Conservative versus liberal oxygen therapy in relation to all-cause mortality among patients in the intensive care unit: A systematic review of randomized controlled trials with meta-analysis and trial sequential analysis / Oxigenoterapia conservadora frente a liberal sobre la mortalidad total en pacientes en la unidad de cuidados intensivos: una revisión sistemática de ensayos controlados aleatorizados con metaanálisis y análisis secuencial de ensayos

Objective To evaluate the benefits and harmful effects of conservative versus liberal oxygen therapy in patients admitted to the Intensive Care Unit (ICU). Design A systematic review and meta-analysis was carried out. Setting ICU. Participants Adult patients (aged 18 years or older) were randomized to either a lower oxygenation target strategy (conservative oxygen therapy) or a higher oxygenation target strategy (liberal oxygen therapy) in the ICU. Interventions Patients received different oxygenation target strategies. Results Ten studies involving 5429 adult patients admitted to the ICU were included in the meta-analysis. The pooled results showed no decreased all-cause mortality at 28 days (RR 0.90; 95%CI 0.75–1.09; p=0.28), 90 days (RR 1.02; 95%CI 0.92–1.13; p=0.71) or longest follow-up (RR 0.97; 95%CI 0.88–1.08; p=0.63) among patients administered conservative oxygen therapy. Secondary outcomes were comparable between the two groups. The results of sensitivity analyses and subgroup analyses were consistent with the main analyses. Conclusion No beneficial or harmful effects of conservative oxygen therapy were found compared to liberal oxygen therapy in relation to all-cause mortality among adult patients in the ICU. Conservative oxygen therapy did not reduce all-cause mortality at 28 days, 90 days or longest follow-up. Other important clinical outcomes were also comparable between the two groups (AU)

Objetivo Evaluar los beneficios y los daños de la oxigenoterapia conservadora frente a la liberal para los pacientes de la unidad de cuidados intensivos (UCI). Diseño Revision sistemática y metaanálisis. Lugar UCI. Participantes Los pacientes adultos (de 18 años o más) fueron asignados al azar para recibir una estrategia de objetivo de oxigenación más baja (terapia de oxígeno conservadora) o una estrategia de objetivo de oxigenación más alta (terapia de oxígeno liberal) en la UCI. Intervenciones Los pacientes recibieron diferentes estrategias de objetivos de oxigenación. Resultados En este metaanálisis se incluyeron 10 estudios con 5.429 pacientes adultos ingresados en la UCI. Los resultados agrupados no mostraron una disminución de la mortalidad total a los 28 días (RR 0,90; IC del 95%: 0,75 a 1,09; p=0,28), 90 días (RR 1,02; IC del 95%: 0,92 a 1,13; p=0,71) ni en el seguimiento más prolongado (RR 0,97; IC del 95%: 0,88 a 1,08; p=0,63) para los pacientes tratados con oxigenoterapia conservadora. Los resultados secundarios fueron comparables entre los dos grupos. Los resultados de los análisis de sensibilidad y los análisis de subgrupos fueron consistentes con los análisis principales. Conclusión No se encontraron efectos beneficiosos o perjudiciales de la oxigenoterapia conservadora en comparación con la oxigenoterapia liberal sobre la mortalidad total entre los pacientes adultos en la UCI. La oxigenoterapia conservadora no redujo la mortalidad por todas las causas a los 28 días, a los 90 días ni en el seguimiento más prolongado. Otros resultados clínicos importantes también fueron comparables entre los dos grupos (AU)

Oxigenoterapia. Consideraciones sobre su uso en el enfermo agudo / Oxygen Therapy. Considerations Regarding its Use in Acute Ill Patients

No disponible

High-Flow Nasal Oxygen for Severe Hypoxemia: Oxygenation Response and Outcome in Patients with COVID-19.

