Randomized, placebo-controlled clinical trial of an aerosolized β2-agonist for treatment of acute lung injury

Michael A. Matthay, Roy G Brower, Shannon Carson, Ivor S. Douglas, Mark Eisner, Duncan Hite, Steven Holets, Richard H. Kallet, Kathleen D. Liu, Neil MacIntyre, Marc Moss, David Schoenfeld, Jay Steingrub, B. Taylor Thompson

Research output: Contribution to journalArticle

Abstract

Rationale: β2-Adrenergic receptor agonists accelerate resolution of pulmonary edema in experimental and clinical studies. Objectives: This clinical trial was designed to test the hypothesis that an aerosolized β2-agonist, albuterol, would improve clinical outcomes in patients with acute lung injury (ALI). Methods: We conducted a multicenter, randomized, placebocontrolled clinical trial in which 282 patients with ALI receiving mechanical ventilation were randomized to receive aerosolized albuterol (5 mg) or saline placebo every 4 hours for up to 10 days. The primary outcome variable for the trial was ventilator-free days. Measurements and Main Results: Ventilator-free days were not significantly different between the albuterol and placebo groups (means of 14.4 and 16.6 d, respectively; 95% confidence interval for the difference, -4.7 to 0.3 d; P = 0.087). Rates of death before hospital discharge were not significantly different between the albuterol and placebo groups (23.0 and 17.7%, respectively; 95% confidence interval for thedifference,-4.0 to14.7%;P=0.30). In the subset of patients with shock before randomization, the number of ventilator-free days was lower with albuterol, althoughmortalitywas not different. Overall, heart rates were significantly higher in the albuterol group by approximately 4 beats/minute in the first 2 days after randomization, but rates of new atrial fibrillation (10% in both groups) and other cardiac dysrhythmias were not significantly different. Conclusions: These results suggest that aerosolized albuterol does not improve clinical outcomes in patients with ALI. Routine use of β2- agonist therapy in mechanically ventilated patients with ALI cannot be recommended. Clinical trial registered with www.clinicaltrials.gov (NCT 00434993).

Original languageEnglish (US)
Pages (from-to)561-568
Number of pages8
JournalAmerican Journal of Respiratory and Critical Care Medicine
Volume184
Issue number5
DOIs
StatePublished - Sep 1 2011

Fingerprint

Albuterol
Acute Lung Injury
Randomized Controlled Trials
Placebos
Mechanical Ventilators
Random Allocation
Therapeutics
Clinical Trials
Confidence Intervals
Adrenergic Agonists
Pulmonary Edema
Artificial Respiration
Atrial Fibrillation
Cardiac Arrhythmias
Shock
Heart Rate
Mortality

Keywords

  • Acute respiratory distress syndrome
  • Alveolar epithelium
  • Pulmonary edema

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine
  • Critical Care and Intensive Care Medicine

Cite this

Randomized, placebo-controlled clinical trial of an aerosolized β2-agonist for treatment of acute lung injury. / Matthay, Michael A.; Brower, Roy G; Carson, Shannon; Douglas, Ivor S.; Eisner, Mark; Hite, Duncan; Holets, Steven; Kallet, Richard H.; Liu, Kathleen D.; MacIntyre, Neil; Moss, Marc; Schoenfeld, David; Steingrub, Jay; Thompson, B. Taylor.

In: American Journal of Respiratory and Critical Care Medicine, Vol. 184, No. 5, 01.09.2011, p. 561-568.

