Wong 2002.

Methods	RCT, single centre Country: Canada Setting: a university hospital Starting dates: not stated.
Participants	Number of participants (N) = 68 Age, years (mean ± S.D.): 71 ± 15 in the BIS group, 70 ± 6 in the Control group Sex Male, n (%): 19 (65.51%) in the BIS group, 21 (67.74%) in the Control group ASA PS Class ASA I to II, n (%): 26 (89.65%) in the BIS group, 30 (96.77%) in the Control group Surgery Type of surgery: elective orthopaedic surgery Knee replacement, n (%): 14 (48.28%) in the BIS group, 10 (32.26%) in the Control group Hip replacement, n (%): 15 (51.72%) in the BIS group, 21 (67.74%) in the Control group Duration of surgery, min: 90 ± 16 in the BIS group, 92 ± 16 in the Control group Anaesthesia Anaesthetic technique: volatile (isoflurane) anaesthesia Premedication: none Induction: propofol 1 to 2 mg/kg, fentanyl 2 µg/kg to 3 µg/kg, and midazolam 1 mg. Intubation: rocuronium: 0.6 mg/kg Maintenance: isoflurane in combination with nitrous oxide, fentanyl, and rocuronium. Intraoperative drug usage: Propofol, mg: 146 ± 44 in the BIS group, 141 ± 43 in the Control group Fentanyl, µg: 307 ± 64 in the BIS group, 310 ± 95 in the control group Isoflurane, mL: 5.6 ± 2.6 in the BIS group, 7.7 ± 3.4 in the Control group Duration of anaesthesia, min: 120 ± 17 in the BIS group, 121 ± 17 in the Control group Exclusion criteria Significant cardiopulmonary diseases or other end‐organ disease Depression or psychiatric disorders, dementia previous CVA, head trauma Inadequate command of English Drug or alcohol abuse Preoperative baseline of Mini Mental State Examination (MMSE) < 24
Interventions	BIS group (n = 29): administration of isoflurane and fentanyl to maintain BIS index of 50 to 60 (model A1050, Aspect Medical System), n = 29 Control group (n = 31): administration of isoflurane and fentanyl adjusted to clinical practice and to provide rapid recovery, n = 31
Outcomes	Time to orientation to person, place and time (main outcome) End tidal concentration (%) Consumption of isoflurane (ml) Time to awakening (eye opening to verbal commands) Time to extubation Time to readiness for transfer to PACU Time to readiness for discharge from PACU (Aldrete score > 9) Symptoms of postoperative cognitive dysfunction reported from nurses, family members, research assistant, or the participant Recall awareness of intraoperative events
Notes	The study was supported in part by a grant from Aspect Medical, Newton, MA, USA
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	A block randomization with concealed varying block sizes was performed with computer‐generated random numbers.
Allocation concealment (selection bias)	Low risk	Block randomization with concealed varying block sizes was performed with computer‐generated random numbers.
Blinding of participants and personnel (performance bias) All outcomes	High risk	Participants blinding ‒ unclear. Anaesthesia personnel blinding ‒ no
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Quote: "symptoms of clinical cognitive dysfunction (i.e., reduced ability to maintain attention to external stimuli, disorganized thinking, disorientation, memory impairment, etc.) reported from nurses, family members, research assistant, or patient (all blinded to group assignment) were recorded."
Incomplete outcome data (attrition bias) All outcomes	Low risk	Quote: "....., eight patients (three from the SP group, and five from the BIS group) were excluded from the analysis for protocol violations." The missing outcome data seem to balance across intervention group. The plausible effect size (difference in mean) among missing outcome probably not enough to have a clinically relevant impact on observed effect size
Selective reporting (reporting bias)	Unclear risk	Detail regarding the trial registration was not found.
Learning contaminating bias	Unclear risk	The unblinded anaesthesiologist could potentially lead to 'learning contamination bias'

AEP: Auditory Evoked Potential; AAI: A‐line autoregressive index; ASA PS: American Society of Anesthesiologists Physical Status; CVA: cerebrovascular accident; MMSE: Mini Mental State Examination; MMT: Mental State test; ISPOCD: International Study of Postoperative Cognitive Dysfunction; TCI: Target Controlled Infusion; MAC equivalent: Minimal Alveolar Concentration equivalent; N: total number of participants in each trial; n: number of participants in each arm after random allocation; mg/kg:milligramme per kilogramme; g: gramme; ml: millilitre; min: minute; mm.Hg: millimetre of mercury; PACU: post anaesthesia care unit; S.D: standard deviation.