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1.
J Appl Physiol (1985) ; 132(4): 1104-1113, 2022 04 01.
Article in English | MEDLINE | ID: covidwho-1759485

ABSTRACT

The common pulmonary consequence of SARS-CoV-2 infection is pneumonia, but vascular clot may also contribute to COVID pathogenesis. Imaging and hemodynamic approaches to identifying diffuse pulmonary vascular obstruction (PVO) in COVID (or acute lung injury generally) are problematic particularly when pneumonia is widespread throughout the lung and hemodynamic consequences are buffered by pulmonary vascular recruitment and distention. Although stimulated by COVID-19, we propose a generally applicable bedside gas exchange approach to identifying PVO occurring alone or in combination with pneumonia, addressing both its theoretical and practical aspects. It is based on knowing that poorly (or non) ventilated regions, as occur in pneumonia, affect O2 more than CO2, whereas poorly (or non) perfused regions, as seen in PVO, affect CO2 more than O2. Exhaled O2 and CO2 concentrations at the mouth are measured over several ambient-air breaths, to determine mean alveolar Po2 and Pco2. A single arterial blood sample is taken over several of these breaths for arterial Po2 and Pco2. The resulting alveolar-arterial Po2 and Pco2 differences (AaPo2, aAPco2) are converted to corresponding physiological shunt and deadspace values using the Riley and Cournand 3-compartment model. For example, a 30% shunt (from pneumonia) with no alveolar deadspace produces an AaPO2 of almost 50 torr, but an aAPco2 of only 3 torr. In contrast, a 30% alveolar deadspace (from PVO) without shunt leads to an AaPO2 of only 12 torr, but an aAPco2 of 9 torr. This approach can identify and quantify physiological shunt and deadspace when present singly or in combination.NEW & NOTEWORTHY Identifying pulmonary vascular obstruction in the presence of pneumonia (e.g., in COVID-19) is difficult. We present here conversion of bedside measurements of arterial and alveolar Po2 and Pco2 into values for shunt and deadspace-when both coexist-using Riley and Cournand's 3-compartment gas exchange model. Deadspace values higher than expected from shunt alone indicate high ventilation/perfusion ratio areas likely reflecting (micro)vascular obstruction.


Subject(s)
COVID-19 , Lung Diseases , Carbon Dioxide , Humans , Pulmonary Gas Exchange/physiology , SARS-CoV-2
2.
BMC Pulm Med ; 22(1): 71, 2022 Feb 25.
Article in English | MEDLINE | ID: covidwho-1698249

ABSTRACT

BACKGROUND: Prone positioning enables the redistribution of lung weight, leading to the improvement of gas exchange and respiratory mechanics. We aimed to evaluate whether the initial findings of acute respiratory distress syndrome (ARDS) on computed tomography (CT) are associated with the subsequent response to prone positioning in terms of oxygenation and 60-day mortality. METHODS: We retrospectively included patients who underwent prone positioning for moderate to severe ARDS from October 2014 to November 2020 at a medical center in Taiwan. A semiquantitative CT rating scale was used to quantify the extent of consolidation and ground-glass opacification (GGO) in the sternal, central and vertebral regions at three levels (apex, hilum and base) of the lungs. A prone responder was identified by a 20% increase in the ratio of arterial oxygen pressure (PaO2) to the fraction of oxygen (FiO2) or a 20 mmHg increase in PaO2. RESULTS: Ninety-six patients were included, of whom 68 (70.8%) were responders. Compared with nonresponders, responders had a significantly greater median dorsal-ventral difference in CT-consolidation scores (10 vs. 7, p = 0.046) but not in CT-GGO scores (- 1 vs. - 1, p = 0.974). Although dorsal-ventral differences in neither CT-consolidation scores nor CT-GGO scores were associated with 60-day mortality, high total CT-GGO scores (≥ 15) were an independent factor associated with 60-day mortality (odds ratio = 4.07, 95% confidence interval, 1.39-11.89, p = 0.010). CONCLUSIONS: In patients with moderate to severe ARDS, a greater difference in the extent of consolidation along the dependent-independent axis on CT scan is associated with subsequent prone positioning oxygenation response, but not clinical outcome regarding survival. High total CT-GGO scores were independently associated with 60-day mortality.