Rationale: The "Berlin definition" of acute respiratory distress syndrome (ARDS) does not allow inclusion of patients receiving high-flow nasal oxygen (HFNO). However, several articles have proposed that criteria for defining ARDS should be broadened to allow inclusion of patients receiving HFNO. Objectives: To compare the proportion of patients fulfilling ARDS criteria during HFNO and soon after intubation, and 28-day mortality between patients treated exclusively with HFNO and patients transitioned from HFNO to invasive mechanical ventilation (IMV). Methods: From previously published studies, we analyzed patients with coronavirus disease (COVID-19) who had PaO2/FiO2 of ⩽300 while treated with ⩾40 L/min HFNO, or noninvasive ventilation (NIV) with positive end-expiratory pressure of ⩾5 cm H2O (comparator). In patients transitioned from HFNO/NIV to invasive mechanical ventilation (IMV), we compared ARDS severity during HFNO/NIV and soon after IMV. We compared 28-day mortality in patients treated exclusively with HFNO/NIV versus patients transitioned to IMV. Measurements and Main Results: We analyzed 184 and 131 patients receiving HFNO or NIV, respectively. A total of 112 HFNO and 69 NIV patients transitioned to IMV. Of those, 104 (92.9%) patients on HFNO and 66 (95.7%) on NIV continued to have PaO2/FiO2 ⩽300 under IMV. Twenty-eight-day mortality in patients who remained on HFNO was 4.2% (3/72), whereas in patients transitioned from HFNO to IMV, it was 28.6% (32/112) (P < 0.001). Twenty-eight-day mortality in patients who remained on NIV was 1.6% (1/62), whereas in patients who transitioned from NIV to IMV, it was 44.9% (31/69) (P < 0.001). Overall mortality was 19.0% (35/184) and 24.4% (32/131) for HFNO and NIV, respectively (P = 0.2479). Conclusions: Broadening the ARDS definition to include patients on HFNO with PaO2/FiO2 ⩽300 may identify patients at earlier stages of disease but with lower mortality.

Supplemental Intraoperative Oxygen and Long-term Mortality: Subanalysis of a Multiple Crossover Cluster Trial.

BACKGROUND: Whether supplemental oxygen worsens long-term mortality remains unclear, with contradictory trial results. The authors therefore tested the hypothesis that supplemental oxygen (80% vs. 30%) increases the hazard for long-term mortality. METHODS: The authors conducted a post hoc analysis of a large multiple crossover cluster trial in which more than 5,000 colorectal surgeries on 4,088 adults were allocated to receive either 30% or 80% inspired oxygen during general anesthesia. The authors assessed the effect of 80% versus 30% target-inspired oxygen on long-term mortality and calculated Kaplan-Meier survival estimates. Analysis was restricted to patients with a home address in Ohio because the authors could obtain reliable vital status information from the Ohio Department of Health (Columbus, Ohio) for them. RESULTS: A total of 3,471 qualifying colorectal surgeries performed in 2,801 patients were analyzed, including 1,753 (51%) surgeries in 1,577 patients given 80% oxygen and 1,718 surgeries in 1,551 patients given 30% oxygen. The observed incidence of death after a median of 3 yr was 13% (234 of 1,753) in the 80% oxygen group and 14% (245 of 1,718) in the 30% oxygen group. The estimated hazard ratio for mortality was 0.94 (95% CI, 0.78 to 1.13; P = 0.493). CONCLUSIONS: In this post hoc analysis of a large, controlled trial, supplemental oxygen did not increase postoperative mortality.

Therapeutic interventions for COVID-19: a living overview of reviews.

BACKGROUND: Coronavirus disease 2019 (COVID-19) has rapidly spread worldwide, but safe and effective treatment options remain unavailable. Numerous systematic reviews of varying qualities have tried to summarize the evidence on the available therapeutic interventions for COVID-19. This overview of reviews aims to provide a succinct summary of the findings of systematic reviews on different pharmacological and non-pharmacological therapeutic interventions for COVID-19. METHODS: We searched PubMed, Embase, Google Scholar, Cochrane Database of Systematic Reviews, and WHO database of publications on COVID-19 from 1 December 2019 through to 11 June 2020 for peer-reviewed systematic review studies that reported on potential pharmacological or non-pharmacological therapies for COVID-19. Quality assessment was completed using A MeaSurement Tool to Assess systematic Reviews-2 (AMSTAR-2) measure. RESULTS: Out of 816 non-duplicate studies, 45 were included in the overview. Antiviral and antibiotic agents, corticosteroids, and anti-malarial agents were the most common drug classes used to treat COVID-19; however, there was no direct or strong evidence to support their efficacy. Oxygen therapy and ventilatory support was the most common non-pharmacological supportive care. The quality of most of the included reviews was rated as low or critically low. CONCLUSION: This overview of reviews demonstrates that although some therapeutic interventions may be beneficial to specific subgroups of COVID-19 patients, the available data are insufficient to strongly recommend any particular treatment option to be used at a population level. Future systematic reviews on COVID-19 treatments should adhere to the recommended systematic review methodologies and ensure that promptness and comprehensiveness are balanced.The reviews of this paper are available via the supplemental material section.

High-flow nasal oxygen reduces endotracheal intubation: a randomized clinical trial.

