By David Stauth
They used to call it “blood poisoning,” and the term is still descriptive, if outdated.
Like a poison, it’s fast and often deadly. A modest infection suddenly turns into a whole-body inflammation complete with fever, flushed skin, swelling and hyperventilation. It can hit anyone from an infant to the elderly. It killed at least two U.S. presidents while they were still in office.
The modern term is “sepsis.” That word was actually coined by Hippocrates around 400 B.C. and meant “the process of decay.” As a syndrome leading to multiple organ failure, sepsis is clearly a type of decay. But it’s a pretty quick process, where every hour of delay in administering an antibiotic can raise the mortality rate by another 6 percent. Even with aggressive treatment, 28 to 50 percent of the people diagnosed with sepsis die from it.
“Sepsis is a hidden killer, the one nobody really talks about,” says Adam Higgins, a bioengineer at Oregon State University. “It kills more people in the U.S. every year than AIDS, prostate cancer and breast cancer combined, and you still don’t hear much about it.”
A group of researchers in the College of Engineering, however, are working with teams of undergraduate and graduate students on a project that may soon have the whole world talking about sepsis. Finally there may be a way to combat this syndrome with something other than antibiotics — which often don’t work.
“A big part of the problem with sepsis is that it moves so rapidly,” says Joe McGuire, professor and head of the OSU School of Chemical, Biological and Environmental Engineering. “By the time it’s apparent what the problem is, it’s often too late to treat it. What we have in mind is a way to process the blood and prevent sepsis, something that could be used at any time.”
The underlying cause of sepsis is “endotoxins,” molecules that are released from bacterial cell walls and lead to rapid, systemic inflammation. These pieces of bacteria can disrupt the immune response, cause it to overreact and to develop clots and other problems that lead to multiple organ failure.
“If given early enough, antibiotics and other treatments can sometimes, but not always, stop this process,” McGuire adds. “Once these bacterial fragments are in the blood stream the antibiotics won’t always work. You can have successfully eradicated the living bacteria even as you’re dying.”
Undergraduates have used research opportunities in Joe McGuire’s lab as a launching pad to grad school and jobs in the biomedical industry.
The approach being developed at OSU is to move blood through a very small processor, about the size of a coffee mug, and literally grab the endotoxins and remove them. The concept is surprisingly simple and builds on some of the university’s revolutionary work with microchannel technology.
By moving fluids through tubes the width of a human hair, microchannels accelerate chemical reactions and heat transfer. Applications are already being studied in heat exchangers, solar energy and chemical manufacturing. Microchannels can be produced in mass quantity at low cost, stamped onto a range of metals or plastics and used to process a large volume of liquid in a comparatively short time.
In this case, the liquid is blood, which may contain the endotoxins that cause sepsis. In the OSU system, blood can be pumped through thousands of microchannels that are coated with what researchers call “pendant polymer brushes,” tiny strands equipped with chemicals that can grab endotoxin molecules like a fishing hook. On the business end of the strand is a peptide, a bioactive agent that binds tightly to the endotoxin and removes it from the blood, which then goes directly back to the patient. To keep blood proteins and cells from sticking or coagulating in the channels, the strands also have been designed with repeating chains of carbon and oxygen atoms anchored on the surface.
“This doesn’t just kill bacteria and leave floating fragments behind; it sticks to and removes the circulating bacteria and endotoxin particles that might help trigger a sepsis reaction,” says Karl Schilke, the OSU Callahan Faculty Scholar in Chemical Engineering.
“We hope to emboss these out of low-cost polymers, so the device itself should be inexpensive enough that it can be used once and then discarded,” Schilke adds. “The low cost would also allow treatment even before sepsis is apparent, a prophylaxis approach to prevent it, not just treat it after the fact. Anytime there’s a concern about sepsis developing, due to an injury, a wound, an operation, an infection, you could get ahead of the problem.”
The risk of sepsis is surprisingly common. It can develop after an injury from an automobile accident, from a dirty wound, during an extended operation in a hospital, or opportunistically when people with a weak or compromised immune system contract an infectious disease.
More development and a demonstration of feasibility are still needed, the researchers say. The National Institutes of Health, the Collins Medical Trust and the Oregon Medical Research Foundation are supporting ongoing research. Advances are also being made in microchannel structures that would increase the adsorption of the endotoxins. But the promise of such systems — and their value in medicine — could be enormous once the work is complete.
“When we first conceived of this approach to prevent sepsis, my initial reaction was, ‘Wow!’” McGuire says. “Think of the number of deaths we could prevent. Think of the billions of dollars spent in intensive care that could be available for something else. Think of all the infants and young people who could have their whole lives given back to them.”
In the United States, one out of every four people in a hospital emergency room is there because of sepsis, and more than $20 billion was spent on this problem in 2011. It’s the single most expensive cause of hospitalization. But as Higgins points out, it’s still a hidden killer and doesn’t always even make it onto the death certificate. Sometimes “cardiac arrest” or “kidney failure” is listed as cause of death instead of the real, underlying cause — sepsis.
Since the dawn of time, sepsis has killed infants. It’s killed countless numbers of people wounded in battles. Millions of people around the world die from it every year. It killed Pope John Paul II.
But if the research at OSU succeeds within the next few years, much of that may become a problem of the past.