[Measures and Recommendations for Ensuring Adequate Inpatient Care Capacities for Pandemic Management within a Region: Results of a Hybrid Delphi Method]. / Maßnahmen und Empfehlungen für die Sicherstellung adäquater stationärer Versorgungskapazitäten für das Pandemiemanagement innerhalb einer Region ­ Ergebnisse eines hybriden Delphi-Verfahrens.

INTRODUCTION: Since the beginning of the pandemic in spring 2020, inpatient healthcare has been under enormous burden, which is reflected especially in overworked staff, imprecise bed planning and/or data transfer. According to the recommendation of the Science Council, university clinics should play a controlling role in regional healthcare and act in conjunction with surrounding hospitals and practices. METHODS: In September 2021, 31 representatives from 18 university hospitals were invited to a hybrid Delphi study with a total of 4 survey rounds to discuss criteria for effective inpatient care in a pandemic situation, which were extracted from previous expert interviews. Criteria that were classified as very important/relevant by≥75% of the participants in the first round of the survey (consensus definition) were then further summarized in 4 different small groups. In a third Delphi round, all participants came together again to discuss the results of the small group discussions. Subsequently, these were prioritized as Optional ("can"), Desirable ("should") or Necessary ("must") recommendations. RESULTS: Of the invited clinical experts, 21 (67.7%) participated in at least one Delphi round. In an online survey (1st Delphi round), 233 criteria were agreed upon and reduced to 84 criteria for future pandemic management in four thematic small group discussions (2nd Delphi round) and divided into the small groups as follows: "Crisis Management and Crisis Plans" (n=20), "Human Resources Management and Internal Communication" (n=16), "Regional Integration and External Communication" (n=24) and "Capacity Management and Case & Care" (n=24). In the following group discussion (3rd Delphi round), the criteria were further modified and agreed upon by the experts, so that in the end result, there were 23 essential requirements and recommendations for effective inpatient care in a pandemic situation. CONCLUSION: The results draw attention to key demands of clinical representatives, for example, comprehensive digitization, standardization of processes and better (supra) regional networking in order to be able to guarantee needs-based care even under pandemic conditions. The present consensus recommendations can serve as guidelines for future pandemic management in the inpatient care sector.

[Mental burden, resilience and tendency towards absenteeism among healthcare personnel in Germany during the first wave of the COVID-19 pandemic in spring 2020 : An ad hoc survey]. / Psychische Belastung, Resilienz und Absentismusneigung bei Gesundheitspersonal in Deutschland während der ersten COVID-19-Pandemiewelle im Frühjahr 2020 : Eine Ad-hoc-Befragung.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic is associated with extensive changes in the public and private life in Germany. Healthcare personnel are particularly exposed to additional stressors. OBJECTIVE: To identify the mental burden, resilience, tendency towards absenteeism and associated factors during the COVID-19 pandemic in an anonymous cross-sectional survey. METHODS: Data on sociodemographics, occupational situation, contact to COVID-19 patients, mental burden, stressors, resilience, risk and protective factors were assessed among a convenience sample of healthcare personnel in spring 2020 (5 April 2020-7 May 2020). A comparison with the general population in Germany before and during the COVID-19 pandemic was conducted. RESULTS: After the evaluation of 650 completed questionnaires, an increased mental burden was found compared to the German general population before the pandemic, while the mental burden was reduced compared to the general population during the pandemic. The self-reported resilience was slightly higher compared to the general population before and during the pandemic. The COVID-19-related stressors and worries were the most important risk factors, self-efficacy and optimism the most important protective factors. The mental burden was moderately correlated with the intention to change the profession and the tendency towards absenteeism. CONCLUSION: Mental burden in healthcare personnel during the COVID-19 pandemic is associated with a higher tendency towards taking sick leave. In order to support healthcare personnel interventions that foster resources, such as self-efficacy and optimism should be offered to particularly vulnerable groups .

[Perioperative Atrial Fibrillation]. / Perioperatives Vorhofflimmern.

