Oxygen therapy limiting peripheral oxygen saturation to 89-93% is associated with a better survival prognosis for critically ill COVID-19 patients at high altitudes.

Patients admitted to the Intensive Care Unit (ICU) with acute hypoxemic respiratory failure automatically receive oxygen therapy to improve inspiratory oxygen fraction (FiO2). Supplemental oxygen is the most prescribed drug for critically ill patients regardless of altitude of residence. In high altitude dwellers (i.e. in La Paz [≈3,400 m] and El Alto [≈4,150 m] in Bolivia), a peripheral oxygen saturation (SatpO2) of 89-95% and an arterial partial pressure of oxygen (PaO2) of 50-67 mmHg (lower as altitude rises), are considered normal values ​​for arterial blood. Consequently, it has been suggested that limiting oxygen therapy to maintain SatpO2 around normoxia may help avoid episodes of hypoxemia, hyperoxemia, intermittent hypoxemia, and ultimately, mortality. In this study, we evaluated the impact of oxygen therapy on the mortality of critically ill COVID-19 patients who permanently live at high altitudes. A multicenter cross-sectional descriptive observational study was performed on 100 patients admitted to the ICU at the "Clinica Los Andes" (in La Paz city) and "Agramont" and "Del Norte" Hospitals (in El Alto city). Our results show that: 1) as expected, fatal cases were detected only in patients who required intubation and connection to invasive mechanical ventilation as a last resort to overcome their life-threatening desaturation; 2) among intubated patients, prolonged periods in normoxia are associated with survival, prolonged periods in hypoxemia are associated with death, and time spent in hyperoxemia shows no association with survival or mortality; 3) the oxygenation limits required to effectively support the intubated patients' survival in the ICU are between 89% and 93%; 4) among intubated patients with similar periods of normoxemic oxygenation, those with better SOFA scores survive; and 5) a lower frequency of observable reoxygenation events is not associated with survival. In conclusion, our findings indicate that high-altitude patients entering an ICU at altitudes of 3,400 - 4,150 m should undergo oxygen therapy to maintain oxygenation levels between 89 and 93 %.

Evaluation of an Initiative to Decrease the Use of Oxygen Supplementation for Category II Fetal Heart Rate Tracings.

OBJECTIVE: To examine compliance with a guideline to reduce exposure to supplemental oxygen for category II fetal heart rate (FHR) tracings in normally oxygenated laboring patients. METHODS: All patients in labor in an urban academic medical center from January 1 to July 31, 2020 were assessed. The preintervention group included those who delivered from January 1 to March 19, 2020. On March 20, 2020, a new guideline took effect that recommended no maternal supplemental oxygen for category II FHR tracings. The postintervention group delivered from March 20 to July 31, 2020. Exclusion criteria were planned cesarean delivery, multiple gestations, delivery at less than 24 weeks of gestation, intrauterine fetal death, and patients who received supplemental oxygen for an oxygen saturation lower than 95%. The primary outcome was the percentage of patients who received oxygen in labor analyzed by control charts and the rules of special cause variation. Chi-squared and t tests were used for secondary outcome assessment. P<.05 was considered significant. RESULTS: A total of 1,333 patients were included, 474 patients in the preintervention group and 859 in the postintervention group. Oxygen was administered to 22.6% of patients before guideline implementation, compared with 0.6% after the guideline. Special cause variation was detected with an 8-point shift starting the month that the guideline was implemented, indicating statistical significance. There were no differences in any studied secondary maternal or fetal outcomes, although our statistical power to detect differences in infrequent outcomes was limited. CONCLUSION: This quality-improvement study demonstrated significant adherence to the guideline that supplemental oxygen would no longer be given to patients with category II FHR tracings in the absence of maternal hypoxemia, with no significant change in maternal or perinatal outcomes.

A randomized crossover pilot study comparing the efficacy of an auto-demand oxygen delivery system with that of a conventional demand oxygen delivery system in patients with chronic respiratory failure.

