bowel transit time. Both are important for the gastrointestinal tract to function properly.10
“One of the key issues of importance in relation to the design of enteral formulae concerns the type and amount of fibre that should be added to the feeds”10
Danone Nutricia Research has developed a unique fibre blend (MF6™) consisting of six different soluble, insoluble, fermentable and non-fermentable fibres. The selection of these six fibres was based on availability in a normal healthy diet and in-vitro digestion experiments at Danone Nutricia Research. The optimal mix was defined having highest short-chain fatty acid production with lowest amount of gas production11. Early clinical trials with MF6™ in healthy volunteers and patients showed positive effects on micro-flora, bowel transit time, diarrhoea and constipation and reduced use of laxatives.12,13,14,15,16,17 A more recent trial comparing the MF6™ containing enteral formula with a fibre-free formula in patients with acute pancreatitis showed less overall complications and shorter hospital stay.18 Furthermore, two recent, randomised clinical trials in hospitalised patients19 and ICU patients showed20 that patients receiving the MF6™ containing enteral formulas had less diarrhoea.
The Danone Nutricia Research contribution to immuno-nutrition guidelines
Improving clinical outcomes by modifying nutritional support towards nutritional therapy by means of immune-modulating nutrition has dominated the scientific agenda in the recent past years. Adding high amounts of anti-oxidants, fish-oils and glutamine to tube-feeding formulas seemed very promising. Previous guidelines indicated that high doses of these nutrients should be considered.21 However, several large randomised clinical trials22,23,24 including the Danone Nutricia Research’ MetaPlus trial with an experimental immune modulating tube feeding formula25 did not show any benefit when using high dosages of these nutrients in ICU patients. A publication of the MetaPlus post-hoc analysis26 as well as a review describing the consequences of the REDOX trial and the MetaPlus trial27 significantly contributed to changing the guidelines, now indicating that immune-modulating enteral formulas should not be used routinely in medical ICU patients28.
Consequences of the REDOXS and METAPLUS Trials: The End of an Era of Glutamine and Antioxidant Supplementation for Critically Ill Patients?
Van Zanten et al, JPEN 201529
Risk factors, clinical consequences, and treatment of enteral feed intolerance during critical illness. Journal of Parenteral and Enteral Nutrition 2015 May;39(4):441-8.
Blaser, A.R. et al. Gastrointestinal function in intensive care patients: terminology, definitions and management. Recommendations of the ESICM Working Group on Abdominal Problems Intensive Care Med (2012) 38:384–394 .
Montejo J.C. et al. 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 Aug;27(8):1447-53.
Mentec, H. Upper digestive intolerance during enteral nutrition in critically ill patients: frequency, risk factors, and complications. Crit Care Med. 2001 Oct;29(10):1955-61.
Gungabissoon, U. et al. Prevalence, risk factors, clinical consequences, and treatment of enteral feed intolerance during critical illness. Journal of Parenteral and Enteral Nutrition 2015 May;39(4):441-8.
Hall, W.L. et al. Casein and whey exert different effects on plasma amino acid profiles, gastrointestinal hormone secretion and appetite. The British Journal of Nutrition 2003 Feb;89(2):239-48.
Van den Braak, C.C. et al. A novel protein mixture containing vegetable proteins renders enteral nutrition products non-coagulating after in vitro gastric digestion. Clinical Nutrition 2013 Oct;32(5):765-71.
M. Klebach et al. Effect of Protein Type in Enteral Nutrition Formulas on Coagulation in the Stomach In Vivo: Post Hoc Analyses of a Randomized Controlled Trial With MRI. Journal of Parenteral and Enteral Nutrition Volume 40 Number 1, January 2016 page134-135.
Kuyumcu, S. et al. Noncoagulating Enteral Formula Can Empty Faster From the Stomach. Journal of Parenteral and Enteral Nutrition 2014; Issue published: July 1, 2015.
Elia, M. et al. Systematic review and meta-analysis: the clinical and physiological effects of fibre-containing enteral formulae by in Alimentation, Pharmacology & Therapeutics 2008 Jan 15;27(2):120-45. .
C. J. GREEN Fibre in enteral nutrition. Clinical Nutrition (2001) 20(Supplement 1): 23-39.
Silk, D.B. et al. The effect of a polymeric enteral formula supplemented with a mixture of six fibres on normal human bowel function and colonic motility. Clin Nutr 2001, 20 (1): 49-58.
