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

Abstract

A multitude of animal studies have shown that virtually all general anesthetics used in clinical practice possibly during a vulnerable period of brain development (i.e., brain growth spurt, peak of synaptogenesis) may lead to neurodegeneration (particularly apoptosis) and abnormal synaptic development with functional deficits in learning and behavior later in life. Initial studies were mainly performed in immature rodent pups, but more recent studies have included nonhumans primates (rhesus monkeys). Given the number of neonates, infants, and young children anesthetized annually worldwide, these findings could have significant public health implications. So far, relatively few human (cohort) studies focusing on this topic have been published with inconsistent results. While some studies have indicated an association between exposure to anesthesia and surgery, other studies have indicated no such association. Prospective studies are underway, but the result will not be available for several years. This paper reviews some of the preclinical background behind anesthesia-related neurotoxicity but focuses mainly on the human studies so far. It is concluded that although disturbing, the animal data lack verification in humans. Fortunately, the humans studies performed so far have been unable to confirm these animal data. A single brief anesthetic seems safe in infants. Multiple anesthetic and surgical exposures on the other hand are different. But there may be other reasons for this than merely the anesthetics. Currently, there is no need to change current anesthetic clinical practice or to postpone or cancel truly urgent surgeries in young children.

A review of paediatric anaesthetic-related mortality, serious adverse events and critical incidents

“…68 • Inexperienced or untrained practitioners. 5,18,20,53,55,58,60,65,69 Cardiac arrest and mortality, as a result of failing to recognise hypovolaemia, is common in developing and developed countries. 13 …”

“…[1][2][3][4][5][6][7] The purpose of this review was to refocus on immediate clinical safety outcomes within 24 hours of anaesthesia ending. 8 There is a significant difference in outcome in developed and developing countries, and the contributory factors are highlighted in this regard.…”

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].…”

The Utility of a Nonhuman Primate Model for Assessing Anesthetic-Induced Developmental Neurotoxicity

“…To date, however, there have been no confirmative prospective human studies regarding general anesthetic induced developmental neurotoxicity [3,4]. Animal models have proven useful in demonstrating that anesthetic-induced apoptotic neurodegeneration is associated with mitochondrial impairment [5,6], disturbances in the release of, and signaling by, neurotrophic factors [7,8,9] and upregulated neuroinflammatory markers [10,11].…”