Arterial Carbon Dioxide Tension Research Articles

Blood oxygenation state in COVID-19 patients: Unexplored role of 2,3-bisphosphoglycerate

BackgroundCOVID-19 reduces lung functionality causing a decrease of blood oxygen levels (hypoxemia) often related to a decreased cellular oxygenation (hypoxia). Besides lung injury, other factors are implicated in the regulation of oxygen availability such as pH, partial arterial carbon dioxide tension (PaCO2), temperature, and erythrocytic 2,3-bisphosphoglycerate (2,3-BPG) levels, all factors affecting hemoglobin saturation curve. However, few data are currently available regarding the 2,3-BPG modulation in SARS-CoV-2 affected patients at the hospital admission. Material and methodsSixty-eight COVID-19 patients were enrolled at hospital admission. The lung involvement was quantified using chest-Computer Tomography (CT) analysed with automatic software (CALIPER). Haemoglobin concentrations, glycemia, and routine analysis were evaluated in the whole blood, while partial arterial oxygen tension (PaO2), PaCO2, pH, and HCO3− were assessed by arterial blood gas analysis. 2,3-BPG levels were assessed by specific immunoenzymatic assays in RBCs. ResultsA higher percentage of interstitial lung disease (ILD) and vascular pulmonary-related structure (VRS) volume on chest-CT quantified with CALIPER had been found in COVID-19 patients with a worse disease outcome (R = 0.4342; and R = 0.3641, respectively). Furthermore, patients with lower PaO2 showed an imbalanced acid-base equilibrium (pH, p = 0.0208; PaCO2, p = 0.0496) and a higher 2,3-BPG levels (p = 0.0221). The 2,3-BPG levels were also lower in patients with metabolic alkalosis (p = 0.0012 vs. no alkalosis; and p = 0.0383 vs. respiratory alkalosis). ConclusionsOverall, the data reveal a different pattern of activation of blood oxygenation compensatory mechanisms reflecting a different course of the COVID-19 disease specifically focusing on 2,3-BPG modulation.

Prognostic value of arterial carbon dioxide tension during cardiopulmonary resuscitation in out-of-hospital cardiac arrest patients receiving extracorporeal resuscitation

BackgroundCurrent guidelines on extracorporeal cardiopulmonary resuscitation (ECPR) recommend careful patient selection, but precise criteria are lacking. Arterial carbon dioxide tension (PaCO2) has prognostic value in out-of-hospital cardiac arrest (OHCA) patients but has been less studied in patients receiving ECPR. We studied the relationship between PaCO2 during cardiopulmonary resuscitation (CPR) and neurological outcomes of OHCA patients receiving ECPR and tested whether PaCO2 could help ECPR selection.MethodsThis single-centre retrospective study enrolled 152 OHCA patients who received ECPR between January 2012 and December 2020. Favorable neurological outcome (FO) at discharge was the primary outcome. We used multivariable logistic regression to determine the independent variables for FO and generalised additive model (GAM) to determine the relationship between PaCO2 and FO. Subgroup analyses were performed to test discriminative ability of PaCO2 in subgroups of OHCA patients.ResultsMultivariable logistic regression showed that PaCO2 was independently associated with FO after adjusting for other favorable resuscitation characteristics (Odds ratio [OR] 0.23, 95% Confidence Interval [CI] 0.08–0.66, p-value = 0.006). GAM showed a near-linear reverse relationship between PaCO2 and FO. PaCO2 < 70 mmHg was the cutoff point for predicting FO. PaCO2 also had prognostic value in patients with less favorable characteristics, including non-shockable rhythm (OR, 3.78) or low flow time > 60 min (OR, 4.66).ConclusionPaCO2 before ECMO implementation had prognostic value for neurological outcomes in OHCA patients. Patients with PaCO2 < 70 mmHg had higher possibility of FO, even in those with non-shockable rhythm or longer low-flow duration. PaCO2 could serve as an ECPR selection criterion.

Relationship between maternal arterial and foetal cord carbon dioxide tension and neonatal outcome in critically ill pregnant women at delivery.

