Differential Effects of Intra-Abdominal Hypertension and ARDS on Respiratory Mechanics in a Porcine Model.

Background and Objectives: Intra-abdominal hypertension (IAH) and acute respiratory distress syndrome (ARDS) are common concerns in intensive care unit patients with acute respiratory failure (ARF). Although both conditions lead to impairment of global respiratory parameters, their underlying mechanisms differ substantially. Therefore, a separate assessment of the different respiratory compartments should reveal differences in respiratory mechanics. Materials and Methods: We prospectively investigated alterations in lung and chest wall mechanics in 18 mechanically ventilated pigs exposed to varying levels of intra-abdominal pressures (IAP) and ARDS. The animals were divided into three groups: group A (IAP 10 mmHg, no ARDS), B (IAP 20 mmHg, no ARDS), and C (IAP 10 mmHg, with ARDS). Following induction of IAP (by inflating an intra-abdominal balloon) and ARDS (by saline lung lavage and injurious ventilation), respiratory mechanics were monitored for six hours. Statistical analysis was performed using one-way ANOVA to compare the alterations within each group. Results: After six hours of ventilation, end-expiratory lung volume (EELV) decreased across all groups, while airway and thoracic pressures increased. Significant differences were noted between group (B) and (C) regarding alterations in transpulmonary pressure (TPP) (2.7 ± 0.6 vs. 11.3 ± 2.1 cmH2O, p < 0.001), elastance of the lung (EL) (8.9 ± 1.9 vs. 29.9 ± 5.9 cmH2O/mL, p = 0.003), and elastance of the chest wall (ECW) (32.8 ± 3.2 vs. 4.4 ± 1.8 cmH2O/mL, p < 0.001). However, global respiratory parameters such as EELV/kg bodyweight (-6.1 ± 1.3 vs. -11.0 ± 2.5 mL/kg), driving pressure (12.5 ± 0.9 vs. 13.2 ± 2.3 cmH2O), and compliance of the respiratory system (-21.7 ± 2.8 vs. -19.5 ± 3.4 mL/cmH2O) did not show significant differences among the groups. Conclusions: Separate measurements of lung and chest wall mechanics in pigs with IAH or ARDS reveals significant differences in TPP, EL, and ECW, whereas global respiratory parameters do not differ significantly. Therefore, assessing the compartments of the respiratory system separately could aid in identifying the underlying cause of ARF.

Extracorporeal life support in COVID-19-related acute respiratory distress syndrome: A EuroELSO international survey.

Extracorporeal life support (ECLS) is a means to support patients with acute respiratory failure. Initially, recommendations to treat severe cases of pandemic coronavirus disease 2019 (COVID-19) with ECLS have been restrained. In the meantime, ECLS has been shown to produce similar outcomes in patients with severe COVID-19 compared to existing data on ARDS mortality. We performed an international email survey to assess how ECLS providers worldwide have previously used ECLS during the treatment of critically ill patients with COVID-19. A questionnaire with 45 questions (covering, e.g., indication, technical aspects, benefit, and reasons for treatment discontinuation), mostly multiple choice, was distributed by email to ECLS centers. The survey was approved by the European branch of the Extracorporeal Life Support Organization (ELSO); 276 ECMO professionals from 98 centers in 30 different countries on four continents reported that they employed ECMO for very severe COVID-19 cases, mostly in veno-venous configuration (87%). The most common reason to establish ECLS was isolated hypoxemic respiratory failure (50%), followed by a combination of hypoxemia and hypercapnia (39%). Only a small fraction of patients required veno-arterial cannulation due to heart failure (3%). Time on ECLS varied between less than 2 and more than 4 weeks. The main reason to discontinue ECLS treatment prior to patient's recovery was lack of clinical improvement (53%), followed by major bleeding, mostly intracranially (13%). Only 4% of respondents reported that triage situations, lack of staff or lack of oxygenators, were responsible for discontinuation of ECLS support. Most ECLS physicians (51%, IQR 30%) agreed that patients with COVID-19-induced ARDS (CARDS) benefitted from ECLS. Overall mortality of COVID-19 patients on ECLS was estimated to be about 55%. ECLS has been utilized successfully during the COVID-19 pandemic to stabilize CARDS patients in hypoxemic or hypercapnic lung failure. Age and multimorbidity limited the use of ECLS. Triage situations were rarely a concern. ECLS providers stated that patients with severe COVID-19 benefitted from ECLS.

