Beta-2 agonists don't reduce mortality from ARDS

SAN JUAN, P.R. – Beta-2 agonists neither reduce mortality nor shorten hospital stays for patients with acute lung injury or acute respiratory distress syndrome, investigators reported at the Critical Care Congress.

A systematic review and meta-analysis showed that in randomized controlled trials, patients with acute lung injury (ALI) or acute respiratory distress syndrome (ARDS) who received either intravenous or aerosolized beta-2 agonists did not have significantly lower in-hospital or 28-day mortality than that of similar patients who did not receive the drugs.

"The current evidence discourages the use of beta-2 agonists among ALI/ARDS patients," Dr. Balwinder Singh, a research fellow in pulmonary and critical care medicine at the Mayo Clinic in Rochester, Minn., and his colleagues wrote in a poster.

In one of the studies included in the meta-analysis – the Beta-Agonist Lung Injury Trial (BALTI), published in 2006 – investigators in the United Kingdom found that patients randomly assigned to receive intravenous albuterol (salbutamol in the United Kingdom) had significantly lower amounts of lung water and plateau airway pressures than did controls (Am. J. Respir. Crit. Care Med. 173;3:281-7). This finding, plus evidence from preclinical studies, prompted other researchers to investigate whether beta-2 agonists could improve survival and other important outcomes.

In a 2011 study, investigators from the ARDS Clinical Trials Network noted that the rationale for the use of beta-2 adrenergic receptor agonists in patients with ALI/ARDS is that they had been shown to accelerate the resolution of pulmonary edema in preclinical studies and in a single controlled trial, and that "decreased resolution of alveolar edema is associated with increased mortality" (Am. J. Respir. Crit. Care Med. 2011;184:561-68).

To see whether those ideas hold water, Dr. Singh and his colleagues trolled the medical literature for randomized controlled trials that used a beta-2 agonist for ALI.

They reviewed 204 total studies, settling on three randomized controlled trials, including the two aforementioned studies and the BALTI-2 trial (Lancet 2012;379:229-35). The studies showed either mortality rates or ventilator-free days for patients on beta-2 agonists, or both. The studies followed a total of 646 patients, of whom 334 (51.7%) were prescribed a beta-2 agonist.

The beta-2 agonists were not associated with a significant decrease in 28-day mortality (relative risk, 1.04; 95% confidence interval, 0.50-2.16) or in-hospital mortality (RR, 1.22; CI, 0.95-1.56).

In addition, patients who received a beta-2 agonist had markedly fewer ventilator-free days, with a mean difference of –2.20 days (CI, –2.41 to –1.99).

The conclusion of Dr. Singh and his colleagues – that the evidence weighs against the use of beta-2 agonists in ALI/ARDS – echoes that of the BALTI-2 researchers, who wrote, "Findings from this multicentre trial provide evidence that intravenous salbutamol in the early course of ARDS was poorly tolerated, is unlikely to be beneficial, and could worsen outcomes. Routine use of beta-2 agonist therapy in mechanically ventilated patients with ARDS cannot be recommended."

The Critical Care Congress was sponsored by the Society for Critical Care Medicine.

The study was internally funded. Dr. Singh reported having no financial disclosures.

SAN JUAN, P.R. – Beta-2 agonists neither reduce mortality nor shorten hospital stays for patients with acute lung injury or acute respiratory distress syndrome, investigators reported at the Critical Care Congress.

A systematic review and meta-analysis showed that in randomized controlled trials, patients with acute lung injury (ALI) or acute respiratory distress syndrome (ARDS) who received either intravenous or aerosolized beta-2 agonists did not have significantly lower in-hospital or 28-day mortality than that of similar patients who did not receive the drugs.

"The current evidence discourages the use of beta-2 agonists among ALI/ARDS patients," Dr. Balwinder Singh, a research fellow in pulmonary and critical care medicine at the Mayo Clinic in Rochester, Minn., and his colleagues wrote in a poster.

In one of the studies included in the meta-analysis – the Beta-Agonist Lung Injury Trial (BALTI), published in 2006 – investigators in the United Kingdom found that patients randomly assigned to receive intravenous albuterol (salbutamol in the United Kingdom) had significantly lower amounts of lung water and plateau airway pressures than did controls (Am. J. Respir. Crit. Care Med. 173;3:281-7). This finding, plus evidence from preclinical studies, prompted other researchers to investigate whether beta-2 agonists could improve survival and other important outcomes.

In a 2011 study, investigators from the ARDS Clinical Trials Network noted that the rationale for the use of beta-2 adrenergic receptor agonists in patients with ALI/ARDS is that they had been shown to accelerate the resolution of pulmonary edema in preclinical studies and in a single controlled trial, and that "decreased resolution of alveolar edema is associated with increased mortality" (Am. J. Respir. Crit. Care Med. 2011;184:561-68).