No studies have evaluated the relationship between maternal arterial partial pressure of carbon dioxide (mPaCO2) and umbilical cord venous partial pressure of carbon dioxide (PCO2) in critically ill pregnant women at delivery. Based on the studies in healthy pregnant women, an mPaCO2 target of ≤50 mmHg is a suggested threshold during mechanical ventilation in critically ill parturients. We evaluated the relationship between mPaCO2 and neonatal cord gases in critically ill parturients at delivery as the primary objective. The relationship between mPaCO2 and APGAR scores at delivery was also analysed as a secondary objective. Maternal and neonatal cord gas data at delivery and APGAR scores were obtained by a retrospective chart review of 25 consecutive parturients with severe respiratory compromise who were delivered during mechanical ventilation. Linear regression was used to assess the relationship between mPaCO2 and umbilical artery and vein PCO2 and between mPaCO2 and APGAR scores at 1 and 5 min. There was a positive correlation between mPaCO2 and neonatal cord venous PCO2 (P = 0.013). Foetal venous PCO2 exceeded predelivery mPaCO2 by 17.5 (7.5) mmHg. There was an inverse relationship between mPaCO2 and neonatal APGAR scores at 1 and 5 min (P = 0.006 and P = 0.007, respectively). Foetal cord venous PCO2 can be predicted if mPaCO2 values are known. Unlike in healthy pregnant women, there was an inverse relationship between rising mPaCO2 levels and neonatal APGAR scores in critically ill pregnant women who had several associated compounding factors.

Association of Arterial Carbon Dioxide Tension Following In-Hospital Cardiac Arrest with Survival and Favorable Neurologic Outcome.

In-hospital cardiac arrest (IHCA) continues to be associated with high morbidity and mortality. The objective of this study was to study the association of arterial carbon dioxide tension (PaCO2) on survival to discharge and favorable neurologic outcome in adults with IHCA. The study population included 353 adults who underwent resuscitation from 2011 to 2021 for IHCA at an academic tertiary medical center with arterial blood gas testing done within 24 hours of arrest. Outcomes of interest included survival to discharge and favorable neurologic outcome, defined as Glasgow Outcome Score of 4-5. Of the 353 patients studied, PaCO2 classification included: hypocapnia (PaCO2 < 35mmg, n=89), normocapnia (PaCO2 35-45mmHg, n=151), and hypercapnia (PaCO2 > 45mmHg, n=113). Hypercapnic patients were further divided into mild (45mmHg < PaCO2 ≤ 55mmHg, n=62) and moderate/severe hypercapnia (PaCO2 > 55mmHg, n=51). Patients with normocapnia had the highest rates of survival to hospital discharge (52.3% vs 32.6% vs 30.1%, p<0.001) and favorable neurologic outcome (35.8% vs 25.8% vs 17.9%, p=0.005) compared those with hypocapnia and hypercapnia respectively. In multivariable analysis, compared to normocapnia, hypocapnia (OR 2.06, 95%CI 1.15-3.70) and hypercapnia (OR 2.67, 95%CI 1.53-4.66) were both found to be independently associated with higher rates of in-hospital mortality. Compared to normocapnia, while mild hypercapnia (OR 2.53, 95%CI 1.29-4.97) and moderate/severe hypercapnia (OR 2.86, 95%CI 1.35-6.06) were both independently associated with higher in-hospital mortality compared to normocapnia, moderate/severe hypercapnia was also independently associated with lower rates of favorable neurologic outcome (OR 0.28, 95%CI 0.11-0.73), while mild hypercapnia was not. In this prospective registry of adults with IHCA, hypercapnia noted within 24 hours after arrest was independently associated with lower rates of survival to discharge and favorable neurologic outcome.

Death by Neurologic Criteria in Children Undergoing Extracorporeal Cardiopulmonary Resuscitation: Retrospective Extracorporeal Life Support Organization Registry Study, 2017-2021.

To determine factors associated with brain death in children treated with extracorporeal cardiopulmonary resuscitation (E-cardiopulmonary resuscitation). Retrospective database study. Data reported to the Extracorporeal Life Support Organization (ELSO), 2017-2021. Children supported with venoarterial extracorporeal membrane oxygenation (ECMO) for E-cardiopulmonary resuscitation. None. Data from the ELSO Registry included patient characteristics, blood gas values, support therapies, and complications. The primary outcome was brain death (i.e., death by neurologic criteria [DNC]). There were 2,209 children (≥ 29 d to < 18 yr of age) included. The reason for ECMO discontinuation was DNC in 138 patients (6%), and other criteria for death occurred in 886 patients (40%). Recovery occurred in 1,109 patients (50%), and the remaining 76 patients (4%) underwent transplantation. Fine and Gray proportional subdistribution hazards' regression analyses were used to examine the association between variables of interest and DNC. Age greater than 1 year ( p < 0.001), arterial blood carbon dioxide tension (Pa co2 ) greater than 82 mm Hg ( p = 0.022), baseline lactate greater than 15 mmol/L ( p = 0.034), and lactate 24 hours after cannulation greater than 3.8 mmol/L ( p < 0.001) were independently associated with greater hazard of subsequent DNC. In contrast, the presence of cardiac disease was associated with a lower hazard of subsequent DNC (subdistribution hazard ratio 0.57 [95% CI, 0.39-0.83] p = 0.004). In children undergoing E-cardiopulmonary resuscitation, older age, pre-event hypercarbia, higher before and during ECMO lactate levels are associated with DNC. Given the association of DNC with hypercarbia following cardiac arrest, the role of Pa co2 management in E-cardiopulmonary resuscitation warrants further studies.

