Innovating to resolve the pressure-oxygenation-paradox created by VA-ECMO could improve outcomes for acute myocardial infarction and cardiogenic shock.

VA-ECMO use is growing exponentially. Recent data shows no clinical benefit with routine use of VA-ECMO in acute myocardial infarction and shock, however clinical experience with ECMO is growing. Two key variables that may impact outcomes with ECMO in acute myocardial infarction and shock include it's effect on systemic pressure and oxygenation. We define the pressure-oxygenaton paradox of ECMO as a potential new avenue for therapeutic discovery.

Comparative effects of variable versus conventional volume-controlled one-lung ventilation on gas exchange and respiratory system mechanics in thoracic surgery patients: A randomized controlled clinical trial.

BACKGROUND: Mechanical ventilation with variable tidal volumes (V-VCV) has the potential to improve lung function during general anesthesia. We tested the hypothesis that V-VCV compared to conventional volume-controlled ventilation (C-VCV) would improve intraoperative arterial oxygenation and respiratory system mechanics in patients undergoing thoracic surgery under one-lung ventilation (OLV). METHODS: Patients were randomized to V-VCV (n = 39) or C-VCV (n = 39). During OLV tidal volume of 5 mL/kg predicted body weight (PBW) was used. Both groups were ventilated with a positive end-expiratory pressure (PEEP) of 5 cm H2O, inspiration to expiration ratio (I:E) of 1:1 (during OLV) and 1:2 during two-lung ventilation, the respiratory rate (RR) titrated to arterial pH, inspiratory peak-pressure ≤ 40 cm H2O and an inspiratory oxygen fraction of 1.0. RESULTS: Seventy-five out of 78 Patients completed the trial and were analyzed (dropouts were excluded). The partial pressure of arterial oxygen (PaO2) 20 min after the start of OLV did not differ among groups (V-VCV: 25.8 ± 14.6 kPa vs C-VCV: 27.2 ± 15.3 kPa; mean difference [95% CI]: 1.3 [-8.2, 5.5], P = 0.700). Furthermore, intraoperative gas exchange, intraoperative adverse events, need for rescue maneuvers due to desaturation and hypercapnia, incidence of postoperative pulmonary and extra-pulmonary complications, and hospital free days at day 30 after surgery did not differ between groups. CONCLUSIONS: In thoracic surgery patients under OLV, V-VCV did not improve oxygenation or respiratory system mechanics compared to C-VCV. Ethical Committee: EK 420092019. TRIAL REGISTRATION: at the German Clinical Trials Register: DRKS00022202 (16.06.2020).

Nasal cannula and face mask gas flow rates when connecting to the Y-piece of the anesthesia circuit.

STUDY OBJECTIVE: To determine the relationship between the delivered gas flows via nasal cannulas and face masks and the set gas flow and the breathing circuit pressure when connecting to the Y-adapter of the anesthesia breathing circuit and using the oxygen blender on the anesthesia machine, relevant to surgery when there is concern for causing a fire. The flow rates that are delivered at various flow rates and circuit pressures have not been previously studied. DESIGN: Laboratory investigation. SETTING: Academic medical center. PATIENTS: None. INTERVENTIONS: The gas flows from each of 3 anesthesia machines from the same manufacturer were systematically increased from 1 to 15 L/min with changes to the adjustable pressure limiting valve to maintain 0-40 cm water pressure in the breathing circuit for nasal cannula testing and at 20-30 cm water circuit pressure for face masks. MEASUREMENTS: The delivered gas flows to the cannula were determined using a float-ball flowmeter for combinations of set gas flows and circuit pressures after connecting the cannula tubing to the Y-piece of the anesthesia circuit via a tracheal tube adapter. Decreasing the supply tubing length on the delivered flow rates was evaluated. MAIN RESULTS: There was a highly linear relationship between the anesthesia circuit pressure and the delivered nasal cannula flow rates, with 0 flow observed when the APL valve was fully open (i.e., 0 cm water). However, even under maximum conditions (40 cm water and 15 L/min), the delivered nasal cannula flow rate was 3.5 L/min. Shortening the 6.5-ft cannula tubing increased the flow at 20 and 30 cm water by approximately 0.12 L/min/ft. The estimated FiO2 assuming a minute ventilation of 5 L/min and 30% FiO2 ranged from 21.7% to 27.0% at nasal cannula flow rates of 0.5 to 4.0 L/min. When using a face mask and the APL fully closed, delivered flow rates were 0.25 L/min less than the set flow rate between 1 and 3 L/min and equal to the set flow rate between 4 and 8 L/min. CONCLUSIONS: When using a nasal cannula adapted to the Y-piece of the anesthesia circuit, the delivery system is linearly dependent on the pressure in the circuit and uninfluenced by the flow rate set on the anesthesia machine. However, only modest flow rates (≤ 3.5 L/min) and a limited increase in the inspired FiO2 are possible when using this delivery method. When using a face mask and the anesthesia circuit, flow rates close to the set flow rate are possible with the APL valve fully closed. Patients scheduled for sedation for head and neck procedures with increased fire risk who require more than a marginal increase in the FiO2 to maintain an acceptable pulse oximetry saturation may need general anesthesia with tracheal intubation.

