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Table 1 Summary of clinical trials of β-agonists in patients with acute respiratory distress syndrome (ARDS)

From: The rise and fall of β-agonists in the treatment of ARDS

First author Basran [22] Pesenti [23] Wright [24] Morina [25] Manocha [26] Perkins [27] Licker [28] Matthay [31] Smith [33]
Publication year 1986 1993 1994 1997 2006 2006 2008 2011 2012
Patient population Adult ARDS Adult ARDS Adult ARDS Adult ARDS Adult ARDS Adult ARDS Lung resection patients at risk of ARDS Adult ARDS Adult ARDS
Setting ICU ICU ICU ICU ICU ICU Intermediate care ICU ICU
Age, years (mean [SD]) Range 23-79 Range 17-55 51 [7] 49 [6] Low dose 54.7 [16.6]; high dose 65.7 [15.1], p< 0.05 Salbutamol arm 68.7 [16]; placebo 57 [14.7], p = 0.021 69 [7]   Salbutamol 55.8 [17.2]; placebo 54.2 [17.5]
Total sample size 10 7 8 11 86 40 24 282 326
Trial type Non randomized interventional study Non randomized interventional study Randomized controlled crossover trial Non randomized interventional study Retrospective, observational study Randomized, double blind, placebo controlled trial Randomized, blinded cross over trial Randomized, double blind, placebo controlled trial Randomized, double blind, placebo controlled trial
Randomized? No No Yes No No Yes Yes Yes Yes
Randomization and concealment N/A N/A Computer generated N/A N/A 1:1 sealed envelope Random number tables, sealed envelopes Web based. Stratified by hospital and shock (1:1) Telephone. Stratified by hospital, age and P/F ratio
Drug Terbutaline Salbutamol Metaproterenol Salbutamol Salbutamol Salbutamol Salbutamol Salbutamol Salbutamol
Route i.v. i.v. Nebulized Nebulized Nebulized i.v. Nebulized Nebulized i.v.
Dose 7 μg/kg over 30 min 15 μg/ml 1 ml 0.5% solution 5 mg High dose > 2.2 mg/day; low dose < 2.2 mg/day 15 μg/kg/h 5 mg salbutamol, 0.5 mg ipratropium bromide 5 mg 15 μg/kg/h
Number of patients 10 7 8 11 22 high dose, 68 low dose 19 salbutamol 21 placebo 24 152 salbutamol, 130 saline 162 salbutamol, 164 saline
Outcome Reduced lung accumulation of radio-labeled transferrin in responder group (n = 5) Max and min airway resistance reduced. No effect on compliance or effective additional resistance Reduced resistance, peak/plateau airway pressures; increased Cdyn. No effect on deadspace, Cstat or oxygenation Reduced resistance, peak and plateau airway pressures. No effect on compliance or oxygenation More days alive and free from ALI in high dose arm (12.2 ± 4.4 days versus 7.6 ± 1.9 days, p = 0.02) Reduced extra-vascular lung water and plateau airway pressures. No effect on lung injury score Reduced lung water and permeability index and improved P/F ratio on postoperative day 1 following salbutamol No difference in VFD, mortality, cytokines or plateau airway pressures Increased 28-day mortality. Reduced VFD and OFFD
28-day mortality 50% survival Not reported Not reported Not reported 46.9% low dose arm, 50.0% high dose arm 66% placebo, 58% salbutamol N/A 90-day mortality 24.3% salbutamol, 18.5% placebo Salbutamol 34.2%, placebo 23.3% (risk ratio 1.47, 95% CI, 1.03 to 2.08)
Adverse effects None reported None reported Tachycardia and hypertension None reported None reported Trend to greater tachycardia and arrhythmia in salbutamol arm Increased heart rate and stroke volume, reduced SVRI and increased CI and Dp/dtmax Increased heart rate Termination of infusion due to tachycardia, new arrhythmia, or lactic acidosis greater in salbutamol arm
  1. ALI, acute lung injury; CI, confidence interval; Cdyn, dynamic compliance; Cstat, static compliance; i.v., intravenous; N/A, not available/applicable; OFFD, organ failure-free days; P/F, PaO2/FiO2; VFD, ventilator-free days.