Inspired O2 Fraction Research Articles

Evaluation of the Nautilus Smart Extracorporeal Membrane Oxygenation in Patients With Hemostatic Alteration: A Case Series.

The intricate management of hemostatic disorders in extracorporeal membrane oxygenation (ECMO) assisted patients poses challenges, particularly when procoagulant administration is necessary. We hereby report the performance of the Nautilus* Smart ECMO Module in three patients with hemostatic disorders. We collected data from ECMO procedures with Nautilus* Smart ECMO Module and analyzed the performance: the operating pressures and resistance of the device in addition to the coagulation status of the patients. During the three procedures, partial pressure oxygen post-oxygenator (paO2) stayed above 100 mm Hg and partial pressure carbon dioxide post-oxygenator (paCO2) did not exceed 45 mm Hg. Membrane FiO2 (fractional inspired O2) did not exceed 75% and air flow remained within a 1:1 ratio with blood flow in veno-arterial ECMO (V-A) and within 1:2 in veno-venous ECMO (V-V). There was no evidence of excessive operating pressure for the device, with a pressure drop consistently below 28 mm Hg and a maximum peak resistance of 7 Δmm Hg/L/min. The Nautilus* Smart ECMO Module showed good performance in patients with hemostatic disorders despite the implications associated with procoagulant administration.

Pulmonary inflammation decreases with ultra-protective ventilation in experimental ARDS under VV-ECMO: a positron emission tomography study.

Experimentally, ultra-protective ventilation (UPV, tidal volumes [VT] < 4 mL.kg-1) strategies in conjunction with veno-venous extracorporeal membrane oxygenation (VV-ECMO) are associated with lesser ventilator-induced lung injuries (VILI) during acute respiratory distress syndrome (ARDS). However, whether these strategies reduce lung inflammation more effectively than protective ventilation (PV) remains unclear. We aimed to demonstrate that a UPV strategy decreases acute lung inflammation in comparison with PV in an experimental swine model of ARDS. ARDS was induced by tracheal instillation of chlorhydric acid in sedated and paralyzed animals under mechanical ventilation. Animals were randomized to receive either UPV (VT 1 mL.kg-1, positive end-expiration pressure [PEEP] set to obtain plateau pressure between 20 and 25 cmH2O and respiratory rate [RR] at 5 min-1 under VV-ECMO) or PV (VT 6 mL.kg-1, PEEP set to obtain plateau pressure between 28 and 30 cmH2O and RR at 25 min-1) during 4 h. After 4 h, a positron emission tomography with [11C](R)-PK11195 (ligand to TSPO-bearing macrophages) injection was realized, coupled with quantitative computerized tomography (CT). Pharmacokinetic multicompartment models were used to quantify regional [11C](R)-PK11195 lung uptake. [11C](R)-PK11195 lung uptake and CT-derived respiratory variables were studied regionally across eight lung regions distributed along the antero-posterior axis. Five pigs were randomized to each study group. Arterial O2 partial pressure to inspired O2 fraction were not significantly different between study groups after experimental ARDS induction (75 [68-80] mmHg in a PV group vs. 87 [69-133] mmHg in a UPV group, p = 0.20). Compared to PV animals, UPV animals exhibited a significant decrease in the regional non-aerated compartment in the posterior lung levels, in mechanical power, and in regional dynamic strain and no statistical difference in tidal hyperinflation after 4 h. UPV animals had a significantly lower [11C](R)-PK11195 uptake, compared to PV animals (non-displaceable binding potential 0.35 [IQR, 0.20-0.59] in UPV animals and 1.01 [IQR, 0.75-1.59] in PV animals, p = 0.01). Regional [11C](R)-PK11195 uptake was independently associated with the interaction of regional tidal hyperinflation and regional lung compliance. In an experimental model of ARDS, 4 h of UPV strategy significantly decreased lung inflammation, in relation to the control of VT-derived determinants of VILI.

Amlodipine and Atropine for Hypoxia During One-Lung Ventilation: A Case Report.

Anesthetists are concerned about the causes and management of hypoxia during one-lung ventilation (OLV). Here, we report a hypoxic case during OLV and video-assisted thoracic surgery (VATS) for pulmonary lobectomy. The preoperative management of hypertension with amlodipine was considered to be responsible for the hypoxia. As a calcium channel blocker, amlodipine may inhibit hypoxic pulmonary vasoconstriction (HPV) and contribute to the reduction of the ventilation/perfusion ratio (or V/Q ratio). The hypoxia efficiently was treated by atropine, where both tracheal effects and the enhancement of HPV through muscarinic receptor blocking may work. For patients undertaking OLV, the effects of calcium channel blockers as a potential cause for hypoxemia should be paid attention to, where atropine administration may be of clinical benefit. One-lung ventilation (OLV) generally is used during anesthesia for thoracic surgeries. For OLV, a double-lumen tracheal tube (DLT) is used to realize lung separation in the airway. This technique is essential because it facilitates the surgical performance as well as isolates a healthy lung from the pathologic one. However, there are some concerns for OLV during anesthesia, where hypoxemia is commonly seen. There are many causes for hypoxemia during OLV. These include, for example, reduced oxygen stores due to the collapse of the non-ventilation lung, ventilation-perfusion mismatch induced by both lateral positions, and decrease in elastic recoil leading to more atelectasis. Accordingly, management of hypoxemia during OLV generally have been applied. Increase fraction of inspiration O2 (Fi O2) to 1, double checking the position of DLT, applying positive end expiratory pressure (PEEP), optimizing cardiac output (CO) all have been proven to be effective. Here, we report an efficiently treated hypoxemia case using atropine during video-assisted thoracic surgery (VATS) for pulmonary lobectomy. Preoperative medication of amlodipine may contribute to the hypoxemia through attenuating HPV during OLV, which may be antagonized by possible HPV augmentation of atropine. Further investigation is therefore suggested.

