Arterial Oxygen Pressure Research Articles

Analysis of microRNA expression in rat kidneys after VEGF inhibitor treatment under different degrees of hypoxia.

Previously, we found that the incidence of kidney injury in patients with chronic hypoxia was related to the partial pressure of arterial oxygen. However, at oxygen concentrations that contribute to kidney injury, the changes in the relationship between microRNAs (miRNAs) and the hypoxia-inducible factor-1α (HIF-1α)-vascular endothelial growth factor (VEGF) axis and the key miRNAs involved in this process have not been elucidated. Therefore, we elucidated the relationship between VEGF and kidney injury at different oxygen concentrations and the mechanisms mediated by miRNAs. Sprague-Dawley rats were exposed to normobaric hypoxia and categorized into six groups based on the concentration of the oxygen inhaled and injection of the angiogenesis inhibitor bevacizumab, a humanized anti-VEGF monoclonal antibody. Renal tissue samples were processed to determine pathological and morphological changes and HIF-1α, VEGF, and miRNA expression. We performed a clustering analysis of high-risk pathways and key hub genes. The results were validated using two Gene Expression Omnibus datasets (GSE94717 and GSE30718). As inhaled oxygen concentration decreased, destructive changes in the kidney tissues became more severe. Although the kidney possesses a self-protective mechanism under an intermediate degree of hypoxia (10% O2), bevacizumab injections disrupted this mechanism, and VEGF expression was associated with the ability of the kidney to repair itself. rno-miR-124-3p was identified as a crucial miRNA; a key gene target, Mapk14, was identified during this process. VEGF plays an important role in kidney protection from injury under different hypoxia levels. Specific miRNAs and their target genes may serve as biomarkers that provide new insights into kidney injury treatment.NEW & NOTEWORTHY Renal tolerance to hypoxic environments is limited, and the degree of hypoxia does not show a linear relationship with angiogenesis. VEGF plays an important role in the kidney's self-protective mechanism under different levels of hypoxia. miR-124-3p may be particularly important in kidney repair, and it may modulate VEGF expression through the miR-124-3p/Mapk14 signaling pathway. These microRNAs may serve as biomarkers that provide new insights into kidney injury treatment.

Failure of First Transition to Pressure Support Ventilation After Spontaneous Awakening Trials in Hypoxemic Respiratory Failure: Influence of COVID-19.

To describe the rate of failure of the first transition to pressure support ventilation (PSV) after systematic spontaneous awakening trials (SATs) in patients with acute hypoxemic respiratory failure (AHRF) and to assess whether the failure is higher in COVID-19 compared with AHRF of other etiologies. To determine predictors and potential association of failure with outcomes. Retrospective cohort study. Twenty-eight-bedded medical-surgical ICU in a private hospital (Argentina). Subjects with arterial pressure of oxygen (AHRF to Fio2 [Pao2/Fio2] < 300 mm Hg) of different etiologies under controlled mechanical ventilation (MV). None. We collected data during controlled ventilation within 24 hours before SAT followed by the first PSV transition. Failure was defined as the need to return to fully controlled MV within 3 calendar days of PSV start. A total of 274 patients with AHRF (189 COVID-19 and 85 non-COVID-19) were included. The failure occurred in 120 of 274 subjects (43.7%) and was higher in COVID-19 versus non-COVID-19 (49.7% and 30.5%; p = 0.003). COVID-19 diagnosis (odds ratio [OR]: 2.22; 95% CI [1.15-4.43]; p = 0.020), previous neuromuscular blockers (OR: 2.16; 95% CI [1.15-4.11]; p = 0.017) and higher fentanyl dose (OR: 1.29; 95% CI [1.05-1.60]; p = 0.018) increased the failure chances. Higher BMI (OR: 0.95; 95% CI [0.91-0.99]; p = 0.029), Pao2/Fio2 (OR: 0.87; 95% CI [0.78-0.97]; p = 0.017), and pH (OR: 0.61; 95% CI [0.38-0.96]; p = 0.035) were protective. Failure groups had higher 60-day ventilator dependence (p < 0.001), MV duration (p < 0.0001), and ICU stay (p = 0.001). Patients who failed had higher mortality in COVID-19 group (p < 0.001) but not in the non-COVID-19 (p = 0.083). In patients with AHRF of different etiologies, the failure of the first PSV attempt was 43.7%, and at a higher rate in COVID-19. Independent risk factors included COVID-19 diagnosis, fentanyl dose, previous neuromuscular blockers, acidosis and hypoxemia preceding SAT, whereas higher BMI was protective. Failure was associated with worse outcomes.

Efficacy of treatment with N-acetylcysteine inhalation for AECOPD: A propensity-score-matched cohort study.

