Background: Oxygen (O2) is a drug with specific biochemical and physiological properties, a range of effective doses and may have side effects. In 2015, 14% of over 55,000 hospital patients in the UK were using oxygen. 42% of patients received this supplemental oxygen without a valid prescription. Health care professionals are frequently uncertain about the relevance of hypoxemia and have low awareness about the risks of hyperoxemia. Numerous randomized controlled trials about targets of oxygen therapy have been published in recent years. A national guideline is urgently needed. Methods: A national S3 guideline was developed and published within the Program for National Disease Management Guidelines (AWMF) with participation of 10 medical associations. A literature search was performed until February 1, 2021, to answer 10 key questions. The Oxford Centre for Evidence-Based Medicine (CEBM) System (“The Oxford 2011 Levels of Evidence”) was used to classify types of studies in terms of validity. Grading of Recommendations, Assessment, Development and Evaluation (GRADE) was used for assessing the quality of evidence and for grading guideline recommendation, and a formal consensus-building process was performed. Results: The guideline includes 34 evidence-based recommendations about indications, prescription, monitoring and discontinuation of oxygen therapy in acute care. The main indication for O2 therapy is hypoxemia. In acute care both hypoxemia and hyperoxemia should be avoided. Hyperoxemia also seems to be associated with increased mortality, especially in patients with hypercapnia. The guideline provides recommended target oxygen saturation for acute medicine without differentiating between diagnoses. Target ranges for oxygen saturation are based depending on ventilation status risk for hypercapnia. The guideline provides an overview of available oxygen delivery systems and includes recommendations for their selection based on patient safety and comfort. Conclusion: This is the first national guideline on the use of oxygen in acute care. It addresses health care professionals using oxygen in acute out-of-hospital and in-hospital settings.

graphic

Abstract

1 Introduction

1.1 Physiology of Blood Gases

1.2 Permissive Hypoxemia

1.3 Hyperoxemia

2 Methods

3 Recommendations

3.1 Patient Assessment

3.2 Oxygen Prescription

3.3 Sources of Oxygen

3.4 Oxygen Delivery Systems

3.5 Application of Oxygen

3.6 Oxygen Saturation Target Ranges in Acute Conditions

3.7 Target Oxygen Saturation Ranges for Patients at Risk of Hypercapnia

3.8 Target Oxygen Saturation Ranges for Ventilated Patients

3.9 Compliance with Oxygen Therapy Target Ranges

3.10 Intractable Hypoxemia

3.11 Oxygen Therapy in Cardiovascular Diseases

3.12 Oxygen Therapy in Neurological Disorders

3.13 Oxygen during Pregnancy and Childbirth

3.14 Oxygen Therapy for the Treatment of Poisoning

3.15 Prehospital Oxygen Therapy

3.16 Oxygen Therapy in COVID-19 and Other Infectious Lung Diseases

3.17 Patients with Cluster Headaches

3.18 Oxygen Use during Procedures Involving Conscious Sedation

4.1 High-Flow Oxygen Therapy

4.2 Humidification of Supplemental Oxygen

4.3 Monitoring and Documentation of Oxygen Therapy

4.4 Discontinuation of Oxygen Therapy

Acknowledgments

Conflict of Interest Statement

Funding Sources

Author Contributions

References

Oxygen was discovered independently by Carl Wilhelm Scheele and Joseph Priestley in 1776. The ability to store oxygen in gas cylinders and the development of compressed gas technology and pressure regulation at the end of the 19th century made it possible to use oxygen for medical purposes.

In 1890, Albert Blodgett from Boston reported the impressive case of a 37-year-old female patient with severe pneumonia, in whom mental confusion and cyanosis were reversed after 2 days of oxygen supplementation, with the symptoms returning when the O2 supply had been exhausted. After the therapy was resumed, the patient fully recovered over 4.5 days [1].

Cells use oxygen to get energy from the nutrients. The primary function of the human lungs is to deliver oxygen (O2) to the blood and to take up carbon dioxide (CO2) from the blood, which is then exhaled. The respiratory system is composed of two parts. The lungs regulate the uptake of oxygen and the release of carbon dioxide (gas exchange), while the respiratory pump takes care of the supply and removal of the gases (ventilation). In pulmonary insufficiency (type 1 respiratory failure), only the O2 uptake, but not the excretion of CO2, is compromised due to superior tissue solubility as compared to O2, whereas in ventilatory insufficiency (type 2 respiratory failure), both O2 uptake and CO2 excretion are compromised.

The present guideline uses oxygen saturation as the key target parameter. For practical reasons, the authors decided to use target ranges of oxygen saturation where the lower and upper limits also indicate when supplemental oxygen should be started/discontinued. The guideline development group decided against recommending specifying target ranges for specific clinical conditions. This approach takes into account the increasing multimorbidity of patients and should help to improve the practical applicability of the guideline. The validity of these target ranges for relevant and common conditions (e.g., acute coronary syndrome, COVID-19, and neurological conditions) is supported by extensive scientific evidence.

1.1 Physiology of Blood Gases

In the blood, O2 binds mostly to the heme component of hemoglobin (Hb) in red blood cells in a reversible reaction. Hemoglobin binds or releases oxygen depending on the partial pressure of oxygen. According to the equation, the physically dissolved oxygen is negligible under normobaric conditions due to the low solubility of O2 in blood. The oxygen content (CaO2) is calculated as follows:

CaO2 = 1.34 × Hb × SO2 + 0.0031 × paO2,

where CaO2 is O2 content (in mL O2/dL blood), Hb is hemoglobin concentration in blood (in g/dL), SO2 is O2 saturation, paO2 is partial pressure of O2 (in mm Hg), and 1.34 is Huefner’s factor.

The amount of O2 in blood can be expressed by measuring the oxygen saturation (SO2) of hemoglobin or by measuring the partial pressure of O2 (paO2). The arterial oxygen saturation (SaO2) indicates the percentage of hemoglobin saturated with oxygen at the time of measurement. The oxygen saturation of hemoglobin (SO2, in %) can be measured from arterial blood (SaO2) and also by pulse oximetry (SpO2). Arterial saturation should be measured photometrically. Alternatively, it can be calculated, with lesser accuracy, from the partial pressure of oxygen using various formulas [2, 3].

paO2 is a key parameter for assessing the pulmonary gas exchange and is obtained by blood gas analysis (BGA) which requires puncture which is painful for the patient and more time-consuming. Neither oxygen saturation nor the partial pressure of oxygen in arterial blood are suitable key parameters for determining the tissue oxygenation.

Hypoxemia, i.e. low blood oxygen levels, is often confused with hypoxia. Tissue oxygenation is essentially determined by hemoglobin levels and cardiac output and is only inadequately characterized by SaO2 or paO2. Nevertheless, much more attention is paid to hypoxemia in clinical practice than to these key parameters, which are not immediately available.

The oxygen binding curve (Fig. 1) characterizes the relationship between arterial oxygen saturation (SaO2) as a function of the partial pressure of O2 (paO2).

Fig. 1.

Relationship between oxygen saturation and the partial pressure of oxygen.

Fig. 1.

Relationship between oxygen saturation and the partial pressure of oxygen.

Close modal

At O2 saturation levels >90%, i.e., when the pulmonary gas exchange is only slightly impaired, an increase in the paO2 results in only a minor SO2 change.

The partial pressure of carbon dioxide (paCO2) is an important marker of alveolar ventilation. In addition, paCO2 is a key parameter for the interpretation of the pH. The generally accepted normal paCO2 range is 36–44 mm Hg. The normal pO2 values when lying down and sitting vary depending on age [4, 5], with the latter being higher. In a large UK study on 37,000 patients, the median SpO2 was 98% for adults aged 18–64 years, and 96% for the elderly.

Normal oxygen saturation in a population depends on altitude. A sample group of 3,812 people living in Tibet at an altitude of approximately 4,000 m, for example, had a mean SaO2 of only 88% [6]. This effect is of minor relevance in Germany.

While pulse oximetry is more sensitive, its specificity for detecting hypoxemia is low. In 64 patients with exacerbation of chronic obstructive pulmonary disease (COPD), a blood oxygen saturation <92% measured by pulse oximetry had a sensitivity to predict arterial hypoxemia (pO2 <60 mm Hg) of 100% and a specificity of 86% [7]. In 664 arterial blood gas analyses and simultaneous pulse oximetry readings taken in an emergency department, pulse oximetry had a sensitivity of less than 92% in 92% of cases and a specificity of 90% for predicting arterial oxygen saturation (SaO2) of 90% [8]. Errors in pulse oximeter readings also need to be considered when defining the target ranges. Even in critically ill patients, the 95% confidence interval for the difference between pulse oximetry and arterial saturation is +4% [9].

Hypoxemia is a decrease in the partial pressure of oxygen or oxygen saturation in arterial blood. Hypoxia, on the other hand, means insufficient organ and tissue oxygenation. In adults, hypoxemia is mostly defined as paO2 <60 mm Hg and SaO2 <90% [10]. There is currently no clear scientific evidence as to when and how much supplemental oxygen is needed to treat hypoxemia. The target ranges recommended in this guideline are based on current evidence which level of hypoxemia and hyperoxemia are likely to be harmful for patients and which target range can be safely used.

Tissue hypoxia may be hypoxemic, anemic, stagnant or histotoxic (e.g., in cyanide poisoning). Oxygen therapy usually serves to correct hypoxemic hypoxia.

Hypoxemic hypoxia is present when the partial pressure of oxygen in the blood is reduced. This may be caused by high altitude, right-to-left shunts, marked pulmonary ventilation-perfusion mismatch, diffusion impairment, or alveolar hypoventilation (Table 1).

Table 1.

Causes, examples, and responsiveness to O2 treatment of various types of hypoxemic hypoxia

Causes, examples, and responsiveness to O2 treatment of various types of hypoxemic hypoxia
Causes, examples, and responsiveness to O2 treatment of various types of hypoxemic hypoxia

The alveolar-arterial partial pressure gradient (according to Helmholz [11]; the normal value at sea level is <(age/4) + 4 mm Hg) is calculated as

(FiO2 × 760) – (paCO2/0.8) – paO2,

where 760 is atmospheric pressure (760 mm Hg at sea level), and FiO2 = 0.21 + O2 flow in liters per minute (L/min) × 0.038 [12].

Hypoxemia is a warning sign and requires immediate medical attention, differential diagnosis, and subsequent treatment. This is why both hypoxemia as well as the presence of oxygen therapy were included as parameters in early warning scores (e.g., NEWS2) [13], to serve as indicators of increased mortality and the necessity of intensive medical care.

Type 1 respiratory failure with reduced paO2 and normal or reduced paCO2 is caused by hypoxemic hypoxia consistent with hypoxemic respiratory failure. Hypercapnic respiratory failure (type 2 respiratory failure) has a paCO2 ≥45 mm Hg, potentially resulting in reduced SaO2 and pO2 levels. In chronic hypercapnia, e.g., in COPD, hyperoxemia may result in a dangerous increase in the paCO2 as the pulmonary vasoconstriction of nonventilated areas is reversed in hyperoxemia. In addition, hypoxemia reduces the respiratory minute volume; in addition, oxygenated hemoglobin has decreased carbon dioxide carriage (Haldane effect) [14].

1.2 Permissive Hypoxemia

Permissive hypoxemia has been proposed as a treatment option to avoid damage as a result of invasive ventilation. This strategy presupposes sufficient hemoglobin levels (usually >10 g/dL) and a supranormal cardiac index (>4.5 L/min/m2) to maintain adequate oxygen supply (DO2). The concept aims for critically ill patients to tolerate a target oxygen saturation between 85 and 89%.

There are so far no randomized trials comparing permissive hypoxemia versus normoxemia in adults.

A 2014 meta-analysis did not identify any studies comparing permissive hypoxemia in ventilated patients versus a control group with normoxemia or mild hypoxemia [15]. Based on our own literature search, the only study investigating the concept of permissive hypoxemia in a randomized approach was the NeOProM collaboration [16], in which 4,965 preterm infants were randomized to receive oxygen therapy with a target SpO2 of 85–89% or 91–95%. There was no difference in mortality, but more cases (9 vs. 7%) in the restrictive oxygen group required surgery for necrotizing enterocolitis or died. Interestingly, in a recently published study comparing liberal and restrictive oxygen therapy in adult acute respiratory distress syndrome (ARDS) patients, isolated mesenteric ischemia was also observed in 5% of patients with a target SpO2 of 88–92% [17]. Hence, the range of hypoxemia that can be tolerated by critically ill patients in the medium term remains unclear.

An association of hypoxemia and increased mortality has repeatedly been described for large cohorts of hospitalized patients and emergency care [18, 19].

It was suggested that, instead of SaO2 and pO2, oxygen content (CaO2) should be used as the target parameter of oxygen therapy. However, no reference ranges exist for CaO2. The parameter has not yet been studied in prospective clinical trials. In a randomized controlled trial (RCT) on 838 patients, 82% of whom were ventilated, a liberal transfusion strategy (hemoglobin >10 g/dL) versus a conservative strategy (hemoglobin >7 g/dL) did not produce a significant difference in the 30-day survival rate [20]. To maintain tissue oxygenation perfusion needs to be considered along with the oxygen content of the blood. This is often done using the cardiac output, which provides the oxygen supply (DO2) by multiplying the oxygen content (CaO2) and the cardiac output. The results of increasing the DO2 in critically ill patients on survival, organ failure, length of hospitalization in RCTs were contradictory [21, 22]. A systematic review provided insufficient data to support a routine increase of DO2 in critically ill patients [23]. The administration of inotropic agents to increase cardiac output may also produce side effects in some patients, and, for example, may negatively affect the cardiac function in ARDS patients and patients with coronary artery disease.

The fetal oxygenation is approximately 70% [24]. This leads some authors to argue that even adult patients may be fully stable at an SpO2 of 70%. There are definitely patients who are adapted to chronic hypoxemia (e.g., populations living at high altitudes or people with chronic hypoventilation) without reporting shortness of breath. Nevertheless, adjustment processes to chronic hypoxemia take several weeks and go along with an increase in hemoglobin levels, minute volume, and respiratory output. The experience that there are people who have adjusted to chronic hypoxemia cannot be transferred to patients with acute hypoxemia.

Acute altitude-induced hypoxemia above 6,700 m with saturation levels below 70% leads to loss of consciousness within a short period of time and is fatal after days even after acclimatization [25]. Even healthy subjects showed cognitive impairment in hypoxemia below 80% [26].

The exact range within which hypoxemia is tolerated in the medium term is unknown for lack of controlled trials. Lactate levels are often used as a surrogate parameter for tissue hypoxia, both in clinical practice and in studies. An increase in lactic acid content was demonstrated after 15 min in healthy subjects at an arterial saturation rate of 78% [27], and myocardial lactate was released at a saturation of <75% [28] when exercising in a low-oxygen environment. In patients with coronary artery disease, myocardial lactate was produced at rest during moderate hypoxemia (SaO2 < 85%) [29]. An oxygen saturation of 85% is therefore frequently regarded as the likely critical threshold of acute hypoxemia, although levels probably vary between individuals.

In the absence of randomized trials on oxygen therapy in acutely ill hypoxemic adults, the impact of oxygen therapy on survival and other patient-relevant outcomes remains unclear. The recommended ranges of this guideline take into account the limitations of pulse oximetry, whose 95% confidence interval (CI) in terms of actual consistency with arterial saturation (SaO2) ranges from 84 to 92% for an SpO2 of 88%, for example.

1.3 Hyperoxemia

Hyperoxemia, like hypoxemia, is not precisely defined. The normal O2 saturation at sea level is 96% [30]. In the studies on O2 therapy in normoxemic patients with acute coronary syndrome, stroke, and during surgery, SpO2 values of more than 96% were measured in the treatment groups with liberal oxygen administration [31]. Patients at risk of hypercapnic respiratory failure were generally excluded in these studies. Numerous arguments speak against hyperoxia and hyperoxemia as a therapy target.

The unnecessary use of oxygen causes claustrophobia, dehydration of mucosa, hoarseness, and in some patients negatively affects patient mobilization, food and fluid intake, and communication [32]. In addition, a number of deleterious side effects of hyperoxemia resulting from the administration of O2 with the goal of achieving hyperoxia have been described [33]. A meta-analysis of 25 randomized controlled O2 trials provided strong evidence of an increased relative risk of in-hospital mortality with hyperoxemia under liberal oxygen therapy [31]. The relative risk of 3-month mortality was 1.18 in ICU patients with a higher oxygen target range and a higher incidence of severe adverse events [34]. High O2 concentrations have a direct toxic effect on the lungs of healthy persons by causing an inflammatory airway response. In addition, resorption atelectasis has been described under high oxygen concentrations, especially in obese healthy subjects [35, 36]. The increased free radical generation during hyperoxia can result in cell damage [37]. Hyperoxemia may result in falsely reassuring SpO2 levels and delay the detection of a deterioration in hypoxemic patients in comparison to conservative O2 therapy [6, 38]. In patients with COPD, prehospital hyperoxia was associated with greater in-hospital mortality and increased the risk of hypercapnic respiratory failure on admission [39]. Hyperoxemia leads to coronary vasoconstriction [40], and routine supplemental oxygen therapy does not improve the mortality after myocardial infarction [41]. In 21 studies on 7,597 patients, hyperoxia did not improve intra- and postoperative wound healing [42].

This is the official translation of the condensed version of the German version of the guideline [43]. The guideline was developed and published within the Program for National Disease Management Guidelines of the Association of the Scientific Medical Societies in Germany.

The methodological approach is based on the AWMF guidelines (http://www.awmf-leitlinien.de).

The guideline was published in June 2021 in its original German version and will be valid for 3 years until June 30, 2024. The following supplementary documents to this guideline are available online: disclosures of conflicts of interest, evidence report, report of existing guidelines and evaluation of evidence for recommendations.

This guideline addresses health care professionals using oxygen in acute out-of-hospital and in-hospital settings. The guideline is intended for out-of-hospital and in-hospital emergency settings and included recommendations for the treatment of critically ill patients including patients on invasive ventilation. Furthermore, the guideline is intended to include recommendations for supplemental oxygen therapy during procedures with conscious sedation, e.g. during endoscopy. Use of oxygen therapy in diving and high-altitude medicine, long-term oxygen therapy in the domestic setting, and the administration of oxygen in the context of general anesthesia and in veterinary medicine was out of scope of this guideline. The guideline also intends to inform other users of oxygen in prehospital and in-hospital settings, such as health care and nursing staff, members of the emergency rescue services, and physicians.

The following medical associations participated in this guideline: German Society of Internal Medicine (DGIM), German Society of Surgery (DGCH), German Society of Medical Intensive Care Medicine and Acute Medicine (DGIIN), German Society of Anesthesiology and Intensive Care Medicine (DGAI), German Society of Neurocritical Care and Acute Medicine (DGNI), German Interdisciplinary Association for Intensive and Emergency Medicine (DIVI), German Cardiac Society (DGK), German Society of Nursing Science (DGP).

The German Rescue Service Association (DBRD) was a designated advisor on specific issues, and a member attended consensus meetings. A patient representative of the Federal Association of Organ Transplant Patients (BDO) was involved in the guideline development process and participated in the consensus meetings.

An independent review of evidence included an independent guideline and literature search on 10 key questions for the guideline in 2019 and led to 2 reports. The guideline search identified 4 guidelines with high-level evidence, 2 of which were considered suitable for answering some of the key questions after being reviewed by the authors. After the independent evidence report in 2019, additional relevant studies had been published in the meantime. An additional literature search and evidence report of the recommendations were made in 2021. The literature search was performed until February 1, 2021.

During development the following key questions were addressed:

1When should oxygen therapy be started in acutely ill adults (lower limit of SpO2)?

2Is oxygen administration useful in acutely ill normoxemic adults (e.g., patients with sepsis, pulmonary embolism, etc.)?

3How much oxygen should be given to acutely ill adult patients (upper limit of SpO2)?

4How should an acute oxygen therapy be administered (e.g., nasal cannula, mask)?

5What is the target saturation range for critically ill adult patients under oxygen therapy?

6How should oxygen therapy be monitored and managed in critically ill adult patients?

7When and how should oxygen therapy be discontinued in critically ill adult patients?

8How should oxygen therapy be prescribed in critically ill adult patients?

9When should oxygen humidification be used in the acute treatment of critically ill patients?

10When is high-flow nasal cannula (HFNC) therapy superior to conventional O2 treatment?

This guideline used the 2011 version of the Oxford Centre for Evidence-Based Medicine (CEBM) System (“The Oxford 2011 Levels of Evidence”) to classify the types of studies in terms of validity. Level 1 consists of systematic review of RCTs, level 2 of RCT or observational study with dramatic effect, level 3 nonrandomized cohort study, level 4 are case series, case-control studies or historically controlled studies and level 5 mechanism-based reasoning (case studies, anecdotes, and personal opinions).

