Russell 1986.

Methods	Study design: randomized parallel groups Study dates: "1982‐1984" (email bias survey, see notes)
Participants	Country: UK Sex: female Age: 19 to 74 ASA: NA Procedure: gynaecological surgery Study size: 55
Interventions	Randomized portion of anaesthetic: TIVA vs "inhaled nitrous oxide with IV fentanyl increments ("balanced" regimen)" otherwise described as intravenous anaesthesia Intervention 1: TIVA: etomidate 100 µg/kg/min for 10 min then...O2/air, 100 mc/kg/min for rest of procedure + fentanyl bolus, N = 25 Intervention 2: N2O + fentanyl bolus ("balanced"), N = 30
Outcomes	Primary outcomes: wakefulness; time to recovery Secondary outcome: awareness/wakefulness as defined using an awareness classification system (see Table 1): class 1 Comments: no recall, 3 dreams, 7% wakeful in the etomidate group, and one 9 dreams; 44% occurrence of recall in the N2O group
Notes	Non‐randomized portion of anaesthetic: TIVA vs "inhaled nitrous oxide with IV. fentanyl increments ("balanced" regimen)" otherwise described as intravenous anaesthesia: muscle relaxants induction yes/maintenance PRN Premedication: temazepam 10 mg to 20 mg + fentanyl 250 µg Anaesthesia induction: thiopentone suxamethonium 1 mg to 1.5 mg/kg Anaesthesia maintenance: N2O:O2 2:1 vecuronium 4 mg + vecuronium 2 mg as needed + fentanyl 100 µg as needed When patient responded to command: thiopentone 100 mg + fentanyl 100 µg or etomidate 5 mg + 100 mc fentanyl; nitrous required significantly more fentanyl boluses and hence is defined as the "light" anaesthesia group Comment: balanced anaesthesia is defined as inhalational agents with small‐dose narcotics; others define it as a regimen based on inhaled N2O with IV fentanyl increments; TIVA anaesthetic is defined as based on a 2‐stage infusion of etomidate plus increments of fentanyl; other definitions of balanced anaesthesia: Lallemand 2003; Lehmann 1985; Lehmann 1992; Myles 1997 Comment: see Dryad topics: definition of light and inadequate anaesthesia; isolated forearm technique (IFT) Comment: wakefulness during anaesthesia has been recognized for many years since Artusio 1955 described this state in spontaneously breathing patients under ether anaesthesia. Using the IFT, Wilson 1980 found some 30% of patients were wakeful Time of outcome determination: before discharge Method of outcome determination: interview Author responded to the email bias survey on 4 February 2011. Responses are recorded in the 'Risk of bias' table Survey response: 4 February 2011, Ian F i.f.@hull.ac.uk
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	High risk	Quote: "Patients were randomised according to whether their unit number was odd or even...no one has control over the unit number assigned to a patient. It is true that the unit number was known before inclusion in the study, but since all patients meeting the entry criteria were included and received their appropriate anaesthetic, I do not think this method of randomisation introduced bias" (email bias survey, see notes) Comment: other experts disagree with Dr. Russell Myles 2015 (personal communication). Despite the 4/7 domains in this RCT having a 'high' risk, we have given this RCT an overall ROB rating that is acceptable for use in our meta‐analysis in this review
Allocation concealment (selection bias)	High risk	Quote: "I was the sole investigator and anaesthetist. Allocation could not be concealed" (email bias survey, see notes) Comment: if the anaesthesiologist is not blinded to the drugs then the lack of allocation concealment will not change the impact of the unblinded state of the anaesthesiologist on the ROB
Blinding of participants and personnel (performance bias) All outcomes	High risk	Quote: "Patient" (email bias survey)
Blinding of outcome assessment (detection bias) All outcomes	High risk	Comment: not blinded
Incomplete outcome data (attrition bias) All outcomes	Low risk	Comment: 3 patients had partial data due to uncontrolled hypertension; 2 in one group, 1 in the other. All patients (N = 55) were included in the awareness evaluation (email bias survey, see notes)
Selective reporting (reporting bias)	Low risk	Quote: "The study protocol is no longer available as this was over 25 years ago. But all of the study’s pre‐specified (primary and secondary) outcomes that are of interest in the review have been reported" (email bias survey, see notes) Quote: "Yes. While all the primary outcomes were significant, some secondary outcomes were not significant" (email bias survey, see notes) Comment: awareness outcome part of inclusion criteria
Other bias	Low risk	Comment: from author survey responses: the author believes that for reasons explain above, there were no other biases