N-acetylcysteine (NAC) prevents acute exacerbations of chronic obstructive pulmonary disease (AECOPD). However, the value of NAC inhalation in the treatment of patients with AECOPD is still poorly understood. The study was conducted to evaluate the efficacy of NAC inhalation in AECOPD patients requiring hospitalization. In this single institutional, retrospective cohort study, all patients with AECOPD requiring hospitalization between January 2021 and January 2022 were included. Patients were divided into NAC group and Non-NAC group according to whether being treated with NAC inhalation and were matched using the propensity score. The primary outcome was a composite of progression to ventilation requirement, in-hospital mortality and readmission for AECOPD within 30 days. The effect on the mean hospitalized days, blood gas indexes and the incidence rate of adverse drug events were compared between the two groups. Ninety-six patients in the NAC group were matched with 96 patients in the Non-NAC group. The differences in the primary composite end point (NAC group vs Non-NAC group, 5.2% vs 16.7%; P = 0.011) were significant. The median time to discharge was shorter in the NAC group (8.3 vs. 9.1 days, P = 0.030). The NAC group presented a larger increase in partial pressure of arterial oxygen (Pa O2 ) and a higher ratio of self-reported symptomatic improvement from admission to day 5. There was no definite difference between the two groups in the frequency of adverse event. NAC inhalation is associated with an improved clinical outcome. A further study should be conducted to confirm the clinical usefulness of NAC inhalation in AECOPD patients.

Blood eosinophils and clinical features of pneumoconiosis complicated with chronic obstructive pulmonary disease: A cross-sectional study

Objective: To analyze the correlation between peripheral blood eosinophil (EOS) level and clinical characteristics of patients with pneumoconiosis complicated with chronic obstructive pulmonary disease (COPD) . Methods: From January 2007 to November 2020, newly diagnosed patients with pneumoconiosis complicated with COPD in Beijing Chaoyang Hospital, were retrospectively analyzed. These patients were stratified into EOS<100 cells/μl group and EOS≥100 cells/μl group, taking 100 cells/μl as the cut-off value. Demographic characteristics, clinical symptoms, lung function and laboratory indexes were compared between the two groups. Results: The median EOS count of patients with pneumoconiosis complicated with COPD was 100 (40, 180) cells/μl. 50.2% (160/319) had blood eosinophil counts ≥100 cells/μl, and 11.0% (35/319) had blood eosinophil counts ≥300 cells/μl. In comparison with EOS<100 cells/μl group, EOS≥100 cells/μl group were older (P=0.035), had higher body mass index (P=0.008), and had lower forced respiratory volume in the first second (P=0.017), had higher the ratio of residual volume to total lung volume (P=0.010), and had lower diffusing capacity of the lung for carbon monoxide (P=0.008). Arterial partial pressure of oxygen was significantly reduced in EOS≥100 cells/μl group (P=0.039). The peripheral blood EOS count was negatively correlated with forced vital capacity, forced breathing volume in the first second, carbon monoxide diffusion, peak expiratory flow, and maximum mid expiratory flow as a percentage of expected values (r(s)=-0.22, -0.18, -0.19, -0.19, -0.19, P=0.000, 0.001, 0.003, 0.008, 0.002), and positively correlated with the ratio of residual air volume to total lung volume (r(s)=0.17, P=0.002) . Conclusion: There was a correlation between blood EOS count and pulmonary function parameters, can proide reference for the diagnosis and treatment of chnoric obstuctive pulmmory disease in clinical practice.

Effect of different analgesic treatments on the pulmonary function in elderly hip fracture patients: A prospective study.

To investigate the effect of different analgesic methods on lungs in elderly patients with hip fractures. A prospective study was conducted on 78 elderly hip fracture patients undergoing spinal anesthesia for surgery, where 3 analgesic methods were used: postoperative Patient-controlled intravenous analgesia pump (PCIA) (group I), pre and postoperative PCIA (group II), and preoperative fascia iliaca compartment block (FICB) + postoperative PCIA (group III). The following indicators were monitored at admission (T1), on the day of surgery before anesthesia (T2), and 7 days after surgery (T3): heart rate (HR), respiratory rate (RR), forced expiratory volume during the first second, arterial partial pressure of oxygen (PaO2) and carbon dioxide (PaCO2), C-reactive protein (CRP), and interleukin 6 (IL-6). Pulmonary complications such as pulmonary atelectasis and respiratory insufficiency were analyzed. The HR, RR, forced expiratory volume during the first second, PaO2, PaCO2, IL-6, and CRP levels at T1 after fracture did not significantly differ among the 3 groups (P > .05). After different analgesic treatments post-admission, all indicators at T2 were significantly higher in group I than in groups II and III (P < .05), while there was no significant difference between groups II and III (P > .05). At T3, there were no significant differences in RR, HR, PaO2, PaCO2, and CRP levels among the groups (P > .05), but IL-6 levels at T3 were significantly higher in group I than in groups II and III (P < .05). The use of effective pain relief during surgery can help protect the lung function of elderly patients with hip fractures. When using PCIA with FICB before surgery, respiratory performance may be better protected compared to using unsustained analgesia. This could be due to a decrease in the levels of inflammatory markers such as CRP and interleukin-6.

