Thomas 2007a.

Methods	Cross‐over trial (3‐treatment, 2‐sequence, 4‐period design) Pre‐specified analysis: linear mixed‐model analysis of group, side, time (measurement intervals) and their interactions, a priori paired contrasts of time (data combined from right lateral and left lateral positions, i.e. grouped as 'lateral positioning' for comparison with data combined from supine position periods). Pre‐specified subgroup analyses included position (within‐subject factor) for unilateral lung pathology (UniLP) (comparison between bad lung down and good lung down)
Participants	34 mechanically ventilated adults who were haemodynamically stable (baseline HR 60 to 130 beats/min, MABP 70 to 120 mmHg, no compromising arrhythmias, ICP < 20 mmHg, mean PAP < 30 mmHg, PCWP 8 to 17 mmHg) and met subgroup classification Sex (M/F) 22/12, mean age 46.1 years ± 17.3                                                                               Subgroup classification (lung pathology locality on CXR): no lung pathology (NoLP) (n = 4), UniLP (n = 13), bilateral lung pathology (BilatLP) consistent with ALI/ARDS criteria based on American‐European consensus conference on ARDS (n = 17) Mean PEEP (NoLP = 5.3 ± 0.5 cmH2O, UniLat = 7.5 ± 3.0 cmH2O, BilatLP = 8.8 ± 2.8 cmH2O), mean Vt (NoLP = 10.2 ± 1.6 mL/kg, UniLat = 9.1 ± 1.9 mL/kg, BilatLP = 7.4 ± 1.5 mL/kg) with Bilevel mode (n = 8), SIMV mode (n = 25) and CPAP mode (n = 1) Diagnosis: respiratory sepsis (n = 15), neurological (n = 9), postop neurosurgical (n = 5), postop abdominal (n = 2), abdominal sepsis (n = 1), non‐operative cardiogenic (n = 1), bacteraemia (n = 1) Severity of illness at baseline: mean APACHE II score (NoLP 16 ± 4.2, UniLP 18.2 ± 5.7, BilatLP 26.5 ± 9.7), mean SOFA score and MFI scores for each subgroup also given Exclusion criteria: < 18 years, pre‐existing severe chronic respiratory disease (FEV < 40%), burn injuries, chest wall abnormalities, pulmonary barotrauma (e.g. pneumothorax), paralysis medications, nitric oxide, contraindications to lateral positioning (e.g. unstable spinal fractures) and unilateral changes on CXR due to effusions or pulmonary masses Setting: ICU, Royal Brisbane and Women's Hospital (tertiary referral university affiliated metropolitan centre) Brisbane, Australia
Interventions	Left lateral and right lateral positions for 120 minutes, first supine position for 60 minutes, second supine position for ≥ 30 minutes Sequences/groups S(baseline T 30),R, S, L, S     S(baseline T 30),L, S, R, S (T in minutes)
Outcomes	(1) P/F ratio, (2) MABP and HR, (3) CO and CI (BilatLP subgroup only), (4) adverse events Measurement intervals for each sequence reported as T0, T30, T120, T150, T0, T30, T120, T150 (T in minutes). Lateral positions measured at T30 and T120. Supine position data measured at T0 (before each lateral turn) and T150 (equivalent to 30 minutes in the supine position)
Standard management	Ventilator settings constant (pre‐planned adjustment of FiO2 ≤ 0.1 to alleviate severe hypoxaemia (SpO2 < 90% or PaO2 < 60 mmHg), change not required). Physiotherapy (manual hyperinflation) withheld. Pre‐oxygenation (hyperoxygenation) with closed circuit suctioning, 20 minutes allowed for equilibrium (minimum) before ABG sampling. Vasopressor medication and sedation altered as deemed clinically necessary by medical staff; changes documented (vasopressor commenced before protocol (n = 4) and during study (n = 1) for hypotension, vasopressor commenced before protocol (n = 1) and during study (n = 1) with 500 mL of fluid bolus for CPP control)
Position description	90 degrees lateral rotation, HOB elevation not described for lateral positions and < 20 degrees for supine position, angle verification method not described for rotation or HOB elevation Other descriptions: pillow placed in front of participant's thorax for cuddling, with care taken to ensure that pelvis and shoulder girdles were at 90 degrees to the support surface; investigator monitored position during study to ensure position maintained and minor adjustment made as necessary
Washout period	Not described
