Cheating Death (4 page)

“I never saw it again, but I was very impressed that something natural and so simple could have such an impact. It was like
his brain was boiling with rage, and they just cooled it down,” said Mayer. “I thought that for such a natural intervention,
it was very powerful.” That little lesson would one day set the template for his life’s crusade.

A hyperactive teenager who loved new wave bands like Blondie and the Ramones and rambling around the big city with his friends,
Mayer was not the most focused student. But he was smart, ambitious, and knew from the first that he wanted to study medicine.
The frosty winters were one reason he chose to go to college at Cornell University in frozen Ithaca, New York. Another reason
is that he didn’t get into his first choice, Yale, or his second choice, Columbia.
¹⁰

He did manage to get into Columbia for medical school and by his senior year was thinking about ways to make his mark. Internal
medicine was fine, Mayer told me, “But I thought it might be too vanilla. Part of me wanted to do neurosurgery, but I knew
in my heart that I would only be average at best with my hands. There are so many great doctors here. I figured if I did neurosurgery,
I would never end up at Columbia—I’d be at some small hospital in the middle of nowhere. But in neurocritical care, I saw
an opportunity. No one was doing it; it was so unexplored. And I got into this field when it was really just being invented.”

Mayer got his appointment in the neurology department at Columbia but found he hated it. He felt it was too cerebral; most
of the patients were comatose and the treating doctors spent most of their time in academic discussions. Mayer yearned for
more action. He wanted to go back to internal medicine. By 1993, however, he discovered a project that would hold his interest.
He designed a pilot study testing the safety of hypothermia for patients who had suffered middle cerebral artery infarctions
or strokes.

When there is a blockage in the middle cerebral artery, the middle of three major blood vessels bringing blood to the brain,
it causes catastrophic brain damage. Here’s the problem: as the brain cells, or neurons, start to die from lack of blood flow,
the brain starts to swell in response. Swelling in the abdomen and other parts of the body can be serious, but when it pushes
the brain against the hard casing of the skull, it’s deadly. In any brain injury, swelling and pressure is the biggest threat.
Many people got a glimpse of this threat when the actress Natasha Richardson died after falling on a ski slope near Montreal.
While the accident seemed minor at first, bleeding inside her head ratcheted up the pressure on Richardson’s brain so quickly
that within hours of her fall the case was deemed hopeless.
¹¹

As Mayer embarked on his very first hypothermia study, he wanted to see if therapeutic cooling might reduce the swelling from
brain injury, reduce the damage, or both. “Decades ago, the only use of hypothermia was in selected, super-high-risk brain
and heart operations, where they needed to completely stop circulation for an extended period of time,” says Mayer. This was
the legacy of the pioneering heart surgeons. In those early years, hypothermia developed an ominous reputation. While it made
daring surgeries possible, patients suffered enough side effects to give doctors serious pause. Patients cooled below 30 degrees
Celsius were prone to developing heart arrhythmias. They were also prone to strokes and other types of internal bleeding,
since blood that is chilled doesn’t clot as well. Most of those early cardiac patients would get better in the short term,
but then eventually die of pneumonia. The problem was that in the 1940s, there were no artificial ventilators, so comatose
patients had to breathe on their own and their lungs often filled with various secretions. On top of that, hypothermia tends
to suppress the immune system, so these patients would develop fatal infections.
¹²

But within a few years there were hints and clues that it might be done safely. For example, in 1958 surgeons at the University
of Minnesota reported cooling a fifty-one-year-old female cancer patient to just 48 degrees Fahrenheit for her surgery, and
rewarming her with no apparent problems.
¹³
Other experimenters, working with monkeys, also reported good results using extremely low temperatures, and there were even
reports of physicians successfully using hypothermia in the treatment of cardiac arrest patients.
¹⁴

By the 1990s, while hypothermia was still out of favor due to safety concerns, Mayer and a few other doctors decided it was
time for a fresh look. Mayer suspected that the real problem in the 1940s and 1950s lay not with the cooling itself, but with
the follow-up care and nascent level of life-support equipment. He and other doctors felt that some of the pitfalls could
be avoided. For one thing, they wouldn’t be cooling people to such an extreme degree—they hoped to get results by cooling
to around 90 degrees Fahrenheit, not 60 or 70. Just as important, in the modern critical care setting, they could do much
better preventing and treating complications like pneumonia.

