None listed
Conditions
Brief summary
Single centre exploratory unblinded observational study. Using a unique method that has been developed to label intact proteins rather than amino acids by infusing cows with large quantities of D5-phenylalanine and then collecting their labelled milk. This labelled cow milk can then be administered to humans for research purposes and the metabolic fate of the protein determined. This technique allows the fate of intact protein to be followed from ingestion, through digestion and absorption to muscle deposition. The biological value of the protein can thus be determined i.e. the proportion that becomes incorporated into body tissues, particularly muscle. This is relevant in the critically ill as the protein content of enteral feed formulae is usually presented as a protein such as casein or whey protein. Reduced amino acid absorption has been reported in rats following haemorrhagic shock, in patients with pancreatitis, and in critically ill patients following trauma. However the mechanisms underlying protein malabsorption are not well understood. A more comprehensive understanding of protein absorption during critical illness, and the effect of feeding intolerance on protein uptake will allow the rational development of feeding strategies to improve nutritional outcomes in these patients.
Interventions
Each subject/patient will be studied on one occasion only. Following consent a small intestinal feeding catheter will be inserted using the Cortrak device by a trained research dietitian or intensive care physician. Patients and healthy subjects will undergo an overnight fast (no food or fluid, including water) from midnight until study commencement. The plasma phenylalanine and leucine pool will primed for 2.5 hours with a single intravenous dose of d5-phenylalanine (2.2 ug/kg), L-[3,5-D2]-tyro
Each subject/patient will be studied on one occasion only. Following consent a small intestinal feeding catheter will be inserted using the Cortrak device by a trained research dietitian or intensive care physician. Patients and healthy subjects will undergo an overnight fast (no food or fluid, including water) from midnight until study commencement. The plasma phenylalanine and leucine pool will primed for 2.5 hours with a single intravenous dose of d5-phenylalanine (2.2 ug/kg), L-[3,5-D2]-tyrosine (0.674 ug/kg) and L-[1-13C]-leucine (0.110 ug/kg), after which a intraduodenal infusion for 1 hour of L-[1-13C]phenylalanine-labelled and L-[1-13C]-leucine casein milk protein will be commenced (25 g, 100 kcal, 1.7 kcal/min). Following this a continuous IV infusion of 5 hours of the tracers d5-phenylalanine (0.055 umol/kg/min), L-[3,5-D2]-tyrosine (0.017 umol/kg/min) and L-[1-13C]-leucine (0.110 umol/kg/min) will be administered. At study completion, healthy subjects will be provided with a buffet meal, and enteral feeds will be recommenced in ICU patients. Protein infusions will be prepared by the hospital pharmacy department to ensure dosing accuracy and safety precautions. Administration of infusions will be by trained intensive care research practitioners.
Sponsors
Royal Adelaide Hospital
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
ICU patients: *Adults (greater than or equal to 18 years of age) *Admitted to the Royal Adelaide Hospital Intensive Care Unit *Mechanically ventilated *Suitable for enteral feeding *Arterial line insitu *Consent obtained Healthy volunteer arm: *Adults (greater than or equal to 18 years of age)
Exclusion criteria
ICU patients: *Recent upper abdominal surgery *Vegan *Lactose intolerance *Any order to withhold active treatment *Jehovah’s Witness *For muscle biopsy: Bleeding diathesis (INR > 1.5; APTT > 50) including those receiving anticoagulants (other than low dose for DVT prophylaxis) and anti-platelet agents Healthy volunteer arm: *Significant illness *Smokers (cigarettes/cigars/marijuana) *Intake of >2 standard drinks on >5 days per week *Intake of >4 cups of caffeinated drinks per day *Intake of any illicit substance *Vegan *Lactose intolerance *Use of prescribed or non-prescribed medications that may affect gastrointestinal function *Significant gastrointestinal symptoms, disease or surgery (apart from uncomplicated appendectomy) *For muscle biopsy: Bleeding diathesis (INR > 1.5; APTT > 50) including those receiving anticoagulants (other than low dose for DVT prophylaxis) and anti-platelet agents
Outcome results
None listed