Subject(s)
Pulmonary Gas Exchange , Respiratory Distress Syndrome , Humans , Prognosis , Prone Position/physiology , Pulmonary Gas Exchange/physiology , Respiratory Distress Syndrome/diagnostic imaging , Respiratory Distress Syndrome/therapy , Retrospective Studies , Tomography, X-Ray Computed
3.
Crit Care ; 25(1): 214, 2021 06 21.
Article in English | MEDLINE | ID: covidwho-1440944

ABSTRACT

BACKGROUND: Critically ill COVID-19 patients have pathophysiological lung features characterized by perfusion abnormalities. However, to date no study has evaluated whether the changes in the distribution of pulmonary gas and blood volume are associated with the severity of gas-exchange impairment and the type of respiratory support (non-invasive versus invasive) in patients with severe COVID-19 pneumonia. METHODS: This was a single-center, retrospective cohort study conducted in a tertiary care hospital in Northern Italy during the first pandemic wave. Pulmonary gas and blood distribution was assessed using a technique for quantitative analysis of dual-energy computed tomography. Lung aeration loss (reflected by percentage of normally aerated lung tissue) and the extent of gas:blood volume mismatch (percentage of non-aerated, perfused lung tissue-shunt; aerated, non-perfused dead space; and non-aerated/non-perfused regions) were evaluated in critically ill COVID-19 patients with different clinical severity as reflected by the need for non-invasive or invasive respiratory support. RESULTS: Thirty-five patients admitted to the intensive care unit between February 29th and May 30th, 2020 were included. Patients requiring invasive versus non-invasive mechanical ventilation had both a lower percentage of normally aerated lung tissue (median [interquartile range] 33% [24-49%] vs. 63% [44-68%], p < 0.001); and a larger extent of gas:blood volume mismatch (43% [30-49%] vs. 25% [14-28%], p = 0.001), due to higher shunt (23% [15-32%] vs. 5% [2-16%], p = 0.001) and non-aerated/non perfused regions (5% [3-10%] vs. 1% [0-2%], p = 0.001). The PaO2/FiO2 ratio correlated positively with normally aerated tissue (ρ = 0.730, p < 0.001) and negatively with the extent of gas-blood volume mismatch (ρ = - 0.633, p < 0.001). CONCLUSIONS: In critically ill patients with severe COVID-19 pneumonia, the need for invasive mechanical ventilation and oxygenation impairment were associated with loss of aeration and the extent of gas:blood volume mismatch.


Subject(s)
Blood Volume/physiology , COVID-19/diagnostic imaging , COVID-19/metabolism , Lung/diagnostic imaging , Lung/metabolism , Pulmonary Gas Exchange/physiology , Aged , Blood Gas Analysis/methods , COVID-19/epidemiology , Cohort Studies , Critical Illness/epidemiology , Female , Humans , Italy/epidemiology , Male , Middle Aged , Respiration, Artificial/methods , Retrospective Studies , Tomography, X-Ray Computed/methods
4.
Respir Physiol Neurobiol ; 294: 103767, 2021 12.
Article in English | MEDLINE | ID: covidwho-1330032

ABSTRACT

A computational model of the transport of gases involved in spontaneous breathing, from the trachea inlet to the alveoli was developed for healthy patients. Convective and diffusive transport mechanisms were considered simultaneously, using a diffusion coefficient (D) that has considered the four main species of gases present in the exchange carried out by the human lung, nitrogen (N2), oxygen (O2), carbon dioxide (CO2) and water vapor (H2O). A Matlab® script was programmed to simulate the trachea-alveolus gas exchange model under three respiratory frequencies: 12, 24 and 40 breaths per minute (BPM), each with three diaphragmatic movements of 2 cm, 4 cm, and 6 cm. During the simulations, the CO2 inlet concentrations in the alveoli and the O2 concentration at the inlet of the trachea were kept constant. A simplified but stable model of mass transport between the trachea and alveoli was obtained, allowing the concentrations to be determined dynamically at the selected test points in the airway.


