Back From the Dead

Researchers have ransacked their arsenal of drugs looking for ways to interrupt this sequence. Over the years they have tried various techniques on nearly 100,000 patients around the world. None has shown any benefits, according to Dr. A. Michael Lincoff, director of cardiovascular research at the Cleveland Clinic. But one thing does seem to work, something so obvious and low-tech that doctors have a hard time accepting it. It's hypothermia, the intentional lowering of body temperature, down to about 92 degrees Fahrenheit, or 33 Celsius. Research by a European team in 2002 reported favorable results from a controlled study of several hundred cardiac-arrest patients; subjects who were cooled both had better survival rates and less brain damage than a control group. The first big international conference on cooling took place in Colorado this February. Despite favorable studies and the endorsement of the American Heart Association, "we were concerned that [hypothermia] still wasn't catching on," says the conference organizer, Dr. Daniel Herr of Washington Hospital Center in Washington, D.C. The two leading manufacturers of cooling equipment—Medivance, Inc., and Gaymar Industries—say only about 225 hospitals, out of more than 5,700 in the United States, have installed machines for inducing hypothermia. Herr says the treatment requires a "paradigm shift" by doctors. "People have a hard time believing that something as simple as cooling can make such a big difference." Perhaps that's because no one quite understands how cooling works. It appears to work globally on apoptosis, rather than on any of the individual biochemical pathways involved in it. "The short answer is, we don't know," says Neumar.

Researchers have also been looking into the way patients get oxygen during resuscitation, and afterward. The treatment goal in cardiac arrest has been to rush oxygen to the heart and brain at maximum concentration; the mask the paramedic pops on your mouth supplies it at 100 percent. "The problem with that," says Dr. Ronald Harper of UCLA, "is it does some very nasty things to the brain." Harper believes a mixture containing 5 percent carbon dioxide would buffer those negative effects, but the idea is still controversial. At the University of Maryland, Dr. Robert Rosenthal and Dr. Gary Fiskum have been looking into whether oxygen concentrations should be dialed down much more aggressively. In their lab, dogs with induced cardiac arrest recovered better when they were taken off full oxygen after just 12 minutes, compared with an hour in the control group. Rosenthal says in practice patients sometimes are left on pure oxygen for much longer than an hour—in one hospital he studied, for as much as 121 hours.

At Penn, Becker's Resuscitation Center coordinates with the Emergency Department on a protocol for cooling patients in cardiac arrest. "We look at their prior mental state," says Dr. Dave Gaieski. "If someone was in a coma in a nursing home, we're not going to cool them." The same goes for patients whose hearts stopped for longer than an hour. Since 2005 just 14 patients have met Penn's criteria for hypothermia. Eight survived, six of them with complete recovery. No one knows how many others were saved by cooling around the country.

Bondar arrived at Penn at about 1:30 a.m., still comatose, minutes ticking away while he was evaluated for cooling. Once the decision was made, the team sprang into action, injecting him with an infusion of chilled saline—two liters at about 40 degrees—then wrapping him in plastic tubes filled with chilled, circulating water. Becker believes, based on animal work, that cooling patients even sooner—ideally, on their way to the hospital—would be even more effective, and part of the work of his lab involves perfecting an injectable slurry of saline and ice that could be administered by a paramedic. Bondar was kept at about 92 degrees for about a day, then allowed to gradually return to normal temperature. He remained stable, but unresponsive, over the next three days, while Monica stayed at his bedside. She finally went home Sunday evening, and was awakened Monday by a call from the hospital that she was sure meant bad news.

"Guess what?" said the voice on the other end. "Bill's awake."

Bondar's first words were, "How did I get here?" He had lost track of a full week, from about two days before his heart attack until he woke up. That's not unusual; short-term memory is often the first casualty of cardiac arrest. Neumar says certain cells in the hippocampus, the part of the brain that forms new memories, are for unknown reasons especially sensitive to ischemia. Another Penn patient, Sean Quinn, was 20 and a student at Drexel University when he went into unexplained cardiac arrest in 2005. He was one of the earliest patients cooled at Penn, and there's reason to believe that it saved his life, but the continuing memory deficit has prevented him from returning to college.