Could Anesthesia Cause Developmental Disorders?

Medicine changed for the better one day in 1846 when a Boston man became the first human to undergo an operation without feeling any pain. The magic bullet? Anesthesia. Today, drugs that dull the agony of surgery are used routinely, even in very young children who receive the meds when they need bad cuts stitched up or tubes inserted into their ears to reduce infections. But the drugs are not risk-free. This week, Columbia University researchers presented a study at the annual meeting of the American Society of Anesthesiologists showing a possible link between exposure to anesthesia and behavioral and developmental disorders in young children. Scientists say the new research is in no way conclusive and parents should not be alarmed. Still, says the study's lead author, Dr. Lena Sun, this is "something we can't ignore."

Using a database of Medicaid patients in New York, the Columbia scientists compared a group of 625 children under the age of 3 who had received general anesthesia for hernia repair to a group of 5,000 kids who never had the surgery. They found that kids who had hernia surgery and received anesthesia were twice as likely to be diagnosed with a developmental or behavior disorder within two years. Because the study relied on past history and billing codes, "there are definitely limitations," says Sun. One example: researchers don't know any details about the kinds of disorders the children actually had. The study is "provocative," says Sun, "but very preliminary." An estimated 4 million children receive anesthesia every year, Sun says, not just for surgery but for diagnostic procedures like MRI and CAT scans.

The new report, not yet published, was prompted by prior studies showing that anesthesia can harm the developing brain in animals. In one 2003 study, scientists found that a combination of three anesthetic drugs given to seven-day-old rats resulted in brain-cell death at a critical time in brain development. And rats that received the medications had persistent learning and memory problems. That study and others got the attention of pediatric anesthesiologists and neurologists and prompted the Food and Drug Administration (FDA) to organize a meeting in 2007 to discuss the research. At that time, FDA scientists stressed that there was no evidence that anesthesia caused problems in children, but they called on the anesthesia community to continue to study the medications. In a special report published last year, FDA researchers said anesthesiologists should "attempt to minimize exposure to potentially offending drugs when possible, to consider alternative therapies as may be available, and to remain vigilant as new information is developed."

Major trials now in the works may answer more questions. Sun and colleagues are launching a study that will analyze a group of children who had general anesthesia before their 4th birthdays. The kids, who'll be compared to siblings who never had anesthesia, will undergo comprehensive neuro-developmental testing between the ages of 6 and 10. And Dr. Mary Ellen McCann, an assistant professor of anesthesiology at Harvard Medical School, is initiating a study with collaborators in Australia, the United Kingdom and Europe that will compare regional, or localized, anesthesia to general anesthesia in young children. The kids will be given a developmental test at age 2 and an intelligence test at age 5. The goal: to see if there's any difference in cognition between the two groups. If one approach turns out to be safer, parents might be able to make a more informed choice about the kind of anesthesia their child receives.

Anesthesia is both necessary and helpful. Too little can even be harmful in kids: a landmark study published in the early 1990s found that a newborn's chance of surviving a heart operation improved dramatically if he was given deep rather then light anesthesia. The stress of pain, it turned out, made surgery riskier. "That changed the way we felt about newborns," says McCann. It's also too early to tell if the troubling effects seen in animals will translate to humans and if they do, whether or not they'll persist long-term. Sun, who researched the impact of cocaine on fetuses remembers that scientists were extremely concerned about developmental issues in so-called "crack babies." Studies did show problems early on, Sun says, but the children outgrew them over time. "Children are extremely resilient," she says. "The prenatal cocaine story is one we need to remember when we start talking about the neurotoxicity of anesthetic agents."

Still, the possibility that anesthesia could cause brain damage is worrisome, and pediatric anesthesiologists and neurologists are watching developments carefully. Some experts believe that a parent might consider postponing a procedure, especially if the child is an infant and the surgery is totally elective. But many operations performed early on in life cannot be put off. And children receive anesthesia safely all the time, despite the rare risks that are known, such as breathing difficulties and allergic reactions. "I don't think [the new study] should deter any parent from taking their child in for needed surgery," says Sun, "because in the end, that's going to be much worse than any potential problems."

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