Grant: Project Grant

The development of an acute confusional state is a frequent complication of surgery (i.e. postoperative delirium, POD). In some types of non-heart surgery, POD can occur in 1 of 5 patients. Patients with POD are at increased risk of death, re-admission to the hospital, nursing home admission, and long-term cognitive decline (e.g. decrease in memory and other intellectual abilities). In a recent international study we demonstrated that a significant cognitive decline at 1 year is very frequent (30%) in patients who underwent non-heart surgery. Patients with a significant blood loss during surgery requiring transfusion are at increased risk of POD. Hypotension [i.e. low blood pressure (BP)] can frequently occur around the time of surgery, and has been also associated with an increased risk of POD. We hypothesize that tranexamic acid (TXA), a drug that can reduce perioperative bleeding, and a dedicated strategy to avoid hypotension around the time of surgery, will reduce the occurrence of POD and cognitive decline at 1 year after surgery. We will test our two hypotheses in the cogPOISE-3 trial, a substudy of an international trial in which 10,000 patients aged 45 years or older undergoing noncardiac surgery, with or at risk of cardiovascular disease, will randomly receive TXA or matching placebo (saline) during surgery. Patients on BP medications will be also randomly assigned to a 'hypotension avoidance strategy', or to a strategy aiming more at avoiding relatively higher BP ('hypertension avoidance strategy', which is often the current practice). Upon consent, patients will be assessed for the occurrence of POD while in hospital, and followed up to evaluate their cognitive performance at 1 year. We expect to have up to 4,500 patients from 20 countries wordwide. POD is a major problem that is very distressing for patients and their families, and consumes substantial resources. Conducting this study will facilitate addressing a neglected area at a large cost saving.