Lower Tidal Volume Strategy (3ml/kg) Combined with Extracorporeal CO2 Removal Versus ‘Conventional’ Protective Ventilation (6 ml/kg) in Severe ARDS (Bein et al)

Intensive Care Med Vol 39, Issue 5, pg 847–856, May 2013

QMC AICU Journal Club, April 2013.

Dr Amit Pancholi 



Acute respiratory distress syndrome (ARDS) is characterized by damage to the lung parenchyma, caused by either indirect or direct insults, including ventilation itself.  Tidal hyperinflation and cyclic alveolar recruitment/derecruitment during mechanical ventilation can lead to an entity called ventilator induced lung injury (VILI).

ARDSNet demonstrated that a lung protective strategy with VT of 6 ml/kg PBW and Pplat <30 cmH2O decreased mortality by a relative 22% compared to control. Post hoc analysis of this study found that the lower the Pplat, the better the patient’s chances of survival even for Pplat substantially <30 cmH2O, and these data suggested that even lower tidal volumes might further improve survival. However, in severe ARDS the implementation of such a strategy may be limited by a therapeutic dilemma due to the increased likelihood of more severe hypercapnia and acidosis

Study design

Prospective randomised clinical trial to investigate the effects of combining a very low VT (3 ml/kg PBW) with arteriovenous extracorporeal CO2-elimination (avECCO2-R) in patients suffering from established ARDS compared with conventional ventilation (6ml/kg). Multicentre



79 Patients were enrolled from September 2007 through December 2010 at 8 ICUs in Germany and 2 ICUs in Austria, 40 patients were randomized to avECCO2-R and 39 patients to the control. Patients were selected if they had presence of ARDS according to the AECC defined by bilateral infiltrates on chest X-ray, and a PaO2/ FiO2 <200 present for at least 2h. At the time of screening, patients could not have any evidence of left ventricular failure

Inclusion Criteria: Age ≥18 years, History of mechanical ventilation <7 days, Pplat >25 cmH2O at defined ventilator settings (PEEP/FiO2-table <VT = 6 ml/kg), Absence of severe haemodynamic instability with high demand for vasopressors (MAP ≥70 mmHg with continuous noradrenaline infusion ≤0.4 µg/kg/min)

Exclusion Criteria: Decompensated heart insufficiency, Acute coronary syndrome, Severe chronic obstructive pulmonary disease, Advanced malignancy with life expectancy <6 months, Chronic dialysis treatment, Lung transplant patients, Proven heparin-induced thrombocytopenia (HIT), Morbid obesity (BMI>40 kg/m2), Cirrhosis of the liver Child Class ≥ B (Child–Pugh scores ≥ 7), Acute fulminant hepatic failure, Severe peripheral arterial occlusive disease, Absence of limb Doppler pulse,  Acute brain injury (Glasgow Coma Scale ≤ 9)


Selected patients were stabilised for 24hr with conventional lung protective mechanical ventilation, use of supportive measures and haemodynamic evaluation (ECHO) to help rule out patients with acute cardiogenic pulmonary oedema

Patients who still met ARDS criteria after 24hr were randomised into the study or control group

Study Group: Arteriovenous extracorporeal CO2-elimination (avECCO2-R)  and Low volume ventilation of VT 3ml/kg, PEEP following ARDSNet high-PEEP/FiO2 table, RR 10-25/min with I:E ratio of 1:1


Conventional Ventilation with VT 6ml/kg, PEEP following ARDSNet high-PEEP/FiO2 table, RR 10-25/min with I:E ratio of 1:1


Primary Outcome was Ventilator-free days with 28 days and in a 60 days period


An independent Data Safety Monitoring Board monitored the study and the principal investigator performed visits aimed at information and supervision of the study protocol in the participating centres

Participitants were not blinded

Patients were randomised through phone hot line by a random number table generated by the involved statistician


At randomisation, there were no significant differences in MAP, HR or demand vasopressor uses, however, there was a significantly lower PaO2/FiO2 in the study arm (152 vs 168; p=0.044. No significant statistical difference in VFD-28 or VFD-60 between the groups (VFD-28 10 vs 9.3; p=0.779; VFD-60 33 vs 29; p=0.469). But post hoc analysis demonstrated that surviving patients with greater hypoxaemia (PaO2/FiO2 <150 at randomisation) treated with avECCO2-R had a significantly shorter period of ventilation compared to the control group (VFD-28 11.5 vs 5; p=0.033; VFD-60 40.9 vs 28.2; p=0.033). Non-pulmonary organ failure free days within 60 days, intensive care and hospital days were not statistically different between groups


Low Vventilation assisted by avECCO2-R was not associated with significant reduction of the period of mechanical ventilation within 28 or 60 days or the intensive care and hospital stay but post hoc analysis demonstrated that patients who were more hypoxaemic at baseline and were treated with the low VT strategy had a significantly shorter ventilation period

AvECCO2-R was associated with a significant reduction in analgesic and sedative use, increased spontaneous breathing and was safe and feasible with low rate of adverse events

Further studies needed with a larger sample size looking specifically at patients with severe ARDS


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