Effects of positive end-expiratory pressure and oxygen concentration on non-hypoxemic apnea time during face mask ventilation of anesthesia induction: A randomized controlled trial.

Background: The optimal ventilatory strategy for the face mask ventilation during anesthesia induction is still unknow. Methods: We evaluated the effect of two positive end-expiratory pressure (PEEP) levels (0cmH2O and 6cmH2O) and two oxygen concentration levels (1.0 and .6) on non-hypoxemic apnea time during face mask ventilation of anesthesia induction. Sixty adult patients scheduled for elective surgery were enrolled in this study. The patients were randomized to receive anesthesia induction with four different ventilation strategy under volume-controlled ventilation. Patients assigned to the LOZP group received low fraction of inspiration O2 (FiO2 = .6) and 0 PEEP. Patients assigned to the LOHP group received low fraction of inspiration O2 (FiO2 = .6) and 6cmH2O PEEP. Patients assigned to the HOZP group received high fraction of inspiration O2 (FiO2 = 1.0) and 0 PEEP. Patients assigned to the HOHP group received high fraction of inspiration O2 (FiO2 = 1.0) and 6cmH2O PEEP. After 3min of ventilation, the patient was intubated but disconnected from the breathing circuit. Ventilation was not initiated until the pulse oximetry dropped to 90%. The primary outcome was non-hypoxemic apnea time defined as the time from cessation of ventilation to a pulse oximeter reading of 90%. The secondary outcome was the PaO2/FiO2 ratio immediately after ventilation. Results: The non-hypoxemic apnea time was significantly longer in the group of HOHP when compared to the other three groups (192s ± 70s, 221s ± 74s, 284s ± 101s, and 353s ± 85s in the LOZP, LOHP, HOZP, and HOHP group, respectively). The PaO2/FiO2 ratio immediately after ventilation was significantly higher in the group of LOHP when compared to the other three groups (LOZP 393 ± 130, LOHP 496 ± 97, HOZP 335 ± 58, HOHP 391 ± 50). When compared the PaO2/FiO2 ratio immediately after ventilation to its value before administration of anesthesia, the PaO2/FiO2 ratio in the group of LOHP was improved, the group LOZP and HOHP remained the same, while the group HOZP significantly decreased. Conclusion: Application of PEEP and 100% of oxygen during face mask ventilation of induction could maximize the non-hypoxemic apnea time. However, the use of PEEP and 60% of oxygen during preoxygenation resulted in improved PaO2/FiO2 ratio.

Abstract 15332: Post-Resuscitation Epinephrine Infusion Restores Blood Pressure but Not Blood Flow in a Rat Model of Severe Pediatric Cardiac Arrest

Introduction: In children resuscitated from cardiac arrest (CA), post-arrest hypotension occurs often and worsens outcomes. Continuous infusion of epinephrine (Epi) is the 1st-line treatment for post-arrest hypotension but may worsen organ perfusion due to vasoconstriction. Hypothesis: Epi infusion after resuscitation from pediatric asphyxial CA restores blood pressure but not organ perfusion. Methods: Immature rats (PND18-22, n=34) underwent 11.5 minutes of asphyxial CA followed by resuscitation. Rats with hypotension (mean arterial pressure (MAP)&lt;80% baseline) after resuscitation received infusions of either 0.9% NaCl (NS) or Epinephrine (Epi). MAP, carotid and femoral arterial blood flows (Fc, Ff) and renal oxygen tension (PrO2) were recorded. Results: One hour after resuscitation, MAP, Fc and Ff were 61.73 ± 2.68; 42.58 ± 3.84; and 19.53 ± 7.00 % of baseline, respectively. Epi infusion increased MAP in a dose-dependent manner, reaching 95.13 ± 7.93 % of baseline at 0.5 μg/kg/min. In contrast, Epi infusion up to 0.5 μg/kg/min increased Fc only to 49.55 ± 6.49 and Ff to 53.28 ± 7.13 % of baseline. NS infusion at equivalent volume had a more salutary effect than Epi on improving blood flow (Fc 64.62 ± 6.64 and Ff 60.25 ± 7.60 % of baseline). PrO2 reached 100% of baseline with Epi infusion and inspired O2 fraction (FiO2) = 1. However, at FiO2 = 0.21, Epi failed to restore PrO2 which reached 42% of baseline. Interestingly, a single 10 cc/kg NS bolus increased PrO2 to 100% of baseline at all FiO2 tested. Conclusions: In this rat model of severe pediatric asphyxial CA and resuscitation, post-resuscitation Epi infusion failed to restore carotid and femoral arterial blood flow despite normalizing blood pressure. Furthermore, Epi infusion restored neither renal perfusion nor oxygenation. In contrast, infusion of NS at comparable volumes was more effective than Epi at normalizing carotid and femoral blood flows as well as renal oxygenation. If validated in a large animal model, these results may indicate that Epi infusion after CA resuscitation contributes to organ injury and morbidity in children.