Comparison of preoxygenation using a tight facemask, humidified high-flow nasal oxygen and a standard nasal cannula - a volunteer, randomised, crossover study.

BACKGROUND: Preoxygenation before anaesthesia induction is routinely performed via a tight-fitting facemask or humidified high-flow nasal oxygen. We hypothesised that effective preoxygenation, assessed by end-tidal oxygen (EtO 2 ) levels, can also be performed via a standard nasal cannula. OBJECTIVE: This study compared the efficacy of preoxygenation between a traditional facemask, humidified high-flow nasal oxygen and a standard nasal cannula. DESIGN: A volunteer, randomised, crossover study. SETTING: Karolinska University Hospital, Stockholm. The study was conducted between 2 May and 31 May 2023. PARTICIPANTS: Twenty cardiopulmonary healthy volunteers aged 25-65 years with a BMI <30. INTERVENTIONS: Preoxygenation using a traditional facemask, humidified high-flow nasal oxygen and standard nasal cannula. Volunteers were preoxygenated with all three methods, at various flow rates (10-50 l min -1 ), with open and closed mouths and during vital capacity manoeuvres. MAIN OUTCOME MEASURES: The study's primary outcome compared the efficacy after 3 min of preoxygenation, assessed by EtO 2 levels, between the three methods and various flow rates of preoxygenation. RESULTS: Three methods generated higher EtO 2 levels than others: (i) facemask preoxygenation using normal breathing, (ii) humidified high-flow nasal oxygen, closed-mouth breathing, at 50 l min -1 and (iii) standard nasal cannula, closed-mouth breathing, at 50 l min -1 , and expressed as means (SD): 90% (3), 90% (6) and 88% (5), respectively. Preoxygenation efficacy was greater via the bi-nasal cannulae using closed vs. open mouth breathing as well as with 3 min of normal breathing vs. eight vital capacity breaths. Preoxygenation with a facemask and humidified high-flow nasal oxygen was more comfortable than a standard nasal cannula. CONCLUSION: The efficacy of preoxygenation using a standard nasal cannula at high flow rates is no different to clinically used methods today. The standard nasal cannula provides less comfort but is highly effective and could be an option when alternative methods are unavailable. TRIAL REGISTRATION: Clinicaltrials.gov, NCT05839665.

Optimal flow of high-flow nasal cannula oxygenation to prevent desaturation during sedation for bronchoscopy: a randomized controlled study.

BACKGROUND: Although high-flow nasal cannula (HFNC) oxygenation is currently recommended to prevent desaturation during sedation for bronchoscopy, there is no consensus on an optimal flow rate. OBJECTIVE: To determine the optimal oxygen flow rate for HFNC to effectively prevent desaturation during sedation for bronchoscopy. DESIGN: Prospective, randomized, and controlled study. METHODS: Patients (n = 240) scheduled for bronchoscopy were randomized to receive HFNC with propofol sedation (fraction of inspired oxygen, 100%) at one of six flow rates of 10, 20, 30, 40, 50, and 60 L/min, designated as groups 1-6, respectively. RESULTS: The incidence of desaturation significantly decreased by increasing the oxygen flow rate (42.5%, 17.5%, 15%, 10%, 2.5%, and 0% for groups 1-6, respectively, p < 0.0001). The optimal oxygen flow rate for HFNC determined by probit regression to effectively prevent desaturation in 95% of patients was 43.20 (95% confidence interval, 36.43-55.96) L/min. The requirement for airway intervention was significantly decreased by increasing the oxygen flow rate. CONCLUSION: An HFNC flow rate of 50-60 L/min is recommended to prevent desaturation during sedation for bronchoscopy. REGISTRATION: NCT05298319 at ClinicalTrials.gov.

