Pharmacotherapy of Acute Lung Injury and the Acute Respiratory Distress Syndrome

Abstract

Acute lung injury and the acute respiratory distress syndrome are common syndromes with a high mortality rate that affect both medical and surgical patients. Better understanding of the pathophysiology of acute lung injury and the acute respiratory distress syndrome and advances in supportive care and mechanical ventilation have led to improved clinical outcomes since the syndrome was first described in 1967. Although several promising pharmacological therapies, including surfactant, nitric oxide, glucocorticoids and lysofylline, have been studied in patients with acute lung injury and the acute respiratory distress syndrome, none of these pharmacological treatments reduced mortality. This article provides an overview of pharmacological therapies of acute lung injury and the acute respiratory distress syndrome tested in clinical trials and current recommendations for their use as well as a discussion of potential future pharmacological therapies including β 2 -adrenergic agonist therapy, keratinocyte growth factor, and activated protein C. Keywordsacute lung injury; acute respiratory distress syndrome; pulmonary edema; pharmacologic therapiesThe objective of this article is to review pharmacological therapeutic strategies for acute lung injury (ALI) and acute respiratory distress syndrome (ARDS). Following a brief overview of definitions, epidemiology, pathophysiology, and major nonpharmacological therapies of ALI/ ARDS, we will focus on pharmacological therapies. Given the large number of therapeutic agents tested or implicated for therapy of ALI/ARDS, we attempted to organize this article according to the level of available evidence. The pharmacological therapeutic strategies are divided into 3 sections. The first 2 sections, pulmonary targeted (inhaled) and systemic pharmacological therapy, review all therapeutic agents for which human, phase I, II, or III clinical trials have been conducted. The third section focuses on potential therapies for which there are plausible pathophysiological rationale and preliminary experimental data but no clinical trials. All phase II and III clinical trials are summarized in a table that includes level [1,2] and grade [2,3] of evidence and resulting current recommendations.We searched the MEDLINE database (since 1967), the Cochrane Library, and bibliographies of retrieved articles. The literature search was performed by both authors. In the first 2 sections of this article, we include all therapies for which clinical trials in patients with ALI/ARDS have NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author Manuscript been conducted and all important studies relevant to these therapies. In the third section, potential therapies, we discuss the treatments that are currently the most promising. Definitions and EpidemiologyThe acute respiratory distress syndrome is a clinical syndrome of acute inflammatory lung injury resulting from a variety of etiologies. The syndrome was first described by Ashbaugh and colleagues [4] in 1967 in a series of 12 patients, and...

Advances in Critical Care for the Nephrologist

“…Numerous clinical trials have evaluated pharmacologic therapies for the treatment of ALI (reviewed in (56,58,59)). Unfortunately, no pharmacologic treatment has yet been shown to reduce mortality.…”

β2Agonist for the Treatment of Acute Lung Injury: A Systematic Review and Meta-analysis

“…9,[30][31][32][33][34][35] In spite of recent advances, the mortality remains high, at Ն 30%. 36,37 There has been an interest in the role of ␤ 2 agonists in managing patients with ALI and ARDS.…”

Translational research in ARDS patients: new biological phenotypes

“…Based on the vascular/inflammatory basis of ARDS pathophysiology, several treatment options like glucocorticoids, inhaled antioxidants, or protease inhibitors have been tested but lack proven overall effectiveness [5]. Promising new approaches towards the development of pathophysiologically driven therapies are based on cellular therapies such as bone marrow-derived progenitor cells [6,7].…”