Mechanical ventilation characteristics and their prediction performance for the risk of moderate and severe bronchopulmonary dysplasia in infants with gestational age &lt;30 weeks and birth weight &lt;1,500 g

Moderate and severe bronchopulmonary dysplasia (BPD) is a common pulmonary complication in premature infants, which seriously affects their survival rate and quality of life. This study aimed to describe the mechanical ventilation characteristics and evaluate their prediction performance for the risk of moderate and severe BPD in infants with gestational age <30 weeks and birth weight <1,500 g on postnatal Day 14. In this retrospective cohort study, 412 infants with gestational age <30 weeks and birth weight <1,500 g were included in the analysis, including 104 infants with moderate and severe BPD and 308 infants without moderate and severe BPD (as controls). LASSO regression was used to optimize variable selection, and Logistic regression was applied to build a predictive model. Nomograms were developed visually using the selected variables. To validate the model, receiver operating characteristic (ROC) curve, calibration plot, and clinical impact curve were used. From the original 28 variables studied, six predictors, namely birth weight, 5 min apgar score, neonatal respiratory distress syndrome (≥Class II), neonatal pneumonia, duration of invasive mechanical ventilation (IMV) and maximum of FiO2 (fraction of inspiration O2) were identified by LASSO regression analysis. The model constructed using these six predictors and a proven risk factor (gestational age) displayed good prediction performance for moderate and severe BPD, with an area under the ROC of 0.917 (sensitivity = 0.897, specificity = 0.797) in the training set and 0.931 (sensitivity = 0.885, specificity = 0.844) in the validation set, and was well calibrated (P Hosmer-Lemeshow test = 0.727 and 0.809 for the training and validation set, respectively). The model included gestational age, birth weight, 5 min apgar score, neonatal respiratory distress syndrome (≥Class II), neonatal pneumonia, duration of IMV and maximum of FiO2 had good prediction performance for predicting moderate and severe BPD in infants with gestational age <30 weeks and birth weight <1,500 g on postnatal Day 14.

A randomized controlled trial of positive end-expiratory pressure on pulmonary oxygenation and biventricular function in esophageal cancer patients receiving one-lung ventilation under a lower FiO2

Arterial oxygenation is often impaired during one-lung ventilation (OLV), due to both pulmonary shunt and atelectasis. Lower fraction of inspiration O2 (FiO2) may reduce inflammation and complications, but may increase the risk of hypoxemia. The aim of this randomized controlled parallel trial was to analyze whether higher positive end-expiratory pressure (PEEP) could improve oxygenation and maintain lower levels of inflammation during OLV under a lower FiO2. One hundred and twenty patients with selective thoracotomy for esophageal cancer (EC) were classified randomly into four groups on a ratio of 1:1:1:1 using a computer-generated list, including Group A (FiO2 =0.6, PEEP =0), Group B (FiO2 =0.6, PEEP =5 cmH2O), Group C (FiO2 =1.0, PEEP =8 cmH2O), and Group D (FiO2 =1.0, PEEP =10 cmH2O). The oxygenation and pulmonary shunt were primary outcomes. Haemodynamics, respiratory mechanics, serum IL-6 and IL-10 levels, and complications were taken as secondary outcomes. Follow-up was terminated until discharge. Two patients in Group A and two in Group D were excluded due to hypoxemia and hypotension, respectively. Then the data of 116 patients (Group A =28, Group B =30 Group C =30, and Group D =28) were assessed for final analysis. Compared with Group B, the partial pressure of oxygen (PaO2) and dynamic compliance during OLV in Group D were significantly increased from 15 minutes to 60 minutes, while pulmonary shunt was significantly decreased (P>0.05). Patients in Group D had higher levels of central venous pressure (CVP) and airway pressure (Paw) during OLV and higher levels of IL-6 and IL-10 after OLV compared with Group B (P>0.05). No statistical differences were found in oxygen saturation (SaO2), PvO2 (partial pressure of oxygen in venous blood), partial pressure of end-tidal carbon dioxide (ETCO2), partial pressure of carbon dioxide in artery (PaCO2), heart rate (HR), mean arterial pressure (MAP), and complications among the four groups (P>0.05). Higher PEEP increased the oxygenation under 60% O2 during OLV. However, the haemodynamics and respiratory mechanics changed, and the levels of inflammation increased. A higher PEEP under 60% O2 during OLV is not recommended. Chinese Clinical Trial Registry ChiCTR1900024726.

Too much tolerance for hyperoxemia in mechanically ventilated patients with SARS-CoV-2 pneumonia? Report from an Italian intensive care unit.