Immune disturbance leads to pulmonary embolism in COVID-19 more than classical risk factors: a clinical and histological study

COVID-19 induces endotheliitis and one of the main complications is enhanced coagulation. The incidence of pulmonary embolism (PE) in COVID-19 (CPE) has increased and clinical features for a rigorous analysis still need to be determined. Thus, we evaluated the clinical characteristics in CPE and the immune infiltration that occurred. Between January 1 and December 31, 2021, 38 patients were affected by CPE (9 ICU, 19 males/19 females, 70.18 ± 11.24 years) out of 459 COVID-19 cases. Controls were subjects who were evaluated for PE between January 1 2015, and December 31, 2019 (92 patients, 9 ICU, 48 males/45 females, 69.55 ± 16.59 years). All patients underwent complete physical examination, pulmonary computed tomography, laboratory tests, D-dimer, and blood gas analysis. There were no differences in laboratory tests or D-dimer. In patients with CPE, pO2, alveolar–arterial oxygen difference (A-aDO2), oxygen saturation %, and the ratio between arterial partial pressure of oxygen (PaO2) and fraction of inspired oxygen (FiO2), P/F, were significantly increased. There were no differences in PaCO2. Platelet count was inversely correlated to P/F (r = − 0.389, p = 0.02) but directly to A-aDO2 (r = 0.699, p = 0.001) only in patients with CPE. Histology of lung biopsies (7 CPE/7 controls) of patients with CPE showed an increase in CD15+ cells, HMGB1, and extracellular MPO as a marker of NETosis, while no significant differences were found in CD3+, CD4+, CD8+, and intracellular MPO. Overall, data suggest that CPE has a different clinical setting. Reduced oxygen content and saturation described in Patients with CPE should not be considered a trustworthy sign of disease. Increased A-aDO2 may indicate that CPE involves the smallest vessels as compared to classical PE. The significant difference in NETosis may suggest the mechanism related to thrombi formation.

The normal distribution of the hypoxic ventilatory response and methodological impacts: a meta-analysis and computational investigation.

The hypoxic ventilatory response (HVR) is the increase in breathing in response to reduced arterial oxygen pressure. Over several decades, studies have revealed substantial population-level differences in the magnitude of the HVR as well as significant inter-individual variation. In particular, low HVRs occur frequently in Andean high-altitude native populations. However, our group conducted hundreds of HVR measures over several years and commonly observed low responses in sea-level populations as well. As a result, we aimed to determine the normal HVR distribution, whether low responses were common, and to what extent variation in study protocols influence these findings. We conducted a comprehensive search of the literature and examined the distributions of HVR values across 78 studies that utilized step-down/steady-state or progressive hypoxia methods in untreated, healthy human subjects. Several studies included multiple datasets across different populations or experimental conditions. In the final analysis, 72 datasets reported mean HVR values and 60 datasets provided raw HVR datasets. Of the 60 datasets reporting raw HVR values, 35 (58.3%) were at least moderately positively skewed (skew > 0.5), and 21 (35%) were significantly positively skewed (skew > 1), indicating that lower HVR values are common. The skewness of HVR distributions does not appear to be an artifact of methodology or the unit with which the HVR is reported. Further analysis demonstrated that the use of step-down hypoxia versus progressive hypoxia methods did not have a significant impact on average HVR values, but that isocapnic protocols produced higher HVRs than poikilocapnic protocols. This work provides a reference for expected HVR values and illustrates substantial inter-individual variation in this key reflex. Finally, the prevalence of low HVRs in the general population provides insight into our understanding of blunted HVRs in high-altitude adapted groups. KEY POINTS: The hypoxic ventilatory response (HVR) plays a crucial role in determining an individual's predisposition to hypoxia-related pathologies. There is notable variability in HVR sensitivity across individuals as well as significant population-level differences. We report that the normal distribution of the HVR is positively skewed, with a significant prevalence of low HVR values amongst the general healthy population. We also find no significant impact of the experimental protocol used to induce hypoxia, although HVR is greater with isocapnic versus poikilocapnic methods. These results provide insight into the normal distribution of the HVR, which could be useful in clinical decisions of diseases related to hypoxaemia. Additionally, the low HVR values found within the general population provide insight into the genetic adaptations found in populations residing in high altitudes.

Transnasal Humidified Rapid-Insufflation Ventilatory Exchange Versus Conventional Facemask Breathing for Preoxygenation During Rapid Sequence Induction.