BACKGROUND: The benefits of high-flow nasal cannula (HFNC) as primary intervention in patients with acute hypoxemic respiratory failure (AHRF) are still a matter in debate. Our objective was to compare HFNC therapy versus conventional oxygen therapy (COT) in the prevention of endotracheal intubation in this group of patients. METHODS: An open-label, controlled and single-centre clinical trial was conducted in patients with severe AHRF, defined by a PaO2/FIO2 ratio ⩽200, to compare HFNC with a control group (CG) treated by COT delivered through a face mask, with the need to perform intubation as the primary outcome. The secondary outcomes included tolerance of the HFNC device and to look for the predictive factors for intubation in these patients. RESULTS: A total of 46 patients were included (22 in the COT group and 24 in the HFNC group) 48% of whom needed intubation: 63% in the COT group and 33% in the HFNC group, with significant differences both in intention to treat [χ2 = 4.2; p = 0.04, relative risk (RR) = 0.5; confidence interval (CI) 95%: 0.3-1.0] and also in treatment analysis (χ2 = 4.7; p = 0.03; RR = 0.5; IC 95%: 0.3-0.9) We obtained a number needed to treat (NNT) = 3 patients treated to avoid an intubation. Intubation occurred significantly later in the HFNC group. Estimated PaO2/FIO2, respiratory rate and dyspnea were significantly better in the HFNC group. Patients treated with HFNC who required intubation presented significant worsening after the first 8 h, as compared with non-intubated HFNC group patients. Mortality was 22% with no differences. The HFNC group patients were hospitalized for almost half of the time in the intensive care unit (ICU) and in the ward, with significantly less hospital length of stay. A total of 14 patients in the HFNC group (58%) complained of excessive heat and 17% of noise; 3 patients did not tolerate HFNC. CONCLUSION: Patients with severe acute hypoxemic respiratory failure who tolerate HFNC present a significantly lower need for endotracheal intubation compared with conventional oxygen therapy. CLINICAL TRIAL REGISTER: EUDRA CT number: 2012-001671-36The reviews of this paper are available via the supplemental material section.

COVID-19 challenge for modern medicine.

Coronaviruses cause disease in animals and people around the world. Human coronaviruses (HCoV) are mainly known to cause infections of the upper and lower respiratory tract but the symptoms may also involve the nervous and digestive systems. Since the beginning of December 2019, there has been an epidemic of SARS-CoV-2, which was originally referred to as 2019-nCoV. The most common symptoms are fever and cough, fatigue, sputum production, dyspnea, myalgia, arthralgia or sore throat, headache, nausea, vomiting or diarrhea (30%). The best prevention is to avoid exposure. In addition, contact per-sons should be subjected to mandatory quarantine. COVID-19 patients should be treated in specialist centers. A significant number of patients with pneumonia require passive oxygen therapy. Non-invasive ventilation and high-flow nasal oxygen therapy can be applied in mild and moderate non-hypercapnia cases. A lung-saving ventilation strategy must be implemented in acute respiratory distress syndrome and mechanically ventilated patients. Extracorporeal membrane oxygenation is a highly specialized method, available only in selected centers and not applicable to a significant number of cases. Specific pharmacological treatment for COVID-19 is not currently available. Modern medicine is gearing up to fight the new coronavirus pandemic. The key is a holistic approach to the patient including, primar-ily, the use of personal protective equipment to reduce the risk of further virus transmission, as well as patient management, which consists in both quarantine and, in the absence of specific pharmacological therapy, symptomatic treatment.

Pulse oximetric saturation to fraction of inspired oxygen (SpO2/FIO2) ratio 24 hours after high-flow nasal cannula (HFNC) initiation is a good predictor of HFNC therapy in patients with acute exacerbation of interstitial lung disease.

BACKGROUND: High-flow nasal cannula (HFNC) oxygen therapy provides effective respiratory management in patients with hypoxemic respiratory failure. However, the efficacy and tolerability of HFNC for patients with acute exacerbation of interstitial lung disease (AE-ILD) have not been established. This study was performed to assess the efficacy and tolerability of HFNC for patients with AE-ILD and identify the early predictors of the outcome of HFNC treatment. METHODS: We retrospectively reviewed the records of patients with AE-ILD who underwent HFNC. Overall survival, the success rate of HFNC treatment, adverse events, temporary interruption of treatment, discontinuation of treatment at the patient's request, and predictors of the outcome of HFNC treatment were evaluated. RESULTS: A total of 66 patients were analyzed. Of these, 26 patients (39.4%) showed improved oxygenation and were successfully withdrawn from HFNC. The 30-day survival rate was 48.5%. No discontinuations at the patient's request were observed, and no serious adverse events occurred. The pulse oximetric saturation to fraction of inspired oxygen (SpO2/FIO2) ratio 24 h after initiating HFNC showed high prediction accuracy (area under the receiver operating characteristic curve, 0.802) for successful HFNC treatment. In the multivariate logistic regression analysis, an SpO2/FIO2 ratio of at least 170.9 at 24 h after initiation was significantly associated with successful HFNC treatment (odds ratio, 51.3; 95% confidence interval, 6.13-430; p < 0.001). CONCLUSIONS: HFNC was well tolerated in patients with AE-ILD, suggesting that HFNC is a reasonable respiratory management for these patients. The SpO2/FIO2 ratio 24 h after initiating HFNC was a good predictor of successful HFNC treatment. The reviews of this paper are available via the supplemental material section.

