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The newly developed portable oxygen concentrator with an auto-demand oxygen delivery system (auto-DODS) automatically switches between 3 sensitivities according to the negative pressure gradient of inhalation and supplies oxygen only during inhalation. The aim of this study was to verify the effectiveness and safety of auto-demand devices compared with a continuous flow oxygen concentrator, during sleep, in a randomized crossover noninferiority trial. We alternatively used an auto-DODS or a continuous-flow oxygen concentrator, all night on separate days for HOT (Home Oxygen Therapy) patients with nocturnal hypoxemic symptoms. The primary endpoints were the mean value of oxygen saturation (SpO 2 ) over the total sleep time. The secondary endpoints included the efficacy endpoints and the safety endpoints. Regarding the primary endpoint, the difference in SpO 2 between the auto-DODS and continuous flow was 0.835%. Since the upper limit of this difference did not exceed 2.8, which was set as the noninferiority margin, it was shown that the auto-DODS did not reduce SpO 2 by at least 2.8% on average compared to continuous flow. No equipment failure or exacerbation of disease was observed, confirming the safety of the auto-DODS during the night., (© 2024. The Author(s).)

Background: Medical oxygen services are essential for the care of acutely unwell patients. We aimed to assess the effects of a multilevel, multicomponent health-system intervention on hypoxaemia detection, oxygen therapy, and mortality among neonates and children attending level IV health centres and hospitals in Uganda., Methods: For this before-after intervention study, we included children who attended paediatric or neonatal wards of 24 level IV health centres and seven general or regional referral hospitals in the Busoga and North Buganda regions of Uganda between June 1, 2020, and June 30, 2022. All neonates younger than 1 month and children aged 1 month to 14 years were eligible for inclusion. We excluded neonates who were not sick but stayed in the maternity ward for routine postnatal care. The intervention involved clinical training, mentorship, and supportive supervision; provision of pulse oximeters and cylinder-based oxygen sources; biomedical-capacity support; and support to develop and disseminate oxygen supply strategies, oxygen therapy guidelines, and lists of essential oxygen supplies. Trained research assistants extracted individual patient data from case notes using a standardised electronic data collection form. Data were collected on health-facility details, age, sex, clinical signs and symptoms, admission diagnoses, pulse oximetry readings, oxygen therapy details, and final patient outcome. The primary outcome was the proportion of admitted neonates and children with a pulse oximetry oxygen saturation reading documented in their patient case notes on day 1 of health-facility admission (ie, pulse oximetry coverage). We used mixed-effects logistic regression to evaluate the effect of the intervention., Findings: We obtained data on 71 997 eligible neonates and children admitted to 31 participating health facilities; the primary analysis included 10 001 patients in the pre-intervention period (ie, June 1 to Oct 30, 2020) and 51 329 patients in the post-intervention period (ie, March 1, 2021, to June 30, 2022). Because 1356 patients had missing data for sex, 4365 (46·7%) of 9347 in the pre-intervention group and 22 831 (46·2%) of 49 410 in the post-intervention group were female; 4982 (53·3%) in the pre-intervention group and 26 579 (53·8%) in the post-intervention group were male. The proportion of neonates and children with pulse oximetry at admission increased from 2365 (23·7%) of 10 001 in the pre-intervention period to 45 029 (87·7%) of 51 328 in the post-intervention period. Adjusted analysis indicated greater likelihood of a patient receiving pulse oximetry during the post-intervention period compared with the pre-intervention period (adjusted odds ratio 40·10, 95% CI 37·38-42·93; p<0·0001)., Interpretation: Large-scale improvements in hospital oxygen services are achievable and have the potential to improve clinical outcomes. Governments should be encouraged to develop national oxygen plans and focus investment on interventions that have been shown to be effective, including the introduction of pulse oximetry into routine hospital care and clinical and biomedical mentoring and support., Funding: Bill & Melinda Gates Foundation and ELMA Philanthropies., Translations: For the Luganda and Lusoga translations of the abstract see Supplementary Materials section., Competing Interests: Declaration of interests HRG is an adviser to the Lifebox Foundation and Unitaid and receives a salary from the University of Melbourne. YK, JM, BK, SE, DK, AZ, LNK, and FL were employed by Clinton Health Access Initiative during implementation of the oxygen programme in Uganda. YK, BK, SE, AZ, DK, and LNK received a salary from Clinton Health Access Initiative Uganda. CO is employed by the Ugandan Ministry of Health. FEK and FS receive a salary from Makerere University. HA declares no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Objectives: To clarify the mechanistic basis for the success or failure of noninvasive ventilation (NIV) in acute hypoxemic respiratory failure (AHRF)., Design: We created digital twins based on mechanistic computational models of individual patients with AHRF., Setting: Interdisciplinary Collaboration in Systems Medicine Research Network., Subjects: We used individual patient data from 30 moderate-to-severe AHRF patients who had failed high-flow nasal cannula (HFNC) therapy and subsequently underwent a trial of NIV., Interventions: Using the digital twins, we evaluated lung mechanics, quantified the separate contributions of external support and patient respiratory effort to lung injury indices, and investigated their relative impact on NIV success or failure., Measurements and Main Results: In digital twins of patients who successfully completed/failed NIV, after 2 hours of the trial the mean (sd) of the change in total lung stress was -10.9 (6.2)/-0.35 (3.38) cm H2O, mechanical power -13.4 (12.2)/-1.0 (5.4) J/min, and total lung strain 0.02 (0.24)/0.16 (0.30). In the digital twins, positive end-expiratory pressure (PEEP) produced by HFNC was similar to that set during NIV. In digital twins of patients who failed NIV vs. those who succeeded, intrinsic PEEP was 3.5 (0.6) vs. 2.3 (0.8) cm H2O, inspiratory pressure support was 8.3 (5.9) vs. 22.3 (7.2) cm H2O, and tidal volume was 10.9 (1.2) vs. 9.4 (1.8) mL/kg. In digital twins, successful NIV increased respiratory system compliance +25.0 (16.4) mL/cm H2O, lowered inspiratory muscle pressure -9.7 (9.6) cm H2O, and reduced the contribution of patient spontaneous breathing to total driving pressure by 57.0%., Conclusions: In digital twins of AHRF patients, successful NIV improved lung mechanics, lowering respiratory effort and indices associated with lung injury. NIV failed in patients for whom only low levels of positive inspiratory pressure support could be applied without risking patient self-inflicted lung injury due to excessive tidal volumes., Competing Interests: Prof. Bates received support for article research from Research Councils UK. Dr. Tonelli declared patent N. 102021000007478; he disclosed that he and his wife are co-founders of IREC (VAT 02959080355). Dr. Laviola received funding from the Lorentz Center and the Institute of Electrical and Electronics Engineers Engineering in Medicine and Biology Conference. Prof. Bates’ institution received funding from Fisher & Paykel. The remaining authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the Society of Critical Care Medicine and Wolters Kluwer Health, Inc.)

This Thoracic Society of Australia and New Zealand Guideline on the provision of home oxygen therapy in adults updates a previous Guideline from 2015. The Guideline is based upon a systematic review and meta-analysis of literature to September 2022 and the strength of recommendations is based on GRADE methodology. Long-term oxygen therapy (LTOT) is recommended for its mortality benefit for patients with COPD and other chronic respiratory diseases who have consistent evidence of significant hypoxaemia at rest (PaO2 ≤ 55 mm Hg or PaO2 ≤59 mm Hg in the presence of hypoxaemic sequalae) while in a stable state. Evidence does not support the use of LTOT for patients with COPD who have moderate hypoxaemia or isolated nocturnal hypoxaemia. In the absence of hypoxaemia, there is no evidence that oxygen provides greater palliation of breathlessness than air. Evidence does not support the use of supplemental oxygen therapy during pulmonary rehabilitation in those with COPD and exertional desaturation but normal resting arterial blood gases. Both positive and negative effects of LTOT have been described, including on quality of life. Education about how and when to use oxygen therapy in order to maximize its benefits, including the use of different delivery devices, expectations and limitations of therapy and information about hazards and risks associated with its use are key when embarking upon this treatment., (© 2024 The Author(s). Respirology published by John Wiley & Sons Australia, Ltd on behalf of Asian Pacific Society of Respirology.)

Humidified high-flow nasal oxygen therapy (HFNO) has, in recent years, come to assume a key role in the management of hypoxemic acute respiratory failure (ARF). While non-invasive ventilation (NIV) currently represents the first-line ventilatory strategy in patients exhibiting hypercapnic ARF, the operating principles and physiological effects of HFNO could be interesting and useful in the initial management of hypercapnic ARF and/or after extubation, particularly in acute exacerbations of chronic obstructive pulmonary disease. Under these conditions, HFNO could be used either alone continuously or in combination with NIV during breaks in spontaneous breathing, depending on the severity and etiology of the underlying hypercapnic ARF., (Copyright © 2024 SPLF. Published by Elsevier Masson SAS. All rights reserved.)