New atrial fibrillation is a risk factor for increased morbidity and mortality in the perioperative phase. The prevalence and incidence of atrial fibrillation depend on age, previous illnesses and the intercurrent diagnoses in the perioperative phase. Pathomechanisms for both permanent and acute forms of atrial fibrillation relate to electrophysiological, histopathological and other pathophysiological abnormalities. In the perioperative phase, decompensated heart failure, systemic inflammation, sepsis and cardiac surgery are risk factors for conversion to atrial fibrillation and/or rapid transition. The consequences of newly occurring and/or rapidly transferred atrial fibrillation are cardiac instability due to a drop in blood pressure or cardiac output volume or coronary underperfusion due to tachycardia and the risk of thromboembolism. Associated with this is a significantly increased long-term mortality risk in the elderly if atrial fibrillation occurs again in the perioperative phase. The diagnosis of atrial fibrillation is made in the monitor or 12-channel electrocardiogram. Echocardiography and the adenosine test can be included in the differential diagnosis in cases of doubt. Important current guidelines for the treatment of atrial fibrillation are the ESC (atrial fibrillation) and the ERC (Advanced Cardiac Life Support) guidelines. The conversion into the sinus rhythm can be done electrically or medicinally. It is indicated in cases of acute instability or symptomatic atrial fibrillation despite frequency control after cardiac thrombi have been excluded by echocardiography. A step-by-step concept for thromboembolism prophylaxis from initial parenteral and secondary oral therapy must take place up to four weeks after conversion to sinus rhythm or permanently in the case of permanent atrial fibrillation. The individual indication for thromboembolism prophylaxis results from the CHA2-DS2-VASc score.

Effect of Regional Citrate Anticoagulation vs Systemic Heparin Anticoagulation During Continuous Kidney Replacement Therapy on Dialysis Filter Life Span and Mortality Among Critically Ill Patients With Acute Kidney Injury: A Randomized Clinical Trial.

Importance: Although current guidelines suggest the use of regional citrate anticoagulation (which involves the addition of a citrate solution to the blood before the filter of the extracorporeal dialysis circuit) as first-line treatment for continuous kidney replacement therapy in critically ill patients, the evidence for this recommendation is based on few clinical trials and meta-analyses. Objective: To determine the effect of regional citrate anticoagulation, compared with systemic heparin anticoagulation, on filter life span and mortality. Design, Setting, and Participants: A parallel-group, randomized multicenter clinical trial in 26 centers across Germany was conducted between March 2016 and December 2018 (final date of follow-up, January 21, 2020). The trial was terminated early after 596 critically ill patients with severe acute kidney injury or clinical indications for initiation of kidney replacement therapy had been enrolled. Interventions: Patients were randomized to receive either regional citrate anticoagulation (n = 300), which consisted of a target ionized calcium level of 1.0 to 1.40 mg/dL, or systemic heparin anticoagulation (n = 296), which consisted of a target activated partial thromboplastin time of 45 to 60 seconds, for continuous kidney replacement therapy. Main Outcomes and Measures: Coprimary outcomes were filter life span and 90-day mortality. Secondary end points included bleeding complications and new infections. Results: Among 638 patients randomized, 596 (93.4%) (mean age, 67.5 years; 183 [30.7%] women) completed the trial. In the regional citrate group vs systemic heparin group, median filter life span was 47 hours (interquartile range [IQR], 19-70 hours) vs 26 hours (IQR, 12-51 hours) (difference, 15 hours [95% CI, 11 to 20 hours]; P < .001). Ninety-day all-cause mortality occurred in 150 of 300 patients vs 156 of 296 patients (Kaplan-Meier estimator percentages, 51.2% vs 53.6%; unadjusted difference, -2.4% [95% CI, -10.5% to 5.8%]; unadjusted hazard ratio, 0.91 [95% CI, 0.72 to 1.13]; unadjusted P = .38; adjusted difference, -6.1% [95% CI, -12.6% to 0.4%]; primary adjusted hazard ratio, 0.79 [95% CI, 0.63 to 1.004]; primary adjusted P = .054). Of 38 prespecified secondary end points, 34 showed no significant difference. Compared with the systemic heparin group, the regional citrate group had significantly fewer bleeding complications (15/300 [5.1%] vs 49/296 [16.9%]; difference, -11.8% [95% CI, -16.8% to -6.8%]; P < .001) and significantly more new infections (204/300 [68.0%] vs 164/296 [55.4%]; difference, 12.6% [95% CI, 4.9% to 20.3%]; P = .002). Conclusions and Relevance: Among critically ill patients with acute kidney injury receiving continuous kidney replacement therapy, anticoagulation with regional citrate, compared with systemic heparin anticoagulation, resulted in significantly longer filter life span. The trial was terminated early and was therefore underpowered to reach conclusions about the effect of anticoagulation strategy on mortality. Trial Registration: ClinicalTrials.gov Identifier: NCT02669589.

Chest electrical impedance tomography examination, data analysis, terminology, clinical use and recommendations: consensus statement of the TRanslational EIT developmeNt stuDy group.