Transnasal humidified rapid-insufflation ventilatory exchange (THRIVE), if used for pre-oxygenation and apnoeic oxygenation, has the propensity to extend the safe apnoea time and thereby decrease the incidence of desaturation during rapid sequence induction (RSI) for emergency surgeries. Hence, we proposed to evaluate the comparative efficacy of pre-oxygenation with the use of conventional facemask breathing versus THRIVE during RSI in patients undergoing general anaesthesia (GA) for emergency surgeries. Eighty patients undergoing RSI under GA for emergency abdominopelvic surgery were divided randomly into two groups. Patients were preoxygenated for three minutes with 100% oxygen via either a high-flow nasal cannula at a flow of 60 L/minute using THRIVE or a tightly-held, snuggly-fitting facemask at a flow of 12L/minute using a circle system. RSI was administered followed by laryngoscopy and endotracheal intubation. Arterial partial pressure of oxygen (PaO2) measured immediately after successful endotracheal intubation was our primary outcome. The lowest peripheral oxygen saturation (SpO2), apnoea time, number of attempts at laryngoscopy, use of any rescue manoeuvres, and any adverse event were also recorded. Data thus collected were statistically analysed. No statistically significant difference in PaO2 value was observed after successful intubation, lowest SpO2, apnoea time, number of attempts at laryngoscopy, use of any rescue manoeuvres, and adverse event between both the groups (p>0.05). We conclude that though not superior to conventional facemasks, THRIVE is a safe, practicable, and efficient pre-oxygenation tool during RSI of GA for patients undergoing emergency surgeries.

Therapeutic Hypothermia for Refractory Hypoxemia on Venovenous Extracorporeal Membrane Oxygenation: An In Silico Study.

Patients with respiratory failure may remain hypoxemic despite treatment with venovenous extracorporeal membrane oxygenation (VV-ECMO). Therapeutic hypothermia is a potential treatment for such hypoxia as it reduces cardiac output () and oxygen consumption. We modified a previously published mathematical model of gas exchange to investigate the effects of hypothermia during VV-ECMO. Partial pressures were expressed as measured at 37°C (α-stat). The effect of hypothermia on gas exchange was examined in four clinical scenarios of hypoxemia on VV-ECMO, each with different physiological derangements. All scenarios had arterial partial pressure of oxygen (PaO2) ≤ 46 mm Hg and arterial oxygen saturation of hemoglobin (SaO2) ≤ 81%. Three had high with low extracorporeal blood flow to ratio (). The problem in the fourth scenario was recirculation, with normal . Cooling to 33°C increased SaO2 to > 89% and PaO2 to > 50 mm Hg in all scenarios. Mixed venous oxygen saturation of hemoglobin as % () increased to > 70% and mixed venous partial pressure of oxygen in mm Hg () increased to > 34 mm Hg in scenarios with low . In the scenario with high recirculation, and increased, but to < 50% and < 27 mm Hg, respectively. This in silico study predicted cooling to 33°C will improve oxygenation in refractory hypoxemia on VV-ECMO, but the improvement will be less when the problem is recirculation.

Application of in Vitro Membrane Pulmonary Oxygenation Technology (ECMO) in Neonatal Respiratory Failure

Objective: To explore the application of Extracorporeal Membrane Oxygenation technology (ECMO) in neonatal respiratory failure and provide guidance for future ECMO technology for critically ill newborns. Methods: Retrospective analysis of the basic data, ECMO support process, and long-term neurological development of nine children supported by ECMO at Zhongshan People’s Hospital from January 2015 to August 2021. Results: From January 2015 to August 2021, the number of admissions to the neonatal department of our hospital was 10,325, with 433 cases of neonatal respiratory failure, which was in line with ECMO support indication of 21 cases, of which 12 were non-ECMO groups and 12 were ECMO groups. In nine cases, the differences in sex, birth weight, gestational age, birth pattern, Apgar score, NCIS score, OI value, hospitalization days, mortality rate, and incidence of intracranial bleeding were not statistically significant (P&gt;0.05). However, the average daily hospitalization cost for children in the ECMO group was significantly higher than that in the non-ECMO group, and the difference was statistically significant (P&lt;0.05). ECMO after 12 h operation, arterial oxygen pressure, and intravenous oxygen saturation are substantially enhanced, while arterial carbon dioxide pressure oxygenation index is considerably reduced, with a statistically significant difference (P&lt;0.05). ECMO pre-operation survival group lactic acid (6.46±2.70) was lower than the death group (17.66±14.62), after operation lactic acid decreased significantly, and after ECMO operation of the death group lactic acid showed an increase in conductivity. During the early stage of ECMO establishment, PT and APTT rapidly rise, while FIB decline. The ACT of both groups of children increased in the early stages of ECMO establishment and then gradually declined. In the ECMO group, seven children survived to discharge, six had no neurological developmental problems, and one had residual neurological sequelae. Conclusion: ECMO can be employed as a complementary supportive treatment for newborns with respiratory failure, and the oxygenation condition can be effectively improved for newborns with respiratory failure who have failed to respond to traditional treatment.

