Saturday, July 14, 2007

Advances in Resuscitation Science ( revival after heart attacks etc. )

Recent medical research is questioning fundamental ideas about how to best revive victims of heart attacks and oxygen deprivation. Dr. Lance Becker of Penn is on the forefront of research that indicates opportunities in patient revival exist where otherwise current practice of administering concentrated oxygen at normal body temperatures might actually be finalizing or contributing to unnecessary deaths.

A key technical observation seems to be that the rate/(concentration) at which oxygen is returned to the patient in present revival protocols, if too fast as presently quite common practice, seems to inadvertently kill the patient by permanently triggering a death sequence initiated by cell mitochondria.

Dr. Becker observes that cooling the patient and slowing the return of oxygen with revived heartbeat, might inhibit the catalysis of permanent death by a mitochondrial switch, and seems to offer increased chances of revival from death in numerous cases otherwise conventionally deemed hopeless.

Sounds like fantastic science and great experimental observations.

Here are some interesting links

Recent Newsweek article The Science of Death: Reviving the Dead
Dr. Becker's profile at Penn
and his research group
New York Times Chill Therapy Is Endorsed for Some Heart Attacks
Univ of Chicago Rapid Cooling Technique May Save Victims of Sudden Cardiac Death
Univ of Chicago Induced hypothermia is underused after resuscitation from cardiac
Wake County EMS Blog ICE - Induced Cooling by EMS
an Emergency Medical Service that is implementing these methods
University of Pittsburgh Health Sciences matching faculty found for hypothermia, induced
Laura’s Psychology Blog Rethinking death…
Maddy's ramblings straight to the heart of the matter
RN Web The big chill: Improving the odds after cardiac arrest
The Hypothermia Network
American Heart Association Therapeutic Hypothermia After Cardiac Arrest
Society of Cardiovascular Anesthesiologists Recommendation for Application of Therapeutic Hypothermia to Cardiac Arrest Victims
American College of Emergency Physicians Focus On: Therapeutic Hypothermia
EMS Responder COLD Care Wake County EMS develops protocols for induced hypothermia
Massachusetts General Hospital Hypothermia after Cardiac Arrest
Northern Hypothermia Network Protocols

8 commercial medical equipment suppliers for Critical Hypothermia induction needed to cool the body to prevent rapid permanent death from mitochondrial catalysis are linked below.

Of only about 225 hospitals, out of more than 5,700 hospitals in the United States have this critical equipment needed for saving lives from permanent death.

Ask if your local hospitals have this critical hypothermia(cooling) inducing equipment, if they don't, then bang the doors of complacency DOWN, crack open the inertia of the physicians, and get the hospital to both BUY the hypothermia induction equipment, and for staff in emergency medicine to read the later and earlier articles linked above, and many protocols to start saving heart attack victims NOW.

If your local hospital does not do this quickly, then plaster copies of these articles throughout hospital department staff mailboxes, and get your local newspapers to write articles about Dr. Becker's work ASAP.

If all it took was cooling your loved one soon after an otherwise fatal heart attack to bring them back to life, and your hospital did not do this just because of complacency with current commonly accepted but WRONG therapies, shame them into learning Dr. Becker's techniques NOW, even for ambulance treatments.

Cooling Device Manufacturers and Assigned Patents (note these may in some cases include patents unrelated to patient cooling)

A presentation by Penn "Hypothermia after cardiac arrest"

here is a list of hypothermia clinical protocols from different hospitals - links from Penn
Here is a list of research journal articles using the Medivance system for inducing hypothermia for medical treatment benefits.

