NHLBI ARDS Network

Prospective, Randomized, Multi-Center Trial of Higher End-expiratory Lung Volume/Lower FiO2 versus Lower End-expiratory Lung Volume/Higher FiO2 Ventilation in Acute Lung Injury and Acute Respiratory Distress Syndrome.

This study was a prospective, randomized, controlled multi-center trial. The objective was to compare clinical outcomes of patients with acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) treated with a higher end-expiratory lung volume/lower FiO2 versus a lower end-expiratory lung volume/higher FiO2 ventilation strategy. The study was named ALVEOLI and was based on a Phase II study of patients with ARDS showing a remarkable improvement in survival in patients managed with this open lung approach (Amato MB, et al. Effect of a protective-ventilation strategy on mortality in the acute respiratory distress syndrome. N Engl J Med 1998;338:347-354). This approach involved both low tidal volumes and higher PEEP, among other interventions, to keep the lung open and it was not clear if the lower tidal volumes or the higher PEEP levels, or both contributed to the marked improvement. The ALVEOLI study tested lower tidal volumes with higher PEEP and, after enrolling 549 patients, found no further improvement in survival with higher PEEP (Brower RG, Lanken PN, MacIntyre N, Matthay MA, Morris A, Ancukiewicz M, Schoenfeld D, Thompson BT; National Heart, Lung, and Blood Institute ARDS Clinical Trials Network. Higher vs. lower positive end-expiration pressures in patients with the acute respiratory distress syndrome. N Engl J Med. 2004 Jul 22;351(4):327-36).

In the absence of data proving superiority of lower or higher PEEP for survival, clinicians may elect to use lower PEEP levels to avoid ventilator-induced lung injury from over distension in patients whose airway pressures are high. Lower levels may also be preferable when there is overt barotrauma or when higher PEEP levels cause hypotension. Higher PEEP levels may be preferable in patients who do not have these limiting factors, especially if there is a clear indication of improved oxygenation, reduced dead space, or improved lung compliance when higher PEEP levels are applied.

Two additional trials completed by investigators in Canada and Europe but have yet of be published.