Download It was closing in on 5pm and Pamela Barco was getting antsy

It was closing in on 5pm and Pamela Barco was getting antsy. Only half an hour left until
her shift at the Children's Hospital of Philadelphia ended, and she had a date to look
forward to. First, though, Barco—a 46-year-old ER clerk—had to finish setting up
equipment in the trauma room for an incoming patient. When she was done, she walked
back to her desk to chat with her friend and colleague Sharon Pryce.
As soon as Barco sat down, she felt the room begin to spin. Suddenly the ER was blurry,
out of control. She mumbled to Pryce that she felt dizzy and put her head down on her
desk. Just as quickly, Pryce was up, standing behind her, concerned. She put her hand on
Barco's shoulder. "Pam, you ok? What's wrong?"
That's when Pryce felt her friend take her last breath. Barco's heart had stopped. More
precisely, it was in V-fib—or ventricular fibrillation—meaning that it stopped pumping
out blood, but was still quivering like a spoonful of Jell-O. Pryce grabbed Barco's arms to
keep her from falling out of her chair. She glanced around; the normally bustling ER was
empty. She considered screaming for help but didn't want to scare the patients. "Staff
emergency," she hollered as calmly as she could. Two nurses at the other end of the hall
came running.
Minutes later, a dozen doctors and nurses surrounded Barco's lifeless body. Only one of
out 16 patients survives sudden cardiac arrest—every minute that the heart isn't pumping
is a minute closer to death, as the body becomes more and more deprived of oxygen, its
main source of fuel. Doctors shocked Barco with a defibrillator, which electrically jolts
the heart into normal rhythm. Didn't work. They shocked her again. Twice. A few
seconds of silence. Then: Beep. Beep. Beep. Barco was alive again.
But perhaps not for long. Post-cardiac arrest patients have a nasty habit of dying after
their hearts re-start, a consequence of the shock the brain and heart cells endure when
blood flow stops and then starts back up again. Even if the shock isn't bad enough to kill,
few patients recover without noticeable brain damage, because after a couple of minutes,
oxygen-starved brain cells begin to die. Barco, however, was exceptionally lucky. Not
only did she collapse in a hospital, but she collapsed next door to the Hospital of the
University of Pennsylvania, where a cadre of researchers is pioneering a controversial
treatment that mitigates the aftermath of cardiac arrest.
Called therapeutic hypothermia, the technique is just like it sounds: doctors lower
patients' body temperatures to 91˚F for 24 hours by pumping cold saline through their
IVs and covering them with cold blankets and wraps—hell, even ice packs, sometimes.
Two clinical trials from 2002 suggest that cooling saves one out of five cardiac arrest
patients who would have otherwise died—patients like Barco, who, though alive, was
unconscious and having serious trouble breathing. Barco was the perfect candidate for
therapeutic hypothermia, so as soon as she was stable enough, the doctors wheeled her
next door.
On May 20, 1999, 29-year-old medical student Anna Bagenholm went skiing with friends
near Narvik, Norway, one of the most northerly towns in the world. A little after 6pm,
she skied a favorite path down a waterfall gully and fell headfirst into a river. Her body
wedged between some rocks and overlying ice; luckily, she found an air pocket so she
could breathe. Although she was almost fully immersed underwater, Bagenholm's friends
found her and tried to get her out. They couldn't.
Immediately, they called for help. Ten minutes went by as Bagenholm struggled in the
icy water. Twenty. Thirty. After forty, her body went limp—either she had drowned, or
the extreme cold had stopped her heart. When the rescue team finally arrived at 7:39,
they cut a hole in the ice and took Bagenholm's body out, but she was dead. They
measured her body temperature. 56.7˚F. They started performing CPR.
An hour-long helicopter ride brought Bagenholm to the Tromso University Hospital,
where she was put on a heart-lung machine that breathed for her and pumped blood
through her as she slowly re-warmed. Nine hours later, her body was back up to normal
body temperature. They sedated her for another 72 hours and then slowly took her off the
sedative. The doctors watched and waited. A little while later, she opened her eyes.
Bagenholm was alive and responsive, her brain virtually undamaged despite a full hour
without oxygen. After a long period of recovery, she went on to graduate from medical
school.
Many doctors—including Mads Gilbert, the head of the ER at the Tromso University
hospital—believe that the freezing temperatures that stopped Bagenholm's heart also
saved her ("Hypothermia is a true double-edged sword: it protects you or it kills you,"
Gilbert says.) At lower temperatures, our organs slow down and need less fuel. By the
time Bagenholm's heart had stopped pumping, her brain was so cold it needed little
oxygen anyway. Even so, she was lifeless in the river for an hour before rescue teams
began CPR, which means that her brain was oxygen-deprived for at least that long. How
she did survive without any brain damage?
