CHICAGO – Preliminary findings from a new clinical trial show no adverse neurodevelopmental effects after brief inhaled anesthesia and surgery in infants and young children, reports the Online First edition of Anesthesiology , the peer-reviewed medical journal of the American Society of Anesthesiologists (ASA).
A "balanced" strategy using a lower dose of the inhaled anesthetic sevoflurane did not lead to meaningful short-term differences in IQ or child behavior problems, according to the study by Ji-Hyun Lee, M.D., Ph.D., of Seoul National University Hospital, Republic of Korea, and colleagues. "These findings support existing evidence suggesting that brief anesthetic exposure is unlikely to result in clinically significant neurodevelopmental impairment," the researchers wrote.
Animal studies have raised concerns about possible neurotoxic effects of general anesthetic or sedative drugs in young children. In response, the U.S. Food and Drug Administration issued warnings in 2017 that long-lasting or repeated exposure to these drugs "may negatively affect brain development in children younger than 3 years."
Randomized clinical trials – in which participants are randomly assigned to different treatment groups – are the best way to assess these safety concerns. One previous randomized trial ( the GAS study ) found normal neurodevelopmental outcomes in children receiving sevoflurane. However, that study was published several years ago and evaluated an alternative approach (awake regional anesthesia) that is not widely available.
To address this research gap, Dr. Lee and colleagues designed a clinical trial including 400 children under two years of age undergoing one-time surgery with general anesthesia. Patients were randomly assigned to anesthesia with inhaled sevoflurane alone or a balanced strategy using an intravenous sedative (dexmedetomidine) and a short-acting opioid (remifentanil). The balanced strategy was designed to reduce the amount of sevoflurane needed to maintain anesthesia during surgery. In both groups, anesthesia exposure was brief, with surgery lasting less than 90 minutes.
When the patients were approximately 30 months old, the researchers assessed neurodevelopmental outcomes using a nonverbal intelligence test and a parent-reported child behavior scale. If outcomes were better with the balanced strategy, it could mean that the lower dose of sevoflurane was less neurotoxic. The analysis included complete data on 343 children.
The results showed little or no difference in outcomes for children receiving sevoflurane alone compared to the balanced strategy. Overall IQ and behavioral scores were similar between the groups. Measures of language development were comparable as well.
Although the balanced approach "effectively reduced sevoflurane requirements during surgery, it did not provide measurable developmental advantages," Dr. Lee and coauthors wrote. They emphasize that their results are preliminary; final results will include long-term follow-up at five years old, including full-scale IQ assessment. In the meantime, the findings provide reassurance that one-time general anesthesia does not adversely affect neurodevelopmental outcomes in infants and young children who require surgery.
The new study is "a welcome and important addition" in an area where definitive evidence is difficult to obtain, according to an accompanying editorial by Andrew Davidson, MBBS, M.D., and Caleb Ing, M.D., MS. They discuss the challenges of studying this complex issue – including the fact that children who require surgery may have other health issues affecting neurodevelopmental outcomes.
As anesthesiologists and parents await the results of long-term follow-up and future clinical trials, the new findings "are incredibly helpful in consolidating knowledge" on the safety of inhaled anesthesia in young children, Drs. Davidson and Ing wrote. They conclude: "[T]he lack of an effect of differing sevoflurane dose on neurodevelopment may argue against sevoflurane being a cause of neurotoxicity."
The ASA has further information for parents of children undergoing surgery and anesthesia .
THE AMERICAN SOCIETY OF ANESTHESIOLOGISTS
Founded in 1905, the American Society of Anesthesiologists (ASA) is an educational, research and scientific society with more than 59,000 members organized to advance the medical practice of anesthesiology and secure its future. ASA is committed to ensuring anesthesiologists evaluate and supervise the medical care of all patients before, during, and after surgery. ASA members also lead the care of critically ill patients in intensive care units, as well as treat pain in both acute and chronic settings.
