Reviving the dead

Picture a typical American family sitting down for Sunday dinner at a nice restaurant. The father in this scenario, a physically fit man in his early 40s, orders the roasted lamb, his wife has the coddled duck and their three children split a large tray of tiger shrimp.

Reviving the dead

Peter Tobia

Top: Lance Becker (left), director of Penn’s Center for Resuscitation Science, on duty in the HUP emergency room with David F. Gaieski, assistant professor of emergency medicine. Bottom: Becker with Manuel Boller (left), a senior research investigator in critical care at Penn Vet.

An adventurous eater, the youngest begs his mother for a piece of her duck, so his father begins slicing a bite-sized portion. Suddenly, the father’s heart stops. There is no forewarning, no shortness of breath or tightening in the chest; his heart was beating rhythmically only moments before—then it just stopped.

The father collapses to the floor. His terrified wife rushes to his side. Did he faint? Is he choking? Did he have a stroke? Is it a heart attack?

A female bystander springs into action. She taps the man on his shoulder. He doesn’t respond. She checks for a pulse. She can’t find one. He isn’t breathing.

Tick, tick, tick. The man has been out for a minute now. A few more and it may be too late.

The man has suffered a cardiac arrest, the rapid, unexpected loss of heart function.

Unlike a heart attack, which often presents warning signs like chest discomfort, neck pain and nausea, a cardiac arrest can occur spontaneously and strike those with or without any previous coronary injury or disease.

When a person goes into cardiac arrest, he or she is clinically dead. But Lance B. Becker, a professor of emergency medicine at Penn and director of the University’s Center for Resuscitation Science, says that doesn’t necessarily mean the person is in a permanent state of death. Efficient resuscitation, he says, can bring many near-death patients back physically unchanged.

“The truth of the matter,” Becker says, “is if a patient comes into the emergency room and they don’t have a heartbeat, we agree they’re technically dead. But what we’ve figured out is there are more and more people who are what I’m going to call temporarily dead, meaning there are people who don’t have a heartbeat, but we can get them back.”

According to the American Heart Association (AHA), emergency medical services (EMS) treat nearly 300,000 victims of out-of-hospital cardiac arrest each year in the United States, and less than 8 percent of those patients survive.

Research at the Center for Resuscitation Science is dedicated to saving the lives of those who suffer a cardiac arrest, investigating everything from basic biochemical mechanisms to more effective ways of performing cardiopulmonary resuscitation (CPR). Specialists at the Center operate in a gray area between life and death, what Becker calls a “border zone”— where words like “death” no longer have the same meaning.

He says his research into this border zone makes doctors uncomfortable because “we like to have things be right or left, not in between.” He jokes that his residents sometimes even ask, like the Munchkins in “The Wizard of Oz,” if a patient is “really most sincerely dead.”

“It’s almost like we’re going to need words like that in the future,” he says.
Robert W. Neumar, an associate professor of emergency medicine at Penn and an associate director at the Center, says there is a window of opportunity after a cardiac arrest in which intervening actions can restart the heart and the victim can resume breathing.

“One of the things that we’re doing research-wise is pushing the borders of what those limits are,” he says, “and maybe even potentially extending those limits with different ways of resuscitating patients.”

The ambulance screeches to a halt outside the emergency room. Tick, tick, tick. The man who collapsed in the restaurant has been out for about 10 minutes now; he is still not breathing and his heart is not beating. An emergency medical technician continues chest compressions as he is rushed inside.

A team of medical professionals surround the man. It is a chaotic but controlled scene. One continues chest compressions. Another hooks him to a heart monitor. A third checks his airway. A fourth connects an IV. The team leader ponders what caused the arrest and if there is something they can treat specifically and immediately.

A doctor grabs a defibrillator and shocks the man. No pulse.

Raina Merchant, an assistant professor of emergency medicine at Penn and a research fellow at the Center, says resuscitating cardiac arrest patients in the emergency room takes “a major team effort” with each individual dedicated to doing everything possible to save the patient’s life.

“There’s a certain amount of energy and anticipation and focus that goes on when someone comes in,” she says. “The environment is very emotional. It’s a life-or-death situation so we really try to get people back.”

