Association of ROX Index with Mechanical Ventilator Use in Sepsis Patients in the Emergency Department

Detecting sepsis patients who are at a high-risk of mechanical ventilation is important in emergency departments (ED). The respiratory rate oxygenation (ROX) index is the ratio of tissue oxygen saturation/fraction of inspired oxygen to the respiratory rate. This study aimed to investigate whether the ROX index could predict mechanical ventilator use in sepsis patients in an ED. This retrospective observational study included quick sequential organ failure assessment (qSOFA) ≥ 2 sepsis patients that presented to the ED between September 2019 and April 2020. The ROX and ROX-heart rate (HR) indices were significantly lower in patients with mechanical ventilator use within 24 h than in those without the use of a mechanical ventilator (4.0 [3.2–5.4] vs. 10.0 [5.9–15.2], p < 0.001 and 3.9 [2.7–5.8] vs. 10.1 [5.4–16.3], p < 0.001, respectively). The area under the receiver operating characteristic (ROC) curve of the ROX and ROX-HR indices were 0.854 and 0.816 (both p < 0.001). The ROX and ROX-HR indices were independently associated with mechanical ventilator use within 24 h (adjusted hazard ratio = 0.78, 95% CI: 0.68–0.90, p < 0.001 and adjusted hazard ratio = 0.87, 95% CI 0.79–0.96, p = 0.004, respectively). The 28-day mortality was higher in the low ROX and low ROX-HR groups. The ROX and ROX-HR indices were associated with mechanical ventilator use within 24 h in qSOFA ≥ 2 patients in the ED.

Efficacy and safety of endotracheal instillation of iloprost for persistent pulmonary hypertension of the newborn

Objective: To determine the efficacy and safety of endotracheal instillation of iloprost as a rescue therapy for persistent pulmonary hypertension of the newborn. Methods: Neonates diagnosed with persistent pulmonary hypertension who were unresponsive to standard treatment protocol applied for persistent pulmonary hypertension in our unit, and who were being followed up with mechanical ventilation, were included in the study. Iloprost was instilled endotracheally as a rescue treatment. Systolic pulmonary artery pressure, oxygen saturation index, mean airway pressure, fraction of inspired oxygen, preductal and postductal venous oxygen saturation, heart rate, and blood pressure were recorded before and after 30 minutes of endotracheal iloprost instillation. Adverse events after endotracheal iloprost were recorded. Results: Twenty neonates were included. The median gestational age and birth weight were found to be 37 (30.5-38) weeks and 2975 (2125-3437.5) grams, respectively. When compared to the period before endotracheal iloprost instillation, systolic pulmonary artery pressure, oxygen saturation index, mean airway pressure, and fraction of inspired oxygen values significantly decreased (p < 0.001, p < 0.001, p = 0.021, p = 0.001, respectively), whereas preductal and postductal oxygen saturation values significantly increased 30 minutes after the endotracheal iloprost instillation (p = 0.002, p < 0.001, respectively). There were no significant differences in heart rate and blood pressure values before and after the iloprost administration. No adverse events were observed. Conclusion: Endotracheal instillation of iloprost was found to be an effective and safe therapy for persistent pulmonary hypertension unresponsive to conventional treatment.

Can Fraction of Inspired Oxygen Predict Extubation Failure in Preterm Infants?

Background: Prolonged mechanical ventilation in preterm infants may cause complications. We aimed to analyze the variables affecting extubation outcomes in preterm infants at high risk of extubation failure. Methods: This was a single-center, observational, retrospective study. Extubation failure was defined as survival with the need for reintubation within 72 h. Successfully extubated neonates (group 1) were compared to those with failed extubation (group 2). Multivariate logistic regression analysis evaluated factors that predicted extubation outcomes. Results: Eighty infants with a birth weight under 1000 g and/or gestational age (GA) under 28 weeks were included. Extubation failure occurred in 29 (36.2%) and success in 51 (63.8%) neonates. Most failures (75.9%) occurred within 24 h. Pre-extubation inspired oxygen fraction (FiO2) of 27% had a sensitivity of 58.6% and specificity of 64.7% for extubation failure. Post-extubation FiO2 of 32% had a sensitivity of 65.5% and specificity of 62.8% for failure. Prolonged membrane rupture (PROM) and high GA were associated with extubation success in multivariate logistic regression analysis. Conclusions: High GA and PROM were associated with extubation success. Pre- and post-extubation FiO2 values were not significantly predictive of extubation failure. Further studies should evaluate if overall assessment, including ventilatory parameters and clinical factors, can predict extubation success in neonates.

