Rationale and design of the Balanced Anesthesia Study: a prospective randomized clinical trial of two levels of anesthetic depth on patient outcome after major surgery

BACKGROUND: An association between relatively deep anesthesia, as guided by the bispectral index (BIS), and increased postoperative mortality has been demonstrated in 6 of 8 published observational studies, but association does not necessarily mean causality. Small clinical trials of anesthetic depth have demonstrated increased delirium and postoperative cognitive dysfunction in patients who were relatively deeply anesthetized, but have been inadequately powered to study mortality. A large-scale randomized study is required to determine whether causality exists. METHODS: The primary hypothesis of our study is that light anesthesia, defined as a BIS target of 50, will reduce all-cause mortality within 1 year of surgery in comparison with deep anesthesia, defined as a BIS target of 35, in patients aged =60 years presenting for major surgery under general anesthesia. The trial is an international multicenter, randomized, parallel-group, double-blind (patients and investigators) prospective, intention-to-treat, safety and efficacy study. The relative reduction in mortality in the light anesthesia group is expected to be 20 , giving an absolute risk reduction from 10 to 8 . Power analysis using a = 0.049 and b = 0.2 indicates that 3250 patients are required in each group. RESULTS: The study is underway, and 1325 patients have been recruited in 40 centers in 5 countries. It is anticipated that the study will be completed in 3 years. CONCLUSIONS: This randomized controlled trial should definitively answer the question of whether titrating anesthetic depth makes a difference to patient outcome in a vulnerable patient group.