Neurotoxicity, General Anesthesia, and the Developing Brain: What have We Learned from the Human Studies so Far?

Abstract

A multitude of animal studies have shown that virtually all general anesthetics used in clinical practice exert detrimental effects on the developing brain, notably enhanced neuroapoptosis. Some studies have also indicated that animals exposed to general anesthesia may experience long term neurobehavioral deficits later in life. The neurotoxic effects seem to be dose-dependent and have been suspected to occur at certain early developmental stages. Initially, the animal studies comprised primarily rodents but recently they have been confirmed in non-human primates. Recently, a number of (mainly retrospective) human cohort studies have been published with inconsistent results. While some studies have indicated an association between anesthesia and surgery and adverse neurobehavioral outcome, other studies have indicated no association. The cohort studies have many constraints and shortcomings. While prospective studies are underway, they will not provide any answers for several more years. The aim of this review is to provide the reader with a summary of recent human cohort studies and discuss their limitations and weaknesses. Although disturbing, the animal data lacks verification in humans. To date there are no data to support any change in clinical pediatric anesthetic practice. Any such change will be premature and potentially dangerous until we have evidence as to if and how general anesthesia impairs neurocognition and behaviour in infants and young children.

Anesthesia‐related neurotoxicity and the developing animal brain is not a significant problem in children

“…Compared with the magnitude of animal investigations, the number of human studies is relatively limited. The majority of these have been reviewed in details elsewhere recently .…”

Effects of Anesthesia on Children’s Brain Development

“…At 2 years of age the brain cortex will have hundreds of trillions of synapses working. This means that the brain continues to develop after birth [3]. The stages of brain development are divided in neurogenesis and proliferations, differentiation, synapse formation, and myelination.…”

Safe Anesthesia For Every Tot – The SAFETOTS initiative

“…A major difficulty these studies are struggling with is that it is virtually impossible to separate the pharmacodynamic effects of general anesthetics per se from a multitude of other factors that might also cause neurological damage, such as the stress of surgery or impairment of physiological parameters because of inadequate anesthesia management [3]. Therefore, to date, no definite causal link between certain anesthetic drugs or techniques and poor neurological outcome in children has been established [4][5][6][7][8].…”