Frank M P van Haren1,2, Lex M van Loon1, Anne Steins1, Thomas L Smoot3, Caitlin Sas3, Sabrina Staas3, Alicia B Vilaseca4, Ruben A Barbera4, Gustavo Vidmar4, Hugo Beccari4, Frida Popilevsky5, Eleonora Daribayeva5, Bhuvaneshwari Venkatesan5, Susan Mozes5, Rachel Postel5, Natalie Popilevski5, Andrew Webb6, Quentin Nunes7, John G Laffey8,9, Antonio Artigas10, Roger Smith11, Barry Dixon11, Alice Richardson12, Hwan-Jin Yoon12, Clive Page13. 1. Australian National University, College of Health and Medicine, Canberra, Australia. 2. Intensive Care Unit, Saint George Hospital, Sydney, Australia. 3. Frederick Health Hospital, Frederick, Maryland, USA. 4. Service of Haematology and Haemostasis, San Camilo Clinic, Buenos Aires, Argentina. 5. Surgical Intensive Care Unit, Coney Island Hospital, Brooklyn, New York, USA. 6. Clinical Pharmacology, School of Cardiovascular Medicine & Sciences, King's College, London, United Kingdom. 7. Institute of Systems, Molecular and Integrative Biology, University of Liverpool, Liverpool, United Kingdom. 8. Anaesthesia and Intensive Care Medicine, School of Medicine, and Regenerative Medicine Institute (REMEDI) at CÚRAM Centre for Research in Medical Devices, Biomedical Sciences Building, National University of Ireland Galway, Galway, Ireland. 9. Department of Anaesthesia, University Hospital Galway, Saolta Hospital Group, Ireland. 10. Critical Center, Corporació Universitaria Sanitaria Parc Tauli, CIBER Enfermedades Respiratorias, Autonomous University of Barcelona, Sabadell, Spain. 11. Department of Critical Care Medicine, St Vincent's Hospital, Melbourne, Australia. 12. Statistical Consulting Unit, Australian National University, Canberra, Australia. 13. Sackler Institute of Pulmonary Pharmacology, King's College London, United Kingdom.
Abstract
AIMS: To determine the safety and efficacy-potential of inhaled nebulised unfractionated heparin (UFH) in the treatment of hospitalised patients with COVID-19. METHODS: Retrospective, uncontrolled multicentre single-arm case series of hospitalised patients with laboratory-confirmed COVID-19, treated with inhaled nebulised UFH (5000 IU q8h, 10 000 IU q4h, or 25 000 IU q6h) for 6 ± 3 (mean ± standard deviation) days. Outcomes were activated partial thromboplastin time (APTT) before treatment (baseline) and highest-level during treatment (peak), and adverse events including bleeding. Exploratory efficacy outcomes were oxygenation, assessed by ratio of oxygen saturation to fraction of inspired oxygen (FiO2 ) and FiO2 , and the World Health Organisation modified ordinal clinical scale. RESULTS: There were 98 patients included. In patients on stable prophylactic or therapeutic systemic anticoagulant therapy but not receiving therapeutic UFH infusion, APTT levels increased from baseline of 34 ± 10 seconds to a peak of 38 ± 11 seconds (P < .0001). In 3 patients on therapeutic UFH infusion, APTT levels did not significantly increase from baseline of 72 ± 20 to a peak of 84 ± 28 seconds (P = .17). Two patients had serious adverse events: bleeding gastric ulcer requiring transfusion and thigh haematoma; both were on therapeutic anticoagulation. Minor bleeding occurred in 16 patients, 13 of whom were on therapeutic anticoagulation. The oxygen saturation/FiO2 ratio and the FiO2 worsened before and improved after commencement of inhaled UFH (change in slope, P < .001). CONCLUSION: Inhaled nebulised UFH in hospitalised patients with COVID-19 was safe. Although statistically significant, inhaled nebulised UFH did not produce a clinically relevant increase in APTT (peak values in the normal range). Urgent randomised evaluation of nebulised UFH in patients with COVID-19 is warranted and several studies are currently underway.
AIMS: To determine the safety and efficacy-potential of inhaled nebulised unfractionated heparin (UFH) in the treatment of hospitalised patients with COVID-19. METHODS: Retrospective, uncontrolled multicentre single-arm case series of hospitalised patients with laboratory-confirmed COVID-19, treated with inhaled nebulised UFH (5000 IU q8h, 10 000 IU q4h, or 25 000 IU q6h) for 6 ± 3 (mean ± standard deviation) days. Outcomes were activated partial thromboplastin time (APTT) before treatment (baseline) and highest-level during treatment (peak), and adverse events including bleeding. Exploratory efficacy outcomes were oxygenation, assessed by ratio of oxygen saturation to fraction of inspired oxygen (FiO2 ) and FiO2 , and the World Health Organisation modified ordinal clinical scale. RESULTS: There were 98 patients included. In patients on stable prophylactic or therapeutic systemic anticoagulant therapy but not receiving therapeutic UFH infusion, APTT levels increased from baseline of 34 ± 10 seconds to a peak of 38 ± 11 seconds (P < .0001). In 3 patients on therapeutic UFH infusion, APTT levels did not significantly increase from baseline of 72 ± 20 to a peak of 84 ± 28 seconds (P = .17). Two patients had serious adverse events: bleeding gastric ulcer requiring transfusion and thigh haematoma; both were on therapeutic anticoagulation. Minor bleeding occurred in 16 patients, 13 of whom were on therapeutic anticoagulation. The oxygen saturation/FiO2 ratio and the FiO2 worsened before and improved after commencement of inhaled UFH (change in slope, P < .001). CONCLUSION: Inhaled nebulised UFH in hospitalised patients with COVID-19 was safe. Although statistically significant, inhaled nebulised UFH did not produce a clinically relevant increase in APTT (peak values in the normal range). Urgent randomised evaluation of nebulised UFH in patients with COVID-19 is warranted and several studies are currently underway.
Authors: Adrian Ceccato; Marta Camprubí-Rimblas; Elena Campaña-Duel; Aina Areny-Balagueró; Luis Morales-Quinteros; Antonio Artigas Journal: J Clin Med Date: 2022-05-10 Impact factor: 4.964
Authors: Frank M P van Haren; John G Laffey; Antonio Artigas; Clive Page; Marcus J Schultz; David Cosgrave; Bairbre McNicholas; Thomas L Smoot; Quentin Nunes; Alice Richardson; Hwan-Jin Yoon; Lex M van Loon; Angajendra Ghosh; Simone Said; Rakshit Panwar; Roger Smith; John D Santamaria; Barry Dixon Journal: Br J Clin Pharmacol Date: 2022-02-20 Impact factor: 3.716