Over the next decade, Mayer navigated the stepping-stones of an academic career. Along with a handful of other physicians—most
notably from Johns Hopkins—he helped to found the first society of neurocritical care specialists and the journal
Neurocritical Care
.
¹⁵
And he pushed ahead with studies on hypothermia. One, published in 2001, found that severe stroke patients who were cooled
did no worse than uncooled patients.
¹⁶
The field of neuroscience, long seen as one where doctors could do little for their patients, was finally shifting and so
was that line between life and death.

A
S IS USUALLY
the case in medical discovery, our best new research is built on existing research. For example, one of the early articles
in Mayer’s journal was about a discovery that took place when I was still a resident. The Food and Drug Administration (FDA)
approved the use of a drug called tissue plasminogen activator, or tPA, to treat patients with strokes.

In one type of stroke, blood flow to part or all of the brain is cut off by a clot. Without blood flow, that portion of the
brain dies. Using tPA is a great option, because it can almost immediately break open the clot and restore blood flow to the
brain. The problem is, tPA needs to be given very quickly—within three hours of the start of symptoms—for it to help. For
this reason, it’s estimated that fewer than 5 percent of stroke patients actually receive this vitally important drug. Enter
the Ice Doctor.

A handful of neurologists—Mayer included—thought that hypothermia could be a vital addition to the arsenal. They started experimenting—on
the theory that hypothermia would reduce the brain’s need for oxygen during the first crucial days of recovery and so reduce
the permanent damage. This would reduce the damage caused by lack of oxygen and perhaps extend the window of effectiveness
for other therapies, like tPA. Unlike the early cardiac surgeons, Mayer and these other Ice Doctors used a mild form of hypothermia,
generally cooling the body by 5 to 10 degrees Fahrenheit.

No doubt, Mayer had cold on the brain, and in 2000, he got more encouragement. A European research team, led by the Austrian
emergency medicine specialist Dr. Fritz Sterz, reported that chilling patients by about 7 degrees Fahrenheit was enough to
sharply improve the outcome in patients who suffered a life-threatening cardiac arrest.
¹⁷
Think about that. Think about the number of times we hear, “He or she died of a heart attack.” All the technology in the
world’s best hospitals could only do so much, but take away 7 degrees Fahrenheit… . When Mayer described all this to me, it
seemed counterintuitive that a neurologist would dedicate himself to changing cardiac care around the country. But the Ice
Doctor was hooked.

The thing was, Mayer couldn’t start cooling cardiac patients on his own simply because he thought it was a good idea. Just
because an article gets published doesn’t mean its ideas will become accepted practice. That’s doubly true if the work is
published overseas and even truer in a field like cardiac care, which is so strictly bound by rules and guidelines. In the
United States, no one was doing hypothermia. But in Europe, its use continued to grow, and a decade later—medicine moves slowly—there
was more ammunition for people like Mayer and for other devotees like the Penn Medicine team led by Lance Becker.

Once again, it came from Sterz’ group in Austria, this time under the heading of the Hypothermia After Cardiac Arrest Study
Group. The Austrians, led by Dr. Michael Holzer and Sterz, reported in the
New England Journal of Medicine
that they had cooled 136 cardiac arrest patients and 55 percent emerged from the hospital with healthy brain function. In
a control group of 137 patients—cardiac arrest victims who were
not
cooled—just 39 percent got better.
¹⁸
It wasn’t a large study, but it was a strong result published in a major U.S. medical journal. Mayer thought it would be
decisive, a triumphant breakthrough, for doctors like him who thought that hypothermia should be the standard treatment.

