Randomized, Placebo-controlled Clinical Trial of an Aerosolized β2-Agonist for Treatment of Acute Lung Injury

被引:335
作者
Matthay, Michael A. [1 ]
Brower, Roy G. [2 ]
Carson, Shannon [3 ]
Douglas, Ivor S. [3 ]
Eisner, Mark [4 ]
Hite, Duncan [3 ]
Holets, Steven [5 ]
Kallet, Richard H. [6 ]
Liu, Kathleen D.
MacIntyre, Neil [7 ]
Moss, Marc [8 ]
Schoenfeld, David [9 ]
Steingrub, Jay [10 ]
Thompson, B. Taylor [9 ]
Hudson, L. [11 ]
Hough, C. [11 ]
Neff, M. [11 ]
Sims, K. [11 ]
Watkins, T. [11 ]
Steingrub, J. [10 ]
Tidswell, M. [10 ]
DeSouza, L. [10 ]
Kardos, C. [10 ]
Kozikowski, L. [10 ]
Kozikowski, K. [10 ]
Guntupalli, K. [12 ]
Bandi, V. [12 ]
Pope, C. [12 ]
Brower, R. [13 ]
Fessler, H. [13 ]
Hager, D. [13 ]
Mendez-Tellez, P. [13 ]
Oakjones, K. [13 ]
Needham, D. [13 ]
Sevransky, J.
Workneh, A.
Han, S.
Murray, S.
Shanholtz, C. [14 ]
Netzer, G. [14 ]
Rock, P. [14 ]
Sampaio, A. [14 ]
Titus, J. [14 ]
Harrington, T. [14 ]
Herr, D. [15 ]
Lee, B. [15 ]
Bolouri, N. [15 ]
Wiedemann, H. P. [16 ]
Ashton, R. W. [16 ]
Culver, D. A. [16 ]
机构
[1] Univ Calif San Francisco, Cardiovasc Res Inst, San Francisco, CA 94143 USA
[2] Johns Hopkins Univ, Baltimore, MD USA
[3] Univ N Carolina, Chapel Hill, NC USA
[4] Genentech Inc, San Francisco, CA USA
[5] Mayo Clin, Rochester, MN USA
[6] San Francisco Gen Hosp, San Francisco, CA 94110 USA
[7] Duke Univ, Durham, NC USA
[8] Univ Colorado, Denver, CO 80202 USA
[9] Massachusetts Gen Hosp, Boston, MA 02114 USA
[10] Baystate Med Ctr, Springfield, MA USA
[11] Univ Washington, Harborview, WA USA
[12] Baylor Coll Med, Houston, TX 77030 USA
[13] Johns Hopkins Univ Hosp, Baltimore, MD 21287 USA
[14] Univ Maryland, College Pk, MD 20742 USA
[15] Washington Hosp Ctr, Washington, DC USA
[16] Cleveland Clin Fdn, Cleveland, OH USA
[17] Univ Hosp Cleveland, Cleveland, OH 44106 USA
[18] Denver Hlth Med Ctr, Denver, CO USA
[19] Vanderbilt Univ, Nashville, TN USA
[20] Wake Forest Univ, Winston Salem, NC 27109 USA
[21] Univ Virginia, Charlottesville, VA 22903 USA
[22] Univ Calif San Francisco, Fresno, CA USA
[23] Univ Calif Davis, Davis, CA USA
[24] Louisiana State Univ, Baton Rouge, LA 70803 USA
[25] Baton Rouge Gen Med Ctr Mid City, Baton Rouge, LA USA
[26] Baton Rouge Gen Med Ctr Bluebonnet, Baton Rouge, LA USA
[27] Tulane Univ, New Orleans, LA 70118 USA
[28] Massachusetts Gen Hosp, Clin Coordinating Ctr, Boston, MA 02114 USA
[29] Harvard Univ, Sch Med, Cambridge, MA 02138 USA
关键词
pulmonary edema; acute respiratory distress syndrome; alveolar epithelium; RESPIRATORY-DISTRESS-SYNDROME; ALVEOLAR FLUID CLEARANCE; PULMONARY-EDEMA FLUID; BETA(2)-ADRENERGIC RECEPTOR; EPITHELIAL TRANSPORT; DECREASES EXPRESSION; VENTILATED PATIENTS; RAT LUNGS; PROGRESS; CELLS;
D O I
10.1164/rccm.201012-2090OC
中图分类号
R4 [临床医学];
学科分类号
1002 ; 100602 ;
摘要
Rationale: beta(2)-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 beta(2)-agonist, albuterol, would improve clinical outcomes in patients with acute lung injury (ALI). Methods: We conducted a multicenter, randomized, placebo-controlled 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 to 14.7%; P = 0.30). In the subset of patients with shock before randomization, the number of ventilator-free days was lower with albuterol, although mortality was 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 beta(2)-agonist therapy in mechanically ventilated patients with ALI cannot be recommended.
引用
收藏
页码:561 / 568
页数:8
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