Schneider, S.M. et al. Effects of total enteral nutrition supplemented with a multi-fibre mix on faecal short-chain fatty acids and microbiota. Clin Nutr 2006, 25 (1); 82-90.
Hofman Z, van Drunen JDE, Brinkman JG, Valerio PG. Tolerance and efficacy of a multi-fibre enriched tube-feed in paediatric burn patients. Clin Nutr 2001;20 (Suppl 3): 63–64 (abstract).
Trier E, Wells JCK, Thomas AG. Effects of a multifibre supplemented paediatric enteral feed on gastrointestinal function. J Pediatr Gastroenterol Nutr 1999;27:595 (abstract).
Wierdsma NJ, Kruizenga HM, Droop A, Arjaans W, Stok A, van Bokhorst-de van der Schueren M. Voedingsvezel in sondevoeding. Een vergelijking van een voeding met guargom met een voeding met vezelmix (Comparison of two tube feeding formulas enriched with guar gum or mixed dietary fibres). Ned Tijdsch Dietisten 2001;56:243–7.
Daly et al. Is fibre supplementation in paediatric sip feeds beneficial? J Hum Nutr Diet. 2004 Aug;17(4):365-70. .
Karakan, T. Comparison of early enteral nutrition in severe acute pancreatitis with prebiotic fiber supplementation versus standard enteral solution: A prospective randomized double-blind study. World Journal of Gastroenterology 2007 May 21; 13(19): 2733–2737.
Jakobsen, L.H. et al. Gastrointestinal tolerance and plasma status of carotenoids, EPA and DHA with a fiber-enriched tube feed in hospitalized patients initiated on tube nutrition: Randomized controlled trial Clin Nutr. 2017 Apr;36(2):380-388.
Enteral nutrition preference in critical care: fibre-enriched or fibre-free? Hatice Yagmurdur MD, Figen Leblebici MD Asia Pac J Clin Nutr 2016;25(4):740-746.
McClave SA, Martindale RG, Vanek VW, McCarthy M, Roberts P, Taylor B, et al. Guidelines for the Provision and Assessment of Nutrition Support Therapy in the Adult Critically Ill Patient: Society of Critical Care Medicine (SCCM) and American Society for Parenteral and Enteral Nutrition (A.S.P.E.N.). J Parenter Enteral Nutr 2009; 33:277-316.
Andrews PJ, Avenell A, Noble DW, Campbell MK, Croal BL, Simpson WG, et al. Randomised trial of glutamine, selenium, or both, to supplement parenteral nutrition for critically ill patients. BMJ 2011; 342:d1542.
Heyland D, Muscedere J, Wischmeyer PE, Cook D, Jones G, Albert M, et al. A randomized trial of glutamine and antioxidants in critically ill patients. N Engl J Med 2013; 368:1489-97.
Rice TW, Wheeler AP, Thompson BT, deBoisblanc BP, Steingrub J, Rock P. Enteral omega-3 fatty acid, gamma-linolenic acid, and antioxidant supplementation in acute lung injury. JAMA 2011; 306:1574-81.
Arthur R. H. van Zanten et al. High-ProteinEnteralNutritionEnrichedWithImmune-Modulating Nutrients vs Standard High-Protein Enteral Nutrition and Nosocomial Infections in the ICU A Randomized Clinical Trial JAMA. 2014;312(5):514-524. doi:10.1001/jama.2014.7698.
Hofman, Z. et al. Glutamine, fish oil and antioxidants in critical illness: MetaPlus trial post hoc safety analysis. Ann. Intensive Care (2016) 6:119.
Van Zanten AR, Hofman Z, Heyland DK. Consequences of the REDOXS and METAPLUS Trials: The End of an Era of Glutamine and Antioxidant Supplementation for Critically Ill Patients? JPEN J Parenter Enteral Nutr. 2015 Nov;39(8):890-2. Epub 2015 Jan 7. No abstract available.
McClave, S.A. et al. Guidelines for the Provision and Assessment of Nutrition Support Therapy in the Adult Critically Ill Patient. Journal of Parenteral and Enteral Nutrition 2016 Volume: 40 issue: 2, page(s): 159-211.
Consequences of the REDOXS and METAPLUS Trials: The End of an Era of Glutamine and Antioxidant Supplementation for Critically Ill Patients? Van Zanten AR, Hofman Z, Heyland DK. JPEN J Parenter Enteral Nutr. 2015 Nov;39(8):890-2. doi: 10.1177/0148607114567201. Epub 2015 Jan 7. No abstract available.
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