A formal consensus-building process was performed. A total of 3 structured consensus conferences were held in accordance with the model described by the National Institutes of Health, with presentation of the recommendation including background text by the spokesperson of the working group/expert responsible for developing the recommendation, clarification of content-related queries, request for proposal of substantiated amendments and summarization of proposals, as necessary, voting on the original version and on the amendments and repeat discussion and voting if no consensus was reached.

A consensus was reached if endorsed by >75% of participants, and a strong consensus was defined if endorsed by >95% of participants. Consensus (n = 4) or strong consensus (n = 30) was reached for all 34 recommendations.

For all recommendations, the guideline indicated the level of evidence of the supporting studies as well as the strength of the recommendation (grade of recommendation). This guideline distinguishes three levels of recommendation in terms of strength of recommendation (Table 2).

Table 2.

Grades of recommendation

Grades of recommendation
Grades of recommendation

The grade of each recommendation resulted from the quality of the evidence and the rationale for the strength of recommendation. Thus, a strong recommendation could be issued even without a high degree of certainty, if the recommendation was based on clinical assessment/experience.

Grading of Recommendations, Assessment, Development and Evaluation (GRADE) was used for assessing the quality of evidence and for grading guideline recommendations. The guideline group started by defining patient-relevant end points.

Critical end points were mortality and quality of life. Important (but not critical) end points were new ischemic cardiovascular events, relief of shortness of breath, correction of hypoxemia, costs, necessity of ventilation (safety), adverse effects – like immobility/disability, discomfort, claustrophobia, mucosal desiccation, hoarseness (safety) – and functional outcome (Rankin scale: http://www.neuroreha.at/assets/rankin-scale-deu.pdf).

After adjusting for confounders, the quality of evidence was considered as high ⊕⊕⊕⊕, moderate ⊕⊕⊕⊖, low ⊕⊕⊖⊖ or very low ⊕⊖⊖⊖ for each end point. The overall quality of the evidence for all end points was assessed based on the lowest quality of the critical end points.

Recommendations were based on expert consensus if the systematic search failed to identify suitable studies or was deemed to be too time-consuming. In this case, a recommendation is identified as “expert consensus” with no level of evidence or grading of recommendation.

“Practice points” included practice point recommendations the authors considered relevant for the users of oxygen therapy and were not subject to a consensus voting process. The recommendations are often based on case reports, isolated literature references, and include clinically significant observations.

As for independence and disclosure of potential conflicts of interest, the guideline was developed independently of the funding organization. All members of the guideline group submitted a written disclosure of conflicts of interest. The conflicts of interest were screened by the guideline coordinator and the AWMF representative for any relevant conflicts. Presentations of companies or authorship based on a fee-for-service agreement were rated as low direct conflicts of interest. Membership in a scientific advisory board or expert activities for a company in the health care sector with a thematic relevance as well as the conduct of studies financed by these companies were rated as moderate direct conflicts of interest. Patents or ownership interests were rated as high conflicts of interest. As a result, no member of the guideline group was found to have a low conflict of interest, 3 were found to have a moderate conflict of interest and no one was found to have a high conflict of interest. Moderate conflicts of interest resulted in abstention from voting. S.K. and C.K. had a potential conflict of interest with regard to extracorporeal membrane oxygenation, which were rated as moderate in both cases. This guideline does not give a recommendation on extracorporeal membrane oxygenation. T.V. had a possible moderate conflict of interest on the subject of humidification. He did not participate in voting on the recommendation 6.6. on this topic.

graphic

Three meta-analyses involving mostly cancer patients and COPD patients with breathlessness (the majority had an SpO2 ≥90%) demonstrated that either perceived dyspnea was not improved by oxygen versus compressed air therapy or only a small effect was seen regarding the impact of oxygen on dyspnea, whereby the placebo effect of an airflow could not be reliably differentiated [44-46].

Practice Points:

In addition to oxygen therapy, general measures such as positioning the patient to improve oxygenation are useful in hypoxemia.

When positioning hypoxemic patients who are awake, the patient’s preference should be taken into account in addition to the oxygen therapy. Putting the upper body in an upright position may improve oxygenation in some patients. Acute respiratory failure has been described in morbidly obese patients (BMI >50 kg/m2) when lying on their back [47].

To treat and prevent the aortocaval compression syndrome, hypoxemic pregnant women need to be positioned on their left side.

In palliative care, nonpharmacological measures are initially used to manage dyspnea in nonhypoxemic patients: relaxation exercises, cooling of the face, airflow from a table fan, and walking aids.

Opioids have been thoroughly studied for the treatment of dyspnea and have proven to be an effective intervention in nonhypoxemic patients with dyspnea.

3.1 Patient Assessment

graphic

SpO2 is only one of several physiological parameters – so-called vital signs – for the assessment of patients, which are easily obtainable at the bedside by nursing staff. More than 1 million vital signs were measured in 27,722 patients upon admission [18]. A critical level for any of the vital signs measured was defined as the limit which, when undercut or exceeded, resulted in in-hospital mortality ≥5% [18]. The critical levels identified in this context were: systolic blood pressure <85 mm Hg, heart rate >120/min, body temperature <35°C or >38.9°C, oxygen saturation <91%, respiration rate ≤12/min or ≥24/min, and altered mental state.

Respiratory signs and symptoms of hypoxemia include: dyspnea, tachypnea, mouth breathing, increasing use of accessory respiratory muscles, changes in respiratory muscle and nasal flaring. Hypoxemia may influence vital signs and symptoms [48]. Relevant hypoxemia can, for example, result in impaired consciousness, pectoral angina, arrhythmia or hypotensive/hypertensive circulatory response [10]. However, arterial hypoxemia does not necessarily lead to changes in vital signs [49]. Studies indicate that vital signs are insufficient in terms of predicting arterial hypoxemia [50-52].

Changes in consciousness may already be seen in the early stages of hypoxemia [53, 54]. Warning signs are anxiety, restlessness, and agitation followed by confusion and loss of consciousness [10]. “Track and trigger” systems are point-based scores of vital signs and serve as an early warning system with regard to emerging or relevant changes. The National Early Warning Score (NEWS2) assigns a point score to the above-mentioned 6 vital signs, and in addition for the presence of supplemental oxygen therapy. The total NEWS2 score can range from 0 to 20 [13].

Practice Points:

The respiration rate is of key importance among the vital signs, since it is not only used in track and trigger systems (e.g., NEWS2), but also in prognostic scores (qSOFA, CRB65). The respiration rate is of particular importance in hypoxemia and in patients on supplemental oxygen.

The normal respiration rate is 12–20 breaths/min.

Patients are considered clinically stable when they have a NEWS2 score <5 and their vital signs are predominantly in the noncritical range [13].

Training oxygen users in how to measure their respiration rate is useful if no monitor is available [55].

Smartphone-based timers are useful tools for measuring the respiration rate (e.g., Android: “Stopwatch and Tally counter”, IOS: “Tap counter with sets”).

graphic

Pulse oximetry is a simple, noninvasive method for estimating arterial oxygen saturation and is universally used in out-of-hospital and in-hospital settings, in intensive care units as well as in the periprocedural environment. It can significantly reduce the number of blood gas tests required, and hence the invasiveness and costs of a treatment, without compromising on the quality of health care [57, 58]. Pulse oximetry is less accurate than measuring the O2 saturation of arterial blood, especially in the range below 80% [59, 60]. In the clinically relevant range (oxygen saturation 80–100%), SaO2 and SpO2 have an acceptable correlation. In clinically stable COPD patients, an SpO2 <92% has high sensitivity and specificity for detecting an arterial saturation <90%.

The authors identified a Cochrane analysis of pulse oximetry in postoperative monitoring [56]. With the use of pulse oximetry hypoxemic episodes were 1.5–3 times less likely with than without pulse oximetry monitoring with no significant differences in mortality or ICU admission. The use of pulse oximeters improved the detection of hypoxemia versus clinical monitoring alone, and this was demonstrated in various populations, and in the prehospital setting [7, 8, 50, 51, 61, 62]. We identified no high-level randomized trials to support this recommendation but it was supported by a systematic review in the field of emergency medicine [63].

Simultaneous pulse oximetry and arterial oxygen saturation recordings found that approximately 80% of the saturation levels measured by pulse oximetry on 396 patients in 2 intensive care units were by 2% above or below the arterial oxygen saturation, and 100% were in the +4% range [9].

Artifacts are a frequent occurrence in pulse oximetry, and trigger alerts. The devices do not require calibration, but it was found in 29 UK hospitals that 10.5% of sensors were defective and 22.3% had a deviation of more than 4% [64] from the arterial saturation levels which was attributable to technical reasons.

In a large cohort study of almost 10,000 patients, occult hypoxemia was 3 times as high among African American patients versus Caucasians [65]. Overestimation of oxygen saturation by pulse oximetry has also been described in crisis situations of patients with sickle cell disease [66].

Practice Points:

If a patient’s oxygen saturation is below the prescribed target range, check the oxygen system and the pulse oximeter for errors (e.g., sensor signal) first.

Devices displaying the pulse oximetry plethysmographic curve or indicating the signal strength are useful for the assessment of pulse oximetry.

Repeated SpO2 measurements are useful for all patients under O2 therapy. Continuous pulse oximetry monitoring may be indicated in patients with risk factors.

Pulse oximetry may overestimate oxygen saturation in patients with a dark skin color or in sickle cell crises. A lower trigger threshold should be set for blood gas analyses in patients with a darker skin color.

Alternative measuring methods such as capnometry and the transcutaneous measurement of O2 or partial pressures of CO2 have not gained acceptance in the acute care setting for determining whether or not oxygen therapy is indicated or for the monitoring of an oxygen therapy [67].

graphic

Blood gases should be measured in emergency situations in critically ill [68] hypoxemic patients and are recommended for ventilated patients in the S3 guideline on ventilation [69]. According to expert opinion, blood gas analyses are required to monitor oxygen therapy if pulse oximetry is not available or fails to provide a reliable signal. Due to the high intubation rate (35–40%) of patients with severe hypoxemia (oxygenation index <150 mm Hg corresponding to an oxygen flow rate >6 L/min or FiO2 >0.4) [70-72] it is imperative, according to expert opinion, to measure blood gases in order to exclude hypercapnia, among other conditions.

Stable hypoxemic patients who are not at risk of hypercapnic respiratory failure can generally be clinically assessed without BGA [63]. The downside of arterial puncture is the potential of complications and the fact that they are painful for the patients.

Practice Point:

Indwelling arterial catheters are useful in situations where patients are likely to require multiple arterial blood gas analyses over a short period of time.

graphic

Due to the increased complication rate associated with arterial puncture, BGA (BGA) for non-ICU patients is often done using earlobe blood, which is arterialized by rendering it hyperemic (= capillary BGA) [76].

The benefit of a less invasive method must be weighed against the lesser accuracy of the result. Our guideline search found an identical recommendation in the BTS guideline [63]. It was based on a meta-analysis of 29 studies of 664 matched earlobe samples and 222 samples from the fingertip to determine capillary and arterial paO2 [73]. In this analysis, the pO2 from earlobe blood was found to be lower by 3.9 mm Hg on average, and from the fingertip by as much as 11.5 mm Hg.

Two other studies with 83 and 120 matched samples of stable long-term oxygen therapy patients showed the capillary pO2 to be lower than the arterial pO2 by 5.6 and 6.0 mm, respectively, on average [74, 75]. Major sources of error in capillary BGA include inadequate arterialization, shunts in the earlobe region, and hemolysis due to mechanical pressure as well as clot formation or air in capillary samples. In addition, the studies also looked at patient comfort; arterial sampling was significantly more painful for patients (measured by visual analog scale) [74, 75]. According to expert opinion, capillary BGA can be used in stable patients outside the intensive care setting after thorough arterialization of the earlobe blood, but not in emergency situations when patients are unstable.

Practice Points:

Standard operation procedures should be established for capillary BGA. At least 5 min at a constant O2 flow rate, at least 10 min of arterialization, and at least 15 min of rest are considered necessary preparatory steps for capillary BGA [76].

Both capillary BGA and pulse oximetry may underestimate arterial oxygen saturation. If SpO2 and SaO2 are measured simultaneously, oxygen therapy should be based on the higher of the two readings; alternatively, arterial BGA should be performed.

graphic

Blood gas measurements from venous blood samples have significantly fewer complications than those obtained through arterial puncture, they are less painful, and readily available. The partial pressure of oxygen in venous blood is by 13–37 mm Hg lower than in arterial blood. It is therefore not suitable for measuring oxygenation [77-79]. Venous BGAs are not suitable for monitoring oxygen therapy. There is also a difference of +3 to +6 mm Hg in the partial pressure of carbon dioxide compared to arterial measurements [77-80]. Three studies with used a cut-off of 30–46 mm Hg [81-84]. In three studies with matched arterial and venous BGAs, pvCO2 was able to exclude arterial hypercapnia with a negative predictive value of 100% at a venous pCO2 cutoff of <45 mm Hg (106–109).

3.2 Oxygen Prescription

graphic

Our literature search could not identify relevant studies demonstrating that oxygen prescription is associated with the predefined clinically relevant aspects. The proportion of inpatients with O2 prescription ranges from 40 to 60% [85, 86]. Medical oxygen was classified as drug in Germany in 2005, and a prescription is required for supplemental oxygen administration.

Practice Points:

In prescribing the delivery system (nasal cannula/prongs, mask, Venturi mask, reservoir mask, high-flow, etc.), consider O2 requirement, breathing pattern (i.e., respiration rate, depth of breath), mouth opening, and risk of hypercapnia [12].

Oxygen therapy must be prescribed by a doctor. The prescription shall specify the type of delivery, amount of oxygen, target saturation ranges, and monitoring intervals. Figure 6 shows a sample prescription form as proposed by the guideline development group.

In an emergency situation, oxygen should be administered without a formal prescription (see 7.4) and documented in retrospect.

graphic

The guideline search did not identify any evidence-based recommendations in this regard in other guidelines. The authors’ own and independent literature search did not find any randomized trials or meta-analyses [87-89].

According to retrospective analyses, hypoxemia is a negative prognostic indicator in inpatients and emergency room patients [18, 19]. Oxygen prescription therefore requires reassessing the patient to be able to detect clinical deterioration at an early stage and prevent events such as cardiopulmonary resuscitation (CPR), transfer to ICU, or death. The reassessment intervals are determined by the severity of vital sign abnormalities and the extent of hypoxemia. In the UK, reassessment is recommended every 12 h, even in patients with normal vital signs. For hospitalized patients, the UK recommends reassessments every 4–6 h for patients with freshly started or ongoing oxygen therapy [90].

Based on expert opinion, the BTS guideline recommends 6-h intervals for patients on oxygen therapy and continuous monitoring depending on where the oxygen therapy takes place (ICU/emergency room/regular ward, etc.) if multiple vital signs are outside the normal range and patients have a NEWS2 score ≥7. Continuous monitoring is recommended in track and trigger systems when multiple vital signs are outside the normal range. No RCTs are available in this regard, but it is known, for example, that approximately 40% of inpatients on high-flow oxygen therapy are intubated [70, 71]. Therefore, the amount of oxygen required to achieve the target oxygen saturation may be associated with the occurrence of a life-threatening deterioration in the patient’s condition [91].

Practice Points:

Vital signs shall be checked at least every 6 h during oxygen therapy.

It is recommended to continuously monitor SpO2, pulse, and respiration rate from flow rates above 6 L/min in patients under high-flow oxygen (HFNC), and to closely monitor the other vital signs (mental state, blood pressure, body temperature).

3.3 Sources of Oxygen

It needs to be ensured in an inpatient setting that oxygen is delivered via wall outlets providing pure oxygen, not from other outlets for compressed air or other gases. In Germany, medical O2 in health care facilities is commonly provided by a central system supplying pure, compressed oxygen (100%). Central storage tanks must be refilled on a regular basis. In other countries (e.g., Canada), hospitals use oxygen concentrators to obtain oxygen 93% [92]. Pressure regulators are used to reduce high gas cylinder pressure to a lower pressure suitable for use with medical equipment or for delivering gas directly to a patient. Tube flow meters can be set from 0.5 to 4, 2 to 16, and 4 to 32 L/min with a flow accuracy of +10% (+15% at the lowest setting). It must be ensured that medical staff is able to correctly read the O2 flow rate on a tube flow meter (for example, some manufacturers have the reading on the “north pole” of thefloating ball while others may provide it on the “equator”).

Compressed O2 gas cylinders with pressure regulators and notches are the mobile oxygen sources commonly used in acute medicine. It is important to ensure that portable oxygen cylinders have sufficient oxygen, e.g., for transporting a patient. Cylinder volume, filling level, and oxygen flow rate must be checked.

Oxygen-gas mixtures (e.g., oxygen-helium, Heliox) do not play a major role in the routine acute care provided in a clinical setting. Care must be taken to ensure that the gases and their connections are clearly labeled to avoid mixups. Oxygen outlets are hexagonal (Fig. 3). Nitrous oxide/oxygen mixtures (Livopan®) for analgesia shall not be used in patients at risk of hypercapnia.

graphic

For optimum nebulization performance in connection with inhalation masks, manufacturers generally recommend a flow rate of the driving gas of no less than 8 L/min. High-dose oxygen administration may result in hyperoxemia with acute hypercapnic respiratory failure [39].

In 1984, Gunawardena et al. [93] found a significant increase in paCO2 in 9 hypercapnic COPD patients after 15 min of oxygen-driven nebulization, with a return to baseline values only 20 min after terminating nebulization. Two studies analyzed partial pressure of carbon dioxide during high-dose oxygen therapy versus compressed air in patients at risk for hypercapnia ADDIN EN.CITE. (The proportion of patients in whom the transcutaneously measured partial pressure of carbon dioxide (PtCO2) had increased was higher in patients after nebulization with high-flow oxygen in comparison to compressed air-driven nebulization. This is important in emergency out-of-hospital situations where patients at risk of hypercapnia (e.g. COPD) are administered drugs (e.g., bronchodilators) via nebulizers using high-dose oxygen as a driving gas instead of compressed air. The inhalation time in this constellation shall be less than 10 min to limit the increase in the partial pressure of carbon dioxide [93-95]. Compressed air-driven nebulizers or ultrasonic nebulizers shall be preferred in these patients.

Practice Points:

Continuous monitoring (SpO2, respiration rate, breathing pattern and pulse, mental state) is advisable during oxygen-driven nebulization drug therapy for patients at risk of hypercapnia [63].

If the defined target saturation range cannot be reached under nebulization, additional oxygen is recommended to be administered during inhalation, e.g., via nasal prongs.

Inhalation under high-flow oxygen therapy may result in changes in the aerosol, transport of particles to airways, and drug efficacy.

graphic

For lack of relevant studies, the recommendation provided in this guideline also relies on expert opinion. However, it is a strong recommendation, as the group of experts unanimously considers staff training and patient information to be indispensable elements of oxygen therapy. In addition, they should be able to correctly read and document the readings and flow rates on the equipment and maintain a stable target saturation range [63].

Practice Points:

Patient information about oxygen therapy by the medical staff (especially nurses and respiratory therapists) is helpful, as is the involvement of the patient’s family members.

Patient involvement and training may prevent oxygen misuse.

3.4 Oxygen Delivery Systems

graphic

This recommendation is based on 4 crossover studies [96, 97, 99, 100], and 3 randomized trials investigating the patient comfort of different oxygen delivery systems [70, 87, 101].

In conclusion, nasal prongs offered greater patient comfort and had lower dislocation rates than masks. Only 1 out of 3 RCTs indicated that HFNCs provided slightly superior comfort than masks. No randomized controlled studies with nasal prongs as comparator were identified. Higher flow rates went along with more adverse effects [102] so that the differences in patient comfort between the delivery systems used in the studies may also be attributable to different flow rates.

Oxygen delivery systems are selected based on clinical circumstances and patient needs (Table 3).

Table 3.

Pros and cons of different oxygen delivery systems

Pros and cons of different oxygen delivery systems
Pros and cons of different oxygen delivery systems

Venturi masks use Bernoulli’s principle by introducing the oxygen through a tapered nozzle and swirling the air/oxygen mix entering at a high flow rate for inhalation. For patients with high respiration rates (>30/min), the flow rate for Venturi masks shall be set above the minimum flow rates indicated in Table 4 [99]. Oxygen delivery of 1–4 L/min via nasal prongs corresponds to O2 delivery using a 24, 28, 31, 35, or 40% Venturi mask [100, 103]. Unlike with nasal prongs, a Venturi mask does not increase the FiO2 at higher flow rates.

Table 4.

Overview of Venturi masks and recommended flow rates

Overview of Venturi masks and recommended flow rates
Overview of Venturi masks and recommended flow rates

Practice Points:

The minimum O2 flow rates as indicated by the manufacturer shall be observed when using Venturi masks.

