PROtein dose and Muscle Synthesis in critically ill patients (PROMS)

Increased protein delivery is recommended during critical illness, yet there is little understanding on how the body handles protein during critical illness. Given this, our study aims to understand whether the ability of critically ill patients to utilise amino acids is dependent on the amount of amino acids available (e.g. the dose of protein provided). This is a prospective, single-centre, parallel-group, interventional study, where critically ill patients will be randomised into receiving either 20g or 40g of protein. The study will be recruiting patients who are admitted to the Intensive Care Unit at the Royal Adelaide Hospital (RAH), South Australia. All patients will be studied on one occasion only. Following informed consent from patient's next of kin, a post-pyloric feeding tube will be inserted. Patients will undergo a 4 hour fast (no enteral feeds) prior to study commencement. The plasma phenylalanine and tyrosine pool will be primed with a single intravenous dose of L-ring-[13C6] phenylalanine (2.25 µmol/kg) and L-[3,5-2H2]-tyrosine (0.867 µmol/kg), followed by continuous intravenous infusion of these two tracers for the whole study day (10 hours). Following 4 hours from the start of IV tracer infusion, an intra-duodenal infusion of protein (20g or 40g diluted to 240ml with water) enriched with L-ring-[13C6] phenylalanine will be delivered to the patient over 60 mins. The intervention will be provided by research staff and documented on the Case Report Form. Blood samples and muscle biopsies (from the middle region of the vastus lateralis muscle) will be collected at pre-determined time points. At study completion, the enteral feeds be will recommenced. Tracer infusions will be prepared by the hospital pharmacy department to ensure dosing accuracy and safety precautions. Muscle biopsies will be conducted by trained intensive care physicians.