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Chapter: Clinical Anesthesiology: Clinical Pharmacology: Pharmacological Principles

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Anesthetic Neurotoxicity

In recent years, there has been ongoing concern that general anesthetics damage the developing brain.

ANESTHETIC NEUROTOXICITY

In recent years, there has been ongoing concern that general anesthetics damage the developing brain. It has been suggested that early exposure to anesthet-ics can promote cognitive impairment in later life. Concern has been raised that anesthetic exposureaffects the development and the elimination of synapses in the infant brain. For example, animal studies have demonstrated that isoflurane exposure promotes neuronal apoptosis and subsequent learn-ing disability. Volatile anesthetics have been shown to promote apoptosis by altering cellular calcium homeostatic mechanisms.

Human studies exploring whether anesthesia is harmful in children are difficult, as conducting a ran-domized controlled trial for that purpose only would be unethical. Studies that compare populations of children who have had anesthetics with those who have not are also complicated by the reality that the former population is likewise having surgery and receiving the attention of the medical community. Consequently, children receiving anesthetics may be more likely to be diagnosed with learning difficulties in the first place. Data from one large study dem-onstrated that children who underwent surgery and anesthesia had a greater likelihood of carrying the diagnosis of a developmental disorder; however, the finding was not supported in twins (ie, the incidence of developmental disability was not greater in a twin who was exposed to anesthesia and surgery than in one who was not).

Human, animal, and laboratory trials demon-strating or refuting that anesthetic neurotoxicity leads to developmental disability in children are underway. As of this writing, there is insufficient and conflicting evidence to warrant changes in anes-thetic practice (see: www. smarttots .org).

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