Anticoagulant therapy in acute respiratory distress syndrome

Camprubí-Rimblas, Marta; Tantinyà, Neus; Bringué, Josep; Guillamat-Prats, Raquel; Artigas, Antonio

doi:10.21037/atm.2018.01.08

Cited by 52 publications

(43 citation statements)

References 95 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Despite evidence about coagulation activation and impaired fibrinolysis leading to fibrin deposition in the alveolar compartment in non-COVID-19 ARDS patients [18], data about therapeutic anticoagulation's efficacy and safety is very limited in these patients [19]. Some recent investigations showed that low molecular weight heparin (LMWH) could reduce acute lung injury (ALI) in experimental models [20,21] [15].…”

Section: Discussionmentioning

confidence: 99%

Therapeutic versus prophylactic anticoagulation for severe COVID-19: A randomized phase II clinical trial (HESACOVID)

Lemos

Santo

Salvetti³

et al. 2020

Thrombosis Research

240

276

View full text Add to dashboard Cite

Introduction: Coronavirus disease 2019 (COVID-19) causes a hypercoagulable state. Several autopsy studies have found microthrombi in pulmonary circulation. Methods: In this randomized, open-label, phase II study, we randomized COVID-19 patients requiring mechanical ventilation to receive either therapeutic enoxaparin or the standard anticoagulant thromboprophylaxis. We evaluated the gas exchange over time through the ratio of partial pressure of arterial oxygen (PaO2) to the fraction of inspired oxygen (FiO2) at baseline, 7, and 14 days after randomization, the time until successful liberation from mechanical ventilation, and the ventilator-free days. Results: Ten patients were assigned to the therapeutic enoxaparin and ten patients to prophylactic anticoagulation. There was a statistically significant increase in the PaO2/FiO2 ratio over time in the therapeutic group (163 [95% confidence interval-CI 133-193] at baseline, 209 [95% CI 171-247] after 7 days, and 261 [95% CI 230-293] after 14 days), p = 0.0004. In contrast, we did not observe this improvement over time in the prophylactic group (184 [95% CI 146-222] at baseline, 168 [95% CI 142-195] after 7 days, and 195 [95% CI 128-262] after 14 days), p = 0.487. Patients of the therapeutic group had a higher ratio of successful liberation from mechanical ventilation (hazard ratio: 4.0 [95% CI 1.035-15.053]), p = 0.031 and more ventilator-free days (15 days [interquartile range IQR 6-16] versus 0 days [IQR 0-11]), p = 0.028 when compared to the prophylactic group. Conclusion: Therapeutic enoxaparin improves gas exchange and decreases the need for mechanical ventilation in severe COVID-19. Trial registration: REBEC RBR-949z6v.

show abstract

Section: Discussionmentioning

confidence: 99%

Therapeutic versus prophylactic anticoagulation for severe COVID-19: A randomized phase II clinical trial (HESACOVID)

Lemos

Santo

Salvetti³

et al. 2020

Thrombosis Research

240

276

View full text Add to dashboard Cite

show abstract

“…Nebulised UFH targets pulmonary fibrin deposition and inflammation, and local administration to the lungs allows higher dosages and increases local efficacy, reduces the risk of systemic bleeding and is more effective than intravenous administration [84,85]. Importantly, previous studies have shown that following nebulisation, UFH does not enter the systemic circulation significantly which means it can be used in addition to systemic therapeutic or prophylactic anti-coagulation without concerns of furthering systemic anti-coagulation.…”

Section: Anti-coagulant Effectsmentioning

confidence: 99%

Nebulised heparin as a treatment for COVID-19: scientific rationale and a call for randomised evidence

et al. 2020

Self Cite

View full text Add to dashboard Cite

Nebulised unfractionated heparin (UFH) has a strong scientific and biological rationale and warrants urgent investigation of its therapeutic potential, for COVID-19-induced acute respiratory distress syndrome (ARDS). COVID-19 ARDS displays 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. Patients infected with SARS-CoV-2 who manifest severe disease have high levels of inflammatory cytokines in plasma and bronchoalveolar lavage fluid and significant coagulopathy. There is a strong association between the extent of the coagulopathy and poor clinical outcomes. The anti-coagulant actions of nebulised UFH limit fibrin deposition and microvascular thrombosis. Trials in patients with acute lung injury and related conditions found inhaled UFH reduced pulmonary dead space, coagulation activation, microvascular thrombosis and clinical deterioration, resulting in increased time free of ventilatory support. In addition, UFH has anti-inflammatory, mucolytic and anti-viral properties and, specifically, has been shown to inactivate the SARS-CoV-2 virus and prevent its entry into mammalian cells, thereby inhibiting pulmonary infection by SARS-CoV-2. Furthermore, clinical studies have shown that inhaled UFH safely improves outcomes in other inflammatory respiratory diseases and also acts as an effective mucolytic in sputum-producing respiratory patients. UFH is widely available and inexpensive, which may make this treatment also accessible for low-and middle-income countries. These potentially important therapeutic properties of nebulised UFH underline the need for expedited large-scale clinical trials to test its potential to reduce mortality in COVID-19 patients.

show abstract

“…Adaptable nebulizer technology is ideal for combination in aerosol delivery systems where the objective is to augment lung dose by controlling, and possibly calculating and adapting to, a patient's breathing patterns. The role of nebulizers in treating respiratory disease, and symptoms of disease is the subject of numerous recent reviews, including in acute respiratory distress syndrome (ARDS) [2,3], chronic obstructive pulmonary disorder (COPD) [4,5], cystic fibrosis (CF) [6,7], ventilator-associated pneumonia (VAP) [8,9], dyspnea [10], and acute asthma [11], among others.…”

Section: Introductionmentioning

confidence: 99%

Future Trends in Nebulized Therapies for Pulmonary Disease

McCarthy

González

Higgins

2020

JPM

View full text Add to dashboard Cite

Aerosol therapy is a key modality for drug delivery to the lungs of respiratory disease patients. Aerosol therapy improves therapeutic effects by directly targeting diseased lung regions for rapid onset of action, requiring smaller doses than oral or intravenous delivery and minimizing systemic side effects. In order to optimize treatment of critically ill patients, the efficacy of aerosol therapy depends on lung morphology, breathing patterns, aerosol droplet characteristics, disease, mechanical ventilation, pharmacokinetics, and the pharmacodynamics of cell-drug interactions. While aerosol characteristics are influenced by drug formulations and device mechanisms, most other factors are reliant on individual patient variables. This has led to increased efforts towards more personalized therapeutic approaches to optimize pulmonary drug delivery and improve selection of effective drug types for individual patients. Vibrating mesh nebulizers (VMN) are the dominant device in clinical trials involving mechanical ventilation and emerging drugs. In this review, we consider the use of VMN during mechanical ventilation in intensive care units. We aim to link VMN fundamentals to applications in mechanically ventilated patients and look to the future use of VMN in emerging personalized therapeutic drugs.

show abstract

Anticoagulant therapy in acute respiratory distress syndrome

Cited by 52 publications

References 95 publications

Therapeutic versus prophylactic anticoagulation for severe COVID-19: A randomized phase II clinical trial (HESACOVID)

Therapeutic versus prophylactic anticoagulation for severe COVID-19: A randomized phase II clinical trial (HESACOVID)

Nebulised heparin as a treatment for COVID-19: scientific rationale and a call for randomised evidence

Future Trends in Nebulized Therapies for Pulmonary Disease

Contact Info

Product

Resources

About