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Oxygen is the most commonly used drug in critical care. However, because it is a gas, most clinicians and most patients do not regard it as a drug. For this reason, the use of medical oxygen over the past century has been driven by custom, practice, and "precautionary principles" rather than by scientific principles. Oxygen is a life-saving drug for patients with severe hypoxemia, but, as with all other drugs, too much can be harmful. It has been known for many decades that the administration of supplemental oxygen is hazardous for some patients with COPD and other patients who are vulnerable to retention of carbon dioxide (ie, hypercapnia). It has been recognized more recently that excessive oxygen therapy is associated with significantly increased mortality in critically ill patients, even in the absence of risk factors for hypercapnia. This paper provides a critical overview of past and present oxygen use for critically ill patients and will provide guidance for safer oxygen use in the future., Competing Interests: The authors have disclosed no conflicts of interest., (Copyright © 2019 by Daedalus Enterprises.)

The Royal Air Force (RAF) came into being during World War I as the world's first independent air force on the 1 April 1918, amalgamating elements of the Royal Flying Corps (RFC), itself established in 1912 and the Royal Naval Air Service which had formally separated from the Admiralty's administered Air Wing of the RFC in 1915. The RAF therefore celebrates its 100th anniversary in the same year that the Royal College of Physicians of London celebrates its 500th. This article will cover the contribution that military aviation has made to medicine since 1913 with the emphasis of three examples focusing on delivering care by air, providing care in the air and in developing systems for supporting aircrew or patients at the extremes of physiological stress., (© Royal College of Physicians 2018. All rights reserved.)

The history of oxygen from discovery to clinical application for patients with chronic lung disease represents a long and storied journey. Within a relatively short period, early investigators not only discovered oxygen but also recognized its importance to life and its role in respiration. The application of oxygen to chronic lung disease, however, took several centuries. In the modern era, physiologists pursued the chemical nature of oxygen and its physiologic interaction with cellular metabolism and gas transport. It took brazen clinicians, however, to pursue oxygen as a therapeutic resource for patients with chronic lung disease because of the concern in the 20th century of the risks of oxygen toxicity. Application of ambulatory oxygen devices allowed landmark investigations of the long-term effects of continuous oxygen that established its safety and efficacy. Although now well established for hypoxic patients, many questions remain regarding the benefits of oxygen for varying severity and types of chronic lung disease.

Oxygen is necessary for all aerobic life, and nothing is more important in respiratory care than its proper understanding, assessment, and administration. By the early 1970s P(aO(2)) had become the gold standard for clinically assessing oxygenation in the body. Since the 1980s the measurement of arterial oxygen saturation by pulse oximetry has also been increasingly used as an adjunct to (but not a replacement for) P(aO(2)). Despite the desirability of measuring tissue oxygenation directly, no reliable and clinically relevant such measure has emerged. The 2 areas in which oxygen has proven most important in respiratory care are long-term oxygen therapy (LTOT) and the management of potentially life-threatening hypoxemia in acute respiratory failure. That LTOT improves survival in appropriately selected patients with COPD was demonstrated by multicenter studies published more than 30 years ago, and their original selection criteria have so far not been improved upon. Severe hypoxemia in acute lung injury and ARDS can be improved by ventilation with PEEP, and also in many patients by various adjunctive techniques and alternative support strategies. However, the latter measures have not brought clear improvements in survival or other patient-relevant outcomes. In addition, the original goals of "normalizing" arterial oxygenation with high tidal volumes and lung-distending pressures have required modification as appreciation for ventilator-related lung injury has emerged. High concentrations of inspired oxygen may play a role in such injury, but aggressive measures to reduce them in order to avoid oxygen toxicity-which dominated ventilator management in previous decades-have been tempered in the present era of lung-protective ventilation. Although some additions and modifications have emerged, much of what we understand today about oxygen in respiratory care is owed to the pioneering work of Thomas L Petty more than 40 years ago.

