She thought it was just a cold. Her throat was sore, and she felt tired all over. But as JoAnn Barr got her son ready for school that morning in March, she started gasping for breath. Within a few hours, Barr was on a ventilator in intensive care, her blood pressure bottoming out, her kidneys failing.
For a month, the 41-year-old Westminster woman hovered near death, a victim of the fast-moving, often-lethal condition known as sepsis. It's an illness that rages through the victim's bloodstream, unleashing a fury of reactions that kill tissues and shut down organs.After years of frustration, doctors believe a new frontier might be opening in treating sepsis. Last year, large clinical trials showed the benefits of early intervention, and researchers hit on a drug that might reverse the illness' fatal course.
Yet sepsis remains one of the most devastating and humbling conditions in medicine. A third of the 750,000 Americans per year who develop sepsis will die, a toll that equals that of heart attacks, or of all deaths from breast, colon, prostate and pancreatic cancers combined.
And as in Barr's case, sepsis can move with a swiftness that is shocking. In hours or a few days, the illness can kill. Doctors have a saying for it: "Fine in the morning, dead in the evening."
"It's the most awful, scary thing to actually take care of," said Dr. Trish Perl, Johns Hopkins Hospital's epidemiologist. "You just watch people die, and it doesn't matter what you do."
Early symptoms subtle
With an aging population and more aggressive, invasive procedures driving up the number of sepsis cases - by about 90 percent in the past decade - treatment questions are becoming more urgent.
"It's a huge problem," said Dr. Carl B. Shanholtz, director of the medical intensive care unit at the University of Maryland Medical Center. "This is probably the most common diagnosis we take care of."
Unfortunately, the early signs are subtle and mimic many other conditions, so many patients dismiss it, as Barr did. Without a simple diagnostic test, physicians miss as many as a quarter of the cases.
Then, the illness explodes with symptoms including violent chills, delirium, a spiking fever or faintness. When Barr felt short of breath, she called a neighbor, but when they arrived at Carroll County General Hospital's emergency room 10 minutes later, Barr's blood pressure was so low she was almost unconscious.
Nurses and doctors raced to get antibiotics pumping into Barr. They tried to push up her blood pressure with fluid and medicines. But soon, as in 80 percent of patients with sepsis, Barr needed to be put on a ventilator.
"She just went straight downhill, like she was falling off a cliff," said her husband, Ray Barr. Just 24 hours before, JoAnn had been healthy, exercising every other day, working in disease prevention at Baltimore's health department, raising their 9-year-old son, Ian. Now, she was hooked up to at least eight IV pumps, and she was so swollen from fluids that her hospital bracelet was embedded in her wrist. Feeling like she was suffocating on the ventilator, she frantically scribbled on a piece of paper, "I can't breathe."
Then she lost consciousness. It would be weeks later, after a transfer to the University of Maryland, before she would wake up again, and eventually recover.
Sepsis starts out simply enough, with an infection.
An otherwise-healthy person can get pneumonia, a urinary tract infection, gall bladder disease or diverticulitis. Barr had a group A strep infection in her throat that traveled to her lungs, causing pneumonia. People who are in car accidents or suffer burns or undergo medical procedures might get staph or other infections. Or most commonly, the elderly, or those with weakened immune systems, like cancer or AIDS patients, contract an infection.
Most of the time, a person is able to fight the infection and keep it from spreading. But in sepsis, the infection moves into the bloodstream, probably because of factors including the type of germ, the patient's immune system health, and even his or her genes.
Once the bacteria get into the blood, the body launches an overwhelming, system-wide counterattack. Blood vessels become inflamed, and their cell walls leak fluid. The body's clotting system goes awry, simultaneously causing bleeding and throwing clots that block the tiny blood vessels that feed organs.
One by one - or sometimes all at once - tissues start to die, organs fail. It can happen in a day or over weeks. In septic shock, the patient's cardiovascular system shuts down. One author described sepsis in 1881 as "the rude unhinging of the machinery of life," said Dr. Gordon R. Bernard, a Vanderbilt University professor of medicine and founding chairman of the International Sepsis Forum. That's an apt description, Bernard noted, because "everything falls apart."
Said Dr. Steven Johnson, chief of the division of critical care at Maryland Shock Trauma Center: "There are some bacteria that can take somebody who is normal at lunch time, and by dinner time that evening, they'll be in a situation where the mortality rate is more than 50 percent."
Doctors try to kill the infection with antibiotics, but if they are to have a chance against the condition, they must give the antibiotics before they know for certain the patient has sepsis and before they've identified the bacteria responsible.