Intermittent hypoxia (IH) and intermittent transcutaneous electrical stimulation (ITES) might benefit patients with obstructive sleep apnea (OSA). However, the therapeutic value of combined IH and ITES in OSA is unknown. In this prospective, randomized, controlled crossover study, normoxia (air exposure for 50 min before sleep and sham stimulation for 6 h during sleep), IH (5 repeats of 5 min 10-12 % O 2 alternating with 5 min air for 50 min, and sham stimulation for 6 h), ITES (air exposure for 50 min and 6 repeats of 30 min transcutaneous electrical stimulation alternating with 30 min of sham stimulation for 6 h), and IH&ITES (10-12 % O 2 alternating with air for 50 min and transcutaneous electrical stimulation alternating with sham stimulation for 6 h) were administered to patients with OSA over four single-night sessions. The primary endpoint was difference in OSA severity between the interventions according to apnea-hypopnea index (AHI) and oxygen desaturation index (ODI). The efficacy was response to IH, ITES, IH&ITES defined as a ≥50 % reduction in AHI compared with normoxia. Twenty participants (17 male, 3 female) completed the trial. The median (IQR) AHI decreased from 14.5 (10.8, 17.5) events/h with normoxia to 6.9 (3.9, 14.8) events/h with IH (p=0.020), 5.7 (3.4, 9.1) events/h with ITES (p=0.001), and 3.5 (1.8, 6.4) events/h with IH&ITES (p=0.001). AHI was significantly different between IH and IH&ITES (p=0.042) but not between ITES and IH&ITES (p=0.850). For mild-moderate OSA (n=17), IH, ITES, and IH&ITES had a significant effect on AHI (p=0.013, p=0.001, p=0.001, respectively) compared with normoxia, but there were no differences in post hoc pairwise comparisons between intervention groups. No serious adverse events were observed. In conclusion, IH, ITES, and IH&ITES significantly reduced OSA severity. IH&ITES showed better efficacy in mild-moderate OSA than IH and was comparable to ITES. Our data do not support recommending IH&ITES over ITES for OSA., Competing Interests: Declaration of Competing Interest The authors have no relevant disclosures., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Long-term oxygen therapy (LTOT) is a treatment that involves the provision of supplemental oxygen to individuals with respiratory disease to correct hypoxemia in the post-acute care environment. Over 1.5 million adults in the United States use supplemental oxygen for various respiratory disorders. This paper explores literature published on LTOT from September 2022-September 2023. Upon the conclusion of this literature review, 4 distinct categories emerged. This paper highlights the significant findings associated with the 4 categories: supplemental oxygen and COVID-19, telemonitoring, LTOT equipment, and in-home high-flow nasal cannula., Competing Interests: Ms Wiles discloses a relationship with Drive Medical, and was a sponsored speaker for medtrade October 2022., (Copyright © 2024 by Daedalus Enterprises.)

Background: When treating acute respiratory failure, both hypoxemia and hyperoxemia should be avoided. S pO 2 should be monitored closely and O 2 flows adjusted accordingly. Achieving this goal might be easier with automated O 2 titration compared with manual titration of fixed-flow O 2 . We evaluated the feasibility of using an automated O 2 titration device in subjects treated for acute hypoxemic respiratory failure in a tertiary care hospital., Methods: Health-care workers received education and training about oxygen therapy, and were familiarized with an automated O 2 titration device (FreeO 2, ). A coordinator was available from 8:00 am to 5:00 pm during weekdays to provide technical assistance. The ability of the device to maintain S pO 2 within the prescribed therapeutic window was recorded. Basic clinical information was recorded., Results: Subjects were enrolled from November 2020 to August 2022. We trained 508 health-care workers on the use of automated O 2 titration, which was finally used on 872 occasions in 763 subjects, distributed on the respiratory, COVID-19, and thoracic surgery wards, and in the emergency department. Clinical information could be retrieved for 609 subjects (80%) who were on the system for a median (interquartile range) of 3 (2-6) d, which represented 2,567 subject-days of clinical experience with the device. In the 82 subjects (14%) for whom this information was available, the system maintained S pO 2 within the prescribed targets 89% of the time. Ninety-six subjects experienced clinical deterioration as defined by the need to be transferred to the ICU and/or requirement of high flow nasal oxygen but none of these events were judged to be related to the O 2 device., Conclusions: Automated O 2 titration could be successfully implemented in hospitalized subjects with hypoxemic respiratory failure from various causes. This experience should foster further improvement of the device and recommendations for an optimized utilization., Competing Interests: Drs Simon, Lacasse, Lellouche, and Maltais are shareholders of Oxynov, the maker of FreeO2; Dr Lellouche is co-founder of Oxynov., (Copyright © 2024 by Daedalus Enterprises.)

Introduction: Acute respiratory failure is a life-threatening condition frequently found in the emergency department. High-flow nasal oxygen (HFNO) is increasingly used in emergency departments for patients with hypoxaemic acute respiratory failure. However, despite the increasing number of studies, its potential advantages regarding the need for therapeutic escalation and mortality have not been precisely evaluated. Our objective is to compare conventional oxygen therapy to HFNO when they are initiated during the first hour following the patient's arrival at the emergency department, with the hypothesis that HFNO would reduce the need for ventilatory therapy escalation., Methods and Analysis: This is a multicentric, prospective, open and randomised superiority study. 500 inpatients will be randomised (1:1) to receive conventional oxygen therapy or HNFO. The primary outcome is a failure in the oxygen therapy defined as the need for a therapeutic escalation within 4 hours after therapy initiation., Ethics and Dissemination: The study has been submitted and approved by the Comité de Protection des Personnes Nord Ouest IV (20 October 2020). As required, a notification was sent to the Agence nationale de sécurité du médicament et des produits de santé (22 October 2020). The research results will be published in peer-reviewed publications and presented at international conferences., Trial Registration Number: NCT04607967., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: Optimal timing of continuous positive airway pressure (CPAP) cessation in preterm infants remains undetermined. We hypothesised that CPAP extension compared with weaning to low-flow nasal cannula (NC) reduces intermittent hypoxaemia (IH) and respiratory instability in preterm infants meeting criteria to discontinue CPAP., Design: Single-centre randomised clinical trial., Setting: Level 4 neonatal intensive care unit., Patients: 36 infants <34 weeks' gestation receiving CPAP≤5 cmH 2 O and fraction of inspired oxygen (FiO 2 ) ≤0.30 and meeting respiratory stability criteria., Interventions: Extended CPAP was compared with weaning to low-flow NC (0.5 L/kg/min with a limit of 1.0 L/min) for 24 hours., Outcomes: The primary outcome was IH (number of episodes with SpO 2 <85% lasting ≥10 s). Secondary outcomes included: coefficient of variability of SpO 2 , proportion of time in various SpO 2 ranges, episodes (≥10 s) with SpO 2 <80%, median cerebral and renal oxygenation, median effective FiO 2 , median transcutaneous carbon dioxide and bradycardia (<100/min for≥10 s)., Results: The median (IQR) episodes of IH per 24-hour period was 20 (6-48) in the CPAP group and 76 (18-101) in the NC group (p=0.03). Infants continued on CPAP had less bradycardia, time with SpO 2 <91% and <85%, and lower FiO 2 (all p<0.05). There were no statistically significant differences in IH<80%, median transcutaneous carbon dioxide or median cerebral or renal oxygenation., Conclusion: In preterm infants meeting respiratory stability criteria for CPAP cessation, extended CPAP decreased IH, bradycardia and other hypoxaemia measures compared with weaning to low-flow NC during the 24-hour intervention., Trial Registration Number: NCT04792099., Competing Interests: Competing interests: NA is on the advisory board for Radiometer, Shire and Resbiotic. CPT has applied for a patent with the USPTO for a bradycardia predictor and interrupter unrelated to the current study., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Purpose: Although noninvasive ventilation (NIV) may reduce reintubation in patients with acute hypoxemic respiratory failure following abdominal surgery, this strategy has not been specifically assessed in patients with obesity., Methods: We conducted a post hoc analysis of a multicenter randomized controlled trial comparing NIV delivered via facial mask to standard oxygen therapy among patients with obesity and acute hypoxemic respiratory failure within 7 days after abdominal surgery. The primary outcome was reintubation within 7 days. Secondary outcomes were invasive ventilation-free days at day 30, intensive care unit (ICU)-acquired pneumonia and 30-day survival., Results: Among 293 patients with hypoxemic respiratory failure following abdominal surgery, 76 (26%) patients had obesity and were included in the intention-to-treat analysis. Reintubation rate was significantly lower with NIV (13/42, 31%) than with standard oxygen therapy (19/34, 56%) within 7 days (absolute difference: - 25%, 95% confidence interval (CI) - 49 to - 1%, p = 0.03). NIV was associated with significantly more invasive ventilation-free days compared with standard oxygen therapy (27.1 ± 8.6 vs 22.7 ± 11.1 days; p = 0.02), while fewer patients developed ICU-acquired pneumonia (1/42, 2% vs 6/34, 18%; p = 0.04). The 30-day survival was 98% in the NIV group (41/42) versus 85% in the standard oxygen therapy (p = 0.08). In patients with body mass index (BMI) < 30 kg/m 2 , no significant difference was observed between NIV (36/105, 34%) and standard oxygen therapy (47/109, 43%, p = 0.03). An interaction test showed no statistically significant difference between the two subsets (BMI ≥ 30 kg/m 2 and BMI < 30 kg/m 2 )., Conclusions: Among patients with obesity and hypoxemic respiratory failure following abdominal surgery, use of NIV compared with standard oxygen therapy reduced the risk of reintubation within 7 days, contrary to patients without obesity. However, no interaction was found according to the presence of obesity or not, suggesting either a lack of power to conclude in the non-obese subgroup despite existing differences, or that the statistical difference found in the overall sample was driven by a large effect in the obese subsets., (© 2024. Springer-Verlag GmbH Germany, part of Springer Nature.)

Objective: To determine the relative effectiveness of Helmet-CPAP (H&#95;CPAP) with respect to high-flow nasal cannula oxygen therapy (HFNO) in avoiding greater need for intubation or mortality in a medium complexity hospital in Chile during the year 2021., Design: Cohort analytical study, single center., Setting: Units other than intensive care units., Patients: Records of adults with mild to moderate hypoxemia due to coronavirus type 2., Interventions: None., Main Variables of Interest: Need for intubation or mortality., Results: 159 patients were included in the study, with a ratio by support of 2:10 (H&#95;CPAP:HFNO). The 46.5% were women, with no significant differences by sex according to support (p = 0.99, Fisher test). The APACHE II score, for HFNO, had a median of 10.5, 3.5 units higher than H&#95;CPAP (p < 0.01, Wilcoxon rank sum). The risk of intubation in HFNO was 42.1% and in H&#95;CPAP 3.8%, with a significant risk reduction of 91% (95% CI: 36.9%-98.7%; p < 0.01). APACHE II does not modify or confound the support and intubation relationship (p > 0.2, binomial regression); however, it does confound the support and mortality relationship (p = 0.82, RR homogeneity test). Despite a 79.1% reduction in mortality risk with H&#95;CPAP, this reduction was not statistically significant (p = 0.11, binomial regression)., Conclusions: The use of Helmet CPAP, when compared to HFNO, was an effective therapeutic ventilatory support strategy to reduce the risk of intubation in patients with mild to moderate hypoxemia caused by coronavirus type 2 in inpatient units other than intensive care. The limitations associated with the difference in size, age and severity between the arms could generate bias., (Copyright © 2024 Elsevier España, S.L.U. and SEMICYUC. All rights reserved.)