Overview: Oxygen has been a generally accepted treatment method for cluster headache attacks ever since Kudrow (1981) conducted a controlled trial showing that oxygen was equally or even more effective than ergotamine injections., Purpose: The aim of the present study was to provide a historical perspective of oxygen treatment in cluster headache and to find the origin of this treatment. Oxygen for cluster headache was first described by Horton in 1952 and for migraine patients in 1940 by Alvarez. At the time, neither of the authors provided any reason why they chose for this treatment method. The vasoconstrictive effect of oxygen was not described by Horton until 1961., Conclusion: We suggest that these authors originally adhered to the vasoconstrictive theory of vascular headache that was prevalent in the early 20th century until Wolff demonstrated the contrary in the late 1930s. The early literature describes an analogy between angina pectoris and migraine, as both being due to vasoconstriction. As oxygen was described as a treatment for angina pectoris, this may be the reason why oxygen was tried for migraine and cluster headache at a time when they were not recognized as separate entities. Later it turned out to be more effective for cluster headache.

Pulmonary rehabilitation is widely accepted as effective therapy for patients with chronic obstructive pulmonary disease (COPD). This paper presents a brief (and somewhat subjective) history of pulmonary rehabilitation, and stresses the development of the exercise component. Until the middle of the 20th century, patients with COPD were advised to avoid the dyspnea that activity brings. Barach can be credited with positing that patients with COPD should strive to be more active. In the 1960s Petty created the multi-disciplinary team that was found to be effective in delivering pulmonary rehabilitation. In the 1980s doubts surfaced as to the ability of rehabilitative exercise to improve muscle function in COPD, but in the 1990s studies showed that well-designed exercise programs caused beneficial physiologic adaptations. The current decade has yielded studies that exploited those insights to design interventions that boost the effectiveness of rehabilitative exercise.

Georges Dreyer was the first Professor of Pathology at Oxford University and he held this post from 1907 to 1934. Although his main research interests were in bacteriology and immunity, he made important contributions to respiratory physiology, but these have been almost completely forgotten. He developed a new apparatus for administering low oxygen mixtures to test the effects of hypoxia in airmen during World War I, developed a high successful oxygen delivery system, was responsible for the first low-pressure chamber in a UK academic institution, and carried out some physiological measurements in the chamber that were years ahead of their time. His chamber was also used by a group from Cambridge and Turin, Italy for a series of important physiological studies. In spite of these contributions, almost nobody who works in respiratory physiology today, even in Oxford, recognizes the name of Dreyer.

The search for a connection between James Robinson, the dental surgeon who on 19 December 1846 administered the first general anaesthetic in England by the inhalation of the vapour of ether, and William Hooper, the pharmaceutical chemist who produced the best publicised and most widely used of the early commercial ether vaporisers, has revealed hitherto unrecognised aspects of the early history of general anaesthesia.

The evolution of knowledge concerning COPD and its components--emphysema, chronic bronchitis, and asthmatic bronchitis--covers 200 years. The stethoscope and spirometer became important early tools in diagnosis and assessment. Spirometry remains the most effective means of identification and assessment of the course of COPD and responses to therapy, and is grossly underused for this purpose. Knowledge of the pathogenesis, course and prognosis, and new approaches to therapy have dramatically improved our understanding of this important clinical entity. Smoking cessation improves the early course of disease. Long-term oxygen improves the length and quality of life in selected patients with hypoxemia. Surgery benefits a select few. Today, COPD is a steadily growing global healthcare problem, with increasing morbidity and mortality. Early identification and prevention, and treatment of emerging stages of disease through smoking cessation and a growing number of bronchoactive drugs promises to change the outcome.

A commemorative plaque in York Hospital in Pennsylvania, USA, records that George E Holtzapple MD is the physician 'who discovered the use of oxygen for the treatment of pneumonia on March 6, 1885'. This paper suggests that Dr Holtzapple was not the first to use oxygen for pneumonia patients but was the first to publish a case report with a reasoned physiological explanation of oxygen therapy. His publication was intended, in his own words, to benefit 'average country practitioners' who had no other means of learning about this valuable therapy.

