Evidence map›Paper›PMID 34400339›Full record

ArticleNitric oxide : biology and chemistry2021

Inhaled high dose nitric oxide is a safe and effective respiratory treatment in spontaneous breathing hospitalized patients with COVID-19 pneumonia.

Bijan Safaee Fakhr, Raffaele Di Fenza, Stefano Gianni, Steffen B Wiegand, Yusuke Miyazaki, Caio C Araujo Morais, Lauren E Gibson, Marvin G Chang, Ariel L Mueller, Josanna M Rodriguez-Lopez and 9 more

2 registry-linked trialsOpen access · hybridAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Nitric oxide : biology and chemistry, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 2 registered trials, which are not on this map. Cited by 25 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
25citing papers in PubMed, 1 pooled it
8.1field-weighted citation impact, top 2% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT05612074 early_phase1active not recruitingnot on this mapstarted 2023, after this paper: background citation

Kinetics of Methemoglobin Concentration in Healthy Subjects Exposed to High Dose Inhaled Nitric Oxide

TypeinterventionalSponsorMassachusetts General HospitalRan2023 to 2027Enrolled10ConditionsHealthy SubjectsArmsInhaled Nitric Oxide
NCT06950294 early_phase1recruitingnot on this mapstarted 2026, after this paper: background citation

High Dose Inhaled Nitric Oxide Therapy in Critically Ill Patients With Pneumonia: a Pilot, Double-blinded, Randomized, Controlled Trial

TypeinterventionalSponsorMassachusetts General HospitalRan2026 to 2026Enrolled34ConditionsCritical Illness, PneumoniaArmsHigh dose inhaled nitric oxide, Sham treatment, standard therapy
3 · Its place in the literature

Who cites it

25 citing papers in PubMed, 1 synthesis or guideline pooled it, 67 citations in OpenAlex.

  1. Inhaled Nitric Oxide for Clinical Management of COVID-19: A Systematic Review and Meta-Analysis.International journal of environmental research and public health · 2022
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  14. Utility of NO and HNitric oxide : biology and chemistry · 2022
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  17. Nitric oxide: Clinical applications in critically ill patients.Nitric oxide : biology and chemistry · 2022
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

19 authors at 5 institutions in 1 country.

Bijan Safaee FakhrDepartment of Anaesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, 55 Fruit St, Boston, MA, 02114, USA; Harvard Medical School, 25 Shattuck St, Boston, MA, 02115, USA.
Raffaele Di FenzaDepartment of Anaesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, 55 Fruit St, Boston, MA, 02114, USA; Harvard Medical School, 25 Shattuck St, Boston, MA, 02115, USA.
Stefano GianniDepartment of Anaesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, 55 Fruit St, Boston, MA, 02114, USA; Harvard Medical School, 25 Shattuck St, Boston, MA, 02115, USA.
Steffen B WiegandDepartment of Anaesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, 55 Fruit St, Boston, MA, 02114, USA; Harvard Medical School, 25 Shattuck St, Boston, MA, 02115, USA.
Yusuke MiyazakiDepartment of Anaesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, 55 Fruit St, Boston, MA, 02114, USA; Harvard Medical School, 25 Shattuck St, Boston, MA, 02115, USA.
Caio C Araujo MoraisDepartment of Anaesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, 55 Fruit St, Boston, MA, 02114, USA; Harvard Medical School, 25 Shattuck St, Boston, MA, 02115, USA.
Lauren E GibsonDepartment of Anaesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, 55 Fruit St, Boston, MA, 02114, USA; Harvard Medical School, 25 Shattuck St, Boston, MA, 02115, USA.
Marvin G ChangDepartment of Anaesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, 55 Fruit St, Boston, MA, 02114, USA; Harvard Medical School, 25 Shattuck St, Boston, MA, 02115, USA.
Ariel L MuellerDepartment of Anaesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, 55 Fruit St, Boston, MA, 02114, USA; Harvard Medical School, 25 Shattuck St, Boston, MA, 02115, USA.
Josanna M Rodriguez-LopezHarvard Medical School, 25 Shattuck St, Boston, MA, 02115, USA; Pulmonary and Critical Care Medicine, Department of Medicine, Massachusetts General Hospital, 55 Fruit St, Boston, MA, 02114, USA.
Jeanne B AckmanHarvard Medical School, 25 Shattuck St, Boston, MA, 02115, USA; Division of Thoracic Imaging and Intervention, Department of Radiology, Massachusetts General Hospital, 55 Fruit St, Boston, MA, 02114, USA.
Pankaj AroraDivision of Cardiovascular Disease, University of Alabama at Birmingham, Tinsley Harrison Tower, Suite 311, 1900 University Boulevard, Birmingham, AL, 35233, USA.
Louie K ScottCritical Care Medicine, Department of Medicine, LSU Health Shreveport, 1501 Kings Hwy, Shreveport, LA, 71103, USA.
Donald B BlochDepartment of Anaesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, 55 Fruit St, Boston, MA, 02114, USA; Harvard Medical School, 25 Shattuck St, Boston, MA, 02115, USA; Center for Immunology and Inflammatory Diseases and Division of Rheumatology, Allergy, and Immunology, Department of Medicine, Massachusetts General Hospital, 55 Fruit St, Boston, MA, 02114, USA.
Warren M ZapolDepartment of Anaesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, 55 Fruit St, Boston, MA, 02114, USA; Harvard Medical School, 25 Shattuck St, Boston, MA, 02115, USA.
Ryan W CarrollHarvard Medical School, 25 Shattuck St, Boston, MA, 02115, USA; Division of Pediatric Critical Care Medicine, Department of Pediatrics, Massachusetts General Hospital, 55 Fruit St, Boston, MA, 02114, USA.
Fumito IchinoseDepartment of Anaesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, 55 Fruit St, Boston, MA, 02114, USA; Harvard Medical School, 25 Shattuck St, Boston, MA, 02115, USA.
Lorenzo BerraDepartment of Anaesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, 55 Fruit St, Boston, MA, 02114, USA; Harvard Medical School, 25 Shattuck St, Boston, MA, 02115, USA; Respiratory Care Services, Massachusetts General Hospital, 55 Fruit St, Boston, MA, 02114, USA. Electronic address: lberra@mgh.harvard.edu.
Nitric Oxide Study Investigators
Harvard University · USLemuel Shattuck Hospital · USMassachusetts General Hospital · USLouisiana State University Health Sciences Center Shreveport · USUniversity of Alabama at Birmingham · US

