Estrés oxidativo en la asfixia perinatal y la encefalopatía hipóxico-isquémica / Oxidative stress in perinatal asphyxia and hypoxic-ischaemic encephalopathy

La asfixia intraparto es una de las causas más frecuentes de muerte neonatal precoz pero también puede, en los supervivientes, evolucionar a una encefalopatía hipóxico-isquémica responsable de una elevada morbilidad neurológica. La presencia de episodios de hipoxia-isquemia prolongados conduce a un rápido agotamiento energético en los tejidos exclusivamente dependientes del metabolismo aeróbico, como el sistema nervioso central. El déficit energético conlleva una paralización de las bombas ATP-dependientes y subsiguiente pérdida del potencial neuronal transmembrana. La población neuronal de las regiones más sensibles del SNC mueren por necrosis, mientras que en otras áreas se produce una hiperexcitabilidad neuronal con entrada masiva de calcio iónico, activación de NO-sintasa, generación de radicales libres que alteran el funcionamiento mitocondrial, provocando un fallo energético secundario y muerte neuronal por apoptosis. Recientemente se ha propuesto una tercera fase en la que factores como la inflamación persistente y los cambios epigenéticos causarían un bloqueo de la maduración de los oligodendrocitos, alteración de la neurogénesis, del crecimiento axonal y de la sinaptogénesis. En este contexto, el estrés oxidativo va a tener un papel protagonista como responsable tanto en causar daño directo al SNC como en activar cascadas metabólicas conducentes a la apoptosis e inflamación. La hipotermia moderada precoz, al preservar las reservas energéticas y disminuir la formación de especies reactivas de oxígeno, atenuará el daño cerebral posreanimación. La combinación de la hipotermia con terapias coadyuvantes para modular el estrés oxidativo podría contribuir a mejorar el pronóstico

Birth asphyxia is one of the principal causes of early neonatal death. In survivors it may evolve to hypoxic-ischaemic encephalopathy and major long-term neurological morbidity. Prolonged and intense asphyxia will lead to energy exhaustion in tissues exclusively dependent on aerobic metabolism, such as the central nervous system. Energy deficit leads to ATP-dependent pumps blockage, with the subsequent loss of neuronal transmembrane potential. The most sensitive areas of the brain will die due to necrosis. In more resistant areas, neuronal hyper-excitability, massive entrance of ionic calcium, activation of NO-synthase, free radical generation, and alteration in mitochondrial metabolism will lead to a secondary energy failure and programmed neuronal death by means of the activation of the caspase pathways. A third phase has recently been described that includes persistent inflammation and epigenetic changes that would lead to a blockage of oligodendrocyte maturation, alteration of neurogenesis, axonal maturation, and synaptogenesis. In this scenario, oxidative stress plays a critical role causing direct damage to the central nervous system and activating metabolic cascades leading to apoptosis and inflammation. Moderate whole body hypothermia to preserve energy stores and to reduce the formation of oxygen reactive species attenuates the mechanisms that lead to the amplification of cerebral damage upon resuscitation. The combination of hypothermia with coadjuvant therapies may contribute to improve the prognosis

[Oxidative stress in perinatal asphyxia and hypoxic-ischaemic encephalopathy]. / Estrés oxidativo en la asfixia perinatal y la encefalopatía hipóxico-isquémica.

Birth asphyxia is one of the principal causes of early neonatal death. In survivors it may evolve to hypoxic-ischaemic encephalopathy and major long-term neurological morbidity. Prolonged and intense asphyxia will lead to energy exhaustion in tissues exclusively dependent on aerobic metabolism, such as the central nervous system. Energy deficit leads to ATP-dependent pumps blockage, with the subsequent loss of neuronal transmembrane potential. The most sensitive areas of the brain will die due to necrosis. In more resistant areas, neuronal hyper-excitability, massive entrance of ionic calcium, activation of NO-synthase, free radical generation, and alteration in mitochondrial metabolism will lead to a secondary energy failure and programmed neuronal death by means of the activation of the caspase pathways. A third phase has recently been described that includes persistent inflammation and epigenetic changes that would lead to a blockage of oligodendrocyte maturation, alteration of neurogenesis, axonal maturation, and synaptogenesis. In this scenario, oxidative stress plays a critical role causing direct damage to the central nervous system and activating metabolic cascades leading to apoptosis and inflammation. Moderate whole body hypothermia to preserve energy stores and to reduce the formation of oxygen reactive species attenuates the mechanisms that lead to the amplification of cerebral damage upon resuscitation. The combination of hypothermia with coadjuvant therapies may contribute to improve the prognosis.

La bioética en el final de la vida en neonatología: cuestiones no resueltas / Bioethics in end-of-life decisions in neonatology: Unresolved issues

El presente documento es fruto del trabajo previo realizado por diferentes grupos de expertos y presentado a debate multidisciplinar en unas jornadas sobre aspectos controvertidos, deficientes o nuevos en el cuidado paliativo neonatal, como son: 1) el procedimiento deliberativo en la toma de decisiones; 2) el cuidado paliativo hospitalario y domiciliario; 3) la donación en asistolia controlada, y 4) el estrés moral en los profesionales. Las conclusiones más relevantes fueron la necesidad de que los profesionales adquieran formación en bioética y se ejerciten en la práctica de la metodología deliberativa para facilitar la toma de decisiones prudentes y razonables; la falta de desarrollo en los hospitales que atienden recién nacidos, del cuidado paliativo perinatal y del cuidado paliativo domiciliario neonatal; la necesidad de facilitar a las Unidades Neonatales recursos que ayuden a capacitar a los profesionales en técnicas de comunicación y de gestión del estrés emocional, así como delinear procesos operativos y protocolos para la donación de órganos (AU)

This document is the result of previous work carried out by different expert groups and submitted to multidisciplinary debate at a Conference about controversial, deficient, or new aspects in the field of neonatal palliative care, such as: 1) the deliberative decision-making process, 2) hospital and domiciliary palliative care, 3) donation after controlled cardiac death, and 4) moral stress in professionals. The most relevant conclusions were: the need to instruct professionals in bioethics and in the deliberative method to facilitate thorough and reasonable decision-making; the lack of development in the field of perinatal palliative care and domiciliary palliative care in hospitals that attend newborns; the need to provide neonatal units with resources that help train professionals in communication skills and in the management of moral distress, as well as delineate operational procedure and guidelines for neonatal organ donation (AU)

[Bioethics in end-of-life decisions in neonatology: Unresolved issues]. / La bioética en el final de la vida en neonatología: cuestiones no resueltas.

This document is the result of previous work carried out by different expert groups and submitted to multidisciplinary debate at a Conference about controversial, deficient, or new aspects in the field of neonatal palliative care, such as: 1) the deliberative decision-making process, 2) hospital and domiciliary palliative care, 3) donation after controlled cardiac death, and 4) moral stress in professionals. The most relevant conclusions were: the need to instruct professionals in bioethics and in the deliberative method to facilitate thorough and reasonable decision-making; the lack of development in the field of perinatal palliative care and domiciliary palliative care in hospitals that attend newborns; the need to provide neonatal units with resources that help train professionals in communication skills and in the management of moral distress, as well as delineate operational procedure and guidelines for neonatal organ donation.