All members of the research Volasertib clinical trial team will receive training and a standardised procedure manual (detailing protocol, plans

for dealing with intervention fidelity issues, and monitoring the delivery and receipt of the intervention27), to ensure protocol consistency. All patients will receive identical information and instructions regarding the study, relayed by RRN and also in an information sheet provided at enrolment. Concurrent treatment Patients in both groups will have a standardised anaesthetic protocol for premedication, anaesthesia and postoperative pain and nausea management. In cardiac anaesthesia, it is very unusual to give PONV prophylaxis either in the operating theatre or in the ICU. The treatment of PONV in this population is expectant: that is, patients are treated for PONV only when they display signs/symptoms of nausea or vomiting. This is consistent with standards of care, in Australia and internationally,

given that the variable time of waking and ventilator weaning of patients is often unpredictable at the time of surgical case completion in theatre. Premedication will be standardised to temazepam 10–30 mg/diazepam 5–10 mg 1 h prior to surgery; anaesthesia induced with midazolam 0.03–0.1 mg/kg, fentanyl 5–15 g/kg, propofol 0.25–1.25 mg/kg and pancuronium 0.1 mg/kg/rocuronium 0.75–1.2 mg/kg. Anaesthesia will be maintained with: propofol infusion 2–5 mg/kg/h, sevoflurance administered precardiopulmonary bypass for ischaemic preconditioning at discretion of attending anaesthetist, air/O2 mix at discretion of attending anaesthetist. Transfer to ICU, patients will be maintained on propofol infusion and fentanyl infusion at 5–25 µg/h with no prophylactic antiemetics administered (current usual care). Participants will be sedated with the aforementioned propofol and fentanyl infusions until determined appropriate to extubation of the artificial

Brefeldin_A airway, and then maintained on fentanyl via patient-controlled analgesia (background of 0–25 µg/h; bolus of 5–25 µg every 5 min) for 48 h or until cardiac drain are removed postoperatively. A standardised rescue antiemetic protocol involving the use of a grading system will be used (see table 1). For any patient requiring nasogastric treatment postoperatively this will be recorded (given this prevents gastric distension and vomiting) and gastric volume recorded for 36 h. Table 1 Rescue antiemetic protocol Outcome measures All data will be collected using structured case report forms by staff blinded to treatment groups. This method of interviewer-led self-report data collection will minimise missing data.