This is part of a recurring series examining landmark articles in Emergency Medicine, in the style of ALiEM’s 52 Articles.
Discussing: 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 Eng J Med, May 2000; 342(18): 1301-08
This landmark study was stopped early! It determined that in patients with acute respiratory distress syndrome (ARDS) who are treated with lower tidal volumes than those treated with traditional volumes:
- Mortality is decreased by 31.0% vs 39.8% (P = 0.007)
- Breathing without assistance increases by the 28th day by 65.7% vs 55.0%
- The number of ventilator free days increases by 12 ± 11 vs 10 ± 11. days (P = 0.007)
ARDS is a life-threatening condition for which the mortality was quoted in this study to be approximately 40 to 50 percent. (To be blunt, any study that uses death as its primary outcome is looking at a very ill cohort.)
Much has been learned about the pathophysiology of ARDS, but very little headway has been made in the treatment of it. The authors of this study looked at adjusting ventilatory tidal volume and plateau pressures for treatment for ARDS. The authors also measured plasma interleukin-6 in the first 204 of 234 patients as a measure of lung inflammation. The results were significantly in favor of the lower tidal volume group.
This was a prospective, randomized controlled study that assorted 861 patients into two groups. Patients were randomly selected to be treated with tradition ventilation treatments, initial tidal volumes of 12 ml per kilogram of predicted body weight and a plateau pressure of 50 cm of water or less, versus lower tidal volumes of 6 ml per kilogram of predicted body weight and a plateau pressure of 30 cm of water or less.
Mean tidal volumes on days 1 to 3 were for the respected groups 6.2 ± 0.8 and 11.8 ± 0.8 ml per kg of predicted body weight, and plateau pressures were 25 ± 6 and 33 ± 8 cm of water.
Ventilator rate was adjusted to achieve a pH goal of 7.3 to 7.45 as well as treatment with bicarbonate infusions were permitted to correct mild-to-moderate acidosis.
The primary outcome was death before the patient was discharged home and was breathing without assistance. The second primary outcome was the number of days without ventilator use from day 1 to day 28. Other outcomes were the number of days without organ or system failure, and the occurrence of barotrauma.
This trial was discontinued because mortality was significantly less in the lower tidal volume group 31.0 percent vs 39.8 percent (P = 0.007). Also, ventilator free days within the first 28 days was greater in the lower tidal volume group 12 ± 11 vs 10 ± 11 (P = 0.007).
Finally, plasma interleukin-6 values decreased from 2.5 ± 0.7 pg per ml on day 0 to 2.3 ± 0.7 pg per ml on day 3 in the traditional lung volume group versus 2.5 ± 0.7 pg per ml to 2.0 ± 0.5 pg per ml in the lower tidal volume group (P < 0.001). This was attributed to decreased lung inflammation and possibly reduced systemic inflammatory response to lung injury. The authorize hypothesize that these decreases may contribute to the higher number of days without organ failure or system failure in the lower mortality group.
Level of Evidence
According to the ACEP grading scheme this trial receives a grade one level of evidence for having a randomized control design with excellent study design, applicability to a clinical question, adequate sample size and generalizability.
Maybe not so surprising, patients who received lower tidal volumes also required higher positive end-expiratory pressure and higher fraction of inspired oxygen, and the lower ratio of partial pressure of arterial oxygen to fraction of inspired oxygen.
Also, the mortality in this study was lower for both groups than statistically stated by the authors.
Finally, there was specific exclusion criteria which included patients under the age of 18. This begs the question, are the results of this study applicable to the pediatric population?
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 Eng J Med, May 2000; 342(18): 1301-08