BackgroundIn COVID-19 patients requiring mechanical ventilation, the administration of high oxygen (O2) doses for prolonged time periods may be necessary. Although life-saving in most cases, O2 may exert deleterious effects if administered in excessive concentrations. We aimed to describe the prevalence of hyperoxemia and excessive O2 administration in mechanically ventilated patients with SARS-CoV-2 pneumonia and determine whether hyperoxemia is associated with mortality in the Intensive Care Unit (ICU) or the onset of ventilator-associated pneumonia (VAP).Materials and methodsRetrospective single-center study on adult patients with SARS-CoV-2 pneumonia requiring invasive mechanical ventilation for ≥48 h. Patients undergoing extracorporeal respiratory support were excluded. We calculated the excess O2 administered based on the ideal arterial O2 tension (PaO2) target of 55–80 mmHg. We defined hyperoxemia as PaO2 > 100 mmHg and hyperoxia + hyperoxemia as an inspired O2 fraction (FiO2) > 60% + PaO2 > 100 mmHg. Risk factors for ICU-mortality and VAP were assessed through multivariate analyses.ResultsOne hundred thirty-four patients were included. For each day of mechanical ventilation, each patient received a median excess O2 of 1,121 [829–1,449] L. Hyperoxemia was found in 38 [27–55]% of arterial blood gases, hyperoxia + hyperoxemia in 11 [5–18]% of cases. The FiO2 was not reduced in 69 [62–76]% of cases of hyperoxemia. Adjustments were made more frequently with higher PaO2 or initial FiO2 levels. ICU-mortality was 32%. VAP was diagnosed in 48.5% of patients. Hyperoxemia (OR 1.300 95% CI [1.097–1.542]), time of exposure to hyperoxemia (OR 2.758 [1.406–5.411]), hyperoxia + hyperoxemia (OR 1.144 [1.008–1.298]), and daily excess O2 (OR 1.003 [1.001–1.005]) were associated with higher risk for ICU-mortality, independently of age, Sequential Organ failure Assessment score at ICU-admission and mean PaO2/FiO2. Hyperoxemia (OR 1.033 [1.006–1.061]), time of exposure to hyperoxemia (OR 1.108 [1.018–1.206]), hyperoxia + hyperoxemia (OR 1.038 [1.003–1.075]), and daily excess O2 (OR 1.001 [1.000–1.001]) were identified as risk factors for VAP, independently of body mass index, blood transfusions, days of neuromuscular blocking agents (before VAP), prolonged prone positioning and mean PaO2/FiO2 before VAP.ConclusionExcess O2 administration and hyperoxemia were common in mechanically ventilated patients with SARS-CoV-2 pneumonia. The exposure to hyperoxemia may be associated with ICU-mortality and greater risk for VAP.

Pulmonary gas exchange evaluated by machine learning: a computer simulation

Using computer simulation we investigated whether machine learning (ML) analysis of selected ICU monitoring data can quantify pulmonary gas exchange in multi-compartment format. A 21 compartment ventilation/perfusion (V/Q) model of pulmonary blood flow processed 34,551 combinations of cardiac output, hemoglobin concentration, standard P50, base excess, VO2 and VCO2 plus three model-defining parameters: shunt, log SD and mean V/Q. From these inputs the model produced paired arterial blood gases, first with the inspired O2 fraction (FiO2) adjusted to arterial saturation (SaO2) = 0.90, and second with FiO2 increased by 0.1. ‘Stacked regressor’ ML ensembles were trained/validated on 90% of this dataset. The remainder with shunt, log SD, and mean ‘held back’ formed the test-set. ‘Two-Point’ ML estimates of shunt, log SD and mean utilized data from both FiO2 settings. ‘Single-Point’ estimates used only data from SaO2 = 0.90. From 3454 test gas exchange scenarios, two-point shunt, log SD and mean estimates produced linear regression models versus true values with slopes ~ 1.00, intercepts ~ 0.00 and R2 ~ 1.00. Kernel density and Bland–Altman plots confirmed close agreement. Single-point estimates were less accurate: R2 = 0.77–0.89, slope = 0.991–0.993, intercept = 0.009–0.334. ML applications using blood gas, indirect calorimetry, and cardiac output data can quantify pulmonary gas exchange in terms describing a 20 compartment V/Q model of pulmonary blood flow. High fidelity reports require data from two FiO2 settings.

Development and validation of a survival prediction model for patients received mechanical ventilation in the intensive care unit: a large sample size cohort from the MIMIC database.