Electrical impedance tomography (EIT) has undergone 30 years of development. Functional chest examinations with this technology are considered clinically relevant, especially for monitoring regional lung ventilation in mechanically ventilated patients and for regional pulmonary function testing in patients with chronic lung diseases. As EIT becomes an established medical technology, it requires consensus examination, nomenclature, data analysis and interpretation schemes. Such consensus is needed to compare, understand and reproduce study findings from and among different research groups, to enable large clinical trials and, ultimately, routine clinical use. Recommendations of how EIT findings can be applied to generate diagnoses and impact clinical decision-making and therapy planning are required. This consensus paper was prepared by an international working group, collaborating on the clinical promotion of EIT called TRanslational EIT developmeNt stuDy group. It addresses the stated needs by providing (1) a new classification of core processes involved in chest EIT examinations and data analysis, (2) focus on clinical applications with structured reviews and outlooks (separately for adult and neonatal/paediatric patients), (3) a structured framework to categorise and understand the relationships among analysis approaches and their clinical roles, (4) consensus, unified terminology with clinical user-friendly definitions and explanations, (5) a review of all major work in thoracic EIT and (6) recommendations for future development (193 pages of online supplements systematically linked with the chief sections of the main document). We expect this information to be useful for clinicians and researchers working with EIT, as well as for industry producers of this technology.

Low tidal volume pressure support versus controlled ventilation in early experimental sepsis in pigs.

BACKGROUND: In moderate acute respiratory distress syndrome (ARDS) several studies support the usage of assisted spontaneous breathing modes. Only limited data, however, focus on the application in systemic sepsis and developing lung injury. The present study examines the effects of immediate initiation of pressure support ventilation (PSV) in a model of sepsis-induced ARDS. METHODS: 18 anesthetized pigs received a two-staged continuous lipopolysaccharide infusion to induce lung injury. The animals were randomly assigned to PSV or volume controlled (VCV) lung protective ventilation (tidal volume each 6 ml kg-1, n = 2x9) over six hours. Gas exchange parameters, hemodynamics, systemic inflammation, and ventilation distribution by multiple inert gas elimination and electrical impedance tomography were assessed. The post mortem analysis included histopathological scoring, wet to dry ratio, and alveolar protein content. RESULTS: Within six hours both groups developed a mild to moderate ARDS with comparable systemic inflammatory response and without signs of improving gas exchange parameters during PSV. The PSV group showed signs of more homogenous ventilation distribution by electrical impedance tomography, but only slightly less hyperinflated lung compartments by multiple inert gas elimination. Post mortem and histopathological assessment yielded no significant intergroup differences. CONCLUSIONS: In a porcine model of sepsis-induced mild ARDS immediate PSV was not superior to VCV. This contrasts with several experimental studies from non-septic mild to moderate ARDS. The present study therefore assumes that not only severity, but also etiology of lung injury considerably influences the response to early initiation of PSV.

Hints for cyclical recruitment of atelectasis during ongoing mechanical ventilation in lavage and oleic acid lung injury detected by SpO2 oscillations and electrical impedance tomography.

PURPOSE OF THE STUDY: Detection of cyclical recruitment of atelectasis after induction of lavage (LAV) or oleic acid injury (OAI) in mechanically ventilated pigs. Primary hypothesis is that oxygen oscillations within the respiratory cycle can be detected by SpO2 recordings (direct hint). SpO2 oscillations reflect shunt oscillations that can only be explained by cyclical recruitment of atelectasis. Secondary hypothesis is that electrical impedance tomography (EIT) depicts specific regional changes of lung aeration and of pulmonary mechanical properties (indirect hint). MATERIALS AND METHODS: Three groups (each n = 7) of mechanically ventilated pigs were investigated applying above mentioned methods before and repeatedly after induction of lung injury: (1) sham treated animals (SHAM), (2) LAV, and (3) OAI. RESULTS: Early oxygen oscillations occurred in the LAV group (mean calculated amplitude: 73.8 mmHg reflecting shunt oscillation of 11.2% in mean). In the OAI group oxygen oscillations occurred hours after induction of lung injury (mean calculated amplitude: 57.1 mmHg reflecting shunt oscillations of 8.4% in mean). The SHAM group had no relevant oxygen oscillations (<30 mmHg, shunt oscillations < 1.5%). Synchronously to oxygen oscillations, EIT depicted (1) a decrease of ventilation in dorsal areas, (2) an increase in ventral areas, (3) a decrease of especially dependent expiratory impedance, 3) an increase in late inspiratory flow especially in the dependant areas, (4) an increase in the speed of peak expiratory flow (PEF), and (5) a decrease of dorsal late expiratory flow. CONCLUSIONS: SpO2 and EIT recordings detect events that are interpreted as cyclical recruitment of atelectasis.