Pumpless Extracorporeal Hemadsorption Technique: A New Method for Early Cytokine Elimination?

In recent years, extracorporeal hemadsorption (HA) techniques capable of adsorbing pro- and anti-inflammatory cytokines are increasingly used in various clinical situations. The therapeutic benefit of cytokine elimination likely depends on timing. Although treatment seems to be most effective when started within the first 24 h, therapy is often delayed as it must be combined with another extracorporeal circuit. Thus, using a pumpless extracorporeal HA technique might be a valuable option in order to expedite the commencement of cytokine elimination in critically ill patients.

Evaluation of Different Positive End-Expiratory Pressures Using Supreme™ Airway Laryngeal Mask during Minor Surgical Procedures in Children.

Background and objectives: The laryngeal mask is the method of choice for airway management in children during minor surgical procedures. There is a paucity of data regarding optimal management of mechanical ventilation in these patients. The Supreme™ airway laryngeal mask offers the option to insert a gastric tube to empty the stomach contents of air and/or gastric juice. The aim of this investigation was to evaluate the impact of positive end-expiratory positive pressure (PEEP) levels on ventilation parameters and gastric air insufflation during general anesthesia in children using pressure-controlled ventilation with laryngeal mask. Materials and Methods: An observational trial was carried out in 67 children aged between 1 and 11 years. PEEP levels of 0, 3 and 5 mbar were tested for 5 min in each patient during surgery and compared with ventilation parameters (dynamic compliance (mL/cmH2O), etCO2 (mmHg), peak pressure (mbar), tidal volume (mL), respiratory rate (per minute), FiO2 and gastric air (mL)) were measured at each PEEP. Air was aspirated from the stomach at the start of the sequence of measurements and at the end. Results: Significant differences were observed for the ventilation parameters: dynamic compliance (PEEP 5 vs. PEEP 3: p < 0.0001, PEEP 5 vs. PEEP 0: p < 0.0001, PEEP 3 vs. PEEP 0: p < 0.0001), peak pressure (PEEP 5 vs. PEEP 3: p < 0.0001, PEEP 5 vs. PEEP 0: p < 0.0001, PEEP 3 vs. PEEP 0: p < 0.0001) and tidal volume (PEEP 5 vs. PEEP 3: p = 0.0048, PEEP 5 vs. PEEP 0: p < 0.0001, PEEP 3 vs. PEEP 0: p < 0.0001). All parameters increased significantly with higher PEEP, with the exception of etCO2 (significant decrease) and respiratory rate (no significant difference). We also showed different values for air quantity in the comparisons between the different PEEP levels (PEEP 5: 2.8 ± 3.9 mL, PEEP 3: 1.8 ± 3.0 mL; PEEP 0: 1.6 ± 2.3 mL) with significant differences between PEEP 5 and PEEP 3 (p = 0.0269) and PEEP 5 and PEEP 0 (p = 0.0209). Conclusions: Our data suggest that ventilation with a PEEP of 5 mbar might be more lung protective in children using the Supreme™ airway laryngeal mask, although gastric air insufflation increased with higher PEEP. We recommend the use of a laryngeal mask with the option of inserting a gastric tube to evacuate potential gastric air.

Monitoring of Electrical Activity of the Diaphragm Shows Failure of T-Piece Trial Earlier than Protocol-Based Parameters in Prolonged Weaning in Non-communicative Neurological Patients.

