Ventilation with Lower Tidal Volumes as Compared with Traditional Tidal Volumes for Acute Lung Injury and the Acute Respiratory Distress Syndrome

Background. Traditional approaches to mechanical ventilation use tidal volumes of 10 to 15 ml per kilogram of body weight and may cause stretch-induced lung injury in patients with acute lung injury and the acute respiratory distress syndrome. We therefore conducted a trial to determine whether ventilation with lower tidal volumes would improve the clinical outcomes in these patients. Methods. Patients with acute lung injury and the acute respiratory distress syndrome were enrolled in a multicenter, randomized trial. The trial compared traditional ventilation treatment, which involved an initial tidal volume of 12 ml per kilogram of predicted body weight and an airway pressure measured after a 0.5-second pause at the end of inspiration (plateau pressure) of 50 cm of water or less, with ventilation with a lower tidal volume, which involved an initial tidal volume of 6 ml per kilogram of predicted body weight and a plateau pressure of 30 cm of water or less. The primary outcomes were death before a patient was discharged home and was breathing without assistance and the number of days without ventilator use from day 1 to day 28. Results. The trial was stopped after the enrollment of 861 patients because mortality was lower in the group treated with lower tidal volumes than in the group treated with traditional tidal volumes (31.0 percent vs. 39.8 percent, P=0.007), and the number of days without ventilator use during the first 28 days after randomization was greater in this group (mean [±SD], 12±11 vs. 10±11; P=0.007). The mean tidal volumes on days 1 to 3 were 6.2±0.8 and 11.8±0.8 ml per kilogram of predicted body weight (P<0.001), respectively, and the mean plateau pressures were 25±6 and 33±8 cm of water (P<0.001), respectively. Conclusions. In patients with acute lung injury and the acute respiratory distress syndrome, mechanical ventilation with a lower tidal volume than is traditionally used results in decreased mortality and increases the number of days without ventilator use. (N Engl J Med 2000;342.) Page 1 of 9 Original Articles -NEJM 6/23/2002 file://C:\Buteyko\Articles\LowerTidalVolume.htm The mortality rate from acute lung injury and the acute respiratory distress syndrome (1) is approximately 40 to 50 percent. (2,3,4) Although substantial progress has been made in elucidating the mechanisms of acute lung injury, (5) there has been little progress in developing effective treatments. Traditional approaches to mechanical ventilation use tidal volumes of 10 to 15 ml per kilogram of body weight. (6) These volumes are larger than those in normal subjects at rest (range, 7 to 8 ml per kilogram), but they are frequently necessary to achieve normal values for the partial pressure of arterial carbon dioxide and pH. Since atelectasis and edema reduce aerated lung volumes in patients with acute lung injury and the acute respiratory distress syndrome, (7,8) inspiratory airway pressures are often high, suggesting the presence of excessive distention, or "stretch," of the aerated lung. In animals, ventilation with the use of large tidal volumes caused the disruption of pulmonary epithelium and endothelium, lung inflammation, atelectasis, hypoxemia, and the release of inflammatory mediators. (9,10,11,12,13,14) The release of inflammatory mediators could increase lung inflammation and cause injury to other organs. (10,15) Thus, the traditional approach to mechanical ventilation may exacerbate or perpetuate lung injury in patients with acute lung injury and the acute respiratory distress syndrome and increase the risk of nonpulmonary organ or system failure. The use of lower tidal volumes during ventilation in patients with acute lung injury and the acute respiratory distress syndrome may reduce injurious lung stretch and the release of inflammatory mediators. (16,17,18) However, this approach may cause respiratory acidosis (16,17) and decrease arterial oxygenation (19,20) and may therefore require changes in the priority of some objectives in the care of these patients. With the traditional approach, the attainment of normal partial pressure of arterial carbon dioxide and pH is given a higher priority than is protection of the lung from excessive stretch. With an approach that involves lower tidal volumes, the reverse is true. Uncontrolled studies suggested that the use of a lower tidal volume would reduce mortality in patients with acute lung injury and the acute respiratory distress syndrome, (17) but the results of four randomized trials of lungprotecting ventilation strategies have been conflicting. (21,22,23,24) The present trial was conducted to determine whether the use of a lower tidal volume with mechanical ventilation would improve important clinical outcomes in such patients.