Determination of respiratory gas flow by electrical impedance tomography in an animal model of mechanical ventilation.

BACKGROUND: A recent method determines regional gas flow of the lung by electrical impedance tomography (EIT). The aim of this study is to show the applicability of this method in a porcine model of mechanical ventilation in healthy and diseased lungs. Our primary hypothesis is that global gas flow measured by EIT can be correlated with spirometry. Our secondary hypothesis is that regional analysis of respiratory gas flow delivers physiologically meaningful results. METHODS: In two sets of experiments n = 7 healthy pigs and n = 6 pigs before and after induction of lavage lung injury were investigated. EIT of the lung and spirometry were registered synchronously during ongoing mechanical ventilation. In-vivo aeration of the lung was analysed in four regions-of-interest (ROI) by EIT: 1) global, 2) ventral (non-dependent), 3) middle and 4) dorsal (dependent) ROI. Respiratory gas flow was calculated by the first derivative of the regional aeration curve. Four phases of the respiratory cycle were discriminated. They delivered peak and late inspiratory and expiratory gas flow (PIF, LIF, PEF, LEF) characterizing early or late inspiration or expiration. RESULTS: Linear regression analysis of EIT and spirometry in healthy pigs revealed a very good correlation measuring peak flow and a good correlation detecting late flow. PIFEIT = 0.702 · PIFspiro + 117.4, r(2) = 0.809; PEFEIT = 0.690 · PEFspiro-124.2, r(2) = 0.760; LIFEIT = 0.909 · LIFspiro + 27.32, r(2) = 0.572 and LEFEIT = 0.858 · LEFspiro-10.94, r(2) = 0.647. EIT derived absolute gas flow was generally smaller than data from spirometry. Regional gas flow was distributed heterogeneously during different phases of the respiratory cycle. But, the regional distribution of gas flow stayed stable during different ventilator settings. Moderate lung injury changed the regional pattern of gas flow. CONCLUSIONS: We conclude that the presented method is able to determine global respiratory gas flow of the lung in different phases of the respiratory cycle. Additionally, it delivers meaningful insight into regional pulmonary characteristics, i.e. the regional ability of the lung to take up and to release air.

Influence of fluid and volume state on PaO2 oscillations in mechanically ventilated pigs.

Varying pulmonary shunt fractions during the respiratory cycle cause oxygen oscillations during mechanical ventilation. In artificially damaged lungs, cyclical recruitment of atelectasis is responsible for varying shunt according to published evidence. We introduce a complimentary hypothesis that cyclically varying shunt in healthy lungs is caused by cyclical redistribution of pulmonary perfusion. Administration of crystalloid or colloid infusions would decrease oxygen oscillations if our hypothesis was right. Therefore, n=14 mechanically ventilated healthy pigs were investigated in 2 groups: crystalloid (fluid) versus no-fluid administration. Additional volume interventions (colloid infusion, blood withdrawal) were carried out in each pig. Intra-aortal PaO2 oscillations were recorded using fluorescence quenching technique. Phase shift of oxygen oscillations during altered inspiratory to expiratory (I:E) ventilation ratio and electrical impedance tomography (EIT) served as control methods to exclude that recruitment of atelectasis is responsible for oxygen oscillations. In hypovolemia relevant oxygen oscillations could be recorded. Fluid and volume state changed PaO2 oscillations according to our hypothesis. Fluid administration led to a mean decline of 105.3 mmHg of the PaO2 oscillations amplitude (P<0.001). The difference of the amplitudes between colloid administration and blood withdrawal was 62.4 mmHg in pigs not having received fluids (P=0.0059). Fluid and volume state also changed the oscillation phase during altered I:E ratio. EIT excluded changes of regional ventilation (i.e., recruitment of atelectasis) to be responsible for these oscillations. In healthy pigs, cyclical redistribution of pulmonary perfusion can explain the size of respiratory-dependent PaO2 oscillations.

Cerebrovascular autoregulation in critically ill patients during continuous hemodialysis.