That's a question that's now been partially answered thanks to Lance Becker, the director
of the Penn Center for Resuscitative Medicine. Bald, wiry, and mischievous, Becker is
the kind of guy you'd more easily picture in a jester's costume than a doctor's coat. When
he was a medical resident in Chicago in the early 80s, he found himself oddly attracted to
the ER—to the "really really sick patients," he says—because he was more interested in
figuring out what was wrong with them than in actually treating them. (He's like a
friendlier, funnier, and shorter version of House. And, no limp.)
After working in the ER of Chicago's Michael Reese Hospital for several years, Becker
started questioning the published statistics about cardiac arrest. He'd read that 20 percent
of cardiac arrest patients survive, but "I knew after working in the emergency department
for a while that that wasn't anything close to reality," he says. He decided to perform his
own study and found that the rates were off by more than a factor of ten—only 1.8
percent of cardiac arrest patients in Chicago lived. "That was a major wake-up call," he
says.
But why did people die after cardiac arrest, even when their hearts had re-started? The
question nagged at Becker. To answer it, he thought it best to start small—by looking at
cells. Up until that point, scientists believed that when the heart stopped pumping oxygen,
cells started to die. If that were true, then cells should fare better when the heart starts
pumping again. "What we saw was almost the opposite," Becker recalls.
Becker watched heart cells under a microscope as he deprived them of oxygen for an
hour. Then he gave them oxygen, or reperfused them, for another three hours. He couldn't
believe what he saw: only four percent of the cells were damaged by the lack of oxygen,
but 17 percent started showing signs of injury immediately after the oxygen reperfusion.
That suggested to Becker that perhaps what killed cardiac arrest patients wasn't the heart
stopping, but the heart re-starting—and the sudden recirculation of oxygen. Totally
counterintuitive, but auspicious, he thought. "If we could get on top of and understand
this reperfusion injury, we could drastically alter the way people live or die," Becker
realized.
Becker has since learned why reperfusion injury occurs. Tiny organelles inside our cells
called mitochondria use oxygen to produce energy, but these powerhouses are kind of
like nuclear power plants—"very useful, generate a lot of power, but a little bit on the
dangerous side," says Ben Abella, the clinical research director of the Center for
Resuscitation Science and Becker's right hand man. (Abella decided to start working with
Becker after a fateful day in 1999 when, as a resident team leader at the University of
Chicago Hospital, he saw a whopping eight cardiac arrest patients in one day.)
Mitochondria have back-up systems in place to prevent dangerous oxygen chainreactions, but when cells are deprived of oxygen, these systems break down. Then, when
oxygen flow returns, the mitochondria go nuts and start producing reactive molecules
called free radicals, which damage the cell and other nearby cells. The problem is most
pronounced in the brain, which uses more oxygen than any other organ. The injured cells
start killing themselves, and the body's immune system, alerted to the impending chaos,
releases chemicals that make the problem worse.
Soon after performing his first lab experiments, Becker noticed something else odd. As
all scientists do, he kept his cells in incubators at 98.6°F. But when he left them out for a
few hours to do experiments, "we found that there were differences in rates of cell death,"
he says. When the cells had cooled a little, they didn't suffer as much reperfusion injury,
perhaps because the mitochondria and the immune system don't work as well at low
temperatures. Cold, in other words, appeared to temper the mitochondrial meltdown that
occurs after cardiac arrest. It explained why Bagenholm recovered. Becker knew what he
had to do next—try it on others.
It was 2001, and anesthesiologist Markus Födisch was an on-call physician for the
Advanced Life Support unit in Bonn, Germany. His unit received a call from a local
supermarket: A 37-year-old man had collapsed from cardiac arrest. Födisch and his team
rushed over. By the time they got there, another unit had already arrived and re-started
his heart, albeit after 37 minutes of cardiac arrest. Födisch knew the man would sustain
some serious brain damage.
Several supermarket employees approached Födisch and asked him if he needed any
help. Sure, he said. How about some ice packs? Födisch was familiar with the concept of
therapeutic hypothermia, and thought it might be better to start cooling the patient now
than to wait for him to get to the hospital, which was 45 minutes away.
The employee came back a couple minutes later, but not with ice packs. They didn’t have
any. Instead, he arrived with a bunch of frozen pizza boxes. Födisch shook his head. "We
told him we can't use pizza because it's too stiff," Födisch says. "We can't cover the body
with them."
The employee rushed back to the freezer. A minute later, he was back, his arms full of
packages of frozen french fries. Födisch figured, why not? He grabbed them and covered
the patient's body with as many packages has he could, then transferred him to the
ambulance. "So we transported him covered with french fries," Födisch says.