BACKGROUND: The weaning target in tracheotomised patients is not extubation, but spontaneous breathing without the support of a ventilator. Overloading the respiratory pump during such spontaneous breathing trials is unfavorable, prolongs weaning time, and increases morbidity and mortality. The goal of this study was to evaluate the electrical activity of the diaphragm during a t-piece trial in non-communicative neurological patients and the comparison to clinical parameters of exhaustion. METHODS: During multiple t-piece trials, the electrical activity of the diaphragm was obtained before, during and after the end of the trial. T-piece trials were grouped based on the reason for stopping the trial (exhaustion or allotted time period). RESULTS: Twenty-nine tracheotomised patients in prolonged weaning (29 ± 22 days ventilated at the start of the study) were included in a prospective observational study. T-piece trials (n = 152; 5 ± 2 per patient) were grouped based on the reason for stopping the trial (n = 91 because of exhaustion; n = 61 because of the allotted time period). We found that the electrical activity of the diaphragm exhibits an earlier increase than protocol-based clinical parameters in patients who failed the trial due to exhaustion. The electrical activity of the diaphragm shows no relevant difference during the t-piece trial in patients in whom the trial was stopped due to the allotted time period per protocol. CONCLUSIONS: Monitoring the electrical activity of the diaphragm in non-communicative neurological patients in prolonged weaning allows earlier detection of exhaustion than protocol-based parameters.

End-Expiratory Lung Volume in Patients with Acute Respiratory Distress Syndrome: A Time Course Analysis.

PURPOSE: Lung injury can be caused by ventilation and non-physiological lung stress (transpulmonary pressure) and strain [inflated volume over functional residual capacity ratio (FRC)]. FRC is severely decreased in patients with acute respiratory distress syndrome (ARDS). End-expiratory lung volume (EELV) is FRC plus lung volume increased by the applied positive end-expiratory pressure (PEEP). Measurement using the modified nitrogen multiple breath washout technique may help titrating PEEP during ARDS and allow determining dynamic lung strain (tidal volume over EELV) in patients ventilated with PEEP. In this observational study, we measured EELV for up to seven consecutive days in patients with ARDS at different PEEP levels. RESULTS: Thirty sedated patients with ARDS (10 mild, 14 moderate, 6 severe) underwent decremental PEEP testing (20, 15, 10, 5 cm H2O) for up to 7 days after inclusion. At all PEEP levels examined, over a period of 7 days the measured absolute EELVs showed no significant change over time [PEEP 20 cm H2O 2464 ml at day 1 vs. 2144 ml at day 7 (p = 0.78), PEEP 15 cm H2O 2226 ml vs. 1990 ml (p = 0.36), PEEP 10 1835 ml vs. 1858 ml (p = 0.76) and PEEP 5 cm H2O 1487 ml vs. 1612 ml (p = 0.37)]. In relation to the predicted body weight (pbw), no significant change in EELV/kg pbw over time could be detected either at any PEEP level or over time [PEEP 20 36 ml/kg pbw at day 1 vs. 33 ml/kg pbw at day 7 (p = 0.66); PEEP 15 33 vs. 29 ml/kg pbw (p = 0.32); PEEP 10 27 vs. 27 ml/kg pbw (p = 0.70) and PEEP 5 22 vs. 24 ml/kg pbw (p = 0.70)]. Oxygenation significantly improved over time from PaO2/FiO2 of 169 mmHg at day 1 to 199 mmHg at day 7 (p < 0.01). CONCLUSIONS: EELV did not change significantly for up to 7 days in patients with ARDS. By contrast, PaO2/FiO2 improved significantly. Bedside measurement of EELV may be a novel approach to individualise lung-protective ventilation on the basis of calculation of dynamic strain as the ratio of VT to EELV.

Pulmonary Events in ICU patients with hyperoxia: is it possible to relate arterial partial pressure of oxygen to coded diseases? A retrospective analysis.