Two days before the first ascent of Mt. Everest in 1953, Tom Bourdillon and Charles Evans climbed to within 90 m of the summit at unprecedented speeds. By breathing pure oxygen from a closed circuit, the pair were able to obtain an enormous physiological advantage. Unfortunately, due to a malfunction in Evans's circuit, the pair abandoned their attempt on the South Summit. For many who used the circuit in the 1930s and 1950s, the device proved too heavy, uncomfortable, and tiring for mountaineering. These factors, together with the wider ethical concerns of using supplemental oxygen at altitude, have meant that closed-circuit oxygen has been ignored for more than 50 years. In this article the authors will attempt to describe the history of this discarded circuit and the experience of those who utilized it.

Oxygen was identified at the end of the 18th century by three independent researchers. It was first used indiscriminately with other gases for treatment of pulmonary diseases by Thomas Beddoes. In the 19th century, the physiological properties of oxygen were identified by many researchers. In that same century, physicians used oxygen empirically for a variety of conditions. Osler, who wrote on pneumonia, appreciated that blood was "imperfectly oxidised" (sic) in pneumonia, but concluded that the toxicity of oxygen more than outweighed its possible benefits. Meakins applied the lessons he learned from studying the hypoxemia that resulted from poison gas in World War I to pneumonia. He confirmed that patients with severe pneumonia were hypoxemic and that many of their symptoms appeared to be relieved by inhalation of oxygen. Oxygen then became the standard therapy for pneumonia.

The therapeutic use of oxygen was pioneered in the early 20(th) century by the respiratory physiologist John Scott Haldane. His work followed Claude Bernard's description of the toxic effects of carbon monoxide. Haldane, having also observed the effects of carbon monoxide poisoning, became aware of the therapeutic benefits of oxygen in this condition. He was also an advocate of oxygen as a therapeutic agent in other respiratory illness, and made efforts to define how the gas could best be administered. The history of identification of oxygen as a chemical element is convoluted. In the 17(th) century, the controversial John Mayow suggested that only a portion of air was necessary for sustaining life. Mayow's work was largely overlooked during his lifetime, and his insight was subsequently eclipsed by the phlogiston theory, an erroneous concept widely believed for nearly a century after his death. This theory was ultimately disproved by Joseph Priestley in 1774. Although the point of primacy is somewhat contentious, Priestley shares the distinction of discovering elemental oxygen with Antoine-Laurent Lavoisier, the French chemist, and Carl Wilhelm Scheele, the Swedish apothecary.

Nearly 50 years after it was thought to be conquered, retinopathy of prematurity (ROP) continues to cause vision disturbances and blindness among prematurely born infants. During the 1940s and early 1950s, researchers and caregivers first identified and struggled to eliminate this problem, which seemed to come from nowhere and was concentrated among the most advanced premature nurseries in the U.S. Research studies initially identified many potential causes, none of which could be proved conclusively. By the mid 1950s, oxygen was identified as the culprit, and its use was immediately restricted. The rate of blindness among premature infants decreased significantly. ROP was not cured, however. By the 1960s, it had reappeared. The history of ROP serves to remind us that, despite our best intentions, the care and treatment of premature newborns will always carry with it the possibility of iatrogenic disease. This caution is worth remembering as we work to expand the quality and quantity of clinical research.

George Ingle Finch (1888-1970) was the first person to prove the great value of supplementary oxygen for climbing at extreme altitudes. He did this during the 1922 Everest expedition when he and his companion, Geoffrey Bruce, reached an altitude of 8,320 m, higher than any human had climbed before. Finch was well qualified to develop the oxygen equipment because he was an eminent physical chemist. Many of the features of the 1922 design are still used in modern oxygen equipment. Finch also demonstrated an extraordinary tolerance to severe acute hypoxia in a low-pressure chamber experiment. Remarkably, despite Finch's desire to participate in the first three Everest expeditions in 1921-1924, he was only allowed to be a member of one. His rejection from the 1921 expedition was based on medical reports that were apparently politically biased. Then, following his record ascent in 1922, he was refused participation in the 1924 expedition for complex reasons related to his Australian origin, his forthright and unconventional views, and the fact that some people in the climbing establishment in Britain saw Finch as an undesirable outsider.

