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Is a New Sepsis Treatment on the Horizon?

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April 4, 2017 -- The possibility of curing sepsis with a common vitamin has put one of history's greatest killers back in the spotlight.

Sepsis has been in the medical books since Hippocrates. It occurs when the body’s immune system responds to an infection with overwhelming force. That can trigger complications that can cause blood clots and other problems, leading to organ failure and death.

In the days before sterile instruments and antibiotics, sepsis was a frequent and deadly complication of wounds. But today, there are hundreds of thousands of U.S. cases each year -- and 25% to 50% of them are fatal. It’s one of the leading causes of death for people in hospitals, particularly those in intensive care. Survival often depends on an early dose of the right antibiotic and intravenous fluids, along with tests to look for signs of an infection or organ failure.

“We have simple treatments that work, but so far, none of the fancier treatments have worked,” says Jonathan Sevransky, MD, who works with critically ill patients at Emory University Hospital in Atlanta.

To treat sepsis, doctors have to tackle not only the underlying infection, but the complications that come from the body’s immune response, Sevransky says. In addition, there’s no simple test to identify sepsis early -- something that’s particularly dangerous for patients in intensive care, Sevransky says.

“When you look at people who die in the hospital, between one in three or even one in two will die from sepsis,” he says. “Sometimes it’s because they have so many other problems that we can’t solve all the problems and the infection, but sometimes it’s because we don’t think of it early enough.”

The problem got a new look in recent months after Virginia doctors who used a cocktail of vitamin C, corticosteroids, and vitamin B1 said it helped fight off organ failure and death in patients with sepsis. Among 47 patients who received that mix, all but four survived, the doctors reported in a recent study.

But that study involved a small number of patients in one hospital, and the authors noted that more research is needed to confirm those findings.

“For the type of study that it was, it was nicely done,” Sevransky says. But he says a follow-up study will need to involve more patients, some of whom would get the treatment and others who wouldn't.

Previous research has suggested vitamin C can improve blood flow to tissues in the body of a sepsis patient, keeping the cells supplied with nutrients and oxygen and preventing organ failure. Other studies have tried to focus on restraining the immune overreaction that causes sepsis.

That overreaction makes it harder for blood to flow. And it’s possible that non-steroidal anti-inflammatory drugs (NSAIDs) -- a group that includes popular over-the-counter painkillers like ibuprofen -- may be able to offset that response, said Hang Hubert Yin, a biochemist at the University of Colorado.

Yin has been studying a family of naturally occurring enzymes called caspases, which fuel the kind of aggressive immune response that can lead to sepsis. When he and his colleagues sorted through a list of more than 1,200 drugs that can restrain caspases, he found about a dozen NSAIDs on that list.

Those findings, published in February, could help doctors find new drugs to help treat sepsis and other problems. But it’s not without risk: Yin notes that NSAIDs can cause heart and stomach problems, and those complications kill as many as 16,000 people a year. It will take several years before NSAIDS are tested to treat sepsis in humans.

But other potential anti-sepsis drugs failed to live up to their initial promise. A drug that targeted a protein involved in the body’s immune response failed a phase III clinical trial in 2011, while another aimed at improving blood flow in sepsis patients was pulled from the market the same year after disappointing results.

“The basic biology here, the pathology of sepsis, is extremely challenging to fight with pharmaceuticals,” Yin says. Once sepsis sets in, death can occur in 24 to 48 hours. The underlying infection may be resistant to antibiotics, and organ damage that happens can be “extremely difficult” to halt with drugs.

For now, Sevransky says the most important thing doctors can do is detect signs of sepsis early -- something that is often difficult. Patients with certain types of infections, infants, people over 65, and those with weakened immune systems are more likely to get sepsis. Symptoms include fever, chills, and sweating; extreme pain or discomfort; difficulty breathing; and an elevated heart rate. And in some patients, confusion is the first outward sign of the problem, he says.

“They often have symptoms that don’t often jump and say, ‘I have an infection.’ Somebody gets confused, somebody gets sore, somebody has trouble breathing -- that suggests that they’re sick, but may not necessarily have a flag sticking up that says, ‘I have a bad infection, and I need treatment rapidly,’ “ Sevransky says.

The CDC has started urging doctors to "Think Sepsis." A similar push is under way by the Society for Critical Care Medicine and its European counterpart, the European Society of Intensive Care Medicine.

“It’s tremendously important, because a lot of people have it,” Sevransky says. “But it’s not complicated, which is maybe why people haven’t paid a lot of attention to this. It’s really bread-and-butter medicine, but we don’t do as good as a job as we’d like to do.”

WebMD Article Reviewed by Hansa D. Bhargava, MD on April 4, 2017

Sources

SOURCES:

Jonathan Sevransky, MD, Emory University Hospital, Atlanta.

Hang Hubert Yin, PhD, University of Colorado, Boulder.

National Institute of General Medical Sciences: “Sepsis Fact Sheet.”

German Sepsis Society: “Sepsis History.”

CDC.

Chest journal: “Hydrocortisone, Vitamin C and Thiamine for the Treatment of Severe Sepsis and Septic Shock: A Retrospective Before-After Study.”

Subcellular Biochemistry: “Vitamin C in sepsis.”

Cell Chemical Biology: “Non-steroidal Anti-inflammatory Drugs Are Caspase Inhibitors.”

Journal of the American Medical Association: “Effect of Eritoran, an Antagonist of MD2-TLR4, on Mortality in Patients With Severe Sepsis.”

U.S. Food and Drug Administration: “Voluntary market withdrawal of Xigris [drotrecogin alfa (activated)] due to failure to show a survival benefit.”

Society of Critical Care Medicine: “Surviving Sepsis Campaign.” 

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