OBJECTIVE: Oxygen has been used liberally in ICUs for a long time to prevent hypoxia in ICU- patients. Current evidence suggests that paO2 >300 mmHg should be avoided, it remains uncertain whether an "optimal level" exists. We investigated how "mild" hyperoxia influences diseases and in-hospital mortality. DESIGN: This is a retrospective study. SETTING: 112 mechanically ventilated ICU-patients were enrolled. PATIENTS OR PARTICIPANTS: 112 ventilated patients were included and categorized into two groups based on the median paO2 values measured in initial 24 h of mechanical ventilation: normoxia group (paO2 ≤ 100 mmHg, n = 43) and hyperoxia group patients (paO2 > 100 mmHg, n = 69). INTERVENTIONS: No interventions were performed. MAIN VARIABLES OF INTEREST: The primary outcome was the incidence of pulmonary events, the secondary outcomes included the incidence of other new organ dysfunctions and in-hospital mortality. RESULTS: The baseline characteristics, such as age, body mass index, lactate levels, and severity of disease scores, were similar in both groups. There were no statistically significant differences in the incidence of pulmonary events, infections, and new organ dysfunctions between the groups. 27 out of 69 patients (39.1%) in the "mild" hyperoxia group and 12 out of 43 patients (27.9%) in the normoxia group died during their ICU or hospital stay (p = 0.54). The mean APACHE Score was 29.4 (SD 7.9) in the normoxia group and 30.0 (SD 6.7) in the hyperoxia group (p = 0.62). CONCLUSIONS: We found no differences in pulmonary events, other coded diseases, and in-hospital mortality between both groups. It remains still unclear what the "best oxygen regime" is for intensive care patients.

Response of rat lung tissue to short-term hyperoxia: a proteomic approach.

An inspiratory oxygen fraction of 1.0 is often required to avoid hypoxia both in many pre- and in-hospital situations. On the other hand, hyperoxia may lead to deleterious consequences (cell growth inhibition, inflammation, and apoptosis) for numerous tissues including the lung. Whereas clinical effects of hyperoxic lung injury are well known, its impact on the expression of lung proteins has not yet been evaluated sufficiently. The aim of this study was to analyze time-dependent alterations of protein expression in rat lung tissue after short-term normobaric hyperoxia (NH). After approval of the local ethics committee for animal research, N = 36 Wistar rats were randomized into six different groups: three groups with NH with exposure to 100 % oxygen for 3 h and three groups with normobaric normoxia (NN) with exposure to room air (21 % oxygen). After the end of the experiments, lungs were removed immediately (NH0 and NN0), after 3 days (NH3 and NN3) and after 7 days (NH7 and NN7). Lung lysates were analyzed by two-dimensional gel electrophoresis (2D-GE) followed by peptide mass fingerprinting using mass spectrometry. Statistical analysis was performed with Delta 2D (DECODON GmbH, Greifswald, Germany; ANOVA, Bonferroni correction, p < 0.01). Biological functions of differential regulated proteins were studied using functional network analysis (Ingenuity Pathways Analysis, IPA). pO2 was significantly higher in NH-groups compared to NN-groups (581 ± 28 vs. 98 ± 12 mmHg; p < 0.01), all other physiological parameters did not differ. Expression of 14 proteins were significantly altered: two proteins were up-regulated and 12 proteins were down-regulated. Even though NH was comparatively short termed, significant alterations in lung protein expression could be demonstrated up to 7 days after hyperoxia. The identified proteins indicate an association with cell growth inhibition, regulation of apoptosis, and approval of structural cell integrity.

Implementation of a spontaneous awakening/spontaneous breathing trial protocol in a surgical intensive care unit: a before and after study.