The Effect of High-Flow Nasal Oxygen Therapy on Postoperative Pulmonary Complications and Hospital Length of Stay in Postoperative Patients: A Systematic Review and Meta-Analysis.

OBJECTIVE: To evaluate the effect of high-flow nasal cannula oxygen (HFNO) therapy on hospital length of stay (LOS) and postoperative pulmonary complications (PPCs) in adult postoperative patients. DATA SOURCES: PubMed, Embase, the Cochrane Library, Web of Science of Studies, China National Knowledge Index, and Wan Fang databases were searched until July 2018. STUDY SELECTION: Randomized controlled trials (RCTs) comparing HFNO with conventional oxygen therapy or noninvasive mechanical ventilation in adult postoperative patients were included. The primary outcomes were hospital LOS and PPCs; short-term mortality (defined as intensive care unit, hospital, or 28-day mortality) and intubation rate were the secondary outcomes. DATA EXTRACTION: Demographic variables, high-flow oxygen therapy application, effects, and side effects were retrieved. Data were analyzed by the methods recommended by the Cochrane Collaboration. The strength of evidence was assessed by the Grading of Recommendations Assessment, Development and Evaluation. Random errors were evaluated with trial sequential analysis. DATA SYNTHESIS: Fourteen studies (2568 patients) met the inclusion criteria and were included. Compared to the control group, the pooled effect showed that HFNO was significantly associated with a shorter hospital stay (mean difference: -0.81; 95% confidence interval [CI]: -1.34 to -0.29, P = .002), but not mortality (risk ratio [RR]: 1.0, 95% CI: 0.63 to 1.59, P = 1.0). Weak evidence of a reduction in reintubation rate (RR: 0.76, 95% CI: 0.57-1.01, P = .06) and PPC rate (RR: 0.89, 95% CI: 0.75-1.06, P = .18) with HFNO versus control group was recorded. CONCLUSIONS: The available RCTs suggest that, among the adult postoperative patients, HFNO therapy compared to the control group significantly reduces hospital LOS.

Effect of Oxygen Therapy on Cardiovascular Outcomes in Relation to Baseline Oxygen Saturation.

OBJECTIVES: The aim of this study was to determine the effect of supplemental oxygen in patients with myocardial infarction (MI) on the composite of all-cause death, rehospitalization with MI, or heart failure related to baseline oxygen saturation. A secondary objective was to investigate outcomes in patients developing hypoxemia. BACKGROUND: In the DETO2X-AMI (Determination of the Role of Oxygen in Suspected Acute Myocardial Infarction) trial, 6,629 normoxemic patients with suspected MI were randomized to oxygen at 6 l/min for 6 to 12 h or ambient air. METHODS: The study population of 5,010 patients with confirmed MI was divided by baseline oxygen saturation into a low-normal (90% to 94%) and a high-normal (95% to 100%) cohort. Outcomes are reported within 1 year. To increase power, all follow-up time (between 1 and 4 years) was included post hoc, and interaction analyses were performed with oxygen saturation as a continuous covariate. RESULTS: The composite endpoint of all-cause death, rehospitalization with MI, or heart failure occurred significantly more often in patients in the low-normal cohort (17.3%) compared with those in the high-normal cohort (9.5%) (p < 0.001), and most often in patients developing hypoxemia (23.6%). Oxygen therapy compared with ambient air was not associated with improved outcomes regardless of baseline oxygen saturation (interaction p values: composite endpoint, p = 0.79; all-cause death, p = 0.33; rehospitalization with MI, p = 0.86; hospitalization for heart failure, p = 0.35). CONCLUSIONS: Irrespective of oxygen saturation at baseline, we found no clinically relevant beneficial effect of routine oxygen therapy in normoxemic patients with MI regarding cardiovascular outcomes. Low-normal baseline oxygen saturation or development of hypoxemia was identified as an independent marker of poor prognosis. (An Efficacy and Outcome Study of Supplemental Oxygen Treatment in Patients With Suspected Myocardial Infarction; NCT01787110).

