To recover from ARDS, one’s alveoli must clear fluid across the epithelial membrane in a process partly controlled by cAMP. Beta-agonists upregulate cAMP pathways. In a related vein, giving prophylactic salmeterol reduces the incidence of high-altitude pulmonary edema in those at risk. B-agonists also have some anti-inflammatory properties. In ex vivo studies, spraying a little beta-agonist on cells upregulates cAMP production and doubles the rate of alveolar fluid clearance.
But, it seems, not in real live people with ARDS. Led by Matthay, the ARDSNet folks randomized 282 patients with ALI or ARDS to receive either 5 mg of nebulized albuterol or placebo every 4 hours for 10 days (or until 24 hours after being extubated).
The trial was stopped early for futility (n=1,000 original enrollment target). There was no difference in the number of ventilator-free days (1′ endpoint), nor in survival to hospital discharge (2′ endpoint). The albuterol patients’ heart rates were 4 beats faster but there were no dysrhythmias or other adverse events to speak of.
Matthay M et al (ARDSNet investigators). Randomized, Placebo-controlled Clinical Trial of an Aerosolized B2-Agonist for Treatment of Acute Lung Injury. Am J Respir Crit Care Med 2011;184: 561-568.
A pro-con debate ensued. My take on it:
PRO: Salmeterol is more B-selective and anti-inflammatory than albuterol; maybe that would have worked. Still, we probably shouldn’t use these without more data unless airflow obstruction is present.
CON: Yep, looks like any benefits of B-agonists were canceled out by negative effects. Let’s wait for final results from BALTI-2 (n=326 patients testing IV salbutamol, also stopped early for futility, publication pending) and put this to bed then.