Anesthesia and the developing brain: A way forward for laboratory and clinical research

Abstract

All commonly used general anesthetics have been shown to cause neurotoxicity in animal models, including nonhuman primates. Opinion, however, remains divided over how cumulative evidence from preclinical and human studies in this field should be interpreted and its translation to current practices in pediatric anesthesia and surgery. A group of international experts in laboratory and clinical sciences recently convened in Genoa, Italy, to evaluate the current state of both laboratory and clinical research and discuss future directions for basic, translational, and clinical studies in this field. This paper describes those discussions and conclusions. A central goal identified was the importance of continuing to pursue laboratory research efforts to better understand the biological pathways underlying anesthesia neurotoxicity. The distinction between basic and translational experimental designs in this field was highlighted, and it was acknowledged that it will be important for future animal research to try to causally link structural changes with long-term cognitive abnormalities. While inherent limitations will continue to affect the ability of even large observational cohorts to determine if anesthesia impacts neurodevelopment or behavioral outcomes, the importance of conducting further large well-designed cohort studies was also emphasized. Adequately powered cohorts could clarify which populations are at increased risk, provide information on environmental and healthcare-related risk modifiers, and guide future interventional trials. If anesthetics cause structural or functional adverse neurological effects in young children, alternative or mitigating strategies need to be considered. While protective or mitigating strategies have been repeatedly studied in animals, there are currently no human data to support alternative anesthetic strategies in clinical practice. Lastly, it was noted that there is still considerable debate over the clinical relevance of anesthesia neurotoxicity, and the need to evaluate the impact of other aspects of perioperative care on neurodevelopment must also be considered.

Techniques for minimizing sedation in pediatric MRI

“…With the use of pediatric MRI rising, there has been an increase in the need for pediatric sedation/anesthesia to reduce motion artifacts and achieve acceptable image quality and diagnostic efficacy. However, over the last decade concerns have been raised that sedation in children not only exposes the child to potential acute risks, but may be associated with delayed long‐term effects such as neurotoxicity and long‐term cognitive deficits …”

“…A sizeable body of literature has studied the incidence of adverse events following pediatric sedation. Some studies have noted an incidence of adverse events as high as >10%, particularly in small children with severe diseases and significant disabilities . The risk of upper respiratory infections and hypoxia has been reported to be as high as 17% in children sedated with intravenous pentobarbital .…”

“…The risk of upper respiratory infections and hypoxia has been reported to be as high as 17% in children sedated with intravenous pentobarbital . The Pediatric Sedation Research Consortium reported a 5.3% incidence of adverse events in pediatric sedations performed outside the operating room for imaging . Delayed complications in pediatric sedation for imaging included prolonged drowsiness, paradoxical hyperstimulation, gastrointestinal upset and motor imbalance, and long‐term developmental disability .…”

“…However, over the last decade concerns have been raised that sedation in children not only exposes the child to potential acute risks, but may be associated with delayed long-term effects such as neurotoxicity and long-term cognitive deficits. 5,6 A sizeable body of literature has studied the incidence of adverse events following pediatric sedation. Some studies have noted an incidence of adverse events as high as >10%, particularly in small children with severe diseases and significant disabilities.…”

The hydra of anesthetic neurotoxicity: Myth or reality?

“…In the current issue of Pediatric Anesthesia , Disma et al summarize the discussions from a recent symposium held in Genoa, Italy, in May 2017— The 2nd International Conference on Pediatric Anesthesia and Neurotoxicity: from the GAS study to future collaborative trials , which brought together 28 international experts in the field to review our progress. The authors are to be commended for providing a cogent overview of the current state of laboratory and clinical research, with recommendations for future directions for basic, translational, and clinical studies.…”