Early Adjunctive Vasopressin for Vasodilatory Shock - A Stepped Wedge Vanguard Feasibility Trial: The EAVES Study

Intensive care units randomised to the intervention group will administer adjunctive intravenous vasopressin as early as possible after ICU admission for eligible patients receiving inotropic and/or vasopressor support. Vasopressin will be prescribed by ICU medical staff and administered by ICU nursing staff. All other aspects of care should conform to usual ICU practice. Other vasopressors can continue to be administered to support a clinician-prescribed mean arterial pressure following initiation of vasopressin. Intravenous vasopressin will be started early at a clinician-determined dose with a maximum dose of 0.04 units/min to achieve the target mean arterial pressure. If the patient has persistent vasodilatory shock despite maximal dose vasopressin, the treating team can consider commencing and/or increasing infusion doses of noradrenaline and/or additional adjunctive agents (e.g. adrenaline, phenylephrine, angiotensin II, methylene blue) as per usual practice. If a patient is receiving adjunctive vasopressor infusions, these should be weaned preferentially to maintain the target mean arterial pressure as determined by the treating clinical team. Once all other vasopressor infusions have been weaned completely, vasopressin will be weaned and ceased. There is no maximal duration of vasopressin infusion. Adherence to the intervention will form the primary outcome of this feasibility trial and will be reviewed through the electronic medical record and ANZICS APD data. All six participating sites currently use arginine vasopressin (Argipressin) as an adjunctive vasopressor in routine ICU practice. Arginine vasopressin (Argipressin) is supplied in a 1 mL single dose vial containing 20 units vasopressin as a sterile liquid. It is usually diluted in 100 mL of 5% Glucose (preferred) or 0.9% Sodium Chloride to provide a 0.2 unit/mL solution. Each participating site may prepare arginine vasopressin in a slightly different volume of diluent (e.g. 40 mL) as per their local protocols. Ampoules will be stored stored refrigerated at 2-8°C and infusion solutions are stable for 18 hours at room temperature. It is preferred that administration is via a dedicated central venous access lumen. Onset of action is within 1 to 2 minutes and duration of effect is up to 20 minutes (half life 10 to 20 minutes).