title: 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.
abstract: 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.
authors.affiliation: From the *Department of Anaesthesia and Perioperative Medicine, Auckland City Hospital, Auckland, New Zealand; †Department of Anaesthesia and Pain Management, Royal Melbourne Hospital, Melbourne, Victoria, Australia; ‡Anaesthesia, Perioperative and Pain Medicine Unit, Department of Pharmacology, University of Melbourne, Melbourne, Victoria, Australia; §Department of Epidemiology and Preventive Medicine, Monash University, Melbourne, Victoria, Australia; ∥Department of Anaesthesia and Intensive Care, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong, People's Republic of China; ¶Department of Statistics, University of Otago, Christchurch, New Zealand; #Department of Anaesthesia and Perioperative Medicine, Alfred Hospital, Melbourne, Victoria, Australia; and **Academic Board of Anaesthesia and Perioperative Medicine, Department of Epidemiology and Preventive Medicine, Monash University, Melbourne, Victoria, Australia.
authors.forename: Timothy G
authors.initials: TG
authors.lastname: Short
authors.forename: Kate
authors.initials: K
authors.lastname: Leslie
authors.forename: Matthew T V
authors.initials: MT
authors.lastname: Chan
authors.forename: Douglas
authors.initials: D
authors.lastname: Campbell
authors.forename: Christopher
authors.initials: C
authors.lastname: Frampton
authors.forename: Paul
authors.initials: P
authors.lastname: Myles
mesh_terms: D000368:Aged; D000768:Anesthesia, General / Q000009:adverse effects / Q000295:instrumentation / Q000379:methods* / Q000401:mortality*; D003243:Consciousness / Q000187:drug effects*; D056805:Consciousness Monitors; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D057194:Intention to Treat Analysis; D008297:Male; D008875:Middle Aged; D016343:Monitoring, Intraoperative / Q000295:instrumentation; D011183:Postoperative Complications / Q000401:mortality*; D011446:Prospective Studies; D012107:Research Design; D018570:Risk Assessment; D012307:Risk Factors; D013997:Time Factors; D016896:Treatment Outcome