scholarly journals Can Nebulised Heparin Reduce Time to Extubation in SARS-CoV-2 (CHARTER Study) – Protocol

Author(s):  
Barry Dixon ◽  
Roger J Smith ◽  
Antonio Artigas ◽  
John Laffey ◽  
Bairbre McNicholas ◽  
...  

AbstractIntroductionCOVID-19 is associated with the development of ARDS displaying the typical features of diffuse alveolar damage with extensive pulmonary coagulation activation resulting in fibrin deposition in the microvasculature and formation of hyaline membranes in the air sacs. The anti-coagulant actions of nebulised heparin limit fibrin deposition and progression of lung injury. Serendipitously, unfractionated heparin also inactivates the SARS-CoV-2 virus and prevents its entry into mammalian cells. Nebulisation of heparin may therefore limit both fibrin-mediated lung injury and inhibit pulmonary infection by SARS-CoV-2. For these reasons we have initiated a multi-centre international trial of nebulised heparin in patients with COVID-19.Methods and interventionMechanically ventilated patients with confirmed or strongly suspected SARS-CoV-2 infection, hypoxaemia and an acute pulmonary opacity in at least one lung quadrant on chest X-ray, will be randomised to nebulised heparin 25,000 Units every 6 hours or standard care for up to 10 days while mechanically ventilated. The primary outcome is the time to separation from invasive ventilation to day 28, where non-survivors to day 28 are treated as though not separated from invasive ventilation.Ethics and disseminationThe study protocol has been submitted to the human research and ethics committee of St Vincent’s Hospital, Melbourne, Australia. Submission is pending in other jurisdictions. Results of this study will be published in scientific journals and presented at scientific meetings.Trial RegistrationACTRN: 12620000517976

2006 ◽  
Vol 104 (2) ◽  
pp. 278-289 ◽  
Author(s):  
Marcelo Gama de Abreu ◽  
André Domingues Quelhas ◽  
Peter Spieth ◽  
Götz Bräuer ◽  
Lilla Knels ◽  
...  

Background It is currently not known whether vaporized perfluorohexane is superior to partial liquid ventilation (PLV) for therapy of acute lung injury. In this study, the authors compared the effects of both therapies in oleic acid-induced lung injury. Methods Lung injury was induced in 30 anesthetized and mechanically ventilated pigs by means of central venous infusion of oleic acid. Animals were assigned to one of the following groups: (1) control or gas ventilation (GV), (2) 2.5% perfluorohexane vapor, (3) 5% perfluorohexane vapor, (4) 10% perfluorohexane vapor, or (5) PLV with perfluorooctane (30 ml/kg). Two hours after randomization, lungs were recruited and positive end-expiratory pressure was adjusted to obtain minimal elastance. Ventilation was continued during 4 additional hours, when animals were killed for lung histologic examination. Results Gas exchange and elastance were comparable among vaporized perfluorohexane, PLV, and GV before the open lung approach was used and improved in a similar fashion in all groups after positive end-expiratory pressure was adjusted to optimal elastance (P < 0.05). A similar behavior was observed in functional residual capacity (FRC) in animals treated with vaporized perfluorohexane and GV. Lung resistance improved after recruitment (P < 0.05), but values were higher in the 10% perfluorohexane and PLV groups as compared with GV (P < 0.05). Interestingly, positive end-expiratory pressure values required to obtain minimal elastance were lower with 5% perfluorohexane than with PLV and GV (P < 0.05). In addition, diffuse alveolar damage was significantly lower in the 5% and 10% perfluorohexane vapor groups as compared with PLV and GV (P < 0.05). Conclusions Although the use of 5% vaporized perfluorohexane permitted the authors to reduce pressures needed to stabilize the lungs and was associated with better histologic findings than were PLV and GV, none of these perfluorocarbon therapies improved gas exchange or lung mechanics as compared with GV.


2018 ◽  
Vol 128 (6) ◽  
pp. 1193-1206 ◽  
Author(s):  
Raquel S. Santos ◽  
Ligia de A. Maia ◽  
Milena V. Oliveira ◽  
Cíntia L. Santos ◽  
Lillian Moraes ◽  
...  

