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Concept: Oxygen therapy


Background The clinical effect of routine oxygen therapy in patients with suspected acute myocardial infarction who do not have hypoxemia at baseline is uncertain. Methods In this registry-based randomized clinical trial, we used nationwide Swedish registries for patient enrollment and data collection. Patients with suspected myocardial infarction and an oxygen saturation of 90% or higher were randomly assigned to receive either supplemental oxygen (6 liters per minute for 6 to 12 hours, delivered through an open face mask) or ambient air. Results A total of 6629 patients were enrolled. The median duration of oxygen therapy was 11.6 hours, and the median oxygen saturation at the end of the treatment period was 99% among patients assigned to oxygen and 97% among patients assigned to ambient air. Hypoxemia developed in 62 patients (1.9%) in the oxygen group, as compared with 254 patients (7.7%) in the ambient-air group. The median of the highest troponin level during hospitalization was 946.5 ng per liter in the oxygen group and 983.0 ng per liter in the ambient-air group. The primary end point of death from any cause within 1 year after randomization occurred in 5.0% of patients (166 of 3311) assigned to oxygen and in 5.1% of patients (168 of 3318) assigned to ambient air (hazard ratio, 0.97; 95% confidence interval [CI], 0.79 to 1.21; P=0.80). Rehospitalization with myocardial infarction within 1 year occurred in 126 patients (3.8%) assigned to oxygen and in 111 patients (3.3%) assigned to ambient air (hazard ratio, 1.13; 95% CI, 0.88 to 1.46; P=0.33). The results were consistent across all predefined subgroups. Conclusions Routine use of supplemental oxygen in patients with suspected myocardial infarction who did not have hypoxemia was not found to reduce 1-year all-cause mortality. (Funded by the Swedish Heart-Lung Foundation and others; DETO2X-AMI number, NCT01787110 .).

Concepts: Oxygen, Epidemiology, Clinical trial, Myocardial infarction, Atherosclerosis, Randomness, Troponin, Oxygen therapy


Background Long-term treatment with supplemental oxygen has unknown efficacy in patients with stable chronic obstructive pulmonary disease (COPD) and resting or exercise-induced moderate desaturation. Methods We originally designed the trial to test whether long-term treatment with supplemental oxygen would result in a longer time to death than no use of supplemental oxygen among patients who had stable COPD with moderate resting desaturation (oxyhemoglobin saturation as measured by pulse oximetry [Spo2], 89 to 93%). After 7 months and the randomization of 34 patients, the trial was redesigned to also include patients who had stable COPD with moderate exercise-induced desaturation (during the 6-minute walk test, Spo2 ≥80% for ≥5 minutes and <90% for ≥10 seconds) and to incorporate the time to the first hospitalization for any cause into the new composite primary outcome. Patients were randomly assigned, in a 1:1 ratio, to receive long-term supplemental oxygen (supplemental-oxygen group) or no long-term supplemental oxygen (no-supplemental-oxygen group). In the supplemental-oxygen group, patients with resting desaturation were prescribed 24-hour oxygen, and those with desaturation only during exercise were prescribed oxygen during exercise and sleep. The trial-group assignment was not masked. Results A total of 738 patients at 42 centers were followed for 1 to 6 years. In a time-to-event analysis, we found no significant difference between the supplemental-oxygen group and the no-supplemental-oxygen group in the time to death or first hospitalization (hazard ratio, 0.94; 95% confidence interval [CI], 0.79 to 1.12; P=0.52), nor in the rates of all hospitalizations (rate ratio, 1.01; 95% CI, 0.91 to 1.13), COPD exacerbations (rate ratio, 1.08; 95% CI, 0.98 to 1.19), and COPD-related hospitalizations (rate ratio, 0.99; 95% CI, 0.83 to 1.17). We found no consistent between-group differences in measures of quality of life, lung function, and the distance walked in 6 minutes. Conclusions In patients with stable COPD and resting or exercise-induced moderate desaturation, the prescription of long-term supplemental oxygen did not result in a longer time to death or first hospitalization than no long-term supplemental oxygen, nor did it provide sustained benefit with regard to any of the other measured outcomes. (Funded by the National Heart, Lung, and Blood Institute and the Centers for Medicare and Medicaid Services; LOTT number, NCT00692198 .).