To see whether those ideas hold water, Dr. Singh and his colleagues trolled the medical literature for randomized controlled trials that used a beta-2 agonist for ALI.

They reviewed 204 total studies, settling on three randomized controlled trials, including the two aforementioned studies and the BALTI-2 trial (Lancet 2012;379:229-35). The studies showed either mortality rates or ventilator-free days for patients on beta-2 agonists, or both. The studies followed a total of 646 patients, of whom 334 (51.7%) were prescribed a beta-2 agonist.

The beta-2 agonists were not associated with a significant decrease in 28-day mortality (relative risk, 1.04; 95% confidence interval, 0.50-2.16) or in-hospital mortality (RR, 1.22; CI, 0.95-1.56).

In addition, patients who received a beta-2 agonist had markedly fewer ventilator-free days, with a mean difference of –2.20 days (CI, –2.41 to –1.99).

The conclusion of Dr. Singh and his colleagues – that the evidence weighs against the use of beta-2 agonists in ALI/ARDS – echoes that of the BALTI-2 researchers, who wrote, "Findings from this multicentre trial provide evidence that intravenous salbutamol in the early course of ARDS was poorly tolerated, is unlikely to be beneficial, and could worsen outcomes. Routine use of beta-2 agonist therapy in mechanically ventilated patients with ARDS cannot be recommended."

The Critical Care Congress was sponsored by the Society for Critical Care Medicine.

The study was internally funded. Dr. Singh reported having no financial disclosures.

SAN JUAN, P.R. – Beta-2 agonists neither reduce mortality nor shorten hospital stays for patients with acute lung injury or acute respiratory distress syndrome, investigators reported at the Critical Care Congress.

A systematic review and meta-analysis showed that in randomized controlled trials, patients with acute lung injury (ALI) or acute respiratory distress syndrome (ARDS) who received either intravenous or aerosolized beta-2 agonists did not have significantly lower in-hospital or 28-day mortality than that of similar patients who did not receive the drugs.

"The current evidence discourages the use of beta-2 agonists among ALI/ARDS patients," Dr. Balwinder Singh, a research fellow in pulmonary and critical care medicine at the Mayo Clinic in Rochester, Minn., and his colleagues wrote in a poster.

In one of the studies included in the meta-analysis – the Beta-Agonist Lung Injury Trial (BALTI), published in 2006 – investigators in the United Kingdom found that patients randomly assigned to receive intravenous albuterol (salbutamol in the United Kingdom) had significantly lower amounts of lung water and plateau airway pressures than did controls (Am. J. Respir. Crit. Care Med. 173;3:281-7). This finding, plus evidence from preclinical studies, prompted other researchers to investigate whether beta-2 agonists could improve survival and other important outcomes.

In a 2011 study, investigators from the ARDS Clinical Trials Network noted that the rationale for the use of beta-2 adrenergic receptor agonists in patients with ALI/ARDS is that they had been shown to accelerate the resolution of pulmonary edema in preclinical studies and in a single controlled trial, and that "decreased resolution of alveolar edema is associated with increased mortality" (Am. J. Respir. Crit. Care Med. 2011;184:561-68).

To see whether those ideas hold water, Dr. Singh and his colleagues trolled the medical literature for randomized controlled trials that used a beta-2 agonist for ALI.

They reviewed 204 total studies, settling on three randomized controlled trials, including the two aforementioned studies and the BALTI-2 trial (Lancet 2012;379:229-35). The studies showed either mortality rates or ventilator-free days for patients on beta-2 agonists, or both. The studies followed a total of 646 patients, of whom 334 (51.7%) were prescribed a beta-2 agonist.

The beta-2 agonists were not associated with a significant decrease in 28-day mortality (relative risk, 1.04; 95% confidence interval, 0.50-2.16) or in-hospital mortality (RR, 1.22; CI, 0.95-1.56).

In addition, patients who received a beta-2 agonist had markedly fewer ventilator-free days, with a mean difference of –2.20 days (CI, –2.41 to –1.99).

The conclusion of Dr. Singh and his colleagues – that the evidence weighs against the use of beta-2 agonists in ALI/ARDS – echoes that of the BALTI-2 researchers, who wrote, "Findings from this multicentre trial provide evidence that intravenous salbutamol in the early course of ARDS was poorly tolerated, is unlikely to be beneficial, and could worsen outcomes. Routine use of beta-2 agonist therapy in mechanically ventilated patients with ARDS cannot be recommended."

The Critical Care Congress was sponsored by the Society for Critical Care Medicine.

The study was internally funded. Dr. Singh reported having no financial disclosures.