ARDS

Diagnosis, risk factors, and long-term outcomes

Bernard GR, Artigas A, Brigham KL, et al., The American European consensus conference on ARDS: definitions mechanisms, relevant outcomes and clinical trial coordination, Am J Respir Crit Care Med 1994; 149:818–24. Noteworthy for establishing the standard for the clinical diagnosis of ARDS for subsequent clinical trials. http://www.ncbi.nlm.nih.gov/pubmed/7509706?ordinalpos=2&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum

Rubenfeld GD, Caldwell E, Granton J, et al. Interobserver variability in applying a radiographic definition for ARDS. Chest 1999;116:1347-53. A group of 21 experts in ARDS were asked to determine whether a series of CXRs met the American-European Consensus Conference radiographic criterion for ARDS. Interobserver agreement was only moderate.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=10559098

Hudson LD, Milberg JA, Anardi D, Maunder RJ. Clinical risks for development of ARDS. Am J Respir Crit Care Med 1995;151:293-301. Study describes the incidence of ARDS in patients with various clinical risk factors. Also found 1) greater mortality in at-risk patients that develop ARDS and 2) ARDS develops within 48 to 72 hours of the time clinical risk is identified in the vast majority of patients.http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=7842182

Herridge MS, Cheung AM, Tansey CM, et al. One-year outcomes in survivors of the acute respiratory distress syndrome. N Engl J Med. 2003; 348:683-93. This thorough follow-up evaluation is noteworthy for finding survivors are commonly impaired by non-pulmonary, rather than pulmonary factors. Fatigue, weakness, reduced quality of life, and decreased exercise tolerance are common 12 months after discharge. Aside from diffusing capacity, pulmonary function tests generally normalized. At 12 months,none of the 109 patients required supplemental oxygen at rest and 6% of patients had exertional hypoxemia. http://www.ncbi.nlm.nih.gov/pubmed/12594312?ordinalpos=28&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DefaultReportPanel.Pubmed_RVDocSum   

Treatment

Ventilator Strategies

Ashbaugh DG, Bigelow DB, Petty TL, et al. Acute respiratory distress in adults. Lancet 1967;2:319-23. Original description of ARDS and use of PEEP in treating ARDS. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=4143721

ARDS Network. Ventilation with lower tidal volumes as compared with traditional tidal volumes for ALI and ARDS. N Engl J Med. 2000;342:1301-8. Results of the ARMA study found the use of low (6 ml/kg predicted weight) rather than “standard” (12 ml/kg predicted weight) tidal volumes reduced mortality from 40 to 30%. These results form much of the basis for use of low- stretch/low tidal volume ventilation strategy in acute lung injury.
http://content.nejm.org/cgi/content/abstract/342/18/1301

Eichacker PQ, Gerstenberger EP, Banks SM, et al. Meta-analysis of ALI and ARDS trials testing low tidal volumes. Am J Respir Crit Care Med 2002;166:1510-4.  In this controversial analysis, the authors question the validity of the ARDS network study above, arguing that 1) the mortality benefit resulted from excess mortality in the traditional arm, 2) the traditional arm did not receive the standard of care (authors argue the traditional arm received excessively large tidal volumes), and 3) very low tidal volumes are harmful.  This analysis and the authors' conclusions have been vigorously challenged and rebutted by others. See links to commentaries at the end of article.
http://ajrccm.atsjournals.org/cgi/content/full/166/11/1510          

Amato MBP, Barbas CSV, Medeiros DM, et al. Effect of a protective-ventilation strategy on mortality in ARDS. N Engl J Med. 1998;338:347-54. Small, randomized, study famous for using a combination of the lower inflection point of the pressure-volume curve to set PEEP, recruitment maneuvers (CPAP 35-40 cm x 40 sec.), and low-tidal volumes (< 6cc/kg). 28-day mortality was lower in the intervention group, but the conventional group had an unusually high mortality (71%). Patients overall received higher PEEP than in the ARMA study.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=9449727

Brower RG, Lanken PN, MacIntyre N, et al. Higher versus lower positive end-expiratory pressures in patients with the acute respiratory distress syndrome. N Engl J Med 2004;351:327-36.  A NHLBI ARDS net randomized trial comparing high and low PEEP strategies in 549 patients with ALI or ARDS found no significant difference in mortality, ventilator-free days, ICU-free days, or organ failure-free days in the two groups.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15269312

