Repeated early exposure to anesthesia associated with learning disability

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April 7, 2009 — Repeated exposure to anesthesia before the age of 4 years is associated with almost double the risk of developing a learning disability (LD) later on, according to a new study published in the April issue of the journal Anesthesiology.

However, though the research showed a clear association between multiple episodes of anesthesia and learning disabilities, it cannot yet be concluded that anesthesia causes the disability, said Randall P. Flick, MD, chair of the division of pediatric anesthesiology and an assistant professor of anesthesiology and pediatrics at the Mayo Clinic in Rochester, Minnesota.

Dr. Flick and his colleagues analyzed outcomes in a cohort of children born in and around Rochester, Minnesota, between January 1, 1976, and December 31, 1982.  The data index included information on the type and duration of surgery, number of anesthetic exposures, age at exposure, type of anesthetic agent, and mode of delivery (inhaled, intravenous, sedative), as well as information on comorbidities. From the original cohort, 5357 children were included in this current study. Of these, 593 underwent procedures requiring general anesthesia before the age of 4 years. These 593 children underwent 875 procedures. Most anesthetics included halothane (88%) and nitrous oxide (91%). Dr. Flick said this was typical practice at the time of the study, although halothane is no longer used in the United States, having been replaced by a similar agent.

Assessing Disabilities

To test for LD, they used standard formulas, IQ scores, and academic-achievement results to detect the presence of reading, writing, language, or mathematics disabilities.

A total of 932 children developed an LD before the age of 19 years. Compared with children not exposed to anesthesia, the risk of developing an LD was not increased for the 449 children exposed to a single anesthetic. However, the risk was significantly increased for children exposed to 2 or more doses of anesthesia. Risk for Learning Disabilities Associated With Exposure to Anesthetics The estimated incidence of LD by the age of 19 years was 20.0% (95% confidence interval [CI], 18.8% – 21.3%) in those with no exposure to anesthesia, 20.4% (95% CI, 16.3% – 24.3%) in those with a single exposure, and 35.1% (95% CI, 26.2% – 42.9%) in those with multiple exposures.

In addition, the risk for LD was increased with longer duration of anesthesia exposure; it reached statistical significance at a cumulative duration of 120 minutes or more. Exposure Before the Age of 2 Years Although the study included surgeries up to the age of 4 years, the authors repeated their analysis restricting exposure to anesthesia to before the age of 2 years and found the risk for LD to be similar.

In fact, "the analysis showed that the effect seemed most pronounced among children whose initial exposure to anesthesia occurred between their first and second birthday," said Dr. Flick.

This study was the next step following extensive animal research that had similar results. "We have a large and growing body of animal evidence that not only is there pathologic brain injury but there are also learning deficits, memory deficits, and behavioral deficits in animals" exposed to anesthesia at an early stage, said Dr. Flick. "These findings have been repeated in various labs with various species and using different tests, so the animal data is pretty strong. The question was, does this translate to humans or not?" Among the study's limitations is its inability to distinguish the effects of anesthesia from that of other factors such as the stress response to surgical injury. As well, the authors said they could not exclude the possibility that requiring anesthesia is a marker for something other than LD. Because of its superior healthcare, the population under study may overrepresent children with medical needs.

The study population is also predominantly white and middle class, so these findings may not apply to other populations.

Best Learning Opportunities

The message is that parents should be cautious about any surgery their child undergoes and make sure the intervention is necessary. He pointed out that once it was common for children to routinely have their tonsils removed and be treated with antibiotics for any ear infection — practices now judged unnecessary.
Support was provided by the Department of Anesthesiology at the College of Medicine, Mayo Clinic, and from research grants from the National Institutes of Health. The authors have disclosed no relevant financial relationships. Anesthesiology. 2009;110:796–804.

Clinical Context

Laboratory studies have shown that immature animals given anesthetic drugs may develop neurohistopathologic abnormalities and behavioral changes. In some studies, even relatively brief single exposures resulted in changes, especially when combinations of agents were used.

Pearls for Practice •

In a population-based birth cohort in Olmsted County, Minnesota, exposure to anesthesia before 4 years of age was a significant risk factor for the later development of LD in children.
A single exposure to anesthesia (n = 449) was not associated with an increased risk for LD compared with those not receiving anesthesia, but risk for LD was increased in children receiving 2 anesthetics and increased further for those receiving 3 or more anesthetics. •
Longer cumulative duration of anesthesia exposure, expressed as a continuous variable, was associated with increased risk for LD. These findings suggest a dose–response relation between anesthetic exposure and LD.

Matthew.wang

“"the analysis showed that the effect seemed most pronounced among children whose initial exposure to anesthesia occurred between their first and second birthday,"

3岁以后会不会对LD影响就比较小，19岁以后exposure to anesthesia基本没有影响

shenxiu2

2# Matthew.wang
The study seems to show this . Probably due to the anesthetic effect on the developing brain tissue. As you know, the brain is still developing until  the age of 2-3 years old.

635878089

Clinical Context

Laboratory studies have shown that immature animals given anesthetic drugs may develop neurohistopathologic abnormalities and behavioral changes. In some studies, even relatively brief single exposures resulted in changes, especially when combinations of agents were used.

临床背景

实验室研究表明，在一些研究中，即使是相对短暂的暴露导致的变化，不成熟的动物麻醉药物可能发展的神经组织病理学异常和行为改变，尤其是当使用的药物组合。