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, 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.

Figure 1.

Enrollment and outcomes. *Patients may have had more than one reason for exclusion. The full exclusion criteria are listed in the online supplement. **Pharmacy errors resulted in the wrong treatment being given for one patient in each study group. These patients were assigned and analyzed on the basis of the treatment received. MI = mycocardial infarction.

Figure 2.

Probabilities of survival and of discharge home and breathing without assistance, from the day of randomization (Day 0) to Day 60, according to whether patients received albuterol or placebo.

Figure 3.

Boxplot of maximal changes in heart rate from immediately before each nebulization treatment to the 15-minute interval after treatment. Upper and lower margins of the boxes represent the 75th and 25th quartiles, respectively. The bars in the boxes represent medians. The asterisks indicate mean values. The mean maximal change in heart rate over 10 days was 12.6 beats/minute after albuterol administration and 10.5 beats/minute after placebo administration (P = 0.02 by analysis of variance).