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Reidy Center/EVMS Collaboration Leads to Possible Sepsis Cure

By Brendan O'Hallarn

A research partnership between Eastern Virginia Medical School and Old Dominion University led to a breakthrough that has the potential to save the lives of millions of hospitalized patients worldwide who are threatened by sepsis.

A medical complication marked by the presence in tissues of harmful bacteria and their toxins, sepsis causes a significant percentage of hospital deaths worldwide. But a discovery by an EVMS physician at Sentara Norfolk General Hospital, validated by Old Dominion's Frank Reidy Research Center for Bioelectrics, could have far-reaching implications.

Dr. Paul Marik, a critical care physician at EVMS, developed the new treatment while caring for patients in the general intensive care unit at Sentara Norfolk. Marik found that by giving patients a combined dose of vitamin C steroids and thiamine, the number of deaths at the intensive care unit due to sepsis dropped to zero.

Marik reached out to John Catravas, interim executive director professor and Sentara endowed chair at the Reidy Center, who has studied sepsis for many years.

Catravas researches the "barrier function" of endothelial cells - the thin layer of cells that line blood vessels - using bioelectric technologies. Properly functioning endothelial cells permit air to mix with blood in the lungs. Leakage of blood from the loss of that function is one of the primary causes of death from sepsis, through a condition known as pulmonary edema.

To test Marik's protocol in his lab, Catravas used endothelial cells cultured from human lung tissue and exposed them to the endotoxin commonly found in septic patients. As expected, the endothelial cells suffered a loss in function.

Neither vitamin C nor steroids alone had any therapeutic effect. But when Catravas added both vitamin C and steroids, the combination quickly counteracted the endotoxin. "The cells repair themselves," Catravas said, likening it to the "holy grail" in sepsis care.

More than 250,000 people in the United States die from sepsis annually, according to the Sepsis Alliance. It is the most common cause of death among hospitalized patients in the United States. The Global Sepsis Alliance estimates that 8 million people die worldwide as a result of sepsis each year.

"Dr. Marik has developed a brilliant and elegantly simple hypothesis in the treatment of sepsis," said Dr. Richard Homan, president and provost of Eastern Virginia Medical School and dean of the EVMS School of Medicine. "The implications of the findings of this study are profound and, if replicated, may transform the treatment of sepsis worldwide."

Old Dominion University Provost Augustine "Austin" Agho said this innovative treatment could save many lives worldwide.

"This is an excellent example of the benefits of interdisciplinary collaboration. I commend Dr. John Catravas for working with his colleagues at EVMS to validate the effectiveness of the newly developed treatment for sepsis," Agho said.

The initial finding was the result of a medical hunch by Marik as he treated a critically ill patient at Sentara.

"My intention was never to discover the cure for sepsis," said Marik, chief of critical care at EVMS and the EVMS Foundation Distinguished Professor in Internal Medicine. "It just kind of happened by mistake."

After the patient recovered quickly following an intravenous injection of vitamin C and steroids, Marik attempted the protocol on two more patients in critical condition from sepsis. They also recovered.

The finding led Marik to reach out to Catravas, who was just as encouraged by his laboratory findings. "There is amazing serendipity in how this partnership came together," he said. "We have been trying to find a way to help these people."

In a study published in CHEST, Marik and his co-authors compared two groups - treated in the same ICU - before and after discovery of the vitamin C-hydrocortisone-thiamine protocol. Before the treatment was available, 19 of 47 patients diagnosed with sepsis died from the disease. In contrast, there were no deaths from sepsis among the 47 patients who received the new treatment.

"What Dr. Marik and his team have accomplished is quite inspiring," said Kurt Hofelich, president of Sentara Norfolk General Hospital. "When you can improve the quality of care and reduce patient mortality with a cost-effective approach, that's a home run."

Hofelich says Sentara is expanding the hospital's research to other ICUs to validate the benefits across a much larger patient population.

Catravas is excited for what this breakthrough could also mean for the study of bioelectric reactions in endothelial cells, whose "amazing function" allows the body to operate.

"They are the contact point with blood," Catravas said. "In the lab for the past 30 years, researchers have been trying to figure out how these little cells operate. If we can improve the barrier function in these cells, this opens up many possibilities."

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