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

Author(s):  
Omar Valenzuela ◽  
Sebastian E Ibanez ◽  
Maria Poli ◽  
Patricia Roessler ◽  
Mabel Aylwin ◽  
...  

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.

2002 ◽  
Vol 97 (3) ◽  
pp. 682-692 ◽  
Author(s):  
Muneyuki Takeuchi ◽  
Sven Goddon ◽  
Marisa Dolhnikoff ◽  
Motomu Shimaoka ◽  
Dean Hess ◽  
...  

Background The most appropriate method of determining positive end-expiratory pressure (PEEP) level during a lung protective ventilatory strategy has not been established. Methods In a lavage-injured sheep acute respiratory distress syndrome model, the authors compared the effects of three approaches to determining PEEP level after a recruitment maneuver: (1) 2 cm H(2)O above the lower inflection point on the inflation pressure-volume curve, (2) at the point of maximum curvature on the deflation pressure-volume curve, and (3) at the PEEP level that maintained target arterial oxygen partial pressure at a fraction of inspired oxygen of 0.5. Results Positive end-expiratory pressure set 2 cm H(2)O above the lower inflection point resulted in the least injury over the course of the study. PEEP based on adequate arterial oxygen partial pressure/fraction of inspired oxygen ratios had to be increased over time and resulted in higher mRNA levels for interleukin-8 and interleukin-1beta and greater tissue inflammation when compared with the other approaches. PEEP at the point of maximum curvature could not maintain eucapneia even at an increased ventilatory rate. Conclusion Although generating higher plateau pressures, PEEP levels based on pressure-volume curve analysis were more effective in maintaining gas exchange and minimizing injury than PEEP based on adequate oxygenation. PEEP at 2 cm H(2)O above the lower inflection point was most effective.


2021 ◽  
Vol 10 (15) ◽  
pp. 3236
Author(s):  
Serena Vita ◽  
Daniele Centanni ◽  
Simone Lanini ◽  
Pierluca Piselli ◽  
Silvia Rosati ◽  
...  

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.


2011 ◽  
Vol 115 (3) ◽  
pp. 492-498 ◽  
Author(s):  
John R. Feiner ◽  
Heather E. Finlay-Morreale ◽  
Pearl Toy ◽  
Jeremy A. Lieberman ◽  
Maurene K. Viele ◽  
...  

Background Anemia is associated with morbidity and mortality and frequently leads to transfusion of erythrocytes. The authors sought to directly compare the effect of high inspired oxygen fraction versus transfusion of erythrocytes on the anemia-induced increased heart rate (HR) in humans undergoing experimental acute isovolemic anemia. Methods The authors combined HR data from healthy subjects undergoing experimental isovolemic anemia in seven studies performed by the group. HR changes associated with breathing 100% oxygen by nonrebreathing facemask versus transfusion of erythrocytes at their nadir hemoglobin concentration of 5 g/dl were examined. Data were analyzed using a mixed-effects model. Results HR had an inverse linear relationship to hemoglobin concentration with a mean increase of 3.9 beats per min per gram of hemoglobin (beats/min/g hemoglobin) decrease (95% CI, 3.7-4.1 beats/min/g hemoglobin), P &lt; 0.0001. Return of autologous erythrocytes significantly decreased HR by 5.3 beats/min/g hemoglobin (95% CI, 3.8-6.8 beats/min/g hemoglobin) increase, P &lt; 0.0001. HR at nadir hemoglobin of 5.6 g/dl (95% CI, 5.5-5.7 g/dl) when breathing air (91.4 beats/min; 95% CI, 87.6-95.2 beats/min) was reduced by breathing 100% oxygen (83.0 beats/min; 95% CI, 79.0-87.0 beats/min), P &lt; 0.0001. The HR at hemoglobin 5.6 g/dl when breathing oxygen was equivalent to the HR at hemoglobin 8.9 g/dl when breathing air. Conclusions High arterial oxygen partial pressure reverses the heart rate response to anemia, probably because of its usability rather than its effect on total oxygen content. The benefit of high arterial oxygen partial pressure has significant potential clinical implications for the acute treatment of anemia and results of transfusion trials.