Neumar describes the collaboration required as similar to that of a racecar pit team, where each person has a specific job to do, and must do it quickly.

Becker says: “You can imagine how mentally challenging it is, how chaotic in a way, to have a dead person there, and you’re trying to do everything you can to save them. It takes a village to really save somebody.”

Time, Becker and Neumar stress, is the most important factor in cardiac arrest resuscitation. The clock starts as soon as the blood supply stops. Doctors have a window of about four minutes to act before permanent damage may begin to occur.

The sooner CPR is started, the greater the chance that the person will survive. While chest compressions do not solve the cardiac arrest, Becker says they can stretch the critical four-minute window into six or eight minutes.

“We mostly identify people (in cardiac arrest) by noting that there is something dramatically wrong with their blood pressure,” Becker says. “The pumping of blood is what brings oxygen to everything in the body. So in most of these people, the common denominator is they have a problem bringing oxygen to all of their tissues.”

Neumar says the longer one waits to start CPR, the less effective it is. “In someone who gets CPR within a minute of going into cardiac arrest, the blood flow is very good. But if it’s 10 minutes before someone starts CPR, the blood flow is not good. So the effectiveness of CPR declines with time.”
CPR however, does not create enough blood flow to keep a person in cardiac arrest alive so eventually the heart must be restarted.

Back in the intensive care unit, the cardiac arrest victim is breathing and has a pulse. But he is still unconscious, and his distress is not over. Neumar, a neuroscientist, says that when the heart stops, the brain’s supply of oxygen and nutrients is cut off. Because the patient in this scenario was in arrest for more than four minutes, his brain and heart may be severely damaged beyond repair.

Becker says the Center is pioneering “super advanced techniques” that could improve outcomes for patients following resuscitation from a cardiac arrest. The main technique is called hypothermia—literally putting people on ice.

“As crazy as it may sound, we’ve now figured out that actually cooling a person down after an event like this helps them out,” says Becker. “It seems to help protect the brain from that period of time when it didn’t have oxygen. It also seems to protect everything else, and by that I mean the heart and the liver and kidneys. All the organs seem to do better when they get cooled down for about 24 hours.”

Patients treated with hypothermia are cooled down from their normal 98.6 degrees Fahrenheit to somewhere between 89.6 and 91.1 degrees Fahrenheit (37 degrees Celsius down to 33 degrees Celsius).

“Not every single person makes a great recovery,” Becker says. “A certain percentage of people are just too sick, and they have permanent brain damage or permanent heart damage, but we’re trying to do everything we can to avoid that.”

One of Becker’s cases recently received national media attention because the patient—22-year-old Christopher Brooks from Middletown Township, Pa.,—was successfully revived and then treated with hypothermia after having been without a pulse for more than 15 minutes. Despite his lengthy arrest, Brooks survived without any brain damage. CNN’s Sanjay Gupta presented a special report on Brooks in October 2009 titled “Another Day: Cheating Death.”

“There would have been some doctors who said, ‘He’s been down for so long, it’s not worth trying,’ and they just would have let him die,” Becker says. “And obviously, in Chris’s case, we can see that would have been a mistake. But the question is: How many people do we do that to? That’s one of the things we’re trying to figure out. Nobody knows.”

 The American Heart Association traces the origins of CPR back to 1740, when the Paris Academy of Sciences officially recommended mouth-to-mouth resuscitation for drowning victims. Further advancements, including external chest compressions and closed-chest cardiac massage, were made in succeeding centuries.

Drs. Peter Safar and James Elam invented the modern day version of CPR in 1956. Safer, who served as an anesthesiology resident at Penn early in his career, went on to establish the International Resuscitation Research Center at the University of Pittsburgh in 1979, later renamed the Safar Center for Resuscitation Research.

Both Becker and Neumar have long worked at the forefront of resuscitation research, breaking new ground and shattering previous assumptions about the space between life and death.

While he was a student at the Pitt School of Medicine in the late 1980s, and as an emergency medicine resident at Pitt in the early 1990s, Neumar worked with Safer—whom The New York Times called “The Father of C.P.R.”—on research focused on post-cardiac arrest care and minimizing any brain damage caused by the arrest.