Concepts: Asthma, Lung, Pneumonia, Chronic obstructive pulmonary disease, Emphysema, Centers for Medicare and Medicaid Services, Pulse oximetry, Oxygen therapy


Background Whether noninvasive ventilation should be administered in patients with acute hypoxemic respiratory failure is debated. Therapy with high-flow oxygen through a nasal cannula may offer an alternative in patients with hypoxemia. Methods We performed a multicenter, open-label trial in which we randomly assigned patients without hypercapnia who had acute hypoxemic respiratory failure and a ratio of the partial pressure of arterial oxygen to the fraction of inspired oxygen of 300 mm Hg or less to high-flow oxygen therapy, standard oxygen therapy delivered through a face mask, or noninvasive positive-pressure ventilation. The primary outcome was the proportion of patients intubated at day 28; secondary outcomes included all-cause mortality in the intensive care unit and at 90 days and the number of ventilator-free days at day 28. Results A total of 310 patients were included in the analyses. The intubation rate (primary outcome) was 38% (40 of 106 patients) in the high-flow-oxygen group, 47% (44 of 94) in the standard group, and 50% (55 of 110) in the noninvasive-ventilation group (P=0.18 for all comparisons). The number of ventilator-free days at day 28 was significantly higher in the high-flow-oxygen group (24±8 days, vs. 22±10 in the standard-oxygen group and 19±12 in the noninvasive-ventilation group; P=0.02 for all comparisons). The hazard ratio for death at 90 days was 2.01 (95% confidence interval [CI], 1.01 to 3.99) with standard oxygen versus high-flow oxygen (P=0.046) and 2.50 (95% CI, 1.31 to 4.78) with noninvasive ventilation versus high-flow oxygen (P=0.006). Conclusions In patients with nonhypercapnic acute hypoxemic respiratory failure, treatment with high-flow oxygen, standard oxygen, or noninvasive ventilation did not result in significantly different intubation rates. There was a significant difference in favor of high-flow oxygen in 90-day mortality. (Funded by the Programme Hospitalier de Recherche Clinique Interrégional 2010 of the French Ministry of Health; FLORALI number, NCT01320384 .).

Concepts: Oxygen, Intensive care medicine, Hypoxia, Partial pressure, Oxygen therapy, Breathing gas, Nasal cannula, Hypoxemia


Background High-flow oxygen therapy through a nasal cannula has been increasingly used in infants with bronchiolitis, despite limited high-quality evidence of its efficacy. The efficacy of high-flow oxygen therapy through a nasal cannula in settings other than intensive care units (ICUs) is unclear. Methods In this multicenter, randomized, controlled trial, we assigned infants younger than 12 months of age who had bronchiolitis and a need for supplemental oxygen therapy to receive either high-flow oxygen therapy (high-flow group) or standard oxygen therapy (standard-therapy group). Infants in the standard-therapy group could receive rescue high-flow oxygen therapy if their condition met criteria for treatment failure. The primary outcome was escalation of care due to treatment failure (defined as meeting ≥3 of 4 clinical criteria: persistent tachycardia, tachypnea, hypoxemia, and medical review triggered by a hospital early-warning tool). Secondary outcomes included duration of hospital stay, duration of oxygen therapy, and rates of transfer to a tertiary hospital, ICU admission, intubation, and adverse events. Results The analyses included 1472 patients. The percentage of infants receiving escalation of care was 12% (87 of 739 infants) in the high-flow group, as compared with 23% (167 of 733) in the standard-therapy group (risk difference, -11 percentage points; 95% confidence interval, -15 to -7; P<0.001). No significant differences were observed in the duration of hospital stay or the duration of oxygen therapy. In each group, one case of pneumothorax (<1% of infants) occurred. Among the 167 infants in the standard-therapy group who had treatment failure, 102 (61%) had a response to high-flow rescue therapy. Conclusions Among infants with bronchiolitis who were treated outside an ICU, those who received high-flow oxygen therapy had significantly lower rates of escalation of care due to treatment failure than those in the group that received standard oxygen therapy. (Funded by the National Health and Medical Research Council and others; Australian and New Zealand Clinical Trials Registry number, ACTRN12613000388718 .).

Concepts: Oxygen, Clinical trial, Randomized controlled trial, Clinical research, Adverse event, Emergency medical services, Oxygen therapy, Nasal cannula


High-flow nasal cannula oxygen (HFNC) is a relatively new therapy used in adults with respiratory failure. Whether it is superior to conventional oxygen therapy (COT) or to noninvasive mechanical ventilation (NIV) remains unclear. The aim of the present study was to investigate whether HFNC was superior to either COT or NIV in adult acute respiratory failure patients.

Concepts: Time, Oxygen, Pulmonology, Mechanical ventilation, Emergency medical services, Respiration, Oxygen therapy, Nasal cannula


Animals have a carefully orchestrated relationship with oxygen. When exposed to low environmental oxygen concentrations, and during periods of increased energy expenditure, animals maintain cellular oxygen homeostasis by enhancing internal oxygen delivery, and by enabling the anaerobic production of ATP. These low-oxygen responses are thought to be controlled universally across animals by the hypoxia-inducible factor (HIF). We find, however, that sponge and ctenophore genomes lack key components of the HIF pathway. Since sponges and ctenophores are likely sister to all remaining animal phyla, the last common ancestor of extant animals likely lacked the HIF pathway as well. Laboratory experiments show that the marine sponge Tethya wilhelma maintains normal transcription under oxygen levels down to 0.25% of modern atmospheric saturation, the lowest levels we investigated, consistent with the predicted absence of HIF or any other HIF-like pathway. Thus, the last common ancestor of all living animals could have metabolized aerobically under very low environmental oxygen concentrations.