PURPOSE: In chronic renal failure, intermittent hemodialysis decreases cerebral blood flow velocity (CBFV); however, in critically ill patients with acute renal failure, the effect of continuous venovenous hemodialysis (CVVHD) on CBFV and cerebrovascular autoregulation (AR) is unknown. Therefore, a study was undertaken to investigate the potential effect of CVVHD on CBFV and AR in patients with acute renal failure. METHODS: This cohort study investigated 20 patients with acute renal failure who required CVVHD. In these patients, the CBFV and index of AR (Mx) were measured using transcranial Doppler before and during CVVHD. RESULTS: The median Mx values at baseline were 0.33 [interquartile range (IQR): 0.02-0.55], and during CVVHD, they were 0.20 [0.07-0.40]. The differences in Mx (CVVHD--baseline) was (median [IQR]) -0.015 [-0.19-0.05], 95% confidence interval (CI) -0.16 to 0.05. The Mx was > 0.3 in 11/20 patients at baseline measurement. Six of these patients recovered to Mx < 0.3 during CVVHD. The CBFV was (median [IQR]) 47 [36-59] cm · sec(-1) at baseline and 49 [36-66] cm · sec(-1) during CVVHD. The difference of CBFV was 0.0 [-4 - 2.7], 95% CI -2.5 to 4.2. CONCLUSION: Compared with patients with intermittent hemodialysis, CVVHD did not influence CBFV and AR in critically ill patients with acute renal failure, possibly due to lower extracorporeal blood flow, slower change of plasma osmolarity, and a lower fluid extraction rate. In a subgroup of patients with sepsis, the AR was impaired at baseline in more than half of the patients, and this was reversed during CVVHD. The trial was registered at ClinicalTrials.gov ID: NCT01376531.

Evidence for the utility of cfDNA plasma concentrations to predict disease severity in COVID-19: a retrospective pilot study.

Background: COVID-19 is a worldwide pandemic caused by the highly infective SARS-CoV-2. There is a need for biomarkers not only for overall prognosis but also for predicting the response to treatments and thus for improvements in the clinical management of patients with COVID-19. Circulating cell-free DNA (cfDNA) has emerged as a promising biomarker in the assessment of various pathological conditions. The aim of this retrospective and observational pilot study was to investigate the range of cfDNA plasma concentrations in hospitalized COVID-19 patients during the first wave of SARS-CoV-2 infection, to relate them to established inflammatory parameters as a correlative biomarker for disease severity, and to compare them with plasma levels in a healthy control group. Methods: Lithium-Heparin plasma samples were obtained from COVID-19 patients (n = 21) during hospitalization in the University Medical Centre of Mainz, Germany between March and June 2020, and the cfDNA concentrations were determined by quantitative PCR yielding amplicons of long interspersed nuclear elements (LINE-1). The cfDNA levels were compared with those of an uninfected control group (n = 19). Results: Plasma cfDNA levels in COVID-19 patients ranged from 247.5 to 6,346.25 ng/ml and the mean concentration was 1,831 ± 1,388 ng/ml (± standard deviation), which was significantly different from the levels of the uninfected control group (p < 0.001). Regarding clinical complications, the highest correlation was found between cfDNA levels and the myositis (p = 0.049). In addition, cfDNA levels correlated with the "WHO clinical progression scale". D-Dimer and C-reactive protein (CRP) were the clinical laboratory parameters with the highest correlations with cfDNA levels. Conclusion: The results of this observational pilot study show a wide range in cfDNA plasma concentrations in patients with COVID-19 during the first wave of infection and confirm that cfDNA plasma concentrations serve as a predictive biomarker of disease severity in COVID-19.

Elevated lactate levels and impaired lactate clearance during extracorporeal life support (ECLS) are associated with poor outcome in cardiac surgery patients.

The use of extracorporeal life support (ECLS) as part of cardio-circulatory support has increased rapidly in recent years. Severe hyperlactatemia is not uncommon in this group of patients. Lactate peak concentrations and lactate clearance have already been identified as independent marker for mortality in critical ill patients without mechanical device support. The aim of this study was to determine a supposed correlation between the variables lactate peak concentration and clearance in the blood and mortality in the ECLS context. Therefore, a total of 51 cardiac surgery ICU patients with ECLS therapy were included in this retrospective, clinical observational study (survivors n = 23; non-survivors n = 28). Lactate measurement was performed before, during and after ECLS therapy. Further, common ICU scores (SAPSII, SOFA, TISS28), the rates of transfusion and the different vasopressor therapies will be compared. Significant elevated peak lactate levels and poor lactate clearance were associated with higher mortality during ECLS therapy (p < 0.001). Deceased patients had higher SAPSII scores (p < 0.001), received more transfusions (p < 0.001) and presented with higher rates of epinephrine (p < 0.001). In conclusion, hyperlactatemia during ECLS therapy is a time sensitive emergency. Lactate cannot be cleared in all patients. Reversible causes should be explored and treated. In cases where the cause is irreversible, the prognosis of elevated lactate concentrations and reduced clearance is very poor.

