I.V. beta-agonists for ARDS harmed people; BALTI-2 stopped early (RCT, Lancet)

It wasn't such a crazy idea, injecting beta-agonists continuously into the veins of people with acute respiratory distress syndrome (ARDS) for a week. After all, if you spray some albuterol on alveolar epithelial cells in a dish, it upregulates their cAMP production and doubles the rate at which they clear fluid across their basement membranes. And in the single-center 2006 BALTI trial, intravenous albuterol given to people with ARDS reduced their plateau pressures by 6 cm H2O and seemed to substantially reduce their "lung water" (measured by thermodilution). Although those getting IV beta-agonists also had a much higher rate of supraventricular arrhythmias -- ominously, as it turned out -- the BALTI-2 randomized trial went forward in the U.K. to test the therapy more definitively.

What They Did: Fang Gao Smith et al randomized 326 adolescent & adult patients with ARDS to receive a continuous infusion of either salbutamol (albuterol), a short-acting beta agonist, or placebo intravenously for up to 7 days. The trial was funded by the U.K.'s Department of Health.

Results: When given to people with ARDS, intravenous salbutamol/albuterol hurt people: 55 of 161 patients receiving IV salbutamol died (34%) vs. 38 of 163 receiving placebo (23%), a statistically significant difference. This was at an early interim analysis -- the trial was stopped at this point.

The causes of death were not identifiable with precision, because recording cause of death was not part of the study protocol, and the information had to be sought post-hoc. But among patients receiving albuterol, ten times as many patients had tachycardias or arrhythmias necessitating study drug stoppage, and 10 had lactic acidosis requiring study drug stoppage (vs. 1 in the placebo group).

As we reported, the ARDSNet folks recently showed in a U.S. trial that aerosolized beta-agonists don't improve outcomes in people with ARDS, either.

Smith FG et al. Effect of intravenous β-2 agonist treatment on clinical outcomes in acute respiratory distress syndrome (BALTI-2): a multicentre, randomised controlled trial. Lancet 2012;379:21-27.