A special section of the November issue of Anesthesia & Analgesia, official journal of the International Anesthesia Research Society (IARS), presents new research, updates, and commentaries about possible toxic effects of anesthetics and sedatives in infants and young children. The IARS is a key partner in the SmartTots initiative, dedicated to finding scientific answers to these urgent public health concerns.
SmartTots is a public-private partnership between the IARS and the U.S. Food and Drug Administration, with involvement other scientific organizations, pharmaceutical companies, and medical and scientific experts from around the world. "We are optimistic through SmartTots we will be able to determine the neurologic risks, if any, of exposure to sedative and anesthetic agents to our infants and children," according to an introductory article by Drs James G.
SmartTots was organized in response to studies showing evidence of neurotoxicity (toxic effects on the brain and nervous system) caused by exposure to anesthetic drugs in developing animals. Since many of the same drugs are also used as sedatives—especially in critically ill children—it's critical to determine whether similar neurotoxic effects occur in humans.
"With more than 6 million infants and children exposed to sedation and anesthesia in the United States on an annual basis, the implications of any recommendation regarding these agents are immense," write Drs Ramsay and Rappaport.
However, firm scientific evidence is needed to guide any recommendation for changing clinical practice in children. The goal of SmartTots is to raise the funds needed to support the critical research studies that will provide the data on which to base these recommendations.
So far, the SmartTots Scientific Advisory Board has set a scientific research agenda and issued a request for research applications. The IARS has contributed $200,000 to fund the initial studies. Closing the gaps in research is expected to take several years, at a cost of up to $40 million. Major fund-raising and public awareness efforts are underway, with an Executive Board led by well-known physician and author Dr Michael Roizen.
Experts Agree—More Research Needed before Making Changes in Anesthesia Practice
Meanwhile, research is moving forward in several key areas. The November Anesthesia & Analgesia discusses several reports presented at a special session on neurotoxicity of anesthesia in children held at this year's IARS Annual Meeting.
These include an important new study reporting a possible increase in developmental and behavioral disorders among children exposed to anesthetics before age three. The study, based on New York State Medicaid data was led by Charles DiMaggio, PhD, of Columbia University. With adjustment for other factors, children with early anesthetic exposure were 60 percent more likely to be diagnosed with developmental or behavioral disorders, compared to a group of siblings who did not undergo surgery. (The use of a sibling comparison group helps to avoid genetic and other differences that might contribute to risk.)
However, there was no apparent increase among children who had only one operation—although risk increased progressively for those with two or more operations. In addition, a more tightly matched analysis of 138 sibling pairs (one with and the other without exposure to surgery/anesthesia) found no increase in risk.
In an accompanying editorial, Dr Joss Thomas of University of Iowa Carver College of Medicine and colleagues write, "[W]e believe that evidence is most consistent with the premise that anesthesia per se, given to a healthy child who needs only a 'routine' surgical procedure, is not neurotoxic." They emphasize the need for "conclusive evidence" before making any changes in practice.
The November A&A also includes a pair of experimental studies examining one possible mechanism by which anesthetics might cause neurotoxic effects in the brains of young animals—specifically, through calcium overload in brain cells. In another article, Dr Greg Stratmann of University of California San Francisco reviews the evidence on neurotoxicity associated with anesthetic exposure in the developing brain. He echoes the call for definitive evidence before making any change in clinical practice: "Until we know if and how pediatric anesthesia affects cognition in humans, a change in anesthetic practice would be premature, not guided by evidence of better alternatives, and therefore potentially dangerous."
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