Sonographic assessment of low muscle quantity identifies mortality risk during COVID-19: a prospective single-centre study.

BACKGROUND: Assessment of muscle quantity by sonographic muscle indices could help identify patients at risk for fatal outcome during coronavirus disease-2019 (COVID-19). The aim of this study was to explore sonographic muscle indices as predictors of COVID-19 outcome and to test the feasibility of sonographic muscle measurement in an isolation context. METHODS: Muscle indices, derived from the psoas muscle or thigh muscles, were quantified by sonography in a cohort of patients without COVID-19 to obtain reference values for low muscle quantity. Gender-specific median of different muscle indices were defined as threshold value for low muscle quantity. The prognostic relevance of low muscle quantity, was prospectively explored in two cohorts of hospitalized COVID-19 patients. Optimal muscle index cutoff values predictive for 30 day mortality during COVID-19 were determined by receiver operating characteristic-area under the curve and Youden index calculation. Muscle quantity and known prognostic factors of COVID-19 were analysed by multivariable log-regression. RESULTS: Compared with other muscle indices, the psoas muscle area index (PMAI) showed the most favourable characteristics to predict outcome of COVID-19 disease. Sonographic morphometry of patients without COVID-19 (n = 136) revealed a gender-specific median for PMAI (male: 291.1 mm2 /m2 , female 260.6 mm2 /m2 ) as threshold value of low muscle quantity. Subsequently, COVID-19 patients (Cohort I: n = 58; Cohort II: n = 55) were prospectively assessed by bedside sonography. The studied COVID-19 patients developed a critical course of disease in 22.4% (Cohort I: n = 13/58) and 34.5% (Cohort II: n = 20/55). Mortality rate reached 12.1% (Cohort I: n = 7/58) and 20.0% (Cohort I: n = 11/55) within 30 days of follow up. COVID-19 patients with a PMAI below the gender-specific median showed a higher 30 day mortality in both COVID-19 cohorts (log rank, P < 0.05). The optimal PMAI cutoff value (206 mm2 /m2 ) predicted 30 day mortality of hospitalized COVID-19 patients with a sensitivity of 72% and specificity of 78.5% (receiver operating characteristic-area under the curve: 0.793, 95% confidence interval 0.671-0.914, P = 0.008). Multivariable log-regression analysis of PMAI, age, gender, BMI and comorbidities confirmed an independent association of low PMAI with 30 day mortality of COVID-19 patients (P = 0.018). CONCLUSIONS: Sonographic morphometry provides reliable muscle quantification under hygienic precautions and allows risk stratification of patients with COVID-19.

Pathogenic lipid-binding antiphospholipid antibodies are associated with severity of COVID-19.

BACKGROUND: Coronavirus disease 19 (COVID-19)-associated coagulopathy is a hallmark of disease severity and poor prognosis. The key manifestations of this prothrombotic syndrome-microvascular thrombosis, stroke, and venous and pulmonary clots-are also observed in severe and catastrophic antiphospholipid syndrome. Antiphospholipid antibodies (aPL) are detectable in COVID-19 patients, but their association with the clinical course of COVID-19 remains unproven. OBJECTIVES: To analyze the presence and relevance of lipid-binding aPL in hospitalized COVID-19 patients. METHODS: Two cohorts of 53 and 121 patients from a single center hospitalized for PCR-proven severe acute respiratory syndrome-coronavirus 2 infection were analyzed for the presence of aPL and clinical severity of COVID-19. RESULTS: We here demonstrate that lipid-binding aPL are common in COVID-19. COVID-19 patients with lipid-binding aPL have higher median concentrations of C-reactive protein and D-dimer, and are more likely to have a critical clinical course and fatal outcome. Lipid-binding aPL isolated from COVID-19 patients target the recently described cell surface complex of lysobisphosphatidic acid (LBPA) with the protein C receptor (EPCR) to induce prothrombotic and inflammatory responses in monocytes and endothelial cells. We show that B1a cells producing lipid-reactive aPL of the IgG isotype circulate in the blood of COVID-19 patients. In vivo, COVID-19 aPL accelerate thrombus formation in an experimental mouse model dependent on the recently delineated signaling pathway involving EPCR-LBPA. CONCLUSIONS: COVID-19 patients rapidly expand B1a cells secreting pathogenic lipid-binding aPL with broad thrombotic and inflammatory effects. The association with markers of inflammation and coagulation, clinical severity, and mortality suggests a causal role of aPL in COVID-19-associated coagulopathy.