Do not use simple face masks or reservoir masks in patients at risk of hypercapnia or with oxygen flow rates <5 L/min.

3.5 Application of Oxygen

Target ranges for oxygen saturation recommended in this guideline are chosen to prevent hypoxemia and hyperoxemia at levels which are likely to be harmful for acutely ill patients. Whether or not a patient is ventilated and whether or not a patient is at risk of hypercapnia plays a role in this context. The target oxygen therapy ranges listed in Figure 2 shall be used for these 3 patient groups.

Fig. 2.

Target ranges of oxygen therapy for the different groups of patients. BMI, body mass index; SpO2, oxygen saturation measured by pulse oximetry; SaO2, arterial oxygen saturation. From https://www.awmf.org/leitlinien/detail/ll/020-021.html.

Fig. 2.

Target ranges of oxygen therapy for the different groups of patients. BMI, body mass index; SpO2, oxygen saturation measured by pulse oximetry; SaO2, arterial oxygen saturation. From https://www.awmf.org/leitlinien/detail/ll/020-021.html.

Close modal

Exceptions without a target oxygen saturation range are patients with cluster headache, carbon monoxide poisoning, and critically ill patients in whom pulse oximetry cannot be used.

The recommended O2 therapy for patients with spontaneous breathing is shown in Figure 3.

Fig. 3.

Oxygen therapy in nonventilated patients. CPR, cardiopulmonary resuscitation; SpO2, oxygen saturation as measured by pulse oximetry; O2, oxygen; NIV, noninvasive ventilation; HFNC, high-flow oxygen; BMI, body mass index; art., arterial; cap., capillary; pCO2, partial pressure of carbon dioxide; HCP, health care provider. * e.g., COPD, BMI ≥40 kg/m2, cystic fibrosis, adults with neuromuscular or chest wall disorders. # Do not start O2 below SpO2 88 or 92%, respectively. ## Stop or reduce O2 above 92 or 96%, respectively.

Fig. 3.

Oxygen therapy in nonventilated patients. CPR, cardiopulmonary resuscitation; SpO2, oxygen saturation as measured by pulse oximetry; O2, oxygen; NIV, noninvasive ventilation; HFNC, high-flow oxygen; BMI, body mass index; art., arterial; cap., capillary; pCO2, partial pressure of carbon dioxide; HCP, health care provider. * e.g., COPD, BMI ≥40 kg/m2, cystic fibrosis, adults with neuromuscular or chest wall disorders. # Do not start O2 below SpO2 88 or 92%, respectively. ## Stop or reduce O2 above 92 or 96%, respectively.

Close modal

3.6 Oxygen Saturation Target Ranges in Acute Conditions

graphic

Three meta-analyses and four RCTsrandomized controlled trials on target oxygen ranges were identified by independent literature search [17, 31, 41, 104-106]. The meta-analysis by Chu et al. [31] of 25 RCTs with 16,037 hospitalized patients demonstrated that liberal oxygen administration was associated with increased 30-day mortality (and at longest follow-up). This meta-analysis included patients with sepsis, critical illness, stroke, trauma or emergency surgery, acute coronary syndrome, and cardiac arrest. Most randomized trials covered by the meta-analysis compared high-dose oxygen (with resulting hyperoxemia) in normoxemic patients against patients on ambient air or compressed air as placebo group. Increased mortality associated with hyperoxemia may have been caused by proinflammatory effects, vasoconstriction, particularly in the myocardium and CNS, and increased oxidative stress. The upper limit of SpO2 of 96% recommended in the meta-analysis by Chu et al. is also based on the mean saturation at enrollment.

In the largest randomized trials on patients with stroke and acute myocardial infarction, the limit of SpO2 below which oxygen was administered in any case ranged from 90 to 94% [104, 106, 107]. Almost 38,000 patients with a median age of 69 years in 3 UK hospitals had a mean SpO2 on ambient air of 97% on admission (25th and 75th quartiles of 95 and 98%) [30].

Routine high-dose oxygen administration in the perioperative period (the inspiratory oxygen fraction (FiO2) based on a large meta-analysis [108] conducted for this indication, hyperoxemia is not reasonable during surgery.

Practice Point:

If oxygen saturation falls below 92%, starting or increasing oxygen therapy is reasonable in patients not at risk of hypercapnia. If the saturation exceeds 96%, it is indicated to discontinue or reduce the oxygen therapy.

The specified target oxygen saturation applies at rest. In acutely ill patients, values below the target range can be tolerated for a short period of time during exertion or coughing, if the oxygen saturation subsequently quickly returns to the target range (as a rule within less than 1 min).

Oxygen cards indicating the SpO2 target range at the bedside are useful for all patients on oxygen therapy (Fig. 4, 5).

Fig. 4.

O2 card for patients not at risk of hypercapnia.

Fig. 4.

O2 card for patients not at risk of hypercapnia.

Close modal
Fig. 5.

O2 card for patients at risk of hypercapnia.

Fig. 5.

O2 card for patients at risk of hypercapnia.

Close modal

3.7 Target Oxygen Saturation Ranges for Patients at Risk of Hypercapnia

graphic

The authors’ own literature search identified one meta-analysis in addition to the evidence report [109]. However, this meta-analysis is based on 1 RCT only [39]. In this RCT [49], 403 patients with suspected COPD (the diagnosis was retrospectively confirmed in 214 patients) were treated by emergency staff with either high-dose oxygen (6–8 L/min by mask) or with cautious oxygen administration titrated to a target saturation between 88 and 92%. 9% of patients treated with high-dose oxygen versus 3% of those treated with conservative oxygen therapy died while in hospital (treatment effect 0.05–0.91). Intubation rates were not significantly increased under liberal oxygen therapy.

A study of 3,524 blood gas samples in a single UK hospital found that 27% had a partial pressure of carbon dioxide of more than 45 mm Hg [63]. In a German analysis of 6,750 hospitalized patients, 2,710 of whom suffered from respiratory distress, 588 (22%) had a PaCO2 of 45 mm Hg and more [110]. Patients with COPD in particular, but also those with cystic fibrosis, thoracic deformities, neuromuscular disease, and obesity (BMI >40 kg/m2), are at risk of hypercapnic respiratory failure in the context of ventilatory insufficiency [111-117]. In 22–34% of high-risk patients (including COPD and obesity), a significant increase in the transcutaneously measured partial pressure of carbon dioxide was observed under high-dose oxygen therapy. Hence, the risk of hypercapnic respiratory failure was increased three- to fivefold versus conservative oxygen therapy [95, 118-121].

In a prospective observational study on 2,645 COPD patients with in-hospital exacerbation in the UK, SpO2 >92% on admission was associated with increased in-hospital mortality (adjusted risk of death 1.98 (95% CI 1.09–3.60) and 2.97 (95% CI 1.58–5.58), respectively, independent of the presence of hypercapnia [122].

3.8 Target Oxygen Saturation Ranges for Ventilated Patients

graphic

Ventilated patients should be viewed separately, as they are usually continuously monitored in the ICU and the risk of hypercapnic respiratory failure is lower under mechanical ventilation. Recent publications have shown harmful effects of hyperoxemia in intensive care patients, especially those who are ventilated.

Three large retrospective observational studies (36,307 patients [126], 19,515 patients [127], 152,680 patients [128]) investigated the effect of hypoxemia and hyperoxemia on the in-hospital mortality of ICU patients.

In a meta-analysis of 10 randomized trials and 1,458 subjects, no association was found between 3-month mortality and hyperoxemia (target SpO2 >96%); however, hyperoxemia went along with a relative risk of 1.13 (1.04–1.23) of more adverse events such as infections, with a very low level of evidence [34]. For ARDS, a 2020 meta-analysis including a single study (26) indicated a conservative SpO2 target range of 88–92% with a very low level of evidence [129]. The authors of a 2017 meta-analysis (4 studies with 372 patients) found conservative oxygen therapy to be associated with lower ICU mortality, 28-day mortality, in-hospital mortality, and nonrespiratory organ failure than liberal O2 therapy [130].

Six randomized trials compared liberal versus conservative oxygen therapy for mostly invasively ventilated ICU patients. Oxygen saturation target ranges were not consistent across studies, and the included patient populations were heterogeneous. About a quarter of the ventilation time was spent without supplemental oxygen administration under a conservative O2 regime, without adverse effects being observed [105]. The French study on 205 patients with ARDS was terminated prematurely due to safety concerns, as the conservative therapy group showed increased mortality versus other studies with a particularly low target saturation range of 88–92%, and 5 patients in the conservative therapy group died of mesenteric ischemia. Mortality was also increased in the conservative therapy group in the Australian multicenter study [124] with the same SpO2 target range, albeit not significantly.

The HOT-ICU trial [131] was published after the consensus process had been completed. It is the largest RCT on oxygen target ranges in ICU patients to date. In this study, 2,928 patients with severe hypoxemia (median oxygenation index 125 mm Hg, 58% with invasive ventilation at randomization) were randomized to a conservative oxygen target range (paO2 60 mm Hg with a maximum tolerance of 7.5 mm Hg, achieving a median SaO2 of 93%) and a liberal oxygen target range (paO2 90 mm Hg with a maximum tolerance of 7.5 mm Hg, achieving a median SaO2 of 96%). The 90-day mortality (primary end point) was not different between the conservative and the liberal O2 group, with 42 and 43%, respectively.

In numerous RCTs comparing noninvasive ventilation (NIV) or continuous positive airway pressure (CPAP) therapy and supplemental oxygen therapy, the lower limit of oxygen saturation as measured by pulse oximetry at which the amount of oxygen was adjusted, was mostly between 90 and 92% [71, 132-134]. The guideline authors therefore believe that the SpO2 target range for oxygen therapy should be between 92 and 96%, even under NIV or CPAP.

3.9 Compliance with Oxygen Therapy Target Ranges

In a large observational study in the Netherlands, 32% of measured partial pressures of oxygen were outside the target range of 55–86 mm Hg in 3,007 ICU patients in whom O2 delivery was manually adjusted based on BGA results. 90% of oxygen readings were above the target range. Just under 27% of over 272,000 readings measured by pulse oximetry in the same study were within target range, which in this study was 92–96%. A large percentage of (SpO2 or pO2) readings were outside the target range, also in the randomized studies with ICU patients. In particular, between 14 and 75% of readings were above target range in the conservative oxygen therapy arms.

In 4 (randomized or crossover) controlled trials with 16–187 patients on automatic oxygen titration, among them patients at risk of hypercapnic respiratory failure, 10–24% of the readings were above the target SpO2 range under manual oxygen titration. The use of automated closed-loop O2 titration systems resulted in significantly fewer (1–5%) readings above the target range [135-138]. Closed-loop systems (automatic titration) have been well studied for the treatment of preterm infants. A randomized trial with ventilated adults demonstrated that patients treated with closed-loop systems spend more time in the target oxygen saturation range [139].

In two small case series, the resorption of pneumothorax was accelerated by giving high-dose oxygen (up to 16 L/min via mask) [140, 141], without the method having found its way into any guidelines [142]. In an RCT comparing treatment by drainage and conservative therapy in 316 patients with major spontaneous pneumothorax, spontaneous re-expansion was observed in 94% of patients in the conservative group at 8 weeks [143]. High-dose oxygen therapy was not part of routine therapy in the group without drainage; patients were treated with oxygen only at a saturation rate <92%. In secondary spontaneous pneumothorax, experts are concerned about hypercapnic respiratory failure under high-dose oxygen.

Practice Point:

There is no recommendation for high-dose oxygen without a target SpO2 range in spontaneous pneumothorax.

graphic

Breathlessness can have many causes and is not always accompanied by hypoxemia. Helpful tools in diagnosing patients with dyspnea without hypoxemia include their clinical history, vital signs, and BGAs.

An increased respiration rate is associated with increased in-hospital mortality [18] and considered a warning signal, not only of pulmonary disease, but also of sepsis. Tachypnea in normoxemic patients may be attributable to serious causes but can also be the result of a harmless condition. BGA, for example, may show metabolic disorders such as severe acidosis, whereas hyperventilation syndrome can usually be differentiated based on clinical findings.

3.10 Intractable Hypoxemia

graphic

Oxygen flow rates >6 L/min frequently lead to the use of O2 reservoir masks and high-flow oxygen therapy in clinical routine. In RCTs as well as in large cohort studies, the intubation rate of HFNC collectives was 35–40%. Patients with a severe gas exchange disorder are therefore a high-risk group and require immediate attention and, if possible, assessment by a health care professional experienced in critical care.

SpO2 levels <92% under >6 L O2/min correspond to an oxygenation index (pO2/FiO2 ratio) <150 mm Hg. Clinical experience shows that patients with persistent hypoxemia despite receiving 6 L/min of oxygen frequently require treatment in the ICU. In the subgroup of ARDS patients treated with NIV, ICU mortality was increased below an oxygenation index of 150 [144].

The study by Austin et al. [39], on the other hand, impressively demonstrated that high-dose oxygen with a high risk of hypercapnic respiratory failure resulted in a significantly higher incidence of in-hospital deaths. Patients with hypercapnic respiratory failure usually respond insufficiently to oxygen administration alone. In these patients, NIV is the primary line of treatment for hypoxemia and can be used either alone or in combination with oxygen to correct hypoxemia. Patients in the study of Austin et al. had a mean SpO2 of 84–87% prior to randomization. The assessment of this patient population by experienced health care practitioners and the early use of NIV may therefore prevent intubation by avoiding the undiscerning administration of high-flow oxygen. In the clinical routine, SpO2 values like these unfortunately often prompt an unreflected administration of high-dose oxygen. Liberal oxygen therapy is therefore usually contraindicated in patients with a relevant risk of hypercapnic respiratory failure.

If oxygenation in the target range cannot be achieved by nasal cannula or Venturi mask and hypercapnia is ruled out, alternative delivery systems shall be used. When using simple face masks or even reservoir masks, flow rates below 5 L/min should be avoided due to the increased risk of hypercapnia from carbon dioxide rebreathing [145, 146] (see chapter 5.2).

graphic

A Cochrane meta-analysis for cardiogenic pulmonary edema (24 randomized trials, 2,664 patients) [147] and COPD exacerbation (17 randomized studies, 1,264 patients) [148] showed – with a moderate level of evidence – that both NIV in comparison to standard of care was associated with reduced in-hospital mortality and intubation rates. A meta-analysis found no increased risk of acute coronary events for cardiogenic pulmonary edema [147]. This meta-analysis on pulmonary edema failed to establish superiority of NIV versus CPAP, whereas NIV is superior to CPAP for the treatment of COPD. NIV should also be considered for other hypercapnic and hypoxemic patients, e.g., those with neuromuscular disorders, class 3 obesity, cystic fibrosis, and thoracic deformities, when the partial pressure of carbon dioxide is >45 mm Hg and pH <7.35. With the exception of individual cases, however, there are no randomized controlled studies on this topic [149, 150].

The S3 guideline on “Noninvasive ventilation in the treatment of acute respiratory failure” [151] advocates NIV for hypercapnic patients with a pH of 7.3–7.35.

There are 7 randomized studies directly comparing HFNC and NIV in the acute management of 40–803 hypoxemic patients, and another study [133] comparing NIV and conventional oxygen therapy in addition. The 5 randomized trials, some of which included hypercapnic patients (pCO2 52–61 mm Hg), demonstrated the noninferiority of HFNC versus NIV in terms of intubation rate after 72 h of use [152-156]. In a randomized trial, the intubation rate of 204 emergency patients with all-cause respiratory failure (mean pCO2 of 55 mm Hg) was 13% under NIV and 7% under HFNC [152]. The in-hospital mortality or 28-day-mortality in 3 studies with mainly patients early after extubation ranged from 12 to 18% under NIV and from 15–20% under HFNC and, hence, did not differ [154, 156-158]. A crossover study in 24 stable COPD patients [159] showed that NIV reduced the transcutaneously measured partial pressure of carbon dioxide more significantly than HFNC (5.3 vs. 2.5 mm Hg). In many HFNC studies, new-onset or progressive respiratory acidosis is a discontinuation criterion [72].

Practice Points:

NIV is an important option for the acute treatment of markedly hypercapnic and hypoxemic patients with COPD exacerbation.

NIV, CPAP, and HFNC are reasonable treatment alternatives for patients with cardiogenic pulmonary edema and severe hypoxemia (FiO2 >0.4 or >6 L/min) under conventional oxygen therapy.

HFNC does not seem to be inferior to NIV for patients with moderate hypercapnia.

graphic

The meta-analysis by Ferreyro et al. [160] analyzed 25 studies with a total of 3,804 patients comparing various types of respiratory support versus standard oxygen administration in patients with acute hypoxemic pulmonary failure. Seven of these studies compared high-flow oxygen therapy, in part versus NIV. The 90-day mortality in this meta-analysis was reduced for all types of support (HFNC, NIV, CPAP) versus conventional oxygen therapy, with a relative risk of 0.83 (95% CI 0.68–0.99) [160].

Another meta-analysis [161] studied NIV versus conventional oxygen therapy in nosocomial and community-acquired pneumonia and found – with a low level of evidence – that NIV reduces ICU mortality (odds ratio (OR) 0.28, 95% confidence interval (CI) 0.09–0.88) as well as the intubation rate (OR 0.26, 95% CI 0.11–0.61).

However, the proportion of patients with type 1 respiratory failure (i.e., those with isolated hypoxemia) and those with concomitant hypercapnia (type 2 respiratory failure) was not reported in these studies. In conclusion, the role of NIV in patients with isolated hypoxemia is difficult to assess at present. Hospital mortality rates (15–81%) in these patient groups, especially for patients with acute respiratory failure under immunosuppressive therapy, as well as intubation rates (10–77%) are very high [162-164]. The guideline authors believe that a treatment attempt is medically reasonable, at least in the latter subgroup. In the LUNGsafe study, however, a moderate to severe gas exchange disorder (pO2/FiO2 <150 mm Hg) was associated with failed NIV therapy in more than 41% of the 436 ARDS patients on NIV [144].

According to the National S3 guideline on “Non-invasive ventilation in the treatment of acute respiratory failure,” CPAP or NIV, respectively, may be considered in order to avoid intubation in immunocompromised patients with AIDS, mild ARDS, and pneumonia, with due consideration of contraindications and discontinuation criteria [151].

3.11 Oxygen Therapy in Cardiovascular Diseases

Randomized trials of oxygen therapy in patients with acute coronary syndrome generally excluded those at risk of hypercapnic respiratory failure [104, 107, 165]. In these trials, the lower limit of oxygen saturation as measured by pulse oximetry below which oxygen was administered in each case ranged from 85 to 94%.

According to expert consensus, a target arterial saturation rate of 94–98% is recommended in cardiogenic shock due to myocardial infarction [166]. The guideline references the meta-analysis by Chu et al. [31] and the largest randomized DETO2X-AMI trial on patients with acute coronary syndrome, although only 1% of them had cardiogenic shock [104]. In ST elevation myocardial infarction, oxygen administration is recommended internationally only at a SaO2 <90% with a target saturation of 95% (moderate level of evidence) [167]. This recommendation is based on three RCTsrandomized controlled trials and a Cochrane meta-analysis [104, 165, 168, 169]. At a lower limit of 94%, approximately 25% of participants in the DETO2X-AMI trial would already have received O2 at baseline. However, even in a subgroup analysis of patients with O2 saturations between 90 and 94%, this approach was not associated with improved survival [170].

Two Cochrane meta-analyses found no evidence to support routine oxygen administration in acute myocardial infarction [168, 171]. A meta-analysis of 8 studies with 7,998 patients also found no difference in the 30-day mortality between patients treated with compressed air/ambient air and those on routine oxygen therapy (3–8 L/min) [41].

Strong evidence speaks for an upper limit of 96% because it corresponds to the median level before randomization in trials involving patients with myocardial infarction and it is the normal saturation in a population living at sea level [32].

The clinical practice guideline by Siemieniuk et al. [32] strongly recommends that patients with stroke and those with myocardial infarction should only be started on oxygen once their saturation drops below 93%. This recommendation was based on fewer coronary events and/or coronary revascularization procedures at 6 and 12 months in the meta-analysis. In conclusion, experts agree that the target ranges of oxygen therapy for patients with acute coronary syndrome are not different than for other patients.

An unblinded RCT including 50 patients with heart failure (excluding those requiring oxygen >10 L/min) also showed no difference with regard to B-type natriuretic peptide levels, in-hospital mortality and rehospitalization rates under conservative oxygen therapy (target SpO2 90–92%) versus liberal O2 therapy (SpO2 >96%) [172].

3.12 Oxygen Therapy in Neurological Disorders

At a lower limit of 95%, as recommended in the guidelines on the management of patients with stroke [173, 174], more than a quarter of the patients included in the largest randomized SOS trial would already have been treated with O2 at baseline [106]. However, the O2 therapy was not associated with improved survival in this study, and no upper limit was defined.

