The rise and fall of β-agonists in the treatment of ARDS

Christopher R Bassford,Gavin D Perkins,David R Thickett

doi:10.1186/cc11221

Abstract

The acute respiratory distress syndrome (ARDS) is a severe inflammatory condition of the lung, which can be triggered by a number of different pulmonary and extra-pulmonary insults [1]. The characteristic pathological changes of ARDS include an exudative phase, with the accumulation of fluid within the lung, the release of pro-inflammatory cytokines and infiltration of inflammatory cells, especially neutrophils, into the lung parenchyma. Damage to the alveolar epithelium and pulmonary capillary endothelium occur and patients develop the characteristic histological appearance of diffuse alveolar damage [1]. This manifests clinically as non-cardiogenic pulmonary edema, which reduces lung compliance and impairs gas exchange.

Highlights

The acute respiratory distress syndrome (ARDS) is a severe inflammatory condition of the lung, which can be triggered by a number of different pulmonary and extrapulmonary insults [1]
Over three decades of intense research activity has examined the potential role that β-agonists could play in the treatment of ARDS
Pre-clinical trials suggested that these drugs could accelerate alveolar fluid clearance, may have beneficial immunomodulatory effects and may reduce alveolar-epithelial permeability

Summary

Introduction

The acute respiratory distress syndrome (ARDS) is a severe inflammatory condition of the lung, which can be triggered by a number of different pulmonary and extrapulmonary insults [1]. Evidence for a role of β-agonists in epithelial repair comes from in vitro studies showing that β agonists stimulate the closure of mechanically induced wounds of epithelial monolayers by increasing cAMP and activating protein kinase A (PKA). The increase in cAMP levels caused by β-adrenoceptor stimulation promotes bronchial smooth muscle relaxation which results in bronchodilation, reducing airways resistance and the pressures required for adequate mechanical ventilation. The β-agonist Lung Injury Trial (BALTI-1) [27] was a phase II prospective randomized, double blind, placebocontrolled and the first study in humans to evaluate the effect of β-agonists on lung water This single center study randomized 40 adult patients with ARDS to an intravenous infusion of salbutamol 15 μg/kg/hr for 7 days and serially recorded the effect on extravascular lung water (EVLW).

Randomized controlled crossover trial

Findings

Conclusion