BACKGROUND: Prolonged invasive mechanical ventilation (IMV) influences patient outcome in multiple ways. In this regard the early weaning from IMV is a major goal to be achieved in the treatment of ICU patients. Adopting a weaning protocol that incorporates a Spontaneous Awakening Trial (SAT) and a Spontaneous Breathing Trial (SBT) seems to be essential to reach this goal. Most studies investigating the effectiveness of SAT/SBT protocols in ICU patients' outcomes have focused mainly on medical or mixed (medical and surgical), but not on exclusively surgical patient populations. Surgical patients usually experience more complications and often undergo revision surgeries, therefore needing longer sedation periods and adequate analgo-sedation therapy. Moreover, the longer IMV times make the weaning process more arduous. METHODS: Our retrospective data analysis therefore investigates the effectiveness of a SAT/SBT protocol implementation in the surgical ICU of Heidelberg University Hospital, focusing exclusively on surgical patients and their outcome related to the weaning process. The SAT/SBT protocol was adopted in Heidelberg ICU starting from 05/2019. We therefore analyzed the time period before and after the implementation between 03/2018 and 08/2020. Adult patients who required invasive ventilation for at least 48 hours were screened for study entry. Demographic data, clinical data and SOFA Score on admission, were collected to define the baseline characteristics of the two groups. Only patients with full adherence to the protocol were included. The primary outcome was defined as the successful extubation, intended as an extubation not followed by successive re-intubations until discharge from the ICU. We performed an univariate analysis to evaluate the rate of successful extubations between the two groups. RESULTS: In total, 199 patients were included in the analysis, 98 of which before the SAT/SBT protocol implementation (control group) and 101 after the SAT/SBT protocol implementation (intervention group). The successful extubation rate in the intervention group resulted in 82% (83/101 patients) compared to 64% (63/98 patients) in the control group (P<0.004). CONCLUSIONS: We conclude that even for an exclusively surgical patient population, the implementation of a SAT/SBT protocol could result in a higher rate of successful extubation.

High resolution propagation-based lung imaging at clinically relevant X-ray dose levels.

Absorption-based clinical computed tomography (CT) is the current imaging method of choice in the diagnosis of lung diseases. Many pulmonary diseases are affecting microscopic structures of the lung, such as terminal bronchi, alveolar spaces, sublobular blood vessels or the pulmonary interstitial tissue. As spatial resolution in CT is limited by the clinically acceptable applied X-ray dose, a comprehensive diagnosis of conditions such as interstitial lung disease, idiopathic pulmonary fibrosis or the characterization of small pulmonary nodules is limited and may require additional validation by invasive lung biopsies. Propagation-based imaging (PBI) is a phase sensitive X-ray imaging technique capable of reaching high spatial resolutions at relatively low applied radiation dose levels. In this publication, we present technical refinements of PBI for the characterization of different artificial lung pathologies, mimicking clinically relevant patterns in ventilated fresh porcine lungs in a human-scale chest phantom. The combination of a very large propagation distance of 10.7 m and a photon counting detector with [Formula: see text] pixel size enabled high resolution PBI CT with significantly improved dose efficiency, measured by thermoluminescence detectors. Image quality was directly compared with state-of-the-art clinical CT. PBI with increased propagation distance was found to provide improved image quality at the same or even lower X-ray dose levels than clinical CT. By combining PBI with iodine k-edge subtraction imaging we further demonstrate that, the high quality of the calculated iodine concentration maps might be a potential tool for the analysis of lung perfusion in great detail. Our results indicate PBI to be of great value for accurate diagnosis of lung disease in patients as it allows to depict pathological lesions non-invasively at high resolution in 3D. This will especially benefit patients at high risk of complications from invasive lung biopsies such as in the setting of suspected idiopathic pulmonary fibrosis (IPF).

Correlation of clinical outcome and angiographic vasospasm with the dynamic autoregulatory response after aneurysmal subarachnoid hemorrhage.

BACKGROUND: A certain correlation between unfavorable clinical outcome, incidence of vasospasm, and impaired pressure autoregulation in patients following aneurysmal subarachnoid hemorrhage (aSAH) has been suggested. However, determination of vasospasm is inaccurate and the measurement technique of cerebral vasoreactivity seems not to have been sufficiently validated. Therefore, a correlation of clinical outcome and the extent of angiographic VS was performed using an established autoregulation test. MATERIAL AND METHODS: Proximal and global angiographic vasospasm (pVS, gVS) were determined in bilateral M1 segments. Dynamic tests of pressure autoregulation were performed 1 day before and after, and on the day of angiography using Aaslid's thigh leg cuff test. Patient outcome was assessed using the Extended Glasgow Outcome Scale (GOSE). KEY RESULTS: Complete datasets were available for 22 patients. Mean autoregulatory indices (ARI) around the day of angiography were 3.9 ± 2.3. Proximal mean reduction of vessel diameter was -23.3% ± 9.1%. Global vasospasm was not present in 10 hemispheres, mild in 15, moderate in 15, and severe in 4. Hemispheric ARI values and angiographic data showed a significant correlation (pVS -0.382, p = 0.015; gVS -0.477, p = 0.002). The degree of angiographic vasospasm and low ARI values correlated significantly with an unfavorable outcome (0.677, p = 0.001). CONCLUSION: Incidence of angiographic vasospasm and impaired clinical outcome seems to be related to impaired pressure autoregulation following aSAH.