Methaemoglobinaemia due to nitrobenzene poisoning

Abstract Nitrobenzene poisoning presenting as acute methaemoglobinaemia is an uncommon medical emergency. The case of a 17-year-old male with alleged history of consumption of ‘flower all’ (composition-nitrobenzene) is being reported here. At the time of presentation to the emergency department, the patient had cyanosis of lips and feet with Glasgow coma score 12. His pulse was 161/min, blood pressure 70/40 mm Hg and oxygen saturation by pulse oximeter was 72% on room air. His pupils were bilaterally dilated with sluggish reaction. Rest of the physical examination was unremarkable. In view of desaturation, he was intubated and connected to mechanical ventilator. Blood sample taken for arterial blood gas (ABG) analysis was dark brown in colour. ABG showed pH: 7.443, arterial carbon dioxide tension: 27.8 mm Hg, arterial oxygen saturation (SaO2) 95.6% and bicarbonate 18.7 mEq/L. The calculated difference between SaO2 and SPo2 was 23%. Despite being on mechanical ventilation, he continued to have hypoxia. With a suspicion of methaemoglobinaemia, blood samples were sent for methaemoglobin level. Blood methaemoglobin was 13%. The patient was immediately started on injection methylene blue and injection ascorbic acid. Two sessions of haemoperfusion and one session of exchange transfusion were done. He started to improve clinically on day 3. He was gradually weaned off the mechanical ventilator and was discharged in the stable condition after 3 weeks of in hospital stay.

Case Report: Spontaneous pneumothorax revealing multiple myeloma: a case report

Various causes like trauma, infection, pulmonary disease or neoplasm can lead to spontaneous pneumothorax. We report a rare case of a spontaneous pneumothorax as first manifestation of multiple myeloma. A 58-year-old patient presented suffering from dyspnea and right-sided chest pain, with no history of trauma. On examination, the patient had bilateral rib tenderness. The respiratory rate was 30 breaths/min and oxygen saturation was 88%. The chest physical exam revealed unequal breath sounds, an hyperresonance with percussion and decreased wall movement on the right side. The analysis of arterial blood gas revealed hypoxemia (arterial oxygen tension: 7.59 kPa) and hypercapnia (arterial carbon dioxide tension: 5.99 kPa). Laboratory data showed a raised C reactive protein level (133.8 mg/L), hyper-calcemia (serum calcium: 12.18 mg/dL) and a decreased plasma albumin level (31.9 g/L). Chest radiography and thoracic computed tomography revealed multiple ribs and sternum fractures leading to a partial pneumothorax on the right side. Subsequent workup for multiple myeloma showed elevated levels of immunoglobulin. Results of initial laboratory tests revealed an IgG gamma paraprotein, a urine protein electrophoresis of 1450 mg/24 hours and a β-2 microglobulin rate of 3.35. The diagnosis of multiple myeloma was confirmed with a bone marrow infiltration of 20% of atypical plasmatic cells. Cytogenetic investigations did not show any chromosomal abnormalities, especially the t (4,14) translocation. The patient was diagnosed with multiple myeloma stage IIIA according to Durie–Salmon classification. Appropriate treatment with oxygen therapy and systemic analgesic was started, associated with a cure of zoledronic acid in order to decrease the calcium level. The evolution was characterized by the complete resolution of the pneumothorax in 7 days and the normalization of the calcium level. The autologous stem cell transplant was the treatment of choice for this patient.

PULM7: Toward Automatic Control Of Arterial Blood Paco2 Using Artificial Lung Exhaust Gas CO2 As A Surrogate