INTRODUCTION: : When using portable oxygen, a demand oxygen delivery system (DODS), which senses the beginning of inhalation and delivers a bolus of oxygen, is often used. However, conventional DODS may not supply sufficient oxygen when reduced tidal flow fails to trigger the flow sensor. Recently, "auto-DODS," which detects the negative pressure of inhalation and switches among 3 trigger sensitivity levels (standard, high, and extra high), has been developed to improve the efficacy of oxygenation. An auto-DODS can also supply pulsed-flow oxygen when it detects apnea, whereas a conventional DODS has only standard sensitivity. This randomized, open-label, crossover pilot study compared the performance of an auto-DODS with that of a conventional DODS. METHODS: : We recruited patients with chronic obstructive pulmonary disease (COPD) or interstitial pneumonia receiving long-term oxygen therapy. Interventions were performed on 2 different days for each participant. On each day, an auto-DODS or a conventional DODS were tested at rest for 30 minutes and during the 6-minute walk test. The primary outcome was mean oxygen saturation (SpO2). Secondary outcomes were the ratios of time for each sensitivity level and pulsed-flow oxygen when using the auto-DODS, total time desaturated below SpO2 90%, percentage of time desaturated below SpO2 90%, minimum SpO2, mean and maximum pulse rate, six-minute walk distance, recovery time after 6-minute walk test, modified Borg scale, comfort, and discomfort index. RESULTS: : When using the auto-DODS at rest, a high or extra high sensitivity level was observed in addition to standard sensitivity in 6 of 8 participants. During the 6-minute walk test, only standard sensitivity was observed in 6 participants. Mean SpO2 differences between the auto-DODS and conventional DODS at rest and during the 6-minute walk test were -0.6 [-4.5, 3.4] and 0.0 [-2.5, 2.5] ([95% confidence interval]), respectively, neither of which were significant (P = .73 and P = .99). There were no significant differences in secondary outcomes. There were no adverse events when using the auto-DODS. CONCLUSIONS: : This study showed that the auto-DODS did not show superiority in oxygenation either at rest or during exercise compared to a conventional DODS. The auto-DODS was shown to supply oxygen safely and detect inhalations with various trigger sensitivities.

Is oxygen therapy beneficial for normoxemic patients with acute heart failure? A propensity score matched study.

BACKGROUND: The clinical efficiency of routine oxygen therapy is uncertain in patients with acute heart failure (AHF) who do not have hypoxemia. The aim of this study was to investigate the association between oxygen therapy and clinical outcomes in normoxemic patients hospitalized with AHF using real-world data. METHODS: Normoxemic patients diagnosed with AHF on ICU admission from the electronic ICU (eICU) Collaborative Research Database were included in the current study, in which the study population was divided into the oxygen therapy group and the ambient-air group. Propensity score matching (PSM) was applied to create a balanced covariate distribution between patients receiving supplemental oxygen and those exposed to ambient air. Linear regression and logistic regression models were performed to assess the associations between oxygen therapy and length of stay (LOS), and all-cause in-hospital as well as ICU mortality rates, respectively. A series of sensitivity and subgroup analyses were conducted to further validate the robustness of our findings. RESULTS: A total of 2922 normoxemic patients with AHF were finally included in the analysis. Overall, 42.1% (1230/2922) patients were exposed to oxygen therapy, and 57.9% (1692/2922) patients did not receive oxygen therapy (defined as the ambient-air group). After PSM analysis, 1122 pairs of patients were matched: each patient receiving oxygen therapy was matched with a patient without receiving supplemental oxygen. The multivariable logistic model showed that there was no significant interaction between the ambient air and oxygen group for all-cause in-hospital mortality [odds ratio (OR) 1.30; 95% confidence interval (CI) 0.92-1.82; P = 0.138] or ICU mortality (OR 1.39; 95% CI 0.83-2.32; P = 0.206) in the post-PSM cohorts. In addition, linear regression analysis revealed that oxygen therapy was associated with prolonged ICU LOS (OR 1.11; 95% CI 1.06-1.15; P <  0.001) and hospital LOS (OR 1.06; 95% CI 1.01-1.10; P = 0.009) after PSM. Furthermore, the absence of an effect of supplemental oxygen on mortality was consistent in all subgroups. CONCLUSION: Routine use of supplemental oxygen in AHF patients without hypoxemia was not found to reduce all-cause in-hospital mortality or ICU mortality.

