Effect of intravenous β-2 agonist treatment on clinical outcomes in acute respiratory distress syndrome (BALTI-2): a multicentre, randomised controlled trial

Abstract

SummaryBackgroundIn a previous randomised controlled phase 2 trial, intravenous infusion of salbutamol for up to 7 days in patients with acute respiratory distress syndrome (ARDS) reduced extravascular lung water and plateau airway pressure. We assessed the effects of this intervention on mortality in patients with ARDS.MethodsWe did a multicentre, placebo-controlled, parallel-group, randomised trial at 46 UK intensive-care units between December, 2006, and March, 2010. Intubated and mechanically ventilated patients (aged ≥16 years) within 72 h of ARDS onset were randomly assigned to receive either salbutamol (15 μg/kg ideal bodyweight per h) or placebo for up to 7 days. Randomisation was done by a central telephone or web-based randomisation service with minmisation by centre, pressure of arterial oxygen to fractional inspired oxygen concentration (PaO2/FIO2) ratio, and age. All participants, caregivers, and investigators were masked to group allocation. The primary outcome was death within 28 days of randomisation. Analysis was by intention-to-treat. This trial is registered, ISRCTN38366450 and EudraCT number 2006-002647-86.FindingsWe randomly assigned 162 patients to the salbutamol group and 164 to the placebo group. One patient in each group withdrew consent. Recruitment was stopped after the second interim analysis because of safety concerns. Salbutamol increased 28-day mortality (55 [34%] of 161 patients died in the salbutamol group vs 38 (23%) of 163 in the placebo group; risk ratio [RR] 1·47, 95% CI 1·03–2·08).InterpretationTreatment with intravenous salbutamol early in the course of ARDS was poorly tolerated. Treatment is unlikely to be beneficial, and could worsen outcomes. Routine use of β-2 agonist treatment in ventilated patients with this disorder cannot be recommended.FundingUK Medical Research Council, UK Department of Health, UK Intensive Care Foundation.

A randomised controlled trial and cost-effectiveness analysis of high-frequency oscillatory ventilation against conventional artificial ventilation for adults with acute respiratory distress syndrome. The OSCAR (OSCillation in ARDS) study

“…As the OSCAR study commenced, this was in a pilot phase in the West Midlands. It subsequently went to a full study 57 and required the OSCAR study team and the BALTI-2 study team to communicate to prevent competition for patients as the entry criteria for the two studies were near identical.…”

Lipoxin A4 activates alveolar epithelial sodium channel gamma via the microRNA-21/PTEN/AKT pathway in lipopolysaccharide-induced inflammatory lung injury

“…[13][14][15][16] However, we found salbutamol significantly increased the 28-day mortality rate because of its side effects, such as tachycardia, arrhythmia, and lactic acidosis, in a multicenter, randomized, controlled clinical trial. 17 Therefore, new therapeutic agents need to be identified.…”

β2Agonist for the Treatment of Acute Lung Injury: A Systematic Review and Meta-analysis

“…[16][17][18] The detailed description of the included studies is given in the Table 1. The 3 RCTs used salbutamol (albuterol) as the ␤ 2 agonist, and placebo in the control group.…”

“…The 3 RCTs used salbutamol (albuterol) as the ␤ 2 agonist, and placebo in the control group. Two studies 16,18 used intravenous salbutamol, and the other used nebulized salbutamol. 17 The BALTI-1 18 and ALTA trials 17 included ALI patients.…”

“…Lack of consensus about using ␤ 2 agonists in the treatment of ALI/ ARDS patients represents one of the growing controversial issues in the critical care community. 6,[8][9][10][11] This challenging topic has been addressed in physiologic studies [12][13][14][15] and randomized controlled trials (RCTs) [16][17][18] However, 2 of the RCTs (the Aerosolized ␤ 2 Agonist for Treatment of Acute Lung Injury 16 [ALTA] trial, and the second ␤ Agonist Lung Injury trial 17 ) were stopped early because of futility and patient intolerance of the ␤ 2 agonists. Therefore, we performed a systematic review and meta-analysis of the published RCTs, on the effects of ␤ 2 agonists on hospital mortality, 28-day mortality, and ventilator free-days in patients with ALI/ARDS.…”