DEX will be loaded by the anaesthesiologist in the operating room at the completion of surgery (at the time of sternal closure, grafts complete and off cardiopulmonary bypass) prior to ICU transfer at 1.2 µg/kg/hour over approximately 20 min (up to 1 hour) followed by an infusion at 0.7 µg/kg/hour. The rate can be adjusted higher or lower at the discretion of the anaesthesiologist/intensive care physician for clinical indications (sedation requirements, extubation or haemodynamics) between 0.1 and 1.2 µg/kg/hour. If the maximum rate is reached and the participant requires further sedation, the ICU team can introduce additional sedatives at their discretion. After extubation, the infusion will continue in ICU to avoid excess sedation in the judgement of the clinical team up to 24 hours or until ready for discharge from ICU (whichever is earlier). The infusion can also be paused secondary to haemodynamic instability (hypotension—MAP <55 mm Hg requiring vasopressors, bradycardia—HR <50) or if acute kidney injury requiring dialysis develops. After 24 hours or ICU discharge (whichever is earlier), therapy will be at the discretion of the care team. DEX is approved for procedural sedation during surgery and mechanical ventilation in the ICU, and the proposed use in this trial falls within such indications (ie, on-label).

Non-DEX-based sedation protocols, at the discretion of the attending physician in the ICU, include fentanyl, midazolam or propofol while intubated. In extubated patients still in the ICU, this could also include antipsychotics such as quetiapine and haloperidol. All α2R agonist including DEX and clonidine are precluded from use.

Intraoperative anaesthetic care (induction and maintenance medications/dosing) is at the discretion of the attending anaesthesiologist with restrictions precluding the use of intraoperative α2R agonist in participants randomised to the control group.

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