This is the second part of a survey which analyses the history of inhalative oxygen therapy and its interactions with the history of anaesthesiology. Specific emphasis is put here on illustrating inventions of modern pressure gas technology such as pressure reducing valves. These enabled Draeger Inc. to be the first firm to develop and trade on a large scale technically convincing products allowing a rational, therapeutic application of oxygen. Especially Draeger anaesthesia apparatus (e. g. the "Roth-Draeger Anaesthesia Apparatus") and respiratory protective devices, which were available from 1902, proved also internationally successful from the very beginning. In the international historiography on inhalative oxygen therapy, however, these contributions have to our knowledge so far never been systematically considered. Consequently, J. S. Haldane (1860 - 1936) is regarded there to have "founded" of modern oxygen therapy in 1917. Critically reviewing this earlier research, we propose a historical reassessment, concluding that the year 1902 was the historically decisive "turning point" towards the development of modern oxygen therapy.

This series discusses errors in neonatology since the 1920s. Three historical periods are defined: the "Hands-Off" years, 1920 to 1950; the "Heroic" years, 1950 to 1970; and the "Experienced" years, 1970 to 2000. In this article, the "Hands-Off" years, we discuss lowered thermal environment, supplemental oxygen, initial thirsting and starving, synthetic vitamin K, SMA formula, and diaper markings.

This historical survey in two parts analyses the history of inhalative oxygen therapy and its interactions with the history of anaesthesiology. For this purpose, we will start with illustrating "the long way of oxygen" from its first isolation by Carl Wilhelm Scheele (1772) and Joseph Priestley (1774) to its breakthrough for therapeutic application in the 20th century. We will show that the two main factors delaying the successful implementation of a truly rational oxygen therapy were of technical nature: The complicated and costly production of the gas and insufficient means to apply it continuously and with reliable and sufficient dosages to the patients. Both problems could not be satisfactorily solved until 1902. From this year on, however, the "Linde Process" allowed cheap mass-production of oxygen. Simultaneously, various inventions of modern pressure gas technology allowed to solve the application problems. Here, a special significance is to be awarded to pressure reducing valves. These were first introduced into medical technology by Draeger Inc. (Lübeck/Germany) on a significant scale, proving particularly successful in anaesthesia and rescue-devices (e. g. in the "Roth-Draeger Anaesthesia Apparatus" [1902]). Critically discussing earlier research on the history of oxygen therapy, we therefore propose a historical reassessment, accepting the year 1902 as the internationally decisive "turning point" towards the development of modern oxygen therapy.

Attempts at human resuscitation date back to ancient times. Most strategies for resuscitation focused on adults until the early 1800s, when newborn resuscitation captured the interest of noted practitioners. The most promising techniques and strategies for neonatal resuscitation were developed during the latter part of the twentieth century. This article examines the key components of neonatal resuscitation and the discoveries that stimulated the development of current neonatal resuscitation practices.

After a brief outline of some early theories about the effects of thin air, the attempt of Joseph Ch. Hamel on Mont Blanc in 1820 is described. The Russian physician had postulated that lack of oxygen was responsible for muscular weakness at altitude and therefore had planned to study the oxygen content of air and blood on the summit and to administer oxygen to see if it improved performance. During the ascent he observed "pneumatic flatulence," shortness of breath, and fatigue. Shortly before the summit, an avalanche, which killed three of his guides, stopped and terminated the expedition. Although Hamel may have lacked the necessary equipment, he was among the first to try to test his hypothesis on altitude effects by experiments.

The story of the development of oxygen and its role in mitigating the ravages of chronic stable hypoxemia have been fascinating. Today, over one million Americans receive home oxygen each day, usually for COPD, from one of the three available systems. The future requires less expensive, highly portable, and practical devices for use during all activities of daily living.

The gas-therapy unit was founded by professor Oszacki in Cracow's St. Lazarus Hospital in 1937. This was the beginning of the new therapy, well known in West Europe. Well equipped and modern provided unit worked nearly two years. In 1939 the oxygen explosion and subsequent fire completely destroyed it. In this accident three young doctors died. The Second World War interrupted further development of this new therapy.

