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FDA has been investigating the adverse effects of general anesthetics and sedation drugs on childhood brain development since 1999. They issued a warning in December 2016 regarding the use of drugs that potentiate gamma-aminobutyric acid (GABA) activity or block N-methyl-D-aspartate (NMDA) receptors for more than 3 hours in children younger than 3 years old or in the third trimester of pregnancy. Use of these drugs during early brain development may result in long term neurodevelopmental and cognitive problems in children younger than 3 years. The risk may be related to a lengthy single time of exposure or exposure over multiple surgeries. FDA approved a new warning in the product labeling reflecting this risk. It is unknown if these risks vary among the individual anesthetic and sedation drugs. FDA is requiring additional warnings in the labels of the drugs listed below.
- Desflurane (Suprane)
- Halothane
- Isoflurane (Forane)
- Sevoflurane (Ultane, Sojourn)
- Etomidate (Amidate)
- Ketamine (Ketalar)
- Methohexital (Brevital)
- Pentobarbital (Nembutal)
- Propofol (Diprivan)
- Lorazepam injection (Ativan)
- Midazolam injection, syrup (Versed)
A randomized controlled trial and large observational study show that single, or relatively short exposure to general anesthetics and sedation drugs in young children did not result in negative effects on behavior or learning. How early in life anesthetic exposure affects brain development remains unknown. General anesthetics and sedation drugs caused loss of nerve cells in the brain when used for more than 3 hours in young and pregnant animals, resulting in behavior and learning problems. Some epidemiological studies in children supported the findings from animal studies, particularly with repeated or prolonged exposure to general anesthetics and sedation drugs. These studies had limitations, and it is unknown whether behavior and learning problems were caused by the drugs or other factors (eg, the underlying medical condition necessitating the surgery or procedure, the surgery itself). FDA also approved the addition of information from these studies to the product labeling.
Anesthetics and sedation drugs are necessary for patients who require surgery or painful procedures. Untreated pain may harm a child’s developing nervous system. Discuss the risks and benefits of anesthetic and sedation drug use in young children and pregnant women requiring multiple procedures or a single procedure lasting more than 3 hours. Do not delay or avoid medically necessary surgeries in these patient populations. Consider delaying elective surgeries if appropriate to reduce risk of neurodevelopmental problems.
Additional information is available at the following links:
- FDA MedWatch Alert – April 27, 2017
www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm555631.htm - FDA Drug Safety Communication – April 27, 2017
www.fda.gov/Drugs/DrugSafety/ucm554634.htm - FDA MedWatch Alert – December 14, 2016
www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm533195.htm - FDA Drug Safety Communication – December 14, 2016
www.fda.gov/Drugs/DrugSafety/ucm532356.htm