PMID- 35369798 OWN - NLM STAT- MEDLINE DCOM- 20220805 LR - 20221207 IS - 1525-1489 (Electronic) IS - 0885-0666 (Print) IS - 0885-0666 (Linking) VI - 37 IP - 8 DP - 2022 Aug TI - Compassionate use of Pulmonary Vasodilators in Acute Severe Hypoxic Respiratory Failure due to COVID-19. PG - 1101-1111 LID - 10.1177/08850666221086521 [doi] AB - 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. FAU - Matthews, Lewis AU - Matthews L AUID- ORCID: 0000-0001-5967-8615 AD - General Intensive Care Unit, 7425University Hospital Southampton NHS Foundation Trust, Tremona Road, Southampton, SO16 6YD. AD - NIHR Southampton Clinical Research Facility and NIHR Southampton Biomedical Research Centre, University Hospital Southamptom NHS Foundation Trust / University of Southampton, Tremona Road, Southampton, SO16 6YD. AD - 12211Faculty of Medicine, University of Southampton, University Hospital Southamptom NHS Foundation Trust, Tremona Road, Southampton, SO16 6YD. FAU - Baker, Laurence AU - Baker L AD - General Intensive Care Unit, 7425University Hospital Southampton NHS Foundation Trust, Tremona Road, Southampton, SO16 6YD. FAU - Ferrari, Matteo AU - Ferrari M AD - General Intensive Care Unit, 7425University Hospital Southampton NHS Foundation Trust, Tremona Road, Southampton, SO16 6YD. FAU - Sanchez, Weronika AU - Sanchez W AD - General Intensive Care Unit, 7425University Hospital Southampton NHS Foundation Trust, Tremona Road, Southampton, SO16 6YD. FAU - Pappachan, John AU - Pappachan J AD - NIHR Southampton Clinical Research Facility and NIHR Southampton Biomedical Research Centre, University Hospital Southamptom NHS Foundation Trust / University of Southampton, Tremona Road, Southampton, SO16 6YD. AD - 12211Faculty of Medicine, University of Southampton, University Hospital Southamptom NHS Foundation Trust, Tremona Road, Southampton, SO16 6YD. AD - Paediatric Intensive Care Unit, 7425University Hospital Southampton NHS Foundation Trust, Tremona Road, Southampton, SO16 6YD. FAU - Grocott, Mike Pw AU - Grocott MP AD - General Intensive Care Unit, 7425University Hospital Southampton NHS Foundation Trust, Tremona Road, Southampton, SO16 6YD. AD - NIHR Southampton Clinical Research Facility and NIHR Southampton Biomedical Research Centre, University Hospital Southamptom NHS Foundation Trust / University of Southampton, Tremona Road, Southampton, SO16 6YD. AD - 12211Faculty of Medicine, University of Southampton, University Hospital Southamptom NHS Foundation Trust, Tremona Road, Southampton, SO16 6YD. FAU - Dushianthan, Ahilanandan AU - Dushianthan A AD - General Intensive Care Unit, 7425University Hospital Southampton NHS Foundation Trust, Tremona Road, Southampton, SO16 6YD. AD - NIHR Southampton Clinical Research Facility and NIHR Southampton Biomedical Research Centre, University Hospital Southamptom NHS Foundation Trust / University of Southampton, Tremona Road, Southampton, SO16 6YD. AD - 12211Faculty of Medicine, University of Southampton, University Hospital Southamptom NHS Foundation Trust, Tremona Road, Southampton, SO16 6YD. CN - REACT COVID-19 investigators LA - eng PT - Journal Article DEP - 20220404 PL - United States TA - J Intensive Care Med JT - Journal of intensive care medicine JID - 8610344 RN - 0 (Prostaglandins) RN - 0 (Vasodilator Agents) RN - 31C4KY9ESH (Nitric Oxide) SB - IM MH - Administration, Inhalation MH - Adult MH - *COVID-19/complications MH - Compassionate Use Trials MH - Humans MH - Hypoxia/drug therapy/etiology MH - Nitric Oxide/therapeutic use MH - Prospective Studies MH - Prostaglandins/therapeutic use MH - *Respiratory Distress Syndrome MH - *Respiratory Insufficiency/drug therapy/etiology MH - SARS-CoV-2 MH - Vasodilator Agents/therapeutic use MH - *COVID-19 Drug Treatment PMC - PMC9353318 OTO - NOTNLM OT - ARDS OT - COVID-19 OT - Hypoxic respiratory failure OT - Iloprost OT - Intensive care OT - Nitric oxide OT - Pulmonary vasodilators COIS- Declaration of Conflicting Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article. EDAT- 2022/04/05 06:00 MHDA- 2022/08/06 06:00 PMCR- 2022/08/01 CRDT- 2022/04/04 05:23 PHST- 2022/04/05 06:00 [pubmed] PHST- 2022/08/06 06:00 [medline] PHST- 2022/04/04 05:23 [entrez] PHST- 2022/08/01 00:00 [pmc-release] AID - 10.1177_08850666221086521 [pii] AID - 10.1177/08850666221086521 [doi] PST - ppublish SO - J Intensive Care Med. 2022 Aug;37(8):1101-1111. doi: 10.1177/08850666221086521. Epub 2022 Apr 4.