Clinical impact of implementing humidified high-flow nasal cannula on interhospital transport among children admitted to a PICU with respiratory distress: a cohort study.

BACKGROUND: There is a limited evidence for humidified high-flow nasal cannula (HHFNC) use on inter-hospital transport. Despite this, its use during transport is increasing in children with respiratory distress worldwide. In 2015 HHFNC was implemented on a specialized pediatric retrieval team serving for Victoria. The aim of this study is to investigate the effect of the HHFNC implementation on the retrieval team on the paediatric intensive care unit (PICU) length of stay and respiratory support use. METHODS: We performed a cohort study using a comparative interrupted time-series approach controlling for patient and temporal covariates, and population-adjusted analysis. We studied 3022 children admitted to a PICU in Victoria with respiratory distress January 2010-December 2019. Patients were divided in pre-intervention era (2010-2014) and post-intervention era (2015-2019). RESULTS: 1006 children following interhospital transport and 2016 non-transport children were included. Median (IQR) age was 1.4 (0.7-4.5) years. Pneumonia (39.1%) and bronchiolitis (34.3%) were common. On retrieval, HHFNC was used in 5.0% (21/420) and 45.9% (269/586) in pre- and post-intervention era. In an unadjusted model, median (IQR) PICU length of stay was 2.2 (1.1-4.2) and 1.7 (0.9-3.2) days in the pre- and post-intervention era in transported children while the figures were 2.4 (1.3-4.9) and 2.1 (1.2-4.5) days in non-transport children. In the multivariable regression model, the intervention was associated with the reduced PICU length of stay (ratio 0.64, 95% confidential interval 0.49-0.83, p = 0.001) with the predicted reduction of PICU length of stay being - 10.6 h (95% confidential interval - 16.9 to - 4.3 h), and decreased respiratory support use (- 25.1 h, 95% confidential interval - 47.9 to - 2.3 h, p = 0.03). Sensitivity analyses including a model excluding less severe children showed similar results. In population-adjusted analyses, respiratory support use decreased from 4837 to 3477 person-hour per year in transported children over the study era, while the reduction was 594 (from 9553 to 8959) person-hour per year in non-transport children. With regard to the safety, there were no escalations of respiratory support mode during interhospital transport. CONCLUSIONS: The implementation of HHFNC on interhospital transport was associated with the reduced PICU length of stay and respiratory support use among PICU admissions with respiratory distress.

Non-invasive ventilation versus high-flow nasal oxygen for postextubation respiratory failure in ICU: a post-hoc analysis of a randomized clinical trial.

BACKGROUND: In intensive care units (ICUs), patients experiencing post-extubation respiratory failure have poor outcomes. The use of noninvasive ventilation (NIV) to treat post-extubation respiratory failure may increase the risk of death. This study aims at comparing mortality between patients treated with NIV alternating with high-flow nasal oxygen or high-flow nasal oxygen alone. METHODS: Post-hoc analysis of a multicenter, randomized, controlled trial focusing on patients who experienced post-extubation respiratory failure within the 7 days following extubation. Patients were classified in the NIV group or the high-flow nasal oxygen group according to oxygenation strategy used after the onset of post-extubation respiratory failure. Patients reintubated within the first hour after extubation and those promptly reintubated without prior treatment were excluded. The primary outcome was mortality at day 28 after the onset of post-extubation respiratory failure. RESULTS: Among 651 extubated patients, 158 (25%) experienced respiratory failure and 146 were included in the analysis. Mortality at day 28 was 18% (15/84) using NIV alternating with high-flow nasal oxygen and 29% (18/62) with high flow nasal oxygen alone (difference, - 11% [95% CI, - 25 to 2]; p = 0.12). Among the 46 patients with hypercapnia at the onset of respiratory failure, mortality at day 28 was 3% (1/33) with NIV and 31% (4/13) with high-flow nasal oxygen alone (difference, - 28% [95% CI, - 54 to - 6]; p = 0.006). The proportion of patients reintubated 48 h after the onset of post-extubation respiratory failure was 44% (37/84) with NIV and 52% (32/62) with high-flow nasal oxygen alone (p = 0.21). CONCLUSIONS: In patients with post-extubation respiratory failure, NIV alternating with high-flow nasal oxygen might not increase the risk of death. Trial registration number The trial was registered at http://www.clinicaltrials.gov with the registration number NCT03121482 the 20th April 2017.