Pumpless Extracorporeal Hemadsorption Technique (pEHAT): A Proof-of-Concept Animal Study.

Background: Extracorporeal hemadsorption eliminates proinflammatory mediators in critically ill patients with hyperinflammation. The use of a pumpless extracorporeal hemadsorption technique allows its early usage prior to organ failure and the need for an additional medical device. In our animal model, we investigated the feasibility of pumpless extracorporeal hemadsorption over a wide range of mean arterial pressures (MAP). Methods: An arteriovenous shunt between the femoral artery and femoral vein was established in eight pigs. The hemadsorption devices were inserted into the shunt circulation; four pigs received CytoSorb® and four Oxiris® hemadsorbers. Extracorporeal blood flow was measured in a range between mean arterial pressures of 45-85 mmHg. Mean arterial pressures were preset using intravenous infusions of noradrenaline, urapidil, or increased sedatives. Results: Extracorporeal blood flows remained well above the minimum flows recommended by the manufacturers throughout all MAP steps for both devices. Linear regression resulted in CytoSorb® blood flow [mL/min] = 4.226 × MAP [mmHg] - 3.496 (R-square 0.8133) and Oxiris® blood flow [mL/min] = 3.267 × MAP [mmHg] + 57.63 (R-square 0.8708), respectively. Conclusion: Arteriovenous pumpless extracorporeal hemadsorption resulted in sufficient blood flows through both the CytoSorb® and Oxiris® devices over a wide range of mean arterial blood pressures and is likely an intriguing therapeutic option in the early phase of septic shock or hyperinflammatory syndromes.

Hydrocortisone therapy for patients with septic shock.

BACKGROUND: Hydrocortisone is widely used in patients with septic shock even though a survival benefit has been reported only in patients who remained hypotensive after fluid and vasopressor resuscitation and whose plasma cortisol levels did not rise appropriately after the administration of corticotropin. METHODS: In this multicenter, randomized, double-blind, placebo-controlled trial, we assigned 251 patients to receive 50 mg of intravenous hydrocortisone and 248 patients to receive placebo every 6 hours for 5 days; the dose was then tapered during a 6-day period. At 28 days, the primary outcome was death among patients who did not have a response to a corticotropin test. RESULTS: Of the 499 patients in the study, 233 (46.7%) did not have a response to corticotropin (125 in the hydrocortisone group and 108 in the placebo group). At 28 days, there was no significant difference in mortality between patients in the two study groups who did not have a response to corticotropin (39.2% in the hydrocortisone group and 36.1% in the placebo group, P=0.69) or between those who had a response to corticotropin (28.8% in the hydrocortisone group and 28.7% in the placebo group, P=1.00). At 28 days, 86 of 251 patients in the hydrocortisone group (34.3%) and 78 of 248 patients in the placebo group (31.5%) had died (P=0.51). In the hydrocortisone group, shock was reversed more quickly than in the placebo group. However, there were more episodes of superinfection, including new sepsis and septic shock. CONCLUSIONS: Hydrocortisone did not improve survival or reversal of shock in patients with septic shock, either overall or in patients who did not have a response to corticotropin, although hydrocortisone hastened reversal of shock in patients in whom shock was reversed. (ClinicalTrials.gov number, NCT00147004.)

Impact of Different Positive End-Expiratory Pressures on Lung Mechanics in the Setting of Moderately Elevated Intra-Abdominal Pressure and Acute Lung Injury in a Porcine Model.

