Dexamethasone, Olanzapine, Flow-targeted Versus Pressure-targeted Hemodynamic Management, and Low Tidal Volume Ventilation in Patients Undergoing On-pump Cardiac Surgery - a Multifactorial Design Randomized Trial

Status: Recruiting
Location: See location...
Intervention Type: Drug, Procedure
Study Type: Interventional
Study Phase: Not Applicable
SUMMARY

Open heart surgery, including coronary artery bypass grafting (CABG) and/or aortic valve replacement (AVR) is associated with a significant risk of mortality. This study is a randomized clinical trial with the purpose of investigating four different interventions on the primary endpoint 'days alive and outside of hospital within 90 days'. The interventions are: * Dexamethasone vs. placebo administered after induction of anesthesia. * Olanzapine vs. placebo administered prior to anesthesia. * A blood-flow targeted vs. a blod-pressure targeted hemodynamic strategy while the patient is on cardio-pulmonary bypass (CPB) * Low-tidal volume ventilation vs. no ventilation of the lungs while the patient is on CPB

Eligibility
Participation Requirements
Sex: All
Minimum Age: 18
Healthy Volunteers: f
View:

• Adult, i.e., above 18 years of age

• Scheduled for CABG and/or AVR, irrespective of other concomitant valve surgery.

Locations
Other Locations
Denmark
The Heart Centre, Rigshospitalet
RECRUITING
Copenhagen
Contact Information
Primary
Sebastian Wiberg, MD, PhD
sebastian.christoph.wiberg@regionh.dk
+45 35 45 17 10
Backup
Christian Hassager, MD, DMSc
christian.hassager@regionh.dk
Time Frame
Start Date: 2022-11-10
Estimated Completion Date: 2028-02
Participants
Target number of participants: 1200
Treatments
Experimental: Dexamethasone
The dexamethasone kit will contain 20 mg of dexamethasonphosfat (Dexavit®,Vital Pharma Nordic), 4mg/mL, i.e. 5 mL, which corresponds to 16.67 mg of dexamethasone. Dexamethasone will be administered as an intravenous bolus infusion over 2 minutes after induction of anaesthesia.
Placebo_comparator: Placebo (for Dexamethasone)
The placebo kit will contain 5 mL of isotonic (0.9%) normal saline. Placebo will be administered as an intravenous bolus infusion over 2 minutes after induction of anaesthesia.
Experimental: Olanzapine
The olanzapine kit will consist of two capsules each containing two 2.5 mg tablets of olanzapine (Olanzapine Stada®, STADA Nordic); i.e. total dose 10mg. The capsules will be delivered to the patient with instruction to take the capsule orally along with other standardized pre-procedure medicine. Patient intake will be recorded.
Placebo_comparator: Placebo (for Olanzapine)
The placebo kit will consist of two placebo capsules identical to the capsules containing the olanzapine tablet. The capsules will be delivered to the patient with instruction to take the capsule orally along with other standardized pre-procedure medicine. Patient intake will be recorded.
Experimental: Flow-targeted hemodynamic management
In the 'flow group', an arterial oxygen delivery (DO2) above 274 mL/min/m2 BSA AND a central venous oxygen saturation (ScvO2) above 70% will be targeted. CPB pump flow will be initiated at a flow rate of 2.4 L/min/m2. If DO2 or ScvO2 are below target, CPB pump flow will be gradually increased until targets are reached up to a maximum CPB pump flow of 3.2 L/min/m2. If DO2 or ScvO2 are below targets despite a maximum CPB pump flow, PaO2 will be gradually increased from an initial target of 15-20 kPa to a maximum of 40 kPa. A haematocrit level equal to or above 21% will be targeted, however, if DO2 or ScvO2 are below target despite a CPB pump flow of 3.2 L/min/m2, the haematocrit target level will be increased to equal to or above 25%. A MAP down to 35 mmHg will be tolerated throughout. The MAP target will be achieved by administration of boluses of phenylephrine up to a total of 2.0 mg, which can be followed by a continuous infusion of norepinephrine up to 0.6 μg per kg per min.
Active_comparator: Pressure-targeted hemodynamic management
In the 'pressure group' a MAP between 70 to 80 mmHg will be targeted. The assigned MAP target will be achieved by administration of boluses of phenylephrine up to a total of 2.0 mg, which can be followed by a continuous infusion of norepinephrine up to 0.6 μg per kg per min. CPB pump flow will be fixed at a flow rate of 2.4 L per minute per square meter body surface area. A haematocrit level equal to or above 21% will be targeted throughout. A PaO2 of 15-20 kPa will be targeted throughout.
Experimental: Low tidal-volume ventilation
During initiation of CPB, the 'ventilation' group will receive a tidal volume at 3ml/kg and a set PEEP of 3 cm H2O. The respiratory frequency (RF) will be set at 10, and the inspiratory: expiratory (I:E) ratio will be set to 5:1. Peak pressures (Pmax) will be limited to \< 25 cm H2O. FiO2 will be set at 50%. The ventilation strategy will be maintained during CPB.~Any recruitment manoeuvres will be initiated solely at the discretion of the attending anaesthesiologist, and only if the patient's oxygen saturation drops below 88%. All recruitment manoeuvres will be completed by increasing the inspiratory pressure to 20 cmH2O for 10 seconds. The manoeuvre will be repeated three times.
Active_comparator: No ventilation
The 'no-ventilation' group will receive no ventilation or PEEP. The ventilation strategy will be maintained during CPB.~Any recruitment manoeuvres will be initiated solely at the discretion of the attending anaesthesiologist, and only if the patient's oxygen saturation drops below 88%. All recruitment manoeuvres will be completed by increasing the inspiratory pressure to 20 cmH2O for 10 seconds. The manoeuvre will be repeated three times.
Sponsors
Leads: Rigshospitalet, Denmark

This content was sourced from clinicaltrials.gov