Publications Referring to Medivance Arctic Sun®

  1. Calver P, Braungardt T, Kupchik N, Jensen A, Cutler C. The big chill: improving the odds after cardiac arrest. RN 2005; 68:58-62.
  2. Carhuapoma JR, Gupta K, Coplin WM, Muddassir SM, Meratee MM. Treatment of refractory fever in the neurosciences critical care unit using a novel, water-circulating cooling device: a single-center pilot experience. J Neurosurg Anesthesiol 2003; 15:313-318.
  3. Geocadin RG, Carhuapoma JR. Medivance Arctic Sun Temperature Management System. Neurocrit Care 2005; 3:63-67.
  4. Holden M, Makic MB. Clinically induced hypothermia: why chill your patient? AACN Adv Crit Care 2006; 17:125-132.
  5. Ly HQ, Denault A, Dupuis J, Vadeboncoeur A, Harel F, Arsenault A, Gibson CM, Bonan R. A pilot study: The Noninvasive Surface Cooling Thermoregulatory System for Mild Hypothermia Induction in Acute Myocardial Infarction (The NICAMI Study). Am Heart J 2005; 150:933.
  6. Mahmood MA, Voorhees ME, Parnell M, Zweifler RM. Transcranial Doppler ultrasonographic evaluation of middle cerebral artery hemodynamics during mild hypothermia. J Neuroimaging 2005; 15:336-340.
  7. Mayer SA, Kowalski RG, Presciutti M, Ostapkovich ND, McGann E, Fitzsimmons BF, Yavagal DR, Du YE, Naidech AM, Janjua NA, Claassen J, Kreiter KT, Parra A, Commichau C. Clinical trial of a novel surface cooling system for fever control in neurocritical care patients. Crit Care Med 2004; 32:2508-2515.
  8. Scott BD, Hogue T, Fixley MS, Adamson PB. Induced Hypothermia Following Out-of-Hospital Cardiac Arrest; Initial Experience in a Community Hospital. Clin Cardiol. 29, 525-529 2006.
  9. Zweifler RM, Voorhees ME, Mahmood MA, Alday DD. Induction and maintenance of mild hypothermia by surface cooling in non-intubated subjects. J Stroke Cere Dis 2003; 12:237-243.
  10. Zweifler RM, Voorhees ME, Mahmood MA, Parnell M. Rectal Temperature Reflects Tympanic Temperature During Mild Induced Hypothermia in Nonintubated Subjects. J Neurosurg Anesthesiol 2004; 16:232-235.
  11. Zweifler RM, Voorhees ME, Mahmood MA, Parnell M. Magnesium sulfate increases the rate of hypothermia via surface cooling and improves comfort. Stroke 2004; 35:2331-2334.
Here are more general research references
Two books

Therapeutic Hypothermia (Hardcover) by Stephan A. Mayer (Editor), Daniel I. Sessler (Editor)

Therapeutic Hypothermia (Molecular & Cellular Biology of Critical Care Medicine) (Hardcover) by Samuel A. Tisherman (Editor), Fritz Sterz (Editor)

There seem to be a few other research efforts in this area of controlled resuscitation by hypothermia.
This appears to be excellent innovative medical science, that might well soon transform patient prognoses for the better.

Here is an excerpt from the recent Newsweek article of July 2007
By Jerry Adler with Matthew Philips, Joan Raymond and Julie Scelfo

"How long has it been since you've read an article about heart attacks that didn't mention saturated fats? Our age is obsessed with "health," but when health fails, the last line of defense is in the emergency room, where doctors patrol the border between life and death—a boundary that they have come to see as increasingly uncertain, even porous. This is a story about what happens when your heart stops: about new research into how brain cells die and how something as simple as lowering body temperature may keep them alive—research that could ultimately save as many as 100,000 lives a year. And it's about the mind as well, the visions people report from their deathbeds and the age-old questions about what, if anything, outlives the body.

It begins with a challenge to something doctors have always been taught in medical school: that after about five minutes without a pulse, the brain starts dying, followed by heart muscle—the two most voracious consumers of oxygen in the body, victims of their own appetites. The emerging view is that oxygen deprivation is merely the start of a cascade of reactions within and outside the cells that can play out over the succeeding hours, or even days. Dying turns out to be almost as complicated a process as living, and somehow, among its labyrinthine pathways, Bondar found a way out.

Monica tried to recall what she had learned in a CPR class decades earlier. She bent over Bondar and began pushing down on his chest, then rushed back to the kitchen to dial 911. "My husband is dying!" she gasped to the operator.

Compressing Bondar's chest would have sent a trickle of blood to his brain, supplying a fraction of its normal oxygen consumption, not enough to bring him back to consciousness. But the West Deptford police station was only three blocks away, and within two minutes of Monica's call three officers arrived with a defibrillator. They placed the pads on Bondar's chest, delivered two jolts of electricity to his heart, and got a pulse back. Soon paramedics arrived with oxygen and rushed him to a nearby community hospital. The report Monica received there after an hour was equivocal: Bondar was "stable"—his heart rate and blood pressure back to near normal—but he was still in a coma. It was then that Monica made a decision that may have saved his life. She asked that her husband be moved the 15 miles to Penn, the region's leading university hospital.

Dr. Lance Becker, director of Penn's year-old Center for Resuscitation Science, frequently dreams about mitochondria: tubular structures within cells, encasing convoluted membranes where oxygen and glucose combine to produce the energy the body uses in moving everything from molecules across cell membranes to barbells. Recently mitochondria have been in the news because they have their own DNA, which is inherited exclusively down the female line of descent, making them a useful tool for geneticists and anthropologists.