The effects of a moderately elevated intra-abdominal pressure (IAP) on lung mechanics in acute respiratory distress syndrome (ARDS) have still not been fully analyzed. Moreover, the optimal positive end-expiratory pressure (PEEP) in elevated IAP and ARDS is unclear. In this paper, 18 pigs under general anesthesia received a double hit lung injury. After saline lung lavage and 2 h of injurious mechanical ventilation to induce an acute lung injury (ALI), an intra-abdominal balloon was filled until an IAP of 10 mmHg was generated. Animals were randomly assigned to one of three groups (group A = PEEP 5, B = PEEP 10 and C = PEEP 15 cmH2O) and ventilated for 6 h. We measured end-expiratory lung volume (EELV) per kg bodyweight, driving pressure (ΔP), transpulmonary pressure (ΔPL), static lung compliance (Cstat), oxygenation (P/F ratio) and cardiac index (CI). In group A, we found increases in ΔP (22 ± 1 vs. 28 ± 2 cmH2O; p = 0.006) and ΔPL (16 ± 1 vs. 22 ± 2 cmH2O; p = 0.007), with no change in EELV/kg (15 ± 1 vs. 14 ± 1 mL/kg) when comparing hours 0 and 6. In group B, there was no change in ΔP (26 ± 2 vs. 25 ± 2 cmH2O), ΔPL (19 ± 2 vs. 18 ± 2 cmH2O), Cstat (21 ± 3 vs. 21 ± 2 cmH2O/mL) or EELV/kg (12 ± 2 vs. 13 ± 3 mL/kg). ΔP and ΔPL were significantly lower after 6 h when comparing between group C and A (21 ± 1 vs. 28 ± 2 cmH2O; p = 0.020) and (14 ± 1 vs. 22 ± 2 cmH2O; p = 0.013)). The EELV/kg increased over time in group C (13 ± 1 vs. 19 ± 2 mL/kg; p = 0.034). The P/F ratio increased in all groups over time. CI decreased in groups B and C. The global lung injury score did not significantly differ between groups (A: 0.25 ± 0.05, B: 0.21 ± 0.02, C: 0.22 ± 0.03). In this model of ALI, elevated IAP, ΔP and ΔPL increased further over time in the group with a PEEP of 5 cmH2O applied over 6 h. This was not the case in the groups with a PEEP of 10 and 15 cmH2O. Although ΔP and ΔPL were significantly lower after 6 hours in group C compared to group A, we could not show significant differences in histological lung injury score.

Conservative management of COVID-19 associated hypoxaemia.

This correspondence argues that data presented previously cannot justify a novel approach for treating hypoxic patients with severe #COVID19 https://bit.ly/3dLaPlk.

Changes in characteristics and outcomes of critically ill COVID-19 patients in Tyrol (Austria) over 1 year.

BACKGROUND: Widely varying mortality rates of critically ill Coronavirus disease 19 (COVID-19) patients in the world highlighted the need for local surveillance of baseline characteristics, treatment strategies and outcome. We compared two periods of the COVID-19 pandemic to identify important differences in characteristics and therapeutic measures and their influence on the outcome of critically ill COVID-19 patients. METHODS: This multicenter prospective register study included all patients with a SARS-CoV­2 infection confirmed by polymerase chain reaction, who were treated in 1 of the 12 intensive care units (ICU) from 8 hospitals in Tyrol, Austria during 2 defined periods (1 February 2020 until 17 July: first wave and 18 July 2020 until 22 February 2021: second wave) of the COVID-19 pandemic. RESULTS: Overall, 508 patients were analyzed. The majority (n = 401) presented during the second wave, where the median age was significantly higher (64 years, IQR 54-74 years vs. 72 years, IQR 62-78 years, p < 0.001). Invasive mechanical ventilation was less frequent during the second period (50.5% vs 67.3%, p = 0.003), as was the use of vasopressors (50.3% vs. 69.2%, p = 0.001) and renal replacement therapy (12.0% vs. 19.6%, p = 0.061), which resulted in shorter ICU length of stay (10 days, IQR 5-18 days vs. 18 days, IQR 5-31 days, p < 0.001). Nonetheless, ICU mortality did not change (28.9% vs. 21.5%, p = 0.159) and hospital mortality even increased (22.4% vs. 33.4%, p = 0.039) in the second period. Age, frailty and the number of comorbidities were significant predictors of hospital mortality in a multivariate logistic regression analysis of the overall cohort. CONCLUSION: Advanced treatment strategies and learning effects over time resulted in reduced rates of mechanical ventilation and vasopressor use in the second wave associated with shorter ICU length of stay. Despite these improvements, age appears to be a dominant factor for hospital mortality in critically ill COVID-19 patients.