Mercat A, Richard JC, Vielle B, et al. Positive end-expiratory pressure setting in adults with acute lung injury and acute respiratory distress syndrome: a randomized controlled trial. JAMA  2008;299:646-55. The ExPress study compared low vs. high PEEP in 767 patients with ALI/ARDS receiving low tidal volume ventilation. In the high-PEEP group, PEEP was adjusted to a target plateau pressure of 28 to 30 cm H2O regardless of oxygenation while target PEEP in the minimal distension group was 5 to 9 cm H2O.  Mortality at 28 days did not differ, but the high-PEEP group had a higher median number of ventilator-free days and required fewer “rescue” interventions such as proning.  It appears the greatest benefit to a high-PEEP strategy is in patients with more severe lung edema, but whether there is a survival benefit in this subpopulation is still unclear.  See also results of the Lung Open Ventilation Study (LOVS) in the same issue (Stewart TE et al.).
http://www.ncbi.nlm.nih.gov/pubmed/18270353?ordinalpos=1&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum

Derdak S, Mehta S, Stewart TE, et al. High-frequency oscillatory ventilation for acute respiratory distress syndrome in adults: a randomized controlled trial. Am J Respir Crit Care Med. 2002; 166:801-8. There is substantial interest in HFOV, but few trials comparing it to conventional ventilator modes in this population. This trial of 148 adults with ARDS on baseline PEEP of at least 10 cm H2O found no significant difference in 30-day mortality with high-frequency vs. conventional ventilation (37 and 52%, respectively, p = .10). When and how best to use HFO.

Chan KP, Stewart TE, Mehta S. High-frequency oscillatory ventilation for adult patients with ARDS.  Chest 2007; 131:1907-16.  Review of current HFOV literature, report of experimental data, and summary of two randomized control trials comparing HFOV to conventional ventilation.  The RCT results were “encouraging”, but failed to show a mortality benefit of HFOV over conventional ventilation. http://www.ncbi.nlm.nih.gov/pubmed/17565024?ordinalpos=1&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum

Corticosteroids

Steinberg KP, Hudson LD, Goodman RB, et al. Efficacy and safety of corticosteroids for persistent acute respiratory distress syndrome.  N Engl J Med  2006; 354:1671-84. This study randomized 180 patients with persistent ARDS (7 to 28 days after onset) to methylprednisolone (daily dose 2 mg/kg x 14 days then 1 mg/kg x 7 days) vs. placebo.  Hospital mortality and 180-day survival were comparable, but patients enrolled 14 or more days after ARDS onset had increased 60-day mortality (35% vs. 8% placebo, p = .02). http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=16625008&query_hl=1&itool=pubmed_docsum

Meduri GU, Golden E, Freire AX, et al. Methylprenisolone infusion in early severe ARDS: results of a randomized controlled trial. Chest 2007; 131:954-63.  This study of 91 patients with severe ARDS has added fuel to the debate over systemic corticosteroid use in acute lung injury. The intervention group received steroids within 72 hours of ARDS diagnosis and a slow taper.  Steroid recipients had decreased duration of mechanical ventilation and ICU stay. The higher proportion of patients with catecholamine-dependent shock among controls, cross over from control to steroids in “nonresponders” at day 7, and 2:1 randomization of treatment to control are among the concerns raised since its publication. http://www.ncbi.nlm.nih.gov/pubmed/17426195?ordinalpos=4&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum

Fluid management

Wiedemann HP, Wheeler AP, Bernard GR, et al. Comparison of two fluid-management strategies in acute lung injury. N Engl J Med. 2006; 354:2564-75. A randomized study, comparing conservative vs. liberal fluid management (via explicit protocols) applied over seven days to 1000 patients with acute lung injury. Although there was no significant difference in the primary outcome of 60-day mortality, the conservative strategy of fluid management shortened the duration of mechanical ventilation and ICU stay without increasing nonpulmonary-organ failure.
http://www.ncbi.nlm.nih.gov/pubmed/16714767?ordinalpos=2&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum

Wheeler AP, Bernard GR, Thompson BT, et al.  Pulmonary-artery versus central venous catheter to guide treatment of acute lung injury.  N Engl J Med. 2006; 354:2213-24.  PAC-guided therapy did not improve survival or organ function but was associated with more complications than CVC-guided therapy. These results, along with previous studies of PACs in the MICU population, suggest that the PAC should not be routinely used for the management of acute lung injury.
http://www.ncbi.nlm.nih.gov/pubmed/16714768?ordinalpos=1&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum

***See also Mechanical Ventilation, Hemodynamics