Subject(s)
Models, Theoretical , Pulmonary Alveoli/physiology , Pulmonary Gas Exchange/physiology , Respiration , Trachea/physiology , Humans
5.
Crit Care ; 25(1): 248, 2021 07 15.
Article in English | MEDLINE | ID: covidwho-1317127

ABSTRACT

BACKGROUND: Differences in physiology of ARDS have been described between COVID-19 and non-COVID-19 patients. This study aimed to compare initial values and longitudinal changes in respiratory system compliance (CRS), oxygenation parameters and ventilatory ratio (VR) in patients with COVID-19 and non-COVID-19 pulmonary ARDS matched on oxygenation. METHODS: 135 patients with COVID-19 ARDS from two centers were included in a physiological study; 767 non-COVID-19 ARDS from a clinical trial were used for the purpose of at least 1:2 matching. A propensity-matching was based on age, severity score, oxygenation, positive end-expiratory pressure (PEEP) and pulmonary cause of ARDS and allowed to include 112 COVID-19 and 198 non-COVID pulmonary ARDS. RESULTS: The two groups were similar on initial oxygenation. COVID-19 patients had a higher body mass index, higher CRS at day 1 (median [IQR], 35 [28-44] vs 32 [26-38] ml cmH2O-1, p = 0.037). At day 1, CRS was correlated with oxygenation only in non-COVID-19 patients; 61.6% and 68.2% of COVID-19 and non-COVID-19 pulmonary ARDS were still ventilated at day 7 (p = 0.241). Oxygenation became lower in COVID-19 than in non-COVID-19 patients at days 3 and 7, while CRS became similar. VR was lower at day 1 in COVID-19 than in non-COVID-19 patients but increased from day 1 to 7 only in COVID-19 patients. VR was higher at days 1, 3 and 7 in the COVID-19 patients ventilated using heat and moisture exchangers compared to heated humidifiers. After adjustment on PaO2/FiO2, PEEP and humidification device, CRS and VR were found not different between COVID-19 and non-COVID-19 patients at day 7. Day-28 mortality did not differ between COVID-19 and non-COVID-19 patients (25.9% and 23.7%, respectively, p = 0.666). CONCLUSIONS: For a similar initial oxygenation, COVID-19 ARDS initially differs from classical ARDS by a higher CRS, dissociated from oxygenation. CRS become similar for patients remaining on mechanical ventilation during the first week of evolution, but oxygenation becomes lower in COVID-19 patients. TRIAL REGISTRATION: clinicaltrials.gov NCT04385004.


Subject(s)
COVID-19/therapy , Positive-Pressure Respiration/methods , Respiratory Distress Syndrome/therapy , Aged , Blood Gas Analysis , Body Mass Index , COVID-19/physiopathology , Female , Humans , Intensive Care Units , Male , Middle Aged , Propensity Score , Pulmonary Gas Exchange/physiology , Respiration, Artificial/methods , Respiratory Distress Syndrome/physiopathology , Respiratory Function Tests , Respiratory Mechanics/physiology , SARS-CoV-2
6.
Respir Med ; 185: 106481, 2021.
Article in English | MEDLINE | ID: covidwho-1253572

ABSTRACT

Non-invasive respiratory support (NRS) outside of the ICU has played an important role in the management of COVID-19 pneumonia. There is little data to guide selection of NRS modality. We present outcomes of NRS outside the ICU and discuss the effects of NRS on gas exchange with implications for management.


