Benefits of Steroid Therapy in COVID-19 Patients with Different PaO2/FiO2 Ratio at Admission

Introduction: The use of steroid therapy in patients within the context of SARS-CoV-2 infection is still a matter of debate. This study aimed to evaluate if potential steroid benefits could be predicted by the ratio of arterial oxygen partial pressure (PaO2 in mmHg) to fractional inspired oxygen (FiO2) (P/F) in COVID-19 patients at admission. Materials and Methods: Medical records were retrospectively collected from all adult patients admitted because of COVID-19 from 29 January to 31 July 2020. The association of steroid therapy with 28-day all-cause mortality outcome was analysed in a multivariable logistic regression model adjusted for confounding factors. Results: Overall, 511 patients were analysed, of which 39.1% underwent steroid therapy. Steroid treated patients were mostly male, older, and more frequently treated with antiviral drugs and aminoquinolines; the most common comorbidities were hypertension, followed by cardiovascular disease. Overall, 51 patients died within 28-days, and overall 28-days mortality was 19.5% in the cohort of patients exposed to steroids versus 3.9% mortality in unexposed patients (p < 0.001). Steroid therapy on patients with P/F ratio of 235 mmHg or higher at admission can be considered as detrimental, with an 8% increased probability of death. Conclusions: Steroid therapy is associated with increased 28-day mortality in COVID-19 in patients with mild or no ARDS.

Effect of arterial oxygen partial pressure inflection point on Venoarterial extracorporeal membrane oxygenation for emergency cardiac support

Background Temporary circulatory support is a bridge between acute circulatory failure and definitive treatment or recovery. Currently, venoarterial extracorporeal membrane oxygenation (VA-ECMO) is considered to be one of the effective circulatory support methods, although cardiac function monitoring during the treatment still needs further investigation. Inflection point of arterial oxygen partial pressure (IPPaO2) may occur at an early stage in part of patients with a good prognosis after VA-ECMO treatment, and the relationship between time of IPPaO2 (tIPPaO2) and recovery of cardiac function or prognosis remains unclear. Methods To investigate this relationship, we retrospectively analyzed the clinical data of 71 patients with different conditions after treatment with VA-ECMO in the emergency center of Jiangsu Province Hospital between May 2015 and July 2020. Spearman’s correlation analysis was used for the correlation between tIPPaO2 and quantitative data, and ROC curve for the predictive effect of tIPPaO2 on the 28-day mortality. Results Thirty-five patients were admitted because of refractory cardiogenic shock (26 of 35 survived) and the remaining 36 patients due to cardiac arrest (13 of 36 survived). The overall survival rate was 54.9% (39 of 71 survived). Acute physiology and chronic health evaluation II, ECMO time, tIPPaO2, continuous renal replacement therapy time, mechanical ventilation time, and bleeding complications in the survival group were lower than those in the non-survival group, with length of stay, intensive care unit stay, and platelet levels were being higher. The tIPPaO2 was negatively correlated with ejection fraction, and the shorter tIPPaO2 resulted in a higher 28-day survival probability, higher predictive value for acute myocardial infarction and fulminant myocarditis. Conclusions Therefore, tIPPaO2 could be a reliable qualitative indicator of cardiac function in patients treated with VA-ECMO, which can reveal appropriate timing for adjusting VA-ECMO flow or weaning. Trial registration ChiCTR1900026105.

Low arterial oxygen partial pressure induces pulmonary thrombocytopenia in patients and a mouse model