Concepts: Photosynthesis, Animal, Phylum, Cnidaria, Ctenophora, Oxygen therapy, Sponge, Eumetazoa


Supplemental oxygen is administered in the vast majority of patients in the perioperative setting and in the intensive care unit to prevent the potentially deleterious effects of hypoxia. On the other hand, the administration of high concentrations of oxygen may induce hyperoxia that may also be associated with significant complications. Oxygen therapy should therefore be precisely titrated and accurately monitored. Although pulse oximetry has become an indispensable monitoring technology to detect hypoxemia, its value in assessing the oxygenation status beyond the range of maximal arterial oxygen saturation (SpO2 ≥97%) is very limited. In this hyperoxic range, we need to rely on blood gas analysis, which is intermittent, invasive and sometimes delayed. The oxygen reserve index (ORI) is a new continuous non-invasive variable that is provided by the new generation of pulse oximeters that use multi-wavelength pulse co-oximetry. The ORI is a dimensionless index that reflects oxygenation in the moderate hyperoxic range (PaO2 100-200 mmHg). The ORI may provide an early alarm when oxygenation deteriorates well before any changes in SpO2 occur, may reflect the response to oxygen administration (e.g., pre-oxygenation), and may facilitate oxygen titration and prevent unintended hyperoxia. In this review we describe this new variable, summarize available data and preliminary experience, and discuss its potential clinical utilities in the perioperative and intensive care settings.

Concepts: Oxygen, Hypoxia, Arterial blood gas, Pulse oximetry, Oxygen saturation, Oxygen therapy, Oxygen sensor, Pulse oximeter


Oxygen use in prehospital care is aimed at treating or preventing hypoxemia. However, excess oxygen delivery has important consequences in select patients, and hyperoxia can adversely impact outcome. The unique environment of prehospital care poses logistical and educational challenges. Oxygen therapy in prehospital care should be provided to patients with hypoxemia and titrated to achieve normoxemia. Changes to the current practice of oxygen delivery in prehospital care are needed.

Concepts: Oxygen, Emergency medical services, Oxygen therapy


The nasal cannula has been a commonly used patient interface to provide supplemental oxygen since its introduction in the 1940s. Traditionally, it has been categorized as a low-flow device and capable of delivering a 0.4 F(IO(2)) with flows up to 6 L/min to adults with normal minute ventilation. However, there is considerable performance variability among patients and design, which results in an exponential decline in delivered F(IO(2)) as breathing frequencies increase. The nasal cannula has also been successfully adapted for use in perinatal and pediatric respiratory care; flows are reduced, in the range of 0.25-1 L/min, due to smaller minute volumes. A decade or so ago, high-flow nasal cannula (HFNC) oxygen therapy was introduced, accompanied by heated humidification systems to prevent the associated drying of upper airway mucosa and to increase patient comfort. Therapeutic flows for adults were in the 15-40 L/min range; F(IO(2)) could be independently adjusted with air/O(2) blending. The HFNC has also found additional clinical application in perinatal care, as delivery systems with flows > 2 L/min could create a distending pressure similar to nasal CPAP. There is a small but growing body of information from clinical trials that supports use of HFNC as an alternative oxygen interface for adults who present with moderate hypoxemia that persists after receiving oxygen by reservoir-bag masks or similar therapy. Clinical observations report greater patient acceptance and comfort versus oxygen masks. HFNC therapy has also been considered valuable in perinatal care in treating the respiratory distress syndrome or supporting patients after extubation similar to nasal CPAP. At present, research-based evidence for the role of HFNC for its perinatal applications remains unclear. This review will identify proposed mechanisms for therapeutic effectiveness, current delivery equipment, guidelines for rational patient application, and direction for further research.

Concepts: Oxygen, Medicine, Acute respiratory distress syndrome, Oxygen therapy, Oxygen mask, Nasal cannula, Oxygen tent


Approximately 1 million of the 1.4 million Americans (71%) receiving long-term oxygen therapy (LTOT) are Medicare beneficiaries, confirming that LTOT is most often prescribed for individuals 65 years of age or older. Although several conditions create a need for supplemental oxygen, the majority of patients have chronic obstructive pulmonary disease (COPD). People with healthy lungs can extract the oxygen from air, while those with damaged lungs need higher oxygen concentrations. They can supplement their oxygen using one of three options: high-pressure oxygen tanks, liquid oxygen, or oxygen concentrators. The multicenter Nocturnal Oxygen Therapy Trial and the smaller Medical Research Council study identified LTOT as an intervention that improved survival in patients with COPD or chronic respiratory failure, approximately doubling survival at 19 months in patients who were adherent to oxygen. Despite its advantages, LTOT is plagued with problems: compliance with clinical guidelines, patient adherence, and cost. Fires associated with smoking in the vicinity of supplemental oxygen are the leading cause of residential fire deaths in the United States.

Concepts: Oxygen, Medicine, Pneumonia, United States, Chronic obstructive pulmonary disease, Emphysema, Oxygen therapy, Oxygen concentrator