Subject(s)
COVID-19/therapy , Intensive Care Units , Noninvasive Ventilation/methods , Pulmonary Gas Exchange/physiology , SARS-CoV-2 , Aged , Aged, 80 and over , COVID-19/epidemiology , COVID-19/physiopathology , Female , Humans , Male , Middle Aged , Treatment Outcome
7.
J Appl Physiol (1985) ; 130(3): 865-876, 2021 03 01.
Article in English | MEDLINE | ID: covidwho-1028125

ABSTRACT

COVID-19 infection may lead to acute respiratory distress syndrome (CARDS) where severe gas exchange derangements may be associated, at least in the early stages, only with minor pulmonary infiltrates. This may suggest that the shunt associated to the gasless lung parenchyma is not sufficient to explain CARDS hypoxemia. We designed an algorithm (VentriQlar), based on the same conceptual grounds described by J.B. West in 1969. We set 498 ventilation-perfusion (VA/Q) compartments and, after calculating their blood composition (PO2, PCO2, and pH), we randomly chose 106 combinations of five parameters controlling a bimodal distribution of blood flow. The solutions were accepted if the predicted PaO2 and PaCO2 were within 10% of the patient's values. We assumed that the shunt fraction equaled the fraction of non-aerated lung tissue at the CT quantitative analysis. Five critically-ill patients later deceased were studied. The PaO2/FiO2 was 91.1 ± 18.6 mmHg and PaCO2 69.0 ± 16.1 mmHg. Cardiac output was 9.58 ± 0.99 L/min. The fraction of non-aerated tissue was 0.33 ± 0.06. The model showed that a large fraction of the blood flow was likely distributed in regions with very low VA/Q (Qmean = 0.06 ± 0.02) and a smaller fraction in regions with moderately high VA/Q. Overall LogSD, Q was 1.66 ± 0.14, suggestive of high VA/Q inequality. Our data suggest that shunt alone cannot completely account for the observed hypoxemia and a significant VA/Q inequality must be present in COVID-19. The high cardiac output and the extensive microthrombosis later found in the autopsy further support the hypothesis of a pathological perfusion of non/poorly ventilated lung tissue.NEW & NOTEWORTHY Hypothesizing that the non-aerated lung fraction as evaluated by the quantitative analysis of the lung computed tomography (CT) equals shunt (VA/Q = 0), we used a computational approach to estimate the magnitude of the ventilation-perfusion inequality in severe COVID-19. The results show that a severe hyperperfusion of poorly ventilated lung region is likely the cause of the observed hypoxemia. The extensive microthrombosis or abnormal vasodilation of the pulmonary circulation may represent the pathophysiological mechanism of such VA/Q distribution.


Subject(s)
COVID-19/physiopathology , Ventilation-Perfusion Ratio/physiology , Adult , Aged , COVID-19/metabolism , Cardiac Output/physiology , Female , Hemodynamics/physiology , Humans , Lung/metabolism , Lung/physiopathology , Male , Middle Aged , Oxygen/metabolism , Perfusion/methods , Pulmonary Circulation/physiology , Pulmonary Gas Exchange/physiology , Respiration , Retrospective Studies , SARS-CoV-2/pathogenicity
9.
J Card Fail ; 27(1): 105-108, 2021 01.
Article in English | MEDLINE | ID: covidwho-963391

ABSTRACT

BACKGROUND: Exercise testing plays an important role in evaluating heart failure prognosis and selecting patients for advanced therapeutic interventions. However, concern for severe acute respiratory syndrome novel coronavirus-2 transmission during exercise testing has markedly curtailed performance of exercise testing during the novel coronavirus disease-2019 pandemic. METHODS AND RESULTS: To examine the feasibility to conducting exercise testing with an in-line filter, 2 healthy volunteer subjects each completed 2 incremental exercise tests, one with discrete stages of increasing resistance and one with a continuous ramp. Each subject performed 1 test with an electrostatic filter in-line with the system measuring gas exchange and air flow, and 1 test without the filter in place. Oxygen uptake and minute ventilation were highly consistent when evaluated with and without use of an electrostatic filter with a >99.9% viral efficiency. CONCLUSIONS: Deployment of a commercially available in-line electrostatic viral filter during cardiopulmonary exercise testing is feasible and provides consistent data compared with testing without a filter.


