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Compassionate use of Pulmonary Vasodilators in Acute Severe Hypoxic Respiratory Failure due to COVID-19

Compassionate use of Pulmonary Vasodilators in Acute Severe Hypoxic Respiratory Failure due to COVID-19
Compassionate use of Pulmonary Vasodilators in Acute Severe Hypoxic Respiratory Failure due to COVID-19

Background: there have been over 200 million cases and 4.4 million deaths from COVID-19 worldwide. Despite the lack of robust evidence one potential treatment for COVID-19 associated severe hypoxaemia is inhaled pulmonary vasodilator (IPVD) therapy, using either nitric oxide (iNO) or prostaglandins. We describe the implementation of, and outcomes from, a protocol using IPVDs in a cohort of patients with severe COVID-19 associated respiratory failure receiving maximal conventional support. 

Methods: prospectively collected data from adult patients with SARS-CoV-2 admitted to the intensive care unit (ICU) at a large teaching hospital were analysed for the period 14 th March 2020 - 11 th February 2021. An IPVD was considered if the PaO 2/FiO 2 (PF) ratio was less than 13.3kPa despite maximal conventional therapy. Nitric oxide was commenced at 20ppm and titrated to response. If oxygenation improved Iloprost nebulisers were commenced and iNO weaned. The primary outcome was percentage changes in PF ratio and Alveolar-arterial (A-a) gradient. 

Results: fifty-nine patients received IPVD therapy during the study period. The median PF ratio before IPVD therapy was commenced was 11.33kPa (9.93-12.91). Patients receiving an IPVD had a lower PF ratio (14.37 vs. 16.37kPa, p = 0.002) and higher APACHE-II score (17 vs. 13, p = 0.028) at ICU admission. At 72 hours after initiating an IPVD the median improvement in PF ratio was 33.9% (-4.3-84.1). At 72 hours changes in PF ratio (70.8 vs. −4.1%, p < 0.001) and reduction in A-a gradient (44.7 vs. 14.8%, p < 0.001) differed significantly between survivors (n = 33) and non-survivors (n = 26). 

Conclusions: the response to IPVDs in patients with COVID-19 associated acute hypoxic respiratory failure differed significantly between survivors and non-survivors. Both iNO and prostaglandins may offer therapeutic options for patients with severe refractory hypoxaemia due to COVID-19. The use of inhaled prostaglandins, and iNO where feasible, should be studied in adequately powered prospective randomised trials.

ARDS, COVID-19, Hypoxic respiratory failure, Iloprost, Intensive care, Nitric oxide, Pulmonary vasodilators
0885-0666
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Matthews, Lewis
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Baker, Laurence
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Ferrari, Matteo
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Sanchez, Weronika
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Pappachan, John
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Grocott, Mike Pw
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Dushianthan, Ahilanandan
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Wilkinson, Thomas
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Burke, Hannah
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Freeman, Anna
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Celinski, Michael
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Faust, Saul
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Thomas, Gareth
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Kipps, Christopher
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REACT COVID-19 investigators
Matthews, Lewis
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Baker, Laurence
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Ferrari, Matteo
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Sanchez, Weronika
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Pappachan, John
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Grocott, Mike Pw
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Dushianthan, Ahilanandan
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Wilkinson, Thomas
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Burke, Hannah
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Freeman, Anna
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Celinski, Michael
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Faust, Saul
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Thomas, Gareth
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Kipps, Christopher
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Matthews, Lewis, Baker, Laurence, Ferrari, Matteo, Sanchez, Weronika, Pappachan, John, Grocott, Mike Pw, Dushianthan, Ahilanandan, Wilkinson, Thomas, Burke, Hannah, Freeman, Anna, Celinski, Michael, Faust, Saul, Thomas, Gareth and Kipps, Christopher , REACT COVID-19 investigators (2022) Compassionate use of Pulmonary Vasodilators in Acute Severe Hypoxic Respiratory Failure due to COVID-19. Journal of Intensive Care Medicine, 37 (8), 1101-1111. (doi:10.1177/08850666221086521).