Oxygen Therapy Lowers Right Ventricular Afterload in Experimental Acute Pulmonary Embolism.

OBJECTIVES: To investigate if oxygen could unload the right ventricle and improve right ventricle function in a porcine model mimicking intermediate-high risk acute pulmonary embolism. DESIGN: Controlled, blinded, animal study. SETTING: Tertiary university hospital, animal research laboratory. SUBJECTS: Female, Danish pigs (n = 16, approximately 60 kg). INTERVENTIONS: Acute autologous pulmonary embolism was induced until doubling of baseline mean pulmonary arterial pressure. Group 1 animals (n = 8) received increasing Fio2 (40%, 60%, and 100%) for time intervals of 15 minutes returning to atmospheric air between each level of Fio2. In group 2 (n = 8), the effects of Fio2 40% maintained over 75 minutes were studied. In both groups, pulmonary vasodilatation from inhaled nitric oxide (40 parts per million) was used as a positive control. MEASUREMENTS AND MAIN RESULTS: Effects were evaluated by biventricular pressure-volume loop recordings, right heart catheterization, and arterial and mixed venous blood gasses. Pulmonary embolism increased mean pulmonary arterial pressure from 15 ± 4 to 33 ± 6 mm Hg (p = 0.0002) and caused right ventricle dysfunction (p < 0.05) with troponin release (p < 0.0001). In group 1, increasing Fio2 lowered mean pulmonary arterial pressure (p < 0.0001) and pulmonary vascular resistance (p = 0.0056) and decreased right ventricle volumes (p = 0.0018) and right ventricle mechanical work (p = 0.034). Oxygenation was improved and pulmonary shunt was lowered (p < 0.0001). Maximal hemodynamic effects were seen at Fio2 40% with no additional benefit from higher fractions of oxygen. In group 2, the effects of Fio2 40% were persistent over 75 minutes. Supplemental oxygen showed the same pulmonary vasodilator efficacy as inhaled nitric oxide (40 parts per million). No adverse effects were observed. CONCLUSIONS: In a porcine model mimicking intermediate-high risk pulmonary embolism, oxygen therapy reduced right ventricle afterload and lowered right ventricle mechanical work. The effects were immediately present and persistent and were similar to inhaled nitric oxide. The intervention is easy and safe. The study motivates extended clinical evaluation of supplemental oxygen in acute pulmonary embolism.

Post-extubation oxygenation strategies in acute respiratory failure: a systematic review and network meta-analysis.