Higher versus lower fraction of inspired oxygen or targets of arterial oxygenation for adults admitted to the intensive care unit.

BACKGROUND: The mainstay treatment for hypoxaemia is oxygen therapy, which is given to the vast majority of adults admitted to the intensive care unit (ICU). The practice of oxygen administration has been liberal, which may result in hyperoxaemia. Some studies have indicated an association between hyperoxaemia and mortality, whilst other studies have not. The ideal target for supplemental oxygen for adults admitted to the ICU is uncertain. Despite a lack of robust evidence of effectiveness, oxygen administration is widely recommended in international clinical practice guidelines. The potential benefit of supplemental oxygen must be weighed against the potentially harmful effects of hyperoxaemia. OBJECTIVES: To assess the benefits and harms of higher versus lower fraction of inspired oxygen or targets of arterial oxygenation for adults admitted to the ICU. SEARCH METHODS: We identified trials through electronic searches of CENTRAL, MEDLINE, Embase, Science Citation Index Expanded, BIOSIS Previews, CINAHL, and LILACS. We searched for ongoing or unpublished trials in clinical trials registers. We also scanned the reference lists of included studies. We ran the searches in December 2018. SELECTION CRITERIA: We included randomized controlled trials (RCTs) that compared higher versus lower fraction of inspired oxygen or targets of arterial oxygenation for adults admitted to the ICU. We included trials irrespective of publication type, publication status, and language. We included trials with a difference between the intervention and control groups of a minimum 1 kPa in partial pressure of arterial oxygen (PaO2), minimum 10% in fraction of inspired oxygen (FiO2), or minimum 2% in arterial oxygen saturation of haemoglobin/non-invasive peripheral oxygen saturation (SaO2/SpO2). We excluded trials randomizing participants to hypoxaemia (FiO2 below 0.21, SaO2/SpO2 below 80%, and PaO2 below 6 kPa) and to hyperbaric oxygen. DATA COLLECTION AND ANALYSIS: Three review authors independently, and in pairs, screened the references retrieved in the literature searches and extracted data. Our primary outcomes were all-cause mortality, the proportion of participants with one or more serious adverse events, and quality of life. None of the trials reported the proportion of participants with one or more serious adverse events according to the International Conference on Harmonisation Good Clinical Practice (ICH-GCP) criteria. Nonetheless, most trials reported several serious adverse events. We therefore included an analysis of the effect of higher versus lower fraction of inspired oxygen, or targets using the highest reported proportion of participants with a serious adverse event in each trial. Our secondary outcomes were lung injury, acute myocardial infarction, stroke, and sepsis. None of the trials reported on lung injury as a composite outcome, however some trials reported on acute respiratory distress syndrome (ARDS) and pneumonia. We included an analysis of the effect of higher versus lower fraction of inspired oxygen or targets using the highest reported proportion of participants with ARDS or pneumonia in each trial. To assess the risk of systematic errors, we evaluated the risk of bias of the included trials. We used GRADE to assess the overall certainty of the evidence. MAIN RESULTS: We included 10 RCTs (1458 participants), seven of which reported relevant outcomes for this review (1285 participants). All included trials had an overall high risk of bias, whilst two trials had a low risk of bias for all domains except blinding of participants and personnel. Meta-analysis indicated harm from higher fraction of inspired oxygen or targets as compared with lower fraction or targets of arterial oxygenation regarding mortality at the time point closest to three months (risk ratio (RR) 1.18, 95% confidence interval (CI) 1.01 to 1.37; I2 = 0%; 4 trials; 1135 participants; very low-certainty evidence). Meta-analysis indicated harm from higher fraction of inspired oxygen or targets as compared with lower fraction or targets of arterial oxygenation regarding serious adverse events at the time point closest to three months (estimated highest proportion of specific serious adverse events in each trial RR 1.13, 95% CI 1.04 to 1.23; I2 = 0%; 1234 participants; 6 trials; very low-certainty evidence). These findings should be interpreted with caution given that they are based on very low-certainty evidence. None of the included trials reported any data on quality of life at any time point. Meta-analysis indicated no evidence of a difference between higher fraction of inspired oxygen or targets as compared with lower fraction or targets of arterial oxygenation on lung injury at the time point closest to three months (estimated highest reported proportion of lung injury RR 1.03, 95% CI 0.78 to 1.36; I2 = 0%; 1167 participants; 5 trials; very low-certainty evidence). None of the included trials reported any data on acute myocardial infarction or stroke, and only one trial reported data on the effects on sepsis. AUTHORS' CONCLUSIONS: We are very uncertain about the effects of higher versus lower fraction of inspired oxygen or targets of arterial oxygenation for adults admitted to the ICU on all-cause mortality, serious adverse events, and lung injuries at the time point closest to three months due to very low-certainty evidence. Our results indicate that oxygen supplementation with higher versus lower fractions or oxygenation targets may increase mortality. None of the trials reported the proportion of participants with one or more serious adverse events according to the ICH-GCP criteria, however we found that the trials reported an increase in the number of serious adverse events with higher fractions or oxygenation targets. The effects on quality of life, acute myocardial infarction, stroke, and sepsis are unknown due to insufficient data.