Record type: Article

Abstract

Background: there have been over 200 million cases and 4.4 million deaths from COVID-19 worldwide. Despite the lack of robust evidence one potential treatment for COVID-19 associated severe hypoxaemia is inhaled pulmonary vasodilator (IPVD) therapy, using either nitric oxide (iNO) or prostaglandins. We describe the implementation of, and outcomes from, a protocol using IPVDs in a cohort of patients with severe COVID-19 associated respiratory failure receiving maximal conventional support. 

Methods: prospectively collected data from adult patients with SARS-CoV-2 admitted to the intensive care unit (ICU) at a large teaching hospital were analysed for the period 14 th March 2020 - 11 th February 2021. An IPVD was considered if the PaO 2/FiO 2 (PF) ratio was less than 13.3kPa despite maximal conventional therapy. Nitric oxide was commenced at 20ppm and titrated to response. If oxygenation improved Iloprost nebulisers were commenced and iNO weaned. The primary outcome was percentage changes in PF ratio and Alveolar-arterial (A-a) gradient. 

Results: fifty-nine patients received IPVD therapy during the study period. The median PF ratio before IPVD therapy was commenced was 11.33kPa (9.93-12.91). Patients receiving an IPVD had a lower PF ratio (14.37 vs. 16.37kPa, p = 0.002) and higher APACHE-II score (17 vs. 13, p = 0.028) at ICU admission. At 72 hours after initiating an IPVD the median improvement in PF ratio was 33.9% (-4.3-84.1). At 72 hours changes in PF ratio (70.8 vs. −4.1%, p < 0.001) and reduction in A-a gradient (44.7 vs. 14.8%, p < 0.001) differed significantly between survivors (n = 33) and non-survivors (n = 26). 

Conclusions: the response to IPVDs in patients with COVID-19 associated acute hypoxic respiratory failure differed significantly between survivors and non-survivors. Both iNO and prostaglandins may offer therapeutic options for patients with severe refractory hypoxaemia due to COVID-19. The use of inhaled prostaglandins, and iNO where feasible, should be studied in adequately powered prospective randomised trials.

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JICM Revised IPVD manuscript v2.0 210222 - Accepted Manuscript
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Accepted/In Press date: 23 February 2022
Published date: August 2022
Additional Information: MPWG is in part funded by the NIHR Senior Investigator Scheme. MPWG is in part funded by the Southampton NIHR Biomedical Research Centre.
Keywords: ARDS, COVID-19, Hypoxic respiratory failure, Iloprost, Intensive care, Nitric oxide, Pulmonary vasodilators

Identifiers

Local EPrints ID: 468321
URI: http://eprints.soton.ac.uk/id/eprint/468321
ISSN: 0885-0666
PURE UUID: 72830cd2-7159-4021-84d0-203b9390a0d5
ORCID for Mike Pw Grocott: ORCID iD orcid.org/0000-0002-9484-7581
ORCID for Ahilanandan Dushianthan: ORCID iD orcid.org/0000-0002-0165-3359
ORCID for Hannah Burke: ORCID iD orcid.org/0000-0003-3553-4590
ORCID for Anna Freeman: ORCID iD orcid.org/0000-0003-3495-2520
ORCID for Saul Faust: ORCID iD orcid.org/0000-0003-3410-7642

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Date deposited: 10 Aug 2022 17:25
Last modified: 17 Mar 2024 04:06

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Contributors

Author: Lewis Matthews
Author: Laurence Baker
Author: Matteo Ferrari
Author: Weronika Sanchez
Author: John Pappachan
Author: Mike Pw Grocott ORCID iD
Author: Ahilanandan Dushianthan ORCID iD
Author: Hannah Burke ORCID iD
Author: Anna Freeman ORCID iD
Author: Michael Celinski
Author: Saul Faust ORCID iD
Author: Gareth Thomas
Author: Christopher Kipps
Corporate Author: REACT COVID-19 investigators

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