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Oxygen as a therapeutic agent in neonatology: a comprehensive approach
Seminars in Fetal & Neonatal Medicine 15 (2010) 185
Contents lists available at ScienceDirect
Seminars in Fetal & Neonatal Medicine journal homepage: www.elsevier.com/locate/siny
Editorial
Oxygen as a therapeutic agent in neonatology: a comprehensive approach
Oxygen is among the most common elements in nature and probably one of the most frequently employed drugs in neonatology. As a final acceptor of highly energised electrons, oxygen is the key element of aerobic metabolism. Thus, oxidative phosphorylation, which couples the Krebs cycle with the electron transport chain in the mitochondria, allows living organisms to very efficiently extract energy from basic nutrients. However, as by-products of oxidative metabolism, reactive oxygen species (ROS) are produced, some of which are highly reactive free radicals that are capable of causing structural and functional damage to nearby standing molecules. Other ROS will act as signalling molecules implicated in the regulation of metabolic pathways. When the equilibrium between production of free radicals and the enzymatic and non-enzymatic antioxidant defence system is lost in favour of pro-oxidant agents, oxidative stress will ensue with accompanying damage to tissue and enhanced expression of inflammatory transcription factors. In the foetal-to-neonatal transition, abrupt changes in the tissue oxygen availability will cause oxidative stress, which, under physiological conditions, will induce the expression of specific metabolic pathways necessary for an adequate extrauterine adaptation. However, under certain circumstances such as birth asphyxia or extreme prematurity, the need for oxygen as a therapeutic agent will cause collateral damage in the form of acute or chronic pathology, termed ‘oxygen radical disease of the newborn’. At present there is great uncertainty about how to provide adequate oxygenation and thus cause the least damage to the newborn, especially to the very preterm. In this issue of Seminars, internationally recognised experts describe basic aspects of oxygen metabolism and toxicity, antioxidant defence maturation and regulation of the biological response to
1744-165X/$ – see front matter Ó 2010 Elsevier Ltd. All rights reserved. doi:10.1016/j.siny.2010.04.002
oxygen through hypoxia-inducible factor alpha (HIF-a) and the possible therapeutic use of HIF stabilisers. Another important aspect is the adequate control of oxygenation in the clinical setting by pulse oximetry. In this regard, one chapter discusses how to use recently developed reference oxygen saturation curves for term and preterm infants. Another chapter focuses on the concept and clinical applications of oxygen extraction as a means of non-invasively evaluating tissue oxygenation. The following two chapters deal from a clinical pzerspective with resuscitation of term and preterm infants in the delivery room and with the consequences of oxygen therapy upon the lung. Importantly, the last chapter examines the long term consequences of the use of oxygen in the neonatal period, which all neonatologists should bear in mind when treating small babies in the neonatal intensive care unit. It has been the aim of this issue of the journal to give a comprehensive review of oxygen use, from the basics to the clinical applications and deleterious consequences, not only in the neonatal period but also long term. We sincerely hope that our efforts will be informative, helping to enable the proper use of this therapeutic agent. Maximo Vento* Neonatal Research Unit, Division of Neonatology, University Hospital Materno-Infantil La Fe, Valencia, Spain * Corresponding author. E-mail address: [email protected] (M. Vento) Ola Didrik Saugstad Department of Pediatric Research, National Hospital, Oslo, Norway
Contents lists available at ScienceDirect
Seminars in Fetal & Neonatal Medicine journal homepage: www.elsevier.com/locate/siny
Editorial
Oxygen as a therapeutic agent in neonatology: a comprehensive approach
Oxygen is among the most common elements in nature and probably one of the most frequently employed drugs in neonatology. As a final acceptor of highly energised electrons, oxygen is the key element of aerobic metabolism. Thus, oxidative phosphorylation, which couples the Krebs cycle with the electron transport chain in the mitochondria, allows living organisms to very efficiently extract energy from basic nutrients. However, as by-products of oxidative metabolism, reactive oxygen species (ROS) are produced, some of which are highly reactive free radicals that are capable of causing structural and functional damage to nearby standing molecules. Other ROS will act as signalling molecules implicated in the regulation of metabolic pathways. When the equilibrium between production of free radicals and the enzymatic and non-enzymatic antioxidant defence system is lost in favour of pro-oxidant agents, oxidative stress will ensue with accompanying damage to tissue and enhanced expression of inflammatory transcription factors. In the foetal-to-neonatal transition, abrupt changes in the tissue oxygen availability will cause oxidative stress, which, under physiological conditions, will induce the expression of specific metabolic pathways necessary for an adequate extrauterine adaptation. However, under certain circumstances such as birth asphyxia or extreme prematurity, the need for oxygen as a therapeutic agent will cause collateral damage in the form of acute or chronic pathology, termed ‘oxygen radical disease of the newborn’. At present there is great uncertainty about how to provide adequate oxygenation and thus cause the least damage to the newborn, especially to the very preterm. In this issue of Seminars, internationally recognised experts describe basic aspects of oxygen metabolism and toxicity, antioxidant defence maturation and regulation of the biological response to
1744-165X/$ – see front matter Ó 2010 Elsevier Ltd. All rights reserved. doi:10.1016/j.siny.2010.04.002
oxygen through hypoxia-inducible factor alpha (HIF-a) and the possible therapeutic use of HIF stabilisers. Another important aspect is the adequate control of oxygenation in the clinical setting by pulse oximetry. In this regard, one chapter discusses how to use recently developed reference oxygen saturation curves for term and preterm infants. Another chapter focuses on the concept and clinical applications of oxygen extraction as a means of non-invasively evaluating tissue oxygenation. The following two chapters deal from a clinical pzerspective with resuscitation of term and preterm infants in the delivery room and with the consequences of oxygen therapy upon the lung. Importantly, the last chapter examines the long term consequences of the use of oxygen in the neonatal period, which all neonatologists should bear in mind when treating small babies in the neonatal intensive care unit. It has been the aim of this issue of the journal to give a comprehensive review of oxygen use, from the basics to the clinical applications and deleterious consequences, not only in the neonatal period but also long term. We sincerely hope that our efforts will be informative, helping to enable the proper use of this therapeutic agent. Maximo Vento* Neonatal Research Unit, Division of Neonatology, University Hospital Materno-Infantil La Fe, Valencia, Spain * Corresponding author. E-mail address: [email protected] (M. Vento) Ola Didrik Saugstad Department of Pediatric Research, National Hospital, Oslo, Norway