“Effect of aspirin on development of ARDS in at-risk patients presenting to the emergency department, the LIPS-A randomized clinical trial” JAMA, 2016, USA
Question: Does aspirin prevent the development of ARDS in at-risk patients?
Study Type: Multicenter, double-blind, placebo-controlled, parallel-group, randomized clinical trial at 16 medical centers across the United States
Study Population: Adults presenting to the emergency department with a Lung Injury Prediction score ≥ 4 were eligible (see commentary for more regarding LIPS). Numerous exclusions included ARDS on presentation, chronic use of antiplatelet therapy, admission for elective surgery, chronic tracheostomy, presentation due to CHF, active peptic ulcer disease, bleeding disorders, and severe chronic liver disease. Randomization had to occur within 12 hours of presentation.
Study Groups: Patients were randomized to either placebo or daily ASA given as a 325mg loading dose within 24 hours of presentation followed by 81mg daily up to hospital day 7, discharge, or death. Clinicians were encouraged to use the Checklist for Lung Injury Prevention to guide clinical care.
Primary Outcome: Development of ARDS requiring mechanical ventilation within 7 days of hospital admission
Results: 390 patients included in intention-to-treat analysis. Notable patient characteristics: median age (67), Caucasian (72%), suspected sepsis (78%), non-cardiogenic shock (21%), possible PNA (61%), ventilated on day of randomization (17%), median LIPS (≈5.75). ASA did not decrease the development of ARDS (10.3% in ASA group, 8.7% in placebo group, P=0.53). ASA did not significantly impact any secondary outcome measures. There was no difference in adverse events between groups
Caveats: Generalizability a concern as 95% of the 7,673 patients screened were excluded (with prior antiplatelet use, inability to consent with 12 hours, and suspected active bleeding being the most common reasons for exclusions), delay between consent and medication administration (median delay 12.7 hours), development of ARDS occurred almost half as frequently as anticipated.
Take-home Point: Among at-risk patients presenting to the emergency department, daily ASA use did not decrease the development of ARDS at 7 days.
Commentary
– I chose to review this study because it is important for residents to be aware of the increasing focus on ARDS prevention. Indeed, the NHLBI-funded ARDS clinical trial network is named PETAL (Prevention and Early Treatment of Acute Lung Injury). This refocusing of ARDS clinical trials is based on the observation that ARDS incidence has decreased (suggesting perhaps that through early abx, thoughtful IVF, less injurious ventilator strategies, and restrictive transfusion thresholds we have shown that ARDS prevention is possible) and the hypothesis that so many therapeutic trials in ARDS have been negative because therapies have been initiated AFTER significant alveolar-capillary injury has already occurred.
– The Lung Injury Prediction Score has been found to have an AUC for the prediction for ARDS of 0.8 (see attached AJRCCM article). LIPS variables include shock, aspiration, sepsis, PNA, high-risk surgery, high-risk trauma, EtOH abuse, obesity, low albumin, chemotherapy, FIO2>0.35, RR>30, SpO2<95%, pH <7.35, DM. At a cut-off of 4, LIPS has a sensitivity of 69% and specificity of 78% for the development of ARDS. Based on the AJRCCM data, with a LIPS of 6 (roughly the average of pts in the JAMA trial), you would expect roughly 15% to develop ARDS.
– ASA was chosen given the known pathogenic role of platelet activation and aggregation in the development of ARDS, the anti-inflammatory effects of ASA, and encouraging pre-clinical data.