Impact of hyperoxia on patients hospitalized in an intensive care unit for acute heart failure.

BACKGROUND: Oxygen therapy remains a cornerstone of treatment for acute heart failure in patients with pulmonary congestion. While avoiding hypoxaemia has long been a goal of critical care practitioners, less attention has been paid to the potential hazard related to excessive hyperoxia. AIM: To evaluate the impact of early hyperoxia exposure among critically ill patients hospitalized in an intensive care unit for acute heart failure. METHODS: In this preliminary study conducted in a Parisian intensive care unit, we assessed patients with acute heart failure admitted with pulmonary congestion and treated with oxygen therapy from 1 January 2015 to 31 December 2016. The hyperoxia group was defined by having at least one partial pressure of oxygen measurement>100mmHg on the first day following admission to the intensive care unit. The primary endpoint was 30-day all-cause mortality. Secondary endpoints were 30-day unplanned hospital admissions, occurrence of infections and intensive care unit and hospital lengths of stay. RESULTS: Seventy-five patients were included. Forty-three patients (57.3%) presented hyperoxia, whereas 32 patients (42.7%) did not (control group). The baseline clinical characteristics did not differ between the two groups. The primary endpoint was not statistically different between the two groups (14.0% in the hyperoxia group vs 18.8% in the control group; P=0.85). The secondary endpoints were also not significantly different between the two groups. In the multivariable analysis, hyperoxia was not associated with increased 30-day mortality (odds ratio 0.77, 95% confidence interval 0.24-2.41). CONCLUSION: In patients referred to an intensive care unit for acute heart failure, we did not find any difference in outcomes according to the presence of hyperoxia.

PURL: Supplemental oxygen: More isn't always better.

A recent study says that in certain populations, supplemental oxygen above certain levels can increase mortality.

Oxygen systems to improve clinical care and outcomes for children and neonates: A stepped-wedge cluster-randomised trial in Nigeria.

BACKGROUND: Improving oxygen systems may improve clinical outcomes for hospitalised children with acute lower respiratory infection (ALRI). This paper reports the effects of an improved oxygen system on mortality and clinical practices in 12 general, paediatric, and maternity hospitals in southwest Nigeria. METHODS AND FINDINGS: We conducted an unblinded stepped-wedge cluster-randomised trial comparing three study periods: baseline (usual care), pulse oximetry introduction, and stepped introduction of a multifaceted oxygen system. We collected data from clinical records of all admitted neonates (<28 days old) and children (28 days to 14 years old). Primary analysis compared the full oxygen system period to the pulse oximetry period and evaluated odds of death for children, children with ALRI, neonates, and preterm neonates using mixed-effects logistic regression. Secondary analyses included the baseline period (enabling evaluation of pulse oximetry introduction) and evaluated mortality and practice outcomes on additional subgroups. Three hospitals received the oxygen system intervention at 4-month intervals. Primary analysis included 7,716 neonates and 17,143 children admitted during the 2-year stepped crossover period (November 2015 to October 2017). Compared to the pulse oximetry period, the full oxygen system had no association with death for children (adjusted odds ratio [aOR] 1.06; 95% confidence interval [CI] 0.77-1.46; p = 0.721) or children with ALRI (aOR 1.09; 95% CI 0.50-2.41; p = 0.824) and was associated with an increased risk of death for neonates overall (aOR 1.45; 95% CI 1.04-2.00; p = 0.026) but not preterm/low-birth-weight neonates (aOR 1.30; 95% CI 0.76-2.23; p = 0.366). Secondary analyses suggested that the introduction of pulse oximetry improved oxygen practices prior to implementation of the full oxygen system and was associated with lower odds of death for children with ALRI (aOR 0.33; 95% CI 0.12-0.92; p = 0.035) but not for children, preterm neonates, or neonates overall (aOR 0.97, 95% CI 0.60-1.58, p = 0.913; aOR 1.12, 95% CI 0.56-2.26, p = 0.762; aOR 0.90, 95% CI 0.57-1.43, p = 0.651). Limitations of our study are a lower-than-anticipated power to detect change in mortality outcomes (low event rates, low participant numbers, high intracluster correlation) and major contextual changes related to the 2016-2017 Nigerian economic recession that influenced care-seeking and hospital function during the study period, potentially confounding mortality outcomes. CONCLUSIONS: We observed no mortality benefit for children and a possible higher risk of neonatal death following the introduction of a multifaceted oxygen system compared to introducing pulse oximetry alone. Where some oxygen is available, pulse oximetry may improve oxygen usage and clinical outcomes for children with ALRI. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry: ACTRN12617000341325.

