BALTIMORE--Simply by decreasing tidal volume on the ventilator, intensivists can markedly lower mortality in patients with acute respiratory distress syndrome (ARDS) and other forms of acute lung injury and increase the likelihood that these patients can be weaned from mechanical ventilation. That is what researchers in the Acute Respiratory Distress Syndrome Network found when they examined the use of lower tidal volumes in a large multicenter study.[1]

"There's been growing concern over the past 20 years that the traditional way of ventilating patients with ARDS may exacerbate or perpetuate their lung injury," lead study author Roy Brower, MD, recently told PULMONARY REVIEWS. That tradition has been to use large tidal volumes--10 to 15 mL/kg of body weight--which may worsen acute lung injury by overdistending the lungs.

"Textbooks recommended generous tidal volumes to compensate for inefficient gas exchange in the injured lung," noted Dr. Brower, an associate professor of medicine at Johns Hopkins University in Baltimore. "These tidal volumes usually enable us to achieve a normal PCO₂ and pH."

However, the findings he and his colleagues reported have called into serious question the use of generous tidal volumes. Indeed, mortality decreased by 9% (from 40% to 31%) among study subjects who received lower tidal volumes. That is a substantial mortality decrease, stressed Dr. Brower, particularly because studies of ARDS and other forms of acute lung injury infrequently show a benefit for lung protection strategies.

In fact, the researchers were so impressed that they stopped their study nine months early, and the results were released two months before their scheduled May 4th publication in the New England Journal of Medicine. Physicians can access the findings at http://www.nejm.org.

MECHANICAL VENTILATION PROCEDURES

The study, which was sponsored by the National Heart, Lung, and Blood Institute, included 861 mechanically ventilated patients with acute lung injury. These patients most commonly had ARDS related to pneumonia, sepsis, aspiration, or trauma.

To be eligible for the study, patients had to have an acute decrease--to 300 or less--in the ratio of partial pressure of arterial oxygen to fraction of inspired oxygen (PaO₂/FIO₂). They also had to have bilateral pulmonary infiltrates consistent with edema on chest radiography and no clinical signs of left atrial hypertension (if measured, a pulmonary capillary wedge pressure of 18 mm Hg or less was required).

Patients were randomized to traditional or lower tidal volumes, delivered using the volume-assist--control mode. In the group receiving traditional ventilation, the tidal volume was initially set at 12 mL/kg of predicted body weight. This was reduced stepwise by 1 mL/kg as necessary to maintain a plateau pressure less than 50 cm H₂O.

In the lower tidal volume group, the tidal volume was set at 6 mL/kg of predicted body weight within four hours of randomization. The researchers also reduced this group's tidal volume stepwise by 1 mL/kg, if necessary, to maintain a plateau pressure less than 30 cm H₂O. The lower limit for tidal volume in both study groups was 4 mL/kg of predicted body weight.

There were exceptions to these procedures. The researchers permitted plateau pressures above 50 cm H₂O in the traditional group and above 30 cm H₂O in the lower tidal volume group if the tidal volume was 4 mL/kg or if the arterial pH was less than 7.15. In the lower tidal volume group, tidal volume could be increased to 7 or 8 mL/kg for patients with severe dyspnea if the plateau pressure remained at 30 cm H₂O or less.

THE FIRST TRIAL OF ITS KIND

The researchers continued the ventilation procedures for 28 days after randomization. The mean tidal volume and plateau pressure during the first three days were significantly smaller in the lower tidal volume group than in the traditional group (6.2 vs 11.8 mL/kg and 25 cm vs 33 cm H₂O, respectively).

Mortality was 31% in the lower tidal volume group, compared with 40% in the traditional group. Furthermore, patients in the lower tidal volume group had more ventilator-free days (12 vs 10) and were more likely to be weaned by day 28 (66% vs 55%). These patients also had a higher number of days without circulatory, coagulation, or renal failure. No difference emerged between the two groups in the incidence of barotrauma.

"There are many ARDS studies and most of them are negative, including two trials similar to ours that were stopped early because of a lack of efficacy," commented Dr. Brower.[2,3] "So, to our knowledge, ours is the first large multicenter trial to demonstrate that a lower tidal volume is beneficial."

Dr. Brower said he knows of only one other trial that supports the use of lower tidal volumes--a small study of 53 ventilated patients with early ARDS, published about two years ago. The study examined a combination lung protection strategy that included a smaller tidal volume, higher positive end-expiratory pressure, permissive hypercapnia, and other interventions. It, too, demonstrated markedly decreased mortality and increased weaning success.[4]

There is a downside to lower tidal volumes, however. "In some patients, we're unable to achieve a normal pH and PCO₂, so some hypercapnia and acidosis may occur," Dr. Brower pointed out. "Also, when we use smaller breath sizes, ARDS patients frequently become more dyspneic and agitated, and therefore, may require higher doses of sedatives."

Nonetheless, he concluded, "our study has confirmed the intuitive concern intensivists have about higher tidal volumes stretching and injuring the lungs. So we should reprioritize our objectives and recognize that it's more important to use smaller tidal volumes than to achieve a normal pH and PCO₂."

--Timothy Begany

References
1. The Acute Respiratory Distress Syndrome Network. Ventilation with lower tidal volumes as compared with traditional tidal volumes for acute lung injury and the acute respiratory distress syndrome. N Engl J Med. Article released prior to scheduled publishing date of May 4, 2000.
2. Brochard L, Roudot-Thoraval F, Roupie E, et al. Tidal volume reduction for prevention of ventilator-induced lung injury in acute respiratory distress syndrome. The Multicenter Trial Group on Tidal Volume reduction in ARDS. Am J Respir Crit Care Med. 1998;158:1831-1838.
3. Stewart TE, Meade MO, Cook DJ, et al. Evaluation of a ventilation strategy to prevent barotrauma in patients at high risk for acute respiratory distress syndrome. The Pressure- and Volume-Limited Ventilation Strategy Group. N Engl J Med. 1998;338:355-361.
4. Amato MB, Barbas CS, Medeiros DM, et al. Effect of a protective-ventilation strategy on mortality in the acute respiratory distress syndrome. N Engl J Med. 1998;338:347-354.

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