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
1101-1111
Matthews, Lewis
81327a4c-b2a8-44f9-b5b2-fc04f856a930
Baker, Laurence
2f9d9510-e044-4fdc-bd40-99d71e1a5314
Ferrari, Matteo
c31e1074-bdf3-47bb-915a-407add15e8ba
Sanchez, Weronika
060b1e07-5894-44be-b365-63bbe418a2c1
Pappachan, John
8e1bd6bd-1cb9-4dd9-a9af-b9eed5459148
Grocott, Mike Pw
1e87b741-513e-4a22-be13-0f7bb344e8c2
Dushianthan, Ahilanandan
013692a2-cf26-4278-80bd-9d8fcdb17751
Wilkinson, Thomas
8c55ebbb-e547-445c-95a1-c8bed02dd652
Burke, Hannah
a9bb9391-4704-4584-aeb7-e69fe0acbdb8
Freeman, Anna
b5f45a0d-f9e4-4a91-9af0-40efb6730787
Celinski, Michael
f5ddadb6-e935-476c-ab46-0423a031a83b
Faust, Saul
f97df780-9f9b-418e-b349-7adf63e150c1
Thomas, Gareth
2ff54aa9-a766-416b-91ee-cf1c5be74106
Kipps, Christopher
e43be016-2dc2-45e6-9a02-ab2a0e0208d5
REACT COVID-19 investigators
August 2022
Matthews, Lewis
81327a4c-b2a8-44f9-b5b2-fc04f856a930
Baker, Laurence
2f9d9510-e044-4fdc-bd40-99d71e1a5314
Ferrari, Matteo
c31e1074-bdf3-47bb-915a-407add15e8ba
Sanchez, Weronika
060b1e07-5894-44be-b365-63bbe418a2c1
Pappachan, John
8e1bd6bd-1cb9-4dd9-a9af-b9eed5459148
Grocott, Mike Pw
1e87b741-513e-4a22-be13-0f7bb344e8c2
Dushianthan, Ahilanandan
013692a2-cf26-4278-80bd-9d8fcdb17751
Wilkinson, Thomas
8c55ebbb-e547-445c-95a1-c8bed02dd652
Burke, Hannah
a9bb9391-4704-4584-aeb7-e69fe0acbdb8
Freeman, Anna
b5f45a0d-f9e4-4a91-9af0-40efb6730787
Celinski, Michael
f5ddadb6-e935-476c-ab46-0423a031a83b
Faust, Saul
f97df780-9f9b-418e-b349-7adf63e150c1
Thomas, Gareth
2ff54aa9-a766-416b-91ee-cf1c5be74106
Kipps, Christopher
e43be016-2dc2-45e6-9a02-ab2a0e0208d5
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), .
(doi:10.1177/08850666221086521).
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.
Text
JICM Revised IPVD manuscript v2.0 210222
- Accepted Manuscript
More information
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
Catalogue record
Date deposited: 10 Aug 2022 17:25
Last modified: 22 Apr 2024 01:52
Export record
Altmetrics
Contributors
Author:
Lewis Matthews
Author:
Laurence Baker
Author:
Matteo Ferrari
Author:
Weronika Sanchez
Author:
John Pappachan
Author:
Ahilanandan Dushianthan
Author:
Hannah Burke
Author:
Anna Freeman
Author:
Michael Celinski
Author:
Christopher Kipps
Corporate Author: REACT COVID-19 investigators
Download statistics
Downloads from ePrints over the past year. Other digital versions may also be available to download e.g. from the publisher's website.
View more statistics