Tocilizumab, Dexamethasone, Olanzapine, Hemodynamics, and Ventilation in Cardiac Surgery

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 five different interventions on the primary endpoint 'days alive and outside of hospital within 90 days'.The interventions are:Tocilizumab vs. placebo administered after induction of anesthesia.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

Inclusion Criteria:Adult, i.e., above 18 years of ageScheduled for CABG and/or AVR, irrespective of other concomitant valve surgery.Exclusion Criteria:Acute surgery (i.e. off hours surgery)Pregnancy or currently breastfeeding. Pregnancy in all fertile women will be ruled out by pregnancy testing prior to randomization.Known endocarditis at time of screeningPrevious participation in the trialActive infection, including bacterial, viral, and/or fungal infectionKnown hepatic cirrhosisKnown severe thrombocytopenia with thrombocyte levels < 50 x 109/LKnown severe neutropenia with neutrocyte levels < 2 x 109/LOn the waiting list for a heart transplantRecipient of any major organ transplantObstructive hypertrophic cardiomyopathy, active myocarditis, constrictive pericarditis, untreated hypothyroidism or hyperthyroidismHaving received cytotoxic/cytostatic chemotherapy or radiation therapy for treatment of malignancy within the last 6 months.Clinical evidence of current malignancy except for basal or localized squamous cell carcinoma, cervical intraepithelial neoplasia or stable prostate cancer.Known narrow-angle glaucomaKnown phenylketonuriaType I diabetesKnown long QT syndromeKnown allergy for any of the included study drugsHaving received tocilizumab within the past 6 monthsAny condition, where participation in the study, in the investigator's opinion could put the subject at risk, confound the study results or interfere significantly with participation in the study