When they arrived at the hospital, doctors took the man's temperature. It was 91°F—the
target for therapeutic hypothermia. And although everyone expected him to have serious
brain damage, the patient recovered completely—rumor has it, he even decided to enroll
in medical school. Födisch is well aware that his supermarket therapy was a little
unconventional. "It's really crazy," he admits. "But nevertheless, sometimes science is
crazy."
To Becker and Abella, who both moved from Chicago to Penn in 2006 to set up the
Center for Resuscitation Science, Födisch's story embodies the future of cooling. In fact,
they say, it may have even been better if Födisch had cooled the patient before he was
resuscitated. Although it helps to start cooling even six hours after resuscitation—these
patients are up to 20 percent more likely to walk out of the hospital than patients who
aren't cooled at all, according to the two landmark trials published in 2002—Becker and
Abella are convinced that cooling before or during resuscitation will help even more.
"We're only seeing the tip of the proverbial iceberg in terms of what cooling could do,"
Becker says.
Indeed, in a study they published in 2007, they showed that mice in cardiac arrest were
more likely to survive if the experimenters waited to resuscitate them until after cooling
had started—even if that meant the mice spent longer with their hearts stopped. It was a
provocative finding, because it suggested that the damage caused by a few extra minutes
of oxygen deprivation is mitigated by cooling—and then some. "If you apply
hypothermia during cardiac arrest itself, survival and neurologic outcomes are much
better than if you apply it after resuscitation," Abella claims.
A smooth-talking, handsome guy who resembles a young Andy Garcia, Abella says he
was destined for resuscitation research. His mother was born with third degree heart
block, a defect of the heart's electrical system, which gave her a resting heart rate around
30 beats per minute (normal is 70). "They told her she could never give birth, her heart
couldn't take it," Abella explains in his office at Penn, which is cluttered with empty
computer boxes, dozens of packs of microwave popcorn and a life-size resuscitation doll
he calls Annie. Abella's mother was stubborn, he says, so she got pregnant anyway, and
one of the grandfathers of resuscitation research at the time, Richard Langendorf, came to
the hospital to help with the birth. "He was in the room when I first came into the world.
So in some really weird karmic way, I was meant to go into resuscitation," Abella says.
Cooling isn't happening as quickly as Becker and Abella want, though, partially because
it's counterintuitive for doctors to delay resuscitation for any reason. (The mantra has
always been to re-start the heart as soon as possible.) What's more, cooling technology
isn't designed to bring on ambulances or trek around emergency rooms. Even for a patient
like Barco—who collapsed within a few feet of the Penn hospital—the cooling process
didn't begin until three and a half hours after her cardiac arrest, because doctors waited
until her vitals were totally stable.
Becker and Abella are, however, trying to change that. With the help of postdoctoral
engineer Josh Lampe, they have designed a cooling "slurry" machine that uses IVs to
flush an ice-water saline mixture through the body, cooling patients faster. The machine
makes its saline slurry— "like a slushee, a slurpee, a margarita," Lampe says—on
demand, and two and a half liters is all that's needed get patients down to target
temperature. Cooling someone using refrigerated saline requires more than four times the
volume, and therefore a lot more time.
If all goes well with their first machine prototype, which was built earlier this year and is
currently being tested on pigs, Becker and Lampe will apply for FDA approval to use the
machine on cardiac arrest patients in a clinical trial. "Dream comes true, we hit the grand
slam, it's in an ambulance and the EMT does it," Lampe says.
Becker is also organizing a national trial to test a new technology that cools by way of the
nose. The aptly named Rhinochill, made by New York-based biotech Benechill, blows
out a mist of liquid perfluorocarbons—the same stuff that cools refrigerators—and
oxygen. The perfluorocarbons evaporate into the oxygen, a phase change that requires a
lot of energy. And energy, of course, is heat. "With that evaporation, there's intense
cooling," explains Becker. It cools down the back of the nose, the nasal hairs, and the
base of the brain—causing the body to cool very quickly.
Thanks in part to Becker and Abella, who joke that their job is to "spread the gospel of
hypothermia," the American Heart Association added therapeutic hypothermia to its
Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care in
2005, which doctors around the world follow as protocol. Even so, not that many doctors
seem to be using it yet. According to a physician survey that Abella conducted in 2006,
only 26 percent of U.S. emergency room and cardiology doctors had ever cooled a patient
after cardiac arrest. "It's taught me a lot about the inertia of American medicine," Abella
laments.
He speculates that some doctors are afraid of cooling and what it entails. Cooling
equipment is expensive, and although hospitals can cool a lot more cheaply with ice
packs, it's much harder to control temperature that way. And the body is
temperamental—if you cool it below about 86°F, the risk for cardiac arrest goes up
drastically. (Plus, nurses hate ice packs. "Big puddles," Abella jokes.)
