Aspirin Therapy in Patients With Acute Respiratory Distress Syndrome (ARDS) Is Associated With Reduced Intensive Care Unit Mortality

A Prospective Analysis

Andrew J Boyle; Stefania Di Gangi; Umar I Hamid; Linda-Jayne Mottram; Lia McNamee; Griania White; LJ Mark Cross; James J McNamee; Cecilia M O'Kane; Daniel F McAuley

Disclosures

Crit Care. 2015;19(109) 

In This Article

Abstract and Introduction

Abstract

Introduction Acute respiratory distress syndrome (ARDS) is a common clinical syndrome with high mortality and long-term morbidity. To date there is no effective pharmacological therapy. Aspirin therapy has recently been shown to reduce the risk of developing ARDS, but the effect of aspirin on established ARDS is unknown.

Methods In a single large regional medical and surgical ICU between December 2010 and July 2012, all patients with ARDS were prospectively identified and demographic, clinical, and laboratory variables were recorded retrospectively. Aspirin usage, both pre-hospital and during intensive care unit (ICU) stay, was included. The primary outcome was ICU mortality. We used univariate and multivariate logistic regression analyses to assess the impact of these variables on ICU mortality.

Results In total, 202 patients with ARDS were included; 56 (28%) of these received aspirin either pre-hospital, in the ICU, or both. Using multivariate logistic regression analysis, aspirin therapy, given either before or during hospital stay, was associated with a reduction in ICU mortality (odds ratio (OR) 0.38 (0.15 to 0.96) P = 0.04). Additional factors that predicted ICU mortality for patients with ARDS were vasopressor use (OR 2.09 (1.05 to 4.18) P = 0.04) and APACHE II score (OR 1.07 (1.02 to 1.13) P = 0.01). There was no effect upon ICU length of stay or hospital mortality.

Conclusion Aspirin therapy was associated with a reduced risk of ICU mortality. These data are the first to demonstrate a potential protective role for aspirin in patients with ARDS. Clinical trials to evaluate the role of aspirin as a pharmacological intervention for ARDS are needed.

Introduction

Acute respiratory distress syndrome (ARDS) is a common devastating clinical syndrome characterised by life-threatening hypoxaemic respiratory failure often requiring mechanical ventilation and frequently leading to multiple organ failure. ARDS is a major cause of morbidity and mortality within the ICU, and causes long-term reduction in quality of life for survivors.[1–3]

ARDS is an inflammatory condition characterised by neutrophil-mediated[4,5] and macrophage-mediated[6] injury. This uncontrolled local inflammatory response causes alveolar epithelial and capillary endothelial barrier damage, increasing its permeability. This allows the accumulation of an inflammatory infiltrate, and proteinaceous fluid within the alveolar space (non-cardiogenic pulmonary oedema) that contributes to profound hypoxaemia. The accompanying widespread activation of the coagulation cascade leads to microvascular thrombosis and fibroproliferation.[7] Currently there are few effective interventions for ARDS,[8,9] and these primarily involve limiting ventilator-induced lung injury with low tidal volume ventilation,[10] prone positioning,[11] with emerging data for neuromuscular blockade[12] and extra-corporeal therapies.[13,14]

Platelets have an increasingly recognised role in the inflammatory response leading to the development of ARDS. Platelet activation mediates neutrophil-recruitment to the lung in an acid-induced murine model of lung injury, an effect that is inhibited by pre-treatment with aspirin.[15] Platelet depletion in two mouse models of ARDS reduced the severity of lung injury and increased survival, an effect that was reproduced by pre-treatment with aspirin.[16] In addition, delayed neutrophil apoptosis is a feature of ARDS that aspirin can ameliorate to promote resolution of persisting inflammation.[17]

Most, but not all[18,19] observational data suggest that aspirin use prior to ICU admission (without ARDS at the point of admission) may reduce the subsequent development of ARDS.[20–22] Finally, in a cohort of patients admitted with community-acquired pneumonia, those patients being treated with anti-platelet drugs (the majority of whom received aspirin) had a significantly lower rate of critical care admission.[23]

These data suggest that aspirin may prevent ARDS, however, it is unknown if aspirin exposure alters outcome in patients with established ARDS. Aspirin exposure in patients with systemic inflammatory response syndrome (SIRS), severe sepsis or septic shock is associated with reduced mortality,[24,25] but there are no data in patients with ARDS. We hypothesised that aspirin treatment, either prior to, or during ICU admission, would reduce mortality in patients with ARDS. To assess this, we prospectively identified patients with ARDS to determine the effect of aspirin exposure on mortality within ICU.

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