The Utility of Clinical Predictors of Acute Lung Injury
The Utility of Clinical Predictors of Acute Lung Injury
Despite significant advances in our understanding of the pathophysiology of acute lung injury, a lung-protective strategy of mechanical ventilation remains the only therapy with a proven survival advantage. Numerous pharmacologic therapies have failed to show benefit in multicenter clinical trials. The paradigm of early, goal-directed therapy of sepsis suggests greater clinical benefit may derive from initiating therapy prior to the onset of respiratory failure that requires mechanical ventilation. Thus, there is heightened interest in more accurate and complete characterization of high-risk patient populations and identification of patients in the early stage of acute lung injury, prior to the need for mechanical ventilation. This article discusses the growing literature on clinical predictors of acute lung injury (including risk factors for specific subgroups) with an emphasis on transfusion-related risk factors and recent research targeting the early identification of high-risk patients and those with early acute lung injury prior to the onset of respiratory failure.
Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) represent a spectrum of acute hypoxemic respiratory failure disorders, characterized by bilateral airspace consolidation with high permeability and protein-rich edema fluid. ARDS was first described by Ashbaugh and colleagues in a series of 12 patients in 1967. They recognized a common pattern of severe respiratory distress, refractory cyanosis, loss of lung compliance and diffuse alveolar infiltrates in a variety of clinical disorders, including sepsis, pneumonia, aspiration and major trauma. Previously, similar syndromes of acute respiratory failure were recognized only as distinct conditions named for their specific inciting etiology (e.g., Da Nang lung, shock lung, post-traumatic lung and respirator lung). However, lack of consistent definitions and appropriately powered clinical trials diluted the impact of early research efforts and constrained improvements in clinical outcomes. As recently as 1990, the mortality rate was estimated to be as high as 67%.
In 1994, the American and European Consensus Conference (AECC) established more specific clinical criteria for ALI and ARDS, providing standardization for clinical research and multicenter clinical trials. However, despite our improved understanding of the etiologies and pathophysiology of ALI, in the nearly 20 years since the AECC, a lung-protective strategy of mechanical ventilation is the only supportive therapy that clearly improves survival. Other ventilatory strategies, including prone positioning, high levels of positive end-expiratory pressure (PEEP) and a conservative fluid strategy, have shown potential benefit in terms of a reduction in the duration of mechanical ventilation, but none have significantly reduced mortality. While these studies represent advances in the supportive care of patients with ALI, no disease-specific treatments targeting the pathogenesis of the underlying lung injury can currently be recommended. Numerous pharmacologic therapies have shown promise in early phase studies but failed to demonstrate benefit in multicenter clinical trials. The apparent benefit of early goal-directed therapy for sepsis suggests that greater clinical benefit may derive from initiating therapy prior to the onset of mechanical ventilation-dependent respiratory failure. Early intervention to limit tidal volumes and transfusions in at-risk patients may prevent ALI. Multiple pharmacologic therapies that have either failed to show benefit in ALI after progression to mechanical ventilation, such as aerosolized albuterol (NCT00434993), or that are currently being evaluated, such as statins (SAILS Trial [NCT00979121] and HARP study) or antiplatelet agents, may yield additional benefit if initiated earlier in the progression of lung injury. This focus has led to greater interest in earlier identification of ALI and better characterization of high-risk patient populations prior to the onset of lung injury.
Improved understanding of cellular pathways of injury and genomic and proteinomic signatures of ALI offer potential for more accurate and early detection but are not currently sufficiently validated for use in clinical practice. These topics have been reviewed elsewhere and are beyond the scope of this article, which will focus on the growing literature on clinical risk factors and strategies for early identification of ALI.
Abstract and Introduction
Abstract
Despite significant advances in our understanding of the pathophysiology of acute lung injury, a lung-protective strategy of mechanical ventilation remains the only therapy with a proven survival advantage. Numerous pharmacologic therapies have failed to show benefit in multicenter clinical trials. The paradigm of early, goal-directed therapy of sepsis suggests greater clinical benefit may derive from initiating therapy prior to the onset of respiratory failure that requires mechanical ventilation. Thus, there is heightened interest in more accurate and complete characterization of high-risk patient populations and identification of patients in the early stage of acute lung injury, prior to the need for mechanical ventilation. This article discusses the growing literature on clinical predictors of acute lung injury (including risk factors for specific subgroups) with an emphasis on transfusion-related risk factors and recent research targeting the early identification of high-risk patients and those with early acute lung injury prior to the onset of respiratory failure.
Introduction
Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) represent a spectrum of acute hypoxemic respiratory failure disorders, characterized by bilateral airspace consolidation with high permeability and protein-rich edema fluid. ARDS was first described by Ashbaugh and colleagues in a series of 12 patients in 1967. They recognized a common pattern of severe respiratory distress, refractory cyanosis, loss of lung compliance and diffuse alveolar infiltrates in a variety of clinical disorders, including sepsis, pneumonia, aspiration and major trauma. Previously, similar syndromes of acute respiratory failure were recognized only as distinct conditions named for their specific inciting etiology (e.g., Da Nang lung, shock lung, post-traumatic lung and respirator lung). However, lack of consistent definitions and appropriately powered clinical trials diluted the impact of early research efforts and constrained improvements in clinical outcomes. As recently as 1990, the mortality rate was estimated to be as high as 67%.
In 1994, the American and European Consensus Conference (AECC) established more specific clinical criteria for ALI and ARDS, providing standardization for clinical research and multicenter clinical trials. However, despite our improved understanding of the etiologies and pathophysiology of ALI, in the nearly 20 years since the AECC, a lung-protective strategy of mechanical ventilation is the only supportive therapy that clearly improves survival. Other ventilatory strategies, including prone positioning, high levels of positive end-expiratory pressure (PEEP) and a conservative fluid strategy, have shown potential benefit in terms of a reduction in the duration of mechanical ventilation, but none have significantly reduced mortality. While these studies represent advances in the supportive care of patients with ALI, no disease-specific treatments targeting the pathogenesis of the underlying lung injury can currently be recommended. Numerous pharmacologic therapies have shown promise in early phase studies but failed to demonstrate benefit in multicenter clinical trials. The apparent benefit of early goal-directed therapy for sepsis suggests that greater clinical benefit may derive from initiating therapy prior to the onset of mechanical ventilation-dependent respiratory failure. Early intervention to limit tidal volumes and transfusions in at-risk patients may prevent ALI. Multiple pharmacologic therapies that have either failed to show benefit in ALI after progression to mechanical ventilation, such as aerosolized albuterol (NCT00434993), or that are currently being evaluated, such as statins (SAILS Trial [NCT00979121] and HARP study) or antiplatelet agents, may yield additional benefit if initiated earlier in the progression of lung injury. This focus has led to greater interest in earlier identification of ALI and better characterization of high-risk patient populations prior to the onset of lung injury.
Improved understanding of cellular pathways of injury and genomic and proteinomic signatures of ALI offer potential for more accurate and early detection but are not currently sufficiently validated for use in clinical practice. These topics have been reviewed elsewhere and are beyond the scope of this article, which will focus on the growing literature on clinical risk factors and strategies for early identification of ALI.