Hypoxic pulmonary hypertension (HPH) is a serious and life-threatening chronic cardiopulmonary disease characterized by progressive elevation of pulmonary artery pressure and pulmonary vascular remodeling. Mesenchymal stem cell- derived exosomes (MSC-Exos) can relieve HPH by reversing pulmonary vascular remodeling. The HPH model was established in healthy male Sprague-Dawley (SD) rats aged 6 to 8 weeks. The rats were placed in a room with oxygen concentration of (10 ± 1) % for 8 hours a day over 28 days, were then injected intravenously with MSC-Exos (100 ug protein/kg) or equal-volume phosphate buffer saline (PBS) once a day over 1 week. Right ventricular systolic pressure (RVSP), right ventricular hypertrophy index (RVHI) and pulmonary vascular remodeling were observed after anesthesia. In addition, platelet-derived growth factor BB (PDGF-BB) was used to stimulate rat pulmonary artery smooth muscle cells (PASMCs) to construct HPH pathological cell models. The results showed that MSC-Exos could not only reduce the elevation of RVSP, right ventricular hypertrophy and the degree of pulmonary vascular remodeling in HPH rats, but also reduce the proliferation, migration and apoptosis resistance of PASMCs. Finally, GSE53408 and GSE113439 datasets were analyzed and showed that the expression of Hsp90aa1 and pERK/ERK were significantly increased in HPH, also could be inhibited by MSC-Exos. Meanwhile, inhibition of Hsp90aa1 also reduced PASMCs migration and pERK/ERK protein level. In conclusion, MSC-Exos alleviated HPH by suppressing PASMCs proliferation, migration and apoptosis resistance through inhibiting the Hsp90aa1/ERK/pERK pathway., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Inc.)

Purpose: Skin pigmentation influences peripheral oxygen saturation (SpO 2 ) compared to arterial saturation of oxygen (SaO 2 ). Occult hypoxemia (SaO 2  ≤ 88% with SpO 2  ≥ 92%) is associated with increased in-hospital mortality in venovenous-extracorporeal membrane oxygenation (VV-ECMO) patients. We hypothesized VV-ECMO cannulation, in addition to race/ethnicity, accentuates the SpO 2 -SaO 2 discrepancy due to significant hemolysis., Methods: Adults (≥ 18 years) supported with VV-ECMO with concurrently measured SpO 2 and SaO 2 measurements from over 500 centers in the Extracorporeal Life Support Organization Registry (1/2018-5/2023) were included. Multivariable logistic regressions were performed to examine whether race/ethnicity was associated with occult hypoxemia in pre-ECMO and on-ECMO SpO 2 -SaO 2 calculations., Results: Of 13,171 VV-ECMO patients, there were 7772 (59%) White, 2114 (16%) Hispanic, 1777 (14%) Black, and 1508 (11%) Asian patients. The frequency of on-ECMO occult hypoxemia was 2.0% (N = 233). Occult hypoxemia was more common in Black and Hispanic patients versus White patients (3.1% versus 1.7%, P < 0.001 and 2.5% versus 1.7%, P = 0.025, respectively). In multivariable logistic regression, Black patients were at higher risk of pre-ECMO occult hypoxemia versus White patients (adjusted odds ratio [aOR] = 1.55, 95% confidence interval [CI] = 1.18-2.02, P = 0.001). For on-ECMO occult hypoxemia, Black patients (aOR = 1.79, 95% CI = 1.16-2.75, P = 0.008) and Hispanic patients (aOR = 1.71, 95% CI = 1.15-2.55, P = 0.008) had higher risk versus White patients. Higher pump flow rates (aOR = 1.29, 95% CI = 1.08-1.55, P = 0.005) and on-ECMO 24-h lactate (aOR = 1.06, 95% CI = 1.03-1.10, P < 0.001) significantly increased the risk of on-ECMO occult hypoxemia., Conclusion: SaO 2 should be carefully monitored if using SpO 2 during ECMO support for Black and Hispanic patients especially for those with high pump flow and lactate values at risk for occult hypoxemia., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

The optimal timing of intubation in acute hypoxaemic respiratory failure is uncertain and became a point of controversy during the COVID-19 pandemic. Invasive mechanical ventilation is a potentially life-saving intervention but carries substantial risks, including injury to the lungs and diaphragm, pneumonia, intensive care unit-acquired muscle weakness, and haemodynamic impairment. In deciding when to intubate, clinicians must balance premature exposure to the risks of ventilation with the potential harms of unassisted breathing, including disease progression and worsening multiorgan failure. Currently, the optimal timing of intubation is unclear. In this Personal View, we examine a range of parameters that could serve as triggers to initiate invasive mechanical ventilation. The utility of a parameter (eg, the ratio of arterial oxygen tension to fraction of inspired oxygen) to predict the likelihood of a patient undergoing intubation does not necessarily mean that basing the timing of intubation on that parameter will improve therapeutic outcomes. We examine options for clinical investigation to make progress on establishing the optimal timing of intubation., (Copyright © 2024 Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies.)

Introduction: Neuromuscular blockade (NMB) in ventilated patients may cause benefit or harm. We applied "incremental interventions" to determine the impact of altering NMB initiation aggressiveness., Methods: Retrospective cohort study of ventilated patients with PaO2/FiO2 ratio < 150 mmHg and PEEP≥ 8cmH2O from the Medical Information Mart of Intensive Care IV database (MIMIC-IV version 1.0) estimating the effect of incremental interventions on in-hospital mortality and ventilator-free days, modifying hourly propensity for NMB initiation to be aggressive or conservative relative to usual care, adjusting for confounding with inverse probability weighting., Results: 5221 patients were included (13.3% initiated on NMB). Incremental interventions estimated a strong effect on NMB usage: 5-fold higher hourly odds of initiation increased usage to 36.5% (CI = [34.3%,38.7%]) and 5-fold lower odds decreased usage to 3.8% (CI = [3.3%,4.3%]). Aggressive and conservative strategies demonstrated a U-shaped mortality relationship. 5-fold higher or lower propensity increased in-hospital mortality by 2.6% (0.95 CI = [1.5%,3.7%]) or 1.3% (0.95 CI = [0.1%,2.5%]) respectively. In secondary analysis of a healthier patient cohort, results were similar, however conservative strategies also improved ventilator-free days., Interpretation: Aggressive or conservative initiation of NMB may worsen mortality. In healthier populations, marginally conservative NMB initiation strategies may lead to increased ventilator free days with minimal impact on mortality., Competing Interests: Declaration of competing interest Funding was also provided by the MIT-IBM Watson AI Lab. LL was in part funded by NIH grants R01 EB017205 and 1U01TR003528-01A1. EBK and DT having received lecturing fees for educational talks from Hamilton Medical Inc. ZS was primarily employed by IBM Research during some of the work., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Intrauterine growth restriction (IUGR) pathophysiology is driven by abnormal uterine natural killer cell (uNK) activity leading to placental dysfunction. Transamniotic stem cell therapy (TRASCET) with mesenchymal stem cells (MSCs) can improve experimental IUGR by mechanisms not fully understood. We sought to examine TRASCET's effects in downstream products of uNKs in a model of IUGR: 15 Sprague-Dawley dams were exposed to alternating hypoxia (10.5% O 2 ) from gestational day 15 (E15) until term (E21). Their fetuses ( n = 189) were divided into four groups. One group remained untreated ( n = 52), whereas three groups received volume-matched intraamniotic injections of either saline (sham, n = 44) or a suspension of amniotic fluid-derived MSCs, either in their native state (TRASCET, n = 50) or "primed" to an enhanced antiinflammatory phenotype (TRASCET-Primed, n = 43). Normal fetuses served as controls ( n = 33). At term, various analyses were performed, including ELISA for surrogates of placental inflammation and uNK activity. Statistical comparisons included Bonferroni-adjusted criterion. Overall survival from hypoxia was 74% (140/189). Placental efficiency was lower in untreated and sham but normalized in both TRASCET groups ( P < 0.01-0.47). Interleukin-17, a stimulator of uNKs, was elevated from normal in all groups ( P < 0.01 for all). Interferon-gamma, released from activated uNKs, was elevated in all groups except sham but lower than the untreated in both TRASCET groups ( P ≤ 0.01-0.06). Tumor necrosis factor-alpha, also produced by uNKs, was elevated in untreated and sham ( P < 0.01 for both), but normalized by TRASCET ( P = 0.05) and even lowered from normal in TRASCET-Primed ( P < 0.01). Vascular endothelial growth factor, also released by uNKs, was elevated in untreated and sham but lower than normal in both TRASCET groups ( P < 0.01 for all). We conclude that TRASCET with MSCs modulates the activity of placental uNKs in experimental IUGR, with distinct effects on their downstream products. This mechanistic insight may inform the development of novel strategies for the management of this disease.