Safer’s philosophy, Neumar says, was: “If you get the heart restarted, it doesn’t matter much unless the patient wakes up and gets back to normal.”

Becker came to Penn in 2006 from the University of Chicago Department of Medicine, where he was a professor of emergency medicine and founder and director of school’s Emergency Resuscitation Center.

As a student at the University of Illinois School of Medicine in the late 1970s, Becker says he was trained to believe that a person was either dead or alive. There was no such thing as a border zone.

He took basic and advanced life support courses as a resident at Chicago’s former Michael Reese Hospital, classes that he says opened his eyes to resuscitation science.

While working in the emergency department at the University of Chicago in the 1980s, Becker noticed a statistic from the City of Seattle, which at the time had a heightened awareness about CPR.

The statistic noted that 18 percent of the city’s cardiac arrest patients survived if they received CPR and good medical care, a much higher percentage than Becker was seeing in Chicago.

“At first I thought it was me,” he says. “I thought that I must have the darkest cloud ever over my head because most of my patients were dying.”

He went back and studied books on resuscitation and “every single drug” involved with revival, and all that he was taught about resuscitation science. “I thought I had learned it perfectly and I knew that my survival rate was terrible compared to this 18 percent,” he says.

Searching for an explanation for the disparity between the cardiac arrest survival rates in Seattle and Chicago, Becker began a study called “CPR Chicago” in 1986—the largest CPR study completed in an urban area at that time. Over a two-year period, Becker and collaborators collected information on all the cardiac arrests in Chicago—about 7,000. They discovered that the cardiac survival rate in Chicago was only 1.8 percent, 10 times worse than that of Seattle.

“In a way, that made me feel better because it wasn’t me,” he says. “But it sort of lit a fire under my rear end because I said, ‘There’s got to be a way that I can help turn that crummy survival rate into something better.’”

Knowing that doubling Chicago’s survival rate would only increase it to roughly 3.5 percent—still leaving around 97 percent of patients dead—Becker began researching ways to increase the impact of available techniques to treat cardiac arrest and also embarked on a search for others. He conducted further study on CPR and was instrumental in placing automatic external defibrillators, or “shock boxes” in the Chicago airport.

“I was involved in the first study where we put them in the airport and we raised the survival rate from 0 to 65 percent,” he says. “Now that’s a big change.”

That success, he says, has led him back to basic science. He’s become interested in cells and how medical professionals might somehow expand the crucial four-minute window of intervention into 24 minutes.

“What if we had all that time?” he asks. “That’d be enough time to get an ambulance to somebody’s house, to bring them back to the emergency department. If we had 24 minutes instead of four minutes, we would be saving hundreds of thousands of people just in the United States, and there’d be similar advantages all across the world.”

The idea of resuscitating people is not new. People have been trying to bring back the dead for millennia.

“Techniques for resuscitating people go all the way back, thousands of years, and some of them are pretty crazy,” Becker notes. “I’ve seen drawings of them.” One method involved placing a deceased individual on a trotting horse.

So rare was resuscitation until the 18th century that it was often attributed to the divine. In the Hebrew Bible’s Book of Kings, it is written that God, at His prophet Elijah’s request, returned life to a widow’s deceased son. In the New Testament’s Gospel of John, Jesus Christ is said to have raised his friend Lazarus, dead for four days, by simply shouting, “Lazarus, come out!”

Becker says the majority of patients who are resuscitated from cardiac arrest don’t remember anything about their ordeal. “They tell me, ‘Lance, I was there, I was gone, and then I woke up and I was in the hospital,’” he says. A few patients, however, have described the experience as spiritual.

“Each person describes it so differently and uniquely that I haven’t yet seen a common thread,” he says. “But I will say that it affects people’s lives. It affects the kind of person they are in a way that I think is very important. Many of them tell me that it made them a better person.”

Despite the long history of attempts to revive the dead, Becker says resuscitation science is, in fact, a young field of study. And it’s also untraditional. It involves not just the heart, but the brain too. And it concerns not just adults, but also children.