Background Recent basic studies demonstrate that the lung is a primary organ of platelet biogenesis. However, whether the pathophysiological state of the lung affect the platelets is little known. We aim to investigate the incidence of thrombocytopenia in patients with pulmonary infection (PIN) and risk factors associated with pulmonary thrombocytopenia. Methods In total, 11,941 patients with pulmonary infection (PIN) were enrolled, and patients with other three infectious diseases were collected as controls. The incidence of thrombocytopenia was compared, and the risk factors associated with thrombocytopenia in PIN patients were investigated by multivariate analysis. To explore the mechanism of thrombocytopenia, hypoxic model was constructed. Blood platelet counts from the angular vein (PLTs), left ventricle (PLTpost) and right ventricle (PLTpre) were determined. Megakaryocytes identified by anti-CD41 antibody were detected through flow cytometry and immunofluorescence. Results The incidence of thrombocytopenia in PIN was higher than that in other three infectious diseases (9.8% vs. 6.4% ~ 5.0%, P < 0.001). Low arterial oxygen partial pressure (PaO2) was an important risk factor for thrombocytopenia (OR = 0.88; P < 0.001). In a hypoxic mouse model, PLTs decreased (518.38 ± 127.92 vs 840.75 ± 77.30, P < 0.05), which showed that low PaO2 induced thrombocytopenia. The difference between the PLTpost and PLTpre (∆PLTpost-pre), representing the production of platelets in the lungs, was significantly attenuated in hypoxic mice when compared with normoxic mice (F = 25.47, P < 0.05). Additionally, proportions of CD41-positive megakaryocytes in the lungs, marrow, spleen all decreased in hypoxic mice. Conclusion There is a high incidence for thrombocytopenia in PIN patients. Low PaO2-induced thrombocytopenia is associated with impaired generation of platelet in the lungs.

Low Arterial Oxygen Partial Pressure Induces Pulmonary Thrombocytopenia in Patients and a Mouse Model.

Background: Recent basic studies demonstrate that the lung is a primary organ of platelet biogenesis. However, whether the pathophysiological state of the lung affect the platelets is little known. We aim to investigate the incidence of thrombocytopenia in patients with pulmonary infection (PIN) and risk factors associated with pulmonary thrombocytopenia.Methods: In total, 11941 patients with pulmonary infection (PIN) were enrolled, and patients with other three infectious diseases were collected as controls. The incidence of thrombocytopenia was compared, and the risk factors associated with thrombocytopenia in PIN patients were investigated by multivariate analysis. To explore the mechanism of thrombocytopenia, hypoxic model was constructed. Blood platelet counts from the angular vein (PLTs), left ventricle (PLTpost) and right ventricle (PLTpre) were determined. Megakaryocytes identified by anti-CD41 antibody were detected through flow cytometry and immunofluorescence.Results: The incidence of thrombocytopenia in PIN was higher than that in other three infectious diseases (9.8% vs 6.4%~5.0%, P<0.001). Low arterial oxygen partial pressure (PaO2) was an important risk factor for thrombocytopenia (OR=0.88; P<0.001). In a hypoxic mouse model, PLTs decreased (518.38±127.92 vs 840.75±77.30, P<0.05), which showed that low PaO2 induced thrombocytopenia. The difference between the PLTpost and PLTpre (△PLTpost-pre), representing the production of platelets in the lungs, was significantly attenuated in hypoxic mice when compared with normoxic mice (F=25.47, P<0.05). Additionally, proportions of CD41-positive megakaryocytes in the lungs, marrow, spleen all decreased in hypoxic mice.Conclusion: There is a high incidence for thrombocytopenia in PIN patients. Low PaO2-induced thrombocytopenia is associated with impaired generation of platelet in the lungs.

Low Arterial Oxygen Partial Pressure Induces Pulmonary Thrombocytopenia in Patients and a Mouse Model.

