General anesthetic-induced neurotoxicity: an emerging problem for the young and old?

A growing body of evidence from cells, rodents, and sub-human primates suggests that general anesthetics can be neurotoxic to the developing and senescent brain. We review this evidence and put the studies into perspective for the practicing clinician.

Studies indicate that a variety of general anesthetics, which act primarily as gamma-amino-butyric acid receptor modulators and N-methyl-D-aspartic acid glutamate receptor antagonists, produce apoptotic neurodegeneration in the developing rodent and nonhuman primate brain. Vulnerability to this neurotoxicity is greatest during the period of synaptogenesis and presumably reflects disruption of the normal balance between excitation and inhibition during a critical period of brain development. Moreover, in the rodent, the neurodegeneration is associated with cognitive impairment into adulthood. Recent data also reveal that general anesthesia produces enduring cognitive impairment in aged but not young rodents and that halothane and isoflurane increase the generation and toxicity of amyloid beta, a protein strongly implicated in the pathogenesis of Alzheimer's disease. The meaning of these experimental results for human surgical patients is unclear, however, because human studies are lacking.

General anesthetics produce neurotoxicity and enduring cognitive impairment in young and aged animals but it is premature to change clinical practice because the issue has not been adequately studied in humans.