Time-dependent alterations of cerebral proteins following short-term normobaric hyperoxia.

Sufficient oxygenation is indispensable for cognitive performance in mammals. In order to assure adequate oxygenation and to prevent hypoxia in medicine or aviation, different approaches of oxygen delivery are realized. With regard to hyperoxia, it is well known that it increases the risk of tissue toxicity and inflammation by generating radical oxygen species. However, this impact of hyperoxia on the expression of specific brain proteins has not been evaluated in detail yet. The present study analyzes time-dependent changes in protein expression in rat brain after a short-term exposure to normobaric hyperoxia. Thirty-six Wistar rats were randomly assigned to six different groups, three normobaric hyperoxia (NH) groups or three normobaric normoxia (NN) groups, each consisting of n = 6 animals. NH animals were exposed to 100% oxygen, NN rats to 21% oxygen, each group for 3 h. One group of NH and one group of NN were killed immediately after the 3 h, one group each after 3 days and one group each after 7 days. Rat brains were removed for analysis and whole brain detergent protein lysates were separated via two-dimensional gel electrophoresis followed by subsequent identification of protein expression alterations by peptide mass fingerprinting using mass spectrometry. Also, a functional network mapping and molecular pathway analysis were carried out. Statistical analysis was performed using analysis of variance (ANOVA) with Bonferroni correction using P < 0.01. Physiological parameters of the animals did not differ significantly between the two groups except for partial oxygen pressure (580 vs. 89 mmHg; P < 0.05). The expression of nine proteins was found to be significantly altered (five up-regulated: GOT1, CCT2, TCP1, G6PD, and ALB; four down-regulated: PEBP1, PRDX2, ENO1, and MDH1). IPA generated a network with eight focus proteins associated with pathways in "cell death, cancer, and signalling". Although hyperoxia was normobaric and induced for only 3 h, significant changes in brain protein expression were detectable immediately after the 3 h, after 3 days, as well as after 7 days. This may indicate effects on brain protein expression take place in the rat brain following a relatively short period of hyperoxia.

Prospective Observational Study to Evaluate the Effect of Different Levels of Positive End-Expiratory Pressure on Lung Mechanics in Patients with and without Acute Respiratory Distress Syndrome.

BACKGROUND: The optimal level of positive end-expiratory pressure is still under debate. There are scare data examining the association of PEEP with transpulmonary pressure (TPP), end-expiratory lung volume (EELV) and intraabdominal pressure in ventilated patients with and without ARDS. METHODS: We analyzed lung mechanics in 3 patient groups: group A, patients with ARDS; group B, obese patients (body mass index (BMI) > 30 kg/m2) and group C, a control group. Three levels of PEEP (5, 10, 15 cm H2O) were used to investigate the consequences for lung mechanics. RESULTS: Fifty patients were included, 22 in group A, 18 in group B (BMI 38 ± 2 kg/m2) and 10 in group C. At baseline, oxygenation showed no differences between the groups. Driving pressure (ΔP) and transpulmonary pressure (ΔPL) was higher in group B than in groups A and C at a PEEP of 5 cm H2O (ΔP A: 15 ± 1, B: 18 ± 1, C: 14 ± 1 cm H2O; ΔPL A: 10 ± 1, B: 13 ± 1, C: 9 ± 0 cm H2O). Peak inspiratory pressure (Pinsp) rose in all groups as PEEP increased, but the resulting driving pressure and transpulmonary pressure were reduced, whereas EELV increased. CONCLUSION: Measuring EELV or TPP allows a personalized approach to lung-protective ventilation.