Research output: Contribution to journalArticle

Matthay, MA, Brower, RG, Carson, S, Douglas, IS, Eisner, M, Hite, D, Holets, S, Kallet, RH, Liu, KD, MacIntyre, N, Moss, M, Schoenfeld, D, Steingrub, J & Thompson, BT 2011, 'Randomized, placebo-controlled clinical trial of an aerosolized β2-agonist for treatment of acute lung injury', American Journal of Respiratory and Critical Care Medicine, vol. 184, no. 5, pp. 561-568. https://doi.org/10.1164/rccm.201012-2090OC
Matthay, Michael A. ; Brower, Roy G ; Carson, Shannon ; Douglas, Ivor S. ; Eisner, Mark ; Hite, Duncan ; Holets, Steven ; Kallet, Richard H. ; Liu, Kathleen D. ; MacIntyre, Neil ; Moss, Marc ; Schoenfeld, David ; Steingrub, Jay ; Thompson, B. Taylor. / Randomized, placebo-controlled clinical trial of an aerosolized β2-agonist for treatment of acute lung injury. In: American Journal of Respiratory and Critical Care Medicine. 2011 ; Vol. 184, No. 5. pp. 561-568.
@article{edf814ee6cf7471cacbbee72bd946edb,
title = "Randomized, placebo-controlled clinical trial of an aerosolized β2-agonist for treatment of acute lung injury",
abstract = "Rationale: β2-Adrenergic receptor agonists accelerate resolution of pulmonary edema in experimental and clinical studies. Objectives: This clinical trial was designed to test the hypothesis that an aerosolized β2-agonist, albuterol, would improve clinical outcomes in patients with acute lung injury (ALI). Methods: We conducted a multicenter, randomized, placebocontrolled clinical trial in which 282 patients with ALI receiving mechanical ventilation were randomized to receive aerosolized albuterol (5 mg) or saline placebo every 4 hours for up to 10 days. The primary outcome variable for the trial was ventilator-free days. Measurements and Main Results: Ventilator-free days were not significantly different between the albuterol and placebo groups (means of 14.4 and 16.6 d, respectively; 95{\%} confidence interval for the difference, -4.7 to 0.3 d; P = 0.087). Rates of death before hospital discharge were not significantly different between the albuterol and placebo groups (23.0 and 17.7{\%}, respectively; 95{\%} confidence interval for thedifference,-4.0 to14.7{\%};P=0.30). In the subset of patients with shock before randomization, the number of ventilator-free days was lower with albuterol, althoughmortalitywas not different. Overall, heart rates were significantly higher in the albuterol group by approximately 4 beats/minute in the first 2 days after randomization, but rates of new atrial fibrillation (10{\%} in both groups) and other cardiac dysrhythmias were not significantly different. Conclusions: These results suggest that aerosolized albuterol does not improve clinical outcomes in patients with ALI. Routine use of β2- agonist therapy in mechanically ventilated patients with ALI cannot be recommended. Clinical trial registered with www.clinicaltrials.gov (NCT 00434993).",
keywords = "Acute respiratory distress syndrome, Alveolar epithelium, Pulmonary edema",
author = "Matthay, {Michael A.} and Brower, {Roy G} and Shannon Carson and Douglas, {Ivor S.} and Mark Eisner and Duncan Hite and Steven Holets and Kallet, {Richard H.} and Liu, {Kathleen D.} and Neil MacIntyre and Marc Moss and David Schoenfeld and Jay Steingrub and Thompson, {B. Taylor}",
year = "2011",
month = "9",
day = "1",
doi = "10.1164/rccm.201012-2090OC",
language = "English (US)",
volume = "184",
pages = "561--568",
journal = "American Journal of Respiratory and Critical Care Medicine",
issn = "1073-449X",
publisher = "American Thoracic Society",
number = "5",

}

TY - JOUR

T1 - Randomized, placebo-controlled clinical trial of an aerosolized β2-agonist for treatment of acute lung injury

AU - Matthay, Michael A.

AU - Brower, Roy G

AU - Carson, Shannon

AU - Douglas, Ivor S.

AU - Eisner, Mark

AU - Hite, Duncan

AU - Holets, Steven

AU - Kallet, Richard H.

AU - Liu, Kathleen D.

