The impact of the perioperative period on neurocognitive development, with a focus on pharmacological concerns

• Published in: Best practice & research. Clinical anaesthesiology Vol. 24; no. 3; pp. 433 - 449
• Main Authors: Istaphanous, George K., MD, Ward, Christopher G., MD, Loepke, Andreas W., MD, PhD
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Ltd 01.09.2010
• Subjects: anaesthesia; anaesthetics; Analgesics, Opioid - toxicity; Anesthesia & Perioperative Care; Anesthetics - toxicity; animal; Animals; brain; Child Development - drug effects; Cognition - drug effects; critical care; cytotoxicity; disability; foetus; GABA; GABA-A Receptor Agonists - metabolism; Genetic Predisposition to Disease; Humans; infant; Infant, Newborn; Inflammation - physiopathology; intensive care; learning impairment; neonate; neuroapoptosis; neurodegeneration; neurologic; neurotoxicity; newborn; NMDA; pain; Pain - physiopathology; Perioperative Care; Receptors, N-Methyl-D-Aspartate - antagonists & inhibitors; sedation; sedatives; Species Specificity; Stress, Psychological - physiopathology; surgery; pain; intensive care; disability; critical care; neurodegeneration; neonate; anaesthetics; newborn; brain; foetus; infant; neurologic; sedation; neuroapoptosis; neurotoxicity; GABA; learning impairment; NMDA; animal; sedatives; cytotoxicity; anaesthesia; surgery
• ISSN: 1521-6896; 1532-169X
• DOI: 10.1016/j.bpa.2010.02.013

Mounting evidence from animal studies has implicated that all commonly used anaesthetics and sedatives may induce widespread neuronal cell death and result in long-term neurological abnormalities. These findings have led to serious questions regarding the safe use of these drugs in young children. In humans, recent findings from retrospective, epidemiological studies do not exclude the possibility of an association between surgery with anaesthesia early in life and subsequent learning abnormalities. These results have sparked discussions regarding the appropriate timing of paediatric surgery and the safe management of paediatric anaesthesia. However, important questions need to be addressed before findings from laboratory studies and retrospective clinical surveys can be used to guide clinical practice. This article summarises the currently available preclinical and clinical information regarding the impact of anaesthetics, sedatives, opioids, pain and stress, inflammation, hypoxia–ischaemia, co-morbidities and genetic predisposition on brain structure and long-term neurological function. Moreover, this article outlines the putative mechanisms of anaesthetic neurotoxicity, and the phenomenon’s implications for clinical practice in this rapidly emerging field.