Randomized, placebo-controlled clinical trial of an aerosolized β₂-agonist for treatment of acute lung injury
National Heart, Lung, and Blood Institute Acute Respiratory Distress Syndrome (ARDS) Clinical Trials Network, 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, L Hudson, C Hough, M Neff, K Sims, T Watkins, J Steingrub, M Tidswell, L DeSouza, C Kardos, L Kozikowski, K Kozikowski, K Guntupalli, V Bandi, C Pope, R Brower, H Fessler, D Hager, P Mendez-Tellez, K Oakjones, D Needham, J Sevransky, A Workneh, S Han, S Murray, C Shanholtz, G Netzer, P Rock, A Sampaio, J Titus, T Harrington, D Herr, B Lee, N Bolouri, H P Wiedemann, R W Ashton, D A Culver, T Frederick, J J Komara, J A Guzman, A J Reddy, R Hejal, M Andrews, D Haney, A F Connors, S Lasalvia, J D Thornton, E L Warren, M Moss, A Benson, E Burnham, B Clark, L Gray, C Higgins, B J Maloney, M Mealer, S Frankel, T Bost, P Dennen, K Hodgin, I Douglas, K Overdier, K Thompson, R Wolken, N MacIntyre, L Brown, C Cox, M Gentile, J Govert, N Knudsen, S Carson, L Chang, J Lanier, A P Wheeler, G R Bernard, M Hays, S Mogan, T Rice, R D Hite, P E Morris, A Howard, A Harvey, K Bender, P Wright, S Gross, J McLean, A Overton, J Truwit, K Enfield, M Marshall, T Clemmer, L Weaver, M Zenger, J Krueger, A Morris, A Ahmed, A Austin, N Dean, C Grissom, E Hirshberg, N Kumar, R Miller, L Napoli, J Orme, S Pandita, G Schreiber, L Struck, F Thomas, G Thomsen, C Lawton, F Leung, P Kim, T Fujii, J Baughman, B Kerwin, D Hanselman, K Sundar, W Alward, T Hill, E Campbell, K Ludwig, D Nielsen, M Pearce, M A Matthay, C Calfee, B Daniel, M Eisner, O Garcia, E Johnson, R Kallet, K Kordesch, K Liu, H Zhou, M W Peterson, J Blaauw, T Albertson, E Vlastelin, R Hubmayr, D Brown, O Gajic, R Hinds, S Holets, D J Kor, M Passe, B deBoisblanc, P Lauto, C Romaine, G Meyaski, J Hunt, A Marr, Earl K Long, S Brierre, C LeBlanc, D Taylor, S Jain, L Seoane, F Simeone, J Fearon, J Duchesne, D Schoenfeld, M Aquino, D Dorer, M Guha, E Hammond, N Lavery, P Lazar, I Molina, R Morse, C Oldmixon, B Rawal, N Ringwood, A Shui, E Smoot, B T Thompson, A Harabin, S Bredow, M Waclawiw, G Weinmann, R G Spragg, A Slutsky, M Levy, B Markovitz, E Petkova, C Weijer, J Sznajder, M Begg, E Israel, J Lewis, P Parsons, National Heart, Lung, and Blood Institute Acute Respiratory Distress Syndrome (ARDS) Clinical Trials Network, 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, L Hudson, C Hough, M Neff, K Sims, T Watkins, J Steingrub, M Tidswell, L DeSouza, C Kardos, L Kozikowski, K Kozikowski, K Guntupalli, V Bandi, C Pope, R Brower, H Fessler, D Hager, P Mendez-Tellez, K Oakjones, D Needham, J Sevransky, A Workneh, S Han, S Murray, C Shanholtz, G Netzer, P Rock, A Sampaio, J Titus, T Harrington, D Herr, B Lee, N Bolouri, H P Wiedemann, R W Ashton, D A Culver, T Frederick, J J Komara, J A Guzman, A J Reddy, R Hejal, M Andrews, D Haney, A F Connors, S Lasalvia, J D Thornton, E L Warren, M Moss, A Benson, E Burnham, B Clark, L Gray, C Higgins, B J Maloney, M Mealer, S Frankel, T Bost, P Dennen, K Hodgin, I Douglas, K Overdier, K Thompson, R Wolken, N MacIntyre, L Brown, C Cox, M Gentile, J Govert, N Knudsen, S Carson, L Chang, J Lanier, A P Wheeler, G R Bernard, M Hays, S Mogan, T Rice, R D Hite, P E Morris, A Howard, A Harvey, K Bender, P Wright, S Gross, J McLean, A Overton, J Truwit, K Enfield, M Marshall, T Clemmer, L Weaver, M Zenger, J Krueger, A Morris, A Ahmed, A Austin, N Dean, C Grissom, E Hirshberg, N Kumar, R Miller, L Napoli, J Orme, S Pandita, G Schreiber, L Struck, F Thomas, G Thomsen, C Lawton, F Leung, P Kim, T Fujii, J Baughman, B Kerwin, D Hanselman, K Sundar, W Alward, T Hill, E Campbell, K Ludwig, D Nielsen, M Pearce, M A Matthay, C Calfee, B Daniel, M Eisner, O Garcia, E Johnson, R Kallet, K Kordesch, K Liu, H Zhou, M W Peterson, J Blaauw, T Albertson, E Vlastelin, R Hubmayr, D Brown, O Gajic, R Hinds, S Holets, D J Kor, M Passe, B deBoisblanc, P Lauto, C Romaine, G Meyaski, J Hunt, A Marr, Earl K Long, S Brierre, C LeBlanc, D Taylor, S Jain, L Seoane, F Simeone, J Fearon, J Duchesne, D Schoenfeld, M Aquino, D Dorer, M Guha, E Hammond, N Lavery, P Lazar, I Molina, R Morse, C Oldmixon, B Rawal, N Ringwood, A Shui, E Smoot, B T Thompson, A Harabin, S Bredow, M Waclawiw, G Weinmann, R G Spragg, A Slutsky, M Levy, B Markovitz, E Petkova, C Weijer, J Sznajder, M Begg, E Israel, J Lewis, P Parsons
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, 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 the difference,-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 β₂-agonist therapy in mechanically ventilated patients with ALI cannot be recommended. Clinical trial registered with www.clinicaltrials.gov (NCT 00434993).
Trial registration: ClinicalTrials.gov NCT00434993.
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Source: PubMed