AU - MacIntyre, Neil

AU - Moss, Marc

AU - Schoenfeld, David

AU - Steingrub, Jay

AU - Thompson, B. Taylor

PY - 2011/9/1

Y1 - 2011/9/1

N2 - Rationale: β2-Adrenergic receptor agonists accelerate resolution of pulmonary edema in experimental and clinical studies. Objectives: This clinical trial was designed to test the hypothesis that an aerosolized β2-agonist, albuterol, would improve clinical outcomes in patients with acute lung injury (ALI). Methods: We conducted a multicenter, randomized, placebocontrolled clinical trial in which 282 patients with ALI receiving mechanical ventilation were randomized to receive aerosolized albuterol (5 mg) or saline placebo every 4 hours for up to 10 days. The primary outcome variable for the trial was ventilator-free days. Measurements and Main Results: Ventilator-free days were not significantly different between the albuterol and placebo groups (means of 14.4 and 16.6 d, respectively; 95% confidence interval for the difference, -4.7 to 0.3 d; P = 0.087). Rates of death before hospital discharge were not significantly different between the albuterol and placebo groups (23.0 and 17.7%, respectively; 95% confidence interval for thedifference,-4.0 to14.7%;P=0.30). In the subset of patients with shock before randomization, the number of ventilator-free days was lower with albuterol, althoughmortalitywas not different. Overall, heart rates were significantly higher in the albuterol group by approximately 4 beats/minute in the first 2 days after randomization, but rates of new atrial fibrillation (10% in both groups) and other cardiac dysrhythmias were not significantly different. Conclusions: These results suggest that aerosolized albuterol does not improve clinical outcomes in patients with ALI. Routine use of β2- agonist therapy in mechanically ventilated patients with ALI cannot be recommended. Clinical trial registered with www.clinicaltrials.gov (NCT 00434993).

AB - Rationale: β2-Adrenergic receptor agonists accelerate resolution of pulmonary edema in experimental and clinical studies. Objectives: This clinical trial was designed to test the hypothesis that an aerosolized β2-agonist, albuterol, would improve clinical outcomes in patients with acute lung injury (ALI). Methods: We conducted a multicenter, randomized, placebocontrolled clinical trial in which 282 patients with ALI receiving mechanical ventilation were randomized to receive aerosolized albuterol (5 mg) or saline placebo every 4 hours for up to 10 days. The primary outcome variable for the trial was ventilator-free days. Measurements and Main Results: Ventilator-free days were not significantly different between the albuterol and placebo groups (means of 14.4 and 16.6 d, respectively; 95% confidence interval for the difference, -4.7 to 0.3 d; P = 0.087). Rates of death before hospital discharge were not significantly different between the albuterol and placebo groups (23.0 and 17.7%, respectively; 95% confidence interval for thedifference,-4.0 to14.7%;P=0.30). In the subset of patients with shock before randomization, the number of ventilator-free days was lower with albuterol, althoughmortalitywas not different. Overall, heart rates were significantly higher in the albuterol group by approximately 4 beats/minute in the first 2 days after randomization, but rates of new atrial fibrillation (10% in both groups) and other cardiac dysrhythmias were not significantly different. Conclusions: These results suggest that aerosolized albuterol does not improve clinical outcomes in patients with ALI. Routine use of β2- agonist therapy in mechanically ventilated patients with ALI cannot be recommended. Clinical trial registered with www.clinicaltrials.gov (NCT 00434993).

KW - Acute respiratory distress syndrome

KW - Alveolar epithelium

KW - Pulmonary edema

UR - http://www.scopus.com/inward/record.url?scp=79960430979&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=79960430979&partnerID=8YFLogxK

U2 - 10.1164/rccm.201012-2090OC

DO - 10.1164/rccm.201012-2090OC

M3 - Article

VL - 184

SP - 561

EP - 568

JO - American Journal of Respiratory and Critical Care Medicine

JF - American Journal of Respiratory and Critical Care Medicine

SN - 1073-449X

IS - 5

ER -