2018 ◽  
Vol 2018 ◽  
pp. 1-6 ◽  
Author(s):  
Emi Fujii ◽  
Kazunori Fujino ◽  
Sachiko Tanaka-Mizuno ◽  
Yutaka Eguchi

Unexpected reintubation may occur, even if the risk factors are considered and a spontaneous breathing trial is successful. Reintubation is thought to be caused by various factors. Several studies have investigated the risk factors of reintubation, but most did not classify reintubation by cause. We retrospectively classified patients undergoing reintubation at intensive care unit by cause (respiratory insufficiency vs. nonrespiratory insufficiency) to examine the cause-specific risk factors of reintubation. A total of 262 patients were included; reintubation within 48 hours after extubation was performed in 12 patients (reintubation rate, 4.5%). After classification by cause of reintubation, the pressure of arterial oxygen to fractional inspired oxygen concentration (P/F) ratio exhibited a significant association with reintubation only in the respiratory insufficiency group (odds ratio (OR) 0.989, 95% confidence interval (CI) 0.980 to 0.999, p=0.036, and OR 0.989, 95% CI 0.979 to 0.999, p=0.026, in the univariate and multivariate analyses, respectively). In the propensity score analysis, a P/F ratio ≤ 200 may be a risk factor for reintubation in the respiratory insufficiency group (OR 7.811, 95% CI 1.345 to 45.367, p=0.022). In the nonrespiratory insufficiency group, intubation duration was significantly related to reintubation (OR 1.165, 95% CI 1.012 to 1.342, p=0.033, and OR 1.163, 95% CI 1.004 to 1.348, p=0.044, in the univariate and multivariate analyses, respectively). In conclusion, a low P/F ratio at extubation may be a risk factor for reintubation due to respiratory insufficiency. In the nonrespiratory insufficiency group, intubation duration may be significantly related to reintubation. The risk factors for reintubation may differ by the cause of reintubation. Further large-scale randomized controlled trials are required.


2021 ◽  
Vol In Press (In Press) ◽  
Author(s):  
Shirin Sayyahfar ◽  
Abdoulreza Esteghamati ◽  
Seyed Alireza Fahimzad ◽  
Safura Hajisadeghi Isfahani ◽  
Ali Nazari Alam ◽  
...  

Background: Streptococcus pneumoniae is recognized as one of the main pathogens inducing several invasive and non-invasive infections in children. Objective: The present study aimed to evaluate the serotype distribution of S. pneumoniae in six–month–old carriers. Methods: This study encompassed 600 six-month-old healthy infants whose pharyngeal swap samples were collected and then cultured to isolate S. pneumoniae. Twenty- five different serotypes were defined on positive culture samples by multiplex PCR. Results: In this study, 13 cases (2.2%) were positive S. pneumonia. The most common isolated serotypes of S. pneumoniae were serotypes 23F (n = 6, 1%) and 3 (n = 3, 0.5%), respectively. Notably, the most frequent serotype in formula-fed infants (n = 300) was Serotype 23F (n = 5, 1.7%); however, Serotype 3 (n = 3, 1%) was the most frequent one in breastfed participants (n = 300). According to the findings, the overall coverage of PCV10, PCV13, and PPSV23 on the S. pneumoniae serotypes at the age of six months was 50%, 73%, and 85%, respectively. Conclusions: At this age, the type of feeding could not significantly affect the frequency rate of S. pneumoniae colonization, while the serotype distributions in the two breastfed and formula-fed groups were different.


1992 ◽  
Vol 3 (4) ◽  
pp. 285-287 ◽  
Author(s):  
E J Beck ◽  
P D French ◽  
M H Helbert ◽  
D S Robinson ◽  
F M Moss ◽  
...  

