Newswise — Investigators at two major academic medical centers in the United States are analyzing blood chemicals that may identify the patients who are in danger of organ injury after certain types of surgery or organ failure after trauma. The hope is to develop bedside blood tests that will quickly and reliably determine which patients are at risk for organ damage so they may receive preventive treatment. Findings from their initial research studies were reported at the 2008 Clinical Congress of the American College of Surgeons.
The researchers are focusing on two major causes of morbidity and mortality among surgical patients: multiple organ failure after treatment for trauma and kidney failure and kidney injury after cardiac surgery. "While only about 20 percent of patients go into multiple organ failure after trauma, 60 percent of these patients die," said David W. Mercer, MD, FACS. Dr. Mercer is the Jack H. Mayfield Chair in Surgery, professor and vice-chair of the department of surgery at the University of Texas Health Science Center, Houston, and chief of general surgery at Memorial Hermann Hospital in Houston. "If we could predict which of our patients was going to go into multiple organ failure, we might be able to target that patient population with some of the new treatments that we are studying in the lab. We are trying to expand knowledge in this area in order to improve outcomes because multiple organ failure is one of the leading causes of death for patients who are under the age of 45," Dr. Mercer said.
Among patients who have certain types of complex cardiac surgery, such as operations on the thoracic aorta, as many as 40 percent may have moderate kidney failure and eight percent may require dialysis. "If we had a test like a diabetic measurement of blood sugar levels, we might be able to measure at the point-of-care whether a patient is at risk for kidney injury and administer drugs to try to prevent it," Thomas M. Beaver, MD, MPH, FACS, associate professor and director of minimally invasive cardiac, thoracic, and cardiovascular surgery at the University of Florida College of Medicine, Gainesville, said.
The research groups are measuring markers of inflammation and injury that appear in the blood. Dr. Mercer and his colleagues are among the first groups to analyze a panel of cytokines or chemokines in critically injured patients and then separate out differences in the levels of these biomarkers in patients who had multiple organ failure and those who did not. Cytokines are mediators of inflammation. Proinflammatory cytokines cause tissue injury, and antiinflammatory cytokines decrease inflammation. Chemokines are small cytokines or proteins.
In a study of patients who had sustained major trauma to the chest and abdomen, Dr. Mercer found that levels of both types of cytokines were increased in these patients. "We found that not only were the traditional cytokines different in multiple organ failure patients versus nonmultiple organ failure patients, some unique cytokines that have not been previously described also were predictors of multiple organ failure. The limitation of the study is that it is a prospective observational study that was not powered to demonstrate statistical significance at a high level and there were only 48 patients. But the data are very significant. For one of the chemokines--IP 10 (human interferon-inducible protein 10), if patients had a value over 891, they had a 100 percent probability of developing multiple organ failure," Dr. Mercer said.
Dr. Beaver and his associates are evaluating a marker that measures kidney injury earlier than standard forms of monitoring kidney function. He explained that surgeons typically assess blood levels of creatinine, which indicate how well the kidneys are functioning. "The lower the function of the kidneys, the more creatinine that builds up in the blood. Typically, you don't see increases in creatinine for a day or two after surgery, however," he said.
Neutrophil-gelatinase-associated-lipocalin (NGAL) provides evidence of subtle injury to the kidneys before creatinine levels rise. "NGAL allows us to measure changes in creatinine much earlier. We can see within a few hours after surgery that NGAL is increasing, and this gives us a hint that there is going to be kidney injury or the patient has early signs of kidney injury," Dr. Beaver said.
Point-of-care tests for multiple organ failure or kidney injury are some years down the road, Dr. Beaver pointed out. While there is a commercially available testing kit for NGAL, its use as a predictor of kidney injury has not been validated. Assays for testing cytokines are used only in research settings at this time.
There has been little incentive to develop such tests because, until recently, surgeons had few options for treating patients who were in danger of organ damage or failure. However, promising drug treatments are being tested in clinical trials.
"I think maybe five years from now, we'll get an NGAL test on patients who have undergone heart surgery, and assuming we have a point-of-care test that gets immediate results as well as an effective treatment to improve kidney function, then we will be able to treat them with whatever agent we have at the time," Dr. Beaver said.
"We have a ways to go. We have to validate whether cytokines are predictive of multiple organ failure and show that preventing the production of pro- or antiinflammatory cytokines decreases multiple organ failure. But this is a clinical problem that has relevance to the community, and there is potential to improve outcomes. That potential is what we find very exciting," Dr. Mercer
Kenneth M. Jastrow, MD; Mary F. McGuire, MSc; Ernest A. Gonzalez, MD; Rosemary A. Kozar, MD, PhD, FACS; and Sriram Iyengar, PhD, participated in the study of cytokine profiling as a predictor of early multiple organ failure in trauma patients.
Tad Kim, MD; George J. Arnaoutakis, MD; Azra Bihorac, MD; Tomas D. Martin, MD, FACS; Philip J. Hess, Jr., MD, FACS; Charles T. Klodell, MD, FACS; Curtis G. Tribble, MD, FACS; Ahsan A. Ejaz, MD; and Lyle L. Moldawer, PhD, participated in the study of biomarkers of kidney injury after cardiac surgery.