Cai 2012a.

Methods	RCT, parallel design, single‐centre
Participants	Total number of randomized participants: 2216 Inclusion criteria Elderly Han patients (Chinese ethnic group) scheduled to undergo general anaesthesia Exclusion criteria Did not consent to be enrolled Dementia symptoms Hepatic dysfunction Renal dysfunction Heart disease Lung disease Participants who required postoperative intensive care (because of bleeding, inflammation, respiratory failure, heart failure, anastomotic leaks etc.) or required postoperative sedation were excluded from analysis Type of surgery: oesophagectomy, gastrectomy, nephrectomy, fracture reduction Baseline characteristics TIVA group Age, mean (SD): 71.2 (± 3.8) years Gender, M/F: 570/430 ASA grade: not reported Inhalational maintenance group Age, mean (SD): 69.3 (± 5.1) years Gender, M/F: 570/430 ASA grade: not reported Country: China Setting: hospital
Interventions	TIVA group Participants: n = 1106; 106 losses (anastomotic leaks, bleeding, respiratory failure, heart failure, inflammation); 1106 analysed using ITT: 1000 analysed PP Induction details: loading doses of fentanyl 4 µg/kg, propofol 3 mg/kg and vecuronium 0.08 mg/kg Maintenance details: fentanyl continuous infusion 0.03 µg/kg/min, propofol continuous infusion at a rate of 53.8 µg/kg/min injected with gradual increases in concentration of 0.4 µg/mL with initial target level of 1 µg/mL. Continuous infusion of vecuronium 0.5 µg/kg/min. BIS maintained at 40 to 60 Other information: premedication with 10 mg diazepam, 0.5 mg atropine im 30 minutes before GA Inhalational maintenance group Participants: n = 1110; 110 losses (anastomotic leaks, bleeding, respiratory failure, heart failure, inflammation); 1110 analysed using ITT; 1000 analysed PP Induction details: loading doses of fentanyl 4 µg/kg, propofol 3 mg/kg and vecuronium 0.08 mg/kg Maintenance details: continuous inhalation 2% to 3% end‐tidal concentration isoflurane. Continuous infusion of vecuronium 0.5 µg/kg/min. BIS maintained at 40 to 60 Other information: premedication same as TIVA group
Outcomes	MMSE (tested every day for 10 days) Frequency distribution of ApoE alleles and genotypes
Notes	Funding/declarations of interest: supported by grants from National Nature Science Foundation of China, and by Doctor funding Study dates: 2005 to 2010
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Use of a computerized random number generator and block randomization
Allocation concealment (selection bias)	Unclear risk	No details
Blinding of participants and personnel (performance bias) All outcomes	High risk	Not feasible to blind anaesthetists to intervention groups
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Postoperative assessment of MMSE was carried out by psychiatrists who were blinded
Incomplete outcome data (attrition bias) All outcomes	Unclear risk	Reasons for losses are described and balanced between group but number of losses is large (> 10%) and we were unclear whether this could influence outcome data
Selective reporting (reporting bias)	Unclear risk	Study authors do not report clinical trials registration. Not feasible to judge risk of selective outcome reporting
Other bias	Unclear risk	We noted a discrepancy between table 2 and the text in results section of the study report. Table 2 reports a big difference in MMSE scores at baseline, with very low scores in the inhalation group, and text reports no difference at baseline. We have assumed that table 2 has a typo, because baseline MMSE score is unusually low. We noted that data in this study differed from other studies. We did not identify any differences that could explain this, and we could not be certain whether other sources of unidentified bias were present