Notes	Sample size calculation for P/F ratio (20 in each group, moderate effect with magnitude of P/F change 20, σ = 35, α = 0.05, 1‐β = 0.8). Recalculation during interim analysis, with a requirement for 128 participants stated. Recruitment ceased with reason provided (beyond the capacity of single‐centre study) Comment: Study was underpowered to detect differences among primary outcomes CO and CI determined by oesophageal Doppler calculations (single outcome testing (CO/CI) in ALI/ARDS subgroup only) Schema for analysis included baseline, lateral positioning, recovery. Data from the 2 groups (sequences) were combined at each time point (T0, T30, T120, T150) (i.e. lateral position data (right and left side) combined, and supine position periods combined before (i.e. 0 minutes) and after (i.e. 150 minutes) lateral positioning). Paired contrast analysis conducted from supine to lateral or from lateral to supine positions. Comparisons between lateral positioning, baseline and recovery (supine position periods) were not equivalent in terms of duration in each body position (120 minutes vs 30 minutes) and number of measurements taken within each body position (2 repeated measures vs 1 measure for each period) Comments: no extractable lateral position data for meta‐analysis because no period data were provided for each lateral position (right vs left; total sample) and for a unit of analysis error (mean and SD for time points). Supine position order was not randomized within the design; therefore, within‐subject comparisons involving the supine position were not valid for meta‐analysis
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Quotations: "prospective, within subject randomized cross‐over study" .."order of right or left 90° lateral turn was randomized"..."originally generated from a random number table"
Allocation concealment (selection bias)	Unclear risk	Quotation: "concealed allocation" stated. No further description, except principal investigator was unaware of participant's previous responses to position change to reduce selection bias
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 Comment: objective outcome measures taken from digital display of continuous and intermittent physiological monitoring systems and calibrated blood gas analyser; therefore, lack of outcome assessor blinding unlikely to bias results
Incomplete outcome data (attrition bias) All outcomes	Unclear risk	No numerator reported for outcome results. Intention‐to‐treat analysis stated, with data from participants who did not complete protocol included in the analysis. Lateral position data had 11 turns missing, with rationale provided (9 participants did not complete entire protocol) Comments: missing data points unlikely to bias within‐subject differences in primary outcomes. However, given the specific design features and methods of analysis of this study (within‐participant lateral position data collated and analysed as an independent group for comparison with supine position data), it remains unclear how missing data were handled. It was not explicitly clear that supine position data were complete. Unclear whether each group (sequence) and/or each period (body position) had similar rates of attrition
Selective reporting (reporting bias)	Low risk	Pre‐specified outcomes reported; analysis consistent with pre‐specified method stated
Other bias	Unclear risk	Non‐uniform unbalanced cross‐over design with unit of analysis errors and design ambiguity. Methods section did not make it explicitly clear that participants returned to supine position for data collection at 150 minutes after the second lateral position, but results were presented Unclear whether subgroup analysis (comparison between bad lung down vs good lung down in UnilatLP group) was based on average of repeated measures or a single measurement at 30 minutes or 120 minutes after turning. However, discrepancy unlikely to influence main effect testing of group, side and time Comments: Unclear whether carryover, sequence or period effects or other treatment‐by‐period interactions may have been sources of bias. Matched pairs and linear mixed‐model analyses did not account for possible period or carryover effects within the design or analysis. Carryover effects may be due to short active and possibly insufficient washout within some periods. Unclear risk of carryover bias