Abstract Background The authors hypothesized that low tidal volume (VT) would minimize ventilator-induced lung injury regardless of the degree of mechanical power. The authors investigated the impact of power, obtained by different combinations of VT and respiratory rate (RR), on ventilator-induced lung injury in experimental mild acute respiratory distress syndrome (ARDS). Methods Forty Wistar rats received Escherichia coli lipopolysaccharide intratracheally. After 24 h, 32 rats were randomly assigned to be mechanically ventilated (2 h) with a combination of different VT (6 ml/kg and 11 ml/kg) and RR that resulted in low and high power. Power was calculated as energy (ΔP,L2/E,L) × RR (ΔP,L = transpulmonary driving pressure; E,L = lung elastance), and was threefold higher in high than in low power groups. Eight rats were not mechanically ventilated and used for molecular biology analysis. Results Diffuse alveolar damage score, which represents the severity of edema, atelectasis, and overdistension, was increased in high VT compared to low VT, in both low (low VT: 11 [9 to 14], high VT: 18 [15 to 20]) and high (low VT: 19 [16 to 25], high VT: 29 [27 to 30]) power groups. At high VT, interleukin-6 and amphiregulin expressions were higher in high-power than in low-power groups. At high power, amphiregulin and club cell protein 16 expressions were higher in high VT than in low VT. Mechanical energy and power correlated well with diffuse alveolar damage score and interleukin-6, amphiregulin, and club cell protein 16 expression. Conclusions In experimental mild ARDS, even at low VT, high mechanical power promoted ventilator-induced lung injury. To minimize ventilator-induced lung injury, low VT should be combined with low power.


Children ◽  
2021 ◽  
Vol 8 (2) ◽  
pp. 132
Author(s):  
Vikramaditya Dumpa ◽  
Vineet Bhandari

Recent advances in neonatology have led to the increased survival of extremely low-birth weight infants. However, the incidence of bronchopulmonary dysplasia (BPD) has not improved proportionally, partly due to increased survival of extremely premature infants born at the late-canalicular stage of lung development. Due to minimal surfactant production at this stage, these infants are at risk for severe respiratory distress syndrome, needing prolonged ventilation. While the etiology of BPD is multifactorial with antenatal, postnatal, and genetic factors playing a role, ventilator-induced lung injury is a major, potentially modifiable, risk factor implicated in its causation. Infants with BPD are at a higher risk of developing complications including sepsis, pulmonary arterial hypertension, respiratory failure, and death. Long-term problems include increased risk of hospital readmissions, respiratory infections, and asthma-like symptoms during infancy and childhood. Survivors who have BPD are also at increased risk of poor neurodevelopmental outcomes. While the ultimate solution for avoiding BPD lies in the prevention of preterm births, strategies to decrease its incidence are the need of the hour. It is time to focus on gentler modes of ventilation and the use of less invasive surfactant administration techniques to mitigate lung injury, thereby potentially decreasing the burden of BPD. In this article, we discuss the use of non-invasive ventilation in premature infants, with an emphasis on studies showing an effect on BPD with different modes of non-invasive ventilation. Practical considerations in the use of nasal intermittent positive pressure ventilation are also discussed, considering the significant heterogeneity in clinical practices and management strategies in its use.


Author(s):  
Emanuela Barisione ◽  
Federica Grillo ◽  
Lorenzo Ball ◽  
Rita Bianchi ◽  
Marco Grosso ◽  
...  

Abstract Data on the pathology of COVID-19 are scarce; available studies show diffuse alveolar damage; however, there is scarce information on the chronologic evolution of COVID-19 lung lesions. The primary aim of the study is to describe the chronology of lung pathologic changes in COVID-19 by using a post-mortem transbronchial lung cryobiopsy approach. Our secondary aim is to correlate the histologic findings with computed tomography patterns. SARS-CoV-2-positive patients, who died while intubated and mechanically ventilated, were enrolled. The procedure was performed 30 min after death, and all lung lobes sampled. Histopathologic analysis was performed on thirty-nine adequate samples from eight patients: two patients (illness duration < 14 days) showed early/exudative phase diffuse alveolar damage, while the remaining 6 patients (median illness duration—32 days) showed progressive histologic patterns (3 with mid/proliferative phase; 3 with late/fibrotic phase diffuse alveolar damage, one of which with honeycombing). Immunohistochemistry for SARS-CoV-2 nucleocapsid protein was positive predominantly in early-phase lesions. Histologic patterns and tomography categories were correlated: early/exudative phase was associated with ground-glass opacity, mid/proliferative lesions with crazy paving, while late/fibrous phase correlated with the consolidation pattern, more frequently seen in the lower/middle lobes. This study uses an innovative cryobiopsy approach for the post-mortem sampling of lung tissues from COVID-19 patients demonstrating the progression of fibrosis in time and correlation with computed tomography features. These findings may prove to be useful in the correct staging of disease, and this could have implications for treatment and patient follow-up.


Trials ◽  
2013 ◽  
Vol 14 (1) ◽  
pp. 100 ◽  
Author(s):  
Dhruv Parekh ◽  
Rachel C A Dancer ◽  
Sian Lax ◽  
Mark S Cooper ◽  
Adrian R Martineau ◽  
...  

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