Development of Large Clinical Trials in Perioperative Medicine with an Emphasis on the Effectiveness and Safety of Nitrous Oxide

   This thesis describes the development and conduct of large clinical trials in anaesthesia and perioperative medicine. Problems addressed include major complications and pain after surgery, awareness (“waking up”) and the safety of nitrous oxide (“laughing gas”). Many aspects of perioperative care have been based on tradition, with most clinical research being fixated on surrogate measures (eg. physiological variables or blood tests) – these are inadequate and incomplete measures of a person’s recovery after surgery. Patients requiring anaesthesia for surgery are at risk of many serious complications, long-term disability, and poor survival. The solution, outlined in this thesis, is better quality, large pragmatic trials.