Massive pulmonary embolism is a common cause of morbidity and mortality. For patients presenting with massive pulmonary embolism, severe hypoxia is usually associated with severe hypotension. These patients should be considered for thrombectomy should thrombolysis and respiratory support fail to improve their condition. Should thrombectomy not be available or suitable, consideration should be given to offering mechanical chest compressions to 'break up the clot'. We describe a case in which this seemingly led to survival and full recovery., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: We assessed the effect of noninvasive ventilation (NIV) on mortality and length of stay after high flow nasal oxygenation (HFNO) failure among patients with severe hypoxemic COVID-19 pneumonia., Methods: In this multicenter, retrospective study, we enrolled COVID-19 patients admitted in intensive care unit (ICU) for severe COVID-19 pneumonia with a HFNO failure from December 2020 to January 2022. The primary outcome was to compare the 90-day mortality between patients who required a straight intubation after HFNO failure and patients who received NIV after HFNO failure. Secondary outcomes included ICU and hospital length of stay. A propensity score analysis was performed to control for confounding factors between groups. Exploratory outcomes included a subgroup analysis for 90-day mortality., Results: We included 461 patients with HFNO failure in the analysis, 233 patients in the straight intubation group and 228 in the NIV group. The 90-day mortality did not significantly differ between groups, 58/228 (25.4%) int the NIV group compared with 59/233 (25.3%) in the straight intubation group, with an adjusted hazard ratio (HR) after propensity score weighting of 0.82 [95%CI, 0.50-1.35] (p = 0.434). ICU length of stay was significantly shorter in the NIV group compared to the straight intubation group, 10.0 days [IQR, 7.0-19.8] versus 18.0 days [IQR,11.0-31.0] with a propensity score weighted HR of 1.77 [95%CI, 1.29-2.43] (p < 0.001). A subgroup analysis showed a significant increase in mortality rate for intubated patients in the NIV group with 56/122 (45.9%), compared to 59/233 (25.3%) for patients in the straight intubation group (p < 0.001)., Conclusions: In severely hypoxemic COVID-19 patients, no significant differences were observed on 90-day mortality between patients receiving straight intubation and those receiving NIV after HFNO failure. NIV strategy was associated with a significant reduction in ICU length of stay, despite an increase in mortality in the subgroup of patients finally intubated., (© 2024. The Author(s).)

Introduction: The co-existence of chronic obstructive pulmonary disease (COPD) and obstructive sleep apnea (OSA), or the overlap syndrome, is common and associated with a distinct pattern of nocturnal hypoxemia and worse clinical outcomes than either disease alone. Consequently, identifying who and how to treat these patients is essential., Areas Covered: Treatment is recommended in all patients with OSA and symptoms or systemic hypertension, but determining symptoms attributable to OSA can be challenging in patients with COPD. Treatment should be considered in asymptomatic patients with moderate to severe OSA and COPD with pulmonary hypertension and comorbid cardiovascular and cerebrovascular disease, especially if marked hypoxic burden. CPAP is effective, but in patients with the overlap syndrome and daytime hypercapnia, high-intensity noninvasive ventilation aiming to lower PaCO2 may have additional benefits. Additionally, in those with severe resting daytime hypoxemia, supplemental oxygen improves survival and should be added to positive airway pressure. The role of alternative non-positive airway pressure therapies in the overlap syndrome needs further study., Expert Opinion: Both COPD and OSA are heterogeneous disorders with a wide range of disease severity and further research is needed to better characterize and prognosticate patients with the overlap syndrome to personalize treatment.

Introduction: Home oxygen therapy is one of the few interventions that can improve survival in patients with chronic obstructive pulmonary disease (COPD) when administered appropriately, although it may cause side effects and be an unnecessary burden for some patients., Areas Covered: This narrative review summarizes the current literature on the assessment of hypoxemia, different types of home oxygen therapy, potential beneficial and adverse effects, and emerging research on home oxygen therapy in COPD. A literature search was performed using MEDLINE and EMBASE up to January 2024, with additional articles being identified through clinical guidelines., Expert Opinion: Hypoxemia is common in patients with more severe COPD. Long-term oxygen therapy is established to prolong survival in patients with chronic severe resting hypoxemia. Conversely, in the absence of chronic severe resting hypoxemia, home oxygen therapy has an unclear or conflicting evidence base, including for palliation of breathlessness, and is generally not recommended. However, beneficial effects in some patients cannot be precluded. Evidence is emerging on the optimal daily duration of oxygen use, the role of high-flow and auto-titrated oxygen therapy, improved informed decision-making, and telemonitoring. Further research is needed to validate novel oxygen delivery systems and monitoring tools and establish long-term effects of ambulatory oxygen therapy in COPD.

Rationale: Acute hypoxaemic respiratory failure (AHRF) is associated with high mortality in sub-Saharan Africa. This is at least in part due to critical care-related resource constraints including limited access to invasive mechanical ventilation and/or highly skilled acute care workers. Continuous positive airway pressure (CPAP) and high-flow oxygen by nasal cannula (HFNC) may prove useful to reduce intubation, and therefore, improve survival outcomes among critically ill patients, particularly in resource-limited settings, but data in such settings are lacking. The aim of this study is to determine whether CPAP or HFNC as compared with standard oxygen therapy, could reduce mortality among adults presenting with AHRF in a resource-limited setting., Methods: This is a prospective, multicentre, randomised, controlled, stepped wedge trial, in which patients presenting with AHRF in Uganda will be randomly assigned to standard oxygen therapy delivered through a face mask, HFNC oxygen or CPAP. The primary outcome is all-cause mortality at 28 days. Secondary outcomes include the number of patients with criteria for intubation at day 7, the number of patients intubated at day 28, ventilator-free days at day 28 and tolerance of each respiratory support., Ethics and Dissemination: The study has obtained ethical approval from the Research and Ethics Committee, School of Biomedical Sciences, College of Health Sciences, Makerere University as well as the Uganda National Council for Science and Technology. Patients will be included after informed consent. The results will be submitted for publication in peer-reviewed journals., Trial Registration Number: NCT04693403., Protocol Version: 8 September 2023; version 5., Competing Interests: Competing interests: AMD reports fees (lectures and research) from Fisher and Payckel. EA reports personal fees from GBT, personal fees from Hemanext, both unrelated to the present study., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Purpose: Severe acute respiratory distress syndrome (ARDS) with PaO 2 /FiO 2  < 80 mmHg is a life-threatening condition. The optimal management strategy is unclear. The aim of this meta-analysis was to compare the effects of low tidal volumes (V t ), moderate V t , prone ventilation, and venovenous extracorporeal membrane oxygenation (VV-ECMO) on mortality in severe ARDS., Methods: We performed a frequentist network meta-analysis of randomised controlled trials (RCTs) with participants who had severe ARDS and met eligibility criteria for VV-ECMO or had PaO 2 /FiO 2  < 80 mmHg. We applied the Grades of Recommendation, Assessment, Development, and Evaluation (GRADE) methodology to discern the relative effect of interventions on mortality and the certainty of the evidence., Results: Ten RCTs including 812 participants with severe ARDS were eligible. VV-ECMO reduces mortality compared to low V t (risk ratio [RR] 0.77, 95% confidence interval [CI] 0.59-0.99, moderate certainty) and compared to moderate V t (RR 0.75, 95% CI 0.57-0.98, low certainty). Prone ventilation reduces mortality compared to moderate V t (RR 0.78, 95% CI 0.66-0.93, high certainty) and compared to low V t (RR 0.81, 95% CI 0.63-1.02, moderate certainty). We found no difference in the network comparison of VV-ECMO compared to prone ventilation (RR 0.95, 95% CI 0.72-1.26), but inferences were based solely on indirect comparisons with very low certainty due to very wide confidence intervals., Conclusions: In adults with ARDS and severe hypoxia, both VV-ECMO (low to moderate certainty evidence) and prone ventilation (moderate to high certainty evidence) improve mortality relative to low and moderate V t strategies. The impact of VV-ECMO versus prone ventilation remains uncertain., (© 2024. Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Studies in individuals with chronic stroke indicate high-intensity training (HIT) focused on walking improves locomotor function, which may be due to repeated activation of locomotor circuits and serotonin-dependent modulation of motor output. Separate studies in animals and individuals with spinal cord injury suggest acute intermittent hypoxia (AIH) can augment the effects of locomotor interventions through similar serotonin-dependent mechanisms, although no studies have coupled AIH with HIT in individuals poststroke. The goal of this study was to evaluate the safety and efficacy of AIH+HIT versus HIT alone in individuals with chronic stroke., Methods: This phase II double-blind randomized, crossover trial recruited individuals between 18 and 85 years old, >6 months poststroke, and self-selected speeds <1.0 m/s. Participants received up to 15 sessions of AIH for 30 minutes using 15 cycles of hypoxia (60-90 seconds; 8%-9% O 2 ) and normoxia (30-60 seconds; 21% O 2 ), followed by 1 hour of HIT targeting >75% heart rate reserve. The control condition received normoxia for 30 minutes before HIT. Following the first training phase, participants performed the second phase >1 month later. The primary outcomes were self-selected speed and fastest speed, a 6-minute walk test, and peak treadmill speed. A 3-way mixed-model ANOVA assessed the effects of time, training, and order of interventions., Results: Of 55 individuals screened, 35 were randomized to AIH+HIT or normoxia+HIT first, and 28 individuals completed both interventions, revealing greater gains in self-selected speeds (0.14 [0.08-0.18] versus 0.05 [0.01-0.10] m/s), fastest speed (0.16 [0.10-0.21] versus 0.06 [0.02-0.10] m/s), and peak treadmill speed (0.21 [0.14-0.29] versus 0.11 [0.06-0.16] m/s) following AIH+HIT versus normoxia+HIT ( P <0.01) with no order effects. Greater gains in spatiotemporal symmetry were observed with AIH+HIT, with worse outcomes for those prescribed serotonin-mediated antidepressant medications., Conclusions: AIH+HIT resulted in greater gains in locomotor function than normoxia+HIT. Subsequent phase III trials should further evaluate the efficacy of this intervention., Registration: URL: https://clinicaltrials.gov/; Unique identifier: NCT04472442., Competing Interests: Disclosures Dr Hornby is co-owner and Dr Henderson is employed by the Institute for Knowledge Translation, and both receive funding from National Institutes of Health. The other authors report no conflicts.