There is strong evidence supporting an upper limit of 96% as it corresponds to the median level of subjects included in stroke trials before randomization, and to the normal level in a population living at sea level, and higher levels under O2 therapy were associated with more deaths in the meta-analyses [32].

The clinical practice guideline by Siemieniuk et al. [32] strongly recommends that stroke patients should only be started on oxygen once the saturation drops below 93%. This recommendation was based on a meta-analysis, which found lower mortality from stroke under conservative O2 therapy. This meta-analysis found no difference between liberal and conservative oxygen therapy with regard to functional outcomes after cerebral infarction (low level of evidence). This was also the conclusion of another meta-analysis of 11 RCTs on 6,366 patients with cerebral infarction [175].

In a large retrospective analysis of 3,420 patients with craniocerebral injury in the USA, hyperoxemia was associated with increased in-hospital mortality [176]. The national S3 guideline provides a weak recommendation to avoid hypoxemia (SaO2 <90%) in patients with severe craniocerebral injury. The recommendation is based on retrospective analyses [177]. The international guideline for the acute treatment of patients with brain injury recommends to avoid hyperoxemia and, based on expert opinion, advocates a paO2 target range of 80–120 mm Hg [178].

RCTs with patients after restoration of circulation following CPR also did not show a superiority of liberal oxygen administration.

Two large retrospective analyses including 252 and 936 invasively ventilated patients with subarachnoid hemorrhage showed higher in-hospital mortality and inferior functional outcome at 6 months in patients with hyperoxemia (paO2 >172 and 300 mm Hg, respectively) [179, 180]. No RCTs for this condition are available.

Cerebral vasoconstriction has been described under hypoxemia, and neurotoxicity in the form of seizures has been described for hyperbaric oxygenation [33, 181]. A meta-analysis found no beneficial effects of hyperbaric oxygen therapy (HBO) for the treatment of ischemic stroke [182].

In conclusion, oxygen therapy target ranges for patients with neurological diseases do not differ from those specified in chapter 6. In particular, hyperoxemia should be avoided in these patients.

3.13 Oxygen during Pregnancy and Childbirth

Guidelines recommend an oxygen saturation of 95% or more for managing asthma during pregnancy [183]. However, no studies comparing various oxygen target ranges have yet been published. Five RCTs investigated the use of 2–10 liters of oxygen/min versus room air or without O2 flow during delivery in normoxemic pregnant women without asthma. Oxygen administration had no influence on the lactate or oxygen levels or on the pH in umbilical cord blood [184-186]. In a randomized, single-center US study of 99 pregnant women, the administration of 10 liters of oxygen/min did not reduce the rate of cesarean or forceps deliveries and late decelerations as compared to the group on room air [187]. Pregnant women with an initial saturation as measured by pulse oximetry of less than 97% were excluded from this study. The authors therefore conclude that the treatment of pregnant women, including those with asthma, should be based on the target oxygen levels considered adequate for other adult patient groups.

3.14 Oxygen Therapy for the Treatment of Poisoning

graphic

The BTS guideline [63] mentions 2 Cochrane meta-analyses on HBO in carbon monoxide poisoning [188, 189]. The independent literature search identified 2 additional meta-analyses on the role of HBO [190, 191]. There are thus a total of 4 meta-analyses on this subject. All RCTs included in these 2 recent 2018 meta-analyses have already been included in the most recent Cochrane analysis. Just the meta-analysis by Wang et al. [191] demonstrated a benefit for HBO over normobaric therapy, albeit without evidence assessment. None of the meta-analyses established an association between HBO and reduced mortality.

According to experts, high-dose oxygen can achieve hemoglobin saturation and shorten the elimination half-life of CO despite the superior affinity of carbon monoxide [192]. Carbon monoxide poisoning shall therefore be immediately treated with the highest possible oxygen concentration, irrespective of oxygen saturation (SpO2).

The treatment shall be continued until the carbon monoxide bound with hemoglobin (COHb) has dropped to normal levels (<3%) and the patient is no longer symptomatic. This is typically the case after a maximum of 5 physiological COHb half-lives under 100% oxygen (approx. 375 min). Oxygen is typically delivered via NIV/CPAP, reservoir masks and, in intubated patients, via the tube. Successful treatment of CO poisoning with high-flow oxygen therapy has also been described [193].

Conservative oxygen therapy has been recommended for the treatment of poisoning from paraquat (which has been taken off the market) and bleomycin. Some historical studies recommend that oxygen should be administered only once saturation falls below 85%. The rationale is based on pathophysiology, i.e. the formation of free oxygen radicals (reactive oxygen species) when paraquat binds with molecular oxygen, which may be conducive to the development of pulmonary fibrosis. Oxygen administration has also been associated with increased pulmonary complications in bleomycin poisoning. However, no clear upper limit of oxygen saturation above which pulmonary toxicity increases in paraquat and bleomycin poisoning can be derived from the available literature.

The benefits and risks as well as the medical necessity of hyperbaric oxygen therapy have so far not been adequately demonstrated for any indication. HBO therapy for the treatment of carbon monoxide poisoning is based on plausible theories regarding the effectiveness of this method. The benefits of HBO have been evaluated for various indications in the context of numerous randomized clinical trials. The results of studies and meta-analyses on HBO are contradictory in part. There are several meta-analyses which failed to convincingly demonstrate the benefit of the therapy. It can therefore not be recommended for the treatment of carbon monoxide poisoning in this guideline [182, 188, 194-197].

Practice Points:

BGA is useful for assessing carbon monoxide poisoning and determining the amount of COHb. It is irrelevant in this case whether the blood sample is a venous, arterial, or capillary sample.

It is reasonable to treat carbon monoxide poisoning with high-dose oxygen for up to 6 h, regardless of oxygen saturation. In addition to the tube, high-dose O2 therapy can also be delivered via NIV/CPAP, masks, or HFNC.

With the exception of carbon monoxide poisoning, the general target ranges of oxygen saturation (92–96% or 88–92% for patients at risk of hypercapnia) constitute reasonable oxygen ranges for the treatment of other intoxication conditions by oxygen therapy.

3.15 Prehospital Oxygen Therapy

graphic

A meta-analysis on the effect of hyperoxia on survival after cardiovascular arrest was considered in the development of the BTS guideline [199]. Our own evidence search identified a international guideline including evidence assessment and one meta-analysis [198, 200], which can be applied to the subgroup of patients after prehospital CPR. The 2020 meta-analysis by Holmberg et al. [198] reviewed 7 RCTs, which predominantly included patients after prehospital CPR, with highly diverse patient groups. Due to the unacceptable bias of the study results, the authors were unable to provide a recommendation in favor of hyperoxemia or normoxemia.

SpO2 target ranges in the preclinical setting are not different from those recommended in Figure 2. The insights regarding the benefit of lower SpO2 target ranges in the prehospital setting were gained especially for patients at risk of hypercapnia (COPD patients with exacerbation) [39, 109].

The prehospital setting is characterized by special conditions as blood gas analyzers are often not available and oxygen delivery systems (such as HFNC) and O2 sources (usually compressed gas cylinders only) are available to a limited extent only. In the prehospital setting, oxygen may also be administered by nonmedical staff in the context of first aid based on the defense of necessity. According to expert opinion, emergency medical service personnel shall be trained in oxygen therapy at regular intervals.

High-dose oxygen administration is justifiable during CPR or when a reliable pulse oximetry signal cannot be obtained (e.g., patients with shock or centralization). Apart from these special situations, e.g., after return of spontaneous circulation, it is recommended that the oxygen therapy target ranges be observed, also in the prehospital setting.

Three randomized trials on the use of CPAP in patients with cardiogenic pulmonary edema and acute respiratory failure showed a reduction in the out-of-hospital intubation rate [201-203]. Only in the study by Thompson et al. [201] was in-hospital mortality also significantly reduced versus standard oxygen therapy when CPAP had been used in the prehospital setting.

Practice Points:

If the SpO2 signal is not reliable or not available, oxygen shall be administered as if no pulse oximeter were available.

With the exception of critical situations (e.g., during CPR), pulse oximetry is a meaningful tool for assessing a patient before initiating oxygen therapy, even in a prehospital setting.

It is recommended to have the following O2 delivery devices available in the prehospital setting: O2 reservoir mask (for high-concentration oxygen therapy); nasal prongs, Venturi mask, and O2 delivery systems for patients after tracheostomy or laryngectomy, as applicable

A portable pulse oximeter device to assess patients with regard to the presence of hypoxemia and for initial assessment is an essential tool in the out-of-hospital setting, and a portable oxygen source is a useful part of emergency equipment for critically ill patients or those with respiratory distress,

Blood gas analyzers are usually not available outside of hospitals. It is therefore important to recognize the clinical symptoms of patients at risk of hypercapnia.

Emergency cards can help to identify and treat patients at risk of hypercapnia and those with a history of hypercapnia episodes.

graphic

The meta-analysis of Wang et al. [199] covered 14 studies on oxygen therapy following CPR. Patients with hyperoxemia were found to have greater mortality. In this analysis, mortality was higher under hyperoxemia following CPR, however without a significantly inferior outcome for normoxemic patients.

Two smaller randomized trials with 35 and 61 patients, respectively, in whom circulation was restored after CPR demonstrated the noninferiority of conservative oxygen therapy in the out-of-hospital setting [204, 205], while the study by Young et al. [206], in the same clinical constellation, was discontinued early after 17 patients due to safety concerns regarding target saturation ranges of 90–94%. A single-center RCT [205] comparing the effectiveness of hyperoxygenation (target saturation 100%, n = 17) versus titrated oxygen (target saturation 94–98%, n = 18) in the first hour after out-of-hospital CPR showed no improvement with regard to the 90-day survival rate (55% for conservative oxygen administration vs. 18% for hyperoxemia). Target saturation ranges of 90% and more were pursued in 2 Australian studies, without these studies having been designed for the mortality end point [204, 206]. A 2019 meta-analysis by Holmberg et al. [198] analyzed 7 randomized trials and 36 observational studies. No conclusive result was obtained with regard to hyperoxemia versus normoxemia after successful CPR. A recently published meta-analysis [207] of 429 patients found lower mortality in patients on conservative versus those on liberal O2 therapy after return of spontaneous circulation.

Practice Point:

Set FiO2 to 1.0 during CPR.

3.16 Oxygen Therapy in COVID-19 and Other Infectious Lung Diseases

graphic

Most COVID-19 patients without a history of pulmonary disease present with isolated hypoxemia on hospitalization. It has been observed that some COVID-19 patients have no symptoms of shortness of breath despite suffering from severe hypoxemia. This phenomenon is called “silent hypoxemia.” Given the unreliability of pulse oximetry in the lower SpO2 range and the shift of the oxygen dissociation curve in patients with fever, some authors advocate BGA for COVID-19 patients [209]. Hospitalized COVID-19 patients must be closely monitored for vital signs (especially pulse oximetry) and respiration rate due to the dynamic deterioration process following hospitalization. Early warning systems such as NEWS2 have also been successfully used in COVID-19 wards.

An identified guideline recommends (with a low level of evidence) a lower limit of SpO2 of 92% and (with a moderate level of evidence) an upper limit of 96% for COVID-19 patients treated with supplemental O2 [208]. The recommendation is based on 2 RCTs with ventilated subjects and 1 meta-analysis [17, 31, 105]. None of these studies included COVID-19 patients. Based on theoretical considerations such as endothelitis, microthrombi, hypoxic vasoconstriction, and hypoxia-induced modulation of the ACE-2 receptor, lower target ranges are not recommended for the treatment of COVID-19 [210]. The optimal O2 target range for adults with COVID-19 is currently uncertain, and there is currently no evidence to suggest that the target oxygen saturation range for COVID-19 patients should differ from that for other conditions. In addition, hyperoxemia under O2 therapy may lead to the delayed detection of respiratory failure, for example in COVID-19 patients [6]. The oxygen therapy algorithm outlined in Figure 3 should also be used in patients with viral respiratory tract infections.

The 2003 SARS-CoV-1 epidemic saw a relevant number of infections among hospital staff as a result of aerosol-generating medical procedures such as drug nebulization. In patients with SARS-Cov-2 and other RNA viruses such as influenza, respiratory syncytial virus, and rhinoviruses, viral RNA could be isolated from exhaled droplets (≤5 μm). Increased aerosol formation was observed at higher oxygen flow rates in conventional oxygen treatment via nasal cannula and face mask (extending up to 1 m). Increased aerosol formation during exhalation is found under both high-flow oxygen therapy and NIV, depending on the depth of breaths [211].

For high-flow oxygen therapy, it has been demonstrated that expired air extends less than 20 cm from a patient – as long as the nasal cannula is properly placed – which is less than with conventional oxygen administration. This is attributed to the tighter fit of the high-flow cannula. Venturi masks also did not result in increased aerosol formation. Personal protective equipment, distancing, proper fit of HFNC or NIV mask, and the wearing of mouth-nose protection by patients under oxygen therapy appear to be appropriate measures to prevent infection of those in their vicinity. Insulated nose masks should be avoided in NIV, and instead, nonleaking masks and 2-tube systems should be preferred.

3.17 Patients with Cluster Headaches

graphic

Eleven studies with a total of 209 patients were evaluated in the 2015 Cochrane analysis. Oxygen administration at 7 L/min in a historical RCT with 52 patients with cluster headaches provided impressive symptom relief for 39 patients (75%). A second phase of the trial compared ergotamine therapy versus oxygen administration (7 L/min for 15 min) in 50 patients with cluster headache. Oxygen therapy resulted in a headache-related response in 82% of patients versus 70% in the ergotamine group [214].

In another randomized placebo-controlled trial, 109 patients with cluster headache were treated with either 12 L/min O2 for 15 min or 12 L/min of normal air (sham procedure) [212]. The primary end point of freedom from pain after 15 min was achieved in 78% in the concentrated oxygen group versus 20% in the control group (p < 0.01).

3.18 Oxygen Use during Procedures Involving Conscious Sedation

graphic

Hypoxemia is a frequent occurrence in procedures performed with the goal of preserving spontaneous breathing. Clinical monitoring via pulse oximetry is a requirement and stipulated, among others, in the quality assurance in colonoscopy agreement (“Qualitätssicherungsvereinbarung zur Koloskopie”) pursuant to section 135 of the German Social Code, Book V (SGB V) [215]. In gastrointestinal endoscopy, 8–57% of patients were found to have hypoxemia with SpO2 levels <90% in RCTs comparing midazolam versus propofol.

In the light of this frequency, the authors see a clear indication for continuous monitoring via pulse oximetry before, during and after such procedures, an indication for extended hypoxemia monitoring to assess for hypoventilation episodes.

graphic

In the absence of studies supported by high-level evidence, this recommendation is based on expert opinion.

The reported incidence of adverse cardiopulmonary events is 5% under benzodiazepines and 0.1% in propofol studies [216, 217], although the definitions of “adverse cardiopulmonary events” are quite heterogeneous across these studies. In clinical experience, a significant desaturation (SpO2 <90% or a prolonged (>1 min) drop >4% during endoscopy) usually cannot be corrected by supplemental oxygen alone. When oxygen is administered, a target oxygen saturation in a range of 92–96% (or 88–92% for those at risk of hypercapnia) should be set. Bronchoscopy procedures, and in particular interventional bronchoscopy, have an increased risk of hypoxemia, depending on the lung function [218, 219].

The prophylactic administration of oxygen before and during procedures involving conscious sedation, especially in patients at risk of hypercapnic respiratory failure, is controversial. In a randomized study on 389 patients undergoing gastrointestinal endoscopy, half were given prophylactic oxygen (2 L/min), while the other half were administered oxygen only upon desaturation [220]. Desaturation events (SpO2 <95%) occurred in 21% in the O2 group versus 81% in the control group without prophylactic oxygen. 83% of desaturation events were mild (SpO2 90–94%). However, patients at risk of hypercapnia were excluded from this study, and no BGAs to detect hypercapnia were performed. In hypoventilation and resulting hypoxemia, oxygen therapy is not a causal therapy, but rather there are methods such as inserting breathing devices (e.g., Guedel tube) or using assisted ventilation. Routine oxygen supplementation as a “safety buffer” cannot be generally recommended, especially not in patients at risk of hypercapnic respiratory failure (e.g., COPD, morbid obesity) during procedures involving conscious sedation with maintained spontaneous breathing.

Using capnometry to monitor ventilation during endoscopy allows to detect apnea/hypopnea episodes early. In a study on 132 patients, capnometry detected hypo-/apnea on average 60 s early [221]. In 5 RCTs on the use of capnometry in the context of various procedures (bronchoscopy in 2 studies, endoscopic retrograde cholangiography-pancreaticography in 1 study, colonoscopy and various procedures in 1 study) with 132–1,386 participants, hypoxemia according to various definitions was found in 25–44% of study participants [221-225]. Using capnometry, events of apnea or hypopnea were recorded in 22–65% of study participants during the procedure, thus most hypoxemic episodes were likely caused by hypoventilation.

Practice Points:

Continuous monitoring by pulse oximetry is useful to detect hypoxemia, which is a common occurrence in all procedures involving conscious sedation.

Hypoxemia under conscious sedation is often caused by hypoventilation. The oxygen therapy in procedural sedation is oriented on the same target ranges (SpO2 92–96% or 88–92% in patients at risk of hypercapnia) as in other conditions. Oxygen administration alone is often not sufficiently effective in hypoxemia under procedural conscious sedation, and additional measures to correct hypoventilation are helpful.

Another monitoring tool for ventilation is transthoracic impedance, which is easily derived from ECG monitors. No RCTs are available to date, but the method is currently being studied in the context of a clinical trial during endoscopy (NCT04202029).

4.1 High-Flow Oxygen Therapy

graphic

In high-flow oxygen therapy, heated and humidified oxygen is delivered via nasal cannula at flow rates of 40–60 L/min. This is usually well tolerated by patients. High-flow oxygen therapy generates a low positive end-expiratory pressure and also reduces the breathing effort through CO2 washout and the associated reduction of dead space.

A Cochrane meta-analysis by Corley et al. [226] reviewed 11 RCTs on high-flow oxygen versus standard oxygen therapy via nasal cannula, face mask, and/or standard oxygen therapy in pulmonary failure or after extubation. Due to a high risk of bias, the quality of the included studies was insufficient to allow a conclusive assessment. A systematic summary by Marjanovic et al. [227] included 5 RCTs. While dyspnea and respiration rate were improved, there was no difference with regard to the end points of intubation, length of hospitalization, and mortality under high-flow therapy. Ou et al. [228] conducted a systematic review on HFNC after extubation versus standard oxygen therapy with the end point of reintubation. According to this review, the reintubation rate of critically ill patients was lower when HFNC was used. Wen et al. [229] conducted a systematic review of HFNC in immunosuppressed patients with acute pulmonary failure (259), evaluating 8 RCTs. There was no difference in mortality under HFNC, but the intubation rate was lower and hospitalization shorter than with NIV.

In conclusion, HFNC is associated with lower intubation rates, at least in 1 meta-analysis, but the mortality was not significantly reduced versus standard oxygen therapy.

graphic

The literature search failed to identify relevant studies with a strong level of evidence on this question.

In an RCT with HFNC in patients with an oxygenation index (paO2/FiO2) 108–161 mm Hg, 39–51% of participants were intubated [71].

Practice Point:

The respiratory rate-oxygenation (ROX) index is an additional index available at the bedside. It is calculated from SpO2, FiO2, and respiration rate, and a lower ROX value is associated with treatment failure as demonstrated in various patient populations.

In a prospective study, Roca et al. [72] examined the ROX index (SpO2/FiO2/respiration rate) to predict high-flow oxygen therapy failure in patients with community-acquired pneumonia. ROX values <2.85, <3.47, and <3.85 at 2, 6, and 12 h of HFNC initiation, respectively, were predictors of HFNC failure. A ROX index ≥4.88 was consistently associated with positive outcome. The predictive power of the ROX index was confirmed in 289 COVID-19 patients after 6 h of HFNC therapy [230].

According to expert opinion, patients on HFNC should be continuously monitored by pulse oximetry and for clinical symptoms, as 36% of pneumonia [230] and 37% of COVID-19 patients [72] treated with HFNC had to be intubated in the further course, which is consistent with intubation rates of around 40%, in the HFNC therapy groups in randomized trials [70, 71, 231].

HFNC systems are not available outside the hospital; reservoir masks and CPAP/NIV therapy are alternative options for the treatment of refractory hypoxemia in out-of-hospital settings.

