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.
Anesth Analg. 2015 Aug;121(2):357-65. doi: 10.1213/ANE.0000000000000797.
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.
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.
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.
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.
在 8 项已发表的观察性研究中，有 6 项研究表明，在双频谱指数（BIS）指导下相对较深的麻醉与术后死亡率增加之间存在关联，但关联并不一定意味着存在因果关系。较小的麻醉深度临床试验表明，在相对深度麻醉的患者中，谵妄和术后认知功能障碍的发生率增加，但在研究死亡率方面的效力不足。需要进行大规模随机研究以确定是否存在因果关系。
我们研究的主要假设是，与 35 的 BIS 目标相比，“轻度”麻醉（定义为 BIS 目标为 50）将降低 60 岁以上接受全身麻醉下大手术的患者在术后 1 年内的全因死亡率。该试验是一项国际性、多中心、随机、平行组、双盲（患者和研究者）前瞻性、意向治疗、安全性和疗效研究。预计轻度麻醉组的死亡率相对降低 20%，绝对风险降低从 10%降至 8%。使用 a = 0.049 和 b = 0.2 进行的功效分析表明，每组需要 3250 例患者。
该研究正在进行中，在 5 个国家的 40 个中心已经招募了 1325 例患者。预计该研究将在 3 年内完成。
这项随机对照试验应该明确回答在脆弱患者群体中，滴定麻醉深度是否对患者结局产生影响的问题。