During the late nineteenth and early twentieth centuries, gas-pipes were among the most popular therapeutic devices available to an unhealthy public. Spurred on by the explosion of print advertising, mail-order gas-pipes were questionable remedies promoted for such diverse conditions as pneumonia and neurasthenia. Though they are an interesting part of the social history of questionable therapeutics, no historian has recently looked in depth at these devices. This paper examines the clinical, social, and economic environment that facilitated the success of the most ubiquitous gas-pipe, the Oxydonor, and its proprietor, Hercules Sanche.

Long-term oxygen therapy (LTOT) is known since the second half of the present century. In Poland it was introduced in 1986. By the end of 1991, 37 regional LTOT centers, using almost 1000 oxygen concentrators as oxygen source, were organized all over the country. To LTOT are classified two groups of patients with the advanced chronic pulmonary disease complicated with fixed respiratory failure and frequently with cor pulmonale. One group consist of patients with severe hypoxemia (PaO2 < or = 7.3 kPa, i.e. < or = 55 mm Hg) accompanied by the signs of cor pulmonale or tissue hypoxia whereas another consists of patients with moderate hypoxemia (PaO2 7.4-7.8 kPa, i.e. 55-65 mm Hg). A 5-year history of the regional LTOT centres in Poland was assessed. According to questionnaires received from 27 centres, 971 patients (662 males and 309 females), aged 59.3 years on the average, were classified to the long-term oxygen therapy between August 1, 1986 and December 31, 1991. Six hundred fifty seven patients (67.6%) has COPD, 229 (23.6%) had non-COPD pulmonary disease, and 85 patients (8.8%)-other diseases. Six hundred forty four patients (66.3%) were given oxygen concentrators for severe hypoxemia and 327 patients (33.7%) for moderate hypoxemia wit co-existing signs of the cor pulmonale and tissue hypoxia. Mean time of oxygen use in 839 patients was 13.8 hours a day. Long-term oxygen therapy was ceased in 31 patients (3.2%).(ABSTRACT TRUNCATED AT 250 WORDS)

Several intellectual "autopsies" have recently reviewed errors in clinical epidemiologic studies of causation, such as the original claim that amyl nitrite "poppers" caused AIDS. The current autopsy was done to determine why it took more than a decade--1942 to 1954--to end an iatrogenic epidemic in which high-dose oxygen therapy led to retrolental fibroplasia (RLF) in premature infants, blinding about 10,000 of them. The autopsy revealed a museum of diverse intellectual pathology. When first noted, RLF was regarded as neither a new disease nor a postnatal effect. In early investigations, the ophthalmologists did not establish explicit criteria for diagnosis and confused RLF with malformations previously seen in full-term infants. Because the patients were not referred until months after birth, the ophthalmologists assumed that the lesion, which resembled an embryologic structure, must have occurred prenatally. Other events suggesting a prenatal cause for RLF were its strong statistical associations with fetal anomalies, multiple gestations, and maternal infections. Although these events were also associated with prematurity, it was ignored when the RLF cases were compared with controls who were mainly full-term infants. The postnatal timing of RLF was eventually recognized when investigators did cohort studies in premature infants and found that RLF could develop in eyes that were normal at birth. As the search for a cause turned to events occurring after birth, statistical associations were produced for agents such as light, vitamins, iron, vitamin E deficiency, and hypoadrenalism. Each study had its own methodologic flaws: controls were missing for light; co-maneuvers were ignored for vitamins and iron; objective diagnosis was not used for vitamin E deficiency; and the research on hypoadrenalism contained biases in susceptibility and detection as well as problems of a competing outcome event. When the role of oxygen administration was first considered, the statistical association with RLF was stronger for vitamin- and iron-therapy than for oxygen. In addition, many investigators were dissuaded by contradictory evidence from institutions in which RLF was either absent despite high-dose oxygen or persistent despite reduced dosage. The contradictory evidence was later regarded as erroneous because of unsatisfactory delivery systems for the oxygen or failure to check the actual oxygen concentrations. An alternative explanatory hypothesis, rejecting the role of high-dose and long-duration oxygen, was the idea that RLF was due to "relative hypoxia", produced by overly rapid weaning from oxygen therapy rather than the duration of oxygen treatment itself.(ABSTRACT TRUNCATED AT 400 WORDS)