A continuous supply of oxygen, the gaseous waste product of plant photosynthesis, is essential to sustain cellular metabolism in all aerobic organisms, including humans.Oxygen is a highly reactive gas that is capable of combining with most other elements because of the avidity with which it attracts electrons. This process may occur slowly and remorselessly, as is seen when iron rusts, or rapidly and catastrophically, as occurs during forest fires. Controlled oxidation of glucose, and other substrates, to carbon dioxide with the consequent reduction of oxygen to water is the basis of aerobic cellular metabolism, one of the hallmarks of vertebrate physiology.
Reactive oxygen species (ROS), also known as oxygen free radicals, contain one or more unpaired electrons and, as their name suggests, are considerably more reactive than their corresponding non-radical form. They are generated within mitochondria during normal cellular metabolism. ROS generation may be accelerated under certain conditions including hyperoxia and, paradoxically, hypoxia. Imbalance between the generation and breakdown of ROS resulting in net gain of ROS species leads to oxidative stress and the potential for harm. Defence against hyperoxic damage has been a central theme of animal evolution. The endosymbiotic integration of primitive bacteria into early unicellular organisms led to the evolution of the mitochondrion as an intracellular organelle. This unusual amalgamation of dissimilar species both conferred protection against increasing atmospheric oxygen levels (through ROS metabolism) and facilitated respiration in host cells that had previously relied on glycolysis and fermentation as sources of chemical energy. The relationship facilitated the evolution of multicellular organisms, a development that can be considered as a sophisticated response to the challenge of defending against cellular hyperoxia.
Oxygen is arguably the most widely used drug in anaesthesia and in acute hospital care in general. More than 15% of hospital admissions in the UK are being administered oxygen at any point in time.Very few patients receive general anaesthesia or enter a critical care unit without receiving oxygen and there are estimated to be more than 1.5 million major (in-patient) surgical procedures requiring anaesthesia each year in the UK and more than 235 000 critical care admissions.Furthermore, the vast majority of patients with acute pulmonary (>2.5 million hospital bed days per year in UK) or cardiac (>450 000 patients episodes per year in the UK) conditions will be administered oxygen at some time during a hospital admission. More than one-third of patients brought to hospital by ambulance are administered oxygen. Ultimately, the sickest patients, and therefore those at most risk of adverse outcome, are most likely to receive oxygen therapy.
The near universal use of oxygen therapy in acutely ill patients is based on the premise that minimizing cellular hypoxia is among the highest priorities of urgent care, but also rests on the assumption that excess oxygen is not harmful. Clinical data from a variety of contexts suggest that this assumption may not hold, which in turn suggests that greater attention to the precision with which oxygen is administered may be of benefit to patients. Data from clinical studies are highlighting the potential harms of unrestricted administration of oxygen to patients. For example, small clinical trials have shown increased mortality after acute myocardial infarction and ischaemic stroke in patients administering supplemental oxygen, when compared with patients receiving room air.
Within the speciality of anaesthesia, oxygen is mainly administered under three intersecting sets of conditions: (i) perioperative care, (ii) critical care, and (iii) resuscitation. New data highlighting the complex relationship between oxygen therapy and clinical outcome are available in all three of these clinical situations.
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