GB0139, an inhaled small molecule inhibitor of galectin-3, in COVID-19 pneumonitis: a randomised, controlled, open-label, phase 2a experimental medicine trial of the safety, pharmacokinetics, and potential therapeutic value

Rationale: High galectin-3 levels predict poor outcomes in patients with COVID-19. Galectin-3 activates monocytes and macrophages which are directly implicated in COVID-19 immunopathology and the cytokine storm. GB0139 is a potent thiodigalactoside galectin-3 inhibitor and may reduce the severe effects of the disease. We report safety and pharmacokinetics and pharmacodynamics of the inhaled galectin-3 inhibitor, GB0139, and assess clinical outcomes and key systemic inflammatory biomarkers in hospitalised patients with COVID-19 (ClinicalTrials.gov/EudraCT identifier: NCT04473053/2020-002230-32). Methods: Adults with COVID-19 requiring oxygen, and with pneumonitis on x-ray, were randomised to receive standard of care (SOC; including dexamethasone; n=21) or SOC plus 10 mg GB0139 twice daily for 48 hours, then once daily for ≤14 days (n=20). Results: Patients aged 27–87 years were enrolled from July 2020; the final patient completed the 90-day follow-up in April 2021. GB0139+SOC was well tolerated with no treatment-related serious adverse events reported. Incidences of adverse events were similar between treatment arms (40 with GB0139+SOC vs 35 with SOC). Plasma GB0139 was measurable in all patients after inhaled exposure, with moderate interpatient variability, and demonstrated target engagement with decreased circulating galectin (overall treatment effect post-hoc over days 2–7: p=0·0099 vs SOC). Rate of decline in fraction of inspired oxygen (%) requirement was significantly greater in the GB0139+SOC arm with a posterior mean difference of −1 ·51 (95% highest posterior density: −2·90, −0·189) versus SOC. Plasma levels of biomarkers associated with inflammation, coagulopathy, major organ function and fibrosis showed a downward trend versus SOC. Conclusions: GB0139+SOC was well tolerated and achieved clinically relevant plasma concentrations and target engagement. This, and the reduction in markers associated with inflammatory, coagulation, fibrosis, and reduction in inspired oxygen (%) over SOC alone, indicates the therapeutic potential for inhaled GB0139 in hospitalised patients with COVID-19.

Causes and Treatment of Hypoxia during Total Hip Arthroplasty in Elderly Patients: A Case Report

Intraoperative hypoxia occurs in approximately 6.8% of surgeries and requires appropriate management to avoid poor outcomes, such as increased mortality or extended hospitalization. Hypoxia can be caused by a variety of factors, including laryngospasm, inhalational anesthetics, and surgery for abdominal pathology or hip fractures. In particular, elderly patients are more vulnerable to hypoxia due to their existing lung diseases or respiratory muscle weakness. This study presents the cases of two elderly patients who developed hypoxia during total hip arthroplasty under general anesthesia. Positive end expiratory pressure, the recruitment maneuver, and increased fraction of inspired oxygen improved hypoxia only temporarily, and patients’ oxygen saturation level again dropped to 79–80%. We suspected that hypoxia was caused by atelectasis and, therefore, resumed spontaneous respiration. Thereafter, both the patients showed an improvement in hypoxia. Intraoperative hypoxia that is suspected to be caused by atelectasis can be improved by securing sufficient lung volume for respiration through increased muscle tone with spontaneous respiration.

Inspired oxygen: present, past, and future

As earthlings, we take the oxygen in the air that we breathe for granted. Few people realize that this easy access to oxygen makes us unique in the whole universe. Nowhere else in our planetary system or in distant stars has stable oxygen ever been detected. However, the present plentiful supply of oxygen in our atmosphere was not always there. Long after the earth was formed some 4.5 billion years ago, the PO2 in the atmosphere was near zero, and it remained so for millions of years. But about 2 billion years ago, the PO2 dramatically increased to as high as 200 mmHg during the Great Oxygen Event, due to the activity of microorganisms, the cyanobacteria. Subsequently the oxygen level fell to the intermediate values that we have today. Here we also look to the future, for example, the next 50 years. This period will be special because it will include the beginnings of human space exploration, initially to the Moon and Mars. Neither of these has atmospheric oxygen. Nevertheless, plans to visit and live on both of these are developing rapidly. We consider the fascinating problems of how to how to ensure that sufficient oxygen will be available for groups of people . While it is interesting to discuss these issues now, we can expect that major advances will be made in the next few years.