Characteristics and outcome of patients set up on high-flow oxygen therapy at home.

BACKGROUND: High-flow oxygen therapy (HFOT) is increasingly used for acute respiratory failure. Few data support its use at home for the treatment of chronic respiratory failure. Our aim was to report the pattern of the use of long-term HFOT in our center and the outcome of patients setup on long-term HFOT. METHODS: A retrospective monocentric study including all patients setup on long-term HFOT between January 2011 and April 2018 in Rouen University Hospital was carried out. Patients were divided into two groups, patients with hypoxemic respiratory failure treated with nasal HFOT (nHFOT) and tracheotomized patients treated with tracheal HFOT (tHFOT). RESULTS: A total of 71 patients were established on long-term HFOT. Out of these 43 (61%) were included in the nHFOT group and 28 (39%) were included in the tHFOT group. In the nHFOT group, underlying respiratory diseases were interstitial lung disease (n = 15, 35%), pulmonary hypertension (n = 12, 28%), lung cancer (n = 9, 21%), and chronic airway disease (n = 7, 16%). In the tHFOT group, the number of admissions for exacerbation decreased by -0.78 per year (-2 to 0) (p = 0.045). In total, 51 (72%) patients were discharged to their homes and 20 (28%) went to a post-acute re-enablement facility. Median survival following HFOT was 7.5 months. Survival was significantly lower in the nHFOT group with a median survival of 3.6 months whereas median survival was not reached in the tHFOT group (p < 0.001). Monthly costs associated with home delivery of HFOT were €476 (296-533) with significant differences in costs between the nHFOT group of €520 (408-628) and costs in the tHFOT group of €296 (261-475) (p < 0.001). CONCLUSIONS: The use of long-term HFOT allows very severe patients to be discharged at a reasonable cost from acute care facilities. The reviews of this paper are available via the supplementary material section.

The Association between Supraphysiologic Arterial Oxygen Levels and Mortality in Critically Ill Patients. A Multicenter Observational Cohort Study.

Rationale: There is conflicting evidence on harm related to exposure to supraphysiologic PaO2 (hyperoxemia) in critically ill patients.Objectives: To examine the association between longitudinal exposure to hyperoxemia and mortality in patients admitted to ICUs in five United Kingdom university hospitals.Methods: A retrospective cohort of ICU admissions between January 31, 2014, and December 31, 2018, from the National Institute of Health Research Critical Care Health Informatics Collaborative was studied. Multivariable logistic regression modeled death in ICU by exposure to hyperoxemia.Measurements and Main Results: Subsets with oxygen exposure windows of 0 to 1, 0 to 3, 0 to 5, and 0 to 7 days were evaluated, capturing 19,515, 10,525, 6,360, and 4,296 patients, respectively. Hyperoxemia dose was defined as the area between the PaO2 time curve and a boundary of 13.3 kPa (100 mm Hg) divided by the hours of potential exposure (24, 72, 120, or 168 h). An association was found between exposure to hyperoxemia and ICU mortality for exposure windows of 0 to 1 days (odds ratio [OR], 1.15; 95% compatibility interval [CI], 0.95-1.38; P = 0.15), 0 to 3 days (OR 1.35; 95% CI, 1.04-1.74; P = 0.02), 0 to 5 days (OR, 1.5; 95% CI, 1.07-2.13; P = 0.02), and 0 to 7 days (OR, 1.74; 95% CI, 1.11-2.72; P = 0.02). However, a dose-response relationship was not observed. There was no evidence to support a differential effect between hyperoxemia and either a respiratory diagnosis or mechanical ventilation.Conclusions: An association between hyperoxemia and mortality was observed in our large, unselected multicenter cohort. The absence of a dose-response relationship weakens causal interpretation. Further experimental research is warranted to elucidate this important question.

High flow nasal cannula oxygen therapy versus non-invasive ventilation for chronic obstructive pulmonary disease with acute-moderate hypercapnic respiratory failure: an observational cohort study.

