Best practice & research. Clinical anaesthesiology
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Best Pract Res Clin Anaesthesiol · Mar 2023
ReviewNeuroprotective strategies in anesthesia-induced neurotoxicity.
Over the past 20 years, hundreds of preclinical studies of the developing central nervous system have been published concluding that the common γ-aminobutryic acid and N-methyl-d-aspartate binding anesthetic agents cause neuroapoptosis and other forms of neurodegeneration. Some clinical studies, including controlled trials, both prospective and ambidirectional in design, indicate an association between any exposure (single or multiple) to anesthesia and surgery at a young age, generally less than 3-4 years, and later behavioral and neurodevelopmental problems. A consideration of neuroprotective strategies is important, as scientists and clinicians alike ponder methods to potentially improve the neurodevelopmental outcomes of the millions of infants and children who undergo surgery and anesthesia annually around the world. This review will address plausible neuroprotective strategies and include alternative anesthetics, neuroprotective nonanesthetic drugs, and physiologic neuroprotection.
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Providing pain relief during labour is a fundamental human right and can benefit both mother and foetus. Epidural analgesia remains the 'gold standard', providing excellent pain relief, as well as the facility to convert to anaesthesia should operative intervention be required. While maternal well-being remains the primary focus, epidural analgesia may also have implications for the foetus. ⋯ Clinically relevant neonatal outcomes such as Apgar score <7 at 5 min, neonatal resuscitation and need for admission to a neonatal unit are reassuring, with the benefits of epidural analgesia for both mother and neonate outweighing any potential risks. Recent concerns regarding an association of epidural with the development of autism spectrum disorder in childhood appear to be unfounded, with several large observational studies refuting this association. This review discusses the evidence relating to maternal neuraxial analgesia in labour, implications for the foetus in utero, and childhood outcomes both in the immediate peripartum period and longer term.
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Best Pract Res Clin Anaesthesiol · Mar 2023
ReviewClinical investigations on anesthesia-induced developmental neurotoxicity: The knowns, the unknowns and future prospects.
Pre-clinical experimental evidence, along with a plausible biological rational suggests that exposure of neonates and young children to anesthesia may harm brain development. However, the translational relevance of these observations remains unsolved. While a variety of lasting morpho-functional effects can be attributed to early life exposure to anesthetics in laboratory animals, we do not have a convincing human phenotype that reflects any causal effects of general anesthetic exposure on brain development and functional outcome. This review is aimed to provide a comprehensive description of the current state of clinical research alongside exploring future challenges in this field by focusing on the critical appraisal of methodological approaches applied in clinical research into developmental anesthesia neurotoxicity.
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Best Pract Res Clin Anaesthesiol · Mar 2023
ReviewIntroduction and history of anaesthesia-induced neurotoxicity and overview of animal models.
Brain development is initiated at around 3 weeks of gestation. The peak velocity of brain weight gain occurs around birth, with the neural circuitry subsequently being refined until at least 20 years of age. Antenatal and postnatal general anaesthesia suppresses neuronal firing during this critical period and may therefore impair brain development, referred to as "anaesthesia-induced neurotoxicity". ⋯ In this article, the history of preclinical and clinical research in anaesthesia-induced neurotoxicity will be reviewed, starting from the pioneering preclinical study in 1999 until the most recent systematic reviews. The mechanisms of anaesthesia-induced neurotoxicity are introduced. Finally, an overview of the methods used in preclinical studies will be provided, with a comparison of the different animal models that have been employed to investigate this phenomenon.
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Best Pract Res Clin Anaesthesiol · Mar 2023
ReviewPreclinical evidence for anaesthesia-induced neurotoxicity.
Preclinical research concerning anaesthesia-induced neurotoxicity was initiated in 1999. A decade later, the earliest clinical observational data showed mixed results in neurodevelopmental outcomes following anaesthesia exposure at a young age. Hence to date, preclinical studies remain the cornerstone of research in this field, primarily because of the vulnerability of clinical observational studies to confounding bias. ⋯ Across all gestational and postnatal ages, there is evidence that all commonly used general anaesthetics induce neuronal injury (e.g. apoptosis) and cause neurobehavioural impairment (e.g. learning and memory deficits). These deficits were more pronounced when animals were subjected to either repeated exposure, prolonged durations of exposure or higher doses of anaesthesia. To interpret these results in the clinical context, the strengths and limitations of each model and experiment should be carefully considered, as these preclinical studies were often biased by supraclinical durations and a lack of control with regard to physiological homeostasis.