Purpose: Current clinical Extra Corporeal CO2 removal systems rely on human intervention to adjust to changes in patient activity. Previous studies have investigated the use of capnography for measurement of arterial blood carbon dioxide tension (PaCO2) using artificial lungs (AL). The presented work demonstrates an initial implementation of a controller that directly monitors and regulates PaCO2 using exhaust gas CO2 (EGCO2) measurements. Method: The system operates through two cycles, namely measurement and control. First, the sweep gas flow through the AL is temporarily (~60s) reduced to ~400 mL/min to allow the CO2 concentration on the blood and gas phase of the AL to equilibrate. This allows for EGCO2 (measured via a CO2Meter GC-0017) values to be used as an estimate of PaCO2. The control cycle is based on Proportional-Integral-Derivative (PID) principle wherein the system automatically modulates sweep gas flows through the AL to minimize the difference between the desired PaCO2 and the estimated PaCO2 (i.e., measured EGCO2). Blood samples were intermittently collected at the inlet of the AL to monitor actual PaCO2 (measured via a Radiometer ABL800 Flex blood gas analyzer). The in vitro study setup (Fig. 1) consists of a Novalung iLA oxygenator (main AL) and a Capiox RX25 oxygenator (conditioning AL) connected in parallel to model a typical ECMO circuit. The blood reservoir mimics the blood volume (7 L) while the centrifugal pump simulates cardiac output (fixed at ~5 L/min) of a patient. Blood flow through the main AL (AV shunt) was regulated at ~1 L/min using a Hoffman clamp. CO2 concentration in the sweep gas through the conditioning AL was modulated to simulate metabolic activity. The baseline CO2 concentration measured at the outlet of the conditioning AL that projects reservoir PaCO2 level when the main AL is not operational. The baseline blood concentration was varied between 45 and 90 mmHg representing all levels of normocapnia and hypercapnia. Results: Prior to the controller testing, a feasibility study was performed to determine the accuracy of capnography technique in calculating the PaCO2 using the AL. A total of forty-two blood samples were collected at blood flow rates of 0.5, 0.6 and 1.0 L/min. The results show a good correlation between PaCO2 and EGCO2 (r2=0.824, P<0.001). There was a reasonable degree of agreement between the PaCO2 and EGCO2 with accuracy (bias or mean difference between PaCO2 and EGCO2) of 6.04 mmHg with a precision (95% limits of agreement) of ± 9.62 mmHg (Fig. 2). Despite the limitation of the AL in estimating PaCO2 using EGCO2, the PID controller implementation demonstrated that average reservoir CO2 concentration can be maintained at 44.23 ± 8.7 mmHg for a target PaCO2 of 40 mmHg (Fig. 3),against baseline blood reservoir PaCO2 of 60.76 ± 13.81 mmHg.Figure 1. Image showing in vitro test setup. The bovine blood in the test circuit was anticoagulated (ACT > 1200s) with heparin and maintained at 37°C.Figure 2. a) The regression curve generated between PaCO2 samples and measured EGCO2 b) Agreement between PaCO2 samples and measured EGCO2.Figure 3. a) In vitro test results showing changes in all PaCO2 concentrations in the circuit b) Result summary comparing average reservoir PaCO2 level with target PaCO2

Lower Oxygen Tension and Intracranial Hemorrhage in Veno-venous Extracorporeal Membrane Oxygenation.

We examined the relationship between 24-h pre- and post-cannulation arterial oxygen tension (PaO2) and arterial carbon dioxide tension (PaCO2) and subsequent acute brain injury (ABI) in patients receiving veno-venous extracorporeal membrane oxygenation (VV-ECMO) with granular arterial blood gas (ABG) data and institutional standardized neuromonitoring. Eighty-nine patients underwent VV-ECMO (median age = 50, 63% male). Twenty (22%) patients experienced ABI; intracranial hemorrhage (ICH) was the most common diagnosis (n = 14, 16%). Lower post-cannulation PaO2 levels were significantly associated with ICH (66 vs. 81mmHg, p = 0.007) and a post-cannulation PaO2 level < 70mmHg was more frequent in these patients (71% vs. 33%, p = 0.007). PaCO2 parameters were not associated with ABI. By multivariable logistic regression, hypoxemia post-cannulation increased the odds of ICH (OR = 5.06, 95% CI:1.41-18.17; p = 0.01). In summary, lower oxygen tension in the 24-h post-cannulation was associated with ICH development. The precise roles of peri-cannulation ABG changes deserve further investigation, as they may influence the management of VV-ECMO patients.

Supplemental oxygen and noninvasive ventilation.

The respiratory system attempts to maintain normal levels of oxygen and carbon dioxide. However, airflow limitation, parenchymal abnormalities and dysfunction of the respiratory pump may be compromised in individuals with advanced COPD, eventually leading to respiratory failure, with reduced arterial oxygen tension (hypoxaemia) and/or increased arterial carbon dioxide tension (P aCO2 ; hypercapnia). Hypoxaemia may persist in individuals with severe COPD despite smoking cessation and optimisation of pharmacotherapy. Long-term oxygen therapy (LTOT) can improve survival in those with severe daytime hypoxaemia, whereas those with less severe hypoxaemia may only have improved exercise capacity and dyspnoea. Changes in respiratory physiology that occur during sleep further predispose to hypoxaemia, particularly in individuals with COPD. However, the major cause of hypoxaemia is hypoventilation. Noninvasive ventilation (NIV) may reduce mortality and need for intubation in individuals with COPD and acute hypercapnic respiratory failure. However, NIV may also improve survival and quality of life in individuals with stable, chronic hypercapnia and is now suggested for those with prolonged hypercapnia (e.g. P aCO2 >55 mmHg 2-6 weeks after hospital discharge) when clinically stable and after optimisation of medical therapy including LTOT if indicated. Many questions remain about the optimal mode, settings and goal of NIV therapy.