But that’s not how it worked out. With such common and deadly illnesses as heart attacks and strokes, physicians are loathe
to experiment—they stick closely to protocol. This is especially true in the United States, where the fear of lawsuits makes
doctors especially unwilling to deviate from what might be called the accepted standard of care. For three years after the
publication of Fritz Sterz’ groundbreaking European study, a handful of American doctors fumed as the American Heart Association
(AHA) refused to update its guidelines to require cooling as a treatment for cardiac arrest.

Stephan Mayer was especially steamed. In his view, as long as hypothermia was not considered standard of care, hospitals could
rationalize not doing it. After all, if the AHA didn’t think it was absolutely necessary, many would ignore it. In 2005, the
AHA’s guidelines for treating cardiac arrest were rewritten, as they are every five years, and they did list therapeutic hypothermia
as a
recommended
treatment—but still not that elusive standard of care.
¹⁹

A key hurdle to shifting that line, once and for all, was the FDA. In 2004, an FDA panel that makes recommendations on medical
devices gathered to discuss the evidence for hypothermia and whether companies could specifically market cooling systems for
the treatment of cardiac arrest patients. The European study was touted, along with a second study from Australia, which also
showed that cooling helped survival.

But things didn’t go as Mayer, among many, expected. An influential FDA representative was not swayed by evidence of the benefits
from hypothermia. Dr. Julie Swain, a prominent cardiologist, laid into the two studies.
²⁰
She argued that they were too small to suggest a real benefit and pointed to studies of hypothermia in other groups of patients—heart
attack victims and people who suffered head injuries—as showing no benefits at all. What’s more, she said, patients in those
other studies suffered higher rates of side effects like shock and bleeding.

According to Lance Becker, who was at the meeting as an expert consultant, the mood in the room was tense. Becker tried to
persuade the panel that hypothermia was worth the risk. Of course the studies were relatively small, he argued, since most
cardiac arrest patients die before they even reach the hospital. He pushed on, saying that the two studies together provided
more evidence of benefits than existed for many other more accepted therapies. Another consultant, Dr. Joseph Ornato from
Virginia Commonwealth University, backed Becker, saying the European and Australian studies were well designed and that it
would be wrong—and extremely difficult—to wait for larger studies.

But the enthusiasm had gone out of the room. A third consultant, Dr. John Somberg from Cornell, was blunt. “Forget about their
being in the
New England Journal,
” he said. “I just do not believe these two studies meet any FDA advisory standard of approval.”
²¹
Somberg, who was a former member of the FDA committee making the decision, went on to compare the two studies to a poorly
balanced stack of cards. In the end, his opinion carried the day. Despite the efforts of doctors like Stephan Mayer, hypothermia
would not become standard of care.

You may be wondering why I include this losing battle of the Ice Doctors. Well, herein lies one of the great challenges of
medicine. When does an experimental treatment become a standard tool in the doctor’s bag? Move too slowly, and you’re holding
back a treatment that could save thousands of lives. Move too quickly, and you might miss side effects. Look what happened
in the case of Vioxx. The FDA approved Vioxx as an antiarthritis medication only to take it off the market five years later,
when it became apparent that the drug was linked to heart problems. The FDA says Vioxx probably caused more than 88,000 heart
attacks, in all. Maybe they all could have been avoided if the FDA had waited for more evidence before agreeing that the drug
was safe.

Critics like Swain and Somberg say the research on hypothermia is thin and, considering the potential risks, not enough to
justify its widespread use. But there are major hurdles to actually doing more studies. In a true catch-22, in 2008, the National
Institutes of Health (NIH) rejected a proposed study at Duke that would have tested therapeutic cooling against a noncooling
regimen, on the grounds that it wouldn’t be ethical to withhold cooling.
²²
If you think it’s confusing—you’re right. You’ve got the FDA saying it’s wrong to cool cardiac arrest patients because we
don’t know if hypothermia works; the AHA saying it’s probably a good idea to use the treatment; and the NIH saying the evidence
is so strong, it’s unethical
not
to cool them.