Mechanical ventilation remains one of the primary management measures for critically ill patients in intensive care units (ICUs). However, previous studies on the prognosis prediction of ICU patients received mechanical ventilation were limited. This study was to develop and validate a nomogram for predicting short- and long-term survival among patients who received mechanical ventilation in the ICU. This was a retrospective cohort study with a 3-year follow-up. Demographic, laboratory, clinical data of 16,775 participants aged ≥18 years who received mechanical ventilation in the ICU were extracted from the Medical Information Mart for Intensive Care III (MIMIC-III) database. The outcomes of this study were 1-month, 3-month, 1-year, and 3-year survival. All eligible patients were randomly classified into the training and testing groups with a ratio of 7:3. A multivariate Cox regression in the training group was used to explore the predictors and develop the predictive nomogram. Internal and subgroup validations were performed, and the C-index was calculated to estimate the predictive performance of the nomogram. The time-dependent receiver operating characteristic curves were drawn, and corresponding areas under the curve (AUC) were calculated. Totally 6,291 patients died during the follow-up duration. Age, gender, ethnicity, ICU type, comorbidity, days of mechanical ventilation, white blood cell count, blood urea nitrogen, the fraction of inspiration O2, Sequential Organ Failure Assessment scores, and the Glasgow coma score were predictors of the survival of ICU patients who received mechanical ventilation (P<0.05). The C-index of the nomogram was 0.819 and was validated in the testing group at 0.816. The AUCs for the prognostic nomogram for 1-month, 3-month, 1-year, and 3-year survival were 0.889, 0.892, 0.882, and 0.866, respectively. This nomogram showed good predictive performance for short- and long-term survival in ICU patients treated with mechanical ventilation, which may be a useful tool for clinicians to assess the prognosis of patients and to adjust treatment strategies in time.

Risk factors for reintubation and mortality among patients who had unplanned extubation.

Unplanned extubation (UE) occurs among 2%-16% of patients with mechanical ventilation (MV). Failed UE requiring reintubation could be associated with several adverse events. The aim of this study was to investigate the outcomes and prognostic factors of patients with UE in intensive care units (ICUs). We prospectively registered the patients who had UE and retrospectively reviewed the electronic medical records for 96-bed ICUs between 1 January 2009, and 31 December 2020. A total of 392 patients had UE, and 234 patients (59.7%) were ≥65 years (older adult group). The median Acute Physiology and Chronic Health Evaluation (APACHE) II score were 17 and the median Glasgow Coma Scale score was 10. In total, 205 patients (52.3%) were reintubated within 48 h (due to failed UE) and 75 patients (19.1%) died during hospitalization. Multivariate analyses were performed to evaluate those factors predicting failed UE and mortality. These analyses demonstrated that higher positive end-expiratory pressure (PEEP) and the admission APACHE II scores predicted failed UE. A higher fraction of inspiration O2 (FiO2 ) and minute ventilation; lower haemoglobin (Hb); and higher instances of liver cirrhosis, cancer, and failed UE were independently associated with hospital mortality. We concluded that among patients who had UE, higher FiO2 or minute ventilation, or under MV or with lower Hb, liver cirrhosis, cancer, and failed UE tended to have higher mortality. Patients with high disease severity indices who have an increased risk of UE required special attention to techniques to prevent endotracheal tubes from accidental removal.

Reduced Effective Oxygen Delivery and Ventilation with a Surgical Facemask Placed under Compared to over an Oxygen Mask: A Comparative Study.

Objectives Consensus guidelines for perioperative anesthesia management during the COVID-19 pandemic recommend that patients wear a facemask in addition to their oxygen mask or nasal cannulae following tracheal extubation, where this is practical. The effects on effective oxygen delivery and ventilation of a surgical facemask under compared to over an oxygen (O2) mask are unclear. Design Single-center, comparative pilot study. Setting. Endoscopy procedure room at a major academic hospital. Subjects Five healthy anesthesiologists. Interventions. Using a carbon dioxide (CO2) sampling line positioned at the lips, the fraction of inspired O2 (FiO2), fraction of expiratory O2 (FeO2), expiratory end-tidal CO2 (EtCO2), and respiratory rate (RR) were measured under the following conditions: (1) a surgical facemask only, (2) a surgical facemask under an O2 mask, (3) an O2 mask only, and (4) a surgical facemask over an O2 mask. Measurements and Main Results. The sampled fractional expired oxygen (FeO2) at the lips was significantly lower when the surgical facemask was under compared to when over the O2 mask (27.9± 1.68 vs. 49.9 ± 6.27, p = 0.001), while there was no significant difference in inspired oxygen (FiO2). The sampled expiratory EtCO2 was significantly higher when the surgical facemask was under the O2 mask compared to when over the O2 mask (28.3 ± 8.5 vs. 23.5 ± 7.6, p = 0.026). The RR was not significantly different when the surgical facemask was under compared to over the O2 mask. Conclusions Effective oxygen delivery and ventilation was reduced (lower FeO2 and increased EtCO2) when a surgical facemask was placed under compared to over an O2 mask.

Hyperoxia Provokes Time- and Dose-Dependent Gut Injury and Endotoxemia and Alters Gut Microbiome and Transcriptome in Mice.