Pathogenesis and Prevention of Intraventricular Hemorrhage in Preterm Infants.

Intraventricular hemorrhage (IVH) is a serious concern for preterm infants and can predispose such infants to brain injury and poor neurodevelopmental outcomes. IVH is particularly common in preterm infants. Although advances in obstetric management and neonatal care have led to a lower mortality rate for preterm infants with IVH, the IVH-related morbidity rate in this population remains high. Therefore, the present review investigated the pathophysiology of IVH and the evidence related to interventions for prevention. The analysis of the pathophysiology of IVH was conducted with a focus on the factors associated with cerebral hemodynamics, vulnerabilities in the structure of cerebral vessels, and host or genetic predisposing factors. The findings presented in the literature indicate that fluctuations in cerebral blood flow, the presence of hemodynamic significant patent ductus arteriosus, arterial carbon dioxide tension, and impaired cerebral venous drainage; a vulnerable or fragile capillary network; and a genetic variant associated with a mechanism underlying IVH development may lead to preterm infants developing IVH. Therefore, strategies focused on antenatal management, such as routine corticosteroid administration and magnesium sulfate use; perinatal management, such as maternal transfer to a specialized center; and postnatal management, including pharmacological agent administration and circulatory management involving prevention of extreme blood pressure, hemodynamic significant patent ductus arteriosus management, and optimization of cardiac function, can lower the likelihood of IVH development in preterm infants. Incorporating neuroprotective care bundles into routine care for such infants may also reduce the likelihood of IVH development. The findings regarding the pathogenesis of IVH further indicate that cerebrovascular status and systemic hemodynamic changes must be analyzed and monitored in preterm infants and that individualized management strategies must be developed with consideration of the risk factors for and physiological status of each preterm infant.

End-tidal carbon dioxide tension is a reliable surrogate of arterial carbon dioxide tension across different oxygen, carbon dioxide and barometric pressures.

End-tidal CO2 tension provides an accurate estimation of P aCO2 in healthy awake individuals over an extensive range of CO2 pressures induced by 17 environmental conditions combining different O2, CO2 and barometric pressures https://bit.ly/3YuKPAY.

Transcutaneous carbon dioxide monitoring during prolonged apnoea with high-flow nasal oxygen.

The duration of apnoeic oxygenation with high-flow nasal oxygen is limited by hypercapnia and acidosis and monitoring of arterial carbon dioxide level is therefore essential. We have performed a study in patients undergoing prolonged apnoeic oxygenation where we monitored the progressive hypercapnia with transcutaneous carbon dioxide. In this paper, we compared the transcutaneous carbon dioxide level with arterial carbon dioxide tension. This is a secondary publication based on data from a study exploring the limits of apnoeic oxygenation. We compared transcutaneous carbon dioxide monitoring with arterial carbon dioxide tension using Bland-Altman analyses in anaesthetised and paralysed patients undergoing prolonged apnoeic oxygenation until a predefined limit of pH 7.15 or PCO2 of 12 kPa was reached. We included 35 patients with a median apnoea duration of 25 min. Mean pH was 7.14 and mean arterial carbon dioxide tension was 11.2kPa at the termination of apnoeic oxygenation. Transcutaneous carbon dioxide monitoring initially slightly underestimated the arterial tension but at carbon dioxide levels above 10kPa it overestimated the value. Bias ranged from -0.55 to 0.81 kPa with limits of agreement between -1.25 and 2.11 kPa. Transcutaneous carbon dioxide monitoring provided a clinically acceptable substitute for arterial blood gases but as hypercapnia developed to considerable levels, we observed overestimation at high carbon dioxide tensions in patients undergoing apnoeic oxygenation with high-flow nasal oxygen.

Clinical impact of routine sleep assessment by peripheral arterial tonometry in patients with COPD.

