Neurotoxicidad y anestesia / Anesthesia neurotoxicity

Enero 11, 2018. No. 2960

Neurotoxicidad anestésica en pacientes pediátricos Anesthetic Neurotoxicity in Pediatric Patients Ayse B. Ozer and Sibel Ozcan Current Topics in Anesthesiology book edited by Riza Hakan Erbay, ISBN 978-953-51-2918-9, Print ISBN 978-953-51-2917-2, Published: February 8, 2017 under CC BY 3.0 license. © The Author(s). http://dx.doi.org/10.5772/65921 Abstract In recent years, an increasing number of publications have shown the negative effects of anesthetics on the developing brain and have made inquiries about anesthesia for pediatric patients in practice. Anesthesia is applied to millions of children for surgery, imaging, and other invasive procedures; the issue is very serious and concerns. In this chapter, experimental and clinical studies about the issue have been summarized. As a result, anesthetic drugs except alpha-2 adrenergic agonist anesthetic (NMDA antagonist or a GABA agonist) used in pediatric patients (especially if there is no painful situation) have potential neurotoxicity. Particularly, if anesthesia exposure was applied in the fragile period (the first 4 years) and if used at higher concentrations or repeated anesthesia application, adverse effects of anesthesia exposure on the developing brain have been claimed. But, the issue is not fully clarified yet. Keywords: anesthesia, neurotoxicity, neonatal, developing brain PDF Un mecanismo celular reversible por presión de anestésicos generales capaz de alterar un posible mecanismo para la conciencia A pressure-reversible cellular mechanism of general anesthetics capable of altering a possible mechanism for consciousness Kunjumon I. Vadakkan Springerplus. 2015; 4: 485. Published online 2015 Sep 7. doi: 10.1186/s40064-015-1283-1 ASbstract Different anesthetics are known to modulate different types of membrane-bound receptors. Their common mechanism of action is expected to alter the mechanism for consciousness. Consciousness is hypothesized as the integral of all the units of internal sensations induced by reactivation of inter-postsynaptic membrane functional LINKs during mechanisms that lead to oscillating potentials. The thermodynamics of the spontaneous lateral curvature of lipid membranes induced by lipophilic anesthetics can lead to the formation of non-specific inter-postsynaptic membrane functional LINKs by different mechanisms. These include direct membrane contact by excluding the inter-membrane hydrophilic region and readily reversible partial membrane hemifusion. The constant reorganization of the lipid membranes at the lateral edges of the postsynaptic terminals (dendritic spines) resulting from AMPA receptor-subunit vesicle exocytosis and endocytosis can favor the effect of anesthetic molecules on lipid membranes at this location. Induction of a large number of non-specific LINKs can alter the conformation of the integral of the units of internal sensations that maintain consciousness. Anesthetic requirement is reduced in the presence of dopamine that causes enlargement of dendritic spines. Externally applied pressure can transduce from the middle ear through the perilymph, cerebrospinal fluid, and the recently discovered glymphatic pathway to the extracellular matrix space, and finally to the paravenular space. The pressure gradient reduce solubility and displace anesthetic molecules from the membranes into the paravenular space, explaining the pressure reversal of anesthesia. Changes in membrane composition and the conversion of membrane hemifusion to fusion due to defects in the checkpoint mechanisms can lead to cytoplasmic content mixing between neurons and cause neurodegenerative changes. The common mechanism of anesthetics presented here can operate along with the known specific actions of different anesthetics. Keywords: Consciousness, General anesthetics, Pressure reversal, Semblance hypothesis, Inter-membrane contact, Membrane hemifusion, Partial hemifusion, Complete hemifusion, Membrane fusion, Neurodegeneration PDF Una espada de doble filo: efectos anestésicos volátiles en el cerebro neonatal A Double-Edged Sword: Volatile Anesthetic Effects on the Neonatal Brain Sunny Chiao, Zhiyi Zuo Brain Sci. 2014 Jun; 4(2): 273-294. Published online 2014 Apr 16. doi: 10.3390/brainsci4020273 Abstract The use of volatile anesthetics, a group of general anesthetics, is an exceedingly common practice. These anesthetics may have neuroprotective effects. Over the last decade, anesthetic induced neurotoxicity in pediatric populations has gained a certain notoriety based on pre-clinical cell and animal studies demonstrating that general anesthetics may induce neurotoxicity, including neuroapoptosis, neurodegeneration, and long-term neurocognitive and behavioral deficits. With hundreds of millions of people having surgery under general anesthesia worldwide, and roughly six million children annually in the U.S. alone, the importance of clearly defining toxic or protective effects of general anesthetics cannot be overstated. Yet, with our expanding body of knowledge, we have come to learn that perhaps not all volatile anesthetics have the same pharmacological profiles; certain ones may have a more favorable neurotoxic profile and may actually exhibit neuroprotection in specific populations and situations. Thus far, very few clinical studies exist, and have not yet been convincing enough to alter our practice. This review will provide an update on current data regarding volatile anesthetic induced neurotoxicity and neuroprotection in neonatal and infant populations. In addition, this paper will discuss ongoing studies and the trajectory of further research over the coming years. Keywords: anesthesia, anesthetics, neuroprotection, neurotoxicity, pediatrics, volatile anesthetics, preconditioning, postconditioning, ischemic conditioning PDF Safe Anaesthesia Worldwide Delivering safe anaesthesia to the world's poorest people Informes / Information World Congress on Regional Anesthesia & Pain Medicine April 19-21, 2018, New York City, USA Informes / Information International Anesthesia Research Society Annuals Meetings USA Informes / Information