Background: Oxygen therapy usually exposes patients to hyperoxia, which induces injuries in the lung, the heart, and the brain. The gut and its microbiome play key roles in critical illnesses, but the impact of hyperoxia on the gut and its microbiome remains not very clear. We clarified the time- and dose-dependent effects of hyperoxia on the gut and investigated oxygen-induced gut dysbiosis and explored the underlying mechanism of gut injury by transcriptome analysis.Methods: The C57BL/6 mice were randomly divided into the control group and nine different oxygen groups exposed to hyperoxia with an inspired O2 fraction (FiO2) of 40, 60, and 80% for 24, 72, and 168 h (7 days), respectively. Intestinal histopathological and biochemical analyses were performed to explore the oxygen-induced gut injury and inflammatory response. Another experiment was performed to explore the impact of hyperoxia on the gut microbiome by exposing the mice to hyperoxia (FiO2 80%) for 7 days, with the 16S rRNA sequencing method. We prolonged the exposure (up to 14 days) of the mice to hyperoxia (FiO2 80%), and gut transcriptome analysis and western blotting were carried out to obtain differentially expressed genes (DEGs) and signaling pathways related to innate immunity and cell death.Results: Inhaled oxygen induced time- and dose-dependent gut histopathological impairment characterized by mucosal atrophy (e.g., villus shortening: 80% of FiO2 for 24 h: P = 0.008) and enterocyte death (e.g., apoptosis: 40% of FiO2 for 7 days: P = 0.01). Administered time- and dose-dependent oxygen led to intestinal barrier dysfunction (e.g., endotoxemia: 80% of FiO2 for 72 h: P = 0.002) and potentiated gut inflammation by increasing proinflammatory cytokines [e.g., tumor necrosis factor alpha (TNF-α): 40% of FiO2 for 24 h: P = 0.003)] and reducing anti-inflammatory cytokines [Interleukin 10 (IL-10): 80% of FiO2 for 72 h: P < 0.0001]. Hyperoxia induced gut dysbiosis with an expansion of oxygen-tolerant bacteria (e.g., Enterobacteriaceae). Gut transcriptome analysis identified 1,747 DEGs and 171 signaling pathways and immunoblotting verified TLR-4, NOD-like receptor, and apoptosis signaling pathways were activated in oxygen-induced gut injury.Conclusions: Acute hyperoxia rapidly provokes gut injury in a time- and dose-dependent manner and induces gut dysbiosis, and an innate immune response is involved in an oxygen-induced gut injury.

The deleterious effects of acute hypoxia on microvascular and large vessel endothelial function.

What is the central question of this study? The aim was primarily to determine the effect of hypoxia on microvascular function and secondarily whether superior cardiorespiratory fitness is protective against hypoxia-induced impairment in vascular function. What is the main finding and its importance? Hypoxia reduced endothelium-dependent but not endothelium-independent microvascular function. The extent of impairment was twofold higher in the microcirculation compared with the large blood vessels. This study suggests that individuals with superior cardiorespiratory fitness might preserve microvascular function in hypoxia. These findings highlight the sensitivity of the microvascular circulation to hypoxia. Hypoxia is associated with diminished bioavailability of the endothelium-derived vasodilator, nitric oxide (NO). Diminished NO bioavailability can have deleterious effects on endothelial function. The endothelium is a heterogeneous tissue; therefore, a comprehensive assessment of endothelial function is crucial to understand the significance of hypoxia-induced endothelial dysfunction. We hypothesized that acute hypoxia would have a deleterious effect on microvascular and large vessel endothelial function. Twenty-nine healthy adults [24(SD = 4 )years of age] completed normoxic and hypoxic [inspired O2 fraction=0.209] trials in this double-blinded, counterbalanced crossover study. After 30min, we assessed the laser Doppler imaging-determined perfusion response to iontophoresis of ACh as a measure of endothelium-dependent microvascular function and iontophoresis of sodium nitroprusside as a measure of endothelium-independent microvascular function. After 60min, we assessed brachial flow-mediated dilatation as a measure of large vessel endothelial function. Thirty minutes of hypoxia reduced endothelium-dependent microvascular function determined by the perfusion response to ACh (median difference (x̃∆)=-109% {interquartile range: 542.7}, P<0.05), but not endothelium-independent microvascular function determined by the perfusion response to sodium nitroprusside (x̃∆ = 69% {interquartile range: 453.7}, P=0.6). In addition, 60min of hypoxia reduced allometrically scaled flow-mediated dilatation compared with normoxia ( [95% CI = -1.80, -0.58 (Confidence Intervals)]%, P<0.001). The decrease in microvascular endothelial function was associated with cardiorespiratory fitness (r =0.45, P=0.02). In conclusion, acute exposure to normobaric hypoxia significantly reduced endothelium-dependent vasodilatory capacity in small and large vessels. Collectively, these findings highlight the sensitivity of the microvascular circulation to hypoxic insult, particularly in those with poor cardiorespiratory fitness.

The effect of heated humidified nasal high flow oxygen supply on exercise tolerance in patients with interstitial lung disease: A pilot study

Background and objectivesPatients with interstitial lung disease (ILD) experience early symptoms of dyspnoea and leg fatigue during exercise together with severe and rapid oxygen desaturation. Heated and humidified nasal high flow oxygen (NHF) has been proven to enhance exercise endurance and physiological parameters in COPD patients. This study aims to evaluate the effect of NHF on exercise tolerance in ILD patients. MethodsTwenty-five patients (10 female) with severe ILD performed three constant-load (70% maximal workload) cycling tests to exhaustion under different breathing conditions: room air, oxygen supplementation (4 L min−1 O2) and NHF (inspiratory O2 fraction 0.5, 30–50 L min−1, heated 34 °C and humidified). ResultsEndurance time was significantly longer with NHF (618 ± 297 s) compared to O2 (369 ± 217 s, p < 0.001) and room air (171 ± 76 s, p < 0.001). Kinetics of oxygen desaturation, chronotropic response, dyspnoea and leg fatigue sensations were delayed with NHF. At exhaustion with NHF, compared to the two other conditions, oxygen desaturation was less severe while heart rate, dyspnoea and leg fatigue were similar. ConclusionNHF significantly improved endurance time, physiological parameters and sensations during exercise in severe ILD patients. NHF may be useful to improve functional capacities and facilitate pulmonary rehabilitation in ILD.

