PMID- 34984714
OWN - NLM
STAT- MEDLINE
DCOM- 20220517
LR  - 20221207
IS  - 1365-2125 (Electronic)
IS  - 0306-5251 (Linking)
VI  - 88
IP  - 6
DP  - 2022 Jun
TI  - Inhaled nebulised unfractionated heparin for the treatment of hospitalised 
      patients with COVID-19: A multicentre case series of 98 patients.
PG  - 2802-2813
LID - 10.1111/bcp.15212 [doi]
AB  - 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 (FiO(2) ) and FiO(2) , 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/FiO(2) ratio and the 
      FiO(2) 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.
CI  - (c) 2022 British Pharmacological Society.
FAU - van Haren, Frank M P
AU  - van Haren FMP
AUID- ORCID: 0000-0001-8037-4229
AD  - Australian National University, College of Health and Medicine, Canberra, 
      Australia.
AD  - Intensive Care Unit, Saint George Hospital, Sydney, Australia.
FAU - van Loon, Lex M
AU  - van Loon LM
AD  - Australian National University, College of Health and Medicine, Canberra, 
      Australia.
FAU - Steins, Anne
AU  - Steins A
AD  - Australian National University, College of Health and Medicine, Canberra, 
      Australia.
FAU - Smoot, Thomas L
AU  - Smoot TL
AUID- ORCID: 0000-0002-6188-2217
AD  - Frederick Health Hospital, Frederick, Maryland, USA.
FAU - Sas, Caitlin
AU  - Sas C
AD  - Frederick Health Hospital, Frederick, Maryland, USA.
FAU - Staas, Sabrina
AU  - Staas S
AD  - Frederick Health Hospital, Frederick, Maryland, USA.
FAU - Vilaseca, Alicia B
AU  - Vilaseca AB
AD  - Service of Haematology and Haemostasis, San Camilo Clinic, Buenos Aires, 
      Argentina.
FAU - Barbera, Ruben A
AU  - Barbera RA
AD  - Service of Haematology and Haemostasis, San Camilo Clinic, Buenos Aires, 
      Argentina.
FAU - Vidmar, Gustavo
AU  - Vidmar G
AD  - Service of Haematology and Haemostasis, San Camilo Clinic, Buenos Aires, 
      Argentina.
FAU - Beccari, Hugo
AU  - Beccari H
AD  - Service of Haematology and Haemostasis, San Camilo Clinic, Buenos Aires, 
      Argentina.
FAU - Popilevsky, Frida
AU  - Popilevsky F
AD  - Surgical Intensive Care Unit, Coney Island Hospital, Brooklyn, New York, USA.
FAU - Daribayeva, Eleonora
AU  - Daribayeva E
AD  - Surgical Intensive Care Unit, Coney Island Hospital, Brooklyn, New York, USA.
FAU - Venkatesan, Bhuvaneshwari
AU  - Venkatesan B
AD  - Surgical Intensive Care Unit, Coney Island Hospital, Brooklyn, New York, USA.
FAU - Mozes, Susan
AU  - Mozes S
AD  - Surgical Intensive Care Unit, Coney Island Hospital, Brooklyn, New York, USA.
FAU - Postel, Rachel
AU  - Postel R
AD  - Surgical Intensive Care Unit, Coney Island Hospital, Brooklyn, New York, USA.
FAU - Popilevski, Natalie
AU  - Popilevski N
AD  - Surgical Intensive Care Unit, Coney Island Hospital, Brooklyn, New York, USA.
FAU - Webb, Andrew
AU  - Webb A
AUID- ORCID: 0000-0002-8109-1877
AD  - Clinical Pharmacology, School of Cardiovascular Medicine & Sciences, King's 
      College, London, United Kingdom.
FAU - Nunes, Quentin
AU  - Nunes Q
AD  - Institute of Systems, Molecular and Integrative Biology, University of Liverpool, 
      Liverpool, United Kingdom.
FAU - Laffey, John G
AU  - Laffey JG
AUID- ORCID: 0000-0002-1246-9573
AD  - Anaesthesia and Intensive Care Medicine, School of Medicine, and Regenerative 
      Medicine Institute (REMEDI) at CURAM Centre for Research in Medical Devices, 
      Biomedical Sciences Building, National University of Ireland Galway, Galway, 
      Ireland.
AD  - Department of Anaesthesia, University Hospital Galway, Saolta Hospital Group, 
      Ireland.
FAU - Artigas, Antonio
AU  - Artigas A
AD  - Critical Center, Corporacio Universitaria Sanitaria Parc Tauli, CIBER 
      Enfermedades Respiratorias, Autonomous University of Barcelona, Sabadell, Spain.
FAU - Smith, Roger
AU  - Smith R
AD  - Department of Critical Care Medicine, St Vincent's Hospital, Melbourne, 
      Australia.
FAU - Dixon, Barry
AU  - Dixon B
AD  - Department of Critical Care Medicine, St Vincent's Hospital, Melbourne, 
      Australia.
FAU - Richardson, Alice
AU  - Richardson A
AD  - Statistical Consulting Unit, Australian National University, Canberra, Australia.
FAU - Yoon, Hwan-Jin
AU  - Yoon HJ
AD  - Statistical Consulting Unit, Australian National University, Canberra, Australia.
FAU - Page, Clive
AU  - Page C
AD  - Sackler Institute of Pulmonary Pharmacology, King's College London, United 
      Kingdom.
LA  - eng
PT  - Journal Article
PT  - Multicenter Study
DEP - 20220119
PL  - England
TA  - Br J Clin Pharmacol
JT  - British journal of clinical pharmacology
JID - 7503323
RN  - 0 (Anticoagulants)
RN  - 9005-49-6 (Heparin)
SB  - IM
MH  - Anticoagulants
MH  - Hemorrhage/chemically induced/drug therapy
MH  - *Heparin/adverse effects
MH  - Humans
MH  - Partial Thromboplastin Time
MH  - Retrospective Studies
MH  - *COVID-19 Drug Treatment
OTO - NOTNLM
OT  - COVID-19
OT  - SARS-CoV-2
OT  - case series
OT  - inhaled heparin
OT  - nebulised heparin
OT  - pandemic
OT  - respiratory failure
OT  - unfractionated heparin
EDAT- 2022/01/06 06:00
MHDA- 2022/05/18 06:00
CRDT- 2022/01/05 06:10
PHST- 2021/12/19 00:00 [revised]
PHST- 2021/02/08 00:00 [received]
PHST- 2021/12/27 00:00 [accepted]
PHST- 2022/01/06 06:00 [pubmed]
PHST- 2022/05/18 06:00 [medline]
PHST- 2022/01/05 06:10 [entrez]
AID - 10.1111/bcp.15212 [doi]
PST - ppublish
SO  - Br J Clin Pharmacol. 2022 Jun;88(6):2802-2813. doi: 10.1111/bcp.15212. Epub 2022 
      Jan 19.