High-flow nasal cannula oxygenation during bronchoscopyMany patients undergo a special test to check their airways for problems. Sometimes, doctors need to take out a small part of the area that's causing trouble to find out what's wrong. But during this test, some patients can struggle to get enough oxygen, which can even be life-threatening. To help with this, there's a device called a high-flow nasal cannula (HFNC). It gives patients adjustable amounts of oxygen, like a gentle breeze into their nose. But doctors weren't sure how much oxygen was best during this test. So, we studied 240 patients using HFNC at different oxygen levels­like slow, medium, and fast flows. We found that the higher the oxygen flow, the less likely patients were to have oxygen problems. For example, at the lowest flow (10 liters per minute), about 42.5% of patients had oxygen trouble, but at the highest flow (60 liters per minute), none did. And we figured out that a flow rate around 43.2 liters per minute would prevent 95% patients from having oxygen problems. So, we recommend using a flow rate between 50 and 60 liters per minute during this test to keep patients safe from oxygen issues.

Occurrence of hyperoxia during iNO treatment for persistent pulmonary hypertension of the newborn: a cohort study.

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 (PaO2) 10-13 kPa and peripheral oxygen saturation (SpO2) 92-98%. The main study outcomes were the incidence and duration of hyperoxemia and hypoxemia and the fraction of inspired oxygen (FiO2). A total of 181 infants were included. The median FiO2 was 0.43 (IQR 0.34-0.56) and the maximum FiO2 was 1.0 in 156/181 (86%) infants, resulting in at least one PaO2 > 13 kPa in 149/181 (82%) infants, of which 46/149 (31%) infants had minimal one PaO2 > 30 kPa. SpO2 was > 98% in 179/181 (99%) infants for 17.7% (8.2-35.6%) of the iNO time. PaO2 < 10 kPa occurred in 160/181 (88%) infants, of which 81/160 (51%) infants had minimal one PaO2 < 6.7 kPa. SpO2 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.

Influence of acute dietary nitrate supplementation on oxygen delivery/consumption and limit of tolerance during progressive forearm exercise in men: a randomized crossover trial.

Beetroot juice (BRJ) supplementation increases nitric oxide bioavailability with hypoxia and acidosis, characteristics of high-intensity exercise. We investigated whether BRJ improved forearm oxygen delivery:demand matching in an intensity-dependent manner. Healthy men (21 ± 2.5 years) participated in a randomized crossover trial between October 2017 and May 2018 (Queen's University, Kingston, ON, Canada). Participants completed a forearm incremental exercise test to limit of tolerance (IET-LOT) 2.5 h post placebo (PL) versus BRJ (2 completed PL/BRJ vs. 9 completed BRJ/PL) within a 2-week period. Data are presented as mean ± standard deviation. There was a significant main effect of drink (PL < BRJ; P = 0.042, ηp2 = 0.385) and drink × intensity interaction for arteriovenous oxygen difference (PL < BRJ; P = 0.03; ηp2= 0.197; 20%-50% and 90% LOT). BRJ did not influence oxygen delivery (P = 0.893, ηp2 = 0.002), forearm blood flow (P = 0.589, ηp2 = 0.03) (forearm vascular conductance (P = 0.262, ηp2 = 0.124), mean arterial pressure (P = 0.254,ηp2 = 0.128)), oxygen consumption (P = 0.194, ηp2 = 0.179) or LOT (P = 0.432, d = 0.247). In healthy men, BRJ did not improve forearm oxygen delivery (vasodilatory or pressor response) during IET-LOT. Increased arteriovenous oxygen difference at submaximal intensities did not significantly influence oxygen consumption or performance across the entire range of forearm exercise intensities. This study adds to the growing body of evidence that BRJ does not influence small muscle mass blood flow in humans regardless of exercise intensity.

The effect of high-flow nasal oxygen flow rate on gas exchange in apnoeic patients: a randomised controlled trial.

