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Sepsis is redefined — with saving lives in mind

Dr. Clifford Deutschman, vice chair of research at

Dr. Clifford Deutschman, vice chair of research at Cohen Children's Medical Center in New Hyde Park, is one of the heads of an international task force of medical investigators that have redefined sepsis, an often-fatal condition. Credit: Howard Schnapp

An international task force of medical investigators has redefined sepsis — a centuries-old foe that remains a top killer of hospitalized patients.

The redefinition’s aim is to expedite diagnosis and speed up care for a condition initially marked by symptoms so vague they masquerade as lesser disorders.

Sepsis is an extraordinary complication of infection that can swiftly spin out of control, adversely affecting all major physiologic systems. The condition can trigger severe tissue and organ damage, and too often, results in death. More than 1 million people in the United States are affected annually by sepsis and up to half die.

Yet the public doesn’t know much about sepsis, doctors say, a condition with an old-timey name reminiscent of a bygone era.

Task force members — led by a Long Island physician/scientist — say sepsis not only is real, it’s a mounting global health crisis. But deaths can be prevented, these panelists say, by recognizing just three sepsis-specific cues. They expect their conclusions to stoke vigorous debate because the new definition, the first in 15 years, flies in the face of earlier scientific wisdom. The redefinition and three-point diagnostic measure are based on volumes of worldwide data that accrued since 2001.

“There are abnormalities in the brain, the kidneys, the liver — the mitochondria,” Dr. Clifford Deutschman said, referring to the bean-shaped, energy-producing powerhouses of cells.

Deutschman, vice chair of research at Cohen Children’s Medical Center in New Hyde Park, said sepsis leaves no physiologic system unscathed.

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Past definitions blamed sepsis on an immune system gone awry — the production of an explosive flood of tissue-damaging inflammatory proteins, the torrential cytokine storm. The storm was triggered, theorists posited, by infection. Doctors now see sepsis as life-threatening multi-organ dysfunction caused by a totally dysregulated response to an infectious agent.

Christopher Reeve, the late actor, who became quadriplegic after a fall from his horse, reportedly suffered from sepsis on several occasions. Jack Daniel, who made his whiskey famous, is said to have died of it in 1911, following an infection that began in a toe. Eighteenth-century British author Mary Wollstonecraft also died of sepsis after an infection acquired during childbirth.

Despite knowing about sepsis for centuries, doctors said only now have they produced their best definition and even that may change as new scientific information emerges. Sepsis, they say, has persisted as a medical conundrum — difficult to diagnose and tough to define.

The new diagnostic standards, doctors contend, will enable clinicians to quickly tackle it before it snuffs out lives.

“We looked for clinical criteria that could be used at a patient’s bedside in an emergency room at 2 a.m. that could help any clinician in the middle of nowhere,” said Deutschman, who has investigated the pathobiology of sepsis for more than 30 years. He is considered one of the world’s leading authorities on the condition.

He and Dr. Mervyn Singer of University College in London, who served as heads of the task force, said doctors need to recognize only three critical signals as signs of sepsis: low blood pressure, high rate of respiration and altered mental state. According to their research, patients with suspected infections should be considered at risk of sepsis if they meet at least two of those three criteria.

The 19-member panel developed a new measure called the quick-sequential organ failure assessment to help clinicians rapidly identify patients with those three vital signs. The three were chosen because they were the most common among numerous, otherwise vague and deceptive symptoms recorded among people with sepsis.

Sepsis may have been a leading killer for centuries, but it doesn’t have to continue as one, Deutschman, also an investigator at the Feinstein Institute for Medical Research in Manhasset, said.

He and his team defined septic shock — a deadly runaway disorder — as a subset of sepsis and further described it as “profound circulatory, cellular and metabolic abnormalities that are associated with a greater risk of death than sepsis alone.”

Task force members distilled their information from a flurry of studies as well as from more than 800,000 medical records of patients diagnosed with an infection and who went on to develop sepsis. The records involved patients in the United States, Europe, New Zealand and other parts of the developed world.

Patients who have survived the severest form of sepsis say it’s like being swept into a vortex with no certainty of ever emerging the same. Some do not.

