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San Francisco Examiner, Are redheads harder to knock out before surgery?, October 14, 2002

The genetic quirk that makes red hair red may also make carrot-tops harder to knock out — in the operating room, that is.

A new study suggests people with naturally red hair need about 20 percent more anesthesia than patients with other hair colors.

It's a small study that will need confirmation. But it marks the first time scientists have linked a visible genetic trait to anesthesia doses, said Dr. Daniel Sessler of the University of Louisville, whose study will be presented Tuesday at a meeting of the American Society of Anesthesiologists.

Inadequate doses of general anesthesia can allow people to recall surgery, or even wake up during it, problems that occur in 1 percent of cases, Sessler said.

"If redheads require more anesthesia and are not given more, their chances of having recall during surgeries increase," he said.

Determining a patient is properly anesthetized is a partly an art: Physicians must watch for sometimes subtle signs of an underdose, like slight movements or sweating, as well as overdose warnings such as low blood pressure or heart rate. So knowing if a particular group of people is more likely to need a higher- or lower-than-standard dose could be very useful.

Anesthesiologists have long grumbled that redheads can be a little harder to put under, but no one had ever studied if that was real or folklore, said Dr. Andrea Kurz of Washington University in St. Louis, who praised the new research.

It's likely the first of many yet-to-be-discovered genetic factors that will allow anesthesia to be fine-tuned for increased safety, added Dr. James Cottrell, president of the anesthesiology society. "It's a very exciting area."

But why would hair color possibly matter? The theory hinges on melanin, a pigment responsible for skin and hair color.

The sun triggers a hormone that in turn triggers the production of melanin to form a tan. Redheads seldom tan easily because they have a defective receptor for that hormone — a quirk with this "melanocortin-1 receptor" that also leaves their hair red. Without its intended receptor to dock in, the melanin-producing hormone may cross-react with a related receptor on brain cells that influences pain sensitivity, Sessler explained.

That's still a theory. Here's what Sessler can say for certain: He and colleagues gave 10 healthy women with naturally red hair and 10 with dark hair the common inhaled anesthetic desflurane. Then they administered electric shocks — not enough to do damage but enough to cause pain — and inched the desflurane dose up or down according to the pain response until each patient was judged to be at the optimum anesthetic dose. The redheads required a 20 percent higher dose.

Sessler said his lab first tested a few blondes and found they reacted the same as brunettes. That was expected since only redheads have the melanocortin-1 defect.

The study doesn't address if men would react similarly — there are gender differences for many drugs — or if redheads would be similarly affected by non-inhaled types of anesthesia.

Still, the research "gives us a window into what determines anesthetic requirements," said Sessler, whose lab is beginning more studies to see if the melanin theory is right.

Lauran Neergaard

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