imageTrauma patients with severe injuries appear to have a better prognosis if they have been taking aspirin or other antiplatelet drugs before being injured, researchers have found.
The study found that trauma patients at high risk for death were much less likely to develop transfusion-associated lung dysfunction or organ failure if they had been taking antiplatelet agents before being injured compared with others not on antiplatelet therapy.
The findings, reported in the February 2013 issue of Critical Care Medicine (2013;41:399-404), support a growing body of evidence implicating platelets in the development of lung dysfunction and organ failure. They also reinforce preclinical research indicating improved outcomes from antiplatelet therapy administered to patients shortly after trauma and hemorrhagic shock.
“Antiplatelet therapy may have a significant beneficial effect on acute respiratory distress syndrome [ARDS], multiple organ failure [MOF] as well as other outcomes in trauma patients who receive multiple transfusions,” said Jeffrey Harr, MD, MPH, of the Department of Surgery at the University of Colorado Trauma Research Center, in Denver, and lead author of the study. “There have been several preclinical studies showing the benefits of antiplatelet therapy in transfusion-associated lung injury, but clinical data remain lacking. Our study is the first to show these clinical benefits in trauma patients,” Dr. Harr told Anesthesiology News.
The study compared outcomes of 839 patients at nine trauma centers from 2001 to 2008 who were prospectively enrolled in the Inflammation and Host Response to Injury, a project funded by a grant from the National Institute of General Medical Sciences. Of the 839 patients, 128 (15.3%) had been taking acetylsalicylic acid, another antiplatelet agent—including clopidogrel or ticlopidine—or a combination of aspirin and another drug before sustaining their injuries.
After adjusting for age, sex, comorbidities and other possible confounding characteristics, the researchers found that 58% of the patients who received antiplatelet treatment experienced lung dysfunction compared with 64% of the others (P=0.23). Similarly, they found that 17% of patients taking antiplatelet medication experienced multiple organ failure compared with 21% of the others (P=0.37).
And although the patients who had been taking antiplatelet medication were older and more severely injured, they received a similar volume of blood products and were less likely to require a massive transfusion (defined as more than 10 units of packed red blood cells; 17.2% versus 27.7%; P=0.01). The two groups experienced roughly identical rates of mortality—20% versus 21%, respectively (P=0.71).
Age Equalizer?
imageAll this is surprising, Dr. Harr said, because prior studies had found that older people with multiple comorbidities tend to have worse outcomes, including ARDS, MOF and mortality following trauma. “However, these data suggest that older patients with more comorbidities on antiplatelet therapy had similar outcomes to healthier individuals with no increased bleeding complications or increased transfusions,” Dr. Harr said.
“It is fascinating that such an old and cheap class of medications may play an important role, as they have in cardiovascular disease, in the management of one of the major problems in massive blunt trauma, ARDS and MOF,” wrote Peter J. Papadakos, MD, professor of anesthesiology at the University of Rochester, in New York, in an editorial accompanying the journal article (Crit Care Med 2013;41:659-660).
Dr. Papadakos, an Anesthesiology News editorial board member, said that although pharmaceutical companies have little interest in supporting additional clinical studies, meta-analyses of previous studies should be performed. And if the National Institutes of Health were to support large population studies in this area, new government-supported trials might follow.
However, he asked, “What is the downside of giving 81 mg of aspirin to a critically ill patient dying from ARDS and who already has a 40% to 50% chance of dying in the hospital?”
Mark Looney, MD, associate professor of medicine at the University of California, San Francisco, told Anesthesiology News that “more basic science work is needed to determine the mechanisms by which antiplatelet agents are potentially protective in trauma and acute lung injury, including determining whether the protection is common to all antiplatelet agents or perhaps restricted to just aspirin.” Dr. Looney has investigated the effects in mice of aspirin treatment on platelet depletion following transfusion-related acute lung injury (J Clin Invest 2009;119:3450-3461). He was not involved in this study.
Dr. Harr said he believes there is now sufficient evidence to begin prospective clinical studies in giving trauma patients antiplatelet therapy early following injury. “Trauma patients commonly present with advanced coagulopathies, including platelet dysfunction, which cautions the premature use of antiplatelet therapy,” Dr. Harr said. “However, these same patients develop a hypercoagulable state within 72 hours of injury. Therefore, in select patients, early administration of antiplatelet therapy may not only reduce the risk for ARDS and MOF, but may also have a role in decreasing post-injury venous thromboembolic events.”