Therapeutic hypothermia touted for cardiac arrest patients

By Marie McCullough
The Philadelphia Inquirer
Copyright 2008 Philadelphia Newspapers, LLC

PITTSBURGH — Max King is no fan of sensationalism, but he relishes declaring, "I literally died."

The former journalist and current head of the Heinz Endowments, one of the nation's largest independent philanthropies, was speaking to Pittsburgh civic leaders at the Carnegie Museum of Art 18 months ago when his heart suddenly stopped beating.

After he collapsed, six people sprang into action, performing cardiopulmonary resuscitation and restoring his heartbeat with an automated external defibrillator.

Only 6 percent of the 220,000 Americans who suffer cardiac arrest each year survive it. King, who is 63, was among an even tinier fraction — 3 or 4 percent — who come through it without heart or brain damage.

At the University of Pittsburgh Medical Center's Presbyterian Hospital, he received a radical treatment that involved keeping him in a coma and slowly cooling his body to about 91 degrees Fahrenheit.

"Therapeutic hypothermia" — cold therapy — is being used by a growing number of hospitals around the country, and University of Pennsylvania scientists are studying ways to do it more simply and quickly. It is the only intervention clearly shown to protect the brain from the devastating effects of cardiac arrest.

Which does not mean it is a panacea. Not until King regained consciousness — he immediately asked where he was, using an expletive he would not have permitted in this newspaper, which he edited from 1990 to 1997 — were his wife and their two sons sure that he would be fine.

"He was totally confused, but he saw our kids and instantly knew them," Peggy King recalled. "He put his hands on either side of their faces and said, 'You're here.' "

Said King: "I came through with absolutely no damage whatsoever. I feel so grateful to be the beneficiary of cutting-edge technology."

The heart may stop beating because of a severe arrhythmia — as in King's case — a congenital defect, or a clogged artery that triggers a massive heart attack. Cardiac arrest also can be triggered by hypothermia.

"A body temperature below 95 degrees F is a medical emergency and can lead to death if not treated promptly," says Medline, the Web site of the National Institutes of Health.

While the therapeutic effects of being cold seem counterintuitive, they were recognized at least as far back as the days of ancient Egyptians.

"Your gut instinct is not to cool the patient," said Eugene Vallely, coordinator of critical-care education at Doylestown Hospital, which used hypothermia after cardiac arrest for the first time in February. "But you see patients who fall through the ice and neurologically, they do well."

In the 1930s, a brilliant Temple University physician named Temple Fay pioneered what he called "human refrigeration," devising water-cooled rubber blankets and coils to treat head injuries, relieve pain, and slow malignant-tumor growth. Fay stopped this research, despite encouraging results, when the Nazis appropriated his techniques to conduct brutal experiments in concentration camps.

In the 1980s, University of Pittsburgh researchers led by Peter Safar rekindled interest by showing that hypothermia could prevent brain damage in dogs after cardiac arrest.

In 2002, human studies in Australia and Europe found that cooling dramatically reduced death and disability in patients who suffered cardiac arrest outside hospitals.

Your gut instinct is not to cool the patient, but you see patients who fall through the ice and neurologically, they do well.
— Eugene Vallely
Coordinator of Critical-care Education, Doylestown Hospital

Exactly how cooling works, while still unclear, involves another paradox. The brain begins to die when deprived of oxygen-rich blood flow for more than five minutes. (The trickle of blood from CPR keeps the survival window open but is only a stopgap.)

Restoring normal blood flow, however, unleashes a complex cascade of inflammation, calcium imbalances, and oxidation that doctors call "reperfusion injury."

At Penn's Center for Resuscitation Science, emergency-medicine physicians Lance Becker and Benjamin Abella theorize that mitochondria — tube-shaped structures within the cell that convert nutrients into energy — are key to curbing reperfusion injury.

Mitochondria "are like nuclear reactors," Abella said. "Cardiac arrest is like breaking the control rods in the reactor, so when fuel floods it, there's a meltdown.

"Hypothermia cools and slows down the reactor."

Therapeutic hypothermia has not become standard care despite the American Heart Association's endorsement. That is partly because it is a complex medical intervention and partly because relatively few patients are resuscitated in time for cooling to do any good. (Penn says it has treated fewer than 25 patients in two years.)

Ideally, studies suggest, cooling starts within a few hours after circulation has been restored, although it may still help if begun within eight hours.

The patient is given sedating and paralyzing drugs to prevent shivering, put on a ventilator, then gradually chilled over four to eight hours with cold intravenous saline and various external devices connected to sensors.

For 24 hours, body temperature is held between 90 and 93 degrees , while electrolytes, urine output, blood factors, heart rate and more are monitored for signs of problems.

King, for example, developed pneumonia.

"I do have a sense that hypothermia may increase the risk of pneumonia," said William Follansbee, the cardiologist who treated him at Presbyterian in Pittsburgh.

Rewarming is also done gradually, about a degree an hour, as sedation is reduced.

Experts estimate that therapeutic hypothermia protocols are in place at fewer than 500 of the nation's 4,000 hospitals. The number is increasing as cooling shows promise in treating stroke, traumatic brain injury, septic shock, and spinal-cord injury.

Last fall, interest spiked when Buffalo Bills football player Kevin Everett suffered a major spinal injury and was treated with hypothermia.

Adults are not the only patients. Children's Hospital of Philadelphia has begun using hypothermia to treat oxygen deprivation at birth. It has also cooled about 15 cardiac-arrest patients.

One of them, Delon Martin Jr., was 6 months old when he was transferred, on a ventilator, from Crozer-Chester Medical Center. The baby had suddenly gone limp in his father's arms at their Chester home.

"He was fussy, and he wouldn't take his bottle, which was unusual," Martin recalled. "Then he started gasping for air."

Martin, a carpenter, performed CPR and called paramedics, who used a defibrillator. Still, the baby was without normal blood flow for perhaps 20 minutes.

"He was really at risk" of brain damage, said Daniela Davis, the critical-care physician who treated Delon at Children's Hospital.

Last week, days after his first birthday, he walked, pushed the light switch on his toy truck, and babbled "Dada" and "Mama."

Although he sleeps with an apnea monitor and takes medication to prevent another life-threatening heart arrhythmia, Delon is thriving and happy, said his mother, Tressa Martin.

"He picked up where he left off," she said.

If the body could be cooled in minutes, instead of hours, the therapy would be more effective - even if blood flow is interrupted for many minutes, studies in animals and heart-lung bypass patients suggest.

Becker, the Penn researcher, has worked with BeneChill Inc. of San Diego on the "RhinoChill System," which uses the nasal cavity to administer a cooling aerosol spray close to the brain. Human studies are underway in Europe.

Becker has also developed a cold saline slurry that, given intravenously, drops internal body temperature within an hour - at least, in pigs.

"There are no ill effects so far," he said. "It looks very promising."

Copyright © 2013 LexisNexis, a division of Reed Elsevier Inc. All rights reserved.
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