4.2 Humidification of Supplemental Oxygen

graphic

A meta-analysis based on 25 RCTs with a total of 8,876 acutely ill adult patients compared humidified versus nonhumidified oxygen. Most studies focused on a treatment duration of more than 24 h (range: 12 h to >5 days). All studies described the use of low-flow O2 (<5 L/min). The use of nonhumidified oxygen did not prove to have an impact on patient discomfort. However, bacterial contamination was more common in the group receiving humidified oxygen (OR 6.25; 95% CI 2.33–16.67). The authors of the BTS guideline [63] downgraded the meta-analysis to a moderate level of evidence due to study limitations, limited transferability, and inconsistencies [229]. Oxygen was administered 36 h longer, and the rate of subsequent respiratory infections was increased in these patients (OR 2.56; 95% CI 1.37–4.76).

Our own literature search found another RCT published in 2018. The study [232] on 354 subjects investigated the effect of dry versus humidified oxygen on the quality of life of ICU patients. The study was rated as having a low level of evidence due to limitations and low accuracy. The study was not able to demonstrate that nonhumidified oxygen was inferior to humidified oxygen in terms of patient comfort after 6–8 h of oxygen therapy.

4.3 Monitoring and Documentation of Oxygen Therapy

graphic

Only a few systematic studies are available on the time to equilibration after an adjustment in supplemental O2. In general, the oxygen saturation in blood gas samples equilibrates within a few minutes of increasing oxygen delivery [233, 234]. Only indirect indicators are available with regard to CO2. It takes up to 30–60 min to reach equilibrium. The few clinical data were able to demonstrate at least a change in paCO2 for up to 20 min during and after bronchodilator inhalation in the selected patient population (COPD) [93, 235].

graphic

Our literature search did not find any RCTs, meta-analyses, or systematic reviews suitable for answering the key question. This recommendation is therefore also based on expert opinion. Several small observational studies addressed blood oxygen equilibration times [236-239]. The time to equilibration of O2 saturation was 4.5 min in spontaneously breathing patients [236], 6 min in ventilated patients, and 7 min in ventilated COPD patients [240].

Changes in cardiac output, microcirculation, hypoxemia, vasoconstriction, or vasodilation may increase the time to equilibration of O2 saturation [61, 236, 237, 241].

Practice Point:

Oxygen therapy must be documented in written form (template in Fig. 6).

Fig. 6.

Sample template for the documentation of oxygen therapy. N, nasal prongs; VM, Venturi mask; RM, reservoir mask; A, alertness; C, confusion.

Fig. 6.

Sample template for the documentation of oxygen therapy. N, nasal prongs; VM, Venturi mask; RM, reservoir mask; A, alertness; C, confusion.

Close modal

The documentation needs to indicate the delivery system and the amount of oxygen.

The oxygen dose administered shall be indicated each time oxygen saturation is recorded.

All vital signs shall be recorded and documented at predefined intervals during the oxygen therapy (see recommendation 2.2).

According to decisions of the arbitration committee pursuant to section 19 of the German Hospital Financing Act (Krankenhausfinanzierungsgesetz), respiratory failure, the following procedure codes should be used depending on SpO2, ventilation and presence of hypercapnia: J96.00 if SpO2 is <92% without hypercapnia and if oxygen is delivered, J96.01 if paCO2 is >45 mm Hg, and J96.11 if ventilation is applied. The guideline authors recommend updating the coding of oxygen therapy, and of HFNC in particular, as a procedure in the near future.

4.4 Discontinuation of Oxygen Therapy

graphic

Our literature search did not find randomized trials, meta-analyses, or systematic reviews on this topic. The recommendation is therefore based on expert opinion.

In most acutely ill patients, oxygen therapy is gradually reduced as the patient recovers. Oxygen therapy can be discontinued when a stable patient is able to stay in the target saturation range under low-dose oxygen. Signs of clinical stability include a normal respiration rate and other vital signs within the normal range. Some patients experience transient hypoxemia while recovering from an acute condition, e.g., due to the build-up of secretion. Some have acceptable oxygen saturations at rest during recovery, but experience exercise-induced desaturation. However, this is often not a reason for resuming oxygen therapy.

graphic

For patients who experienced hypercapnic respiratory failure after high-dose oxygen therapy, there is a risk of rebound hypoxemia if oxygen is suddenly withdrawn. Rebound hypoxemia can be explained using the alveolar gas equation [242]. Carbon dioxide competes with oxygen in the alveoli. While the body’s capacity to store oxygen is limited, large amounts of carbon dioxide can be stored due to its high solubility. The discontinuation of oxygen therapy in this subgroup of patients results in a faster drop in the partial pressure of arterial oxygen than arterial carbon dioxide due to high alveolar carbon dioxide, as the ability to increase ventilation is limited in these patients. Rebound hypoxemia can be substantial (saturation drop of up to 16% in a group of 10 COPD patients). The drop is greatest in the first 5 min of stopping the oxygen therapy, but the lowest point is only reached after 30–45 min [243]. Two randomized trials comparing HFNC versus standard oxygen therapy were unable to demonstrate the phenomenon of rebound hypoxemia after extubation [157, 244].

Practice Points:

In patients at risk of hypercapnia or with known hypercapnia, stopping oxygen therapy is only advisable after first reducing the flow rate to 0.5–1 L/min. In all other patients, reduce to 2 L/min before stopping oxygen therapy.

Oxygen therapy can be stopped immediately in patients not at risk of hypercapnia who have an oxygen saturation >96% under 2 L/min of oxygen or less for at least 5 min.

If O2 saturation drops below the desired target range after oxygen therapy has been stopped, the lowest O2 flow rate that kept the patient in the target range is recommended to be resumed.

graphic

Patients may occasionally experience transient hypoxemia after oxygen therapy has been stopped, for example in connection with low-level exercise or due to obstruction by mucus. Transient drops in oxygen saturation are also common in sleep-related breathing disorders [245]. The decisive criterion for initiating oxygen therapy is hypoxemia at rest. In COPD patients on oxygen, isolated exercise-induced hypoxemia was not associated with reduced mortality or increased hospitalization [246].

In a retrospective single-center analysis of 71,025 patients after surgery, Rostin et al. [247] found that desaturation episodes below an SpO2 of 90% (4.6% of patients) of more than 1 min were associated with higher pulmonary complication rates in the first 10 min of extubation (OR 1.68; 100% CI 1.50–1.88) and intensive medical care.

graphic

A small number of patients who had severe respiratory or cardiac conditions may require home oxygen to be safe after being discharged from the hospital. This is particularly common in patients with COPD exacerbation. Cohort studies in these patients showed, however, that 21–33% of oxygen prescriptions no longer met the criteria for long-term oxygen therapy at re-evaluation. In Germany, and also in other countries, oxygen therapy initiated in hospitalized patients there is no universal follow-up after discharge [248-251]. The authors recommend to educate patients with regard to oxygen therapy prior to discharge to improve adherence.

Decisions concerning an indication for long-term oxygen therapy should not be made on the basis of blood gas measurements taken during an acute illness. The Guideline for Long-Term Oxygen Therapy recommends following up on oxygen therapy within 12 weeks of starting oxygen therapy, and also as part of the re-evaluation of stable patients [252].

This is the official translation of the condensed version of the German version of the guideline [43], published in English with permission. The authors thank the members of the guideline development group and the experts for their honorary work. The authors are grateful for the support of Susanne Hoyer, Hannover, Gunda Mundt, Stellenbosch/South Africa (translation), and Christina Valtin, Hannover.

The authors would also like to extend their gratitude to the following experts for providing their advice: Bernd Schönhofer, Hannover; Terence Krauß, Hannover; Björn Jüttner, Hannover; Michael Westhoff, Hemer; Peter Haidl, Schmallenberg; Carsten Hermes, Bonn; Guido Michels, Eschweiler; Jan-Christopher Kamp, Hannover; Christian Witt, Berlin; René Wildenauer, Wiesentheid; Andreas Markewitz, Koblenz; Wolfgang Veit, Marne; Susanne Unverzagt, Leipzig; Marco König, Lübeck.

The following conflicts of interests were revealed by independent review: T.V. reported a research grant by Pall (moderate conflict of interest on the subject of humidification). S.K. reported a moderate conflict of interest on the subject of extracorporeal membrane oxygenation to Xenios/Novalung (advisory, speaker fees and research grant). C.K. reported a moderate conflict of interest on the subject of extracorporeal membrane oxygenation to Maquet (speaker fees and research grant). All other authors have no relevant conflicts of interest to declare.

A detailed declaration of interests for individual authors with independent review can be found under https://www.awmf.org/fileadmin/user_upload/Leitlinien/020_D_Ges_fuer_Pneumologie/020-021i_S3_Sauerstoff-in-der-Akuttherapie-beim-Erwachsenen_2021-06.pdf.

This guideline was funded by the German Respiratory Society (DGP) for literature search and travel costs.

J.G. wrote the application to develop the guideline and designed scope and outline of the guideline. J.G., P.C., U.H., U.J., C.K., S.K., M.N., S.R., T.V., H.W., and T.F. performed additional literature search. J.G., P.C., U.H., U.J., C.K., S.K., M.N., S.R., T.V., H.W., and T.F. phrased recommendations, background texts and graded evidence. J.G., P.C., U.H., U.J., C.K., S.K., M.N., S.R., T.V., H.W., and T.F. participated in the consensus process. J.G., H.W., and T.F. contributed to the draft of the manuscript. All authors critically reviewed and approved the final German version of the guideline.