Physiological effects of N95 respirators on rescuers during cardiopulmonary resuscitation

ObjectivesThere is a lack of evidence in the medical literature reporting the physiological stress imposed by the wearing of N95 respirators during cardiopulmonary resuscitation (CPR) in healthcare providers. The aim of this study is to monitor the changes in hemodynamics and blood gas profiles in rescuers during the performance of CPR while wearing N95 respirators. MethodsThirty-two healthy healthcare workers performed standard CPR on manikins, each participant conducted 2 min of chest compression followed by 2 min of rest for 3 cycles. A non-invasive blood gas measuring device via a fingertip detector was used to collect arterial blood gas and hemodynamic data. Student t-test was used for comparison of various physiologic parameters before and after each session of chest compression. ResultsThere were no significant differences in arterial blood gas profiles including partial pressure of arterial carbon dioxide and partial pressure of arterial oxygen before and after each session of chest compression (p > 0.05 for all). Heart rate and cardiac output were significantly higher after CPR (p < 0.05 for all), but no significant changes were found on blood pressure. ConclusionsOur data suggest that healthcare providers wearing N95 respirators during provision of CPR in a short period of time does not cause any significant abnormalities in blood gas profiles and blood pressure. This may provide evidence to reassure the safe use of N95 respirator during performance of CPR.

Lupus eritematoso sistémico en la unidad de cuidados intensivos de urgencias

ObjectivesTo compare the characteristics of patients who died versus those who survived with systemic lupus erythematosus (SLE) in the emergency intensive care unit (UCIE). Material and methodsRetrospective collection of clinical and laboratory findings of clinical histories of patients with SLE in the UCIE of the Hospital Clínico Quirúrgico de Holguín in the period from January 2016 to January 2021. A descriptive statistical study and univariate analysis were carried out for continuous and discrete variables. The APACHE II score was calculated. ResultsThere were 23 patients with SLE during the period worked. The frequency of SLE in the ICU of the Hospital Clínico Quirúrgico de Holguín is 1.5%, it is the most frequent rheumatic pathology in ICU. Mortality in the ICU was 39.13%. The most frequent reason for admission was respiratory failure (52.4%), mostly due to an infectious cause. The variables that were significantly associated with mortality in the UCIE were: high erythrocyte sedimentation rate (ESR), severe anemia, severe hypoalbuminemia, the relationship arterial oxygen pressure between the fraction of inspired oxygen (PaFi)<200 on admission. The APACHE II score in the deceased group was significantly higher (19.9) (P<.01). Acute renal failure requiring hemodialysis and the need for invasive mechanical ventilation in different modalities for variable times were significantly associated with higher mortality in ICU. ConclusionsSLE in the ICU of the Hospital Clínico Quirúrgico de Holguín has a high mortality rate, higher than that reported in previous studies. Poor prognostic factors were high ESR, severe anemia, severe hypoalbuminemia, PaFi<200, high APACHE II score, need for hemodialysis and invasive mechanical ventilation.

Association of Delirium and Depression with Respiratory and Outcome Measures in COVID-19 Inpatients.

Delirium (DEL) and depression (DEP) may impair the course and severity of acute respiratory illness. The impact of such syndromes on respiratory and outcome parameters in inpatients with COVID-19 needs clarification. To clarify the relationship between DEL and DEP and respiratory outcome measures, we enrolled 100 inpatients from COVID-19 units of the Fondazione Policlinico Universitario Agostino Gemelli IRCCS of Rome. Participants were divided into those with DEL, DEP, or absence of either delirium or depression (CONT). Delirium severity was assessed with the Neelson and Champagne Confusion Scale (NEECHAM). Psychopathology was assessed with the Hamilton Rating Scale for Depression (HAM-D), the Hamilton Rating Scale for Anxiety (HAM-A), and the Brief Psychiatric Rating Scale (BPRS). Dependent variables include: (a) respiratory parameters, i.e., partial pressure of oxygen in arterial blood (PaO2), oxygen saturation (SpO2), ratio between arterial partial pressure of oxygen (PaO2), and fraction of inspired oxygen (PaO2/FiO2); (b) outcome parameters, i.e., duration of hospitalization and number of pharmacological treatments used during the hospitalization. We investigated between-group differences and the relationships between severity of delirium/depression and the dependent variables. Duration of hospitalization was longer for DEL than for either DEP or CONT and for DEP compared to CONT. NEECHAM and HAM-D scores predicted lower PaO2 and PaO2/FiO2 levels in the DEL and DEP groups, respectively. In DEP, BPRS scores positively correlated with duration of hospitalization. Delirium impacted the course of COVID-19 more severely than depression. The mechanisms by which delirium and depression worsen respiratory parameters differ.

The Impact of Left Ventricular Diastolic Dysfunction on Respiratory Adverse Events in Cardiac Surgery Patients-An Observational Prospective Single-Center Study.

