A pilot randomized controlled trial Registry #: NCT

 Background & Study Rationale  Study Question  Study Design & Overview  Patient Population  Study Intervention  Outcomes

Shock is lethal + invariably treated with vasopressors Mortality 40% vs 34% Mortality 39% vs 35% Mortality 47% vs 31%

We have focused agents rather than dosing strategies And we typically do not worry about discordances between targets and actual blood pressures Mortality 39% vs 35%

Farand et al Could dosing of vasopressors influence outcomes?

Lamontagne et al. 2011

The OVATION question  Considering : Distributive shock is common Patients with distributive shock are extremely vulnerable Because of their underlying chronic comorbidities Acute instability Vasopressors are used in almost every patient with distributive shock Vasopressors are potent medications with potential for both benefit and harm We are asking In critically ill patients in shock, does titrating vasopressors to higher blood pressure targets (liberal vasopressor use - mean arterial pressure 75 to 80 mmHg) versus lower targets (restrictive vasopressor use – mean arterial pressure 60 to 65 mmHg) result in reduced hospital mortality?

 Is it feasible to conduct a randomized controlled trial in patients in shock from various aetiologies who receive vasopressors comparing titration of vasopressor therapy to higher blood pressure targets (liberal approach - mean arterial pressure 75 to 80 mmHg) versus lower targets (restrictive approach - 60 to 65 mmHg)?

Pilot N=80

 Inclusion Criteria 1. Older than 16 years of age at the time of consent 2. Under the direct care of the ICU team regardless of location 3. Who have receive a minimum of 30 mL/kg of intravenous fluids (2100 mL for a 70 kg patient) before enrolment OR the most responsible physician has good reasons to believe that more fluid resuscitation is no longer required and could be harmful. 4. The treating physician believes will need vasopressors for at least 6 hours once enrolled

 Exclusion Criteria We will exclude patients who meet at least one of the following criteria. 1. Have received vasopressors for more than 24 hours 2. Are judged by the treating physician to be in obvious cardiogenic shock after an acute myocardial infarction (based on new ST segment elevations on ECG or obvious echocardiographic findings) 3. Have obvious haemorrhagic shock as a consequence of a clearly identified source of blood loss 4. Require vasopressors after cardiac surgery as a result of cardiopulmonary bypass-induced hypotension 5. Who have a specific indication for catecholamine therapy other than shock (i.e. angioedema or intracranial hypertension) 6. The attending team has agreed to withhold or withdraw life sustaining Tx 7. Concurrent enrollment in interventional trials that do not meet guidelines for co-enrolment (co-enrolment is permissible if there is no potential interaction between the protocols; this will be addressed case by case) 8. Prior randomization in this study

 Standard of Care plus one of the following:  Liberal Approach: vasopressors titrated to a MAP of mmHg  Restrictive Approach: vasopressors titrated to a MAP of mmHg

 The primary outcome will be the difference in the means of mean arterial pressures while on vasopressors and we define acceptable adherence (the threshold for feasibility) by a difference of at least 5 mmHg while on vasopressors.  As secondary feasibility outcomes, we will also capture the number of protocol violations.  Tertiary outcomes will explore clinical endpoints such as tissue perfusion, organ dysfunction, complications of vasopressor use, overall resource use in each arm and mortality (ICU, hospital and 6- month).

Thank you for taking the time to complete this training module. Proceed to Module 2: Patient Eligibility & Consent