REINSTATE trial: Resolution of Elements Influencing Nutritional STatus After criTical illnEss

Prospective observational study in critically ill adults conducted at three time-points: Study day 1: During mechanical ventilation early in the intensive care admission (within seven days of ICU admission); and Study day 2: Within seven days of discharge to the post-ICU ward Study day 3: 3-months after ICU admission All study procedures are the same on all three study days On study day 1, patients will be mechanically ventilated in the Intensive Care Unit with a nasogastric (NG) tube in situ. Correct NG tube placement will be confirmed radiologically and by measurement of pH aspirates. The NG tube will be aspirated and contents of the stomach discarded prior to the commencement of the study. No prokinetics will be administered during the fasting and study period. After a four hour fast and 20 minute rest period all participants will have their energy expenditure measured via indirect calorimetry using a metabolic cart (Quark CPET, Cosmed) over a 30 minute period. For ventilated patients, this will be via a ventilator attachment to the metabolic cart, and for self-ventilating patients and healthy subjects this will be via a canopy hood. Following measurement of energy expenditure, participants will be administered (enterally or orally) a ‘test meal’ over a five minute period comprising 100 ml Ensure Original (Abbott, 237 ml, 920 kJ, 9 g protein, 33 g carbohydrate, 6 g fat), 100 mg of 13C-octanoic acid (Cambridge Isotope Laboratories, Andover, MA) dissolved in 1 ml water for the measurement of gastric emptying, and 3 g of 3-O-Methyl-D-gluco-pyranose (3-OMG) (Sigma-Aldrich, Castle Hill, New South Wales) dissolved in 5 ml water for the measurement of glucose absorption. Self-ventilating patients on the hospital ward following ICU discharge may or may not have an NG tube in situ. Therefore the test meal will be administered by their current feeding route (enteral or oral). Healthy subjects will consume the test meal orally. Blood samples will be obtained either via an arterial or, where arterial access is not available clinically, via a cannula placed in an antecubital vein. Samples will be taken at t= -5 mins, then every 15 minutes for the first hour, and half hourly for the remaining 3 hours. A total of 143 ml of blood will be collect on each study day (1 x 5 ml serum and 2 x 4 ml plasma samples at each of the 11 time points) for the measurement of glucose absorption, blood glucose and gut hormones. Breath samples will be collected to assess gastric emptying and taken at baseline prior to the ‘test meal’, then 5 minutely for the first hour after the ‘test meal’ and subsequently every 15 minutes for the remaining 3 hours. For mechanical ventilated patients, expiratory breath samples will be collected from the expiratory limb of the ventilation tubing using an airway adapter (Smiths Medical, Waukesha, WI) and venoject holder containing a needle (Venoject Luer Adapter; Terumo, Tokyo, Japan). Breath samples will be collected from the self-ventilating patients and healthy participants during expiration through a straw. Both techniques allowed reliable filling of Exetainer (Labco, Buckinghamshire, UK) breath collection tubes.