Lipid profiles and differential lipids in serum related to severity of community-acquired pneumonia: A pilot study.

This study aimed to characterize the lipidomic responses to community-acquired pneumonia (CAP) and provide new insight into the underlying mechanisms of pathogenesis and potential avenues for diagnostic and therapeutic treatments. This study was performed from January 2017 to October 2018. Lipidomic profiles were generated using ultra high-performance liquid chromatography with tandem mass spectrometry (UHPLC-MS/MS) platform. Spearman’s rank correlation test and multiple linear regression analysis were applied to explore the correlation between changes in the relative abundance of lipids and clinical parameters. Kaplan–Meier methods were used to build 30-day survival curves. From the UHPLC-MS/MS results, a total of 509 and 195 lipid species were detected in the positive and negative ionization mode respectively. Positive ionization covered six lipid classes (glycerol-phospholipids, glycerolipids, sphingolipids, sterol-lipids, prenol-lipids, and fatty acid), whilst negative ionization covered three (glycerol-phospholipids, sphingolipids, fatty acid). Four lipids were selected as targets: PC (16:0_18:1), PC (18:2_20:4), PC (36:4), and PC (38:6). The relative increase of the areas under the curves for all four lipids were superior to the pneumonia severity index and CURB-65 (confusion, urea, respiratory rate, blood pressure, and age ≥65 years old) for discriminating severe CAP from CAP. Decreasing relative levels of PC (18:2_20:4), PC (38:6), and PC (36:4) were negatively related to fraction of inspiration O2; Changes in the relative abundance of PC (16:0_18:1) and PC (18:2_20:4) had significantly linear relationship with procalcitonin. Patients with an elevated level of PC (16:0_18:1) had significantly longer duration of hospital stays. As the relative abundance of PC (18:2_20:4), PC (36:4), and PC (38:6) decreased, the length of hospitalization days and 30-day mortality rate increased significantly (all log-rank p<0.05). Therefore, using the UHPLC-MS/MS platform’s serum lipidomic approach can help reveal changes in lipid abundance during CAP and establish lipid profiles related to disease severity.

Systemic Oxygen Utilization in Severe COVID-19 Respiratory Failure: A Case Series.

Management of hypoxemia in patients with severe COVID-19 respiratory failure is based on the guideline recommendations for specific SpO2 targets. However, limited data exist on systemic O2 utilization. The objective of this study was to examine systemic O2 utilization in a case series of patients with this disease. Between March 24, and April 9, 2020, 8 patients intubated for severe COVID-19 respiratory failure had near-simultaneous drawing of arterial blood gas (ABG), central venous blood gas (cVBG), and central venous oxygen saturation (ScvO2) at a mean of 6.1 days into hospitalization. Three patients were managed with indirect cardiac output (CO) monitoring by FloTrac sensor and Vigileo monitor (Edwards Lifesciences, Irvine, CA). The oxygen extraction index (OEI; SaO2-ScvO2/SaO2) and oxygen extraction fraction (OEF; CaO2-CvO2/CaO2 ≥ 100) were calculated. Values for hyperoxia (ScvO2 ≥ 90%), normoxia (ScvO2 71-89%), and hypoxia (ScvO2 ≤ 70%) were based on the literature. Mean values were calculated. The mean partial pressure of oxygen (PaO2) was 102 with a mean fraction of inspired O2 (FiO2) of 44%. One patient was hyperoxic with a reduced OEI (17%). Five patients were normoxic, but 2 had a reduced OEF (mean 15.9%). Two patients were hypoxic but had increased systemic O2 utilization based on OEF or OEI. In select patients with severe COVID-19 respiratory failure, O2 delivery (DO2) was found to exceed O2 utilization. SpO2 targets based on systemic O2 utilization may help in reducing oxygen toxicity, especially in the absence of anaerobic metabolism. Further data are needed on the prevalence of systemic O2 utilization in COVID-19. Garg RK, Kimbrough T, Lodhi W, DaSilva I. Systemic Oxygen Utilization in Severe COVID-19 Respiratory Failure: A Case Series. Indian J Crit Care Med 2021;25(2):215-218.

The variation of FiO2 with circuit type and peak inspiratory flow rate during non-invasive respiratory support using domiciliary ventilators and its significance during the COVID-19 pandemic.