Background: Tubeless upper airway surgery in children is a complex procedure in which surgeons and anaesthetists share the same operating field. These procedures are often interrupted for rescue oxygen therapy. The efficacy of nasal high-flow oxygen to decrease the frequency of rescue interruptions in children undergoing upper airway surgery is unknown., Methods: In this multicentre randomised trial conducted in five tertiary hospitals in Australia, children aged 0-16 years who required tubeless upper airway surgery were randomised (1:1) by a web-based randomisation tool to either nasal high-flow oxygen delivery or standard oxygen therapy (oxygen flows of up to 6 L/min). Randomisation was stratified by site and age (<1 year, 1-4 years, and 5-16 years). Subsequent tubeless upper airway surgery procedures in the same child could be included if there were more than 2 weeks between the procedures, and repeat surgical procedures meeting this condition were considered to be independent events. The oxygen therapy could not be masked, but the investigators remained blinded until outcome data were locked. The primary outcome was successful anaesthesia without interruption of the surgical procedure for rescue oxygenation. A rescue oxygenation event was defined as an interruption of the surgical procedure to deliver positive pressure ventilation using either bag mask technique, insertion of an endotracheal tube, or laryngeal mask to improve oxygenation. There were ten secondary outcomes, including the proportion of procedures with a hypoxaemic event (SpO 2 <90%). Analyses were done on an intention-to-treat (ITT) basis. Safety was assessed in all enrolled participants. This trial is registered in the Australian New Zealand Clinical Trials Registry, ACTRN12618000949280, and is completed., Findings: From Sept 4, 2018, to April 12, 2021, 581 procedures in 487 children were randomly assigned to high-flow oxygen (297 procedures) or standard care (284 procedures); after exclusions, 528 procedures (267 assigned to high-flow oxygen and 261 assigned to standard care) in 483 children (293 male and 190 female) were included in the ITT analysis. The primary outcome of successful anaesthesia without interruption for tubeless airway surgery was achieved in 236 (88%) of 267 procedures on high-flow oxygen and in 229 (88%) of 261 procedures on standard care (adjusted risk ratio [RR] 1·02, 95% CI 0·96-1·08, p=0·82). There were 51 (19%) procedures with a hypoxaemic event in the high-flow oxygen group and 57 (22%) in the standard care group (RR 0·86, 95% CI 0·58-1·24). Of the other prespecified secondary outcomes, none showed a significant difference between groups. Adverse events of epistaxis, laryngospasm, bronchospasm, hypoxaemia, bradycardia, cardiac arrest, hypotension, or death were similar in both study groups., Interpretation: Nasal high-flow oxygen during tubeless upper airway surgery did not reduce the proportion of interruptions of the procedures for rescue oxygenation compared with standard care. There were no differences in adverse events between the intervention groups. These results suggest that both approaches, nasal high-flow or standard oxygen, are suitable alternatives to maintain oxygenation in children undergoing upper airway surgery., Funding: Thrasher Research Fund, the Australian and New Zealand College of Anaesthetists, the Society for Paediatric Anaesthesia in New Zealand and Australia., Competing Interests: Declaration of interests AS reports consultancy fees from Fisher & Paykel Healthcare, Auckland, New Zealand. SH reports support for travel and accommodation from Fisher & Paykel Healthcare, Auckland, New Zealand. All other authors declare no competing interests., (Crown Copyright © 2024 Published by Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies.)

Objectives: Extracorporeal life support can lead to rapid reversal of hypoxemia but the benefits and harms of different oxygenation targets in severely ill patients are unclear. Our primary objective was to investigate the association between the Pa o2 after extracorporeal membrane oxygenation (ECMO) initiation and mortality in neonates treated for respiratory failure., Design: Retrospective analysis of the Extracorporeal Life Support Organization (ELSO) Registry data, 2015-2020., Patients: Newborns supported by ECMO for respiratory indication were included., Interventions: None., Measurements and Main Results: Pa o2 24 hours after ECMO initiation (H24 Pa o2 ) was reported. The primary outcome was 28-day mortality. We identified 3533 newborns (median age 1 d [interquartile range (IQR), 1-3]; median weight 3.2 kg [IQR, 2.8-3.6]) from 198 ELSO centers, who were placed on ECMO. By 28 days of life, 731 (20.7%) had died. The median H24 Pa o2 was 85 mm Hg (IQR, 60-142). We found that both hypoxia (Pa o2 < 60 mm Hg) and moderate hyperoxia (Pa o2 201-300 mm Hg) were associated with greater adjusted odds ratio (aOR [95% CI]) of 28-day mortality, respectively: aOR 1.44 (95% CI, 1.08-1.93), p = 0.016, and aOR 1.49 (95% CI, 1.01-2.19), p value equals to 0.045., Conclusions: Early hypoxia or moderate hyperoxia after ECMO initiation are each associated with greater odds of 28-day mortality among neonates requiring ECMO for respiratory failure., Competing Interests: Dr. Tonna is supported by a Career Development Award from the National Institutes of Health/National Heart, Lung, and Blood Institute (K23 HL141596). Dr. Tonna is the Chair of the Registry Committee of the Extracorporeal Life Support Organization. Dr. Moscatelli is a consultant for Air Liquide Santé International as a member of the advisory board on the use of inhaled nitric oxide for cardiothoracic indications. The remaining authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2024 by the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies.)

Low oxygen breathing has been the subject of considerable research in recent years. The present review aims to determine the physiological and neuropsychological benefits of lowoxygen training. Specifically, we explored the ways low oxygen affects hormones, neurotransmitters and growth factors responsible for neuroplasticity, higher cognition and positive emotions. In addition, we shed light on the importance of hypoxia to expand the conscious experience. Furthermore, we investigate the role of digital technologies in assisting hypoxic training. The results showed that, when hypoxia occurs, the human body puts into action the amazing survival mission which reveals unexplored alternative plans and healing pathways. Oxygen deprivation, under certain circumstances, has beneficial effects on cognition, mood and consciousness. It was observed an increase in growth factors, which are responsible for tissue repair and regeneration. Hypoxia also was found to stimulate the hormones of pleasure, happiness, pain tolerance, socialization and relaxation. Interestingly, people under hypoxic conditions are more likely to have transcendental experiences -even to develop ‘superhuman’ abilities. Digital technologies facilitate the safe implementation of hypoxic training enabling users to take control of a powerful tool, which is none other than breathing. Metacognition in breathing can help people consciously and safely manipulate their breathing by moving themselves away from their comfort zone and exploring new pathways to rewire their brains and plumb the depths of their physical, cognitive, emotional and spiritual potential. Our findings suggest that hypoxic training could be an effective intervention strategy with important therapeutic benefits for people with learning and other disabilities (i.e adhd, memory deficits, autism, motor, impairments, depression, generalized anxiety disorder). Future educators, therapists and families should be trained to appropriate apply simple hypoxic training exercises even in the educational context. For that reason, research into the physiological and neuropsychological mechanism that is affected by hypoxic training for individuals with learning or other disabilities is necessary. [ABSTRACT FROM AUTHOR]

Background: Closed-loop oxygen control systems automatically adjust the fraction of inspired oxygen (FiO 2 ) to maintain oxygen saturation (SpO 2 ) within a predetermined target range. Their performance with low and high-flow oxygen therapies, but not with non-invasive ventilation, has been established. We compared the effect of automated oxygen on achieving and maintaining a target SpO 2 range with nasal high flow (NHF), bilevel positive airway pressure (bilevel) and continuous positive airway pressure (CPAP), in stable hypoxaemic patients with chronic cardiorespiratory disease., Methods: In this open-label, three-way cross-over trial, participants with resting hypoxaemia (n=12) received each of NHF, bilevel and CPAP treatments, in random order, with automated oxygen titrated for 10 min, followed by 36 min of standardised manual oxygen adjustments. The primary outcome was the time taken to reach target SpO 2 range (92%-96%). Secondary outcomes included time spent within target range and physiological responses to automated and manual oxygen adjustments., Results: Two participants were randomised to each of six possible treatment orders. During automated oxygen control (n=12), the mean (±SD) time to reach target range was 114.8 (±87.9), 56.6 (±47.7) and 67.3 (±61) seconds for NHF, bilevel and CPAP, respectively, mean difference 58.3 (95% CI 25.0 to 91.5; p=0.002) and 47.5 (95% CI 14.3 to 80.7; p=0.007) seconds for bilevel and CPAP versus NHF, respectively. Proportions of time spent within target range were 68.5% (±16.3), 65.6% (±28.7) and 74.7% (±22.6) for NHF, bilevel and CPAP, respectively.Manually increasing, then decreasing, the FiO 2 resulted in similar increases and then decreases in SpO 2 and transcutaneous carbon dioxide (PtCO 2 ) with NHF, bilevel and CPAP., Conclusion: The target SpO 2 range was achieved more quickly when automated oxygen control was initiated with bilevel and CPAP compared with NHF while time spent within the range across the three therapies was similar. Manually changing the FiO 2 had similar effects on SpO 2 and PtCO 2 across each of the three therapies., Trial Registration Number: ACTRN12622000433707., Competing Interests: Competing interests: LK, SK, GB, MB, RS, AS, AE and RB report financial support was provided by Fisher & Paykel Healthcare to conduct this study. RB reports that the Institute responsible for this study manuscript has received research funding from Fisher and Paykel Healthcare and the Health Research Council of New Zealand. LK reports a relationship with Fisher & Paykel Healthcare that includes: travel reimbursement. Coauthor RS reports a relationship with Fisher & Paykel Healthcare that includes conference fees. Coauthor GB is now employed by Johnson & Johnson Pacific. Coauthor AS was on a Data Safety Management Committee for a separate study funded by Fisher & Paykel Healthcare., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Purpose: High-flow nasal cannula (HFNO) reduces the need for invasive mechanical ventilation in COVID-19 patients with hypoxemic-respiratory failure. During HFNO entrainment of room air dilutes the delivered fractional inspiratory oxygen (FiO 2 ), thereby preventing improvement in oxygenation. The placement of a mask over HFNO to improve oxygenation has provided conflicting results. We aimed to determine and compare the effect of placing various mask types over HFNO on oxygen saturation (SPO 2 )., Materials and Methods: In this prospective physiological study 40 patients with COVID-19-associated hypoxemic respiratory failure on HFNO with O 2 concentration <92% were included. The effect of placing different masks over HFNO on oxygenation, respiratory rate, heart rate, blood pressure, patient comfort, and partial pressure of carbon dioxide level (pCO 2 ) was recorded after a prespecified time interval., Results: We observed a significantly higher mean SPO 2 and lower mean respiratory rate on using various study masks over HFNO compared to HFNO alone. On comparing various mask types, the use of N95 masks and nonrebreather (NRB) masks with O 2 showed a significant increase in O 2 concentration and reduction in respiratory rate compared to surgical mask (SM) and NRB without O 2 . The proportion of patients who achieved SPO 2 of >92% was higher with the use of N95 masks (47.5%) or NRB with O 2 (45%) over HFNO compared to SM (35%) and NRB without O 2 (35%). No significant change was observed in heart rate, blood pressure, and CO 2 level with the use of any mask over HFNO., Conclusion: This study demonstrates improvement in oxygenation and reduction in respiratory rate with the use of various masks over HFNO in patients of COVID-19-related hypoxemic-respiratory-failure. Significantly greater benefit was achieved with the use of N95 or NRB with O2 compared to SM or NRB without O2., (© Journal of the Association of Physicians of India 2024.)

