Protein-bound Versus Free Amino Acid Nutrition During INtestinal Malabsorption in Critical Illness

Overview

In the current study, we willquantitate the difference in digestion and absorption kinetics of dietary whole protein versus free amino acids in vivo in critically ill patients admitted to the intensive care unit suffering from malabsorption. 16 adult, mechanically ventilated ICU patients with clinical signs of malabsorption (faecal weight \>350 g/day) will be included. All patients will receive a primed continuous intravenous infusion of L-\[ring2H5\]-phenylalanine and L-\[3,5-2H2\]-Tyrosine for the duration of the study period. After reaching an isotopic steady state (1.5 hours), patients will receive either \[1-13C\]- phenylalanine labelled milk protein or free amino acids with an identical constitution and \[1-13C\]-phenylalanine. Main study endpoint will be the splanchnic extraction of phenylalanine, calculated from systemic \[1-13C\]- and L-\[ring2H5\]-phenylalanine enrichment.

Background of the study: The importance of the provision of sufficient protein in critical illness is increasingly recognized. Protein malabsorption seems to be an underestimated but substantial problem in critically ill patients, limiting the amount of this important nutrient that actually becomes available within the systemic circulation. Among several contributors to malabsorption in critical illness, exocrine pancreatic insufficiency has recently emerged as a regularly occurring phenomenon during critical illness. Pancreatic insufficiency could lead to reduced digestion and subsequent uptake of enteral provided proteins. A proposed solution to this problem could be the use of elementary feeds containing free amino acids instead of whole protein. Due to the lack of easy applicable and reproducible tests for protein malabsorption the true efficacy of these feeds is still unknown. We hypothesize that enteral nutrition containing free amino acids leads to higher systemic levels of amino acids and will therefore increase the amount of dietary amino acids available for protein synthesis. Objective of the study: To quantitate the difference in digestion and absorption kinetics of dietary whole protein versus free amino acids in vivo in patients admitted to the ICU suffering from malabsorption. Study design: Randomized, single-blind controlled, single-centre, intervention study. Study population: 16 adult, mechanically ventilated ICU patients with clinical signs of malabsorption (faecal weight \>350 g/day). Intervention: Normal enteral nutrition will be ceased 8 hours before the start of study participation. All patients will receive a primed continuous intravenous infusion of L-\[ring2H5\]-phenylalanine and L-\[3,5-2H2\]-Tyrosine for the duration of the study period. After reaching an isotopic steady state (1.5 hours), patients will receive either \[1-13C\]- phenylalanine labelled milk protein or free amino acids with an identical constitution and \[1-13C\]-phenylalanine. Primary study parameters/outcome of the study: Main study endpoint will be the splanchnic extraction of phenylalanine, calculated from systemic \[1-13C\]- and L-\[ring2H5\]-phenylalanine enrichment. Secundary study parameters/outcome of the study: Secondary endpoints include the impact of enteral nutrition on whole body protein balance, glucose and insulin concentrations and faecal energy and protein loss as a measure of malabsorption. Nature and extent of the burden and risks associated with participation, benefit and group relatedness: Total study participation will take 16 hours, including 8 hours of fasting. Arterial blood samples will be collected regularly, with 50 ml of blood being sampled in total, amounting to a maximum of 1.0% of total circulating volume. All infusions, as well as blood sample collection, will be performed through indwelling catheters necessary for normal ICU treatment, meaning no lines or nasogastric tubes will have to be placed for the purposes of the study. Both isotopically labelled protein and free amino acids have been proven safe for use in humans and carry no harmful risks for the study participant. Changes in protein digestion, absorption and metabolism are specific to critical illness and their impact on the clinical condition and recovery of patients is severe. Investigating new strategies to modulate these effects are therefore essential, but require experimental studies in a vulnerable population. The risks in the present study are minimal whereas the results could help improve nutritional management in the intensive care.