Acute respiratory distress syndrome: update on the latest developments in basic and clinical research

Abstract

Acute lung injury/acute respiratory distress syndrome is a common, serious condition affecting a heterogeneous population of critically ill patients. Other than low tidal volume ventilation, no specific therapy has improved survival. Understanding the epidemiology, pathogenesis, and lessons to be learned from previous clinical trials is necessary for the development of new therapies and the rational design of studies assessing their efficacy. Acute lung injury/acute respiratory distress syndrome occurs in 6-8% of the general intensive care unit population, with a mortality of 32-45%. A recent epidemiologic study found that multi-organ dysfunction, use of tidal volumes higher than 6 ml/kg, and high mean fluid balance were independent risks for mortality. Although high levels of inflammatory mediators are also markers for acute respiratory distress syndrome development and death, short courses of high-dose steroids are not effective in acute cases. The latest theory of biotrauma proposes cellular mechanisms by which mechanical ventilation incites a local and systemic inflammatory response; protective lung ventilation with low tidal volumes can attenuate this inflammation and injury to distal organs. Endogenous surfactant function is clearly impaired, but no commercially available surfactant preparation has been shown to reduce mortality. Results of trials to determine efficacy of steroids in late cases and optimal fluid management are pending. The results of recent clinical trials have raised more questions. Further study of the inflammatory response, surfactant regulation, and the cellular impact of mechanical ventilation should help to develop new therapies, target patients most likely to benefit, and identify appropriate timing of intervention.