High-flow nasal oxygen can be administered at induction of anaesthesia for the purposes of pre-oxygenation and apnoeic oxygenation. This intervention is claimed to enhance carbon dioxide elimination during apnoea, but the extent to which this occurs remains poorly quantified. The optimal nasal oxygen flow rate for gas exchange is also unknown. In this study, 114 patients received pre-oxygenation with high-flow nasal oxygen at 50 l.min-1. At the onset of apnoea, patients were allocated randomly to receive one of three nasal oxygen flow rates: 0 l.min-1; 70 l.min-1; or 120 l.min-1. After 4 minutes of apnoea, all oxygen delivery was ceased, tracheal intubation was performed, and oxygen delivery was recommenced when SpO2 was 92%. Mean (SD) PaCO2 rise during the first minute of apnoea was 1.39 (0.39) kPa, 1.41 (0.29) kPa, and 1.26 (0.38) kPa in the 0 l.min-1, 70 l.min-1 and 120 l.min-1 groups, respectively; p = 0.16. During the second, third and fourth minutes of apnoea, mean (SD) rates of rise in PaCO2 were 0.34 (0.08) kPa.min-1, 0.36 (0.06) kPa.min-1 and 0.37 (0.07) kPa.min-1 in the 0 l.min-1, 70 l.min-1 and 120 l.min-1 groups, respectively; p = 0.17. After 4 minutes of apnoea, median (IQR [range]) arterial oxygen partial pressures in the 0 l.min-1, 70 l.min-1 and 120 l.min-1 groups were 24.5 (18.6-31.4 [12.3-48.3]) kPa; 36.6 (28.1-43.8 [9.8-56.9]) kPa; and 37.6 (26.5-45.4 [11.0-56.6]) kPa, respectively; p < 0.001. Median (IQR [range]) times to desaturate to 92% after the onset of apnoea in the 0 l.min-1, 70 l.min-1 and 120 l.min-1 groups, were 412 (347-509 [190-796]) s; 533 (467-641 [192-958]) s; and 531 (462-681 [326-1007]) s, respectively; p < 0.001. In conclusion, the rate of carbon dioxide accumulation in arterial blood did not differ significantly between apnoeic patients who received high-flow nasal oxygen and those who did not.

Concentraciones de oxígeno intermitentes tienen impacto en el desarrollo postnatal temprano de ratas Sprague-Dawley: efectos en CA1 del hipocampo / Intermittent oxygen concentrations have an impact on the early postnatal development of Sprague-Dawley rats: effects on hippocampal CA1

El periodo postnatal temprano se caracteriza por rápido crecimiento cerebral, posiblemente relacionado con variaciones del oxígeno tisular. Esto ha motivado el estudio de protocolos que suministran diferentes concentraciones de oxígeno intermitentes, para observar sus efectos morfológicos y cerebrales. Se utilizaron 52 crías de ratas Sprague Dawley, distribuidas en igual número a cuatro grupos experimentales, Control (C, 21 %O2), Hipoxia Intermitente (HI, 11 %O2), Hiperoxia Intermitente (HOI, 30 %O2) e Hipoxia Hiperoxia Intermitente (HHI, 11 % -30 %O2). Los protocolos consideraron 5 ciclos de 5 minutos de dosificación, durante 50 minutos diarios. Se realizó en una cámara semihermética entre los días 5 al 11 postnatales. Las evaluaciones de crecimiento corporal y cuantificación neuronal, se realizaron en las crías macho, en el día 28 postnatal. El peso corporal en el grupo hipoxia intermitente mostró diferencias significativas respecto al grupo hiperoxia intermitente (HI vs HOI, p<0,01) y al grupo hipoxia-hiperoxia Intermitente (HI vs HHI, p< 0,001). La talla corporal disminuyó en el grupo hipoxia-hiperoxia intermitente con diferencias significativas respecto del grupo control (C vs HHI, p<0,05) y respecto del grupo hipoxia intermitente (HHI vs HI, p< 0,01). El conteo neuronal en el área CA1 del hipocampo aumentó en el grupo hipoxia intermitente con diferencias significativas respecto a los grupos control (C vs HI; p<0,05), al grupo hiperoxia intermitente (HI vs HOI; p<0,001) y al grupo hipoxia-hiperoxia intermitente (HI vs HHI; p<0,001). Finalmente, el grupo hipoxia- hiperoxia Intermitente disminuyó significativamente en la cantidad de neuronas en comparación al grupo hiperoxia intermitente (HHI vs HOI; p<0,001). La hipoxia intermitente mostró resultados beneficiosos en el crecimiento corporal y cantidad de neuronas en el área CA1 del hipocampo, en contraste, la hipoxia hiperoxia intermitente experimentó resultados adversos con disminución de estas variables, en el periodo postnatal temprano de la rata.

