News | April 02, 2007

FDA: Anesthesia Harmful to Children?

April 3, 2007 - Anesthesia can be harmful to the developing brain, studies on animals suggest, raising concerns about potential risks in putting young children under for surgery.

FDA scientists stressed Thursday they have no evidence that anesthesia and sedation drugs, which have been commonly administered for decades, can cause brain damage in children.

But numerous animal studies find that a majority of the drugs typically used to knock out children before surgery do kill brain cells in young rats, mice and — preliminary results suggest — rhesus monkeys.

"A safety signal has been identified in animals for many drugs used to provide sedation and anesthesia. This database is growing. The relevance of the animal findings to pediatric patients is unknown," Dr. Arthur Simone, an FDA medical officer, told experts gathered by the agency to discuss the issue.

Experiments on laboratory rats and other animals have shown that the drugs can lead to subtle but prolonged changes in behavior, including memory and learning impairments, according to a study published by FDA scientists this month in the journal Anesthesia & Analgesia.

Scientists don't know if those study findings apply to children. Nor have comparable human studies been done that might provide answers.

Even detecting the effect of ketamine, halothane and other anesthetics on the central nervous system is difficult if not impossible in the young, according to the FDA. Unlike, say, fetal alcohol syndrome, there is no clear-cut collection of disorders associated with anesthesia exposure, said Dr. Bob Rappaport, head of the FDA's anesthesia office and one of the study's authors.

The FDA published the study and convened a public meeting to alert other experts to its concerns, as well as to update them on research and outline tentative plans for future studies.

Some drugs appear to cause more harm to animals than others, the FDA and other experts said. Furthermore, in some drugs both dose size and duration may affect the brain differently. And some combinations of drugs — like the triple "cocktail" of isoflurane, midazolam and nitrous oxide — may be more toxic to the brain than any one used individually.

Still, panel members agreed unanimously that there isn't enough information to say any one drug or drug combination is safer than any other.

The animal studies suggest young animals are most susceptible to the drugs during the period of rapid growth of the brain. In humans, that period begins before birth, in the third trimester, and extends to about age 3. An estimated 600,000 children within that age range receive general anesthesia each year in the United States, including during operations to place ear tubes, repair hernias or stitch up serious wounds, said Dr. C. Dean Kurth, anesthesiologist-in-chief at Cincinnati Children's Hospital Medical Center.

Many of the operations performed on children are to save their lives or improve their quality of life. Since they're typically not elective, skipping or even delaying such surgeries would have its own risks, according to FDA officials.

"We're certainly not looking at saying anesthesia should not be used on children," Rappaport told The Associated Press, adding that it's generally considered one of medicine's greatest advances.

Nor are there any good alternatives to the current menu of anesthetic drugs, experts said. And surgery ethically cannot be performed without anesthesia.

"These findings have potentially important public health implications, and pose a therapeutic dilemma for physicians," said Dr. John Olney, of Washington University School of Medicine.

"You don't come in for anesthesia. You come in for something else and you can't not have it. And not having surgery can have more far-ranging consequences than what the panel's talking about," said Kurth, who's also a spokesman for the American Society of Anesthesiologists. He pointed out that anesthesia in some heart and other surgeries can protect the brain by making it more resilient to decreased levels of oxygen in the blood.

In the short term, Olney recommended studying in animals the potential risk to the developing brain of all anesthetic drugs used singly and in combination. Only those with the widest safety margins then could be used in children. Longer term, Olney suggested developing drugs that could be given with anesthesia to blunt its cell-killing effect.

When asked how the animal findings would affect how they treat children, several panel members recommended delaying surgeries in the very young when possible, even if only for a few months. Others recommended moderation.

"Once you give it, you give it, so try to get away with giving as little as you can," said Dr. Athena Zuppa of Children's Hospital of Philadelphia.

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