Funding

Role of sulfide catabolism in ischemic brain injuryR01NS112373 · NINDS · MASSACHUSETTS GENERAL HOSPITAL · PI ICHINOSE, FUMITO · 2019 to 2023
$1.7M
Hemolysis and Nitric OxideK23HL128882 · NHLBI · MASSACHUSETTS GENERAL HOSPITAL · PI BERRA, LORENZO · 2017 to 2021
$1.0M
Novel Antidotes for H2S PoisoningR21NS116671 · NINDS · MASSACHUSETTS GENERAL HOSPITAL · PI ICHINOSE, FUMITO, XIAN, MING · 2020 to 2021
$437k
NHLBI NIH HHS K23 HL128882NINDS NIH HHS R01 NS112373NINDS NIH HHS R21 NS116671
6 · The paper itself

Abstract

backgroundInhaled nitric oxide (NO) is a selective pulmonary vasodilator. In-vitro studies report that NO donors can inhibit replication of SARS-CoV-2. This multicenter study evaluated the feasibility and effects of high-dose inhaled NO in non-intubated spontaneously breathing patients with Coronavirus disease-2019 (COVID-19).

methodsThis is an interventional study to determine whether NO at 160 parts-per-million (ppm) inhaled for 30 min twice daily might be beneficial and safe in non-intubated COVID-19 patients.

resultsTwenty-nine COVID-19 patients received a total of 217 intermittent inhaled NO treatments for 30 min at 160 ppm between March and June 2020. Breathing NO acutely decreased the respiratory rate of tachypneic patients and improved oxygenation in hypoxemic patients. The maximum level of nitrogen dioxide delivered was 1.5 ppm. The maximum level of methemoglobin (MetHb) during the treatments was 4.7%. MetHb decreased in all patients 5 min after discontinuing NO administration. No adverse events during treatment, such as hypoxemia, hypotension, or acute kidney injury during hospitalization occurred. In our NO treated patients, one patient of 29 underwent intubation and mechanical ventilation, and none died. The median hospital length of stay was 6 days [interquartile range 4-8]. No discharged patients required hospital readmission nor developed COVID-19 related long-term sequelae within 28 days of follow-up.

conclusionsIn spontaneous breathing patients with COVID-19, the administration of inhaled NO at 160 ppm for 30 min twice daily promptly improved the respiratory rate of tachypneic patients and systemic oxygenation of hypoxemic patients. No adverse events were observed. None of the subjects was readmitted or had long-term COVID-19 sequelae.

Indexed as

COVID-19 Drug TreatmentHospitalizationAdministration, InhalationCOVID-19Dose-Response Relationship, DrugHumansNitric OxidePneumonia, ViralRespirationNitric OxideCOVID-19Nitric oxideViral pneumonia

Identifiers

PMID34400339
PMCPMC8361002
OpenAlexW3193631190

What OpenQuestion holds

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Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.