FDA Warns on Anesthetic, Sedative Use in Pregnant Women, Kids

Megan Brooks

December 14, 2016

The repeated or lengthy (>3 hours) use of general anesthetic and sedation drugs during surgeries or procedures in children younger than 3 years or in pregnant women in the third trimester may affect the child's developing brain, the US Food and Drug Administration (FDA) warned today in a Safety Communication.

As a result, the FDA is requiring warnings to be added to the labels of general anesthetic and sedation drugs. No specific anesthetic or sedation drug has been shown to be safer than any other, the FDA notes.

Generic Brand Name
Desflurane Suprane
Etomidate Amidate
Halothane Only generic is available
Isoflurane Forane
Ketamine Ketalar
Lorazepam injection Ativan
Methohexital Brevital
Midazolam injection, syrup Only generic is available
Pentobarbital Nembutal
Propofol Diprivan
Sevoflurane Ultane, Sojourn


In published studies of juvenile animals, use of anesthetic and sedation drugs that block N-methyl-D-aspartate receptors and/or potentiate γ-aminobutyric acid activity for longer than 3 hours increased neuronal apoptosis in the brain, resulting in long-term cognitive deficits, the FDA said.

"Adverse effects on brain development following use of general anesthetic and sedation drugs have been demonstrated in multiple animal species ranging from flatworm to nonhuman primates," they said.

Some epidemiologic studies have found an association between childhood anesthesia exposure and adverse neurodevelopmental outcomes. "In particular, several of the studies have increased concerns that longer or repeated exposures may contribute to various cognitive and behavioral problems, including neurodevelopmental delay-related diagnoses, learning disabilities, and attention deficit hyperactivity disorder," the FDA said. "However, it remains unclear whether these associations represent an effect of the anesthesia drugs as opposed to the surgery itself, or are the result of uncontrolled confounding related to the underlying condition or other factors," they caution.

"The window of vulnerability to these changes in the brain is believed to correlate with exposures in the third trimester of pregnancy through the first year of life, but may extend out to approximately 3 years in humans. The clinical significance of these nonclinical findings is not clear," the FDA said.

Further study is needed to "fully characterize how early life anesthetic exposure might affect children's brain development, particularly for more lengthy or repeated exposures and in more vulnerable children," they note.

Consistent with animal studies, recent human data suggest that a single, relatively short exposure to general anesthetic and sedation drugs in infants or toddlers is unlikely to have negative effects on behavior or learning, the FDA said.

Discuss Risks, Benefits

Decisions regarding the timing of any elective procedures requiring anesthesia should consider the benefits of the procedure weighed against the risks, the FDA advised.

They encourage health providers to discuss with parents, caregivers, and pregnant women the benefits, risks, and appropriate timing and duration of surgery or procedures requiring anesthetic and sedation drugs, as well as the health risks of not treating certain conditions.

"We recognize that in many cases these exposures may be medically necessary and these new data regarding the potential harms must be carefully weighed against the risk of not performing a specific medical procedure," Janet Woodcock, MD, director of FDA's Center for Drug Evaluation and Research, said in a statement.

The FDA will continue to monitor the use of these drugs in children and pregnant women and provide an update if additional information becomes available.

In 2010, the FDA formed a partnership with the International Anesthesia Research Society called SmartTots (Strategies for Mitigating Anesthesia-Related neuroToxicity in Tots) to fund additional research to better understand the safe use of these drugs in young children and pregnant women.

"We hope that this information helps enable the most informed medical decisions possible about the use of anesthesia in young children and pregnant women. We will continue to work collaboratively to leverage our collective resources to address this important issue, and we will update the public with additional information, as it becomes available," Dr Woodcock said.

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