Timothy G Short1, Kate Leslie, Matthew T V Chan, Douglas Campbell, Christopher Frampton, Paul Myles. 1. 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.
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.
RCT Entities:
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: Miles Berger; Niccolò Terrando; S Kendall Smith; Jeffrey N Browndyke; Mark F Newman; Joseph P Mathew Journal: Anesthesiology Date: 2018-10 Impact factor: 7.892
Authors: Troy S Wildes; Angela M Mickle; Arbi Ben Abdallah; Hannah R Maybrier; Jordan Oberhaus; Thaddeus P Budelier; Alex Kronzer; Sherry L McKinnon; Daniel Park; Brian A Torres; Thomas J Graetz; Daniel A Emmert; Ben J Palanca; Shreya Goswami; Katherine Jordan; Nan Lin; Bradley A Fritz; Tracey W Stevens; Eric Jacobsohn; Eva M Schmitt; Sharon K Inouye; Susan Stark; Eric J Lenze; Michael S Avidan Journal: JAMA Date: 2019-02-05 Impact factor: 56.272
Authors: Lisbeth A Evered; Matthew T V Chan; Ruquan Han; Mandy H M Chu; Benny P Cheng; David A Scott; Kane O Pryor; Daniel I Sessler; Robert Veselis; Christopher Frampton; Matthew Sumner; Ade Ayeni; Paul S Myles; Douglas Campbell; Kate Leslie; Timothy G Short Journal: Br J Anaesth Date: 2021-08-28 Impact factor: 11.719
Authors: T S Wildes; A C Winter; H R Maybrier; A M Mickle; E J Lenze; S Stark; N Lin; S K Inouye; E M Schmitt; S L McKinnon; M R Muench; M R Murphy; R T Upadhyayula; B A Fritz; K E Escallier; G P Apakama; D A Emmert; T J Graetz; T W Stevens; B J Palanca; R Hueneke; S Melby; B Torres; J M Leung; E Jacobsohn; M S Avidan Journal: BMJ Open Date: 2016-06-15 Impact factor: 2.692