507. Impact of Baricitinib on Outcomes in Patients Treated with Remdesivir and Dexamethasone for SARS-CoV-2 Pneumonia: A Retrospective Cohort Study

Background There is a lack of data specifically addressing the effects of triple therapy consisting of baricitinib plus remdesivir plus dexamethasone compared to dual therapy with remdesivir plus dexamethasone among patients with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) pneumonia. Methods This retrospective study enrolled hospitalized adults with SARS-CoV-2 receiving supplemental oxygen without invasive mechanical ventilation (IMV) being treated baricitinib (≤10 days) plus remdesivir (≤10 days) plus dexamethasone (≤10 days) or remdesivir (≤10 days) plus dexamethasone (≤10 days). The primary endpoint was 28-day mortality. Secondary objectives of this study were to measure progression to IMV, pulse oximetry (SpO2)/fraction of inspired oxygen (FiO2) from hospitalization to discharge, hospital length of stay (LOS), 14-day mortality, 14-day hospital readmissions, inflammatory markers, and safety outcomes. Results Among patients receiving supplemental oxygen without IMV, 28-day mortality for triple therapy vs. dual therapy was 20% and 24%, respectively (P=1.000). The effect of triple therapy compared to dual therapy on lung function was demonstrated by a 76% vs. 25% increase in SpO2/FiO2. This benefit must be contextualized by an increased progression to IMV among patients receiving triple therapy compared to dual therapy (10 patients [50%] vs. 7 patients [28%], respectively; P=0.130). The increased incidence of IMV translated to a significantly longer hospital LOS among patients receiving triple therapy compared to dual therapy (26 days vs. 17 days, respectively; P=0.001). Conclusion In patients receiving supplemental oxygen without IMV for SARS-CoV-2, triple therapy was not associated with a clinically meaningful reduction in 28-day mortality when compared to dual therapy. Disclosures All Authors: No reported disclosures

Awake craniotomy using a high-flow nasal cannula with oxygen reserve index monitoring - A report of two cases -

Background: Awake craniotomy is a well-tolerated procedure for the resection of brain tumors residing within or close to the eloquent cortical areas. Monitored anesthesia care (MAC) is a dominant anesthetic approach for awake craniotomy; however, it is associated with inherent challenges such as desaturation and hypercapnia, which may lead to various complications. The prevention of respiratory insufficiency is important for successful awake craniotomy. As measures to avoid respiratory depression, the use of high-flow nasal cannula (HFNC) can improve patient oxygenation and monitor the oxygen reserve index (ORi) to detect hypoxia earlier. Case: We report two cases of awake craniotomy with MAC using HFNC and ORi. We adjusted the fraction of inspired oxygen of the HFNC according to the ORi level. The patient underwent successful awake craniotomy without a desaturation event or additional airway intervention. Conclusions: Combined HFNC and ORi monitoring may provide adequate oxygen reserves in patients undergoing awake craniotomy.

Cardiorespiratory Response and Power Output During Submaximal Exercise in Normobaric Versus Hypobaric Hypoxia: A Pilot Study Using a Specific Chamber that Controls Environmental Factors

2021.—Many previous studies have examined hypoxia-induced physiological responses using various conditions, e.g., artificially reduced atmospheric oxygen concentration [normobaric hypoxia (NH) condition] or low barometric pressure at a mountain [hypobaric hypoxia (HH) condition]. However, when comparing the results from these previous studies conducted in artificial NH and HH including real high altitude, we must consider the possibility that environmental factors, such as temperature, humidity, and fraction of inspired carbon dioxide, might affect the physiological responses. Therefore, we examined cardiorespiratory responses and exercise performances during low- to high-intensity exercise at a fixed heart rate (HR) in both NH and HH using a specific chamber where atmospheric oxygen concentration and barometric pressure as well as the abovementioned environmental factors were precisely controlled. Ten well-trained university students (eight males and two females) performed the exercise test consisting of two 20-minute submaximal pedaling at the intensity corresponding to 50% (low) and 70% (high) of their HR reserve, under three conditions [NH (fraction of inspired oxygen, 0.135; barometric pressure, 754 mmHg), HH (fraction of inspired oxygen, 0.209; barometric pressure, 504 mmHg), and normobaric normoxia (NN; fraction of inspired oxygen, 0.209; barometric pressure, 754 mmHg)]. Peripheral oxygen saturation (SpO2) to estimate arterial oxygen saturation and partial pressure of end-tidal carbon dioxide (PETCO2) were monitored throughout the experiment. SpO2, PETCO2, and power output at fixed HRs (i.e., pedaling efficiency) in NH and HH were all significantly lower than those in NN. Moreover, high-intensity exercise in HH induced greater decreases in SpO2 and power output than did high-intensity exercise in NH (NH vs. HH; SpO2, 78.2% - 5.0% vs. 75.1% - 7.1%; power output, 120.7 - 24.9 W vs. 112.4 - 23.2 W, both p < 0.05). However, high-intensity exercise in HH induced greater increases in PETCO2 than did high-intensity exercise in NH (NH vs. HH; 54.2 - 5.9mmHg vs. 57.2 - 3.4 mmHg, p < 0.01). These results suggest that physiological responses and power output at a fixed HR during hypoxic exposure might depend on the method used to generate the hypoxic condition.