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COL New hope for taming deadly septic shock

By Jane E. Brody

New York Times News Service

Can an otherwise healthy 58-year-old man die from a bad cold? He can, and he did.

Through an unfortunate cascade of events, starting with a missed diagnosis of viral pneumonia, Tom Wilson, a systems analyst for Westinghouse, went from bad to worse until every major organ system -- kidneys, liver, lungs and finally his heart -- stopped working.

After 10 days in intensive care during which doctors struggled in vain to get ahead of the rampaging disorder, Tom died. Cause of death: septic shock, the same condition responsible for the death in 1990 of the Muppeteer Jim Henson.

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Tom's death began with a bad cold he caught while abroad on vacation. Upon returning home, he went back to work, despite a lingering cough and fatigue that gradually worsened and prompted a visit to the doctor.

The doctor diagnosed asthma and, without ordering a chest X-ray that could have shown pneumonia, prescribed a steroid inhaler. When Tom's condition rapidly worsened, he also prescribed prednisone, which suppresses the body's immune response and most likely made matters even worse. In 24 hours, Tom was very sick with streptococcal pneumonia in both lungs that landed him in the hospital in intensive care.

Out-of-control response

Sepsis is an overwhelming bodywide response to an infection that at the outset may seem mundane but that suddenly worsens. It is a chain of events involving abnormal inflammation and clotting that can lead to major organ failure and death. Septic shock results when the out-of-control response causes the heart to fail.

More than 750,000 cases of sepsis occur annually in this country, and 215,000 of those afflicted die even with intensive medical care that includes antibiotics, intravenous fluids, blood transfusions, kidney dialysis, nutritional and respiratory support and sometimes surgery to remove the source of an infection.

The incidence of sepsis has nearly doubled in the last decade and is expected to increase to 1 million cases a year by 2010. Although older people and those with chronic ailments like diabetes or HIV infection are most susceptible, sepsis spares no age group, attacking children as well as adults, healthy people as well as the chronically ill.

Despite the use of potent antibiotics and advanced resuscitative equipment costing $17 billion a year, septic shock remains the leading cause of death in intensive care units, killing more people each year than cancers of the breast, colon, pancreas and prostate combined.

Until now, no agent tested in well-designed clinical trials has been able to make a dent in the death rate from sepsis. The Food and Drug Administration recently approved for marketing the first drug proved to reduce mortality from severe sepsis. Although the drug's effects are limited and are of benefit only to some patients, it is an encouraging start toward conquering a devastating and costly health problem.

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In effect, sepsis is the body's runaway attempt to defend itself against an infection. A series of inflammatory and anti-inflammatory compounds are released that attack body tissues above and beyond the original infection.

Perhaps the most damaging effect is intravascular clotting, the formation of clots inside blood vessels that deprives tissues of needed oxygen and can result in organ shutdown. Damaged blood vessels start oozing fluids, the kidneys cannot function, the lungs become stiff, causing breathing difficulties, and ultimately the circulation fails and blood pressure cannot be maintained.

Compounding the many devastating effects of sepsis is that the antibiotics administered to treat the underlying infection can sometimes unleash toxic substances. Certain streptococcal, staphylococcal and other bacteria contain potent toxins -- exotoxins that are released directly into the blood by the live bacteria and endotoxins contained within the organisms.

The devastating and sometimes fatal cases of staphylococcal toxic shock syndrome (caused by an exotoxin) were linked in the late 1970s and 1980s to the use of certain highly absorbent tampons, among other factors. When the walls of endotoxin-containing bacteria are ruptured by an antibiotic, the toxin is released into the bloodstream, unleashing an attack on the tissues throughout the body. This is what happened to Tom and Henson, who were infected with a toxin-containing streptococcus.

The newly licensed drug, Xigris by Eli Lilly, acts to interrupt the downward spiral of sepsis by stemming clotting in the blood vessels. It is approved for adults with severe sepsis who face a high risk of death. Severe sepsis is diagnosed when sepsis causes one or more organs to malfunction. In clinical trials, Xigris used in this group of patients reduced the death rate by nearly 20 percent.

The drug must be used with great care, since by interfering with the ability of the blood to clot it can cause serious internal bleeding. Dr. Gordon R. Bernard, a pulmonologist at Vanderbilt University School of Medicine, who directed the clinical trials of Xigris, said that although the drug was not a cure-all, "it reduces mortality, and it's the only drug ever shown to do that."

Also encouraging, Bernard said, is that the current understanding of the biochemistry of sepsis should soon result in the development of other specific therapies.

Let's start with prevention. Two personal habits that make sepsis more likely are smoking and excessive use of alcohol. Also, anyone with a chronic ailment should be aware of the possibility that sepsis can occur as the result of any infection, although half the time pneumonia is the precipitating cause, Bernard said.

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Time is of the essence

In treating sepsis, time is crucial. Many people are reluctant to seek care until they are so sick they have no choice. Since sepsis develops rapidly and can cause irreversible organ damage, the sooner a suspected case is diagnosed and treated, the better. This is especially so for people who are elderly or who have chronic ailments.

Bernard said people needed to recognize what was a normal response to infection. They should be aware of when their symptoms have gone beyond being just a cold, which should not last more than about five days and cause more than a low-grade fever. When fever rises to 102 or 103 with shaking chills, confusion or difficulty breathing, the patient should be taken to the hospital without delay and receive immediate attention in the emergency room.

The medical profession sometimes contributes to a dangerous delay in treating infections that can lead to sepsis. In part because of pressure from health insurers, doctors are often reluctant to perform or order tests -- like a chest X-ray -- that could reveal a serious infection.

And, with good reason, there is also growing reluctance to prescribe antibiotics unless a bacterial infection can be documented as the cause of the patient's symptoms. But in the effort to avoid unnecessary antibiotic treatment, some patients may end up undertreated, allowing an infection to flourish unchecked until it is too late.

Jane E. Brody is a New York Times staff writer and columnist who specializes in health and medical reporting.

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