Myles 2004

Methods	RCT, multicentre
Participants	Country: Australia N = 2463 ASA: I/II/III/IV 111/179/542/388/5, 127/227/520/354/10 Gender: Male/Female 752/473, 784/454 Age: 58.1 (16.5), 57.5 (16.9) Inclusion: at least one of risk factors for awareness, i.e. caesarean section, high risk cardiac surgery, acute trauma with hypovolaemia, rigid bronchoscopy, significant impairment of cardiovascular status, severe end‐stage lung disease, past history of awareness, unplanned awake intubation, known or suspected heavy alcohol intake, chronic benzodiazepine or opioid use , or current protease inhibitor therapy Operation: minor/intermediate/major 104/216/905, 104/231/903 Duration of anaesthesia: 3.2 (1.5‐4.4), 3.1 (1.3‐4.5) hrs
Interventions	BIS‐guided anaesthesia (A‐2000, version 3.4, Aspect Medical Systems), a target BIS value of 40‐60 Routine anaesthesia (routine care group)
Outcomes	Primary outcome: incidence of confirmed awareness Secondary outcomes: ‐Possible awareness ‐Hypnotic drug administration ‐Marked hypotension (Cn, %) ‐Patient satisfaction ‐Recovery times
Notes	Relaxant general anaesthesia Induction: midazolam (62%, 62%) + propofol (63%, 63%) or thiopentone (15%, 15%) Intubation: non‐depolarizing muscle relaxants (93%, 95%) Maintenance: propofol infusion (43%, 42%) nitrous oxide (35%, 37%) ‐opioids ‐volatiles ‐hypnotic drugs (7%,6%) and combined general and regional anaesthesia (18%, 15%)
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Computer‐generated random group allocation
Allocation concealment (selection bias)	Low risk	Central allocation
Incomplete outcome data (attrition bias) All outcomes	Low risk	" ..40 patients were withdrawn because of cancellation of surgery ( BIS group13, routine group13), withdrawal of consent ( six, twoO, surgery done without general anaesthesia ( four, none), or the patients was under‐age (none, two)" and " All patients.. were included in the intention‐to‐treat population for all .analyses."
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
Blinding of anaesthesiologists?	High risk	Unlikely to blind the anaesthesia providers to the allocated groups
Blinding of outcome assessors?	Low risk	"Follow‐up was undertaken by a blind observer."