Beta-2 agonist treatment disappoints in acute respiratory distress syndrome
MedWire News: Treatment with intravenous salbutamol fails to live up to early promise, instead increasing mortality in patients with acute respiratory distress syndrome (ARDS), show the results of the BALTI-2 trial.
Patients given salbutamol in the previous single-center BALTI-1 (β-agonist lung injury trial) had significant reductions in extravascular lung water and plateau airway pressure, relative to those given placebo. Yet in the multicenter BALTI-2 trial, patients randomly assigned to receive salbutamol (15 µg/kg ideal bodyweight per hour) were more likely to die within 28 days than those given placebo.
"These findings were unexpected; however, they have clarified whether intravenous infusion of β-2 agonists should be used in patients with ARDS," say Fang Gao Smith (University of Birmingham, UK) and colleagues in The Lancet.
The trial was stopped for safety reasons after enrollment of 162 patients to the salbutamol group and 164 to the placebo group. The patients were all aged at least 16 years (average about 55 years), were intubated and mechanically ventilated and within 72 hours of ARDS onset. They were given salbutamol or placebo for up to 7 days.
One patient in each group withdrew consent. The 28-day mortality rates for the rest of the patients were 34% in the salbutamol group and 23% in the placebo group, equating to a significant 47% relative increase in mortality risk.
The researchers note that the survival curves for the salbutamol and placebo groups continued to diverge after the end of the salbutamol infusion, suggesting that the mechanism by which salbutamol increased mortality "could be complex."
Salbutamol was poorly tolerated by the patients, mostly due to increased rates of tachycardia, at 14% versus 1% with placebo, arrhythmias, at 9% versus 2%, and lactic acidosis, at 6% versus less than 1%. In all, 6% of salbutamol-treated patients and 2% of those in the placebo group had serious adverse events, with five of nine events in the active-treatment group thought to be related to the study drug.
B Taylor Thompson (Massachusetts General Hospital, Boston, USA) concludes that, despite the early termination of the trial, the balance of evidence suggests that salbutamol, at the study dose, is harmful to patients with ARDS.
"Much work needs to be done, but the BALTI-2 results should encourage research on approaches to reduce adrenergic upregulation and catecholamine exposure during critical illness and ARDS to identify if these approaches improve outcomes," says Thompson.
"For now, the results of the truncated BALTI-2 trial are sufficient to change practice. β-2 agonist treatment in patients with ARDS should be limited to the treatment of clinically important reversible airway obstruction and should not be part of routine care."
By Eleanor McDermid