Subject(s)
COVID-19/epidemiology , COVID-19/prevention & control , Exercise Test/standards , Heart Failure/diagnosis , Heart Failure/epidemiology , Respiratory Protective Devices/standards , Exercise Test/methods , Feasibility Studies , Humans , Male , Oxygen Consumption/physiology , Pandemics , Pulmonary Gas Exchange/physiology , Reproducibility of Results
10.
Intensive Care Med ; 46(12): 2187-2196, 2020 12.
Article in English | MEDLINE | ID: covidwho-886981

ABSTRACT

PURPOSE: To investigate whether COVID-19-ARDS differs from all-cause ARDS. METHODS: Thirty-two consecutive, mechanically ventilated COVID-19-ARDS patients were compared to two historical ARDS sub-populations 1:1 matched for PaO2/FiO2 or for compliance of the respiratory system. Gas exchange, hemodynamics and respiratory mechanics were recorded at 5 and 15 cmH2O PEEP. CT scan variables were measured at 5 cmH2O PEEP. RESULTS: Anthropometric characteristics were similar in COVID-19-ARDS, PaO2/FiO2-matched-ARDS and Compliance-matched-ARDS. The PaO2/FiO2-matched-ARDS and COVID-19-ARDS populations (both with PaO2/FiO2 106 ± 59 mmHg) had different respiratory system compliances (Crs) (39 ± 11 vs 49.9 ± 15.4 ml/cmH2O, p = 0.03). The Compliance-matched-ARDS and COVID-19-ARDS had similar Crs (50.1 ± 15.7 and 49.9 ± 15.4 ml/cmH2O, respectively) but significantly lower PaO2/FiO2 for the same Crs (160 ± 62 vs 106.5 ± 59.6 mmHg, p < 0.001). The three populations had similar lung weights but COVID-19-ARDS had significantly higher lung gas volume (PaO2/FiO2-matched-ARDS 930 ± 644 ml, COVID-19-ARDS 1670 ± 791 ml and Compliance-matched-ARDS 1301 ± 627 ml, p < 0.05). The venous admixture was significantly related to the non-aerated tissue in PaO2/FiO2-matched-ARDS and Compliance-matched-ARDS (p < 0.001) but unrelated in COVID-19-ARDS (p = 0.75), suggesting that hypoxemia was not only due to the extent of non-aerated tissue. Increasing PEEP from 5 to 15 cmH2O improved oxygenation in all groups. However, while lung mechanics and dead space improved in PaO2/FiO2-matched-ARDS, suggesting recruitment as primary mechanism, they remained unmodified or worsened in COVID-19-ARDS and Compliance-matched-ARDS, suggesting lower recruitment potential and/or blood flow redistribution. CONCLUSIONS: COVID-19-ARDS is a subset of ARDS characterized overall by higher compliance and lung gas volume for a given PaO2/FiO2, at least when considered within the timeframe of our study.


Subject(s)
COVID-19/physiopathology , Respiratory Distress Syndrome/physiopathology , Adult , Aged , Blood Gas Analysis/methods , COVID-19/therapy , Cohort Studies , Female , Humans , Intensive Care Units/organization & administration , Intensive Care Units/statistics & numerical data , Italy , Length of Stay/statistics & numerical data , Lung Compliance/physiology , Male , Middle Aged , Prospective Studies , Pulmonary Gas Exchange/physiology , Respiratory Distress Syndrome/therapy , Simplified Acute Physiology Score , Tomography, X-Ray Computed/methods
13.
Lancet Respir Med ; 8(8): 765-774, 2020 08.
Article in English | MEDLINE | ID: covidwho-611732

