According to the findings of a randomised, controlled trial published early online in the Lancet, treatment with intravenous (IV) salbutamol early in the course of acute respiratory distress syndrome (ARDS) is unlikely to be beneficial (and may be harmful) and is poorly tolerated.

The authors note that ARDS occurs in around 14% of mechanically ventilated patients, and is associated with a high mortality rate (40-60%), and a reduced quality of life in survivors.  Beta-2 agonists could be a potential pharmacological treatment as they act on the pulmonary cellular pathways thought to be associated with the underlying pathophysiology of ARDS; findings of a previous small Phase II study found that IV salbutamol reduced extravascular lung water and plateau airway pressure.  The purpose of the current study was to evaluate the effects of IV salbutamol on mortality in patients with ARDS.

The multicentre UK study included ICU patients (aged ≥16 years) with ARDS who were intubated and mechanically ventilated.  They were randomised within 72 hours of ARDS onset to double-blind treatment with IV salbutamol (15 mcg/kg ideal bodyweight per hour; n=162) or placebo (n=164) for up to 7 days.  The primary endpoint was death within 28 days of randomisation (intention-to-treat).

Recruitment was stopped after the second interim analysis because of safety concerns.  The authors report that salbutamol was associated with increased 28-day mortality: 34% versus 23% of patients allocated to placebo (risk ratio [RR] 1.47, 95% CI 1.03-2.08).  This translated into a 10.9% (95% CI 1.0-20.4) absolute increase in 28-day mortality, with one additional death occurring for every 9.2 (95% CI 4.9-100.9) patients with ARDS given salbutamol.  Adjustment for baseline variables (age, sex, PaO2/FIO2 ratio, and cause) alone or in combination made no substantial difference to the estimate of the treatment effect of salbutamol or its statistical significance (data not shown).  Those in the salbutamol group were more likely to have their infusion stopped early due to death (14/161 versus 8/163) or the development of significant side-effects (47/161 versus 13/163), such as tachycardia, arrhythmia or lactic acidosis.

The authors acknowledge the limitations of their study, including a lower than anticipated mortality in the placebo group; the lack of prospective data on cardiovascular co-morbidity and causes of deaths; the small sample size (due to the early closure); lack of measurement of details of clinical management, and the fact that a lower dose may have been associated with a different risk/benefit profile.  They say that the mechanisms underlying the increased mortality seen remain unclear.

The authors conclude that the routine use of beta-2 agonist therapy in mechanically ventilated patients with ARDS cannot be recommended on the basis of their findings.