Background: High-flow nasal cannula (HFNC) oxygen therapy in acute hypoxic respiratory failure is becoming increasingly popular. However, evidence to support the use of HFNC in acute respiratory failure (ARF) with hypercapnia is limited. Methods: Chronic obstructive pulmonary disease (COPD) patients with moderate hypercapnic ARF (arterial blood gas pH 7.25-7.35, PaCO2>50 mmHg) who received HFNC or non-invasive ventilation (NIV) in the intensive care uint from April 2016 to March 2018 were analyzed retrospectively. The endpoint was treatment failure, defined as either invasive ventilation, or a switch to the other study treatment (NIV for patients in the NFNC group, and vice-versa), and 28-day mortality. Results: Eighty-two COPD patients (39 in the HFNC group and 43 in the NIV group) were enrolled in this study. The mean age was 71.8±8.2 and 54 patients (65.9%) were male. The treatment failed in 11 out of 39 patients with HFNC (28.2%) and in 17 of 43 patients with NIV (39.5%) (P=0.268). No significant differences were found for 28-day mortality (15.4% in the HFNC group and 14% in the NIV group, P=0.824). During the first 24 hrs of treatment, the number of nursing airway care interventions in the HFNC group was significantly less than in the NIV group, while the duration of device application was significantly longer in the HFNC group (all P<0.05). Skin breakdown was significantly more common in the NIV group (20.9% vs 5.1%, P<0.05). Conclusion: Among COPD patients with moderate hypercarbic ARF, the use of HFNC compared with NIV did not result in increased rates of treatment failure, while there were fewer nursing interventions and skin breakdown episodes reported in the HFNC group.

Oxygen therapy for patients with acute myocardial infarction: a meta-analysis of randomized controlled clinical trials.

BACKGROUND: Oxygen therapy is widely used for patients with acute myocardial infarction (AMI). However, there is uncertainty about its safety and benefits. The aim of this study is to perform a systematic review and meta-analysis to assess the effectiveness and safety of oxygen therapy for patients with AMI. MATERIALS AND METHODS: We searched MEDLINE, CINAHL, EMBASE, Cochrane Central Register of Controlled Trials from 1 January 1967, through 31 December 2017. We included randomized controlled clinical trials that used oxygen therapy for patients with suspected or confirmed AMI less than 24 h of symptoms onset. Hyperbaric and aqueous oxygen therapy trials were excluded. RESULTS: A total of six randomized controlled clinical trials with 7190 individuals were included in this meta-analysis. Compared with no oxygen group, oxygen therapy did not reduce the risk of all-cause mortality [pooled risk ratio (RR): 1.06, 95% confidence interval (CI): 0.56-2.02, P=0.19], recurrent myocardial infarction (pooled RR: 1.57, 95% CI: 0.88-2.80, P=0.18), and pain (pooled RR: 0.97, 95% CI: 0.82-1.14, P=0.25). CONCLUSION: In this meta-analysis, oxygen inhalation did not benefit patients with AMI with normal oxygen saturation.

Long-term effects of oxygen-enriched high-flow nasal cannula treatment in COPD patients with chronic hypoxemic respiratory failure.

BACKGROUND: This study investigated the long-term effects of humidified high-flow nasal cannula (HFNC) in COPD patients with chronic hypoxemic respiratory failure treated with long-term oxygen therapy (LTOT). PATIENTS AND METHODS: A total of 200 patients were randomized into usual care ± HFNC. At inclusion, acute exacerbation of COPD (AECOPD) and hospital admissions 1 year before inclusion, modified Medical Research Council (mMRC) score, St George's Respiratory Questionnaire (SGRQ), forced expiratory volume in 1 second (FEV1), 6-minute walk test (6MWT) and arterial carbon dioxide (PaCO2) were recorded. Patients completed phone interviews at 1, 3 and 9 months assessing mMRC score and AECOPD since the last contact. At on-site visits (6 and 12 months), mMRC, number of AECOPD since last contact and SGRQ were registered and FEV1, FEV1%, PaCO2 and, at 12 months, 6MWT were reassessed. Hospital admissions during the study period were obtained from hospital records. Hours of the use of HFNC were retrieved from the high-flow device. RESULTS: The average daily use of HFNC was 6 hours/day. The HFNC group had a lower AECOPD rate (3.12 versus 4.95/patient/year, p<0.001). Modeled hospital admission rates were 0.79 versus 1.39/patient/year for 12- versus 1-month use of HFNC, respectively (p<0.001). The HFNC group had improved mMRC scores from 3 months onward (p<0.001) and improved SGRQ at 6 and 12 months (p=0.002, p=0.033) and PaCO2 (p=0.005) and 6MWT (p=0.005) at 12 months. There was no difference in all-cause mortality. CONCLUSION: HFNC treatment reduced AECOPD, hospital admissions and symptoms in COPD patients with hypoxic failure.