SUMMARY: The early postnatal period is characterized by rapid brain growth, possibly related to variations in tissue oxygen. This has motivated the study of protocols that supply different intermittent oxygen concentrations, to observe their morphological and cerebral effects. Fifty-two pups Sprague-Dawley rats were distributed in equal numbers into four experimental groups, Control (C, 21 %O), Intermittent Hypoxia (HI, 11 %O), Intermittent Hyperoxia (HOI, 30 %O2) and Intermittent Hypoxia Hyperoxia (HHI, 11 % - 30 %O2). The protocols considered 5 cycles of 5 min of dosing, for 50 min diary. It was performed in a semi- hermetic chamber between 5 to 11postnatal days. The evaluations of body growth and neuronal quantification were analyzed in male pups, on postnatal day 28. Body weight in the intermittent hypoxia group showed significant differences compared to the intermittent hyperoxia group (HI vs HOI, p<0.01) and the intermittent hypoxia- hyperoxia group (HI vs HHI, p<0.001). Body size decreased in the Intermittent hypoxia-hyperoxia group with significant differences compared to the control group (C vs HHI, p<0.05) and with respect to the intermittent hypoxia group (HHI vs HI, p<0.01). The neuronal count in the area CA1 of the hippocampus increased in the intermittent hypoxia group with significant differences compared to the control groups (C vs HI; p<0.05), to the intermittent hyperoxia group (HI vs HOI; p< 0.001) and the intermittent hypoxia-hyperoxia group (HI vs HHI; p<0.001). Finally, the intermittent hypoxia- hyperoxia group decreased significantly in the number of neurons compared with the intermittent hyperoxia group (HHI vs HOI; p<0.001). Intermittent hypoxia showed beneficial results in body growth and the number of neurons in the CA1 area of the hippocampus, in contrast, intermittent hypoxia-hyperoxia experienced adverse results with a decrease in these variables, in the early postnatal period of the rat.

Relationship between Anti-SARS-CoV-2 S Abs and IFN-λ3 Levels in the Administration of Oxygen following COVID-19 Vaccination.

Although the effectiveness of vaccination at preventing hospitalization and severe coronavirus disease (COVID-19) has been reported in numerous studies, the detailed mechanism of innate immunity occurring in host cells by breakthrough infection is unclear. One hundred forty-six patients were included in this study. To determine the effects of vaccination and past infection on innate immunity following SARS-CoV-2 infection, we analyzed the relationship between anti-SARS-CoV-2 S Abs and biomarkers associated with the deterioration of COVID-19 (IFN-λ3, C-reactive protein, lactate dehydrogenase, ferritin, procalcitonin, and D-dimer). Anti-S Abs were classified into two groups according to titer: high titer (≥250 U/ml) and low titer (<250 U/ml). A negative correlation was observed between anti-SARS-CoV-2 S Abs and IFN-λ3 levels (r = -0.437, p < 0.001). A low titer of anti-SARS-CoV-2 S Abs showed a significant association with oxygen demand in patients, excluding aspiration pneumonia. Finally, in a multivariate analysis, a low titer of anti-SARS-CoV-2 S Abs was an independent risk factor for oxygen demand, even after adjusting for age, sex, body mass index, aspiration pneumonia, and IFN-λ3 levels. In summary, measuring anti-SARS-CoV-2 S Abs and IFN-λ3 may have clinical significance for patients with COVID-19. To predict the oxygen demand of patients with COVID-19 after hospitalization, it is important to evaluate the computed tomography findings to determine whether the pneumonia is the result of COVID-19 or aspiration pneumonia.

Oxygen-Saturation Targets for Critically Ill Adults Receiving Mechanical Ventilation.