1.
Blodgett
AN
.
The Continuous Inhalation of Oxygen in Cases of Pneumonia Otherwise Fatal, and in Other Diseases
.
Boston Med Surg J
.
1890
;
123
(
21
):
481
5
. 0096-6762
2.
Breuer
HW
,
Groeben
H
,
Breuer
J
,
Worth
H
.
Oxygen saturation calculation procedures: a critical analysis of six equations for the determination of oxygen saturation
.
Intensive Care Med
.
1989
;
15
(
6
):
385
9
.
[PubMed]
0342-4642
3.
Gøthgen
IH
,
Siggaard-Andersen
O
,
Kokholm
G
.
Variations in the hemoglobin-oxygen dissociation curve in 10079 arterial blood samples
.
Scand J Clin Lab Invest Suppl
.
1990
;
203
sup203
:
87
90
.
[PubMed]
0085-591X
4.
Sorbini
CA
,
Grassi
V
,
Solinas
E
,
Muiesan
G
.
Arterial oxygen tension in relation to age in healthy subjects
.
Respiration
.
1968
;
25
(
1
):
3
13
.
[PubMed]
0025-7931
5.
Mellemgaard
K
.
The alveolar-arterial oxygen difference: its size and components in normal man
.
Acta Physiol Scand
.
1966
May
;
67
(
1
):
10
20
.
[PubMed]
0001-6772
6.
Beasley
R
,
Aldington
S
,
Robinson
G
.
Is it time to change the approach to oxygen therapy in the breathless patient?
Thorax
.
2007
Oct
;
62
(
10
):
840
1
.
[PubMed]
0040-6376
7.
Kelly
AM
,
McAlpine
R
,
Kyle
E
.
How accurate are pulse oximeters in patients with acute exacerbations of chronic obstructive airways disease?
Respir Med
.
2001
May
;
95
(
5
):
336
40
.
[PubMed]
0954-6111
8.
Lee
WW
,
Mayberry
K
,
Crapo
R
,
Jensen
RL
.
The accuracy of pulse oximetry in the emergency department
.
Am J Emerg Med
.
2000
Jul
;
18
(
4
):
427
31
.
[PubMed]
0735-6757
9.
Ebmeier
SJ
,
Barker
M
,
Bacon
M
,
Beasley
RC
,
Bellomo
R
,
Knee Chong
C
, et al
A two centre observational study of simultaneous pulse oximetry and arterial oxygen saturation recordings in intensive care unit patients
.
Anaesth Intensive Care
.
2018
May
;
46
(
3
):
297
303
.
[PubMed]
0310-057X
10.
Considine
J
.
The reliability of clinical indicators of oxygenation: a literature review
.
Contemp Nurse
.
2005
Apr-Jun
;
18
(
3
):
258
67
.
[PubMed]
1037-6178
11.
Helmholz
HF
 Jr
.
The abbreviated alveolar air equation
.
Chest
.
1979
Jun
;
75
(
6
):
748
.
[PubMed]
0012-3692
12.
O’Reilly Nugent
A
,
Kelly
PT
,
Stanton
J
,
Swanney
MP
,
Graham
B
,
Beckert
L
.
Measurement of oxygen concentration delivered via nasal cannulae by tracheal sampling
.
Respirology
.
2014
May
;
19
(
4
):
538
43
.
[PubMed]
1440-1843
13.
Physicians
RC
.
National Early Warning Score (NEWS) 2: Standardising the assesment of acute-illness severity in the NHS. Updates report of a working party
.
London
:
RCP
;
2017
.
14.
Abdo
WF
,
Heunks
LM
.
Oxygen-induced hypercapnia in COPD: myths and facts
.
Crit Care
.
2012
Oct
;
16
(
5
):
323
.
[PubMed]
1466-609X
15.
Gilbert-Kawai
ET
,
Mitchell
K
,
Martin
D
,
Carlisle
J
,
Grocott
MP
.
Permissive hypoxaemia versus normoxaemia for mechanically ventilated critically ill patients
.
Cochrane Database Syst Rev
.
2014
May
;(
5
):CD009931.
[PubMed]
1469-493X
16.
Askie
LM
,
Darlow
BA
,
Finer
N
,
Schmidt
B
,
Stenson
B
,
Tarnow-Mordi
W
, et al;
Neonatal Oxygenation Prospective Meta-analysis (NeOProM) Collaboration
.
Association Between Oxygen Saturation Targeting and Death or Disability in Extremely Preterm Infants in the Neonatal Oxygenation Prospective Meta-analysis Collaboration
.
JAMA
.
2018
Jun
;
319
(
21
):
2190
201
.
[PubMed]
1538-3598
17.
Barrot
L
,
Asfar
P
,
Mauny
F
,
Winiszewski
H
,
Montini
F
,
Badie
J
, et al;
LOCO2 Investigators and REVA Research Network
.
Liberal or Conservative Oxygen Therapy for Acute Respiratory Distress Syndrome
.
N Engl J Med
.
2020
Mar
;
382
(
11
):
999
1008
.
[PubMed]
1533-4406
18.
Bleyer
AJ
,
Vidya
S
,
Russell
GB
,
Jones
CM
,
Sujata
L
,
Daeihagh
P
, et al
Longitudinal analysis of one million vital signs in patients in an academic medical center
.
Resuscitation
.
2011
Nov
;
82
(
11
):
1387
92
.
[PubMed]
1873-1570
19.
Goodacre
S
,
Turner
J
,
Nicholl
J
.
Prediction of mortality among emergency medical admissions
.
Emerg Med J
.
2006
May
;
23
(
5
):
372
5
.
[PubMed]
1472-0213
20.
Hébert
PC
,
Wells
G
,
Blajchman
MA
,
Marshall
J
,
Martin
C
,
Pagliarello
G
, et al
A multicenter, randomized, controlled clinical trial of transfusion requirements in critical care. Transfusion Requirements in Critical Care Investigators, Canadian Critical Care Trials Group
.
N Engl J Med
.
1999
Feb
;
340
(
6
):
409
17
.
[PubMed]
0028-4793
21.
Ackland
GL
,
Iqbal
S
,
Paredes
LG
,
Toner
A
,
Lyness
C
,
Jenkins
N
, et al;
POM-O (PostOperative Morbidity-Oxygen delivery) study group
.
Individualised oxygen delivery targeted haemodynamic therapy in high-risk surgical patients: a multicentre, randomised, double-blind, controlled, mechanistic trial
.
Lancet Respir Med
.
2015
Jan
;
3
(
1
):
33
41
.
[PubMed]
2213-2619
22.
Lobo
SM
,
Salgado
PF
,
Castillo
VG
,
Borim
AA
,
Polachini
CA
,
Palchetti
JC
, et al
Effects of maximizing oxygen delivery on morbidity and mortality in high-risk surgical patients
.
Crit Care Med
.
2000
Oct
;
28
(
10
):
3396
404
.
[PubMed]
0090-3493
23.
Heyland
DK
,
Cook
DJ
,
King
D
,
Kernerman
P
,
Brun-Buisson
C
.
Maximizing oxygen delivery in critically ill patients: a methodologic appraisal of the evidence
.
Crit Care Med
.
1996
Mar
;
24
(
3
):
517
24
.
[PubMed]
0090-3493
24.
Meschia
G
.
Fetal oxygenation and maternal ventilation
.
Clin Chest Med
.
2011
Mar
;
32
(
1
):
15
9
.
[PubMed]
1557-8216
25.
Wyss-Dunant
E
.
[Acclimatization shock; studies in the Himalaya mountains]
.
Minerva Med
.
1955
Mar
;
46
(
21
):
675
85
.
[PubMed]
0026-4806
26.
van der Post
J
,
Noordzij
LA
,
de Kam
ML
,
Blauw
GJ
,
Cohen
AF
,
van Gerven
JM
.
Evaluation of tests of central nervous system performance after hypoxemia for a model for cognitive impairment
.
J Psychopharmacol
.
2002
Dec
;
16
(
4
):
337
43
.
[PubMed]
0269-8811
27.
Harboe
M
.
Lactic acid content in human venous blood during hypoxia at high altitude
.
Acta Physiol Scand
.
1957
Oct
;
40
(
2-3
):
248
53
.
[PubMed]
0001-6772
28.
Grubbström
J
,
Berglund
B
,
Kaijser
L
.
Myocardial oxygen supply and lactate metabolism during marked arterial hypoxaemia
.
Acta Physiol Scand
.
1993
Nov
;
149
(
3
):
303
10
.
[PubMed]
0001-6772
29.
Neill
WA
.
Effects of arterial hypoxemia and hyperoxia on oxygen availability for myocardial metabolism. Patients with and without coronary heart disease
.
Am J Cardiol
.
1969
Aug
;
24
(
2
):
166
71
.
[PubMed]
0002-9149
30.
Smith
GB
,
Prytherch
DR
,
Watson
D
,
Forde
V
,
Windsor
A
,
Schmidt
PE
, et al
S(p)O(2) values in acute medical admissions breathing air—implications for the British Thoracic Society guideline for emergency oxygen use in adult patients?
Resuscitation
.
2012
Oct
;
83
(
10
):
1201
5
.
[PubMed]
1873-1570
31.
Chu
DK
,
Kim
LH
,
Young
PJ
,
Zamiri
N
,
Almenawer
SA
,
Jaeschke
R
, et al
Mortality and morbidity in acutely ill adults treated with liberal versus conservative oxygen therapy (IOTA): a systematic review and meta-analysis
.
Lancet
.
2018
Apr
;
391
(
10131
):
1693
705
.
[PubMed]
1474-547X
32.
Siemieniuk
RA
,
Chu
DK
,
Kim
LH
,
Güell-Rous
MR
,
Alhazzani
W
,
Soccal
PM
, et al
Oxygen therapy for acutely ill medical patients: a clinical practice guideline
.
BMJ
.
2018
Oct
;
363
:
k4169
.
[PubMed]
1756-1833
33.
Hafner
S
,
Beloncle
F
,
Koch
A
,
Radermacher
P
,
Asfar
P
.
Hyperoxia in intensive care, emergency, and peri-operative medicine: Dr. Jekyll or Mr. Hyde? A 2015 update
.
Ann Intensive Care
.
2015
Dec
;
5
(
1
):
42
.
[PubMed]
2110-5820
34.
Barbateskovic
M
,
Schjørring
OL
,
Russo Krauss
S
,
Jakobsen
JC
,
Meyhoff
CS
,
Dahl
RM
, et al
Higher versus lower fraction of inspired oxygen or targets of arterial oxygenation for adults admitted to the intensive care unit
.
Cochrane Database Syst Rev
.
2019
Nov
;
2019
(
11
).
[PubMed]
1469-493X
35.
Edmark
L
,
Kostova-Aherdan
K
,
Enlund
M
,
Hedenstierna
G
.
Optimal oxygen concentration during induction of general anesthesia
.
Anesthesiology
.
2003
Jan
;
98
(
1
):
28
33
.
[PubMed]
0003-3022
36.
Sackner
MA
,
Landa
J
,
Hirsch
J
,
Zapata
A
.
Pulmonary effects of oxygen breathing. A 6-hour study in normal men
.
Ann Intern Med
.
1975
Jan
;
82
(
1
):
40
3
.
[PubMed]
0003-4819
37.
Magder
S
.
Reactive oxygen species: toxic molecules or spark of life?
Crit Care
.
2006
Feb
;
10
(
1
):
208
.
[PubMed]
1466-609X
38.
Downs
JB
,
Smith
RA
.
Increased inspired oxygen concentration may delay diagnosis and treatment of significant deterioration in pulmonary function
.
Crit Care Med
.
1999
Dec
;
27
(
12
):
2844
6
.
[PubMed]
0090-3493
39.
Austin
MA
,
Wills
KE
,
Blizzard
L
,
Walters
EH
,
Wood-Baker
R
.
Effect of high flow oxygen on mortality in chronic obstructive pulmonary disease patients in prehospital setting: randomised controlled trial
.
BMJ
.
2010
Oct
;
341
oct18 2
:
c5462
.
[PubMed]
1756-1833
40.
Farquhar
H
,
Weatherall
M
,
Wijesinghe
M
,
Perrin
K
,
Ranchord
A
,
Simmonds
M
, et al
Systematic review of studies of the effect of hyperoxia on coronary blood flow
.
Am Heart J
.
2009
Sep
;
158
(
3
):
371
7
.
[PubMed]
1097-6744
41.
Sepehrvand
N
,
James
SK
,
Stub
D
,
Khoshnood
A
,
Ezekowitz
JA
,
Hofmann
R
.
Effects of supplemental oxygen therapy in patients with suspected acute myocardial infarction: a meta-analysis of randomised clinical trials
.
Heart
.
2018
Oct
;
104
(
20
):
1691
8
.
[PubMed]
1468-201X
42.
Wetterslev
J
,
Meyhoff
CS
,
Jørgensen
LN
,
Gluud
C
,
Lindschou
J
,
Rasmussen
LS
.
The effects of high perioperative inspiratory oxygen fraction for adult surgical patients
.
Cochrane Database Syst Rev
.
2015
Jun
;(
6
):CD008884.
[PubMed]
1469-493X
43.
J., G., et al. German S3 Guideline - Oxygen Therapy in the Acute Care of Adult Patients (German Version).
2021
[cited 2021 26.8.2021]; Available from: https://www.awmf.org/uploads/tx_szleitlinien/020-021l_S3_Sauerstoff-in-der-Akuttherapie-beim-Erwachsenen_2021-06.pdf
44.
Uronis
HE
,
Currow
DC
,
McCrory
DC
,
Samsa
GP
,
Abernethy
AP
.
Oxygen for relief of dyspnoea in mildly- or non-hypoxaemic patients with cancer: a systematic review and meta-analysis
.
Br J Cancer
.
2008
Jan
;
98
(
2
):
294
9
.
[PubMed]
0007-0920
45.
Uronis
H
,
McCrory
DC
,
Samsa
G
,
Currow
D
,
Abernethy
A
.
Symptomatic oxygen for non-hypoxaemic chronic obstructive pulmonary disease
.
Cochrane Database Syst Rev
.
2011
Jun
;(
6
):CD006429.
[PubMed]
1469-493X
46.
Cranston
JM
,
Crockett
A
,
Currow
D
.
Oxygen therapy for dyspnoea in adults
.
Cochrane Database Syst Rev
.
2008
Jul
;(
3
):CD004769.
[PubMed]
1469-493X
47.
Lemyze
M
,
Guiot
A
,
Mallat
J
,
Thevenin
D
.
The obesity supine death syndrome (OSDS)
.
Obes Rev
.
2018
Apr
;
19
(
4
):
550
6
.
[PubMed]
1467-789X
48.
Ahrens
T
.
Changing perspectives in the assessment of oxygenation
.
Crit Care Nurse
.
1993
Aug
;
13
(
4
):
78
83
.
[PubMed]
0279-5442
49.
Thrush
DN
,
Downs
JB
,
Hodges
M
,
Smith
RA
.
Does significant arterial hypoxemia alter vital signs?
J Clin Anesth
.
1997
Aug
;
9
(
5
):
355
7
.
[PubMed]
0952-8180
50.
Bota
GW
,
Rowe
BH
.
Continuous monitoring of oxygen saturation in prehospital patients with severe illness: the problem of unrecognized hypoxemia
.
J Emerg Med
.
1995
May-Jun
;
13
(
3
):
305
11
.
[PubMed]
0736-4679
51.
Brown
LH
,
Manring
EA
,
Kornegay
HB
,
Prasad
NH
.
Can prehospital personnel detect hypoxemia without the aid of pulse oximeters?
Am J Emerg Med
.
1996
Jan
;
14
(
1
):
43
4
.
[PubMed]
0735-6757
52.
Lambert
MA
,
Crinnion
J
.
The role of pulse oximetry in the accident and emergency department
.
Arch Emerg Med
.
1989
Sep
;
6
(
3
):
211
5
.
[PubMed]
0264-4924
53.
Pruitt
WC
,
Jacobs
M
.
Breathing lessons: basics of oxygen therapy
.
Nursing
.
2003
Oct
;
33
(
10
):
43
5
.
[PubMed]
0360-4039
54.
Ryerson
GB
.
ER, Safe use of oxygen therapy: a physiologic approach part 2
.
Respir Ther
.
1983
;
13
(
2
):
25
30
.0048-7392
55.
I, W., Respiratory rate 3: how to take an accurate measurement
.
Nurs Times
.
2018
;
114
(
7
):
21
2
.0954-7762
56.
Pedersen
T
,
Nicholson
A
,
Hovhannisyan
K
,
Møller
AM
,
Smith
AF
,
Lewis
SR
.
Pulse oximetry for perioperative monitoring
.
Cochrane Database Syst Rev
.
2014
Mar
;(
3
):CD002013.
[PubMed]
1469-493X
57.
King
T
,
Simon
RH
.
Pulse oximetry for tapering supplemental oxygen in hospitalized patients. Evaluation of a protocol
.
Chest
.
1987
Oct
;
92
(
4
):
713
6
.
[PubMed]
0012-3692
58.
Kellerman
AL
,
Cofer
CA
,
Joseph
S
,
Hackman
BB
.
Impact of portable pulse oximetry on arterial blood gas test ordering in an urban emergency department
.
Ann Emerg Med
.
1991
Feb
;
20
(
2
):
130
4
.
[PubMed]
0196-0644
59.
Jubran
A
.
Pulse oximetry
.
Crit Care
.
2015
Jul
;
19
(
1
):
272
.
[PubMed]
1466-609X
60.
Nitzan
M
,
Romem
A
,
Koppel
R
.
Pulse oximetry: fundamentals and technology update
.
Med Devices (Auckl)
.
2014
Jul
;
7
:
231
9
.
[PubMed]
1179-1470
61.
Severinghaus
JW
,
Naifeh
KH
.
Accuracy of response of six pulse oximeters to profound hypoxia
.
Anesthesiology
.
1987
Oct
;
67
(
4
):
551
8
.
[PubMed]
0003-3022
62.
Perkins
GD
,
McAuley
DF
,
Giles
S
,
Routledge
H
,
Gao
F
.
Do changes in pulse oximeter oxygen saturation predict equivalent changes in arterial oxygen saturation?
Crit Care
.
2003
Aug
;
7
(
4
):
R67
.
[PubMed]
1364-8535
63.
O’Driscoll
BR
,
Howard
LS
,
Earis
J
,
Mak
V
;
British Thoracic Society Emergency Oxygen Guideline Group
;
BTS Emergency Oxygen Guideline Development Group
.
BTS guideline for oxygen use in adults in healthcare and emergency settings
.
Thorax
.
2017
Jun
;
72
Suppl 1
:
ii1
90
.
[PubMed]
1468-3296
64.
Milner
QJ
,
Mathews
GR
.
An assessment of the accuracy of pulse oximeters
.
Anaesthesia
.
2012
Apr
;
67
(
4
):
396
401
.
[PubMed]
1365-2044
65.
Sjoding
MW
,
Dickson
RP
,
Iwashyna
TJ
,
Gay
SE
,
Valley
TS
.
Racial Bias in Pulse Oximetry Measurement
.
N Engl J Med
.
2020
Dec
;
383
(
25
):
2477
8
.
[PubMed]
1533-4406
66.
Ortiz
FO
,
Aldrich
TK
,
Nagel
RL
,
Benjamin
LJ
.
Accuracy of pulse oximetry in sickle cell disease
.
Am J Respir Crit Care Med
.
1999
Feb
;
159
(
2
):
447
51
.
[PubMed]
1073-449X
67.
Conway
A
,
Tipton
E
,
Liu
WH
,
Conway
Z
,
Soalheira
K
,
Sutherland
J
, et al
Accuracy and precision of transcutaneous carbon dioxide monitoring: a systematic review and meta-analysis
.
Thorax
.
2019
Feb
;
74
(
2
):
157
63
.
[PubMed]
1468-3296
68.
Raffin
TA
.
Indications for arterial blood gas analysis
.
Ann Intern Med
.
1986
Sep
;
105
(
3
):
390
8
.
[PubMed]
0003-4819
69.
Fichtner
F
,
Moerer
O
,
Laudi
S
,
Weber-Carstens
S
,
Nothacker
M
,
Kaisers
U
;
Investigators and the Guideline Group on Mechanical Ventilation and Extracorporeal Membrane Oxygena tion in Acute Respiratory Insufficiency
.
Mechanical Ventilation and Extracorporeal Membrane Oxygena tion in Acute Respiratory Insufficiency
.
Dtsch Arztebl Int
.
2018
Dec
;
115
(
50
):
840
7
.
[PubMed]
1866-0452
70.
Frat
JP
,
Thille
AW
,
Mercat
A
,
Girault
C
,
Ragot
S
,
Perbet
S
, et al;
FLORALI Study Group
;
REVA Network
.
High-flow oxygen through nasal cannula in acute hypoxemic respiratory failure
.
N Engl J Med
.
2015
Jun
;
372
(
23
):
2185
96
.
[PubMed]
1533-4406
71.
Lemiale
V
,
Mokart
D
,
Mayaux
J
,
Lambert
J
,
Rabbat
A
,
Demoule
A
, et al
The effects of a 2-h trial of high-flow oxygen by nasal cannula versus Venturi mask in immunocompromised patients with hypoxemic acute respiratory failure: a multicenter randomized trial
.
Crit Care
.
2015
Nov
;
19
(
1
):
380
.
[PubMed]
1466-609X
72.
Roca
O
,
Caralt
B
,
Messika
J
,
Samper
M
,
Sztrymf
B
,
Hernández
G
, et al
An Index Combining Respiratory Rate and Oxygenation to Predict Outcome of Nasal High-Flow Therapy
.
Am J Respir Crit Care Med
.
2019
Jun
;
199
(
11
):
1368
76
.
[PubMed]
1535-4970
73.
Zavorsky
GS
,
Cao
J
,
Mayo
NE
,
Gabbay
R
,
Murias
JM
.
Arterial versus capillary blood gases: a meta-analysis
.
Respir Physiol Neurobiol
.
2007
Mar
;
155
(
3
):
268
79
.
[PubMed]
1569-9048
74.
Magnet
FS
,
Majorski
DS
,
Callegari
J
,
Schwarz
SB
,
Schmoor
C
,
Windisch
W
, et al
Capillary PO2 does not adequately reflect arterial PO2 in hypoxemic COPD patients
.
Int J Chron Obstruct Pulmon Dis
.
2017
Sep
;
12
:
2647
53
.
[PubMed]
1178-2005
75.
Ekkernkamp
E
,
Welte
L
,
Schmoor
C
,
Huttmann
SE
,
Dreher
M
,
Windisch
W
, et al
Spot check analysis of gas exchange: invasive versus noninvasive methods
.
Respiration
.
2015
;
89
(
4
):
294
303
.
[PubMed]
1423-0356
76.
Richtlinien zur Organtransplantation gem. § 16 TPG. 2017 13.9.
2020
]; Available from: https://www.bundesaerztekammer.de/fileadmin/user_upload/downloads/pdf-Ordner/RL/RiliOrgaWlOvLungeTx-ab20171107.pdf
77.
Lim
BL
,
Kelly
AM
.
A meta-analysis on the utility of peripheral venous blood gas analyses in exacerbations of chronic obstructive pulmonary disease in the emergency department
.
Eur J Emerg Med
.
2010
Oct
;
17
(
5
):
246
8
.
[PubMed]
1473-5695
78.
Byrne
AL
,
Bennett
M
,
Chatterji
R
,
Symons
R
,
Pace
NL
,
Thomas
PS
.
Peripheral venous and arterial blood gas analysis in adults: are they comparable? A systematic review and meta-analysis
.
Respirology
.
2014
Feb
;
19
(
2
):
168
75
.
[PubMed]
1440-1843
79.
Bingheng
L
,
Jianxin
C
,
Yu
C
,
Yijuan
Y
.
J.C., Yu C, Yijuan Y, Comparison of peripheral venous and arterial blood gas in patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD): a metaanalysis
.
Notf Rettmed
.
2019
;
22
(
7
):
620
7
. 1434-6222
80.
Bloom
BM
,
Grundlingh
J
,
Bestwick
JP
,
Harris
T
.
The role of venous blood gas in the emergency department: a systematic review and meta-analysis
.
Eur J Emerg Med
.
2014
Apr
;
21
(
2
):
81
8
.
[PubMed]
1473-5695
81.
Kelly
AM
,
Kyle
E
,
McAlpine
R
.
Venous pCO(2) and pH can be used to screen for significant hypercarbia in emergency patients with acute respiratory disease
.
J Emerg Med
.
2002
Jan
;
22
(
1
):
15
9
.
[PubMed]
0736-4679
82.
Kelly
AM
,
Kerr
D
,
Middleton
P
.
Validation of venous pCO2 to screen for arterial hypercarbia in patients with chronic obstructive airways disease