Aim: A pilot randomised controlled trial assessed the early application of nasal high-flow (NHF) therapy compared with standard oxygen therapy (SOT), in children aged 0 to 16 years presenting to paediatric emergency departments with acute hypoxaemic respiratory failure (AHRF). The study estimated the need to escalate therapy and hospital length of stay in the NHF group compared with SOT. This sub-study then assessed the subsequent cost-effectiveness., Methods: A decision tree-based model was developed, alongside the clinical study, to estimate cost-effectiveness, from the healthcare sector perspective. The primary health economics outcome is measured as incremental cost per length of hospital stay avoided. Incremental cost effectiveness ratios (ICER) measuring change in cost per change in length of stay, were obtained for four samples, depending on responder status and obstructive airways disease. These were (1) obstructive and responder, (2) non-obstructive and responder, (3) obstructive and non-responder and (4) non obstructive and non-responder. Bootstrapping of parameters accounted for uncertainty in estimates of cost and outcome., Results: The ICER for patients randomised to NHF, indicated an additional A$367.20 for a lower hospital length of stay (in days) in the non-obstructive/non-responder sample. In the bootstrap sample, this was found to be cost effective above a willingness to pay threshold of A$10 000. The ICER was A$440.86 in the obstructive/responder sample and A$469.56 in the non-obstructive/responder sample - but both resulted in a longer length of stay. The ICER in the obstructive/non-responder sample was A$52 167.76, also with a longer length of stay, mainly impacted by a small sample of severe cases., Conclusion: As first-line treatment, NHF is unlikely to be cost-effective compared with SOT, but for non-obstructive patients who required escalation in care (non-obstructive non-responder), NHF is likely to be cost-effective if willingness-to-pay per reduced hospital length of stay is more than A$10 000 per patient., (© 2024 The Authors. Journal of Paediatrics and Child Health published by John Wiley & Sons Australia, Ltd on behalf of Paediatrics and Child Health Division (The Royal Australasian College of Physicians).)

Oxygen, like all medicines, is a drug which needs moderation. Hypoxia, as well as excess oxygen supplementation, can be harmful in a patient with chronic obstructive pulmonary disease (COPD). Both the European and the British guidelines recommend a target oxygen saturation of 88-92% in patients with COPD. Hypoxia can result in symptoms, such as restlessness, anxiety, agitation, and headache, while excess oxygen can lead to altered sensorium due to the retention of carbon dioxide (CO2) in patients with COPD. We often come across patients who come with breathlessness and have hypoxia, and the knee-jerk reaction is to start the patient on oxygen support to maintain an oxygen saturation of >95%, and this may result in hypercapnia and type II respiratory failure. Here, we present a descriptive review of the proper application of oxygen therapy in a patient presenting with acute exacerbation of COPD, the rationale behind the target oxygen saturations, and the mechanisms of type II respiratory failure due to hyperoxygenation., (© Journal of the Association of Physicians of India 2024.)

Introduction: Limited data is available regarding the incidence of pressure injuries in patients who have undergone Extracorporeal Membrane Oxygenation (ECMO), a life-saving technique that provides respiratory support for hypoxemia that does not respond to conventional treatment., Aim: To assess the incidence of pressure injuries and identify the risk factors in Acute Respiratory Distress Syndrome patients receiving ECMO., Methods: A retrospective observational study utilizing prospectively collected data was performed in an Italian intensive care unit, between 1 January 2012 and 30 April 2022 enrolling all consecutive patients with Acute Respiratory Distress Syndrome who underwent ECMO., Results: One hundred patients were included in this study. 67 patients (67%) developed pressure injuries during their intensive care unit stay, with a median of 2 (1-3) sites affected. The subgroup of patients with pressure injuries was more hypoxic before ECMO implementation, received more frequent continuous renal replacement therapy and prone positioning, and showed prolonged ECMO duration, intensive care unit and hospital length of stay compared to patients without pressure injuries. The logistic model demonstrated an independent association between the pO 2 /FiO 2 ratio prior to ECMO initiation, the utilization of the prone positioning during ECMO, and the occurrence of pressure injuries., Conclusions: The incidence of pressure injuries was elevated in patients with Adult Respiratory Distress Syndrome who received ECMO. The development of pressure injuries was found to be independently associated with hypoxemia before ECMO initiation and the utilization of prone positioning during ECMO., Implications for Clinical Practice: Patients who require ECMO for respiratory failure are at a high risk of developing pressure injuries. To ensure optimal outcomes during ECMO implementation and treatment, it is vital to implement preventive measures and to closely monitor skin health in at-risk areas., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: Dyspnea is a key symptom of de novo acute hypoxemic respiratory failure. This study explores dyspnea and its association with intubation and mortality in this population., Methods: This was a secondary analysis of a multicenter, randomized, controlled trial. Dyspnea was quantified by a visual analog scale (dyspnea-VAS) from zero to 100 mm. Dyspnea was measured in 259 of the 310 patients included. Factors associated with intubation were assessed with a competing risks model taking into account ICU discharge. The Cox model was used to evaluate factors associated with 90-day mortality., Results: At baseline (randomization in the parent trial), median dyspnea-VAS was 46 (interquartile range, 16-65) mm and was ≥ 40 mm in 146 patients (56%). The intubation rate was 45%. Baseline variables independently associated with intubation were moderate (dyspnea-VAS 40-64 mm) and severe (dyspnea-VAS ≥ 65 mm) dyspnea at baseline (sHR 1.96 and 2.61, p = 0.023), systolic arterial pressure (sHR 2.56, p < 0.001), heart rate (sHR 1.94, p = 0.02) and PaO 2 /FiO 2 (sHR 0.34, p = 0.028). 90-day mortality was 20%. The cumulative probability of survival was lower in patients with baseline dyspnea-VAS ≥ 40 mm (logrank test, p = 0.049). Variables independently associated with mortality were SAPS 2 ≥ 25 (p < 0.001), moderate-to-severe dyspnea at baseline (p = 0.073), PaO 2 /FiO 2 (p = 0.118), and treatment arm (p = 0.046)., Conclusions: In patients admitted to the ICU for de novo acute hypoxemic respiratory failure, dyspnea is associated with a higher risk of intubation and with a higher mortality., Trial Registration: clinicaltrials.gov Identifier # NCT01320384., (© 2024. The Author(s).)

Background: Medical oxygen is essential for managing hypoxaemia, which has a multifactorial origin, including acute and chronic lung diseases such as pneumonia, asthma, and severe malaria. The coronavirus disease 2019 (COVID-19) revealed substantial gaps in the availability and accessibility of safe medical oxygen, especially in low- and middle-income countries (LMICs). This study aimed to assess the availability and sources, as well as the barriers to the availability of functional medical oxygen in hospitals in Cameroon., Methods: This was a nationwide cross-sectional descriptive study conducted from 26 March to 1 June 2021. Using a convenient sampling technique, we sampled accredited public and private COVID-19 treatment centres in all ten regions in Cameroon. Representatives from the selected hospitals were provided with a pre-designed questionnaire assessing the availability, type, and state of medical oxygen in their facilities. All analyses were performed using R., Results: In total, 114 hospitals were included in this study, with functional medical oxygen available in 65% (74/114) of the hospitals. About 85% (23/27) of the reference hospitals and only 59% (51/87) of the district hospitals had available functional medical oxygen. Compared to district hospitals, reference hospitals were more likely to have central oxygen units (reference vs. district: 10 vs. 0%), oxygen cylinders (74 vs. 42%), and oxygen concentrators (79 vs. 51%). The most common barriers to the availability of medical oxygen were inadequate oxygen supply to meet needs (district vs. reference hospitals: 55 vs. 30%), long delays in oxygen bottle refills (51 vs. 49%), and long distances from oxygen suppliers (57 vs. 49%)., Conclusions: The availability of medical oxygen in hospitals in Cameroon is suboptimal and more limited in districts compared to reference hospitals. The cost of medical oxygen, delays related to refills and supplies, and long distances from medical sources were the most common barriers to availability in Cameroon., Competing Interests: Disclosure of interest: The authors completed the ICMJE Disclosure of Interest Form (available upon request from the corresponding author) and disclose no relevant interests., (Copyright © 2024 by the Journal of Global Health. All rights reserved.)

