New Trial to Study Ability of Cold to Improve Outcomes of Resuscitated Cardiac Arrest Patients

Duke University Medical Center
Friday, 11 May 2001

Neurologists have a saying that when the heart stops, "time is brain." Now they may have a new cool way of bettering the odds of preserving brain cells in patients whose hearts have stopped beating.

Duke University Medical Center researchers are testing the ability of cold, or hypothermia, to protect the delicate brain tissue of resuscitated cardiac arrest patients and hope to improve the often dismal outcomes for these patients.

For 32-year-old Durham resident Talario Jenkins, the new approach now being evaluated in a clinical trial shows great promise.

When Jenkins checked in at an urgent care clinic complaining of a rapidly beating heart, the doctors realized that they couldn't control it, so they called an ambulance to take him to the emergency department at Duke University Hospital. While en route, he went into cardiac arrest. Paramedics shocked his heart back into action, but he went about 10 minutes without blood flow to his brain. He arrived at Duke in a coma.

Waiting for him at Duke was neurologist Dr. Carmelo Graffagnino, who organized and leads the four-site trial, which will find out if rapid cooling can prevent brain damage after cardiac arrest.

"Dr. Graffagnino explained the system to me -- why he felt it could help, its benefits and risks -- and I decided to do it," recalled Jenkins' wife, Danisha, who consented to her unconscious husband's participation in the trial. "It seemed like the best chance he had of surviving."

Within minutes, Graffagnino threaded a triple lumen catheter through a vessel in Jenkins' leg to his vena cava -- the body's largest blood vessel and began circulating cool saline throughout the catheter. Within several hours, Jenkins' body had cooled from its normal temperature of 37 C to as low as 32 C (98.6 F to about 90 F).

After spending 24 hours in the neurological intensive care unit in this cooled state, he was slowly rewarmed back to normal body temperature. Days later he received a operation to correct his Wolff-Parkinson-White syndrome, a congenital condition which can cause sudden episodes of extremely fast heart rates. He was discharged the next day, less than a week after the cardiac arrest.

"While every patient is different, someone like Mr. Jenkins would likely have suffered some mental decline as a result of no blood flow for 10 minutes," Graffagnino said. "Had he been out for 20 to 30 minutes, there would have been only a 10 to 20 percent chance he would have survived. He is now back at work and seems perfectly normal. We hope that the cooling played a role in that, but we won't know for sure until the study is done."

After promising results from small clinical trials in Europe and additional animal studies showing that hypothermia can protect brain cells, Graffagnino organized the multi-center trial to test the hypothesis. If the results of this FDA-approved PhaseI/II trial are promising, the researchers plan to launch a much larger study.

Acting quickly to protect the brain is important, the researchers say, because four out of five patients who are unconscious after being resuscitated after their heart has stopped beating suffer serious brain damage or die.

"When the brain is deprived of oxygen, as it is in cardiac arrest, a whole cascade of biochemical events occurs, which lead to brain cells literally 'exciting' themselves to death," Graffagnino explained. "Furthermore, when these patients are resuscitated and blood flow is restored to the brain, another cascade of events wreaks havoc on brain cells.

"We know from previous studies that hypothermia can stop or slow down these biochemical reactions," Graffagnino continued. "During the time of cold, we're offering the brain protection and allowing the healing process to occur."

While European trials cooled cardiac arrest patients from the outside using special cooling blankets, the new trial will cool people from the inside-out. During this period of coldness, participants will be given medications that will sedate and "paralyze" them, so they won't shiver, he added.

"I remember lying there in bed -- I could hear things and people talking, but I couldn't move or open my eyes," Jenkins recalled of his recovery period. "It was very strange."

It is common for cardiac arrest patients not to remember the event, and in many cases, the event can cause patients to lose memories formed days before the arrest.

In order to be considered for the trial, a patient's heart must have stopped beating, and then have been restarted -- usually by cardiopulmonary resuscitation (CPR) -- but still be unconscious. The hypothermia procedure must begin within an hour of the cardiac arrest. Researchers plan to test patients twice after the therapy -- 30 days and 90 days later.

"It is sort of a Catch-22 in that we want everyone to know how to perform CPR, but the reality is that it only works in one out of five cases," Graffagnino said. "With hypothermia, maybe we can improve those outcomes.

"We only have one hour to start cooling the patient down, so the biggest challenge we face is finding next-of-kin and explaining the procedure to them," Graffagnino said. "So much needs to happen in a short period of time."

Researchers hope to enroll 10 patients within six months at the four sites: Duke University Hospital, the University of Houston, the Oschner Clinic in New Orleans, and the Henry Ford Medical Center in Detroit.

Graffagnino said that about 300,000 Americans suffer from a cardiac arrest each year.

For more information, or to contact Duke University Medical Center, see their website at: www.mc.duke.edu