Observation of ventilation-induced Spo(2) oscillations in pigs: first step to noninvasive detection of cyclic recruitment of atelectasis?

High arterial partial oxygen pressure (Pao(2)) oscillations within the respiratory cycle were described recently in experimental acute lung injury. This phenomenon has been related to cyclic recruitment of atelectasis and varying pulmonary shunt fractions. Noninvasive detection of Spo(2) (oxygen saturation measured by pulse oximetry) as an indicator of cyclic collapse of atelectasis, instead of recording Pao(2) oscillations, could be of clinical interest in critical care. Spo(2) oscillations were recorded continuously in three different cases of lung damage to demonstrate the technical feasibility of this approach. To deduce Pao(2) from Spo(2), a mathematical model of the hemoglobin dissociation curve including left and right shifts was derived from the literature and adapted to the dynamic changes of oxygenation. Calculated Pao(2) amplitudes (derived from Spo(2) measurements) were compared to simultaneously measured fast changes of Pao(2), using a current standard method (fluorescence quenching of ruthenium). Peripheral hemoglobin saturation was capable to capture changes of Spo(2) within each respiratory cycle. For the first time, Spo(2) oscillations due to cyclic recruitment of atelectasis within a respiratory cycle were determined by photoplethysmography, a technology that can be readily applied noninvasively in clinical routine. A mathematic model to calculate the respective Pao(2) changes was developed and its applicability tested.

Principles of electrical impedance tomography and its clinical application.

OBJECTIVE: This review outlines the basic principle, in addition to validated and upcoming clinical use of electrical impedance tomography (EIT). EIT generates functional tomograms of the thorax for detection of changes in regional lung aeration. These images allow an intraindividual comparison of changes in regional lung function. Specifically, EIT aims to optimize ventilation therapy in patients with acute lung failure. DATA SOURCES: PubMed: National Library of Medicine and the National Institutes of Health. STUDY SELECTION: Studies with the key words "electrical impedance tomography" since 1983. DATA EXTRACTION: Qualitative and quantitative results of the studies. DATA SYNTHESIS: We summarize basic principles of the technique and subsequent analyzing methods, and give an overview of clinical and scientific questions that can be addressed by EIT. CONCLUSION: Potential applications in the future as well as limitations of EIT technology are described. In summary, EIT is a promising functional tomography technology on the verge of its clinical application.

A comparison of micropore membrane inlet mass spectrometry-derived pulmonary shunt measurement with Riley shunt in a porcine model.

BACKGROUND: The multiple inert gas elimination technique was developed to measure shunt and the ratio of alveolar ventilation to simultaneous alveolar capillary blood flow in any part of the lung (V(A)'/Q') distributions. Micropore membrane inlet mass spectrometry (MMIMS), instead of gas chromatography, has been introduced for inert gas measurement and shunt determination in a rabbit lung model. However, agreement with a frequently used and accepted method for quantifying deficits in arterial oxygenation has not been established. We compared MMIMS-derived shunt (M-S) as a fraction of total cardiac output (CO) with Riley shunt (R-S) derived from the R-S formula in a porcine lung injury model. METHODS: To allow a broad variance of atelectasis and therefore shunt fraction, 8 sham animals did not receive lavage, and 8 animals were treated by lung lavages with 30 mL/kg warmed lactated Ringer's solution as follows: 2 animals were lavaged once, 5 animals twice, and 1 animal 3 times. Variables were recorded at baseline and twice after induction of lung injury (T1 and T2). Retention data of sulfur hexafluoride, krypton, desflurane, enflurane, diethyl ether, and acetone were analyzed by MMIMS, and M-S was derived using a known algorithm for the multiple inert gas elimination technique. Standard formulas were used for the calculation of R-S. RESULTS: Forty-four pairs of M-S and R-S were recorded. M-S ranged from 0.1% to 35.4% and R-S from 3.7% to 62.1%. M-S showed a correlation with R-S described by linear regression: M-S = -4.26 + 0.59 x R-S (r(2) = 0.83). M-S was on average lower than R-S (mean = -15.0% CO, sd = 6.5% CO, and median = -15.1), with lower and upper limits of agreement of -28.0% and -2.0%, respectively. The lower and upper limits of the 95% confidence intervals were -17.0 and -13.1 (P < 0.001, Student's t-test). CONCLUSIONS: Shunt derived from MMIMS inert gas retention data correlated well with R-S during breathing of oxygen. Shunt as derived by MMIMS was generally less than R-S.