BACKGROUND: High-flow nasal cannula oxygenation (HFNC) and noninvasive positive-pressure ventilation (NPPV) possibly decrease tracheal reintubation rates better than conventional oxygen therapy (COT); however, few large-scale studies have compared HFNC and NPPV. We conducted a network meta-analysis (NMA) to compare the effectiveness of three post-extubation respiratory support devices (HFNC, NPPV, and COT) in reducing the mortality and reintubation risk. METHODS: The Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, and Ichushi databases were searched. COT, NPPV, and HFNC use were assessed in patients who were aged ≥ 16 years, underwent invasive mechanical ventilation for > 12 h for acute respiratory failure, and were scheduled for extubation after spontaneous breathing trials. The GRADE Working Group Approach was performed using a frequentist-based approach with multivariate random-effect meta-analysis. Short-term mortality and reintubation and post-extubation respiratory failure rates were compared. RESULTS: After evaluating 4631 records, 15 studies and 2600 patients were included. The main cause of acute hypoxic respiratory failure was pneumonia. Although NPPV/HFNC use did not significantly lower the mortality risk (relative risk [95% confidence interval] 0.75 [0.53-1.06] and 0.92 [0.67-1.27]; low and moderate certainty, respectively), HFNC use significantly lowered the reintubation risk (0.54 [0.32-0.89]; high certainty) compared to COT use. The associations of mortality with NPPV and HFNC use with respect to either outcome did not differ significantly (short-term mortality and reintubation, relative risk [95% confidence interval] 0.81 [0.61-1.08] and 1.02 [0.53-1.97]; moderate and very low certainty, respectively). CONCLUSION: NPPV or HFNC use may not reduce the risk of short-term mortality; however, they may reduce the risk of endotracheal reintubation. TRIAL REGISTRATION NUMBER AND DATE OF REGISTRATION: PROSPERO (registration number: CRD42020139112, 01/21/2020).

The occurrence of delayed neuropsychologic sequelae in acute carbon monoxide poisoning patients after treatment with hyperbaric or normobaric oxygen therapy.

ABSTRACT: This study aimed at assessing which one of the 2 therapies is better for treating carbon monoxide (CO) poisoning from the perspective of reducing delayed neuropsychologic sequelae (DNS).We used Taiwan's National Health Insurance Research Database (NHIRD) to conduct a nationwide population-based cohort study to assess which therapy is better for CO poisoning patients. To accurately identify patients with DNS, the definition of DNS is included neurological sequelae, and cognitive and psychological sequele. The independent variable was therapy and the dependent variable was DNS occurred within 1 year after discharge from a medical institution. The control variables were age, gender, the severity of CO poisoning, and comorbidities present before CO poisoning admission.The risk of developing DNS in patients treated with Hyperbaric Oxygen (HBO) was 1.87-fold (P < .001) than normobaric oxygen (NBO) therapy. The severity of CO poisoning and comorbidities were also found to have significant influences on the risk of developing DNS.HBO may be a risk therapy for treating CO poisoning.

Validity of ROX index in prediction of risk of intubation in patients with COVID-19 pneumonia.

INTRODUCTION: One important concern during the management of COVID-19 pneumonia patients with acute hypoxemic respiratory failure is early anticipation of the need for intubation. ROX is an index that can help in identification of patients with low and those with high risk of intubation. So, this study was planned to validate the diagnostic accuracy of the ROX index for prediction of COVID-19 pneumonia outcome (the need for intubation) and, in addition, to underline the significant association of the ROX index with clinical, radiological, demographic data. MATERIAL AND METHODS: Sixty-nine RT-PCR positive COVID-19 patients were enrolled. The following data were collected: medical history, clinical classification of COVID-19 infection, the ROX index measured daily and the outcome assessment. RESULTS: All patients with severe COVID-19 infection (100%) were intubated (50% of them on the 3rd day of admission), but only 38% of patients with moderate COVID-19 infection required intubation (all of them on the 3rd day of admission). The ROX index on the 1st day of admission was significantly associated with the presence of comorbidities, COVID-19 clinical classification, CT findings and intubation (p ≤ 0.001 for each of them). Regression analysis showed that sex and ROX.1 are the only significant independent predictors of intubation [AOR (95% CI): 16.9 (2.4- 117), 0.77 (0.69-0.86)], respectively. Cut-off point of the ROX index on the 1st day of admission was ≤ 25.26 (90.2% of sensitivity and 75% of specificity). CONCLUSIONS: ROX is a simple noninvasive promising tool for predicting discontinuation of high-flow oxygen therapy and could be used in the assessment of progress and the risk of intubation in COVID-19 patients with pneumonia.

An audit of oxygen supplementation in a large tertiary hospital - we should treat oxygen as any other drug.

