β2 adrenergic agonists in acute lung injury? The heart of the matter

Jae W Lee

doi:10.1186/cc8171

Abstract

Despite extensive research into its pathophysiology, acute lung injury/acute respiratory distress syndrome (ALI/ARDS) remains a devastating syndrome with mortality approaching 40%. Pharmacologic therapies that reduce the severity of lung injury in vivo and in vitro have not yet been translated to effective clinical treatment options, and innovative therapies are needed. Recently, the use of β2 adrenergic agonists as potential therapy has gained considerable interest due to their ability to increase the resolution of pulmonary edema. However, the results of clinical trials of β agonist therapy for ALI/ARDS have been conflicting in terms of benefit. In the previous issue of Critical Care, Briot and colleagues present evidence that may help clarify the inconsistent results. The authors demonstrate that, in oleic acid lung injury in dogs, the inotropic effect of β agonists may recruit damaged pulmonary capillaries, leading to increased lung endothelial permeability.

Highlights

In their manuscript, Briot and colleagues [1] assessed the role of terbutaline, a β2 agonist, on lung microvascular permeability in an acute lung injury (ALI) in vivo model to uncover the underlying mechanisms of therapeutic benefit
Β2 agonist therapy was considered promising for ALI based on several characteristics seen in both animal and human models: the ability to increase the rate of vectorial salt and water transport by increased intracellular cAMP, leading to improved alveolar fluid clearance (AFC) [4,5] - clinically, impaired AFC in patients with ALI is associated with higher mortality [6]; the ability to improve lung endothelial permeability to protein [7]; and the anti-inflammatory properties of β2 agonists
Maris and colleagues [8] demonstrated that pretreatment with an inhaled β2 agonist markedly reduced neutrophil influx, neutrophil degranulation and accumulation of tumor necrosis factor α in the airspaces of human volunteers exposed to inhaled endotoxin

Summary

Introduction

Briot and colleagues [1] assessed the role of terbutaline, a β2 agonist, on lung microvascular permeability in an acute lung injury (ALI) in vivo model to uncover the underlying mechanisms of therapeutic benefit. The results of clinical trials of β agonist therapy for ALI/acute respiratory distress syndrome (ARDS) have been inconsistent. In a randomized placebo controlled clinical trial of 40 patients with ALI (Beta-Agonist Lung Injury Trial (BALTI)), Perkins and colleagues [9] found that salbutamol (albuterol) given intravenously at a dose of 15 μg/kg/h reduced extravascular lung water in patients with ALI/ARDS as measured by thermodilution (PiCCO) at day 7 compared to placebo control subjects.

Results

Conclusion