Oxygen is vital for life—without it, severe brain damage may ensue in as little as three minutes. So doctors routinely treat traumas such as heart attack or stroke by providing victims with more oxygen. Mounting evidence suggests, however, that resuscitating with too much of the gas may actually have a harmful effect. The culprit in brain damage may not be a lack of oxygen but rather its reintroduction into the body.

Researchers at the University of Texas Southwestern Medical Center at Dallas reported in the Journal of Cerebral Blood Flow and Metabolism on March 12 that resuscitating baby mice with pure oxygen caused more brain damage and cerebral palsy–like coordination problems, as compared with mice that breathed air during resuscitation.

“Our results are counterintuitive,” says developmental biologist Steven Kernie, lead author of the study. “Many think oxygen doesn’t hurt and you can give as much as possible to make up for a deficiency. Our study shows this notion is wrong.”

Although Kernie’s study does not exactly mimic patient care—physicians usually administer slightly above air’s 21 percent oxygen and rarely more than 60 percent—it raises the important possibility that doctors are treating patients the wrong way, says Lance Becker, professor of emergency medicine at the University of Pennsylvania School of Medicine and director of its Center for Resuscitation Science*, who similarly showed in 2004 that cells were much more likely to die after being reexposed to oxygen than they were when deprived. In fact, Becker explains, physicians do not know how much is too much or whether administering extra amounts actually benefits patients at all.

So why would treating injuries with a molecule that fuels life actually do the reverse? Evidence suggests that pumping in too much oxygen too quickly can strip the molecule of a single electron, creating a free radical. Free radicals, linked to rapid aging, are highly reactive with other molecules, including vital DNA and proteins, the destruction of which can damage or kill cells.

Treating with too much oxygen, therefore, could increase the production of free radicals and make a bad situation even worse. The key is to find that “sweet spot,” Becker says—the optimal amount to give a person so he or she can recover with minimal damage.

A Chilly Solution
How can doctors avoid the toxic effects of reintroducing oxygen to the body after a trauma? Hypothermia therapy—lower­ing a patient’s body temperature to decrease metabolic rate and thus the need for oxygen—may be a solution, according to Hasan Alam, a trauma surgeon at Massachusetts General Hospital who established that the therapy worked in critically wounded Yorkshire pigs. The technique is popular for preserving transplant organs and reducing the need for oxygenated blood during heart surgery, but it has not been widely tested in trauma patients. De­spite its high-profile use on profes­sion­al football’s Kevin Everett after his paralyzing spine injury in September 2007, hypothermia treatment remains controversial, and studies of its ef­fec­tiveness are inconclusive.

Note: This article was originally printed with the title, "The Oxygen Dilemma".

*Erratum (10/28/08): Lance Becker was originally identified as the director of emergency medicine at the University of Pennsylvania School of Medicine.

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