Life Extension Magazine January 2010
By Sanjay Gupta, MD
Let me let you in on a little secret: When the heart stops beating, it’s not the end. As it turns out, “life and death” is not a black and white issue. There is a gray zone—a faint no man’s land where you are neither truly dead nor actually alive. In order to control it, in order to cheat death, we have to first, better understand it.
We’re used to thinking about dying in stark terms. Dead or alive. You’re here and then you’re gone. In our imagination, this is how the moment of death plays out: the villain, or hero, or soldier, gasping last words, stretching out a hand... until his eyes roll back in his head and we know it’s all over. Or the cancer patient, surrounded by family. A light flickers behind her eyes, then goes out. You’ve read it in a thousand stories, seen it in a thousand movies, a hundred episodes of “ER.” The alarm sounds. The monitor flatlines. Time of death, 2:15.
It only takes a few minutes for life to slip away. Without a heartbeat, circulation slows to a halt. Blood is no longer flowing in your brain, or any other organ. It takes just a couple minutes before everything goes dim, and now you’re blissfully unaware of the catastrophe unfolding inside your body. Starved of blood, the first organ to suffer is the brain, which in happier times consumes about 20 percent of all the oxygen the body takes in, even though it constitutes just two percent of our body mass. After just ten seconds without oxygen, the brain’s function slows.
Without oxygen or signals from the brain, other organs soon break down as well. Our diaphragm muscles no longer contract and release, to bring in air. The kidneys stop filtering blood. At the same time, an elaborate chain of chemical reactions triggers a breakdown in cells throughout the body.
This is the process of dying. Whether because of a car accident, a blockage in an artery or a tumor somewhere in your body, it is generally understood that when the heart stops beating, life has ended. I have seen this play out more times than I care to remember.
As a doctor, I can assure you that when the heart stops beating, it’s not the end. Death is not a single event but a process that may be interrupted, even reversed. And here’s the exciting part: at any point during this process, the course of what seems inevitable can be changed.
It’s been said that life is a terminal condition, that nothing lasts forever, and the minute we’re born we start the long process of our end. I think everyone, at one point or another, has probably wondered: does it really have to be that way?
Therapeutic hypothermia was first used in the 1940s and 50s, when pioneering heart surgeons like Walt Lillehei started using hypothermia to extend their time in the operating room. Prior to the 1940s, most open heart surgeries were thought to be impossible, because anything more than a very simple repair could not be completed in the few minutes that the heart might survive without oxygen. By chilling a patient’s blood, Lillehei found that he could buy precious minutes. A heart that only lasted 10 minutes at room temperature, could survive an hour when it was cooled to 20 degrees.
There’s no easy answer as to how or why hypothermia really works. The first person I thought to ask was Dr. Lance Becker, an emergency physician and researcher who runs the Center for Resuscitation Science at the University of Pennsylvania Hospital. Becker says the hypothermia procedure is still mysterious. “We’re pretty sure it doesn’t work on just one mechanism. I’ve looked at 20 or 30 ideas [in the lab] that have been postulated, but the truth is, nobody knows,” just why or how it helps.
What does seem clear is that as a medical therapy, hypothermia is a way to buy time. I explain it this way: chest compressions and artificial respiration provide oxygen that the body needs, but hypothermia sort of slows the body down. That in turn reduces the need for oxygen, so the body can last longer on what’s already there.
Studies show that every one-degree (Celsius) drop in body temperature will lower cellular metabolism by roughly five to seven percent. Becker’s best guess is that this reduced metabolism also slows the chemical reactions that are triggered by oxygen deprivation and which prove so damaging to cells. There’s no doubt this is complicated. Hibernation is a good example of cold going hand in hand with lower metabolism; mammals who hibernate can survive, even thrive, for long periods at far below their usual body temperature. In these animals, cold doesn’t just slow metabolism the way it thickens a jar of molasses. Rather, it triggers a whole set of biochemical changes.