Left ventricular diastolic dysfunction (LV DD) is the most dominant cause of heart failure with preserved ejection fraction (HFpEF) worldwide. This pathological condition may contribute to postcapillary pulmonary hypertension (pcPH) development. Hypoxemia, often observed in pcPH, may significantly negatively impact the course of hospitalization in patients after cardiac surgery. The aim of our study was to investigate the impact of LV DD on the frequency of postoperative respiratory adverse events (RAE) in patients undergoing Coronary Artery Bypass Grafting (CABG). The left ventricular (LV) diastolic function was assessed in 56 consecutive patients admitted for CABG. We investigated the relationship between LV DD and postoperative respiratory adverse events (RAE) in groups with normal LV diastolic function and LV DD stage I, II, and III. Left ventricular diastolic dysfunction stage I was observed in 11 patients (19.6%) and LV DD stage II or III in 19 patients (33.9%). Arterial blood partial pressure of oxygen (PaO2) to the fraction of inspired oxygen (FiO2) index during postoperative mechanical ventilation was significantly lower in LV DD stage II or III than in the group with normal LV diastolic function. Patients with DD stage II or III had a higher occurrence of postoperative pneumonia than the group with normal LV diastolic function. Left ventricular diastolic dysfunction is widespread in cardiac surgery patients and is an independent risk factor for lower minimal PaO2/FiO2 index during mechanical ventilation and higher occurrence of pneumonia.

Systemic and functional effects of continuous azithromycin treatment in patients with severe chronic obstructive pulmonary disease and frequent exacerbations.

Continuous treatment with azithromycin may lead to fewer acute exacerbations of chronic obstructive pulmonary disease (AECOPD), but little is known of its impact on systemic and functional outcomes in real-life settings. This was a multicenter prospective observational study of patients with severe COPD who started treatment with azithromycin. Tests were compared at baseline and after 3 and 12 months of treatment. These included lung function tests, a 6-min walking test (6MWT), and enzyme-linked immunosorbent assays of serum and sputum markers, such as interleukins (IL-6, IL-8, IL-13, IL-5), tumor necrosis factor receptor 2 (TNFR2), and inflammatory markers. Incidence rate ratios (IRR) and their 95% confidence intervals (95% CI) are reported. Of the 478 eligible patients, the 42 who started azithromycin experienced reductions in AECOPDs (IRR, 0.34; 95% CI, 0.26-0.45) and hospitalizations (IRR, 0.39; 95% CI, 0.28-0.49). Treatment was also associated with significant improvement in the partial arterial pressure of oxygen (9.2 mmHg, 95% CI 1.4-16.9) at 12 months. While TNFR2 was reduced significantly in both serum and sputum samples, IL-13 and IL-6 were only significantly reduced in serum samples. Moreover, an elevated serum and sputum IL-8 level significantly predicted good clinical response to treatment. Continuous azithromycin treatment in a cohort of patients with severe COPD and frequent exacerbations can significantly reduce the number and severity of exacerbations and improve gas exchange. Treatment changes the pattern of microorganism isolates and decreases the inflammatory response. Of note, IL-8 may have utility as a predictor of clinical response to azithromycin treatment.

Evaluation of right ventricular function using two-dimensional speckle tracking echocardiography and analysis of the risk factors for right ventricular dysfunction in patients with silicosis

Objective: To evaluate the right ventricular function using two-dimensional speckle tracking echocardiography (2-D STE) and analyze the associated risk factors of right ventricular dysfunction in patients with silicosis. Methods: All 104 patients with silicosis treated in the Department of Occupational Medicine and Toxicology in Beijing Chao-Yang Hospital, Capital Medical University from May 2021 to September 2022 were enrolled in this study in October 2022. The clinical information of patients such as general data, arterial blood gas analysis and pulmonary function test were collected. The right ventricular function of patients was evaluated by 2-D STE-derived right ventricular free wall longitudinal strain (RVFWLS) and conventional echocardiographic-derived parameters, including right ventricular fractional area change (RVFAC), tricuspid annular plane systolic excursion (TAPSE) and doppler tissue imaging-derived tricuspid lateral annular systolic velocity (S'), respectively. Based on their RVFWLS, the patients were divided into right ventricular dysfunction group and normal right ventricular function group. Risk factors for right ventricular dysfunction in patients with silicosis were analyzed using binary logistic regression analysis. Results: A total of 104 silicosis patients were enrolled, with aneverage age (65.52±11.18) years old, among whom including 57 cases diagnosed with stage Ⅰ/Ⅱ silicosis and 47 cases diagnosed with stage Ⅲ silicosis. 26 (25.00%) patients concurrent right ventricular dysfunction. The abnormal rates of RVFAC, TAPSE and S' in patients were 16.35% (17 cases), 21.15% (22 cases) and 6.73% (7 cases), respectively. The RVFAC and TAPSE in right ventricular dysfunction group were lower than those in normal right ventricular function group, and the incidence of pulmonary arterial systolic pressure ≥36 mmHg was higher than that in normal right ventricular function group (P<0.05). Logistic regression analysis showed that arterial partial pressure of oxygen (OR=0.932, 95%CI: 0.885-0.981, P=0.007) was the protective factor, and the forced expiratory volume in 1 second (FEV(1)) /forced vital capacity (FVC) ratio<70% (OR=5.484, 95%CI: 1.049-28.662, P=0.044) and stage Ⅲ silicosis (OR=6.343, 95%CI: 1.698-23.697, P=0.007) were the risk factors for silicosis patients concurrent right ventricular dysfunction. Conclusion: The incidence of right ventricular dysfunction is higher in patients with stage Ⅲ silicosis than that in patients with stage Ⅰ/Ⅱ silicosis. Using 2-D STE can help the early detection of silicosis with right ventricular dysfunction. Hypoxemia, airflow limitation and the stage Ⅲ silicosis are the risk factors for silicosis patients concurrent right ventricular dysfunction.

