TABLE 1

Baseline characteristics of included randomised controlled trials

Morris et al., 1994 [17]Bein et al., 2013 [18]McNamee et al., 2021 [8]
Planned601201120
Randomised4079412
Randomised to ECCO2R2140202
Received ECCO2R19+40185§
Inclusion criteriaSevere ARDS and met ECMO criteriaƒ; ≤21 days of mechanical ventilation; aged ≥12 and ≤65 yearsModerate–severe ARDS# (PaO2/FIO2 <200 mmHg for ≥2 h); <7 days of mechanical ventilation; plateau airway pressure >25 cmH2O; absence of haemodynamic instabilityModerate–severe AHRF (PaO2/FIO2 <150 mmHg); within 48 h of onset; ≤7 days of mechanical ventilation; potentially reversible
Age, years
 ECCO2R33±350±1260 (51–69)
 Standard care38±349±1762 (50–70)
Sex, female/male
 ECCO2R13/82/3864/138
 Standard care10/99/3079/131
PaO2/FIO2 ratio, mmHg
 ECCO2R63±4152±37118 (96–134)
 Standard care64±4168±37116 (94–133)
APACHE II score, 0–71
 ECCO2R18±1NR19 (15–23)
 Standard care17±1NR20 (16–23)
Aetiology of ARDS/AHRF, % total patients randomised#,¶
 Pneumonia605780
 Sepsis848
 Aspiration99
 Trauma8242
 Inhalation12
 Emboli5
 Other27111
Mode of ECCO2RVeno-venousArterio-venousVeno-venous
Mechanical ventilation protocol in ECCO2R armVariable##
LFPPV
Minimum VT 4 mL·kg−1 (>250 mL)
VT 3 mL⋅kg−1 PBW
PEEP by ARDSNet “high PEEP/FIO2” table
fR 10–25
I:E ratio 1:1
Incremental reduction of VT to ≤3 mL·kg−1 PBW
PEEP by ARDSNet protocol
Mechanical ventilation protocol in control armPC-IRV
Minimum FIO2 and PEEP (maximum 35 cmH2O) to maintain PaO2 55–60 mmHg (60–65 mmHg if no evidence of barotrauma)
VT 6 mL⋅kg−1 PBW
PEEP set by ARDSNet “high PEEP/FIO2” table
fR 10–25
I:E ratio 1:1
Recommendation to use 6 mL⋅kg−1 PBW and set PEEP using the ARDSNet protocol
CrossoverNoNoNo
Primary outcome30-day survival28-day VFDs90-day mortality
Secondary outcomesICU LOSHospital mortalityVT at days 2 and 3
Hospital LOSOrgan-failure-free daysVFDs at day 28
Daily and total costsRequirement for RRTDuration of IMV in survivors
Ventilatory and physiological dataTransfusion requirementsNeed for ECMO up to day 7
Major complicationsUse of adjunctive therapies28-day mortality
Sedative/analgaesic requirementsAdverse event rate
Ventilatory and physiological data
Complications or adverse reactions

Data are presented as n, mean±sd or median (interquartile range), unless otherwise stated. ECCO2R: extracorporeal carbon dioxide removal; PaO2: arterial oxygen tension; FIO2: inspiratory oxygen fraction; APACHE: Acute Physiology and Chronic Health Evaluation; ARDS: acute respiratory distress syndrome; AHRF: acute hypoxaemic respiratory failure; LOS: length of stay; RRT: renal replacement therapy; VFDs: ventilator-free days; IMV: invasive mechanical ventilation; ECMO: extracorporeal membrane oxygenation; NR: not reported; LFPPV: low-frequency positive pressure ventilation; VT: tidal volume; PBW: predicted body weight; PEEP: positive end-expiratory pressure; fR: respiratory frequency; I:E: inspiratory to expiratory time ratio; PC-IRV: pressure controlled inverse ratio ventilation; ICU: intensive care unit. #: American–European Consensus Conference (AECC) definition of ARDS; : McNamee et al. [8] report aetiology only for the subgroup of patients meeting the Berlin definition of ARDS (n=248). Here, patients may have had more than one aetiology and thus the reported percentages do not sum to 100; +: one patient died before initiation of ECCO2R and one patient improved with mechanical ventilation alone; §: eight patients improved prior to ECCO2R, six had a technical issue with ECCO2R, two patients deteriorated and one patient withdrew consent; ƒ: defined as per Fowler et al. [37] and Suchyta et al. [38]. The trial was conducted prior to publication of the AECC definition of ARDS; ##: in the first 10 patients a peak airway pressure limit of 35 cmH2O was used. Thereafter, the study switched to a VT target.