BACKGROUND: Invasive mechanical ventilation in critically ill adults involves adjusting the fraction of inspired oxygen to maintain arterial oxygen saturation. The oxygen-saturation target that will optimize clinical outcomes in this patient population remains unknown. METHODS: In a pragmatic, cluster-randomized, cluster-crossover trial conducted in the emergency department and medical intensive care unit at an academic center, we assigned adults who were receiving mechanical ventilation to a lower target for oxygen saturation as measured by pulse oximetry (Spo2) (90%; goal range, 88 to 92%), an intermediate target (94%; goal range, 92 to 96%), or a higher target (98%; goal range, 96 to 100%). The primary outcome was the number of days alive and free of mechanical ventilation (ventilator-free days) through day 28. The secondary outcome was death by day 28, with data censored at hospital discharge. RESULTS: A total of 2541 patients were included in the primary analysis. The median number of ventilator-free days was 20 (interquartile range, 0 to 25) in the lower-target group, 21 (interquartile range, 0 to 25) in the intermediate-target group, and 21 (interquartile range, 0 to 26) in the higher-target group (P = 0.81). In-hospital death by day 28 occurred in 281 of the 808 patients (34.8%) in the lower-target group, 292 of the 859 patients (34.0%) in the intermediate-target group, and 290 of the 874 patients (33.2%) in the higher-target group. The incidences of cardiac arrest, arrhythmia, myocardial infarction, stroke, and pneumothorax were similar in the three groups. CONCLUSIONS: Among critically ill adults receiving invasive mechanical ventilation, the number of ventilator-free days did not differ among groups in which a lower, intermediate, or higher Spo2 target was used. (Supported by the National Heart, Lung, and Blood Institute and others; PILOT ClinicalTrials.gov number, NCT03537937.).

An Analysis of the Effect of Noninvasive Positive Pressure Ventilation on Patients with Respiratory Failure Complicated by Diabetes Mellitus.

Objective: To observe the clinical effectiveness of noninvasive positive pressure ventilation in patients with respiratory failure complicated by diabetes. Methods: From May 2021 to May 2022, 90 patients with respiratory failure complicated by diabetes treated in our hospital were recruited and randomly assigned to receive either medication (control group) or noninvasive positive pressure ventilation (study group), with 45 patients in each group. The clinical endpoint was therapeutic outcomes. Results: Noninvasive positive pressure ventilation resulted in significantly lower Self-Rating Anxiety Scale (SAS) and Self-Rating Depression Scale (SDS) scores versus medications (P < 0.05). Patients with noninvasive positive pressure ventilation showed better pulmonary function indices versus those with medications (P > 0.05). There was no significant difference in arterial oxygen (PaO2), carbon dioxide partial pressure (PaCO2), and arterial oxygen pressure/inspired fraction of O2 (PaO2/FiO2) between the two groups prior to the intervention (P > 0.05). However, patients in the study group had significantly elevated PaO2 and PaO2/FiO2 and lower PaCO2 levels than those in the control group (P < 0.05). Following the intervention, noninvasive positive pressure ventilation resulted in significantly lower inflammatory factor levels versus medications (P > 0.05). After the intervention, markedly better glucose control was observed in the study group versus the control group (P < 0.05). The incidence of complications in the control group was 2.38%, which was significantly lower than that of the control group (16.67) (P < 0.05). Conclusion: Noninvasive positive pressure ventilation effectively suppresses the inflammatory response, improves the blood gas analysis index, and eliminates the negative emotions of patients, thereby maintaining hemodynamic stability and improving clinical efficacy with a better safety profile. Further studies are recommended prior to clinical promotion.

[Xenon post-conditioning protects against spinal cord ischemia-reperfusion injury in rats by downregulating mTOR pathway and inhibiting endoplasmic reticulum stress-induced neuronal apoptosis].