Hibernation seems to be caused by different factors, depending on the animal, but cold weather is a common trigger. Take ground squirrels. For ground squirrels, as soon as temperatures dip below freezing on a regular basis, the animals go into a near-complete torpor. Their heart rate, usually around 200 beats per minute, slows to less than 10. The squirrel’s body temperature will drop from a warm-blooded 37 degrees to just one or two degrees above the outside temperature. They stay in that state, using just a bare minimum of energy, for at least six months.
True, humans aren’t squirrels, but believe it or not, we have some of the same adaptive ability. For example, immersion in cold water triggers something called the diving reflex, or Vagal reflex. You could think of it as throwing the body into a state of semi-hibernation. Blood flow to the extremities nearly shuts off completely. The heart and brain use as little as a tenth of the oxygen they normally require. Survival time is stretched out.
Dr. Stephan Mayer, too, knew those statistics well. Mayer is a crusader for therapeutic hypothermia, fretting over the doctors who are reluctant to use it as a treatment, and the medical organizations, who in his view, don’t do enough to promote it. Mayer first encountered hypothermia in a very different context, on the grounds of an ancient mental hospital in Westchester County, New York. In October of 1986, Mayer was a third-year medical student, and he spent most of that month looking after young men who had basically fallen apart under the strain of their freshman year in college. “Depression, bipolar disorder, borderline personality disorder—they were all these young guys who had gone off from home for the first time, and just decompensated under the pressure.”
One night, a young man came into the unit in a straitjacket, clearly in the midst of a complete breakdown. “He was in this psychotic rage,” says Mayer. “We were giving him doses, mega doses, of thorazine, haldol, you name it, and it wasn’t touching him at all. He just kept going. And then someone said, ‘Get the cold sheets!’ And I’m like, ‘what’s that?’”
Next thing he knew, says Mayer, he was helping more than a dozen doctors and orderlies to hold down the unruly patient, while someone else soaked the sheets in ice water and rolled up the patient like a caterpillar in his cocoon. “It was amazing. He immediately calmed down. It worked like nothing else. It was right away. [The young man] said something like, ‘oh, I think I feel okay now.’”
Curious, Mayer asked around and learned that cold sheets had been widely used in psychiatric hospitals in the early 20th century. The practice had widely been abandoned, but not by the elderly psychiatrist who ran the institution where Mayer spent that eventful fall. Mayer knew he didn’t really understand what he had witnessed, but something about it left a deep imprint.
“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. 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.
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 neurology and cardiology surgeries, 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 who were cooled below 80 degrees were prone to developing heart arrhythmias. They were also prone to strokes and other types of internal bleeding, since blood that’s chilled doesn’t clot as well. Most of those early cardiac patients would get better in the short term, but then eventually died of pneumonia. The problem was 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.
But even then, there were hints and clues that it might be done safely. For example, a few years later surgeons at the University of Minnesota reported cooling a 51-year-old female cancer patient to just 48 degrees for her surgery, and re-warming her with no apparent problems. Other experimenters, working with monkeys, also reported good results using extreme low temperatures, and there were even reports of physicians using hypothermia, successfully, in the treatment of cardiac arrest patients.
But by the 1990s, 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 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, not 60 or 70. Just as important, in the modern critical care setting they could do much better preventing and treating complications like pneumonia. When the results came back for the pilot study, they were solid—the patients did no worse—and he published them in tandem with a group of German researchers who had done a similar experiment with another 42 patients.
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.
As 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 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. tPA is a great tool, because it can almost immediately break open the clot and restore blood flow to the brain. The problem is, it 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 five percent of stroke patients actually receive this vitally important drug. Enter the Ice Doctor.
Hibernation is a good example of cold going hand in hand with lower metabolism; mammals who hibernate can survive, even thrive, for long periods at far below their usual body temperature... it triggers a whole set of biochemical changes.
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 crucial first 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 five to ten degrees.
No doubt, Mayer had cold on the brain, and in 2000 he got more encouragement. A European research team, led by the Austrian cardiologist Fritz Sterz, reported that chilling patients by about seven degrees Fahrenheit was enough to sharply improve the outcome in patients who suffered a life threatening cardiac arrest. 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 seven degrees Fahrenheit... When he was describing 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 it 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 U.S., no one was doing it. 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 UPenn team led by Lance Becker.
Once again, it came from Fritz 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; 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. 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.