By Carolyn Beans
Posted August 18, 2014
A leading cause of death in U.S. intensive care units is sepsis, an overwhelming immune response to infection that triggers body-wide inflammation and can cause organ failure.
Sepsis is challenging to diagnose and treat. Many of its early signs, such as fever and difficulty breathing, are similar to those of other conditions. When doctors do not detect sepsis until a more advanced stage, they are often unable to stop its progression or prevent its complications.
"Sepsis is a complex problem," says Sarah Dunsmore of the National Institutes of Health (NIH). "We need more research at all levels—from the molecular to the patient—to improve sepsis diagnosis and treatment and to enhance the quality of life for sepsis survivors."
Here's a sampling of NIH-funded research efforts to detect sepsis early, treat it quickly and reduce its later effects.
By the time a person develops the inflammation characteristic of sepsis, the condition may have already progressed to a life-threatening stage. But according to James Mapes of diagnostic test developer Myriad RBM, "If you can identify sepsis earlier, then you can treat it before it gets out of control."
Mapes and his research team are developing a tool for detecting sepsis early in infants with very low birthweights (VLBW). More than 20 percent of infants who weigh less than 3 pounds, 4 ounces are affected by sepsis.
As sepsis progresses, the amounts of certain proteins in an infant's bloodstream increase while others decrease. Mapes' team tested the levels of hundreds of proteins in the blood of VLBW infants with and without sepsis. The scientists are now using statistical techniques to determine which combinations of these proteins are most associated with sepsis.
Their goal is to use this protein profile to develop a rapid blood test to detect sepsis in VLBW infants before the physical signs of the condition appear.
The antibiotics that treat infections do not prevent the dangerous inflammation that is a hallmark of sepsis. But a study led by Luis Ulloa of Rutgers New Jersey Medical School suggests that a form of acupuncture—or a drug that mimics its effect—might one day lead to an anti-inflammatory therapy for people with sepsis.
The research team applied needles with weak electric voltages to an acupuncture point on mice with a sepsis-like condition. The "electro-acupuncture" treatment stimulated the sciatic nerve, which runs from the lower back to the foot. This then set off a nerve network that triggered the adrenal gland to produce the chemical dopamine, and the mice experienced reduced inflammation and greatly improved survival.
But unlike the mice in this study, humans with sepsis often have underperforming adrenal glands. The effectiveness of the electro-acupuncture therapy, however, depended on a working adrenal gland. To overcome this obstacle to developing a potential therapy, the researchers tested whether dopamine-like drugs could have the same effect as electro-acupuncture, even in mice lacking adrenal glands. One of these drugs, fenoldopam, reduced deaths by 40 percent.
The team hopes this research may one day lead to a new way of treating sepsis.
Some people who survive sepsis can develop secondary infections days or even months later. A research team that included Richard Hotchkiss, Jonathan Green and Gregory Storch of Washington University School of Medicine in St. Louis suspected that this is because sepsis might cause lasting damage to the immune system. To test this hypothesis, the scientists compared viral activation in people with sepsis, other critically ill people and healthy individuals. The researchers looked for viruses like Epstein-Barr and herpes simplex that are often dormant in healthy people but can reactivate in those with suppressed immune systems.
Of the three study groups, people with sepsis had much higher levels of these viruses, suggesting reactivation due to compromised immune responses. Immune suppression could make it difficult to defend against the reactivated viruses as well as new infections like pneumonia. The team now plans to test whether immune-boosting drugs can prevent deaths in sepsis survivors.
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