OBJECTIVE: The purpose of this study was to determine whether xenon post-conditioning affects mTOR signaling as well as endoplasmic reticulum stress (ERS)-apoptosis pathway in rats with spinal cord ischemia/reperfusion injury. METHODS: Fifty male rats were randomized equally into sham-operated group (Sham group), I/R model group (I/R group), I/R model+ xenon post-conditioning group (Xe group), I/R model+rapamycin (a mTOR signaling pathway inhibitor) treatment group (I/R+ Rapa group), and I/R model + xenon post- conditioning with rapamycin treatment group (Xe + Rapa group).. In the latter 4 groups, SCIRI was induced by clamping the abdominal aorta for 85 min followed by reperfusion for 4 h. Rapamycin (or vehicle) was administered by daily intraperitoneal injection (4 mg/kg) for 3 days before SCIRI, and xenon post-conditioning by inhalation of 1∶1 mixture of xenon and oxygen for 1 h at 1 h after initiation of reperfusion; the rats without xenon post-conditioning were given inhalation of nitrogen and oxygen (1∶ 1). After the reperfusion, motor function and histopathologic changes in the rats were examined. Western blotting and real-time PCR were used to detect the protein and mRNA expressions of GRP78, ATF6, IRE1α, PERK, mTOR, p-mTOR, Bax, Bcl-2 and caspase-3 in the spinal cord. RESULTS: The rats showed significantly lowered hind limb motor function following SCIRI (P < 0.01) with a decreased count of normal neurons, increased mRNA and protein expressions of GRP78, ATF6, IRE1α, PERK, and caspase-3, and elevated p-mTOR/mTOR ratio and Bax/Bcl-2 ratio (P < 0.01). Xenon post-conditioning significantly decreased the mRNA and protein levels of GRP78, ATF6, IRE1α, PERK and caspase-3 (P < 0.05 or 0.01) and reduced p-mTOR/mTOR and Bax/Bcl-2 ratios (P < 0.01) in rats with SCIRI; the mRNA contents and protein levels of GRP78 and ATF6 were significantly decreased in I/R+Rapa group (P < 0.01). Compared with those in Xe group, the rats in I/R+Rapa group and Xe+Rapa had significantly lowered BBB and Tarlov scores of the hind legs (P < 0.01), and caspase-3 protein level and Bax/Bcl-2 ratio were significantly lowered in Xe+Rapa group (P < 0.05 or 0.01). CONCLUSION: By inhibiting ERS and neuronal apoptosis, xenon post- conditioning may have protective effects against SCIRI in rats. The mTOR signaling pathway is partially involved in this process.

Effect of Helmet Noninvasive Ventilation vs Usual Respiratory Support on Mortality Among Patients With Acute Hypoxemic Respiratory Failure Due to COVID-19: The HELMET-COVID Randomized Clinical Trial.

Importance: Helmet noninvasive ventilation has been used in patients with COVID-19 with the premise that helmet interface is more effective than mask interface in delivering prolonged treatments with high positive airway pressure, but data about its effectiveness are limited. Objective: To evaluate whether helmet noninvasive ventilation compared with usual respiratory support reduces mortality in patients with acute hypoxemic respiratory failure due to COVID-19 pneumonia. Design, Setting, and Participants: This was a multicenter, pragmatic, randomized clinical trial that was conducted in 8 sites in Saudi Arabia and Kuwait between February 8, 2021, and November 16, 2021. Adult patients with acute hypoxemic respiratory failure (n = 320) due to suspected or confirmed COVID-19 were included. The final follow-up date for the primary outcome was December 14, 2021. Interventions: Patients were randomized to receive helmet noninvasive ventilation (n = 159) or usual respiratory support (n = 161), which included mask noninvasive ventilation, high-flow nasal oxygen, and standard oxygen. Main Outcomes and Measures: The primary outcome was 28-day all-cause mortality. There were 12 prespecified secondary outcomes, including endotracheal intubation, barotrauma, skin pressure injury, and serious adverse events. Results: Among 322 patients who were randomized, 320 were included in the primary analysis, all of whom completed the trial. Median age was 58 years, and 187 were men (58.4%). Within 28 days, 43 of 159 patients (27.0%) died in the helmet noninvasive ventilation group compared with 42 of 161 (26.1%) in the usual respiratory support group (risk difference, 1.0% [95% CI, -8.7% to 10.6%]; relative risk, 1.04 [95% CI, 0.72-1.49]; P = .85). Within 28 days, 75 of 159 patients (47.2%) required endotracheal intubation in the helmet noninvasive ventilation group compared with 81 of 161 (50.3%) in the usual respiratory support group (risk difference, -3.1% [95% CI, -14.1% to 7.8%]; relative risk, 0.94 [95% CI, 0.75-1.17]). There were no significant differences between the 2 groups in any of the prespecified secondary end points. Barotrauma occurred in 30 of 159 patients (18.9%) in the helmet noninvasive ventilation group and 25 of 161 (15.5%) in the usual respiratory support group. Skin pressure injury occurred in 5 of 159 patients (3.1%) in the helmet noninvasive ventilation group and 10 of 161 (6.2%) in the usual respiratory support group. There were 2 serious adverse events in the helmet noninvasive ventilation group and 1 in the usual respiratory support group. Conclusions and Relevance: Results of this study suggest that helmet noninvasive ventilation did not significantly reduce 28-day mortality compared with usual respiratory support among patients with acute hypoxemic respiratory failure due to COVID-19 pneumonia. However, interpretation of the findings is limited by imprecision in the effect estimate, which does not exclude potentially clinically important benefit or harm. Trial Registration: ClinicalTrials.gov Identifier: NCT04477668.