Background: Recent basic studies demonstrate that the lung is a primary organ of platelet biogenesis. However, whether the pathophysiological state of the lung affect the platelets is little known. We aim to investigate the incidence of thrombocytopenia in patients with pulmonary infection (PIN) and risk factors associated with pulmonary thrombocytopenia. Methods: In total, 11941 patients with pulmonary infection (PIN) were enrolled, and patients with other three infectious diseases were collected as controls. The incidence of thrombocytopenia was compared, and the risk factors associated with thrombocytopenia in PIN patients were investigated by multivariate analysis. To explore the mechanism of thrombocytopenia, hypoxic model was constructed. Blood platelet counts from the angular vein (PLTs), left ventricle (PLTpost) and right ventricle (PLTpre) were determined. Megakaryocytes identified by anti-CD41 antibody were detected through flow cytometry and immunofluorescence. Results: The incidence of thrombocytopenia in PIN was higher than that in other three infectious diseases (9.8% vs 6.4%~5.0%, P<0.001). Low arterial oxygen partial pressure (PaO2) was an important risk factor for thrombocytopenia (OR=0.88; P<0.001). In a hypoxic mouse model, PLTs were decreased (518.38±127.92 vs 840.75±77.30, P<0.05), which showed that low PaO2 induce thrombocytopenia. The difference between the PLTpost and PLTpre (△PLTpost-pre), represent the production of platelets in the lungs, was significantly attenuated in hypoxic mice when compared with normoxic mice (F=25.47, P<0.05). Additionally, proportions of CD41-positive megakaryocytes in the lungs, marrow, spleen were all decreased in hypoxic mice. Conclusion: There is a high incidence for thrombocytopenia in PIN patients. Low PaO2-induced thrombocytopenia is associated with impaired generation of platelet in the lungs.

Preoperative autologous platelet pheresis reduces allogeneic platelet use and improves the postoperative PaO2/FiO2 ratio in complex aortic surgery: a retrospective analysis

OBJECTIVES An autologous platelet-rich plasma pheresis (aPP) strategy can harvest partial whole blood that is separated into erythrocytes, plasma and platelets, and can reduce blood loss and transfusion during cardiovascular surgery using cardiopulmonary bypass (CPB). However, the blood and organ conservation effects of this technique have not been confirmed in the context of complex aortic surgery. METHODS Perioperative records of 147 adult patients who underwent complex aortic surgery were analysed retrospectively. RESULTS All patients received regular blood conservation treatment, and 57 patients received aPP. Whether or not the participants were propensity matched, decreased platelet and cryoprecipitate transfusions were found in the aPP group (both P &lt; 0.001), but there were non-significant differences in erythrocyte transfusion, Sequential Organ Failure Assessment scores and other outcomes when compared with the same parameters in the non-aPP group. The aPP group had a higher arterial oxygen partial pressure to inhaled oxygen concentration ratio on postoperative days 1, 2 and 7 than the non-aPP group (P &lt; 0.001, P &lt; 0.001 and P = 0.048, respectively). CONCLUSIONS The utilization of aPP was associated with a reduction in allogeneic platelet and cryoprecipitate transfusions as well as minor lung-protective effects during complex aortic surgery using CPB.

Mitochondrial oxygen monitoring with COMET: verification of calibration in man and comparison with vascular occlusion tests in healthy volunteers

Mitochondria are the primary consumers of oxygen and therefore an important location for oxygen availability and consumption measurement. A technique has been developed for mitochondrial oxygen tension (mitoPO2) measurement, incorporated in the COMET. In contrast to most textbooks, relatively high average mitoPO2 values have been reported. The first aim of this study was to verify the validity of the COMET calibration for mitoPO2 measurements in human skin. The second aim was to compare the dynamics of mitoPO2 to several other techniques assessing tissue oxygenation. Firstly, we performed a two-point calibration. Mitochondrial oxygen depletion was achieved with vascular occlusion. A high mitoPO2 was reached by local application of cyanide. MitoPO2 was compared to the arterial oxygen partial pressure (PaO2). Secondly, for deoxygenation kinetics we compared COMET variables with the LEA O2C, SenTec OxiVenT™ and Medtronic INVOS™ parameters during a vascular occlusion test. 20 healthy volunteers were recruited and resulted in 18 datasets (2 times 9 subjects). The lowest measured mitoPO2 value per subject had a median [IQR] of 3.0 [1.0–4.0] mmHg, n = 9. After cyanide application the mitoPO2 was 94.1 mmHg [87.2–110.9] and did not differ significantly (n = 9, p = 0.5) from the PaO2 of 101.0 [98.0–106.0] mmHg. In contrast to O2C, OxiVenT™ and INVOS parameters, mitoPO2 declined within seconds with pressure on the probe. The kinetics from this decline are used to mitochondrial oxygen consumption (mitoVO2). This study validates the calibration of the COMET device in humans. For mitoVO2 measurements not only blood flow cessation but application of local pressure is of great importance to clear the measurement site of oxygen-carrying erythrocytes.