Objectives: To examine the current state of practice of oxygen (O2) supplementation in adults hospitalized in a tertiary hospital admitted to medical-surgical floors.Methods: We recorded: the proportion of patients on O2; their peripheral O2 saturation (SpO2); if the SpO2 was within, above, or below the target range; if patients had an order for O2 supplementation and a target SpO2 range.Results: Among 811 hospitalized patients, 153 (19%) were on supplemental O2. Forty-nine percent were in the recommended range, 55% above, and 1% below. All patients with COPD on O2 supplementation had a SpO2 of more than 92% exposing them to the risk of hypercarbia. Only 43% of patients on oxygen had an associated order and only 52% of patients with an O2 order had an order for a goal SpO2 range.Conclusions: Our results demonstrate widespread hyperoxia among hospitalized patients and that oxygen, a very common therapy, is being administered frequently without any written order. These findings highlight the opportunity to implement safe prescribing measures for O2, similar to other prescribed medications.

A narrative review of hydrogen-oxygen mixture for medical purpose and the inhaler thereof.

Recent development regarding mixture of H2 (concentration of ~66%) with O2 (concentration of ~34%) for medical purpose, such as treatment of coronavirus disease-19 (COVID-19) patients, is introduced. Furthermore, the design principles of a hydrogen inhaler which generates mixture of hydrogen (~66%) with oxygen (~34%) for medical purpose are proposed. With the installation of the liquid blocking module and flame arresters, the air pathway of the hydrogen inhaler is divided by multiple isolation zones to prevent any unexpected explosion propagating from one zone to the other. An integrated filtering/cycling module is utilized to purify the impurity, and cool down the temperature of the electrolytic module to reduce the risk of the explosion. Moreover, a nebulizer is provided to selectively atomize the water into vapor which is then mixed with the filtered hydrogen-oxygen mix gas, such that the static electricity of a substance hardly occurs to reduce the risk of the explosion. Furthermore, hydrogen concentration detector is installed to reduce the risk of hydrogen leakage. Result shows that the hydrogen inhaler implementing the aforesaid design rules could effectively inhibit the explosion, even ignition at the outset of the hydrogen inhaler which outputs hydrogen-oxygen gas (approximately 66% hydrogen: 34% oxygen).

High flow nasal therapy versus noninvasive ventilation as initial ventilatory strategy in COPD exacerbation: a multicenter non-inferiority randomized trial.

BACKGROUND: The efficacy and safety of high flow nasal therapy (HFNT) in patients with acute hypercapnic exacerbation of chronic obstructive pulmonary disease (AECOPD) are unclear. Our aim was to evaluate the short-term effect of HFNT versus NIV in patients with mild-to-moderate AECOPD, with the hypothesis that HFNT is non-inferior to NIV on CO2 clearance after 2 h of treatment. METHODS: We performed a multicenter, non-inferiority randomized trial comparing HFNT and noninvasive ventilation (NIV) in nine centers in Italy. Patients were eligible if presented with mild-to-moderate AECOPD (arterial pH 7.25-7.35, PaCO2 ≥ 55 mmHg before ventilator support). Primary endpoint was the mean difference of PaCO2 from baseline to 2 h (non-inferiority margin 10 mmHg) in the per-protocol analysis. Main secondary endpoints were non-inferiority of HFNT to NIV in reducing PaCO2 at 6 h in the per-protocol and intention-to-treat analysis and rate of treatment changes. RESULTS: Seventy-nine patients were analyzed (80 patients randomized). Mean differences for PaCO2 reduction from baseline to 2 h were - 6.8 mmHg (± 8.7) in the HFNT and - 9.5 mmHg (± 8.5) in the NIV group (p = 0.404). By 6 h, 32% of patients (13 out of 40) in the HFNT group switched to NIV and one to invasive ventilation. HFNT was statistically non-inferior to NIV since the 95% confidence interval (CI) upper boundary of absolute difference in mean PaCO2 reduction did not reach the non-inferiority margin of 10 mmHg (absolute difference 2.7 mmHg; 1-sided 95% CI 6.1; p = 0.0003). Both treatments had a significant effect on PaCO2 reductions over time, and trends were similar between groups. Similar results were found in both per-protocol at 6 h and intention-to-treat analysis. CONCLUSIONS: HFNT was statistically non-inferior to NIV as initial ventilatory support in decreasing PaCO2 after 2 h of treatment in patients with mild-to-moderate AECOPD, considering a non-inferiority margin of 10 mmHg. However, 32% of patients receiving HFNT required NIV by 6 h. Further trials with superiority design should evaluate efficacy toward stronger patient-related outcomes and safety of HFNT in AECOPD. TRIAL REGISTRATION: The study was prospectively registered on December 12, 2017, in ClinicalTrials.gov (NCT03370666).