Ultra-low tidal volume ventilation for COVID-19-related ARDS in France (VT4COVID): a multicentre, open-label, parallel-group, randomised trial

COVID-19-related acute respiratory distress syndrome (ARDS) is associated with a high mortality rate and longer mechanical ventilation. We aimed to assess the effectiveness of ventilation with ultra-low tidal volume (ULTV) compared with low tidal volume (LTV) in patients with COVID-19-related ARDS. This study was a multicentre, open-label, parallel-group, randomised trial conducted in ten intensive care units in France. Eligible participants were aged 18 years or older, received invasive mechanical ventilation for COVID-19 (confirmed by RT-PCR), had ARDS according to the Berlin definition, a partial pressure of arterial oxygen to inspiratory oxygen fraction (PaO2/FiO2) ratio of 150 mm Hg or less, a tidal volume (VT) of 6·0 mL/kg predicted bodyweight or less, and received continuous intravenous sedation. Patients were randomly assigned (1:1) using randomisation blocks to receive ULTV (intervention group) aiming for VT of 4·0 mL/kg predicted bodyweight or LTV (control group) aiming for VT 6·0 mL/kg predicted bodyweight. Participants, investigators, and outcome assessors were not masked to group assignment. The primary outcome was a ranked composite score based on all-cause mortality at day 90 as the first criterion and ventilator-free days among patients alive at day 60 as the second criterion. Effect size was computed with the unmatched win ratio, on the basis of pairwise prioritised comparison of primary outcome components between every patient in the ULTV group and every patient in the LTV group. The unmatched win ratio was calculated as the ratio of the number of pairs with more favourable outcome in the ULTV group over the number of pairs with less favourable outcome in the ULTV group. Primary analysis was done in the modified intention-to-treat population, which included all participants who were randomly assigned and not lost to follow-up. This trial is registered with ClinicalTrials.gov, NCT04349618. Between April 15, 2020, and April 13, 2021, 220 patients were included and five (2%) were excluded. 215 patients were randomly assigned (106 [49%] to the ULTV group and 109 [51%] to the LTV group). 58 (27%) patients were female and 157 (73%) were male. The median age was 68 years (IQR 60-74). 214 patients completed follow-up (one lost to follow-up in the ULTV group) and were included in the modified intention-to-treat analysis. The primary outcome was not significantly different between groups (unmatched win ratio in the ULTV group 0·85 [95% CI 0·60 to 1·19]; p=0·38). 46 (44%) of 105 patients in the ULTV group and 43 (39%) of 109 in the LTV group died by day 90 (absolute difference 4% [-9 to 18]; p=0·52). The rate of severe respiratory acidosis in the first 28 days was higher in the ULTV group than in the LTV group (35 [33%] vs 14 [13%]; absolute difference 20% [95% CI 9 to 31]; p=0·0004). In patients with moderate-to-severe COVID-19-related ARDS, there was no significant difference with ULTV compared with LTV in the composite score based on mortality and ventilator-free days among patients alive at day 60. These findings do not support the systematic use of ULTV in patients with COVID-19-related ARDS. French Ministry of Solidarity and Health and Hospices Civils de Lyon.

Physiologic Markers of Disease Severity in ARDS.

Despite its significant limitations, the PaO2 /FIO2 remains the standard tool to classify disease severity in ARDS. Treatment decisions and research enrollment have depended on this parameter for over 50 years. In addition, several variables have been studied over the past few decades, incorporating other physiologic considerations such as ventilation efficiency, lung mechanics, and right-ventricular performance. This review describes the strengths and limitations of all relevant parameters, with the goal of helping us better understand disease severity and possible future treatment targets.

