Avidan 2011

Methods	RCT, multicentre
Participants	Country: USA N = 5413 ASA: I/II/III/IV 23/ 468/ 1416/ 954, 19/ 407/ 1407/ 1019 Gender: Male, Cn(%): 1621 (56.7%), 1679(58.8%) Age: 60±14.12, 61±14.4 yr Inclusion: patients with at least one major criterion (preoperative long‐term use of anticonvulsant agents, opiates, benzodiazepines, or cocaine; a cardiac ejection fraction less than 40%; a history of anaesthesia awareness; a history of difficult intubation or anticipated difficult intubation, ASA physical status class 4 or class 5; aortic stenosis; end‐stage lung disease; marginal exercise tolerance not resulting from musculoskeletal dysfunction; pulmonary hypertension; planned open‐heart surgery; and daily alcohol consumption) or two minor criteria (preoperative use of beta‐blockers, chronic obstructive pulmonary disease, moderate exercise tolerance not resulting from musculoskeletal dysfunction, smoking two or more packs of cigarettes per day, and obesity, defined as a body‐mass index (the weight in kilograms divided by the square of the of more than 30) Exclusion: the surgical procedure or positioning of the patient prevented BIS monitoring or if the surgery required a wake‐up test Duration of anaesthesia: NA
Interventions	BIS‐guided anaesthesia (A BIS Quatro Sensor, Covidien), A target BIS value of 40‐60 Anaesthesia guided by end tidal anaesthetic gas (ETAG) concentrations between 0.7 MAC and 1.3 MAC (routine care group)
Outcomes	Definite intraoperative awareness (Cn, %) using Michigan Awareness Classification Instrument
Notes
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	"...6100 prerandomization designations were generated electronically in blocks of 100, divided equally between the groups."
Allocation concealment (selection bias)	Low risk	" Labels indicating BIS group to EATC group were sealed in opaque, number envelopes
Incomplete outcome data (attrition bias) All outcomes	Low risk	46 in the BIS group and 50 in the EATC group were lost to follow up. A modified intention‐to‐treat analysis were performed
Selective reporting (reporting bias)	Low risk	All expected outcomes reported
Other bias	Unclear risk	The unblinded anaesthesiologists could potentially lead to 'learning contamination bias'
Blinding of patients?	Low risk	"The anaesthesia practitioners were aware of the assignments of the patients, but the patients, the postoperative interviewers, the expert reviewers, and the statistician were not."
Blinding of anaesthesiologists?	High risk	"The anaesthesia practitioners were aware of the assignments of the patients, but the patients, the postoperative interviewers, the expert reviewers, and the statistician were not."
Blinding of outcome assessors?	Low risk	"The anaesthesia practitioners were aware of the assignments of the patients, but the patients, the postoperative interviewers, the expert reviewers, and the statistician were not."