Coexisting obstructive sleep apnoea (OSA) in patients with COPD, defined as overlap syndrome (OVS), is prevalent and underdiagnosed. Routine assessment of OSA is not common practice in COPD care. Our study assessed the clinical impact of sleep assessment by peripheral arterial tonometry (PAT) in COPD patients. 105 COPD patients (mean age 68.1±9 years, body mass index (BMI) 28.3±6.0 kg·m-2, 44% males, Global Initiative for Chronic Obstructive Lung Disease (GOLD) stages I to IV in 2%, 40%, 42% and 16%, respectively) underwent assessment at an outpatient COPD clinic including anthropometrics, arterial blood gas (ABG) and spirometry in this clinical cohort study. PAT-based sleep studies were performed. Predictors of OVS and ABG were determined. Rapid eye movement (REM) sleep-related OSA (REM-OSA) was analysed in OVS. 49 COPD patients (47%) suffered from moderate to severe OSA (OVS group, mean apnoea-hypopnoea index 30.8±18 events·h-1, REM-oxygen desaturation index (REM-ODI) 26.9±17 events·h-1). OVS was more prevalent in males compared to females (59% and 37%, p=0.029, respectively). Age (70.1±8 versus 66.3±10 years), BMI (30.0±6 versus 26.4±7 kg·m-2) and hypertension prevalence (71% versus 45%) were elevated (all p<0.03, respectively), while deep sleep (12.7±7% and 15.4±6%, p=0.029) and mean overnight oxygenation (90.6±3% and 92.3±2%, p=0.003) were lower in OVS compared to COPD alone. REM-ODI was independently associated with daytime arterial carbon dioxide tension (P aCO2 ) (β=0.022, p<0.001). REM-OSA was associated with an elevated prevalence of atrial fibrillation compared to no REM-OSA (25% and 3%, p=0.022). OVS was highly prevalent, specifically in obese males. REM-related OSA showed strong association with elevated daytime P aCO2 and prevalent cardiovascular disease. PAT was feasible for sleep assessment in COPD.

Efficacy and safety of high-flow nasal cannula therapy in elderly patients with acute respiratory failure.

To assess the efficacy and safety of high-flow nasal cannula (HFNC) in elderly patients with acute respiratory failure (ARF) not due to COVID-19, refractory to treatment with conventional oxygen therapy and/or intolerant to noninvasive ventilation (NIV) or continuous positive airway pressure (CPAP) and without criteria for admission to intensive care units (ICU). Prospective observational study of patients with ARF treated with HFNC who presented clinical and arterial blood gas deterioration after 24h of medical treatment and oxygenation by conventional systems. The degree of dyspnoea, gas exchange parameters (arterial O2 pressure/inspired O2 fraction ratio (PaO2/FiO2); oxygen saturation measured by oximetry/ inspired fraction of oxygen (Sp02/Fi02), ROX index), degree of patient tolerance and mortality were evaluated. These were measured at discharge from the emergency department (ED), 24h after treatment with conventional oxygenation and 60, 120min and 24h after initiation of HFNC. The results were analyzed for all patients as a whole and for patients with hypercapnia (arterial carbon dioxide tension (PaCO2) < 45 mmHg) separately. 200 patients were included in the study between November 2019 and November 2020, with a mean age of 83 years, predominantly women (61.9%), obese (Body Mass Index (BMI) 31.1), with high comorbidity (Charlson index 4) and mild-moderate degree of dependence (Barthel 60). A number of 128 patients (64%) were hypercapnic. None had respiratory acidosis (pH 7.39). Evaluation at 60min, 120min and 24h showed significant improvement in all patients and in the subgroup of hypercapnic patients with respect to baseline parameters in respiratory rate (RR), dyspnoea, ROX index, PaO2/FiO2, SpO2/FiO2 and patient comfort. No changes in PaCO2 or level of consciousness were observed. HFNC was well tolerated. Ten patients (5%) died due to progression of the disease causing ARF. HFNC is an effective and safe alternative in elderly patients with ARF not due to COVID-19, refractory to treatment with conventional oxygen therapy and/or intolerant to NIV or CPAP and without criteria for admission to ICU.

Invasive Mechanical Ventilation in Traumatic Brain Injured Patients with Acute Respiratory Failure.

Patients with severe traumatic brain injury (TBI) need to be admitted to intensive care (ICU) because they require invasive mechanical ventilation (IMV) due to reduced consciousness resulting in loss of protective airway reflexes, reduced ability to cough and altered breathing control. In addition, these patients can be complicated by pneumonia and acute distress syndrome (ARDS). IMV allows these patients to be sedated, decreasing intracranial pressure and ensuring an adequate oxygen delivery and tight control of arterial carbon dioxide tension. However, IMV can also cause dangerous effects on the brain due to its interaction with intrathoracic and intracranial compartments. Moreover, when TBI is complicated by ARDS, the setting of mechanical ventilation can be very difficult as ventilator goals are often different and in conflict with each other. Consequently, close brain and respiratory monitoring is essential to reduce morbidity and mortality in mechanically ventilated patients with severe TBI and ARDS. Recently, recommendations for the setting of mechanical ventilation in patients with acute brain injury (ABI) were issued by the European Society of Intensive Care Medicine (ESICM). However, there is insufficient evidence regarding ventilation strategies for patients with ARDS associated with ABI. The purpose of this paper is to analyze in detail respiratory strategies and targets in patients with TBI associated with ARDS.