.
J Emerg Med
.
2005
May
;
28
(
4
):
377
9
.
[PubMed]
0736-4679
83.
Ak
A
,
Ogun
CO
,
Bayir
A
,
Kayis
SA
,
Koylu
R
.
Prediction of arterial blood gas values from venous blood gas values in patients with acute exacerbation of chronic obstructive pulmonary disease
.
Tohoku J Exp Med
.
2006
Dec
;
210
(
4
):
285
90
.
[PubMed]
0040-8727
84.
Ibrahim
I
,
Ooi
SB
,
Yiong Huak
C
,
Sethi
S
.
Point-of-care bedside gas analyzer: limited use of venous pCO2 in emergency patients
.
J Emerg Med
.
2011
Aug
;
41
(
2
):
117
23
.
[PubMed]
0736-4679
85.
Harper
J
,
Kearns
N
,
Bird
G
,
McLachlan
R
,
Eathorne
A
,
Weatherall
M
, et al
Audit of oxygen administration to achieve a target oxygen saturation range in acutely unwell medical patients
.
Postgrad Med J
.
2021
Feb
;
postgradmedj-2020-139511
.
[PubMed]
1469-0756
86.
O’Driscoll
,
B.R.
British Thoracic Society Emergency Oxygen Audit Report.
2015
[cited 2021 11.3.2021]; Emergency Oxygen Audit Report].
87.
Ayhan
H
,
Iyigun
E
,
Tastan
S
,
Orhan
ME
,
Ozturk
E
.
Comparison of two different oxygen delivery methods in the early postoperative period: randomized trial
.
J Adv Nurs
.
2009
Jun
;
65
(
6
):
1237
47
.
[PubMed]
1365-2648
88.
Eastwood
GM
,
O’Connell
B
,
Gardner
A
,
Considine
J
.
Evaluation of nasopharyngeal oxygen, nasal prongs and facemask oxygen therapy devices in adult patients: a randomised crossover trial
.
Anaesth Intensive Care
.
2008
Sep
;
36
(
5
):
691
4
.
[PubMed]
0310-057X
89.
Wettstein
RB
,
Shelledy
DC
,
Peters
JI
.
Delivered oxygen concentrations using low-flow and high-flow nasal cannulas
.
Respir Care
.
2005
May
;
50
(
5
):
604
9
.
[PubMed]
0020-1324
90.
Physicians
RC
.
Standardising the assessment of acute-illness severity in the NHS NEWS Score
.
London
:
RCP
;
2012
.
91.
Churpek
MM
,
Yuen
TC
,
Edelson
DP
.
Predicting clinical deterioration in the hospital: the impact of outcome selection
.
Resuscitation
.
2013
May
;
84
(
5
):
564
8
.
[PubMed]
1873-1570
92.
Friesen
RM
,
Raber
MB
,
Reimer
DH
.
Oxygen concentrators: a primary oxygen supply source
.
Can J Anaesth
.
1999
Dec
;
46
(
12
):
1185
90
.
[PubMed]
0832-610X
93.
Gunawardena
KA
,
Patel
B
,
Campbell
IA
,
MacDonald
JB
,
Smith
AP
.
Oxygen as a driving gas for nebulisers: safe or dangerous?
Br Med J (Clin Res Ed)
.
1984
Jan
;
288
(
6413
):
272
4
.
[PubMed]
0267-0623
94.
Bardsley
G
,
Pilcher
J
,
McKinstry
S
,
Shirtcliffe
P
,
Berry
J
,
Fingleton
J
, et al
Oxygen versus air-driven nebulisers for exacerbations of chronic obstructive pulmonary disease: a randomised controlled trial
.
BMC Pulm Med
.
2018
Oct
;
18
(
1
):
157
.
[PubMed]
1471-2466
95.
Edwards
L
,
Perrin
K
,
Williams
M
,
Weatherall
M
,
Beasley
R
.
Randomised controlled crossover trial of the effect on PtCO2 of oxygen-driven versus air-driven nebulisers in severe chronic obstructive pulmonary disease
.
Emerg Med J
.
2012
Nov
;
29
(
11
):
894
8
.
[PubMed]
1472-0213
96.
Costello
RW
,
Liston
R
,
McNicholas
WT
.
Compliance at night with low flow oxygen therapy: a comparison of nasal cannulae and Venturi face masks
.
Thorax
.
1995
Apr
;
50
(
4
):
405
6
.
[PubMed]
0040-6376
97.
Nolan
KM
,
Winyard
JA
,
Goldhill
DR
.
Comparison of nasal cannulae with face mask for oxygen administration to postoperative patients
.
Br J Anaesth
.
1993
Apr
;
70
(
4
):
440
2
.
[PubMed]
0007-0912
98.
Stausholm
K
,
Rosenberg-Adamsen
S
,
Skriver
M
,
Kehlet
H
,
Rosenberg
J
.
Comparison of three devices for oxygen administration in the late postoperative period
.
Br J Anaesth
.
1995
May
;
74
(
5
):
607
9
.
[PubMed]
0007-0912
99.
Jones
HA
,
Turner
SL
,
Hughes
JM
.
Performance of the large-reservoir oxygen mask (Ventimask)
.
Lancet
.
1984
Jun
;
1
(
8392
):
1427
31
.
[PubMed]
0140-6736
100.
Waldau
T
,
Larsen
VH
,
Bonde
J
.
Evaluation of five oxygen delivery devices in spontaneously breathing subjects by oxygraphy
.
Anaesthesia
.
1998
Mar
;
53
(
3
):
256
63
.
[PubMed]
0003-2409
101.
Maggiore
SM
,
Idone
FA
,
Vaschetto
R
,
Festa
R
,
Cataldo
A
,
Antonicelli
F
, et al
Nasal high-flow versus Venturi mask oxygen therapy after extubation. Effects on oxygenation, comfort, and clinical outcome
.
Am J Respir Crit Care Med
.
2014
Aug
;
190
(
3
):
282
8
.
[PubMed]
1535-4970
102.
Brainard
A
,
Chuang
D
,
Zeng
I
,
Larkin
GL
.
A randomized trial on subject tolerance and the adverse effects associated with higher- versus lower-flow oxygen through a standard nasal cannula
.
Ann Emerg Med
.
2015
Apr
;
65
(
4
):
356
61
.
[PubMed]
1097-6760
103.
Bazuaye
EA
,
Stone
TN
,
Corris
PA
,
Gibson
GJ
.
Variability of inspired oxygen concentration with nasal cannulas
.
Thorax
.
1992
Aug
;
47
(
8
):
609
11
.
[PubMed]
0040-6376
104.
Hofmann
R
,
James
SK
,
Jernberg
T
,
Lindahl
B
,
Erlinge
D
,
Witt
N
, et al;
DETO2X–SWEDEHEART Investigators
.
Oxygen Therapy in Suspected Acute Myocardial Infarction
.
N Engl J Med
.
2017
Sep
;
377
(
13
):
1240
9
.
[PubMed]
1533-4406
105.
Investigators, I.-R., et al., Conservative Oxygen Therapy during Mechanical Ventilation in the ICU. N Engl J Med,
2020
. 382(11): p. 989-998.
106.
Roffe
C
,
Nevatte
T
,
Sim
J
,
Bishop
J
,
Ives
N
,
Ferdinand
P
, et al;
Stroke Oxygen Study Investigators and the Stroke OxygenStudy Collaborative Group
.
Effect of Routine Low-Dose Oxygen Supplementation on Death and Disability in Adults With Acute Stroke: The Stroke Oxygen Study Randomized Clinical Trial
.
JAMA
.
2017
Sep
;
318
(
12
):
1125
35
.
[PubMed]
1538-3598
107.
Ranchord
AM
,
Argyle
R
,
Beynon
R
,
Perrin
K
,
Sharma
V
,
Weatherall
M
, et al
High-concentration versus titrated oxygen therapy in ST-elevation myocardial infarction: a pilot randomized controlled trial
.
Am Heart J
.
2012
Feb
;
163
(
2
):
168
75
.
[PubMed]
1097-6744
108.
Meyhoff
CS
,
Jorgensen
LN
,
Wetterslev
J
,
Christensen
KB
,
Rasmussen
LS
;
PROXI Trial Group
.
Increased long-term mortality after a high perioperative inspiratory oxygen fraction during abdominal surgery: follow-up of a randomized clinical trial
.
Anesth Analg
.
2012
Oct
;
115
(
4
):
849
54
.
[PubMed]
1526-7598
109.
Kopsaftis
Z
,
Carson-Chahhoud
KV
,
Austin
MA
,
Wood-Baker
R
.
Oxygen therapy in the pre-hospital setting for acute exacerbations of chronic obstructive pulmonary disease
.
Cochrane Database Syst Rev
.
2020
Jan
;
1
(
1
):CD005534.
[PubMed]
1469-493X
110.
Vonderbank
S
,
Gibis
N
,
Schulz
A
,
Boyko
M
,
Erbuth
A
,
Gürleyen
H
, et al
Hypercapnia at Hospital Admission as a Predictor of Mortality
.
Open Access Emerg Med
.
2020
Jun
;
12
:
173
80
.
[PubMed]
1179-1500
111.
Pehrsson
K
,
Bake
B
,
Larsson
S
,
Nachemson
A
.
Lung function in adult idiopathic scoliosis: a 20 year follow up
.
Thorax
.
1991
Jul
;
46
(
7
):
474
8
.
[PubMed]
0040-6376
112.
Dreher
M
,
Neuzeret
PC
,
Windisch
W
,
Martens
D
,
Hoheisel
G
,
Gröschel
A
, et al
Prevalence Of Chronic Hypercapnia In Severe Chronic Obstructive Pulmonary Disease: Data From The HOmeVent Registry
.
Int J Chron Obstruct Pulmon Dis
.
2019
Oct
;
14
:
2377
84
.
[PubMed]
1178-2005
113.
Resta
O
,
Foschino-Barbaro
MP
,
Bonfitto
P
,
Talamo
S
,
Legari
G
,
De Pergola
G
, et al
Prevalence and mechanisms of diurnal hypercapnia in a sample of morbidly obese subjects with obstructive sleep apnoea
.
Respir Med
.
2000
Mar
;
94
(
3
):
240
6
.
[PubMed]
0954-6111
114.
Roberts
CM
,
Stone
RA
,
Buckingham
RJ
,
Pursey
NA
,
Lowe
D
;
National Chronic Obstructive Pulmonary Disease Resources and Outcomes Project implementation group
.
Acidosis, non-invasive ventilation and mortality in hospitalised COPD exacerbations
.
Thorax
.
2011
Jan
;
66
(
1
):
43
8
.
[PubMed]
1468-3296
115.
Mountain
RD
,
Sahn
SA
.
Clinical features and outcome in patients with acute asthma presenting with hypercapnia
.
Am Rev Respir Dis
.
1988
Sep
;
138
(
3
):
535
9
.
[PubMed]
0003-0805
116.
Ogna
A
,
Quera Salva
MA
,
Prigent
H
,
Mroue
G
,
Vaugier
I
,
Annane
D
, et al
Nocturnal hypoventilation in neuromuscular disease: prevalence according to different definitions issued from the literature
.
Sleep Breath
.
2016
May
;
20
(
2
):
575
81
.
[PubMed]
1522-1709
117.
Waterhouse
DF
,
McLaughlin
AM
,
Gallagher
CG
.
Time course and recovery of arterial blood gases during exacerbations in adults with Cystic Fibrosis
.
J Cyst Fibros
.
2009
Jan
;
8
(
1
):
9
13
.
[PubMed]
1569-1993
118.
Wijesinghe
M
,
Williams
M
,
Perrin
K
,
Weatherall
M
,
Beasley
R
.
The effect of supplemental oxygen on hypercapnia in subjects with obesity-associated hypoventilation: a randomized, crossover, clinical study
.
Chest
.
2011
May
;
139
(
5
):
1018
24
.
[PubMed]
1931-3543
119.
Wijesinghe
M
,
Perrin
K
,
Healy
B
,
Weatherall
M
,
Beasley
R
.
Randomized controlled trial of high concentration oxygen in suspected community-acquired pneumonia
.
J R Soc Med
.
2012
May
;
105
(
5
):
208
16
.
[PubMed]
1758-1095
120.
Perrin
K
,
Wijesinghe
M
,
Healy
B
,
Wadsworth
K
,
Bowditch
R
,
Bibby
S
, et al
Randomised controlled trial of high concentration versus titrated oxygen therapy in severe exacerbations of asthma
.
Thorax
.
2011
Nov
;
66
(
11
):
937
41
.
[PubMed]
1468-3296
121.
Pilcher
J
,
Richards
M
,
Eastlake
L
,
McKinstry
SJ
,
Bardsley
G
,
Jefferies
S
, et al
High flow or titrated oxygen for obese medical inpatients: a randomised crossover trial
.
Med J Aust
.
2017
Nov
;
207
(
10
):
430
4
.
[PubMed]
1326-5377
122.
Echevarria
C
,
Steer
J
,
Wason
J
,
Bourke
S
.
Oxygen therapy and inpatient mortality in COPD exacerbation
.
Emerg Med J
.
2021
Mar
;
38
(
3
):
170
7
.
[PubMed]
1472-0213
123.
Girardis
M
,
Busani
S
,
Damiani
E
,
Donati
A
,
Rinaldi
L
,
Marudi
A
, et al
Effect of Conservative vs Conventional Oxygen Therapy on Mortality Among Patients in an Intensive Care Unit: The Oxygen-ICU Randomized Clinical Trial
.
JAMA
.
2016
Oct
;
316
(
15
):
1583
9
.
[PubMed]
1538-3598
124.
Panwar
R
,
Hardie
M
,
Bellomo
R
,
Barrot
L
,
Eastwood
GM
,
Young
PJ
, et al;
CLOSE Study Investigators
;
ANZICS Clinical Trials Group
.
Conservative versus Liberal Oxygenation Targets for Mechanically Ventilated Patients. A Pilot Multicenter Randomized Controlled Trial
.
Am J Respir Crit Care Med
.
2016
Jan
;
193
(
1
):
43
51
.
[PubMed]
1535-4970
125.
Asfar
P
,
Schortgen
F
,
Boisramé-Helms
J
,
Charpentier
J
,
Guérot
E
,
Megarbane
B
, et al;
HYPER2S Investigators
;
REVA research network
.
Hyperoxia and hypertonic saline in patients with septic shock (HYPERS2S): a two-by-two factorial, multicentre, randomised, clinical trial
.
Lancet Respir Med
.
2017
Mar
;
5
(
3
):
180
90
.
[PubMed]
2213-2619
126.
de Jonge
E
,
Peelen
L
,
Keijzers
PJ
,
Joore
H
,
de Lange
D
,
van der Voort
PH
, et al
Association between administered oxygen, arterial partial oxygen pressure and mortality in mechanically ventilated intensive care unit patients
.
Crit Care
.
2008
;
12
(
6
):
R156
.
[PubMed]
1466-609X
127.
Palmer
E
,
Post
B
,
Klapaukh
R
,
Marra
G
,
MacCallum
NS
,
Brealey
D
, et al
The Association between Supraphysiologic Arterial Oxygen Levels and Mortality in Critically Ill Patients. A Multicenter Observational Cohort Study
.
Am J Respir Crit Care Med
.
2019
Dec
;
200
(
11
):
1373
80
.
[PubMed]
1535-4970
128.
Eastwood
G
,
Bellomo
R
,
Bailey
M
,
Taori
G
,
Pilcher
D
,
Young
P
, et al
Arterial oxygen tension and mortality in mechanically ventilated patients
.
Intensive Care Med
.
2012
Jan
;
38
(
1
):
91
8
.
[PubMed]
1432-1238
129.
Cumpstey
AF
,
Oldman
AH
,
Smith
AF
,
Martin
D
,
Grocott
MP
.
Oxygen targets in the intensive care unit during mechanical ventilation for acute respiratory distress syndrome: a rapid review
.
Cochrane Database Syst Rev
.
2020
Sep
;
9
:CD013708.
[PubMed]
1469-493X
130.
Hirase
T
,
Ruff
ES
,
Ratnani
I
,
Surani
SR
.
Impact of Conservative Versus Conventional Oxygenation on Outcomes of Patients in Intensive Care Units: A Systematic Review and Meta-analysis
.
Cureus
.
2019
Sep
;
11
(
9
):
e5662
.
[PubMed]
2168-8184
131.
Schjørring
OL
,
Klitgaard
TL
,
Perner
A
,
Wetterslev
J
,
Lange
T
,
Siegemund
M
, et al;
HOT-ICU Investigators
.
Lower or Higher Oxygenation Targets for Acute Hypoxemic Respiratory Failure
.
N Engl J Med
.
2021
Apr
;
384
(
14
):
1301
11
.
[PubMed]
1533-4406
132.
Crane
SD
,
Elliott
MW
,
Gilligan
P
,
Richards
K
,
Gray
AJ
.
Randomised controlled comparison of continuous positive airways pressure, bilevel non-invasive ventilation, and standard treatment in emergency department patients with acute cardiogenic pulmonary oedema
.
Emerg Med J
.
2004
Mar
;
21
(
2
):
155
61
.
[PubMed]
1472-0213
133.
Gray
A
,
Goodacre
S
,
Newby
DE
,
Masson
M
,
Sampson
F
,
Nicholl
J
;
3CPO Trialists
.
Noninvasive ventilation in acute cardiogenic pulmonary edema
.
N Engl J Med
.
2008
Jul
;
359
(
2
):
142
51
.
[PubMed]
1533-4406
134.
Nava
S
,
Carbone
G
,
DiBattista
N
,
Bellone
A
,
Baiardi
P
,
Cosentini
R
, et al
Noninvasive ventilation in cardiogenic pulmonary edema: a multicenter randomized trial
.
Am J Respir Crit Care Med
.
2003
Dec
;
168
(
12
):
1432
7
.
[PubMed]
1073-449X
135.
Lellouche
F
,
L’Her
E
,
Bouchard
PA
,
Brouillard
C
,
Maltais
F
.
Automatic Oxygen Titration During Walking in Subjects With COPD: A Randomized Crossover Controlled Study
.
Respir Care
.
2016
Nov
;
61
(
11
):
1456
64
.
[PubMed]
1943-3654
136.
L’Her
E
,
Dias
P
,
Gouillou
M
,
Riou
A
,
Souquiere
L
,
Paleiron
N
, et al
Automatic versus manual oxygen administration in the emergency department
.
Eur Respir J
.
2017
Jul
;
50
(
1
):
1602552
.
[PubMed]
1399-3003
137.
Hansen
EF
,
Bech
CS
,
Vestbo
J
,
Andersen
O
,
Kofod
LM
.
Automatic oxygen titration with O2matic® to patients admitted with COVID-19 and hypoxemic respiratory failure
.
Eur Clin Respir J
.
2020
Oct
;
7
(
1
):
1833695
.
[PubMed]
2001-8525
138.
Lellouche
F
,
Bouchard
PA
,
Roberge
M
,
Simard
S
,
L’Her
E
,
Maltais
F
, et al
Automated oxygen titration and weaning with FreeO2 in patients with acute exacerbation of COPD: a pilot randomized trial
.
Int J Chron Obstruct Pulmon Dis
.
2016
Aug
;
11
:
1983
90
.
[PubMed]
1178-2005
139.
Johannigman
JA
,
Branson
R
,
Lecroy
D
,
Beck
G
.
Autonomous control of inspired oxygen concentration during mechanical ventilation of the critically injured trauma patient
.
J Trauma
.
2009
Feb
;
66
(
2
):
386
92
.
[PubMed]
1529-8809
140.
Chadha
TS
,
Cohn
MA
.
Noninvasive treatment of pneumothorax with oxygen inhalation
.
Respiration
.
1983
;
44
(
2
):
147
52
.
[PubMed]
0025-7931
141.
Northfield
TC
.
Oxygen therapy for spontaneous pneumothorax
.
BMJ
.
1971
Oct
;
4
(
5779
):
86
8
.
[PubMed]
0007-1447
142.
Schnell
J
,
Beer
M
,
Eggeling
S
,
Gesierich
W
,
Gottlieb
J
,
Herth
FJ
, et al
Management of Spontaneous Pneumothorax and Post-Interventional Pneumothorax: german S3 Guideline
.
Respiration
.
2019
;
97
(
4
):
370
402
.
[PubMed]
1423-0356
143.
Brown
SG
,
Ball
EL
,
Perrin
K
,
Asha
SE
,
Braithwaite
I
,
Egerton-Warburton
D
, et al;
PSP Investigators
.
Conservative versus Interventional Treatment for Spontaneous Pneumothorax
.
N Engl J Med
.
2020
Jan
;
382
(
5
):
405
15
.
[PubMed]
1533-4406
144.
Bellani
G
,
Laffey
JG
,
Pham
T
,
Madotto
F
,
Fan
E
,
Brochard
L
, et al;
LUNG SAFE Investigators
;
ESICM Trials Group
.
Noninvasive Ventilation of Patients with Acute Respiratory Distress Syndrome. Insights from the LUNG SAFE Study
.
Am J Respir Crit Care Med
.
2017
Jan
;
195
(
1
):
67
77
.
[PubMed]
1535-4970
145.
Jensen
AG
,
Johnson
A
,
Sandstedt
S
.
Rebreathing during oxygen treatment with face mask. The effect of oxygen flow rates on ventilation
.
Acta Anaesthesiol Scand
.
1991
May
;
35
(
4
):
289
92
.
[PubMed]
0001-5172
146.
Bethune
DW
,
Collis
JM
.
The evaluation of oxygen masks. A mechanical method
.
Anaesthesia
.
1967
Jan
;
22
(
1
):
43
54
.
[PubMed]
0003-2409
147.
Berbenetz
N
,
Wang
Y
,
Brown
J
,
Godfrey
C
,
Ahmad
M
,
Vital
FM
, et al
Non-invasive positive pressure ventilation (CPAP or bilevel NPPV) for cardiogenic pulmonary oedema
.
Cochrane Database Syst Rev
.
2019
Apr
;
4
(
4
):CD005351.
[PubMed]
1469-493X
148.
Osadnik
CR
,
Tee
VS
,
Carson-Chahhoud
KV
,
Picot
J
,
Wedzicha
JA
,
Smith
BJ
.
Non-invasive ventilation for the management of acute hypercapnic respiratory failure due to exacerbation of chronic obstructive pulmonary disease
.
Cochrane Database Syst Rev
.
2017
Jul
;
7
(
7
):CD004104.
[PubMed]
1469-493X
149.
Gupta
D
,
Nath
A
,
Agarwal
R
,
Behera
D
.
A prospective randomized controlled trial on the efficacy of noninvasive ventilation in severe acute asthma
.
Respir Care
.
2010
May
;
55
(
5
):
536
43
.
[PubMed]
0020-1324
150.
Young
AC
,
Wilson
JW
,
Kotsimbos
TC
,
Naughton
MT
.
Randomised placebo controlled trial of non-invasive ventilation for hypercapnia in cystic fibrosis
.
Thorax
.
2008
Jan
;
63
(
1
):
72
7
.
[PubMed]
1468-3296
151.
Westhoff
M
,
Schönhofer
B
,
Neumann
P
,
Bickenbach
J
,
Barchfeld
T
,
Becker
H
, et al
[Noninvasive Mechanical Ventilation in Acute Respiratory Failure]
.
Pneumologie
.
2015
Dec
;
69
(
12
):
719
56
.
[PubMed]
1438-8790
152.
Doshi
P
,
Whittle
JS
,
Bublewicz
M
,
Kearney
J
,
Ashe
T
,
Graham
R
, et al
High-Velocity Nasal Insufflation in the Treatment of Respiratory Failure: A Randomized Clinical Trial
.
Ann Emerg Med
.
2018
Jul
;
72
(
1
):
73
83.e5
.
[PubMed]
1097-6760
153.
Haywood
ST
,
Whittle
JS
,
Volakis
LI
,
Dungan
G
 2nd
,
Bublewicz
M
,
Kearney
J
, et al
HVNI vs NIPPV in the treatment of acute decompensated heart failure: subgroup analysis of a multi-center trial in the ED
.
Am J Emerg Med
.
2019
Nov
;
37
(
11
):
2084
90
.
[PubMed]
1532-8171
154.
Hernández
G
,
Vaquero
C
,
González
P
,
Subira
C
,
Frutos-Vivar
F
,
Rialp
G
, et al
Effect of Postextubation High-Flow Nasal Cannula vs Conventional Oxygen Therapy on Reintubation in Low-Risk Patients: A Randomized Clinical Trial
.
JAMA
.
2016
Apr
;
315
(
13
):
1354
61
.
[PubMed]
1538-3598
155.
Stéphan
F
,
Barrucand
B
,
Petit
P
,
Rézaiguia-Delclaux
S
,
Médard
A
,
Delannoy
B
, et al;
BiPOP Study Group
.