Jack Griffin, a cancer patient weakened by a recent bone marrow transplant, happened to have a scheduled appointment at Johns Hopkins Hospital the morning after he had suffered violent chills and pain. On a hunch, Griffin's oncologist, Dr. Louis Diehl, decided to admit Griffin and start antibiotics. By the time Griffin, 55, got to his hospital room that day in February, the Northern Virginia lawyer was confused and turning beet red, his temperature soaring from 102 to 106 degrees, his blood pressure plummeting so low that machines couldn't measure it.
"He was reading The Wall Street Journal at 3 p.m., and by 5 p.m., it was hard to believe it was the same person," said Janet Goetz, who was with him throughout the ordeal. "I kept saying, `What's happening to him? What's happening to him?'"
Sometimes, even getting antibiotics early won't help. But in this case, the quick action saved Griffin, and by the next morning he was sitting in bed, reading the newspaper again.
Other patients need much more intervention to survive sepsis. About a quarter of them will require dialysis, at least for a time, to do the work of their failing kidneys. As many as a third to half of them will undergo surgery to remove infected tissue, drain abscesses or take out pockets of pus from areas like the brain, liver, skin wounds or heart valves, Johnson said. In severe cases, some people suffer strokes. Some must have fingers or toes amputated.
At Maryland's medical intensive care unit last week, as with most such units around the country, more than half the patients had sepsis. In one room, Nancy Howard, 54, lay under a clean white sheet, still except for the rise and fall of her chest, pushed by the ventilator. Shanholtz believes the Calvert County woman developed sepsis from deep ulcers caused by her diabetes. Just 24 hours before, she had survived a cardiac arrest.
Earlier, her husband, Owen, had heard her calling the names of relatives who have died.
"I've never heard of anything like it," he said, referring to sepsis. "I know her chances are 50-50. People don't go this far down and make it."
Supportive therapies such as fluids and dialysis have helped boost survival, but finding a drug to stop the body's over-reaction to infection has been much more difficult.
During the past 15 years or so, more than 20 agents in more than 30 studies failed to show any benefit against sepsis. But last fall, the U.S. Food and Drug Administration approved Xigris, a synthetic version of a human protein. Physicians believe the medicine works by helping to normalize the body's clotting system and calming inflammation. A large, multicenter study found that the medicine reduced mortality among the most severe sepsis patients by 24 percent.
"In most diseases, that would be viewed as miraculous," said Dr. Michael A. Matthay, a professor of medicine at the University of California, San Francisco. "It does start a new frontier."
Other physicians don't see the drug as a significant breakthrough. First, Xigris is supposed to be used only in the most critical cases. Doctors are also worried about the drug's side effect, bleeding, and hospitals are concerned with its cost, about $6,800 for a four-day intravenous dose. Dr. Alan Cross, an infectious disease specialist at Maryland's Greenebaum Cancer Center, who voted against Xigris on the narrowly split FDA review committee, said physicians also don't understand why two similar drugs didn't work.
Many aspects of sepsis are still a mystery.
Doctors don't know what drives a patient's organs to shut down - the clots, the low blood pressure or something going awry in cells. Physicians also debate the best supportive care. Administering fluid will help blood pressure, but that can also backfire and fluid might leak into the lungs, as happened to Barr. A national network of 24 hospitals are probing another long-standing question: what role steroids have in treatment.
One reason many questions haven't been answered is political, doctors say. With various medical specialties treating sepsis, there has not been one group rallying dollars and attention, as cardiologists have done for heart attacks or neurologists have done for strokes.
"Sepsis is not a chic disease," said Dr. Emanuel Rivers, research director in emergency medicine at Henry Ford Hospital in Detroit.
The approval of the new drug, however, is finally winning attention for sepsis, and recent studies are changing how doctors and hospitals handle the condition. In a key finding, researchers showed last year that patients treated earlier and more aggressively in the emergency room had significantly better survival rates.
"A lot of patients don't get definitive treatment until they get to the ICU. By then, several hours may have elapsed," said Rivers, who led the study. "And once you get past a certain phase, there's not a lot you can do."
Scars follow ordeal
As Barr lingered for weeks in a critical state, her husband struggled to understand how something he had never heard of was destroying his wife. He kept notes each day on her up-and-down course. He thought about her funeral.
Eventually, though, after treatment with Xigris and other medicines, JoAnn Barr was weaned from the ventilator. Nearly a month had passed when Barr returned home in late March, so weak she could barely lift a pencil. She slept 12 hours at a time. Her husband once saw her slowly climbing the stairs and, for a moment, he thought she was an old woman.
Sepsis scars some patients, leaving them with neurological or other permanent deficits. For Barr, all that's left is fatigue, a weak, throaty voice from the ventilator, and a dim memory of the morning she first got sick.
Mercifully, like most sepsis patients, she can't remember anything else.