In 2012, Shannon Smith of Buffalo, accompanied by her mother, traveled to a Deer Park prosthetist where she was outfitted with new artificial extremities. She had lost most of all four limbs to septic shock.

Smith was stricken in December 2010 at age 26 with the fast-moving disorder, which cut off the blood supply to her arms and legs forcing doctors to amputate one arm below the elbow, the other above. The situation was similar with her legs: One was amputated below the knee; the other above.

Smith, who was six months pregnant, lost her unborn child. She fell into a coma and was put on life support. For months, Smith, who had been working as a pharmacy technician before the life-threatening nightmare, was in and out hospitals.

She told Newsday shortly after receiving her new bionic limbs that she woke up one morning and felt out of sorts, unlike her usual self and went to a hospital emergency room. Septic shock quickly consumed her. Smith learned after the devastating ordeal that pneumonia triggered her near-death experience.

“Sepsis is a very protean disorder,” said Deutschman, noting that sepsis is highly variable and initially can be mistaken for far less devastating conditions.

Arriving at the redefinition, he said, required months of plowing through what he described as “tons and tons” of data.

Task Force member Dr. Christopher Seymour, of the University of Pittsburgh School of Medicine, noted that unlike earlier attempts to define sepsis, investigators this time around sought data from real patients.

“Because sepsis is so complex, patients can present in many different ways,” Seymour said. “This can lead to delays in care and missed opportunities. The updated definition was crafted to help doctors and hospitals sort through the many sepsis symptoms and get to the diagnosis quickly.”

Earlier this month, Dr. Thomas Frieden, director of the Centers for Disease Control and Prevention, pointed to six so-called superbugs as potential triggers of sepsis among patients confined to long-term-care institutions. Infection control measures are not as fastidious in these facilities as in acute-care hospitals, and because of that, more people are likely to be exposed to bugs that trigger sepsis, he said.

“No one should get sick while trying to get well,” Frieden said.

Infections that trigger sepsis may begin innocuously, from a cat scratch, for example, or pneumonia. Legend holds that Jack Daniel developed an infection after stubbing a toe. Yet, it is the rapid, downward course of sepsis that makes it lethal.

Treatment involves intravenous fluids and a regimen of antibiotics — when the infection is triggered by bacteria. But sepsis is often so complex that patients may wind up on kidney dialysis, or as in Smith’s case, on full-blown life-support technology.

The task force was convened in January 2014 by the Society of Critical Care Medicine in this country and the European Society of Intensive Care Medicine. Task force members hailed from research centers worldwide.

They concluded that the old definition failed to capture the full scope and complexity of sepsis.

“When we looked at the pathobiology we found that there was a lot that is now known that was not known in 2001,” Deutschman said.

He added that the previous sepsis definition was inextricably hinged to the “cytokine storm theory.” Cytokines are infinitesimal proteins, many produced by cells of the immune system.

“That’s a big part of what led us to look at the definition in the first place,” Deutschman said. “The cytokine storm theory, that’s something we don’t think happens.”

With the redefinition and new diagnostic measures, Deutschman said, medical science finally is on course to halt a killer that has stalked patients for centuries. And with the quick-assessment measures in hand, there’s no longer a need to deliberate.

“It’s really important for clinicians to treat the infection, even if there is doubt in their minds. Nothing should delay the start of antibiotics and fluids, and the basics of treatment,” Deutschman said.

Facts about sepsis

  • Sepsis is a life-threatening complication of infection
  • More patients die of sepsis in the U.S. than AIDS, breast and prostate cancers combined
  • Each 60 seconds patients go without diagnosis and treatment increases the risk of death
  • The condition frequently strikes weakened, hospitalized patients, often in intensive care units
  • The redefinition and new three-point diagnostic measure are based on patients in countries with first-tier economies
  • Patients with infection who develop low blood pressure, high respiration rate and altered mental state are more likely to develop sepsis
  • While only one 1 in 4 patients have at least 2 of those measures, they account for 3 out of 4 sepsis deaths
  • Treatment costs for sepsis run $20 billion annually

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