BackgroundThe COVID-19 pandemic has resulted in increased admissions with respiratory failure and there have been reports of oxygen failure and shortages of machines to deliver ventilation and Continuous Positive Airway Pressure (CPAP). Domiciliary ventilators which entrain room air have been widely used during the pandemic. Poor outcomes reported with non-invasive respiratory support using ventilators which lack an oxygen blender could be related to an unreliable Fraction of inspired O2 (FiO2). Additionally, with concerns about oxygen failure, the variety of ventilator circuits used as well as differing peak inspiratory flow rates (PIFR) could impact on the FiO2 delivered during therapy with domiciliary ventilators.MethodsIn a series of bench tests, we tested the effect of choice of circuit and different PIFR on the FiO2 achieved during simulation of ventilation and CPAP therapy using domiciliary ventilators.ResultsFiO2 was highly dependent upon the type of circuit used with circuits with an active exhalation valve achieving similar FiO2 at lower oxygen flow rates than circuits using an exhalation port. During CPAP therapy, high PIFR resulted in significantly lower FiO2 than low PIFR.ConclusionsThis study has implications for oxygen usage as well as delivery of non-invasive respiratory support during therapy with domiciliary ventilators when these are used during the second wave of COVID-19.

Right ventricular-arterial uncoupling independently predicts survival in COVID-19 ARDS

AimTo investigate the prevalence and prognostic impact of right heart failure and right ventricular-arterial uncoupling in Corona Virus Infectious Disease 2019 (COVID-19) complicated by an Acute Respiratory Distress Syndrome (ARDS).MethodsNinety-four consecutive patients (mean age 64 years) admitted for acute respiratory failure on COVID-19 were enrolled. Coupling of right ventricular function to the pulmonary circulation was evaluated by a comprehensive trans-thoracic echocardiography with focus on the tricuspid annular plane systolic excursion (TAPSE) to systolic pulmonary artery pressure (PASP) ratioResultsThe majority of patients needed ventilatory support, which was noninvasive in 22 and invasive in 37. There were 25 deaths, all in the invasively ventilated patients. Survivors were younger (62 ± 13 vs. 68 ± 12 years, p = 0.033), less often overweight or usual smokers, had lower NT-proBNP and interleukin-6, and higher arterial partial pressure of oxygen (PaO2)/fraction of inspired O2 (FIO2) ratio (270 ± 104 vs. 117 ± 57 mmHg, p < 0.001). In the non-survivors, PASP was increased (42 ± 12 vs. 30 ± 7 mmHg, p < 0.001), while TAPSE was decreased (19 ± 4 vs. 25 ± 4 mm, p < 0.001). Accordingly, the TAPSE/PASP ratio was lower than in the survivors (0.51 ± 0.22 vs. 0.89 ± 0.29 mm/mmHg, p < 0.001). At univariate/multivariable analysis, the TAPSE/PASP (HR: 0.026; 95%CI 0.01–0.579; p: 0.019) and PaO2/FIO2 (HR: 0.988; 95%CI 0.988–0.998; p: 0.018) ratios were the only independent predictors of mortality, with ROC-determined cutoff values of 159 mmHg and 0.635 mm/mmHg, respectively.ConclusionsCOVID-19 ARDS is associated with clinically relevant uncoupling of right ventricular function from the pulmonary circulation; bedside echocardiography of TAPSE/PASP adds to the prognostic relevance of PaO2/FIO2 in ARDS on COVID-19.

Hypoxic Exposure Increases Energy Expenditure by Increasing Carbohydrate Oxidation in Mice

Aims. Hypoxic exposure improves glucose metabolism. We investigated to validate the hypothesis that carbohydrate (CHO) oxidation could increase in mice exposed to severe hypoxic conditions.Methods. Seven-week-old male ICR mice (n=16) were randomly divided into two groups: the control group (CON) was kept in normoxic condition (fraction of inspiredO2=21%) and the hypoxia group (HYP) was exposed to hypoxic condition (fraction of inspiredO2=12%, ≈altitude of 4,300 m). The CON group was pair-fed with the HYP group. After 3 weeks of hypoxic exposure, we measured respiratory metabolism (energy expenditure and substrate utilization) at normoxic conditions for 24 hours using an open-circuit calorimetry system. In addition, we investigated changes in carbohydrate mechanism-related protein expression, including hexokinase 2 (HK2), pyruvate dehydrogenase (PDH), pyruvate dehydrogenase kinase 4 (PDK4), and regulator of the genes involved in energy metabolism (peroxisome proliferator-activated receptor gamma coactivator 1-alpha, PGC1α) in soleus muscle.Results. Energy expenditure (EE) and CHO oxidation over 24 hours were higher in the HYP group by approximately 15% and 34% (p&lt;0.001), respectively. Fat oxidation was approximately 29% lower in the HYP group than the CON group (p&lt;0.01). Body weight gains were significantly lower in the HYP group than in the CON group (CON vs. HYP;1.9±0.9vs.−0.3±0.9;p&lt;0.001). Hypoxic exposure for 3 weeks significantly reduced body fat by approximately 42% (p&lt;0.001). PDH and PGC1αprotein levels were significantly higher in the HYP group (p&lt;0.05). Additionally, HK2 was approximately 21% higher in the HYP group.Conclusions. Hypoxic exposure might significantly enhance CHO oxidation by increasing the expression of PDH and HK2. This investigation can be useful for patients with impaired glucose metabolism, such as those with type 2 diabetes.