Randomized clinical trial Randomized clinical trial of gut-specific nutrients in critically ill surgical patients M. Gatt 1 and J. MacFie 1,2 1 Combined Gastroenterology Research Unit, Scarborough Hospital, Scarborough, and 2 Postgraduate Medical Institute, University of Hull, Hull, UK Correspondence to: Professor J. MacFie, Combined Gastroenterology Research Unit, Scarborough Hospital, Woodlands Drive, Scarborough YO12 6QL, UK (e-mail: johnmacfie@aol.com) Background: Inadequate gut function is common and may adversely affect prognosis. However, it is difficult to measure and treatment options are limited. This study evaluated whether gut-specific nutrients (GSNs) could stimulate the return of gut function in critically ill patients, and assessed what effect, if any, this would have on patient outcomes. Methods: Consecutive critically ill patients intolerant to enteral feeding were randomized to receive a cocktail of GSNs or placebo. Administration was for 1 month and patients were followed for 3 months. The primary endpoint was the time to return of normal gut function. Results: Twenty-five patients were randomized to each group. GSN administration was associated with a quicker return of normal gut function (median 164 versus 214 h; P = 0·016), attenuation of the acute-phase response and a lower incidence of sepsis (4 versus 13 patients, P = 0·015) compared with placebo. There were fewer deaths by 3 months in the GSN group but this did not achieve significance (2 versus 7 deaths; P = 0·138). Conclusion: GSNs expedite the return of gut function in the critically ill and improve outcomes. Inadequate gut function may be associated with poor prognosis similar to that of other single organ failures. Registration number: ISRCTN61157513 (http://www.controlled-trials.com). Presented and awarded the Moynihan Prize at a conference of the Association of Surgeons of Great Britain and Ireland, Manchester, UK, April 2007, and at a meeting of the European Society for Clinical Nutrition and Metabolism, Prague, Czech Republic, September 2007, and published in abstract form as Br J Surg 2007; 94(Suppl 2): 3 and Clin Nutr Suppl 2007; 2: 24 Paper accepted 27 April 2010 Published online 13 July 2010 in Wiley Online Library (www.bjs.co.uk). DOI: 10.1002/bjs.7155 Introduction Organ failures are associated with poorer patient outcomes, especially if left untreated. Some years ago the authors published a pragmatic study which compared enteral with parenteral nutrition 1 . In common with other investigators, they found that significant numbers of patients failed to reach their targeted requirements with enteral feeding. Failure to achieve requirements was associated with increased morbidity and mortality. Because of the numerous homeostatic roles of the gastrointestinal system it was hypothesized that inadequate gut function was the prime determinant of outcome rather than the mode of nutritional support per se. Numerous published studies have added support to the importance of gut function on patient outcome 2–5 . This hypothesis was investigated in a large prospective audit which confirmed that inadequate gut function, as defined by enteral intolerance, was an independent indicator of prognosis in multivariable analysis 6,7 . Accepting the princi- ple that untreated organ failure is detrimental to prognosis, the dearth of available therapies to normalize gastrointesti- nal dysfunction in daily clinical practice is disconcerting. The rationale behind this study was to advance the hypothesis that inadequate gut function equates with clin- ical outcome. This was achieved by investigating the putative benefits of gut-specific nutrients (GSNs) on the return of gut function in a group of critically ill patients with ileus as manifested by intolerance to an enteral feeding regimen. GSNs may be defined as substances with specific effects on gut function, morphology, ecoflora or physiol- ogy, over and above their roles as nutrient substrates 8 . An extensive literature exists on their use, but no previous study  2010 British Journal of Surgery Society Ltd British Journal of Surgery 2010; 97: 1629–1636 Published by John Wiley & Sons Ltd