For 227 episodes of Pneumocystis carinii pneumonia (PCP) treated at St Mary's between 1983 and 1989, factors predictive of fatal outcome were age, haemoglobin levels, peripheral lymphocyte count and alveolar-arterial oxygen gradient. Case fatality for the 47 empirically-treated episodes was significantly higher compared with the 180 cytologically proven episodes (55% vs 18%, χ2 = 25.7, P<0.0001). Case fatality for episodes which could not be bronchoscoped was significantly higher compared with bronchoscopy negative cases (66% vs 25%, χ2 = 4.5, P<0.05). Predictive factors for fatal outcome differed significantly for cases which could not be bronchoscoped and cytologically proven cases: haemoglobin level (10.7 g/dl vs 12.0 g/dl, P<0.001), lymphocyte count (0.64 × 109/l vs 0.87×109/l, P=0.05) and oxygen gradient (77.7 mmHg vs 58.9 mmHg, P<0.02). Such differences were not observed between bronchoscopy negative and cytologically proven cases. Case fatality decreased significantly over time ( b = –0.39, SE=0.14, P<0.05). Total and non-fatal first time episodes displayed an inverse relationship between oxygen gradient and time ( r = −0.22, P<0.006 and r = −0.24, P<0.01, respectively). Mean oxygen gradient of fatal episodes for sequential years increased significantly from 73 mmHg in 1983 to 102 mmHg in 1989 ( r = 0.92, P<0.01). This suggests that medical intervention as well as presentation with less severe disease both contributed to improved case fatality over time.


PEDIATRICS ◽  
1975 ◽  
Vol 55 (2) ◽  
pp. 232-235
Author(s):  
Gosta Rooth

Attention is called in this brief review article to the development and clinical uses of a new technique for monitoring blood oxygen tensions in newborn infants. This technique uses an electrode recently developed by Huch et al. in Germany to measure arterial oxygen tensions directly through the skin. This device allows for continuous monitoring with a non-invasive technique. The method is now in use in European hospitals. Clinical experiences are cited to document its usefulness.


Rheumatology ◽  
2020 ◽  
Vol 60 (1) ◽  
pp. 399-407 ◽  
Author(s):  
Jose Luis Rodriguez-Garcia ◽  
Gines Sanchez-Nievas ◽  
Juan Arevalo-Serrano ◽  
Cristina Garcia-Gomez ◽  
Jose Maria Jimenez-Vizuete ◽  
...  

Abstract Objectives The Janus kinase (JAK) inhibitor baricitinib may block viral entry into pneumocytes and prevent cytokine storm in patients with SARS-CoV-2 pneumonia. We aimed to assess whether baricitinib improved pulmonary function in patients treated with high-dose corticosteroids for moderate to severe SARS-CoV-2 pneumonia. Methods This observational study enrolled patients with moderate to severe SARS-CoV-2 pneumonia [arterial oxygen partial pressure (PaO2)/fraction of inspired oxygen (FiO2) &lt;200 mmHg] who received lopinavir/ritonavir and HCQ plus either corticosteroids (CS group, n = 50) or corticosteroids and baricitinib (BCT-CS group, n = 62). The primary end point was the change in oxygen saturation as measured by pulse oximetry (SpO2)/FiO2 from hospitalization to discharge. Secondary end points included the proportion of patients requiring supplemental oxygen at discharge and 1 month later. Statistics were adjusted by the inverse propensity score weighting (IPSW). Results A greater improvement in SpO2/FiO2 from hospitalization to discharge was observed in the BCT-CS vs CS group (mean differences adjusted for IPSW, 49; 95% CI: 22, 77; P &lt; 0.001). A higher proportion of patients required supplemental oxygen both at discharge (62.0% vs 25.8%; reduction of the risk by 82%, OR adjusted for IPSW, 0.18; 95% CI: 0.08, 0.43; P &lt; 0.001) and 1 month later (28.0% vs 12.9%, reduction of the risk by 69%, OR adjusted for IPSW, 0.31; 95% CI: 0.11, 0.86; P = 0.024) in the CS vs BCT-CS group. Conclusions . In patients with moderate to severe SARS-CoV-2 pneumonia a combination of baricitinib with corticosteroids was associated with greater improvement in pulmonary function when compared with corticosteroids alone. Trial registration European Network of Centres for Pharmacoepidemiology and Pharmacovigilance, ENCEPP (EUPAS34966, http://www.encepp.eu/encepp/viewResource.htm? id = 34967)


Author(s):  
R. Ubbink ◽  
M. A. Wefers Bettink ◽  
W. van Weteringen ◽  
E. G. Mik

Abstract 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.


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