Effects of a clinical trial on mechanical ventilation practices in patients with acute lung injury

Am J Respir Crit Care Med. 2008 Jun 1;177(11):1215-22. doi: 10.1164/rccm.200709-1424OC. Epub 2008 Mar 20.


Rationale: In a clinical trial by the Acute Respiratory Distress Syndrome Network (ARDSNet), mechanical ventilation with tidal volumes of 6 ml/kg decreased mortality from acute lung injury. However, interpretations of these results generated controversy and it was unclear if this trial would change usual-care practices.

Objectives: First, to determine if clinical practices at ARDSNet hospitals changed after the tidal volume trial. Second, to determine if tidal volume and plateau pressure (Pplat) within 48 hours before randomization affected hospital mortality in patients subsequently managed with 6 ml/kg predicted body weight (PBW).

Methods: We used preenrollment data from 2,451 patients enrolled in six trials (1996-2005) to describe changes in tidal volume over time. We used logistic regression to determine if preenrollment tidal volume or Pplat affected mortality.

Measurements and main results: Median preenrollment tidal volume decreased from 10.3 ml/kg PBW (range, 4.3-17.1) during the tidal volume trial (1996-1999) to 7.3 ml/kg PBW (range, 3.9-16.2) after its completion (P < 0.001). Preenrollment tidal volume was not associated with mortality (P = 0.566). The odds of death increased multiplicatively with each cm H(2)O of preenrollment Pplat (P < 0.001) (e.g., the odds of death was 1.37 times greater when preenrollment Pplat increased by 10 cm H(2)O).

Conclusions: Physicians used lower tidal volumes after publication of the tidal volume trial. Preenrollment Pplat was strongly associated with mortality, and may reflect disease severity independent of tidal volume. Pplat measured early in the course of acute lung injury, after accounting for tidal volume, is a respiratory system-specific value with strong prognostic significance.

Publication types

  • Multicenter Study
  • Research Support, N.I.H., Extramural

MeSH terms

  • Airway Resistance
  • Clinical Trials as Topic
  • Cohort Studies
  • Hospital Mortality
  • Humans
  • Logistic Models
  • Odds Ratio
  • Practice Patterns, Physicians' / statistics & numerical data*
  • Respiration, Artificial / methods*
  • Respiratory Distress Syndrome / mortality
  • Respiratory Distress Syndrome / physiopathology
  • Respiratory Distress Syndrome / therapy*
  • Retrospective Studies
  • Tidal Volume / physiology