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New hope for halting a killer illness

Sun Staff

She thought it was just a cold. Her throat was sore, and she felt tired allover. 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 ventilatorin intensive care, her blood pressure bottoming out, her kidneys failing.

For a month, the 41-year-old Westminster woman hovered near death, a victimof the fast-moving, often-lethal condition known as sepsis. It's an illnessthat rages through the victim's bloodstream, unleashing a fury of reactionsthat kill tissues and shut down organs.

After years of frustration, doctors believe a new frontier might be openingin treating sepsis. Last year, large clinical trials showed the benefits ofearly intervention, and researchers hit on a drug that might reverse theillness' fatal course.

Yet sepsis remains one of the most devastating and humbling conditions inmedicine. A third of the 750,000 Americans per year who develop sepsis willdie, 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. TrishPerl, Johns Hopkins Hospital's epidemiologist. "You just watch people die, andit doesn't matter what you do."

Early symptoms subtle

With an aging population and more aggressive, invasive procedures drivingup 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 medicalintensive care unit at the University of Maryland Medical Center. "This isprobably 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, shecalled a neighbor, but when they arrived at Carroll County General Hospital'semergency room 10 minutes later, Barr's blood pressure was so low she wasalmost unconscious.

Nurses and doctors raced to get antibiotics pumping into Barr. They triedto push up her blood pressure with fluid and medicines. But soon, as in 80percent of patients with sepsis, Barr needed to be put on a ventilator.

"She just went straight downhill, like she was falling off a cliff," saidher husband, Ray Barr. Just 24 hours before, JoAnn had been healthy,exercising every other day, working in disease prevention at Baltimore'shealth department, raising their 9-year-old son, Ian. Now, she was hooked upto at least eight IV pumps, and she was so swollen from fluids that herhospital bracelet was embedded in her wrist. Feeling like she was suffocatingon the ventilator, she frantically scribbled on a piece of paper, "I can'tbreathe."

Then she lost consciousness. It would be weeks later, after a transfer tothe University of Maryland, before she would wake up again, and eventuallyrecover.

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 inher throat that traveled to her lungs, causing pneumonia. People who are incar accidents or suffer burns or undergo medical procedures might get staph orother infections. Or most commonly, the elderly, or those with weakened immunesystems, like cancer or AIDS patients, contract an infection.

Most of the time, a person is able to fight the infection and keep it fromspreading. But in sepsis, the infection moves into the bloodstream, probablybecause of factors including the type of germ, the patient's immune systemhealth, 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 wallsleak fluid. The body's clotting system goes awry, simultaneously causingbleeding and throwing clots that block the tiny blood vessels that feedorgans.

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'scardiovascular system shuts down. One author described sepsis in 1881 as "therude unhinging of the machinery of life," said Dr. Gordon R. Bernard, aVanderbilt University professor of medicine and founding chairman of theInternational 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 MarylandShock Trauma Center: "There are some bacteria that can take somebody who isnormal at lunch time, and by dinner time that evening, they'll be in asituation where the mortality rate is more than 50 percent."

Doctors try to kill the infection with antibiotics, but if they are to havea chance against the condition, they must give the antibiotics before theyknow for certain the patient has sepsis and before they've identified thebacteria responsible.

Jack Griffin, a cancer patient weakened by a recent bone marrow transplant,happened to have a scheduled appointment at Johns Hopkins Hospital the morningafter he had suffered violent chills and pain. On a hunch, Griffin'soncologist, Dr. Louis Diehl, decided to admit Griffin and start antibiotics.By the time Griffin, 55, got to his hospital room that day in February, theNorthern Virginia lawyer was confused and turning beet red, his temperaturesoaring from 102 to 106 degrees, his blood pressure plummeting so low thatmachines couldn't measure it.

"He was reading The Wall Street Journal at 3 p.m., and by 5 p.m., it washard to believe it was the same person," said Janet Goetz, who was with himthroughout the ordeal. "I kept saying, `What's happening to him? What'shappening to him?'"

Sometimes, even getting antibiotics early won't help. But in this case, thequick 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 aquarter of them will require dialysis, at least for a time, to do the work oftheir failing kidneys. As many as a third to half of them will undergo surgeryto remove infected tissue, drain abscesses or take out pockets of pus fromareas like the brain, liver, skin wounds or heart valves, Johnson said. Insevere cases, some people suffer strokes. Some must have fingers or toesamputated.

At Maryland's medical intensive care unit last week, as with most suchunits 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 andfall of her chest, pushed by the ventilator. Shanholtz believes the CalvertCounty woman developed sepsis from deep ulcers caused by her diabetes. Just 24hours before, she had survived a cardiac arrest.

Earlier, her husband, Owen, had heard her calling the names of relativeswho have died.

"I've never heard of anything like it," he said, referring to sepsis. "Iknow her chances are 50-50. People don't go this far down and make it."

Supportive therapies such as fluids and dialysis have helped boostsurvival, but finding a drug to stop the body's over-reaction to infection hasbeen much more difficult.

During the past 15 years or so, more than 20 agents in more than 30 studiesfailed to show any benefit against sepsis. But last fall, the U.S. Food andDrug Administration approved Xigris, a synthetic version of a human protein.Physicians believe the medicine works by helping to normalize the body'sclotting system and calming inflammation. A large, multicenter study foundthat the medicine reduced mortality among the most severe sepsis patients by24 percent.

"In most diseases, that would be viewed as miraculous," said Dr. Michael A.Matthay, a professor of medicine at the University of California, SanFrancisco. "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 arealso worried about the drug's side effect, bleeding, and hospitals areconcerned with its cost, about $6,800 for a four-day intravenous dose. Dr.Alan Cross, an infectious disease specialist at Maryland's Greenebaum CancerCenter, 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 alsodebate the best supportive care. Administering fluid will help blood pressure,but that can also backfire and fluid might leak into the lungs, as happened toBarr. A national network of 24 hospitals are probing another long-standingquestion: 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 grouprallying dollars and attention, as cardiologists have done for heart attacksor neurologists have done for strokes.

"Sepsis is not a chic disease," said Dr. Emanuel Rivers, research directorin emergency medicine at Henry Ford Hospital in Detroit.

The approval of the new drug, however, is finally winning attention forsepsis, and recent studies are changing how doctors and hospitals handle thecondition. In a key finding, researchers showed last year that patientstreated earlier and more aggressively in the emergency room had significantlybetter survival rates.

"A lot of patients don't get definitive treatment until they get to theICU. 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 tounderstand how something he had never heard of was destroying his wife. Hekept notes each day on her up-and-down course. He thought about her funeral.

Eventually, though, after treatment with Xigris and other medicines, JoAnnBarr was weaned from the ventilator. Nearly a month had passed when Barrreturned home in late March, so weak she could barely lift a pencil. She slept12 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 otherpermanent deficits. For Barr, all that's left is fatigue, a weak, throatyvoice 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.

Signs of sepsis

People with these symptoms should go to the emergency room:

• Violent, uncontrollable shakes or chills

• Spiking fever

• Mental confusion

• Shortness of breath

• Weakness, inability to stand

Source: National Initiative in Sepsis Education

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