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 |