George 2002.

Methods	Randomized cross‐over trial (3‐treatment, 3‐sequence, 3‐period design), with stratification by diagnosis 3:2 (emphysema: fibrosis) Pre‐specified analysis: MANOVA of group, time (measurement intervals) and diagnosis (hypothesis testing); univariate ANOVA of group and position (with no time point specified)
Participants	15 mechanically ventilated adults within 24 hours of single lung transplant (SLT) surgery, with functional arterial catheter and oximeter catheter (no cardiopulmonary bypass), who were haemodynamically stable (no unstable arrhythmias or hypotension, not on ECMO) Sex (M/F) 8/7, mean age 54 years ± 8 Mean FiO2 0.43 ± 0.06, mean PEEP 8.5 cmH2O ± 3.1, mean Vt 600 mL ± 190 with SIMV mode (n = 11) or double‐lumen endobronchial tube with differential lung ventilation (n = 4) Diagnosis: emphysema (n = 9), lung fibrosis (n = 6); right lung allograft (n = 5), left lung allograft (n = 10) Termination criteria: ectopy, desaturation (SpO2 < 85%), hypotension (MABP < 90 mmHg) Setting: Cardiothoracic ICU, University Medical Center, Southwestern Pennsylvania, USA, September 1997 to December 1998 Comment: discrepancy in number of females. Possible typographical error for MABP < 90 mmHg as exclusion/termination criterion
Interventions	Left lateral, right lateral and supine positions for 30 minutes Lateral positions described according to locations of transplanted (allograft) lung and non‐transplanted (native) lung lowermost in lateral position (i.e. allograft lung down (A) and native lung down (N)) Sequences/groups: 1 (n = 5)= NAS, 2 (n = 5)= SAN, 3 (n = 5)= NSA
Outcomes	Oxygenation effects (PaO2 and SvO2) at 5 and 15 minutes; blood flow effects (MABP and HR) at 5, 15 and 30 minutes; blood flow effects (CO) at 25 minutes. All outcome measures recorded at baseline Other co‐primary outcomes reported but not relevant for this review were PaCO2 and minute ventilation (Vmin) (ventilation variables)
Standard management	Pre‐planned ventilation changes based on measured PaCO2 and Vmin (0.1 FiO2 increase before second turn (n = 1)). Vasoactive medication not controlled for (commenced NTG at turn 3 for non‐specific ST changes on ECG (n = 1)). Likert pain score with threshold set for standardization of pain medication during data collection and rationale provided. Pain relief delivered (n = 3) on the basis of pain score, otherwise at the discretion of bedside nurse (11 participants received analgesia (IV or epidural) before or during study) No further description provided
Position description	45 degrees lateral rotation, 45 degrees wedge, angle verification method not described 30 degrees HOB elevation for all body positions, HOB verification method: angle indicator on bed frame
Washout period	Not described
Notes	Study commenced mean 5 hours 37 minutes ± 4 hours 58 minutes after surgery (calculated from minutes, 1 outlier at 1289 minutes) A priori sample size calculation (effect size 0.185 for position, 0.551 for time and 1.16 for interaction with α = 0.05 and 1‐β = 0.8). Post hoc power analysis: 60 to 80 participants required to achieve statistical significance Comment: study underpowered to detect differences in primary outcomes CXR obtained closest to data collection (2 hours to 24 hours postop) for ischaemic‐reperfusion injury identification. Scoring system for degree of infiltration developed by one of the investigators. Pre‐specified effects of ischaemic‐reperfusion injury score on dependent variables, but not relevant for this review Other descriptions for analysis: immediate response (1 to 5 minutes), short‐term response (15 minutes), long‐term response (25 to 30 minutes) to turning. Discrepancy in baseline measurement (unclear whether taken for each body position or once before the first turn) Comments: Summary statistics (mean and SE for each body position) included unit of analysis errors for meta‐analysis. Within‐subject differences for all pair‐wise comparisons were calculated and extracted from individual patient data (group allocation identified) Discrepancy between mean values for PaO2 and SvO2 was reported within the tables and raw data calculations for each body position (differences included single time point and average score for all time points)
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Not described Quotation: "stratified randomized design", participants "randomly assigned to three different sequencing patterns of turning" with 3:2 stratification for each sequence (group), "randomized to group I, II, or III using prepared assignment cards". Unclear random sequence generation for sequentially numbered envelopes
Allocation concealment (selection bias)	Low risk	Individual, not associated with data collection; placed cards in sealed envelopes. Envelopes coded by diagnosis (stratified randomization) and sequentially numbered
Blinding of participants and personnel (performance bias) All outcomes	Unclear risk	Not described
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Not described for primary outcomes. CXR assessor for ischaemic‐reperfusion injury score blinded to group allocation Comment: objective outcome measures taken from real‐time physiological monitoring systems and calibrated blood gas and oximeter analysers; therefore, lack of outcome assessor blinding unlikely to bias results
Incomplete outcome data (attrition bias) All outcomes	Low risk	19 consecutive SLT patients recruited; 4 did not meet inclusion criterion of haemodynamic stability. Missing data acknowledged and left blank (2 dependent variables for 1 participant, and single data entry point for another participant). Unclear whether investigator conducted a review of potential bias' from missing data, as stated within the methods Comment: missing data unlikely to bias within‐subject difference for primary outcomes
Selective reporting (reporting bias)	Unclear risk	Most participants met termination criterion (MABP) and were not excluded or withdrawn Comment: possible typographical error, but not explicitly clear whether SBP < 90 mmHg was intended parameter to indicate hypotension Analysis does not appear to be conducted in accordance with protocol for blood flow effects. Results and analyses of HR and MABP were conducted separately from CO for hypothesis testing of blood flow effects. CO range for each group was reported only, without analysis. CO as an outcome measure was not reported in the publication Comment: unclear selective reporting of blood flow effects due to ambiguity between hypotheses, methods of data collection and analysis for all measures
Other bias	Unclear risk	No baseline position described. Baseline ventilator settings presented separately for each group (mean and SD) with comparable group settings; other dependent variables taken at baseline but not reported Uniform cross‐over design without balance (not all body positions preceded each other the same number of times, and the supine position did not precede native lung down). Sequence (group) effect reported for PaO2 (univariate analysis), with higher mean PaO2 for group 3 for all body positions compared with other groups. However, not all possible sequence combinations examined in the design. No explanation for group effect provided. Unknown whether period effects or treatment‐by‐period interactions were investigated Comment: unclear whether group (sequence) differences due to baseline differences (random error in small sample and/or possible selection bias as unclear randomization procedures) or differences in standard care (unclear performance bias) or a genuine sequencing effect. Overall, unclear whether groups were comparable on trial entry. Carryover effects may be due to short active and possibly insufficient washout, with unclear carryover bias