Hypothermia also requires hospital-wide collaboration. "It's not like one doctor can say,
I'm going to start giving the blue pill as opposed to the red pill," Abella says. "Patients
come into the ER, they then go to the intensive care unit, and the care needs to be
coordinated. Cooling is a 24 hour process." That also means that everyone needs to know
how to do it. Penn set up a cooling hotline so that anytime day or night, Penn doctors and
nurses could send a page to 4233—that spells out ICEE—and get a call back from one of
Penn's cooling experts who answers any questions.
Other doctors aren't convinced that hypothermia really works. Although there are a
dozens of animal studies showing hypothermia to be beneficial after cardiac arrest, the
two 2002 trials are the only studies showing that it saves human lives. And they aren't
flawless: a lot of the patients in the trials' control groups—those who were not cooled—
actually had a slight fever after cardiac arrest. So some of the purported benefits of
hypothermia may not be in lowering normal body temperature, but in preventing fever.
There are many remaining questions about hypothermia, and this, too, could be scaring
doctors away. Although Becker and Abella know that cooling slows down mitochondrial
meltdown and the immune response, it's unclear exactly why. "Like many things in life
and in medicine, you first find out something works, and you start applying it, and then
you say, no wait a minute, we have to find out why it works," Abella says. "Maybe some
of the things it does are bad. But in net, it definitely saves lives."
To find out exactly how hypothermia works, the field of needs funding—and there's also
little of that. "For the impact that [hypothermia] has, it just doesn't get anything close the
funding that it needs," Becker says. Cardiac arrest isn't even included on the list of
medical conditions and research areas that the National Institutes of Health funds. Yet
compared to any other disease or medical emergency, it is the most time-sensitive and the
most deadly. "There are no other diseases in which minutes count," Abella says.
Back in the Cardiac Care Unit, Pamela Barco was being cooled. It was a miracle she even
made it that far—after being transported next door to Penn, doctors had spent hours
trying to raise her systolic blood pressure, the pressure exerted when the heart contracts.
It was fluctuating between 70 and 100 mmHg—normal is about 115. And although they
had given her a breathing tube and were feeding her 100 percent oxygen, her blood
oxygen levels were still dangerously low. Even worse, according to her post-cardiac
arrest echocardiogram, her heart was a mess.
To cool her, nurses sedated Barco and then paralyzed her so that she wouldn't shiver
(muscles that shiver use more oxygen, which is exactly the opposite of what you want).
Nurses gave her two liters of refrigerated saline through an IV and wrapped her legs and
torso with cooling wraps resembling big slabs of bubble wrap with cold water flowing
through them. By morning, Barco's body temperature had cooled down to 91°F, and they
kept her at that temperature for 24 hours. Her family—she has three daughters, a son, and
four grandchildren—spent day and night couped up Barco's tiny hospital room, the
smallest in the unit, stroking her hair and talking to her. And waiting.
The waiting continued for several days. Barco was re-warmed over an eight hour stretch,
after which nurses took out her breathing tube and stopped giving her the paralytic drugs
and the sedatives. Her heart didn't look good; the doctors told her family she might need a
transplant. No one knew yet how her brain had fared, either, because they needed her to
wake up first. She started having problems breathing again, so they put the breathing tube
back in. Her daughter Jihan started calling her name. Two or three times, Barco opened
her eyes and then just as quickly closed them again. She was in and out of consciousness.
She started grabbing her breathing tube to try to pull it out. Doctors had to put her on
restraints for a while.
Eventually, Barco started waking up for longer stretches and talking. At first, she couldn't
remember things very well—she'd talk to her kids, but then forget the next day what had
been said—but each day she improved. The breathing tube came out for good. Doctors
put a defibrillator in her chest that would automatically shock her if the heart ever
stopped again.
Oddly enough, no one knew why Barco's heart stopped in the first place. After the birth
of her fourth child 16 years ago, her heart had developed an abnormality called a
cardiomyopathy. She had visited Penn cardiologist Jonathan Gomberg regularly over the
years, and the condition had healed by itself. "She wasn't supposed to do this," Gomberg
said after a follow-up appointment with Barco in October. Why it happened is still a
mystery.
But Barco, now fully recovered, isn't too concerned about solving it. She is back working
at the Children's Hospital and is finishing up the nursing degree she has been working on
for the last four years. Graduation is May 28. Her heart is perfectly healthy now, although
no one knows how that is possible.
So how does she feel about being cooled—about the treatment that may have saved her
life?
"Grateful. Very grateful," she says softly, her throat still scratchy from the breathing tube.
Tears well up as she looks over at Jihan and her four-year-old granddaughter Aniyah.
"Life is good. I'm here," she says. "My only priority is to just be here with my family and
enjoy every day."