Moderate-to-severe ARDS: COVID-19 patients compared to influenza patients for ventilator parameters and mortality.

This study aimed to compare ventilatory parameters recorded in the first days of acute respiratory distress syndrome (ARDS) and mortality at day 60 between coronavirus disease 2019 (COVID-19) and influenza ARDS patients with arterial oxygen tension (P aO2 )/inspiratory oxygen fraction (F IO2 ) ≤150 mmHg. We compared 244 COVID-19 ARDS patients with 106 influenza ARDS patients. Driving pressure, respiratory system compliance (C rs), ventilator ratio, corrected minute ventilation (V'Ecorr) and surrogate of mechanical power (index=(4×driving pressure)+respiratory rate) were calculated from day 1 to day 5 of ARDS. A propensity score analysis and a principal component analysis (PCA) were performed. On day 1 of ARDS, COVID-19 patients had significantly higher P aO2 /F IO2 (median (interquartile range) 97 (79-129.2) versus 83 (62.2-114) mmHg; p=0.001), and lower driving pressure (13.0 (11.0-16.0) versus 14.0 (12.0-16.7) cmH2O; p=0.01), ventilatory ratio (2.08 (1.73-2.49 versus 2.52 (1.97-3.03); p<0.001), V'Ecorr (12.7 (10.2-14.9) versus 14.9 (11.6-18.6) L·min-1; p<0.001) and index (80 (70-89) versus 84 (75-94); p=0.004). PCA demonstrated an important overlap of ventilatory parameters recorded on day 1 between the two groups. From day 1 to day 5, repeated values of P aO2 /F IO2 , arterial carbon dioxide tension, ventilatory ratio and V'Ecorr differed significantly between influenza and COVID-19 patients in the unmatched and matched populations. Mortality at day 60 did not differ significantly after matching (29% versus 21.7%; p=0.43). Ventilation was more impaired in influenza than in COVID-19 ARDS patients on the first day of ARDS with an important overlap of values. However, mortality at day 60 did not differ significantly in the matched population.

Sevoflurane Exposure of Clinical Doses in Pregnant Rats Induces Vcan Changes without Significant Neural Apoptosis in the Offspring

Background and Objectives: Sevoflurane is a commonly used inhalational anaesthetic in clinics. Prolonged exposure to sevoflurane can induce significant changes in lipid metabolism and neuronal damage in the developing brain. However, the effect of exposure of pregnant rats to clinical doses of sevoflurane remains unclear. Materials and Methods: Twenty-eight pregnant rats were randomly and equally divided into sevoflurane exposure (S) group, control (C) and a blank group at gestational day (G) 18; Rats in S group received 2% sevoflurane with 98% oxygen for 6 h in an anesthetizing chamber, while C group received 100% oxygen at an identical flow rate for 6 h in an identical chamber. Partial least squares discriminant analysis (PLS-DA), ultra performance liquid chromatography/time-of-flight mass spectrometry(UPLC/TOF-MS) and MetaboAnalyst were used to analysis acquire metabolomics profiles, and immunohistochemical changes of neuronalapoptosis in hippocampus and cortex of neonatal rats were also analyzed. Results: This study aimed to explore lipidomics and transcriptomics changes related to 2% sevoflurane exposure for 6 h in the developing brains of newborn offspring rats. Ultra-performance liquid chromatography/time-of-flight mass spectrometry (UPLC/TOF-MS) and RNA sequencing (RNA-seq) analyses were used to acquire metabolomics and transcriptomics profiles. We used RNA-seq to analyse the expression of the coding and non-coding transcripts in neural cells of the cerebral cortex. No significant differences in arterial oxygen tension (PaO2), arterial carbon dioxide tension (PaCO2), or arterial blood gas were found between the groups. The relative standard deviation (RSD) of retention times was <1.53%, and the RSDs of peak areas ranged from 2.13% to 8.51%. Base peak chromatogram (BPC) profiles showed no differences between the groups. We evaluated the partial least square-discriminant analysis (PLS-DA) model. In negative ion mode, R2X was over 70%, R2Y was over 93%, and Q2 (cum) was over 80%. Cell apoptosis was not remarkably enhanced by TUNEL and haematoxylin and eosin (HE) staining in the sevoflurane-exposed group compared to the control group (p > 0.05). Glycerophospholipid (GP) and sphingolipid metabolism disturbances might adversely influence neurodevelopment in offspring. The expression of mRNAs (Vcan gene, related to neuronal development, function and repair) of the sevoflurane group was significantly increased in the differential genes by qRT-PCR verification. Conclusions: GP and sphingolipid metabolism homeostasis may be potential therapeutic approaches against inhalational anaesthetic-induced neurodegenerative disorders. Meanwhile, sevoflurane-induced Vcan changes indicated some lipidomic and transcriptomic changes, even if neural cell apoptosis was not significantly changed in the usual clinical dose of sevoflurane exposure.

