General anaesthetics and the developing brain: an overview

Abstract

Summary Various experimental studies in animals have shown that general anaesthetics are potentially toxic to the developing brain. By inducing apoptosis or interfering with neurogenesis, anaesthetic exposure during a critical period of neuronal development can have significant impact on neurocognitive function later in life. It remains controversial whether these experimental results can be transferred to human beings and this is under intensive scientific evaluation. To gain more insight into possible neurotoxic effects on the human brain of infants and small children, a number of retrospective studies have been performed. At present, there is no clear evidence that exposure to anaesthesia up to the age of 3–4 years is associated with neurocognitive or behavioural deficits. Currently, the PANDA, MASK and GAS studies are underway to explore this relationship. Anaesthesia is not an end in itself, but necessary to facilitate surgical procedures. There is evidence that maintaining physiological conditions is important for the overall outcome following anaesthesia and surgery. Until proven otherwise, it can be recommended to keep anaesthesia and surgery as short as possible, to use short‐acting drugs and/or a combination of general anaesthesia and multimodal pain therapy including systemic analgesics, and local or regional anaesthesia, to reduce the overall drug dosage.

Neurodevelopmental Outcomes After Neonatal Surgery for Major Noncardiac Anomalies

“…55 The discussion on the neurotoxic effect of inhalational anesthetics on the immature brain is also ongoing. 10 To date, there is no clinical evidence of the adverse effect in the human brain.…”

“…In vitro and in vivo experimental studies have demonstrated the neurotoxic effect of general anesthetics on the young, animal brain. [10][11][12][13] Large retrospective cohort studies in humans show a significantly higher rate of behavioral problems in children who have undergone multiple surgical procedures at a young age, 14,15 although the causes for this are unclear. 16 In short, data for both incidence and risk factors regarding neurodevelopmental delay are scarce and inconsistent.…”

Persistent neuronal apoptosis and synaptic loss induced by multiple but not single exposure of propofol contribute to long-term cognitive dysfunction in neonatal rats

“…It has been reported that general anesthetic-induced widespread neuronal apoptosis is not simply related to the acceleration of physiologic apoptosis (Sinner et al, 2014;Konno et al, 2016), it can be assumed that apoptotic neurons induced by propofol may be from those both with and without synaptic connections. Moreover, our results indicate that propofol-induced neuronal apoptosis could be the cause of neuronal deficit, and persistent neuronal apoptosis induced by multiple propofol exposures can lead to longlasting neuronal damage.…”

Guidelines for Monitoring and Management of Pediatric Patients Before, During, and After Sedation for Diagnostic and Therapeutic Procedures: Update 2016

“…At this point, the research in this area is preliminary and inconclusive at best, but it would seem prudent to avoid unnecessary exposure to sedation if the procedure is unlikely to change medical/dental management (eg, a sedated MRI purely for screening purposes in preterm infants). [379][380][381][382] …”