But Becker is interested in mitochondria for another reason: he believes they are the key to his audacious goal of tripling the time during which a human being can go without a heartbeat and still be revived. That the five-minute rule is not absolute has been known for a long time, and the exceptions seem to involve low temperatures.

Children who fall through ice may survive unexpectedly long immersions in cold water. On Napoleon's Russian campaign, his surgeon general noticed that wounded infantrymen, left on the snowy ground to recover, had better survival rates than officers who stayed warm near the campfire. Becker is hoping to harness this effect to save lives today.

Becker is 53, slender and boyish in a way that belies his thinning hair; his typical greeting to colleagues is a jaunty "What's up, guys?" For his lab he has assembled a high-powered team from a wide range of specialties, including a brilliant young neuroscientist, Dr. Robert Neumar; an emergency-medicine specialist, Dr. Ben Abella; plus cardiologists, biochemists, bioengineers and a mouse-heart surgeon. His associate director, Dr. Vinay Nadkarni, comes from pediatrics.

Becker has in effect re-created at Penn, on a more ambitious scale, the laboratory he founded in 1995 at the University of Chicago, with a grant of $50,000 from the philanthropist Jay Pritzker. Ten years earlier Pritzker had walked into the emergency room at Chicago's Michael Reese Hospital complaining of chest pains, and crumpled to the floor. Becker resuscitated him, the beginning of both a rewarding friendship (Pritzker lived for 14 more years) and a new direction for Becker's career. "Every day since then," he says, "I would go home and wonder why Jay Pritzker got a second chance and so many other people didn't."

Becker's interest in mitochondria reflects a new understanding about how cells die from loss of circulation, or ischemia. Five minutes without oxygen is indeed fatal to brain cells, but the actual dying may take hours, or even days. Doctors have known for a long time that the consequences of ischemia play out over time. "Half the time in cardiac arrest, we get the heart going again, blood pressure is good, everything is going along," says Dr. Terry Vanden Hoek, director of the Emergency Resuscitation Center at the University of Chicago, "and within a few hours everything crashes and the patient is dead."

It took some time, though, for basic research to supply an explanation. Neumar, working with rats, simulates cardiac arrest and resuscitation, and then examines the neurons at intervals afterward. Up to 24 hours later they appear normal, but then in the next 24 hours, something kicks in and they begin to deteriorate. And Dr. James R. Brorson of the University of Chicago has seen something similar in neural cells grown in culture; deprive them of oxygen and watch for five minutes, or even much longer, and not much happens. "If your car runs out of gas, your engine isn't destroyed, it just needs fuel," he says.

Cell death isn't an event; it's a process. And in principle, a process can be interrupted. The process appears to begin in the mitochondria, which control the cell's self-destruct mechanism, known as apoptosis, and a related process, necrosis.

Apoptosis is a natural function, destroying cells that are no longer needed or have been damaged in some way. Cancer cells, which might otherwise be killed by apoptosis, survive by shutting down their mitochondria; cancer researchers are looking for ways to turn them back on. Becker is trying to do the opposite, preventing cells that have been injured by lack of oxygen from, in effect, committing suicide.

It's a daunting problem. "We're asking the questions," says one leading researcher, Dr. Norm Abramson of the University of Pittsburgh. "We just haven't found the answers." Until recently, the conventional wisdom was that apoptosis couldn't be stopped once it was underway. It proceeds by a complex sequence of reactions—including inflammation, oxidation and cell-membrane breakdown—none of which seems to respond to traditional therapies. Becker views cell death in cardiac arrest as a two-step process, beginning with oxygen deprivation, which sets up the cell for apoptosis; then the heart starts up again and the patient gets a lungful of oxygen, triggering what is called reperfusion injury. The very substance required to save the patient's life ends up injuring or killing him.

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."


"We are, Becker believes, at the forefront of a revolution in emergency medicine destined to save millions of lives in the years ahead. This is doctoring at its most basic, wresting people back from death. "I have been fighting with death for 20 years," he says. "And I'll keep doing it, I think, until I meet him in person."

Bless you Dr. Becker .... we need more physicians using your excellent research work NOW.

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Anonymous greg said...

Mr. Wendman,

Thank you for your article. I am actively involved inthis field as a clinical professional. Feel free to contact me if you would like to get your hands on some of the technology ;)


4:41 PM  

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