Arterial partial pressure of oxygen and procalcitonin combined with ROX index predict the timing of tracheal intubation in patients with acute severe pancreatitis

To investigate the efficacy of arterial partial pressure of oxygen (PaO2), procalcitonin (PCT) combined with ROX index in predicting the timing of tracheal intubation in patients with acute severe pancreatitis (SAP). A case-control study was conducted. A total of 148 patients with SAP admitted to Hunan Provincial People's Hospital from January 2019 to December 2022 were selected as the research objects. According to whether endotracheal intubation was used after admission during hospitalization, the patients were divided into the intubation group (102 cases) and non-intubation group (46 cases). Gender, age, white blood cell count (WBC), lymphocyte count (LYM), platelet count (PLT), C-reactive protein (CRP), hemoglobin (Hb), PCT, PaO2, arterial partial pressure of carbon dioxide (PaCO2), arterial bicarbonate ion (HCO3-) 1 day after admission, arterial lactic acid (Lac), lactate dehydrogenase (LDH), heart rate (HR), respiratory rate (RR), pulse oxygen saturation (SpO2), oxygenation index (PaO2/FiO2), blood pressure, worst ROX index (ROX index = SpO2/FiO2/RR) within 30 minutes of admission and 30 minutes before intubation of the two groups were measured. Multivariate Logistic regression was used to analyze the independent risk factors for the timing of endotracheal intubation in patients with SAP. The receiver operator characteristic curve (ROC curve) was used to determine the optimal predictive cut-off value for endotracheal intubation. There were no significant differences in age, gender, WBC, LYM, CRP, Hb, LDH, HR and blood pressure at admission between the two groups. The PLT, Lac, PCT and RR in the intubation group were significantly higher than those in the un-intubation group, and HCO3-, PaO2, SpO2, PaO2/FiO2, the worst ROX index within 30 minutes after admission and 30 minutes before intubation were significantly lower than those in the non-intubation group (all P < 0.05). Logistic regression analysis showed that the worst ROX index within 30 minutes before intubation was the largest negative influencing factor for the timing of tracheal intubation in SAP patients [odds ratio (OR) = 0.723, 95% confidence interval (95%CI) was 0.568-0.896, P = 0.000], followed by PaO2 (OR = 0.872, 95%CI was 0.677-1.105, P < 0.001). PCT was the positive influencing factor (OR = 1.605, 95%CI was 1.240-2.089, P < 0.001). ROC curve analysis showed that the area under the ROC curve (AUC) of PaO2, PCT, the worst ROX index within 30 minutes before intubation and the combination to evaluate the tracheal intubation time of patients with SAP were 0.715, 0.702, 0.722 and 0.808, the sensitivity was 78.1%, 75.0%, 81.5% and 89.3%, the specificity was 66.7%, 59.0%, 73.2% and 86.4%, and the best cut-off value was 60.23 mmHg (1 mmHg ≈ 0.133 kPa), 2.72 μg/L, 4.85, and 0.58, respectively. The AUC of the combination of PaO2, PCT and the worst ROX index within 30 minutes before intubation predicted the timing of tracheal intubation in patients with SAP was significantly greater than using each index alone (all P < 0.01). The worst ROX index within 30 minutes before intubation combined with PaO2 and PCT is helpful for clinicians to make a decision for tracheal intubation in patients with SAP.

Arterial partial pressure of oxygen as a marker of airway closure does not correlate with the efficacy of pre-oxygenation: A prospective cohort study.

The prerequisites for the early formation of anaesthesia-related atelectasis are pre-oxygenation with its resulting high alveolar oxygen content, and airway closure. Airway closure increases with age, so it seems counterintuitive that atelectasis formation during anaesthesia does not. One proposed explanation is that pre-oxygenation is impaired in the elderly by airway closure present in the waking state. The extent of airway closure cannot be assessed at the bedside, but arterial partial pressure of oxygen (PaO2) as a surrogate variable of the resulting ventilation to perfusion mismatch can. The primary aim was to test the hypothesis that a decreased efficacy of pre-oxygenation, measured as the fraction of end-tidal oxygen (FE'O2) after 3 min of pre-oxygenation, correlates with decreased PaO2 on room air. We also re-investigated the influence on FE'O2 by age. Prospective observational study. Two regional hospitals, Västerås and Köping County Hospitals, Västmanland, Sweden, between 30 October 2018 and 17 September 2021. We included 120 adults aged 40 to 79 years presenting for elective noncardiac surgery. An arterial blood gas was sampled before commencing pre-oxygenation. No linear correlation was found between FE'O2 at 3 min and PaO2 or age (Pearson's r = -0.038, P = 0.684; and Pearson's r = -0.113, P = 0.223, respectively). The mean ± SD FE'O2 at 3 min for the population studied was 0.87 ± 0.05. The lack of correlation between FE'O2 at 3 min and PaO2 or age during pre-oxygenation has implications for further studies concerning the interaction between airway closure and atelectasis. After 3 min of pre-oxygenation, FE'O2, even in the elderly, indicated a high enough alveolar oxygen concentration to promote atelectasis after induction, therefore, it is still unclear why atelectasis formation diminishes after middle age. ClinicalTrials.gov, identifier: NCT03395782.