Clinical developments for treating ARDS.

Abstract

Acute respiratory distress syndrome (ARDS), is characterised by capillary permeability and pulmonary oedema formation and may complicate a variety of medical and surgical illnesses. As a self-perpetuating state of inflammatory derangement, acute lung injury (ALI)/ARDS is manifest clinically as rapid development of radiographic infiltrates, severe hypoxaemia and reduced lung compliance. Over the years, researchers have made significant progress in elucidating the pathophysiology of this complex syndrome. Therapies targeting specific pathophysiologic steps in the development or persistence of this syndrome are in various stages of laboratory and clinical testing. Results to date have shown nitric oxide (NO) to improve oxygenation in the majority of patients but fail to improve mortality. Surfactant replacement has had limited success in adults, but new formulations and delivery methods may prove beneficial. Several inflammatory mediator-targeted therapies have progressed successfully through early clinical evaluation. Among these, neutrophil elastase inhibitors have shown the most promise and are currently undergoing Phase III trials. Other mediator-targeted therapies, such as prostaglandin E1, IL-10 and platelet activating factor antagonists, have not been found efficacious in large clinical trials of ARDS. However, these therapies, along with coagulation modulators, may have a favourable impact on ARDS by improving outcomes in sepsis, the greatest risk factor for developing this condition. In the interim, supportive care through improvements in mechanical ventilation are beneficial, while specific fluid balance and nutrition strategies may prove advantageous.