Quicker Sepsis Treatment Saves Lives: Q & A With Sepsis Researcher Christopher Seymour

Sepsis is a serious medical condition caused by an overwhelming immune response to infection. The body’s infection-fighting chemicals trigger widespread inflammation, which can lead to blood clots and leaky blood vessels. As a result, blood flow is impaired, depriving organs of nutrients and oxygen. In severe cases, one or more organs fail. In the worst cases, blood pressure drops, the heart weakens, and the patient spirals toward septic shock. Once this happens, multiple organs—lungs, kidneys, liver—may quickly fail, and the patient can die.

Because sepsis is traditionally hard to diagnose, doctors do not always recognize the condition in its early stages. In the past, it has been unclear how quickly sepsis needs to be diagnosed and treated to provide patients with the best chance of surviving.

Credit: University of Pittsburgh.

Now we may have an answer: A large-scale clinical study, published recently in the New England Journal of Medicine Exit icon, found that for every hour treatment is delayed, the odds of a patient’s survival are reduced by 4 percent. Christopher Seymour Exit icon, assistant professor of critical care and emergency medicine at the University of Pittsburgh, and his team analyzed the medical records of nearly 50,000 sepsis patients at 149 clinical centers to determine whether administering the standard sepsis treatment—antibiotics and intravenously administered fluids—sooner would save more lives.

I spoke with Seymour about his experience treating sepsis patients and his research on the condition, including the new study.

CP: How big a public health problem is sepsis?

CS: Our recent work with the Centers for Disease Control and Prevention suggests there might be as many as 2 million sepsis cases in the United States each year. I can share personally that sepsis, or septic shock, is far and away the most common life-threatening condition that I treat in the ICU (intensive care unit). It’s quite devastating, particularly among our elders, and it requires prompt care. Although the mortality rate may be decreasing, it’s still quite high. About 1 in 10 patients with sepsis don’t survive their hospital stay. Even young, healthy people can succumb from sepsis. And if you’re fortunate to survive, you can have significant problems with cognitive and physical function for many months to years down the line.

Unfortunately, the incidence of sepsis may even be increasing. More patients are surviving serious illnesses that used to be fatal. They’re alive, but their health is compromised, so they are at higher risk for sepsis. Also—and this is a positive—we are seeing greater recognition and increased reporting of sepsis. Both factors probably contribute to the higher numbers of reported sepsis cases.

CP: What are some of the biggest challenges in fighting sepsis?

CS: The first challenge is public awareness. It’s important that the public knows the word sepsis, that they’re familiar with sepsis being a life-threatening condition that results from an infection, and that they know it can strike anyone—young, old, healthy, or sick. But it’s also important to know that not every infection is septic, nor will every cut or abrasion lead to life-threatening organ dysfunction.

Another part of the problem is that sepsis is not as easy for patients to recognize as, say, myocardial infarction (heart attack). When patients clutch their chest in pain, they intuitively recognize what’s happening. Patients frequently don’t recognize that they’re septic. People should know that when they have an infection or take antibiotics as an outpatient, and they’re starting to feel worse or having other new symptoms Exit icon [PDF, 147KB], they may be at risk of sepsis. They should go to the emergency department or seek medical help.

The second challenge in fighting sepsis is that it’s just hard to diagnose, even for well-trained clinicians. Both issues can lead to delays in care, the most important of which is the delay in treatment with antibiotics.

CP: Tell me about your recent clinical trial. What question did you set out to answer?

CS: There’s been a lot of interest in the early recognition and treatment of sepsis over the past decade. Recently, the National Institutes of Health/National Institute of General Medical Sciences funded a large, multicenter trial called ProCESS, which tested various strategies for treating sepsis. This trial told us that a standardized sepsis protocol among people who had already received antibiotics didn’t necessarily change survival rates. But what it left unanswered was the very important question of when the patient first arrives at the emergency department, how fast do we need to provide antibiotics and fluids for the best possible outcome? Continue reading

Preventing Sepsis in Half the Time

Human digestive system
A new study suggests that an antibiotic regimen half as long as the standard course could be just as effective in treating intra-abdominal infections and preventing sepsis. Credit: Stock image.

When treating infections, the most critical actions are to quash the infection at its site of origin and prevent it from spreading. If allowed to spread to the bloodstream, an infection could result in body-wide inflammation known as sepsis that can cause organ failure and death.

Intra-abdominal infections, most often caused by gut bacteria, can lead to painful inflammation and present a high risk for sepsis. These infections, which include appendicitis, are some of the most common illnesses around the world.

