Saturday, June 9, 2007

Holy Crap: Doctor's Create Fake Blood That Can Save Lives!

A man-made, pure-white compound called Oxycyte carries oxygen 50 times as effectively as our own blood and researchers are betting that it’s the best way to treat America’s leading cause of accidental death: traumatic brain injury. Oxycyte is a completely synthetic substance made from perfluorocarbons, or PFCs, a compound whose chemical makeup closely resembles the nonstick Teflon in your frying pan. PFCs have the highest gas-dissolving capacity of any liquid and, when used with supplemental oxygen, allow blood to carry many times more oxygen than it normally does (and to carry more oxygen faster and more easily than hemoglobin-based substitutes).

In an example of this drugs effectivness, two women were bicycling down a steep hill, headed toward a busy intersection, when Bess-Lyn yelled that her brakes weren’t working and she couldn’t slow down. Her friend screamed for her to turn into an alley just before the intersection. But Bess-Lyn didn’t turn sharply enough and crashed, headfirst, into a concrete wall. She wasn’t wearing a helmet. By the time the ambulance reached the hospital, Bess-Lyn was officially counted among the 1.5 million Americans who will suffer a traumatic brain injury (TBI) this year. With her mother’s verbal consent, Bess-Lyn was treated with a type of artificial blood called Oxycyte, the subject of a clinical trial led by doctors at the teaching hospital of Virginia Commonwealth University. In animal tests, the compound has been proven to cut the effects of brain damage nearly in half, presumably because its tiny particles can ferry oxygen through swollen, injured vessels our own red blood cells can’t squeeze through. (The suffocation of brain cells is a major contributor to brain damage.) The doctors’ next step is to get the same result in accident victims like Bess-Lyn, who became the third of eight patients to be enrolled in the hospital’s pilot Phase II clinical trial, designed to test the drug’s safety and efficacy. If Oxycyte performs well in subsequent trials, it will become the first drug the FDA approves to treat traumatic brain injury in the U.S. and in hot spots like Iraq, where TBI has become horrifyingly common.

After two decades and a billion dollars’ worth of research, the most valuable lesson learned was that real blood and artificial bloods were apples and oranges: The life-giving liquid in our veins acts like a supply line for everything from nutrients to hormones to oxygen, even working double-time to regulate our blood pressure and fight infection. The manufactured substances, on the other hand, are one-trick ponies for oxygen delivery. But it’s a trick they perform remarkably well—in the case of PFC-based substitutes, carrying oxygen at rates roughly 50 times that of our own blood. Doctors are betting that a successful pilot trial of Oxycyte will win the attention—and influence—of the armed forces, which would help usher the drug through the clinical-trial process and into the hands of doctors and medics in the near term. At least that’s the hope—or rather, the careful, calculated plan—of Bruce Spiess.

Dr. Bruce Spies heads the Virginia Commonwealth University Reanimation Engineering Shock Center.Formed in 2000, the institute, which goes by the acronym VCURES, comprises some 50 scientists, engineers and doctors, all focused on developing treatments for traumatic injury. Artificial blood, however, is perhaps VCURES’s most ambitious project. And artificial blood’s most dedicated advocate at VCURES is Bruce Spiess. “I realized very early on that going head to head with a unit of blood was going to be difficult,” Spiess, 52, says from behind his cluttered desk. “Instead, why not take these compounds, understand how they deliver oxygen to tissues better than blood stored from a bank, and use that as a real advantage. Go find some diseased states to treat that, right now, we don’t have a treatment for.” He leans back in his chair and smiles, as if this last point is so obvious he can’t believe he’s still making it.

Synthetic Blood International, the maker of the PFC Oxycyte. and Spiess teamed up to design the Phase II pilot trial (Bullock had earlier conducted successful animal studies with the drug). The trial, Spiess says, is the first step in determining whether Oxycyte will ultimately be adopted to treat a wide array of injuries, including traumatic brain injury, which affects everyone from car-accident victims to pummeled boxers to bicyclists. Aside from giving patients oxygen and anti-inflammatories and, in extreme cases, removing part of the skull to release the pressure of the swelling brain, there are few treatments for TBI—and no drug therapy. Which is precisely why Spiess has chosen to focus on it. Once the spinal cord—or any organ—is injured, these incredibly narrow vessels constrict even further, a reaction some researchers believe must be the body’s way of preventing blood loss. The defense mechanism’s unfortunate side effect is that it starves the damaged tissue of oxygen until the veins collapse and, in extreme cases, the tissue dies. Rats that received PFCs in his study maintained a healthy grove of veins even after injury, since the oxygen levels in their spinal cords were six times as high as in the rodents that didn’t get Oxycyte. “It’s like a miracle drug,” he says. “Like pouring oxygen over the tissues.”

A wonder drug, perhaps, but one with caveats. Most of those in the artificial-blood world have hedged their bets on the more common hemoglobin-based substitutes. “The benefit of hemoglobin-based oxygen carriers is that oxygen is loaded onto them when we’re breathing room air,” Gould says. That is, hemoglobin-based substitutes work just like our own blood. To get the full effect from Oxycyte, on the other hand, a patient breathes in 50 to 100 percent oxygen four hours before receiving it and for 12 hours after it’s infused (air contains 21 percent oxygen). “That’s a logistical limitation,” Gould says, “and in general, it’s preferable not to breathe supplemental oxygen if it can be avoided.” Most of today’s ambulances carry oxygen on board, as do military rescue helicopters, so the problem isn’t getting a tank of air to the patient. It’s the risk of inhaling supplemental oxygen for too long. Scientists know that pure oxygen increases the number of free radicals in our bloodstream, which can damage tissues and membranes, but the long-term severity of that damage is unknown. Spiess believes that Oxycyte could still work at even lower levels of oxygen, or even with room air, but he hasn’t yet been able to test out either of those scenarios on humans.

There are other, undeniable side effects. In past PFC studies, patients were found to experience a transient swelling of the liver as it absorbed the oily molecules of the PFC; some patients demonstrated a decrease in platelet count, which can hinder the blood’s ability to clot; and some suffered short-term flu-like effects. Spiess has a quick response to concerns like these: “If you’ve been hit in the head or you’ve been shot or you’re having a stroke, you don’t sweat the flu-like symptoms.” All drugs have some measure of toxicity, Spiess says. It’s simply a case of the good outweighing the bad. Although the sample size is far too small to be statistically definitive, it seems that VCURES’s brain-injury trial may be an example of just that. By August, the hospital had enrolled all of the eight patients it needed to complete the Phase II study. Even at the best trauma centers in the world, the mortality rate for TBI victims is one in three. Of the eight patients Spiess and Bullock treated with Oxycyte, only one died. The recovery process for the surviving patients has been unusually smooth.

Extraordinarily so, in Bess-Lyn’s case. After regaining consciousness two weeks after the accident, she recovered movement in her paralyzed right side and was ultimately deemed well enough to leave rehab a week earlier than predicted. She is expected to make a full recovery. Meanwhile, Spiess and Bullock are busy designing a larger trial that will bring their oxygen therapy to emergency rooms across the country—perhaps as soon as next year.

In my opinion, after seeing stroke victims and people with serious head injuries, I think the benefits of this type of drug exceeds the risk. With all the bad press the FDA gets over "pushing" drugs through clinical trials, I think this one had got incredible potential...for us and our soldiers overseas. Keep up the good work Dr. Spies!