• Mortality [ Time Frame: During the study period until completion of last visit of last patient ]
  Assessed as time to event analysis
• Non-fatal myocardial infarction [ Time Frame: During the study period until completion of last visit of last patient ]
  Assessed as time to event analysis
• Non-fatal Serious Adverse Event [ Time Frame: During the study period until completion of last visit of last patient ]
  Assessed as time to event analysis

• Surgical site infection [ Time Frame: Assessed at postoperative day 30 ]
  Infection in surgical area as defined by the Center for Disease Control
• Pneumonia [ Time Frame: Assessed at postoperative day 30 ]
  Pneumonia as defined by the Center for Disease Control
• Sepsis [ Time Frame: Assessed at postoperative day 30 ]
  Sepsis as defined by the joint task force by the European Society of Intensive Care Medicine and the Society of Critical Care Medicine
• Acute respiratory failure [ Time Frame: Assessed at postoperative day 30 ]
  Acute respiratory failure defined as the need for controlled ventilation or oxygen saturation of 900% or less despite of oxygen therapy
• Acute kidney injury [ Time Frame: Assessed at postoperative day 30 ]
  Acute kidney injury as defined Kidney Disease Improving Global Outcomes guidelines

Adult patients with risk factors for developing postoperative cardiac complications will be enrolled in the study. The patients will be randomised to receiving antioxidants or placebo perioperatively and 30% or 80% inspiratory oxygen concentration during anaesthesia and 2 hours postoperatively. The primary outcome is MINS (myocardial injury after non-cardiac surgery). The antioxidants are ascorbic acid (vitamin C) 3 grams intravenously preoperatively and N-acetylcysteine 100 milligrams/kilogram body weight intravenous infusion for 4 hours, starting at the same time as anaesthesia.

The study is a long-term follow-up study of the risk of mortality, MI and readmissions performed at 1 year after inclusion of the last patient. Two other follow-up studies are planned: One investigation of ischaemic troponin elevations defined as peak troponin levels above the internationally defined thresholds without extracardiac causes; another investigating the intervention effects in the subgroup of patients undergoing vascular surgery with specific emphasis on episodes of intraoperative hypotension within the following thresholds: MAP below 70 mmHg, 65 mmHg, 60 mmHg and 55 mmHg.

• Drug: Oxygen
  80% versus 30% inspiratory oxygen concentration
• Drug: Antioxidants
  Antioxidants versus placebo
  Other Names:

  • Ascorbic acid
  • N-acetylcysteine

• Experimental: 1
  Interventions:

  • Drug: Oxygen
  • Drug: Antioxidants
• Experimental: 2
  Interventions:

  • Drug: Oxygen
  • Drug: Antioxidants

Inclusion criteria:

All of the listed criteria (1.-4.) must be met.

1. Age 45 years or above
2. Elective or acute surgery in general anaesthesia
3. Scheduled for abdominal, orthopaedic, or vascular surgery with expected surgery duration of one hour or more.

4. Fulfil any 1 of the following 5 criteria:

   1. - History of coronary artery disease including angina
   2. - History of stroke
   3. - Undergoing vascular surgery
   4. - History of peripheral arterial disease
   5. - Any 2 of the following 8 criteria: i. Acute surgery ii. Current or previous daily smoking iii. History of hypertension iv. Diabetes mellitus requiring medical treatment v. History of transient cerebral ischemia vi. Plasma creatinine >175 µM vii. Age 70 years or above viii. History of congestive heart failure

Exclusion criteria:

1. Surgery within 30 days prior to operation
2. Arterial oxygen saturation below 90% without oxygen supplementation
3. Inability to give informed consent
4. Drug allergy towards any of the drugs involved in the trial
5. Previous treatment with bleomycin
6. Pregnancy