A standard treatment regimen includes surgically removing the original infection and then prescribing antibiotics to keep the infection from coming back and to prevent sepsis. Currently, doctors administer antibiotics until 2 days after the symptoms disappear, for a total of up to 2 weeks.

Like many other researchers, University of Virginia’s Robert Sawyer Exit icon wondered if treating intra-abdominal infections with shorter antibiotic courses could be just as effective as the standard treatment. To find out, he and a team of researchers from around the country designed the Study to Optimize Peritoneal Infection Therapy (STOP-IT). Continue reading

Improving the Odds of Surviving Sepsis

Acupuncture
A form of acupuncture—or a drug that mimics its effect—may one day lead to an anti-inflammatory therapy for people with sepsis. Credit: Stock image.

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.”

NIH-funded scientists use a variety of tools, including blood tests and acupuncture, in their quest to detect sepsis early, treat it quickly and reduce its later effects.

Read more about sepsis research in this Inside Life Science article.

Dormant Viruses Reactivate, Signaling Effect of Lingering Sepsis

Doctors with a patient
A new study finds that people with lingering sepsis may have suppressed immune systems. Credit: Stock image.

Each year, more than 200,000 people in the United States die from sepsis, a condition caused by an overwhelming immune response that can quickly lead to organ failure. While many people with sepsis survive this immediate threat, they may die days or even months later from secondary infections.

A research team that included Richard Hotchkiss, Jonathan Green and Gregory Storch of Washington University School of Medicine in St. Louis suspected that when sepsis lasts for more than a few days, it compromises the immune system. To test this hypothesis, the scientists compared viral activity in sepsis patients, other critically ill patients and healthy individuals. They looked for viruses like Epstein-Barr and herpes-simplex that are often dormant and innocuous in healthy people but can reactivate and cause problems in those with suppressed immune systems.

Of the three study groups, sepsis patients had much higher levels of these viruses, suggesting that their immune responses may be hindered. 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 people with lingering sepsis.

Learn More:
Washington University in St. Louis News Release Exit icon
NIGMS Sepsis Fact Sheet

Study Comparing Sepsis Treatment Methods Shows Equivalent Survival Rates

Doctors and a patient in a hospital
A 5-year, randomized clinical trial helped resolve a long-standing debate about how best to manage sepsis patients.

For years, doctors have debated the best ways to identify, predict and treat sepsis. The condition, which is usually triggered by infection, is marked by body-wide inflammation and can lead to a dangerous drop in blood pressure known as septic shock. Sepsis affects more than 800,000 people each year and kills about 20 to 30 percent of them. It’s the most expensive condition treated in U.S. hospitals, costing more than $20 billion a year.

Now, a nationwide, 5-year clinical trial that set out to compare three different treatment approaches has shown that survival of patients with septic shock was the same regardless of whether they received treatment based on structured, standardized medical plans (protocols) or the usual high-level standard of care. If patients were diagnosed shortly after the onset of sepsis and treated promptly with fluids and antibiotics, they did equally well whether they received treatment based on either of two specific protocols—one less invasive than the other—or got the usual, high-level care provided by the academic hospitals where the study was conducted.

According to the study’s leaders, the trial “helps resolve a long-standing clinical debate about how best to manage sepsis patients, particularly during the critical first few hours of treatment,” and shows that “there is not a mandated need for more invasive care in all patients.”

Learn more:
NIGMS News Release
University of Pittsburg News Release Exit icon
New England Journal of Medicine Article Exit icon
Sepsis Fact Sheet

Protein Triggers Inflammatory Responses in Hemorrhage and Sepsis

Doctors helping a patient. Credit: U.S. Navy.
Inflammation is part of the body’s natural response to trauma, but when it becomes widespread, it can lead to sepsis. Credit: U.S. Navy.

Inflammation is part of the body’s natural response to trauma, playing a vital role in wound healing and prevention of infection. However, when inflammation becomes widespread, or systemic, it can lead to sepsis, a condition that can damage organs and cause death. Scientists led by Ping Wang Exit icon of the Feinstein Institute for Medical Research have found a way to potentially target harmful systemic inflammation. They identified a protein–cold-inducible RNA-binding protein (CIRP)–that triggers inflammatory responses during hemorrhagic shock and sepsis. Wang then hypothesized that blocking CIRP activity might mitigate the body’s overall inflammatory response and improve patient survival. In a preclinical study using mice, an antibody against CIRP decreased mortality after hemorrhage and sepsis. The molecule could lead to the development of an anti-CIRP drug.

This work also was funded by the NIH Office of the Director and NIH’s National Heart, Lung, and Blood Institute.

Learn more:

Fact Sheets on Physical Trauma and Sepsis
The Body’s Response to Traumatic Injury Video