Anesthetic Neurotoxicity

By June 3, 2019Uncategorized

Delivery of anesthetic drugs undoubtedly work on areas of the brain, spinal cord, and peripheral nerves to achieve their desired effects. The risks of exposure to anesthetic agents during development has become a burgeoning study in basic and clinical science. In laboratory settings, exposure to inhaled anesthetics has resulted in cellular changes in animal and in vitro models [1]. Because of many confounding factors regarding early neural development, types of anesthetic agents used, underlying morbidity, and uncertain neurocognitive trajectories in young children requiring anesthesia and surgery, the risk of anesthesia in the pediatric population on development, behavior, and later cognition, are not certain.

Clarification of the risk of specific agents on the developing brain are underway at multiple centers around the United States [2]. Given the nature of this clinical question, the results are years away and are likely to generate more inquiries. Several observational studies, such as the MASK study from Mayo Clinic, will attempt to elucidate whether developmental differences exist between children who have been exposed to anesthesia and surgery prior to age three and those who have had no early exposure. Other studies, such as the GAS study and T-Rex study, will test whether a specific anesthetic regimen (e.g., general vs. spinal anesthetic or dexmedetomidine with remifentanil) will later correlate with neuropsychiatric problems in children as they are followed after their anesthetic encounters. Appropriate use of anesthetic drugs in any age can facilitate surgery. Clinically meaningful downstream effects of have yet to be elucidated.

Among patients of advanced age, several efforts have investigated whether anesthetic exposure modifies amyloid plaque deposition, which is a hallmark of Alzheimer’s disease (3). Despite the paucity of high-quality studies, there does not seem to be a risk to exposure of these agents per se and the further development or exacerbation of Alzheimer’s disease. Instead, the stress of the perioperative period, genetics and epigenetics, medical comorbidities, and lifestyle factors likely play more prominent roles in this disease process.

The use of local anesthetics (e.g., lidocaine, bupivacaine) for regional and neuraxial anesthesia defines a different type of anesthetic neurotoxicity [4]. These chemicals produce the desired clinical effect by traversing the cell membrane of neurons and binding to current-generating sodium channels. This decreases the conductance of a neuron and diminishes neural transmission of sensation and motor signals. Unfortunately, off-sight effects of local anesthetics within the nerve cell have been observed and apoptosis can be observed in neuronal cells exposed to high concentrations of local anesthetics. Furthermore, mechanical and surgical factors can potentiate the toxicity which local anesthetics pose to neurons.

Overall, anesthetic agents are safe for use in the general population. Special populations at the extremes of age warrant careful attention to the doses of anesthetics used to achieve the goals of amnesia, analgesia, sedation, or motor inactivity. Ongoing clinical trials and investigations will hopefully elucidate agent-specific risks to pediatric populations. Dosing of local anesthetics should be carefully planned for all patients.


  1. Soriano SG et al. Thinking, fast and slow: highlights from the 2016 BJA seminar on anaesthetic neurotoxicity and neuroplasticity. Br J Anaesth. 2017;119(3):443-447. doi: 10.1093/bja/aex238.
  2. Pinyavat T et al. Summary of the Update Session on Clinical Neurotoxicity Studies. J Neurosurg Anesthesiol. 2016;28(4):356-360.
  3. Seitz DP et al. Exposure to general anesthesia and risk of Alzheimer’s disease: a systematic review and meta-analysis. BMC Geriatr. 2011;11:83.
  4. Verlinde M et al. Local Anesthetic-Induced Neurotoxicity. Int J Mol Sci. 2016;17(3):339. doi: 10.3390/ijms17030339.