First report of tocilizumab use in a cohort of Latin American patients hospitalized for severe COVID-19 pneumonia

Introduction/objectives: An interleukin-6 inhibition strategy could be effective in selected COVID-19 patients. The objective is to present our experience of tocilizumab use in patients with severe COVID-19. Methods: Observational retrospective cohort study. Hospitalized patients were evaluated by our multidisciplinary team for eventual use of tocilizumab. Patients with progressive ventilatory impairment and evidence of a hyperinflammatory state despite usual treatment received tocilizumab 8 mg/kg intravenous (maximum dose 800 mg), in addition to standard treatment. The use and time of use of mechanical ventilation (MV), the change of the Alveolar-arterial (A-a) gradient, of the ratio of arterial oxygen partial pressure to fractional inspired oxygen (PaO2/FiO2) and of inflammation laboratory parameters after 72 hours of tocilizumab use was evaluated. Results: 29 patients received tocilizumab. 93.1% were men, 37.9% were obese, and 34.5% had hypertension. Of the 20 patients who were not on MV when receiving tocilizumab, 11 required non-invasive MV, for an average of five days, and one of them required intubation. A-a gradient, PaO2/FiO2, and inflammation parameters improved significantly. A better lymphocyte count, which improved significantly after tocilizumab use, was significantly associated with less use of MV. Five patients presented positive culture samples after tocilizumab, three being of clinical significance. A lower lymphocyte count was associated with having a positive culture. No other significant adverse events were seen. Conclusion: Our study suggests the utility and shows the safety of tocilizumab use in COVID-19 patients who have respiratory failure and evidence of hyperinflammation. Lymphocyte improvement was a predictor of good response.

Low Arterial Oxygen Partial Pressure Induces Pulmonary Thrombocytopenia in Patients and a Mouse Model

Background Recent basic studies demonstrate that the lung is a primary organ of platelet biogenesis. However, whether the pathophysiological state of the lung affect the platelets is little known. We aim to investigate the incidence of thrombocytopenia in patients with pulmonary infection (PIN) and risk factors associated with pulmonary thrombocytopenia. Methods In total, 11941 patients with pulmonary infection (PIN) were enrolled, and patients with three other infectious diseases were collected as controls. The incidence of thrombocytopenia was compared, and the risk factors associated with thrombocytopenia in PIN patients were investigated by multivariate analysis. To explore the mechanism of thrombocytopenia, hypoxic model were constructed. Blood platelet counts from the angular vein (PLTs), left ventricle (PLTpost) and right ventricle (PLTpre) were determined. Megakaryocyte staining with a CD41-specific antibody in the lungs was detected by flow cytometry and immunofluorescence. Results The incidence of thrombocytopenia in PIN patients was higher than that in the other three types of infectious disease patients(9.8% vs 6.4%~5.0%, P < 0.001). Relatively low arterial oxygen partial pressure (PaO2) was an important risk factor for thrombocytopenia (OR = 0.88; P < 0.001). In a hypoxic mouse model, PLTs were decreased (518.38 ± 127.92 vs 840.75 ± 77.30, P < 0.05), which showed that the low PaO2 could induce thrombocytopenia. The difference between the PLTpost and PLTpre (△PLTpost−pre) represented the production of platelets in the lungs, which was significantly attenuated in hypoxic mice compared with normoxic mice (F = 25.47, P < 0.05). Additionally, CD41-positive megakaryocyte numbers in the lungs were decreased in hypoxic mice. Conclusion PIN is a susceptibility factor for thrombocytopenia. Low PaO2-induced thrombocytopenia is associated with impaired platelet generation in the lungs.