Zapol 1979.

Methods	This multi‐centre randomized clinical trial sought to define which, if any, types of patients with acute lung injury might experience increased survival rates when extracorporeal membrane oxygenation (ECMO) therapy supplements mechanical ventilation.
Participants	9 medical centres collaborated in a prospective randomized study of ICU patients with acute respiratory failure. With the exception of patients suffering from chronic and irreversible diseases, adult patients with acute respiratory failure of all causes were treated. Inclusion criteria for patients with acute respiratory failure via fast entry: PaO2< 50 mmHg for longer than 2 hours with FiO2 1 and PEEP > 5 cm H2O. Inclusion criteria for patients with acute respiratory failure via slow entry: maximal medical treatment for 48 hours: PaO2 < 50 mmHg for longer than 12 hours with FiO2 > 0.6 and PEEP > 5 cm H2O and Qs/Qt > 30% when measured at FiO2 1 and PEEP > 5 cm H2O. Patients were excluded from the study if any of the following criteria were applicable: age < 12 or > 65 years; duration of pulmonary insult > 21 days; pulmonary capillary wedge pressure > 25 mmHg; chronic systemic disease, including irreversible CNS injury, chronic pulmonary disease, rapidly fatal malignancy and chronic heart, liver or renal failure; severe body burns; or lack of physician or patient consent.
Interventions	For 42 participants, veno‐arterial partial bypass was performed at the 9 centres using 4 membrane oxygenator designs (Kolobow Scimed, Lande‐Edwards, Bramson and General Electric Peirce). Venous blood was roller‐pumped through the membrane oxygenator and was returned to the systemic circulation. All bypass participants received intravenous heparin, and their kaolin‐activated coagulation time was monitored at least hourly. To assess changes in pulmonary haemodynamics, 45 participants had a flow‐directed pulmonary artery catheter inserted. When possible, bypass flow was reduced to 0.5 L/min every 12 hours and arterial blood gas tensions were sampled without substantial extracorporeal support. 48 participants in the control group were treated with conventional mechanical ventilation.
Outcomes	Survival.
Notes	This study was supported by the Division of Lung Diseases, National Heart, Lung and Blood Institute.
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	"Therapy, either mechanical ventilation alone (control) or supplemented with partial bypass, was randomly assigned by the data centre after entry into the study"
Allocation concealment (selection bias)	Low risk	"…randomly assigned by the data centre after entry into the study"
Blinding of outcome assessment (detection bias) All outcomes	Unclear risk	Not reported
Incomplete outcome data (attrition bias) All outcomes	Low risk	"Of the eight patients who survived, seven had serial pulmonary function studies"
Selective reporting (reporting bias)	Unclear risk	Information insufficient to permit a judgement
Other bias	Unclear risk	"Although specific mechanical ventilation patterns may have differed between centres, each patient was treated in an established intensive care unit employing broadly accepted regimens of medical therapy"

ARDS = Acute respiratory distress syndrome.

BMI = body mass index.

cm H₂O = centimetre of water.

CNS = central nervous system.

CO₂ = carbon dioxide.

CPAP = continuous positive airway pressure.

CPPV = continuous positive‐pressure ventilation.

CTH = total thoracic compliance.

CVP = central venous pressure.

ECMO = extracorporeal membrane oxygenation.

FiO₂ = fraction of inspired oxygen.

HIT = heparin‐induced thrombocytopenia.

IBW = ideal body weight.

ICU = intensive care unit.

iLA = interventional lung assist.

LFPPV‐ECCO₂ = low‐frequency positive‐pressure ventilation/extracorporeal carbon dioxide removal.

LOS = length of stay.

MAP = mean arterial pressure.

mcg/kg/min = microgram/kilogram/minute.

mmHg = millimetre of mercury.

PAO₂= partial alveolar oxygen pressure.

PaO₂ = partial arterial pressure of oxygen.

PCIRV = pressure‐controlled inverse ratio ventilation.

PEEP = positive end‐expiratory pressure.

pH = potential hydrogen.

pHa = arterial potential hydrogen.

Ppeak = peak airway pressure.

Pplat = plateau pressure levels.

PW = pulmonary artery wedge pressure.

RASS = Richmond Agitation Sedation Scale.

SaO₂ = arterial saturation of oxygen.

SEM = standard error of the mean.

VFD = ventilator‐free day.

VR = ventilation rate.

VT = volume tidal.

VV = veno‐venous.