Effect of lower body negative pressure and gravity on regional lung ventilation determined by EIT.

The aim of our study was to check the effect of varying blood volume in the chest and gravity on the distribution of ventilation and aeration in the lungs. The change in intrathoracic blood volume was elicited by application of lower body negative pressure (LBNP) of -50 cmH2O. The variation of gravity in terms of hypogravity (approximately 0g) and hypergravity (approximately 2g) was induced by changes in vertical acceleration achieved during parabolic flights. Local ventilation magnitude and end-expiratory lung volume were determined in eight human subjects in the ventral and dorsal lung regions within a transverse cross-section of the lower chest by electrical impedance tomography. The subjects were studied in a 20 degrees head-down tilted supine body position during tidal breathing and full forced expirations. During tidal breathing, a significant effect of gravity on local magnitude of ventilation and end-expiratory lung volume was detected in the dorsal lung regions both with and without LBNP. In the ventral regions, this gravity dependency was only observed during LBNP. During forced expiration, LBNP had almost no effect on local ventilation and end-expiratory lung volume in either lung region. Gravity significantly influenced the end-expiratory lung volumes in dorsal lung regions. The results indicate that exposure to LBNP exerts a less appreciable effect on regional lung ventilation than the acute changes in gravity.

Assessment of regional ventilation distribution: comparison of vibration response imaging (VRI) with electrical impedance tomography (EIT).

BACKGROUND: Vibration response imaging (VRI) is a bedside technology to monitor ventilation by detecting lung sound vibrations. It is currently unknown whether VRI is able to accurately monitor the local distribution of ventilation within the lungs. We therefore compared VRI to electrical impedance tomography (EIT), an established technique used for the assessment of regional ventilation. METHODOLOGY/PRINCIPAL FINDINGS: Simultaneous EIT and VRI measurements were performed in the healthy and injured lungs (ALI; induced by saline lavage) at different PEEP levels (0, 5, 10, 15 mbar) in nine piglets. Vibration energy amplitude (VEA) by VRI, and amplitudes of relative impedance changes (rel.ΔZ) by EIT, were evaluated in seven regions of interest (ROIs). To assess the distribution of tidal volume (VT) by VRI and EIT, absolute values were normalized to the VT obtained by simultaneous spirometry measurements. Redistribution of ventilation by ALI and PEEP was detected by VRI and EIT. The linear correlation between pooled VT by VEA and rel.ΔZ was R(2) = 0.96. Bland-Altman analysis showed a bias of -1.07±24.71 ml and limits of agreement of -49.05 to +47.36 ml. Within the different ROIs, correlations of VT-distribution by EIT and VRI ranged between R(2) values of 0.29 and 0.96. ALI and PEEP did not alter the agreement of VT between VRI and EIT. CONCLUSIONS/SIGNIFICANCE: Measurements of regional ventilation distribution by VRI are comparable to those obtained by EIT.

Influence of crystalloid and colloid fluid infusion and blood withdrawal on pulmonary bioimpedance in an animal model of mechanical ventilation.

Electrical impedance tomography (EIT) is considered useful for monitoring regional ventilation and aeration in intensive-care patients during mechanical ventilation. Changes in their body fluid state modify the electrical properties of lung tissue and may interfere with the EIT measurements of lung aeration. The aim of our study was to assess the effects of crystalloid and colloid infusion and blood withdrawal on bioimpedance determined by EIT in a chest cross-section. Fourteen anaesthetized mechanically ventilated pigs were subjected to interventions affecting the volume state (crystalloid and colloid infusion, blood withdrawal). Six animals received additional crystalloid fluids (fluid group) whereas eight did not (no-fluid group). Global and regional relative impedance changes (RIC, dimensionless unit) were determined by backprojection at end-expiration. Regional ventilation distribution was analyzed by calculating the tidal RIC in the same regions. Colloid infusion led to a significant fall in the global end-expiratory RIC (mean differences: fluid: -91.2, p < 0.001, no-fluid: -38.9, p < 0.001), which was partially reversed after blood withdrawal (mean differences, fluid: +45.1, p = 0.047 and no-fluid: +26.2, p = 0.009). The RIC was significantly lower in the animals with additional crystalloids (mean group difference: 45.5, p < 0.001). Global and regional tidal volumes were not significantly affected by the fluid and volume states.