Objective: To explore the association between PaCO 2 and noninvasive ventilation (NIV) failure in patients with hypoxemic respiratory failure., Methods: A retrospective study was performed in a respiratory ICU of a teaching hospital. Patients admitted to ICU between 2011 and 2019 were screened. We enrolled the patients with hypoxemic respiratory failure. However, patients who used NIV due to acute-on-chronic respiratory failure or heart failure were excluded. Data before the use of NIV were collected. Requirement of intubation was defined as NIV failure., Results: A total of 1029 patients were enrolled in final analysis. The rate of NIV failure was 45% (461/1029). A nonlinear relationship between PaCO 2 and NIV failure was found by restricted cubic splines (p = 0.03). The inflection point was 32 mmHg. The rate of NIV failure was 42% (224/535) in patients with PaCO 2 >32 mmHg. However, it increased to 48% (237/494) in those with PaCO 2  ≤ 32 mmHg. The crude and adjusted hazard ratio (HR) for NIV failure was 1.36 (95%CI:1.13-1.64) and 1.23(1.01-1.49), respectively, if the patients with PaCO 2 >32 mmHg were set as reference. In patients with PaCO 2  ≤ 32 mmHg, one unit increment of PaCO 2 was associated with 5% reduction of NIV failure. However, it did not associate with NIV failure in patients with PaCO 2 >32 mmHg., Conclusions: PaCO 2 and NIV failure was nonlinear relationship. The inflection point was 32 mmHg. Below the inflection point, lower PaCO 2 was associated with higher NIV failure. However, it did not associate with NIV failure above this point., (© 2024. The Author(s).)

Purpose: Invasive ventilation is a fundamental treatment in intensive care but its precise timing is difficult to determine. This study aims at assessing the effect of initiating invasive ventilation versus waiting, in patients with hypoxemic respiratory failure without immediate reason for intubation on one-year mortality., Methods: Emulation of a target trial to estimate the benefit of immediately initiating invasive ventilation in hypoxemic respiratory failure, versus waiting, among patients within the first 48-h of hypoxemia. The eligible population included non-intubated patients with SpO 2 /FiO 2  ≤ 200 and SpO 2  ≤ 97%. The target trial was emulated using a single-center database (MIMIC-IV) which contains granular information about clinical status. The hourly probability to receive mechanical ventilation was continuously estimated. The hazard ratios for the primary outcome, one-year mortality, and the secondary outcome, 30-day mortality, were estimated using weighted Cox models with stabilized inverse probability weights used to adjust for measured confounding., Results: 2996 Patients fulfilled the inclusion criteria of whom 792 were intubated within 48 h. Among the non-invasive support devices, the use of oxygen through facemask was the most common (75%). Compared to patients with the same probability of intubation but who were not intubated, intubation decreased the hazard of dying for the first year after ICU admission HR 0.81 (95% CI 0.68-0.96, p = 0.018). Intubation was associated with a 30-day mortality HR of 0.80 (95% CI 0.64-0.99, p = 0.046)., Conclusion: The initiation of mechanical ventilation in patients with acute hypoxemic respiratory failure reduced the hazard of dying in this emulation of a target trial., (© 2024. The Author(s).)

Importance: Patients presenting to the emergency department (ED) with hypoxemia often have mixed or uncertain causes of respiratory failure. The optimal treatment for such patients is unclear. Both high-flow nasal cannula (HFNC) and noninvasive ventilation (NIV) are used., Objectives: We sought to compare the effectiveness of initial treatment with HFNC versus NIV for acute hypoxemic respiratory failure., Design Setting and Participants: We conducted a retrospective cohort study of patients with acute hypoxemic respiratory failure treated with HFNC or NIV within 24 hours of arrival to the University of Michigan adult ED from January 2018 to December 2022. We matched patients 1:1 using a propensity score for odds of receiving NIV., Main Outcomes and Measures: The primary outcome was major adverse pulmonary events (28-d mortality, ventilator-free days, noninvasive respiratory support hours) calculated using a win ratio., Results: A total of 1154 patients were included. Seven hundred twenty-six (62.9%) received HFNC and 428 (37.1%) received NIV. We propensity score matched 668 of 1154 (57.9%) patients. Patients on NIV versus HFNC had lower 28-day mortality (16.5% vs. 23.4%, p = 0.033) and required noninvasive treatment for fewer hours (median 7.5 vs. 13.5, p < 0.001), but had no difference in ventilator-free days (median [interquartile range]: 28 [26, 28] vs. 28 [10.5, 28], p = 0.199). Win ratio for composite major adverse pulmonary events favored NIV (1.38; 95% CI, 1.15-1.65; p < 0.001)., Conclusions and Relevance: In this observational study of patients with acute hypoxemic respiratory failure, initial treatment with NIV compared with HFNC was associated with lower mortality and fewer composite major pulmonary adverse events calculated using a win ratio. These findings underscore the need for randomized controlled trials to further understand the impact of noninvasive respiratory support strategies., Competing Interests: Dr. Munroe was supported by grant number T32 HL 007749 (Multidisciplinary Training Program in Lung Disease), grant number F32 HL 172463 and grant number L30 HL 170379 (Loan Repayment Award) from the National Institutes of Health (NIH) and the National Heart, Lung, and Blood Institute (NHLBI). This work was also supported in part by a grant from NIH (NINDS and NHLBI) for infrastructure for the Clinical Coordinating Center for the Strategies to Innovate EmeRgENcy Care Clinical Trials Network—2U24NS100659. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH. This article does not represent the views of the Department of Veterans Affairs or the U.S. government. Dr. Mosier has received travel support from Fisher & Paykel. The remaining authors have disclosed that they do not have any potential conflicts of interest.

High concentrations of oxygen are often needed to optimize oxygenation in infants with persistent pulmonary hypertension (PPHN), but this can also increase the risk of hyperoxemia. We determined the occurrence of hyperoxemia in infants treated for PPHN. Medical records of infants ≥ 34 + 0 weeks gestational age (GA) who received inhaled nitric oxide (iNO) were retrospectively reviewed for oxygenation parameters during iNO therapy. Oxygen was manually titrated to target arterial oxygen tension (PaO 2 ) 10-13 kPa and peripheral oxygen saturation (SpO 2 ) 92-98%. The main study outcomes were the incidence and duration of hyperoxemia and hypoxemia and the fraction of inspired oxygen (FiO 2 ). A total of 181 infants were included. The median FiO 2 was 0.43 (IQR 0.34-0.56) and the maximum FiO 2 was 1.0 in 156/181 (86%) infants, resulting in at least one PaO 2  > 13 kPa in 149/181 (82%) infants, of which 46/149 (31%) infants had minimal one PaO 2  > 30 kPa. SpO 2 was > 98% in 179/181 (99%) infants for 17.7% (8.2-35.6%) of the iNO time. PaO 2  < 10 kPa occurred in 160/181 (88%) infants, of which 81/160 (51%) infants had minimal one PaO 2  < 6.7 kPa. SpO 2 was < 92% in 169/181 (93%) infants for 1.6% (0.5-4.3%) of the iNO time.    Conclusion: While treatment of PPHN is focused on preventing and reversing hypoxemia, hyperoxemia occurs inadvertently in most patients. What is Known: • High concentrations of oxygen are often needed to prevent hypoxemia-induced deterioration of PPHN, but this can also increase the risk of hyperoxemia. • Infants with persistent pulmonary hypertension may be particularly vulnerable to the toxic effects of oxygen, and hyperoxemia could further induce pulmonary vasoconstriction, potentially worsening the condition. What is New: • Hyperoxemia occurs in the majority of infants with PPHN during treatment with iNO. • Infants with PPHN spent a considerably longer period with saturations above the target range compared to saturations below the target range., (© 2024. The Author(s).)

Background: The safety and efficacy of bubble continuous positive airway pressure (bCPAP) for treatment of childhood severe pneumonia outside tertiary care hospitals is uncertain. We did a cluster-randomised effectiveness trial of locally made bCPAP compared with WHO-recommended low-flow oxygen therapy in children with severe pneumonia and hypoxaemia in general hospitals in Ethiopia., Methods: This open, cluster-randomised trial was done in 12 general (secondary) hospitals in Ethiopia. We randomly assigned six hospitals to bCPAP as first-line respiratory support for children aged 1-59 months who presented with severe pneumonia and hypoxaemia and six hospitals to standard low-flow oxygen therapy. Cluster (hospital) randomisation was stratified by availability of mechanical ventilation. All children received treatment in paediatric wards (in a dedicated corner in front of a nursing station) with a similar level of facilities (equipment for oxygen therapy and medications) and staffing (overall, one nurse per six patients and one general practitioner per 18 patients) in all hospitals. All children received additional care according to WHO guidelines, supervised by paediatricians and general practitioners. The primary outcome was treatment failure (defined as any of the following: peripheral oxygen saturation <85% at any time after at least 1 h of intervention plus signs of respiratory distress; indication for mechanical ventilation; death during hospital stay or within 72 h of leaving hospital against medical advice; or leaving hospital against medical advice during intervention). The analysis included all children enrolled in the trial. We performed both unadjusted and adjusted analyses of the primary outcome, with the latter adjusted for the stratification variable and for the design effect of cluster randomisation, as well as selected potentially confounding variables, including age. We calculated effectiveness as the relative risk (RR) of the outcomes in the bCPAP group versus low-flow oxygen group. This trial is registered with ClinicalTrial.gov, NCT03870243, and is completed., Findings: From June 8, 2021, to July 27, 2022, 1240 children were enrolled (620 in hospitals allocated to bCPAP and 620 in hospitals allocated to low-flow oxygen). Cluster sizes ranged from 103 to 104 children. Five (0·8%) of 620 children in the bCPAP group had treatment failure compared with 21 (3·4%) of 620 children in the low-flow oxygen group (unadjusted RR 0·24, 95% CI 0·09-0·63, p=0·0015; adjusted RR 0·24, 0·07-0·87, p=0·030). Six children died during hospital stay, all of whom were in the low-flow oxygen group (p=0·031). No serious adverse events were attributable to bCPAP., Interpretation: In Ethiopian general hospitals, introduction of locally made bCPAP, supervised by general practitioners and paediatricians, was associated with reduced risk of treatment failure and in-hospital mortality in children with severe pneumonia and hypoxaemia compared with use of standard low-flow oxygen therapy. Implementation research is required in higher mortality settings to consolidate our findings., Funding: SIDA Sweden and Grand Challenges Ethiopia., Competing Interests: Declaration of interests We declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC-ND 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Acute respiratory distress syndrome (ARDS), first described in 1967, is characterized by acute respiratory failure causing profound hypoxemia, decreased pulmonary compliance, and bilateral CXR infiltrates. After several descriptions, the Berlin definition was adopted in 2012, which established three categories of severity according to hypoxemia (mild, moderate and severe), specified temporal aspects for diagnosis, and incorporated the use of non-invasive ventilation. The COVID-19 pandemic led to changes in ARDS management, focusing on continuous monitoring of oxygenation and on utilization of high-flow oxygen therapy and lung ultrasound. In 2021, a New Global Definition based on the Berlin definition of ARDS was proposed, which included a category for non-intubated patients, considered the use of SpO2, and established no particular requirement for oxygenation support in regions with limited resources. Although debates persist, the continuous evolution seeks to adapt to clinical and epidemiological needs, and to the search of personalized treatments., (Copyright © 2024 Elsevier España, S.L.U. and SEMICYUC. All rights reserved.)