It’s a truly interdisciplinary field of medicine, Becker says. Experts from a wide spectrum of medical specialties work at and collaborate with the Center: basic scientists, emergency medicine professionals, surgeons, pediatricians, epidemiologists and clinicians, as well as veterinarians and bioengineers.

Josh Lampe, a post-doctoral researcher, is a bioengineer studying better ways to induce hypothermia and blood flow in people who have suffered a cardiac arrest.

“The reason hypothermia is an engineering problem is because the body is very well designed to retain heat,” he says. “The blood vessels in your skin restrict if they get cold, that reduces heat loss. We all have a layer of fat underneath our skin, that reduces heat loss.” The body is so adept at retaining heat that it takes a precious one to two hours to cool a person down through hypothermia.

“Because we believe that time matters, we’re trying to develop methods that would allow you to achieve that same amount of cooling in 10 minutes or less,” Lampe says.

Becker recruited Manuel Boller to the Center from Penn’s School of Veterinary Medicine in order to learn more about resuscitation through animal research.

“His background in animal care is ideal ... so that our animal experiments are just as sophisticated and as good as possible so that we learn just as much as we can from them,” Becker says.

Boller, a senior research investigator in critical care at Penn Vet, says that treating cardiac arrest in animals and humans is similar. And while they are different species, in principle, he says researchers are looking to accomplish the same thing—to get blood and oxygen flowing to tissues once again.

“We obviously use animals to model the human condition, but there are also naturally occurring diseases in animals that are very similar,” he says. “There’s human translational potential there where I think human doctors can learn from us veterinarians and vice-versa.”

Penn is by far one of the world’s leading institutions in resuscitation research. Becker says he recently returned from a European conference on resuscitation where Penn “sort of dominated the meeting” with more experts than any other American or European university.

“It’s incredible,” says Lampe of the many resuscitation experts working at Penn.

Neumar is the chairman of the AHA’s Advanced Cardiac Life Support Subcommittee, which creates national guidelines for resuscitation care. He also helped craft the AHA’s 2010 Guidelines for CPR and Emergency Cardiovascular Care (ECC).

Robert A. Berg is chair of the AHA’s Basic Life Support Committee, a critical care medicine division chief at the Children’s Hospital of Philadelphia (CHOP) and a professor of anesthesia and critical care and pediatrics at Penn.

Other specialists include Vinay M. Nadkarni, an associate professor of anesthesiology and critical care at the Hospital of the University of Pennsylvania, the endowed chair of pediatric critical care medicine at CHOP and associate director of the Center; and Benjamin Abella, an assistant professor of emergency medicine at Penn and director of clinical research at the Center.

Science and engineering research can often be isolating, says Lampe, but “when you work at a place where the person a room over is thinking about a totally different problem or a totally different way to address the same problem, it helps you see where your research fits into the puzzle and helps you keep your eye on the whole continuum.”

As resuscitation research continues to move forward, time will still be the major focus, Neumar says. One of the ways medical professionals can begin to make significant strides in improving cardiac arrest care is by increasing early recognition, providing quicker CPR treatment and defibrillation and shortening EMS response time.

He can imagine that, in the future, there will be monitoring devices that are compatible with watches and cell phones that will be able to identify whether a person has gone into cardiac arrest and automatically notify emergency services.

From the basic science perspective, Neumar says resuscitation scientists continue to seek a better understanding of the molecular events that are triggered by the cardiac arrest itself, and continue after the heart is restarted. “A better understanding of that will allow us to resuscitate patients in a way that damage is minimized,” he says.

Becker says he is still trying to convince many of his medical colleagues that his life’s work is worthwhile. But it’s not easy. The majority of doctors, he says, continue to believe that dead is dead, and resuscitation research is a waste of time and money. It’s still difficult, he says, for his research to receive federal funding.

“I am an advocate for trying to educate doctors, educating the public, educating patients and educating hospital administrators that no, a dead person is not a dead person,” Becker explains. “A dead person, in the right setting, has a damn good chance we could

bring them back to life. And I spend a lot of my time trying to convince people of that.”

Originally published on January 20, 2011