High-Flow Nasal Oxygen vs Noninvasive Positive Airway Pressure in Hypoxemic Patients After Cardiothoracic Surgery: A Randomized Clinical Trial
.
JAMA
.
2015
Jun
;
313
(
23
):
2331
9
.
[PubMed]
1538-3598
156.
Tan
D
,
Walline
JH
,
Ling
B
,
Xu
Y
,
Sun
J
,
Wang
B
, et al
High-flow nasal cannula oxygen therapy versus non-invasive ventilation for chronic obstructive pulmonary disease patients after extubation: a multicenter, randomized controlled trial
.
Crit Care
.
2020
Aug
;
24
(
1
):
489
.
[PubMed]
1466-609X
157.
Futier
E
,
Paugam-Burtz
C
,
Constantin
JM
,
Pereira
B
,
Jaber
S
.
The OPERA trial - comparison of early nasal high flow oxygen therapy with standard care for prevention of postoperative hypoxemia after abdominal surgery: study protocol for a multicenter randomized controlled trial
.
Trials
.
2013
Oct
;
14
(
1
):
341
.
[PubMed]
1745-6215
158.
Papachatzakis
Y
,
Nikolaidis
PT
,
Kontogiannis
S
,
Trakada
G
.
High-Flow Oxygen through Nasal Cannula vs. Non-Invasive Ventilation in Hypercapnic Respiratory Failure: A Randomized Clinical Trial
.
Int J Environ Res Public Health
.
2020
Aug
;
17
(
16
):
E5994
.
[PubMed]
1660-4601
159.
McKinstry
S
,
Singer
J
,
Baarsma
JP
,
Weatherall
M
,
Beasley
R
,
Fingleton
J
.
Nasal high-flow therapy compared with non-invasive ventilation in COPD patients with chronic respiratory failure: A randomized controlled cross-over trial
.
Respirology
.
2019
Nov
;
24
(
11
):
1081
7
.
[PubMed]
1440-1843
160.
Ferreyro
BL
,
Angriman
F
,
Munshi
L
,
Del Sorbo
L
,
Ferguson
ND
,
Rochwerg
B
, et al
Association of Noninvasive Oxygenation Strategies With All-Cause Mortality in Adults With Acute Hypoxemic Respiratory Failure: A Systematic Review and Meta-analysis
.
JAMA
.
2020
Jul
;
324
(
1
):
57
67
.
[PubMed]
1538-3598
161.
Zhang
Y
,
Fang
C
,
Dong
BR
,
Wu
T
,
Deng
JL
.
Oxygen therapy for pneumonia in adults
.
Cochrane Database Syst Rev
.
2012
Mar
;(
3
):CD006607.
[PubMed]
1469-493X
162.
Antonelli
M
,
Conti
G
,
Bufi
M
,
Costa
MG
,
Lappa
A
,
Rocco
M
, et al
Noninvasive ventilation for treatment of acute respiratory failure in patients undergoing solid organ transplantation: a randomized trial
.
JAMA
.
2000
Jan
;
283
(
2
):
235
41
.
[PubMed]
0098-7484
163.
Hilbert
G
,
Gruson
D
,
Vargas
F
,
Valentino
R
,
Gbikpi-Benissan
G
,
Dupon
M
, et al
Noninvasive ventilation in immunosuppressed patients with pulmonary infiltrates, fever, and acute respiratory failure
.
N Engl J Med
.
2001
Feb
;
344
(
7
):
481
7
.
[PubMed]
0028-4793
164.
Squadrone
V
,
Massaia
M
,
Bruno
B
,
Marmont
F
,
Falda
M
,
Bagna
C
, et al
Early CPAP prevents evolution of acute lung injury in patients with hematologic malignancy
.
Intensive Care Med
.
2010
Oct
;
36
(
10
):
1666
74
.
[PubMed]
1432-1238
165.
Stub
D
,
Smith
K
,
Bernard
S
,
Nehme
Z
,
Stephenson
M
,
Bray
JE
, et al;
AVOID Investigators
.
Air Versus Oxygen in ST-Segment-Elevation Myocardial Infarction
.
Circulation
.
2015
Jun
;
131
(
24
):
2143
50
.
[PubMed]
1524-4539
166.
Werdan
K
,
Boeken
U
,
Briegel
MJ
,
Buerke
M
,
Geppert
A
,
Janssens
U
, et al
[Short version of the 2nd edition of the German-Austrian S3 guidelines “Cardiogenic shock complicating myocardial infarction-Diagnosis, monitoring and treatment”]
.
Anaesthesist
.
2021
Jan
;
70
(
1
):
42
70
.
[PubMed]
1432-055X
167.
Ibanez
B
,
James
S
,
Agewall
S
,
Antunes
MJ
,
Bucciarelli-Ducci
C
,
Bueno
H
, et al;
ESC Scientific Document Group
.
2017 ESC Guidelines for the management of acute myocardial infarction in patients presenting with ST-segment elevation: the Task Force for the management of acute myocardial infarction in patients presenting with ST-segment elevation of the European Society of Cardiology (ESC)
.
Eur Heart J
.
2018
Jan
;
39
(
2
):
119
77
.
[PubMed]
1522-9645
168.
Cabello
JB
,
Burls
A
,
Emparanza
JI
,
Bayliss
SE
,
Quinn
T
.
Oxygen therapy for acute myocardial infarction
.
Cochrane Database Syst Rev
.
2016
Dec
;
12
:CD007160.
[PubMed]
1469-493X
169.
Rawles
JM
,
Kenmure
AC
.
Controlled trial of oxygen in uncomplicated myocardial infarction
.
BMJ
.
1976
May
;
1
(
6018
):
1121
3
.
[PubMed]
0007-1447
170.
James
SK
,
Erlinge
D
,
Herlitz
J
,
Alfredsson
J
,
Koul
S
,
Fröbert
O
, et al;
DETO2X-SWEDEHEART Investigators
.
Effect of Oxygen Therapy on Cardiovascular Outcomes in Relation to Baseline Oxygen Saturation
.
JACC Cardiovasc Interv
.
2020
Feb
;
13
(
4
):
502
13
.
[PubMed]
1876-7605
171.
Burls
A
,
Emparanza
JI
,
Quinn
T
,
Cabello
JB
.
Oxygen use in acute myocardial infarction: an online survey of health professionals’ practice and beliefs
.
Emerg Med J
.
2010
Apr
;
27
(
4
):
283
6
.
[PubMed]
1472-0213
172.
Sepehrvand
N
,
Alemayehu
W
,
Rowe
BH
,
McAlister
FA
,
van Diepen
S
,
Stickland
M
, et al
High vs. low oxygen therapy in patients with acute heart failure: HiLo-HF pilot trial
.
ESC Heart Fail
.
2019
Aug
;
6
(
4
):
667
77
.
[PubMed]
2055-5822
173.
Mader
FM
,
Schlaganfall
SR
. S3-Leitlinie [AWMF National German S3 Guideline] 2020 1.2.
2020
[cited 2021 12.4.2021]; Available from: https://www.awmf.org/uploads/tx_szleitlinien/053-011l_S3_Schlaganfall_2021-03.pdf
174.
Powers
WJ
,
Rabinstein
AA
,
Ackerson
T
,
Adeoye
OM
,
Bambakidis
NC
,
Becker
K
, et al
Guidelines for the Early Management of Patients With Acute Ischemic Stroke: 2019 Update to the 2018 Guidelines for the Early Management of Acute Ischemic Stroke: A Guideline for Healthcare Professionals From the American Heart Association/American Stroke Association
.
Stroke
.
2019
Dec
;
50
(
12
):
e344
418
.
[PubMed]
1524-4628
175.
Ding
J
,
Zhou
D
,
Sui
M
,
Meng
R
,
Chandra
A
,
Han
J
, et al
The effect of normobaric oxygen in patients with acute stroke: a systematic review and meta-analysis
.
Neurol Res
.
2018
Jun
;
40
(
6
):
433
44
.
[PubMed]
1743-1328
176.
Davis
DP
,
Meade
W
 Jr
,
Sise
MJ
,
Kennedy
F
,
Simon
F
,
Tominaga
G
, et al
Both hypoxemia and extreme hyperoxemia may be detrimental in patients with severe traumatic brain injury
.
J Neurotrauma
.
2009
Dec
;
26
(
12
):
2217
23
.
[PubMed]
1557-9042
177.
Polytrauma Guideline Update
G
;
Polytrauma Guideline Update Group
.
Level 3 guideline on the treatment of patients with severe/multiple injuries : AWMF Register-Nr. 012/019
.
Eur J Trauma Emerg Surg
.
2018
Apr
;
44
(
S1
Suppl 1
):
3
271
.
[PubMed]
1863-9941
178.
Robba
C
,
Poole
D
,
McNett
M
,
Asehnoune
K
,
Bösel
J
,
Bruder
N
, et al
Mechanical ventilation in patients with acute brain injury: recommendations of the European Society of Intensive Care Medicine consensus
.
Intensive Care Med
.
2020
Dec
;
46
(
12
):
2397
410
.
[PubMed]
1432-1238
179.
Rincon
F
,
Kang
J
,
Maltenfort
M
,
Vibbert
M
,
Urtecho
J
,
Athar
MK
, et al
Association between hyperoxia and mortality after stroke: a multicenter cohort study
.
Crit Care Med
.
2014
Feb
;
42
(
2
):
387
96
.
[PubMed]
1530-0293
180.
Jeon
SB
,
Choi
HA
,
Badjatia
N
,
Schmidt
JM
,
Lantigua
H
,
Claassen
J
, et al
Hyperoxia may be related to delayed cerebral ischemia and poor outcome after subarachnoid haemorrhage
.
J Neurol Neurosurg Psychiatry
.
2014
Dec
;
85
(
12
):
1301
7
.
[PubMed]
1468-330X
181.
Heyboer
M
 3rd
,
Jennings
S
,
Grant
WD
,
Ojevwe
C
,
Byrne
J
,
Wojcik
SM
.
Seizure incidence by treatment pressure in patients undergoing hyperbaric oxygen therapy
.
Undersea Hyperb Med
.
2014
Sep-Oct
;
41
(
5
):
379
85
.
[PubMed]
1066-2936
182.
Bennett
MH
,
Weibel
S
,
Wasiak
J
,
Schnabel
A
,
French
C
,
Kranke
P
.
Hyperbaric oxygen therapy for acute ischaemic stroke
.
Cochrane Database Syst Rev
.
2014
Nov
;(
11
):CD004954.
[PubMed]
1469-493X
183.
Busse
WW
;
National Heart, Lung, and Blood Institute
;
National Asthma Education and Prevention Program Asthma and Pregnancy Working Group
.
NAEPP expert panel report. Managing asthma during pregnancy: recommendations for pharmacologic treatment-2004 update
.
J Allergy Clin Immunol
.
2005
Jan
;
115
(
1
):
34
46
.
[PubMed]
0091-6749
184.
Thorp
JA
,
Trobough
T
,
Evans
R
,
Hedrick
J
,
Yeast
JD
.
The effect of maternal oxygen administration during the second stage of labor on umbilical cord blood gas values: a randomized controlled prospective trial
.
Am J Obstet Gynecol
.
1995
Feb
;
172
(
2 Pt 1
):
465
74
.
[PubMed]
0002-9378
185.
Nesterenko
TH
,
Acun
C
,
Mohamed
MA
,
Mohamed
AN
,
Karcher
D
,
Larsen
J
 Jr
, et al
Is it a safe practice to administer oxygen during uncomplicated delivery: a randomized controlled trial?
Early Hum Dev
.
2012
Aug
;
88
(
8
):
677
81
.
[PubMed]
1872-6232
186.
Chuai
Y
,
Jiang
W
,
Xu
X
,
Wang
A
,
Yao
Y
,
Chen
L
.
Maternal oxygen exposure may not change umbilical cord venous partial pressure of oxygen: non-random, paired venous and arterial samples from a randomised controlled trial
.
BMC Pregnancy Childbirth
.
2020
Sep
;
20
(
1
):
510
.
[PubMed]
1471-2393
187.
Raghuraman
N
,
Wan
L
,
Temming
LA
,
Woolfolk
C
,
Macones
GA
,
Tuuli
MG
, et al
Effect of Oxygen vs Room Air on Intrauterine Fetal Resuscitation: A Randomized Noninferiority Clinical Trial
.
JAMA Pediatr
.
2018
Sep
;
172
(
9
):
818
23
.
[PubMed]
2168-6211
188.
Buckley
NA
,
Juurlink
DN
,
Isbister
G
,
Bennett
MH
,
Lavonas
EJ
.
Hyperbaric oxygen for carbon monoxide poisoning
.
Cochrane Database Syst Rev
.
2011
Apr
;(
4
):CD002041.
[PubMed]
1469-493X
189.
Juurlink
DN
,
Stanbrook
MB
,
McGuigan
MA
.
Hyperbaric oxygen for carbon monoxide poisoning
.
Cochrane Database Syst Rev
.
2000
;(
2
):CD002041.
[PubMed]
1469-493X
190.
Lin
CH
,
Su
WH
,
Chen
YC
,
Feng
PH
,
Shen
WC
,
Ong
JR
, et al
Treatment with normobaric or hyperbaric oxygen and its effect on neuropsychometric dysfunction after carbon monoxide poisoning: A systematic review and meta-analysis of randomized controlled trials
.
Medicine (Baltimore)
.
2018
Sep
;
97
(
39
):
e12456
.
[PubMed]
1536-5964
191.
Wang
W
,
Cheng
J
,
Zhang
J
,
Wang
K
.
Effect of Hyperbaric Oxygen on Neurologic Sequelae and All-Cause Mortality in Patients with Carbon Monoxide Poisoning: A Meta-Analysis of Randomized Controlled Trials
.
Med Sci Monit
.
2019
Oct
;
25
:
7684
93
.
[PubMed]
1643-3750
192.
Rose
JJ
,
Wang
L
,
Xu
Q
,
McTiernan
CF
,
Shiva
S
,
Tejero
J
, et al
Carbon Monoxide Poisoning: Pathogenesis, Management, and Future Directions of Therapy
.
Am J Respir Crit Care Med
.
2017
Mar
;
195
(
5
):
596
606
.
[PubMed]
1535-4970
193.
Tomruk
O
,
Karaman
K
,
Erdur
B
,
Armagan
HH
,
Beceren
NG
,
Oskay
A
, et al
A New Promising Treatment Strategy for Carbon Monoxide Poisoning: High Flow Nasal Cannula Oxygen Therapy
.
Med Sci Monit
.
2019
Jan
;
25
:
605
9
.
[PubMed]
1643-3750
194.
Bennett
MH
,
Feldmeier
J
,
Hampson
NB
,
Smee
R
,
Milross
C
.
Hyperbaric oxygen therapy for late radiation tissue injury
.
Cochrane Database Syst Rev
.
2016
Apr
;
4
:CD005005.
[PubMed]
1469-493X
195.
Bennett
MH
,
Trytko
B
,
Jonker
B
.
Hyperbaric oxygen therapy for the adjunctive treatment of traumatic brain injury
.
Cochrane Database Syst Rev
.
2012
Dec
;
12
:CD004609.
[PubMed]
1469-493X
196.
Eskes
A
,
Vermeulen
H
,
Lucas
C
,
Ubbink
DT
.
Hyperbaric oxygen therapy for treating acute surgical and traumatic wounds
.
Cochrane Database Syst Rev
.
2013
Dec
;(
12
):CD008059.
[PubMed]
1469-493X
197.
Kranke
P
,
Bennett
MH
,
Martyn-St James
M
,
Schnabel
A
,
Debus
SE
,
Weibel
S
.
Hyperbaric oxygen therapy for chronic wounds
.
Cochrane Database Syst Rev
.
2015
Jun
;(
6
):CD004123.
[PubMed]
1469-493X
198.
Holmberg
MJ
,
Nicholson
T
,
Nolan
JP
,
Schexnayder
S
,
Reynolds
J
,
Nation
K
, et al;
Adult Pediatric Advanced Life Support Task Forces at the International Liaison Committee on Resuscitation (ILCOR)
.
Oxygenation and ventilation targets after cardiac arrest: A systematic review and meta-analysis
.
Resuscitation
.
2020
Jul
;
152
:
107
15
.
[PubMed]
1873-1570
199.
Wang
CH
,
Chang
WT
,
Huang
CH
,
Tsai
MS
,
Yu
PH
,
Wang
AY
, et al
The effect of hyperoxia on survival following adult cardiac arrest: a systematic review and meta-analysis of observational studies
.
Resuscitation
.
2014
Sep
;
85
(
9
):
1142
8
.
[PubMed]
1873-1570
200.
Berg
KM
,
Soar
J
,
Andersen
LW
,
Böttiger
BW
,
Cacciola
S
,
Callaway
CW
, et al;
Adult Advanced Life Support Collaborators
.
Adult Advanced Life Support: 2020 International Consensus on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science With Treatment Recommendations
.
Circulation
.
2020
Oct
;
142
(
16_suppl_1
suppl_1
):
S92
139
.
[PubMed]
1524-4539
201.
Thompson
,
J.
, et al
,
Out-of-hospital continuous positive airway pressure ventilation versus usual care in acute respiratory failure: a randomized controlled trial.
Ann Emerg Med,
2008
. 52(3): p. 232-41, 241 e1.
202.
Plaisance
P
,
Pirracchio
R
,
Berton
C
,
Vicaut
E
,
Payen
D
.
A randomized study of out-of-hospital continuous positive airway pressure for acute cardiogenic pulmonary oedema: physiological and clinical effects
.
Eur Heart J
.
2007
Dec
;
28
(
23
):
2895
901
.
[PubMed]
0195-668X
203.
Ducros
L
,
Logeart
D
,
Vicaut
E
,
Henry
P
,
Plaisance
P
,
Collet
JP
, et al;
CPAP collaborative study group
.
CPAP for acute cardiogenic pulmonary oedema from out-of-hospital to cardiac intensive care unit: a randomised multicentre study
.
Intensive Care Med
.
2011
Sep
;
37
(
9
):
1501
9
.
[PubMed]
1432-1238
204.
Bray
JE
,
Hein
C
,
Smith
K
,
Stephenson
M
,
Grantham
H
,
Finn
J
, et al;
EXACT Investigators
.
Oxygen titration after resuscitation from out-of-hospital cardiac arrest: A multi-centre, randomised controlled pilot study (the EXACT pilot trial)
.
Resuscitation
.
2018
Jul
;
128
:
211
5
.
[PubMed]
1873-1570
205.
Thomas
M
,
Voss
S
,
Benger
J
,
Kirby
K
,
Nolan
JP
.
Cluster randomised comparison of the effectiveness of 100% oxygen versus titrated oxygen in patients with a sustained return of spontaneous circulation following out of hospital cardiac arrest: a feasibility study. PROXY: post ROSC OXYgenation study
.
BMC Emerg Med
.
2019
Jan
;
19
(
1
):
16
.
[PubMed]
1471-227X
206.
Young
P
,
Bailey
M
,
Bellomo
R
,
Bernard
S
,
Dicker
B
,
Freebairn
R
, et al
HyperOxic Therapy OR NormOxic Therapy after out-of-hospital cardiac arrest (HOT OR NOT): a randomised controlled feasibility trial
.
Resuscitation
.
2014
Dec
;
85
(
12
):
1686
91
.
[PubMed]
1873-1570
207.
Young
PJ
,
Bailey
M
,
Bellomo
R
,
Bernard
S
,
Bray
J
,
Jakkula
P
, et al
Conservative or liberal oxygen therapy in adults after cardiac arrest: an individual-level patient data meta-analysis of randomised controlled trials
.
Resuscitation
.
2020
Dec
;
157
:
15
22
.
[PubMed]
1873-1570
208.
Alhazzani
W
,
Møller
MH
,
Arabi
YM
,
Loeb
M
,
Gong
MN
,
Fan
E
, et al
Surviving Sepsis Campaign: guidelines on the management of critically ill adults with Coronavirus Disease 2019 (COVID-19)
.
Intensive Care Med
.
2020
May
;
46
(
5
):
854
87
.
[PubMed]
1432-1238
209.
Tobin
MJ
,
Laghi
F
,
Jubran
A
.
Why COVID-19 Silent Hypoxemia Is Baffling to Physicians
.
Am J Respir Crit Care Med
.
2020
Aug
;
202
(
3
):
356
60
.
[PubMed]
1535-4970
210.
Shenoy
N
,
Luchtel
R
,
Gulani
P
.
Considerations for target oxygen saturation in COVID-19 patients: are we under-shooting?
BMC Med
.
2020
Aug
;
18
(
1
):
260
.
[PubMed]
1741-7015
211.
Grensemann
,
J.K.S.
, Nichtinvasive Beatmung und Ansteckungsrisiko - Aerosole von COVID-19-Patienten. Dtsch Arztebl
2020
. 117(31-32): p. A-1498 / B-1286.
212.
Cohen
AS
,
Burns
B
,
Goadsby
PJ
.
High-flow oxygen for treatment of cluster headache: a randomized trial
.
JAMA
.
2009
Dec
;
302
(
22
):
2451
7
.
[PubMed]
1538-3598
213.
Bennett
MH
,
French
C
,
Schnabel
A
,
Wasiak
J
,
Kranke
P
,
Weibel
S
.
Normobaric and hyperbaric oxygen therapy for the treatment and prevention of migraine and cluster headache
.
Cochrane Database Syst Rev
.
2015
Dec
;(
12
):CD005219.
[PubMed]
1469-493X
214.
Kudrow
L
.
Response of cluster headache attacks to oxygen inhalation
.
Headache
.
1981
Jan
;
21
(
1
):
1
4
.
[PubMed]
0017-8748
215.
Riphaus
A
,
Wehrmann
T
,
Hausmann
J
,
Weber
B
,
von Delius
S
,
Jung
M
, et al
[S3-guidelines “sedation in gastrointestinal endoscopy” 2014 (AWMF register no. 021/014)]
.
Z Gastroenterol
.
2015
Aug
;
53
(
8
):
E1
.
[PubMed]
0044-2771
216.
Rex
DK
,
Deenadayalu
VP
,
Eid
E
,
Imperiale
TF
,
Walker
JA
,
Sandhu
K
, et al
Endoscopist-directed administration of propofol: a worldwide safety experience
.
Gastroenterology
.
2009
Oct
;
137
(
4
):
1229
37
.
[PubMed]
1528-0012
217.
Arrowsmith
JB
,
Gerstman
BB
,
Fleischer
DE
,
Benjamin
SB
.
Results from the American Society for Gastrointestinal Endoscopy/U.S. Food and Drug Administration collaborative study on complication rates and drug use during gastrointestinal endoscopy
.
Gastrointest Endosc
.
1991
Jul-Aug
;
37
(
4
):
421
7
.
[PubMed]
0016-5107
218.
Bauer
TT
,
Torres
A
,
Ewig
S
,
Hernández
C
,
Sanchez-Nieto
JM
,
Xaubet
A
, et al
Effects of bronchoalveolar lavage volume on arterial oxygenation in mechanically ventilated patients with pneumonia
.
Intensive Care Med
.
2001
Feb
;
27
(
2
):
384
93
.
[PubMed]
0342-4642
219.
Jones
AM
,
O’Driscoll
R
.
Do all patients require supplemental oxygen during flexible bronchoscopy?
Chest
.
2001
Jun
;
119
(
6
):
1906
9
.
[PubMed]
0012-3692
220.
Rozario
L
,
Sloper
D
,
Sheridan
MJ
.
Supplemental oxygen during moderate sedation and the occurrence of clinically significant desaturation during endoscopic procedures
.
Gastroenterol Nurs
.
2008
Jul-Aug
;
31
(
4
):
281
5
.
[PubMed]
1538-9766
221.
Deitch
K
,
Miner
J
,
Chudnofsky
CR
,
Dominici
P
,
Latta
D
.
Does end tidal CO2 monitoring during emergency department procedural sedation and analgesia with propofol decrease the incidence of hypoxic events? A randomized, controlled trial
.
Ann Emerg Med
.
2010
Mar
;
55
(
3
):
258
64
.
[PubMed]
1097-6760
222.
Lin
Y
,
Zhang
X
,
Li
L
,
Wei
M
,
Zhao
B
,
Wang
X
, et al
High-flow nasal cannula oxygen therapy and hypoxia during gastroscopy with propofol sedation: a randomized multicenter clinical trial
.
Gastrointest Endosc
.
2019
Oct
;
90
(
4
):
591
601
.
[PubMed]
1097-6779