A randomised, double-blind, double-dummy study of the effects of insulin and glucagon-like peptide-1 on glycaemia, gastric emptying, gastro-oesophageal reflux and mesenteric blood flow in the critically ill

INTERVENTION: Intravenous GLP‐1 at an initial dose of 1.2pmol.kg.min (10mL/h) and ‘placebo insulin’ (0.9% saline) commenced as per the Royal Adelaide Hospital unit protocol. The drug will be administered for a minimum of 18 hours and a maximum of 30 hours. The infusion will span Day 0 and Day 1 of the study (minimum of 18 hours, maximum 30 hours). Due to differences in the rate of gastric emptying throughout the day, the length of infusion on Day 0 will change depending on time of randomization so that scintigraphy on Day 1 will be standardized to 9am. The GLP‐1 rate is altered if the blood sugar remains above 10mmol/L in a stepped fashion (to 2.4 and 3.6 pmol/kg/min). Saline will be run as if insulin is being administered (1U/mL e.g if 2 units required, rate will be 2 ml/hr). CONDITION: Critical Illness Gastric emptying Glycaemic control PRIMARY OUTCOME: Glycaemic control which will be measured using a variety of mechanisms including: glycaemic penalty index, recording hypo and hyperglycaemic events, time in ideal range and assessing glycaemic variability. SECONDARY OUTCOME: Gastric emptying via Scinitigraphy and 2D ultrasound Glucose absorption (3‐OMG absorption) Manometry/pH data will be assessed using basal LOS pressure, Gastro‐oesophageal motility, reflux events and oesophageal pH Oesophageal impedance via number of liquid and non‐acid reflux episodes. Plasma concentrations of GLP‐1, GIP, Glucagon and C‐peptide Superior mesenteric artery blood flow using doppler ultrasound INCLUSION CRITERIA: Fifty sedated and mechanically ventilated critically ill patients with stress hyperglycaemia will be recruited from the Intensive Care Unit at the Royal Adelaide Hospital. Stress hyperglycaemia will be defined as a single random blood glucose >10 mmol/L in a patient without a history of formally diagnosed type‐1 or type‐2 diabetes mellitus who has a glycated haemoglobin (HbA1c) <6.5%. Patients will be between the ages of 18 and 80 years, anticipated to remain ventilated for at least 24 hours and deemed suitable by the treating intensive care physician to receive intragastric enteral nutrition.