An anesthetic regimen commonly used during surgery on pregnant mothers appears to have no negative effects on the developing brain of the fetus, according to a new study on sheep conducted by Duke University Medical Center researchers.
Furthermore, the researchers found, the use of this regimen to produce general anesthesia appears to improve the oxygenation of the fetal brain, according to their novel system for measuring cerebral oxygenation in the developing fetus.
These findings are an important step toward better understanding this issue, the researchers said, since a study in new-born rats published in 2003 reported that exposure to various anesthetic agents caused neurodegeneration in the developing rat brain. However, the Duke researchers said that the current study may be more realistic, since it is was conducted under circumstances that more closely parallel that which humans would experience.
"The results of this investigation suggest that the moderate inhalation anesthetic exposure during pregnancy may not be deleterious to the fetus," said lead researcher James D. Reynolds, Ph.D., research director of women's anesthesia at Duke. The results of the Duke study were published March 9, 2005, as an advanced on-line publication of the Journal of Cerebral Blood Flow and Metabolism.
"These types of studies are very difficult to conduct in humans, since you can't do the invasive type of monitoring you can in animal models, and it is difficult to separate the effects of the anesthesia from the underlying reasons for the surgery," Reynolds said. "So we felt that in order to come as close as possible to what might be expected in humans, we had to do something new."
General anesthesia, which typically involves a combination of drugs, renders the patients temporarily unconscious during the surgery.
The earlier study -- the results of which led to much discussion in the anesthesia community -- involved putting newborn rat pups in a static chamber, where they inhaled various anesthetics. The results of those studies showed evidence of increased apoptosis, or programmed cell death, in developing nerve cells.
For their new experiments, the Duke team developed a model using pregnant sheep. When the sheep fetus was approximately 17 weeks old – an age that approximates a third-trimester human pregnancy – the researchers exposed the mother to a three-drug anesthetic combination commonly used to produce general anesthesia. The exposures lasted four hours, a length of time that would encompass most surgeries conducted on pregnant patients.
"We found that four hours of maternal general anesthesia produced an initial increase in systematic oxygenation in the fetus, as well as a sustained increase in oxygenation in the brain," Reynolds said.
The researchers could document cerebral oxygenation in real time because of a system they optimized for fetal applications. The technique, called near-infrared spectroscopy, was originally conceived in the 1970s by Duke faculty member Franz Jobsis.
Light in the near-infrared range can easily pass through skin, bone and other tissues. However, within these frequencies of light, the oxygen-carrying molecules within red blood cells known as hemoglobin absorb light to an extent based on their oxygen content -- giving the researchers a reliable indicator of cerebral oxygenation. Researchers place a fiberoptic probe against the skull of the fetus to measure the changing oxygenation levels of blood circulating in the brain, Reynolds said.
Reynolds said that the increase in oxygenation in the fetal brain is likely due to isoflurane, one of the three commonly used agents, which induced reductions in oxygen metabolism along with increases in cerebral blood flow. Isoflurane is known to produce these actions in the adult brain but it had not been appreciated that such effects could also occur in the fetal brain, he said.