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

ROY G. BROWER, MICHAEL A. MATTHAY, ALAN MORRIS, DAVID SCHOENFELD, B. TAYLOR THOMPSON AND ARTHUR WHEELER FOR THE ACUTE RESPIRATORY DISTRESS SYNDROME NETWORK Johns Hopkins University, Baltimore, Maryland; University of California-San Francisco, California; LDS Hospital, Salt Lake City, Utah; Massachusetts General Hospital, Boston, Massachusetts; and Vanderbilt University, Nashville, Tennessee N. Engl. J. Med., 342: 1301–1308, 2000 Traditional approaches to mechanical ventilation, which use tidal volumes of 10 to 15 mL per kg of body weight, can result in stretch-induced lung injury in patients with acute lung injury and the acute respiratory distress syndrome. A trial was conducted to ascertain whether ventilation with lower tidal volumes would improve the clinical outcomes of these patients. The patients were enrolled in a multicenter, randomized trial that compared traditional ventilation treatment involving an initial tidal volume of 12 mL per kg of predicted body weight and an airway pressure measured after a 0.5-sec pause at the end of inspiration (plateau pressure) of 50 cm of water or less, with ventilation with a lower tidal volume, which entailed an initial tidal volume of 6 mL per kg of predicted body weight and a plateau pressure of 30 cm of water or less. The first primary outcome was death before a patient was discharged home and was breathing without assistance. The second primary outcome was the number of days without use of a ventilator from day 1 to day 28. The trial was stopped after 861 patients had been enrolled because mortality was lower in the group treated with lower tidal volumes than in the group treated with traditional tidal volumes (31.0%vs. 39.8%), 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). The mean tidal volumes on days 1 and 3 were 6.2 ± 0.8 and 11.8 ± 0.8 mL per kg of predicted body weight, respectively, and the mean plateau pressures were 25 ± 6 and 33 ± 8 cm of water, respectively. It was found that in patients with acute lung injury and the acute respiratory distress syndrome, mechanical ventilation with a lower tidal volume than is traditionally used leads to decreased mortality and more days without ventilator use. Comment: This article represents a major breakthrough in the treatment of the acute respiratory distress syndrome (ARDS). The management of ARDS has intrigued physicians ever since the first description of the syndrome in 1967. Over the last decade and half evidence has accumulated to show us that ARDS is a heterogeneous process, which does not affect the lung uniformly, and that further lung injury occurs both from overdistention and repeated closure and opening of alveoli. Several researchers have attempted to show that changing ventilatory management would alter the outcome of ARDS patients, but results have been inconclusive. The present study is a large, multicenter, randomized trial that shows conclusively that ventilation with low tidal volume reduces mortality in ARDS patients by about 20%. Unlike previous research the investigators in the present trial managed to prevent the development of hypercapnia and respiratory acidosis, both of which have been considered inconsequential by some clinicians in the last decade. The accompanying editorial stresses that the use of lower airway pressure, rather than the use of low tidal volume, is important in prevention of ventilator-associated lung injury. 1 The low Vt group suffered from reduced inflammatory response as evidenced by lower levels of IL-6 and less organ or system dysfunction. The editorial also emphasizes that, unlike previous investigations, in the present study permissive hypercapnia and respiratory acidosis were not allowed. 1 Hypercapnia was first treated with increasing the respiratory rate to 35 breaths/min, and if acidosis persisted bicarbonate infusion was instituted. Although past attempts to control ARDS with various anti-inflammatory agents have failed, this study shows that by physiologic manipulation the inflammatory response can be controlled, and the outcome of patients improved. This interesting study lights the way to more clinical physiologic research (rather than pharmacologic studies) in the treatment of various ICU conditions. Arieh Eden M.D.