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Sepsis
is a Leading Killer - in Hospitals It was
the second semester of freshman year at Salve Regina University in
Newport, R.I., and John Kach, then 18, and a member of the
basketball team, was in great shape. Until
one night, when he developed a fever of 104 to 105 Fahrenheit and
flu-like symptoms. His girlfriend wanted to take him to the
hospital, but he said no. After
all, Kach was a guy and, as he puts it, “a guy’s not
going to go to the hospital for a high fever.” But by 5
a.m., he was fading in and out of consciousness. By the time they
got to the hospital, he could barely breathe. The pain in his back
was excruciating as his kidneys shut down. His white blood counts
were sky high - like his fever, a sign of rampant infection. Kach
(pronounced “catch”)
had bacterial meningitis, and it was rapidly turning into severe
sepsis, a reaction to infection that causes runaway inflammation,
blood clots and organ damage in 750,000 Americans every year,
killing an estimated 215,000. Kach
turned out to be lucky, sort of. His circulation got so poor he
developed gangrene. Doctors had to amputate his right leg below
the knee, part of his left foot and all his fingers. (This summer,
because of nerve damage, he had the other leg amputated below the
knee.) He needed dialysis because of his failing kidneys. His
heart was pumping so hard his bed shook. But he lived. Many
others are not so lucky: Even in the best hospitals, sepsis can
rapidly become fatal, as one organ after another shuts down. According
to a report two weeks ago in the Journal of the American Medical
Association, sepsis following surgery is the most common medical
“injury” in hospitalized patients. Of all medical
“errors,” sepsis is associated with the greatest increases in
length of stay, costs (on average, $57,727) and in-hospital
deaths. Indeed,
sepsis is the second leading cause of death in non-coronary
intensive care units and the 10th leading cause of
death overall in the US, according to researchers from Emory
University and the National Center for Environmental Health
writing April in the New England Journal of Medicine. Although
the death rate is falling, sepsis still kills 20 to 50 percent of
those who get it. Sepsis
actually kills more Americans than breast cancer, colorectal
cancer, pancreatic cancer and prostate cancer combined, according
to the Society of Critical Care Medicine, which is part of a
public awareness effort called the Surviving Sepsis Campaign. (The
campaign is sponsored by Baxter Healthcare Corp., Edwards
Lifesciences and Eli Lilly and Company, which makes an expensive
anti-sepsis drug called Xigris.) And
current estimates of the incidence of sepsis may actually be low.
A person with a gunshot wound may die from sepsis after two weeks
in the hospital. But the death certificate will only say gunshot
injury, not sepsis, notes Dr. Howard Belzberg, associate director
of trauma/critical care at the Los Angeles County
University of Southern California Medical Center. In the
past, doctors couldn’t even agree on what sepsis was because it
so complex. Now,
they not only have defined its stages precisely but, more
important, know better how to treat each step of the process. (For
the record, sepsis is an inflammatory response that can include
abnormal clotting and bleeding, in the presence of infection.
Septicemia, also known as “blood poisoning,” is sepsis that
begins with a blood-borne infection. Severe sepsis is sepsis with
organ dysfunction. Septic shock is severe sepsis in which the
cardiovascular system fails, blood pressure drops and organs are
deprived of blood.) Septic
problems can begin with infection anywhere in the body. As soon as
the immune system detects infection, it starts pumping out white
blood cells, which secrete chemicals called cytokines. Some of
these (like interleukin-1, interleukin-6, interleukin-8 and tumor
necrosis factor-alpha) keep the aggressive immune response going.
Others (like interleukin-1 receptor antagonists, interleukin-10
and soluble tumor necrosis factor receptors), do the opposite –
they damp down the inflammatory response. In the
early stages, the right antibiotic can often halt sepsis. But
often, the inflammatory response spirals out of control, revving
up the whole body – raising fever, increasing white blood cells,
respiration, cardiac output and heart rate. This
“overexuberant” response soon begins destroying tissues, notes
Dr. Mitchell Levy, director of the medical intensive care unit at
Rhode Island Hospital, a teaching hospital of Brown University. In the
lungs, cytokines trigger chemicals that damage delicate air sacs.
They make blood vessels leaky, allowing fluid to leak into the
lungs, kidneys and other tissues. As blood vessels dilate and
leak, blood pressure drops, forcing the heart to beat faster. Thanks to a series of recent studies, doctors now have a much more precise idea of how to use ventilators (breathing machines) so as not to further destroy lung tissue; this can reduce death by nine percent in patients with sepsis who also have acute respiratory distress syndrome. They
can reduce death by another 15 to 20 percent by giving steroids
(which dampen immune response) at lower doses for longer periods.
And they are armed with better antibiotics, too, including
Linezolid for streptococcus, and Capsofungin for fungal
infections. But
perhaps the most excitement – and controversy - centers around
Lilly’s anti-sepsis drug, Xigris (drotrecogin). It
can reduce the death rate by 6 percent, though it can also
cause abnormal bleeding. Xigris is an activated form of a chemical
called protein C. But
Xigris is so expensive – nearly $7,000 for a several-day
treatment - that some hospitals now ration it and sales have not
met what the company calls the initial “high expectations” of
two years ago, when the drug was approved. That
translates to a situation in which many septic patients still die
because they don’t get state-of-the-art care. Doctors probably
use up-to-date sepsis therapy only 10 to 40 percent of the time,
says Dr. Peter Provonost, associate professor of anesthesiology
and critical care medicine at Johns Hopkins Medical Institutions. Not
surprisingly, John Kach is thrilled to count himself among the
survivors. If his girlfriend hadn’t rushed him to the hospital,
he says, “I would probably have died in my bed.”
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