Anestesiología y Medicina del Dolor 52 664 6848905 vwhizar@anestesia-dolor.org anestesia-dolor.org

Neurotoxicidad por anestesia / Anesthesia neurotoxicity

Mayo 3, 2017. No. 2678

El precondicionamiento isquémico remoto provee neuroprotección. Impacto de la apoptosis inducida por ketamina en el cerebro de ratas en desarrollo Remote ischemic preconditioning provides neuroprotection: impact on ketamine-induced neuroapoptosis in the developing rat brain. Ma W1, Cao YY, Qu S, Ma SS, Wang JZ, Deng LQ, Yuan WJ, Meng JH. Eur Rev Med Pharmacol Sci. 2016 Dec;20(23):4972-4979. Abstract OBJECTIVE: Previous studies have demonstrated that the commonly used anesthetic ketamine can acutely increase apoptosis and have long-lasting detrimental effects on cognitive function as the animal matures. Remote ischemic preconditioning (RIPC) has been confirmed to have a cerebral protective role in animal models of brain damage. The aim of this study was to investigate whether RIPC can protect the developing brain from anesthetic-induced neurotoxicity. MATERIALS AND METHODS: To investigate the protective properties of RIPC, 60 new-born Sprague-Dawley (SD) rats were randomly allocated into four groups: ketamine (20 mg/kg was diluted in saline, six times at an interval of 2 hours); RIPC (left hind row ischemia 5 min, reperfusion 5 min, a total of four cycles); ketamine + RIPC: RIPC was induced at postnatal day 5 and rats underwent the same treatment with the ketamine group after 48 hours; and saline (group vehicle). Neuronal apoptosis in the frontal cortex and hippocampal CA1 region was measured 24 h after treatment using immunohistochemistry of cleaved caspase-3. Learning and memory abilities were tested at the age of 60 days by Morris water maze test. RESULTS: The percentage of cleaved caspase-3 immunohistochemical staining positive cells in the ketamine + RIPC group showed a more marked decline in neuronal apoptosis of the CA1 region than that in the ketamine group (p < 0.05) but not in the CA1 region (p > 0.05). The mice exposed to RIPC alone showed no difference from the saline-treated mice. Moreover, RIPC significantly reversed the learning and memory deficits observed at 60 days of age. CONCLUSIONS: Our data indicate that RIPC treatment provides protection against ketamine-induced neuroapoptosis in the frontal cerebral cortex but not in the hippocampal CA1 region in developing rats and attenuates long-term behavioural deficits as the animals mature, suggesting a new possible strategy for neuroprotection. PDF Monóxido de carbono y neurotoxicidad inducida por anestesia Carbon monoxide and anesthesia-induced neurotoxicity. Levy RJ1. Neurotoxicol Teratol. 2017 Mar - Apr;60:50-58. doi: 10.1016/j.ntt.2016.09.002. Epub 2016 Sep 9. Abstract The majority of commonly used anesthetic agents induce widespread neuronal degeneration in the developing mammalian brain. Downstream, the process appears to involve activation of the oxidative stress-associated mitochondrial apoptosis pathway. Targeting this pathway could result in prevention of anesthetic toxicity in the immature brain. Carbon monoxide (CO) is a gas that exerts biological activity in the developing brain and low dose exposures have the potential to provide neuroprotection. In recent work, low concentration CO exposures limited isoflurane-induced neuronal apoptosis in a dose-dependent manner in newborn mice and modulated oxidative stress within forebrain mitochondria. Because infants and children are routinely exposed to low levels of CO during low-flow general endotracheal anesthesia, such anti-oxidant and pro-survival cellular effects are clinically relevant. Here we provide an overview of anesthesia-related CO exposure, discuss the biological activity of low concentration CO, detail the effects of CO in the brain during development, and provide evidence for CO-mediated inhibition of anesthesia-induced neurotoxicity. KEYWORDS: Anesthesia-induced neurotoxicity; Apoptosis; Carbon monoxide; Cytoprotection; Endogenous; Exogenous; Exposure; General anesthesia; Low-flow anesthesia; Mitochondria; Oxidative stress; Therapy PDF Neurotoxicidad inducida por anestesia en el cerebro en desarrollo. Actualización de la evidencia preclínica Anaesthetics-induced neurotoxicity in developing brain: an update on preclinical evidence. Zhou Z1, Ma D2. Brain Sci. 2014 Mar 14;4(1):136-49. doi: 10.3390/brainsci4010136. Abstract Every year millions of young people are treated with anaesthetic agents for surgery and sedation in a seemingly safe manner. However, growing and convincing preclinical evidence in rodents and nonhuman primates, together with recent epidemiological observations, suggest that exposure to anaesthetics in common clinical use can be neurotoxic to the developing brain and lead to long-term neurological sequelae. These findings have seriously questioned the safe use of general anaesthetics in obstetric and paediatric patients. The mechanisms and human applicability of  anaesthetic neurotoxicity and neuroprotection have remained under intense investigation over the past decade. Ongoing pre-clinical investigation may have significant impact on clinical practice in the near future. This review represents recent developments in this rapidly emerging field. The aim is to summarise recently available laboratory data, especially those being published after 2010, in the field of anaesthetics-induced neurotoxicity and its impact on cognitive function. In addition, we will discuss recent findings in mechanisms of early-life anaesthetics-induced neurotoxicity, the role of human stem cell-derived models in detecting such toxicity, and new potential alleviating strategies. PDF

Anestesiología y Medicina del Dolor 52 664 6848905 vwhizar@anestesia-dolor.org anestesia-dolor.org