Targeted temperature management and PbtO2 in traumatic brain injury

IntroductionTargeted Temperature Management (TTM) to normothermia is widely used in traumatic brain injury (TBI). We investigated the effects to of TTM to normothermia patients with TBI (GCS≤12) monitored with multimodality monitoring, to better understand the physiological consequences of this intervention. Research questionIn TBI patients cooled to normothermia and in which brain oxygenation deteriorates, are there changes in physiological parameters which are pertinent to brain oxygenation? Material and method102 TBI patients with continuous recordings of intracranial pressure (ICP) and brain oxygen tension (PbtO2) were studied retrospectively. Non-continuous arterial carbon dioxide (PaCO2) and oxygen (PaO2) tensions, and core body temperature (Tc) were added. PaO2 and PaCO2 were also corrected for Tc. Transitions from elevated Tc to normothermia were identified in 39 patients. The 8 h pre and post the transition to normothermia were compared. Data is given as median [IQR] or mean (SD). ResultsOverall, normothermia reduced ICP (12 [9–18] −11 [8–17] mmHg, p < 0.009) and Tcore (38.3 [0.3]-36.9 [0.4] oC, p < 0.001), but not PbtO2 (23.3 [16.6]-24.4 [17.2–28.7] mmHg, NS). Normothermia was associated with a fall in PbtO2 in 18 patients (24.5 [9.3] −20.8 [7.6] mmHg). Only in those with a fall in PbtO2 with cooling did ICP (15 [10.8–18.5] −12 [7.8–17.3] mmHg, p = 0.002), and temperature corrected PaCO2 (5.3 [0.5]- 4.9 [0.8] kPa, p = 0.001) decrease. Discussion and conclusionA reduction in PbtO2 was only present in the subgroup of patients with a fall in temperature corrected PaCO2 with cooling. This suggests that even modest temperature changes could result in occult hyperventilation in some patients. pH stat correction of ventilation may be an important factor to consider in future TTM protocols.

Hypoxia-altitude simulation test to predict altitude-related adverse health effects in COPD patients.

Amongst numerous travellers to high altitude (HA) are many with the highly prevalent COPD, who are at particular risk for altitude-related adverse health effects (ARAHE). We then investigated the hypoxia-altitude simulation test (HAST) to predict ARAHE in COPD patients travelling to altitude. This prospective diagnostic accuracy study included 75 COPD patients: 40 women, age 58±9 years, forced expiratory volume in 1 s (FEV1) 40-80% pred, oxygen saturation measured by pulse oximetry (S pO2 ) ≥92% and arterial carbon dioxide tension (P aCO2 ) <6 kPa. Patients underwent baseline evaluation and HAST, breathing normobaric hypoxic air (inspiratory oxygen fraction (F IO2 ) of 15%) for 15 min, at low altitude (760 m). Cut-off values for a positive HAST were set according to British Thoracic Society (BTS) guidelines (arterial oxygen tension (P aO2 ) <6.6 kPa and/or S pO2 <85%). The following day, patients travelled to HA (3100 m) for two overnight stays where ARAHE development including acute mountain sickness (AMS), Lake Louise Score ≥4 and/or AMS score ≥0.7, severe hypoxaemia (S pO2 <80% for >30 min or 75% for >15 min) or intercurrent illness was observed. ARAHE occurred in 50 (66%) patients and 23 out of 75 (31%) were positive on HAST according to S pO2 , and 11 out of 64 (17%) according to P aO2 . For S pO2 /P aO2 we report a sensitivity of 46/25%, specificity of 84/95%, positive predictive value of 85/92% and negative predictive value of 44/37%. In COPD patients ascending to HA, ARAHE are common. Despite an acceptable positive predictive value of the HAST to predict ARAHE, its clinical use is limited by its insufficient sensitivity and overall accuracy. Counselling COPD patients before altitude travel remains challenging and best focuses on early recognition and treatment of ARAHE with oxygen and descent.