Objectives: Improving the efficiency of clinical trials in acute hypoxemic respiratory failure (HRF) depends on enrichment strategies that minimize enrollment of patients who quickly resolve with existing care and focus on patients at high risk for persistent HRF. We aimed to develop parsimonious models predicting risk of persistent HRF using routine data from ICU admission and select research immune biomarkers., Design: Prospective cohorts for derivation ( n = 630) and external validation ( n = 511)., Setting: Medical and surgical ICUs at two U.S. medical centers., Patients: Adults with acute HRF defined as new invasive mechanical ventilation (IMV) and hypoxemia on the first calendar day after ICU admission., Interventions: None., Measurements and Main Results: We evaluated discrimination, calibration, and practical utility of models predicting persistent HRF risk (defined as ongoing IMV and hypoxemia on the third calendar day after admission): 1) a clinical model with least absolute shrinkage and selection operator (LASSO) selecting Pa o2 /F io2 , vasopressors, mean arterial pressure, bicarbonate, and acute respiratory distress syndrome as predictors; 2) a model adding interleukin-6 (IL-6) to clinical predictors; and 3) a comparator model with Pa o2 /F io2 alone, representing an existing strategy for enrichment. Forty-nine percent and 69% of patients had persistent HRF in derivation and validation sets, respectively. In validation, both LASSO (area under the receiver operating characteristic curve, 0.68; 95% CI, 0.64-0.73) and LASSO + IL-6 (0.71; 95% CI, 0.66-0.76) models had better discrimination than Pa o2 /F io2 (0.64; 95% CI, 0.59-0.69). Both models underestimated risk in lower risk deciles, but exhibited better calibration at relevant risk thresholds. Evaluating practical utility, both LASSO and LASSO + IL-6 models exhibited greater net benefit in decision curve analysis, and greater sample size savings in enrichment analysis, compared with Pa o2 /F io2 . The added utility of LASSO + IL-6 model over LASSO was modest., Conclusions: Parsimonious, interpretable models that predict persistent HRF may improve enrichment of trials testing HRF-targeted therapies and warrant future validation., Competing Interests: Drs. Sathe, Morrell, Bhatraju, and Ware received support for article research from the National Institutes of Health (NIH). Dr. Kerchberger’s institution received funding from the National Heart, Lung, and Blood Institute and the American Thoracic Society. Dr. Hough’s institution received funding from the NIH, the American Lung Association, and the Centers for Disease Control and Prevention. Dr. Ware’s institution received funding from the NIH; she received funding from Arrowhead, Akebia, Santhera, Global Blood Therapeutics, and Boehringer Ingelheim; she received support for article research from Genentech and Boehringer Ingelheim; and she disclosed they are a stockholder of Virtuoso Surgical. The remaining authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2024 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.)

Refractory hypoxemia (RH) during venovenous extracorporeal membrane oxygenation (VV ECMO) support is a complex problem that limits the benefit of this therapy. The need for sustained deep sedation and delays in active rehabilitation are considered as a direct consequence of RH. Changing from VV ECMO to a configuration that returns the flow to pulmonary artery, such as venopulmonary extracorporeal membrane oxygenation (VPa ECMO) may decrease recirculation and improve systemic oxygen delivery. We present a retrospective report that describes the impact of VPa ECMO on oxygenation during sedation withdrawal in 41 patients who received VV ECMO for coronavirus disease 2019 (COVID-19). We evidenced that arterial oxygen pressure (PaO 2 ) increased from 68 to 112.3 mm Hg ( p = 0.001) with a reduction of ECMO flow (5.7-4.8 L/m; p = 0.001). Other findings included lower rates of depth sedation (Richmond Agitation Sedation Scale [RASS] ≤3, 37-63%; p = 0.007) and lower requirement inotropic support assessed by LVIS score (4.7-1.1; p = 0.005). Discharge survival was 54% with a sustained benefit until day 79. This cannulation strategy improved effectively PaO 2 in this cohort, it may be an alternative in patients with RH in VV ECMO., Competing Interests: Disclosure: The authors have no conflicts of interest to report., (Copyright © ASAIO 2024.)

Acute respiratory distress syndrome (ARDS) is one of the most common syndromes in the intensive care unit, with a high mortality and morbidity. Refractory hypoxia is the typical feature of ARDS, and improving hypoxia is the key to the treatment of ARDS. Due to the rapid progression of ARDS, invasive ventilation is usually used to improve hypoxia. But in recent years, with the extending of the understanding of ARDS and the development of non-invasive oxygen therapy, high flow nasal oxygen (HFNO) and non-invasive ventilation (NIV) are gradually used in ARDS. Therefore, we reviewed the role of HFNO and NIV in ARDS in this paper.

Objective: To retrieve, evaluate, and summarize the best evidence for the treatment of hypoxemia in patients with COVID-19 infection using the awake prone positioning, with the aim of guiding healthcare professionals in the standardized implementation of this therapy. Methods: A systematic search was conducted in databases including UpToDate, BMJ Best Practice, JBI Evidence-Based Healthcare Center, American Association of Critical-Care Nurses, Intensive Care Society, European Respiratory Society, World Health Organization website, Cochrane Library, PubMed, China National Knowledge Infrastructure (CNKI), and Wanfang. The retrieved literature was subjected to quality assessment and evidence extraction. Results: A total of ten publications were included, consisting of one thematic evidence summary, one guideline, two systematic reviews, three randomized controlled trials, and three expert consensus statements. This summary synthesizes thirty key pieces of evidence in five categories: organizational management and training, risk assessment, preparatory operations, implementation key points, and risk control. Conclusions: Awake prone positioning is beneficial for improving hypoxemia in patients with COVID-19 and is easy to implement. Medical institutions should develop nursing management systems, operational standards, and best practices for awake prone positioning based on evidence-based evidence in order to improve the quality of care management for such patients.

Importance: Supplemental oxygen is ubiquitously used in patients with COVID-19 and severe hypoxemia, but a lower dose may be beneficial., Objective: To assess the effects of targeting a Pao2 of 60 mm Hg vs 90 mm Hg in patients with COVID-19 and severe hypoxemia in the intensive care unit (ICU)., Design, Setting, and Participants: Multicenter randomized clinical trial including 726 adults with COVID-19 receiving at least 10 L/min of oxygen or mechanical ventilation in 11 ICUs in Europe from August 2020 to March 2023. The trial was prematurely stopped prior to outcome assessment due to slow enrollment. End of 90-day follow-up was June 1, 2023., Interventions: Patients were randomized 1:1 to a Pao2 of 60 mm Hg (lower oxygenation group; n = 365) or 90 mm Hg (higher oxygenation group; n = 361) for up to 90 days in the ICU., Main Outcomes and Measures: The primary outcome was the number of days alive without life support (mechanical ventilation, circulatory support, or kidney replacement therapy) at 90 days. Secondary outcomes included mortality, proportion of patients with serious adverse events, and number of days alive and out of hospital, all at 90 days., Results: Of 726 randomized patients, primary outcome data were available for 697 (351 in the lower oxygenation group and 346 in the higher oxygenation group). Median age was 66 years, and 495 patients (68%) were male. At 90 days, the median number of days alive without life support was 80.0 days (IQR, 9.0-89.0 days) in the lower oxygenation group and 72.0 days (IQR, 2.0-88.0 days) in the higher oxygenation group (P = .009 by van Elteren test; supplemental bootstrapped adjusted mean difference, 5.8 days [95% CI, 0.2-11.5 days]; P = .04). Mortality at 90 days was 30.2% in the lower oxygenation group and 34.7% in the higher oxygenation group (risk ratio, 0.86 [98.6% CI, 0.66-1.13]; P = .18). There were no statistically significant differences in proportion of patients with serious adverse events or in number of days alive and out of hospital., Conclusion and Relevance: In adult ICU patients with COVID-19 and severe hypoxemia, targeting a Pao2 of 60 mm Hg resulted in more days alive without life support in 90 days than targeting a Pao2 of 90 mm Hg., Trial Registration: ClinicalTrials.gov Identifier: NCT04425031.