[Guideline for Long-Term Oxygen Therapy - S2k-Guideline Published by the German Respiratory Society]. / Leitlinie zur Langzeit-Sauerstofftherapie.

Long-term oxygen therapy is of great importance both for reducing mortality and for improving performance in patients with chronic lung diseases. The prerequisites for Long-term oxygen therapy are adequate diagnostics and clearly defined indication. A causal distinction into chronic hypoxaemic and hypercapnic respiratory failure is reasonable, from which the differential indication for non-invasive ventilation results.The revised guideline covers the diagnostics and indication of chronic lung and heart diseases, the role of oxygen in terminal illness and gives a detailed description of available oxygen devices. The guideline is intended to help avoid undersupply, oversupply and false prescriptions. Furthermore, the chapter "Postacute Oxygen Therapy" discusses the procedure, relevant in everyday life, but not yet clearly defined, for prescribing oxygen therapy for the home at the end of an inpatient stay. Another important point, the correct prescription of mobile oxygen systems, is also presented in the guideline. This document is a revised version of the guideline for longterm oxygen therapy and replaces the version of 2008.

The safety and effectiveness of heated humidified high-flow nasal cannula as an initial ventilation method in the treatment of neonatal respiratory distress syndrome: A protocol for systematic review and meta-analysis.

BACKGROUND: This study uses a method of systematic evaluation to evaluate the safety and effectiveness of heated humidified high-flow nasal cannula (HHHFNC) as an initial ventilation method in the treatment of neonatal respiratory distress syndrome (NRDS) scientifically. In the field of evidence-based medicine, this study provides a theoretical reference and basis for choosing appropriate initial non-invasive ventilation methods in the treatment of NRDS, thereby providing assistance for clinical treatment. METHODS: The main electronic network databases were searched by computer, including 4 Chinese databases: CNKI, WangFang Data, CQVIP, SinoMed and 3 English databases: PubMed, The Cochrane Library and EMBASE, the time range of retrieval from the beginning of each database to September 1, 2020. The content involves all the published randomized controlled trials on the effectiveness of HHHFNC compared with NCPAP as an initial ventilation method in the treatment of NRDS. Using a search method that combines medical subject words and free words. Based on the Cochrane risk bias assessment tool, 2 researchers independently screen the literature, and then extract the data we needed in the literature, and cross-check. If it is difficult to decide whether to include literature, then turning to a third researcher for help and making a final decision after discussion, and using RevMan 5.3 and STATA 13.0 to analyze the relative data. RESULTS: Based on the method of meta-analysis, this study analyzes the pre-determined outcome indicators through scientific statistical analysis, and compares the effectiveness and safety of HHHFNC compared with NCPAP as an initial ventilation method in the treatment of NRDS. All results will be published in peer-reviewed high-quality professional academic journals. CONCLUSION: Based on evidence-based medicine, this study will obtain the establishing evidence of comparison that the clinical effectiveness and safety of HHHFNC compared with NCPAP as an initial ventilation method in the treatment of NRDS through the existing data and data, which provides the evidence support of evidence-based medicine in the treatment of NRDS. OSF REGISTRATION NUMBER: September 17, 2020. osf.io/f6at4 (https://osf.io/f6at4).