ABSTRACT

BACKGROUND: The COVID-19 pandemic is challenging advanced health systems, which are dealing with an overwhelming number of patients in need of intensive care for respiratory failure, often requiring intubation. Prone positioning in intubated patients is known to reduce mortality in moderate-to-severe acute respiratory distress syndrome. We aimed to investigate feasibility and effect on gas exchange of prone positioning in awake, non-intubated patients with COVID-19-related pneumonia. METHODS: In this prospective, feasibility, cohort study, patients aged 18-75 years with a confirmed diagnosis of COVID-19-related pneumonia receiving supplemental oxygen or non-invasive continuous positive airway pressure were recruited from San Gerardo Hospital, Monza, Italy. We collected baseline data on demographics, anthropometrics, arterial blood gas, and ventilation parameters. After baseline data collection, patients were helped into the prone position, which was maintained for a minimum duration of 3 h. Clinical data were re-collected 10 min after prone positioning and 1 h after returning to the supine position. The main study outcome was the variation in oxygenation (partial pressure of oxygen [PaO2]/fractional concentration of oxygen in inspired air [FiO2]) between baseline and resupination, as an index of pulmonary recruitment. This study is registered on ClinicalTrials.gov, NCT04365959, and is now complete. FINDINGS: Between March 20 and April 9, 2020, we enrolled 56 patients, of whom 44 (79%) were male; the mean age was 57·4 years (SD 7·4) and the mean BMI was 27·5 kg/m2 (3·7). Prone positioning was feasible (ie, maintained for at least 3 h) in 47 patients (83·9% [95% CI 71·7 to 92·4]). Oxygenation substantially improved from supine to prone positioning (PaO2/FiO2 ratio 180·5 mm Hg [SD 76·6] in supine position vs 285·5 mm Hg [112·9] in prone position; p<0·0001). After resupination, improved oxygenation was maintained in 23 patients (50·0% [95% CI 34·9-65·1]; ie, responders); however, this improvement was on average not significant compared with before prone positioning (PaO2/FiO2 ratio 192·9 mm Hg [100·9] 1 h after resupination; p=0·29). Patients who maintained increased oxygenation had increased levels of inflammatory markers (C-reactive protein: 12·7 mg/L [SD 6·9] in responders vs 8·4 mg/L [6·2] in non-responders; and platelets: 241·1 × 103/µL [101·9] vs 319·8 × 103/µL [120·6]) and shorter time between admission to hospital and prone positioning (2·7 days [SD 2·1] in responders vs 4·6 days [3·7] in non-responders) than did those for whom improved oxygenation was not maintained. 13 (28%) of 46 patients were eventually intubated, seven (30%) of 23 responders and six (26%) of 23 non-responders (p=0·74). Five patients died during follow-up due to underlying disease, unrelated to study procedure. INTERPRETATION: Prone positioning was feasible and effective in rapidly ameliorating blood oxygenation in awake patients with COVID-19-related pneumonia requiring oxygen supplementation. The effect was maintained after resupination in half of the patients. Further studies are warranted to ascertain the potential benefit of this technique in improving final respiratory and global outcomes. FUNDING: University of Milan-Bicocca.


Subject(s)
Betacoronavirus , Coronavirus Infections/physiopathology , Pneumonia, Viral/physiopathology , Prone Position , Pulmonary Gas Exchange/physiology , Respiratory Distress Syndrome/physiopathology , Adolescent , Adult , Aged , COVID-19 , Coronavirus Infections/therapy , Critical Care/methods , Feasibility Studies , Female , Humans , Male , Middle Aged , Pandemics , Pneumonia, Viral/therapy , Prospective Studies , Respiratory Distress Syndrome/therapy , Respiratory Distress Syndrome/virology , Respiratory Mechanics/physiology , SARS-CoV-2 , Young Adult
15.
Am J Respir Crit Care Med ; 201(12): 1560-1564, 2020 06 15.
Article in English | MEDLINE | ID: covidwho-155108
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