Conv. Plasma
Nigella Sativa
Peg.. Lambda

All nitric oxide studies
Meta analysis
Home COVID-19 treatment researchNitric OxideNitric Oxide (more..)
Melatonin Meta
Bromhexine Meta Metformin Meta
Budesonide Meta
Cannabidiol Meta Molnupiravir Meta
Colchicine Meta
Conv. Plasma Meta
Curcumin Meta Nigella Sativa Meta
Ensovibep Meta Nitazoxanide Meta
Famotidine Meta Paxlovid Meta
Favipiravir Meta Peg.. Lambda Meta
Fluvoxamine Meta Quercetin Meta
Hydroxychlor.. Meta Remdesivir Meta
Ivermectin Meta
Lactoferrin Meta

All Studies   Meta Analysis   Recent:  
0 0.5 1 1.5 2+ Ventilation -179% Improvement Relative Risk Hospitalization 21% Return to ER -38% Nitric Oxide  Strickland et al.  LATE TREATMENT  RCT Is late treatment with nitric oxide beneficial for COVID-19? RCT 34 patients in the USA Trial underpowered to detect differences Strickland et al., The American J. Eme.., May 2022 Favors nitric oxide Favors control

Safety and practicality of high dose inhaled nitric oxide in emergency department COVID-19 patients

Strickland et al., The American Journal of Emergency Medicine, doi:10.1016/j.ajem.2022.04.052
May 2022  
  Source   PDF   All Studies   Meta AnalysisMeta
Early terminated RCT with 47 ER patients in the USA, less than 12 days of symptoms, showing no significant difference in outcomes with a single high-dose administration of inhaled nitric oxide by mask, 250ppm for 30 min.
Targeted administration to the respiratory tract provides treatment directly to the typical source of initial SARS-CoV-2 infection and replication, and allows for rapid onset of action, higher local drug concentration, and reduced systemic side effects (early treatment may be more beneficial).
risk of mechanical ventilation, 178.9% higher, RR 2.79, p = 1.00, treatment 1 of 19 (5.3%), control 0 of 15 (0.0%), continuity correction due to zero event (with reciprocal of the contrasting arm).
risk of hospitalization, 21.1% lower, RR 0.79, p = 1.00, treatment 1 of 19 (5.3%), control 1 of 15 (6.7%), NNT 71.
return to ER, 38.2% higher, RR 1.38, p = 0.72, treatment 7 of 19 (36.8%), control 4 of 15 (26.7%).
Effect extraction follows pre-specified rules prioritizing more serious outcomes. Submit updates
Strickland et al., 4 May 2022, Randomized Controlled Trial, placebo-controlled, USA, peer-reviewed, 8 authors.
All Studies   Meta Analysis   Submit Updates or Corrections
This PaperNitric OxideAll
Safety and practicality of high dose inhaled nitric oxide in emergency department COVID-19 patients
MD Brian Strickland, MD a , El Lorenzo Albala, El Centro Coffey, MD, MPH b , Ryan W Carroll, MD c , Warren M Zapol, MD Fumito Ichinose, MD Lorenzo Berra, MD N Stuart Harris
The American Journal of Emergency Medicine, doi:10.1016/j.ajem.2022.04.052
Background: Inhaled nitric oxide (iNO) is a selective pulmonary vasodilator and mild bronchodilator that has been shown to improve systemic oxygenation, but has rarely been administered in the Emergency Department (ED). In addition to its favorable pulmonary vascular effects, in-vitro studies report that NO donors can inhibit replication of viruses, including SARS Coronavirus 2 (SARS-CoV-2). This study evaluated the administration of high-dose iNO by mask in spontaneously breathing emergency department (ED) patients with respiratory symptoms attributed to Coronavirus disease 2019 (COVID-19). Methods: We designed a randomized clinical trial to determine whether 30 min of high dose iNO (250 ppm) could be safely and practically administered by emergency physicians in the ED to spontaneously-breathing patients with respiratory symptoms attributed to COVID-19. Our secondary goal was to learn if iNO could prevent the progression of mild COVID-19 to a more severe state. Findings: We enrolled 47 ED patients with acute respiratory symptoms most likely due to COVID-19: 25 of 47 (53%) were randomized to the iNO treatment group; 22 of 47 (46%) to the control group (supportive care only). All patients tolerated the administration of high-dose iNO in the ED without significant complications or symptoms. Five patients receiving iNO (16%) experienced asymptomatic methemoglobinemia (MetHb) > 5%. Thirty-four of 47 (72%) subjects tested positive for SARS-CoV-2: 19 of 34 were randomized to the iNO treatment group and 15 of 34 subjects to the control group. Seven of 19 (38%) iNO patients returned to the ED, while 4 of 15 (27%) control patients did. One patient in each study arm was hospitalized: 5% in iNO treatment and 7% in controls. One patient was intubated in the iNO group. No patients in either group died. The differences between these groups were not significant. Conclusion: A single dose of iNO at 250 ppm was practical and not associated with any significant adverse effects when administered in the ED by emergency physicians. Local disease control led to early study closure and prevented complete testing of COVID-19 safety and treatment outcomes measures.
Declaration of Competing Interest The authors of this study have no conflicts of interest.
Akaberi, Krambrich, Ling, Mitigation of the replication of SARS-CoV-2 by nitric oxide in vitro, Redox Biol
Akerström, Gunalan, Keng, Tan, Mirazimi, Dual effect of nitric oxide on SARS-CoV replication: viral RNA production and palmitoylation of the S protein are affected, Virology
Anand, Prasad, Chugh, Rao, Cornfield et al., Effects of inhaled nitric oxide and oxygen in high-altitude pulmonary edema, Circulation, doi:10.1161/01.cir.98.22.2441
Archer, Huang, Hampl, Nelson, Shultz et al., Nitric oxide and cGMP cause vasorelaxation by activation of a charybdotoxin-sensitive K channel by cGMPdependent protein kinase, Proc Natl Acad Sci U S A, doi:10.1073/pnas.91.16.7583
Chen, Liu, Gao, Inhalation of nitric oxide in the treatment of severe acute respiratory syndrome: a rescue trial in Beijing, Clin Infect Dis
Deppisch, Herrmann, Graepler-Mainka, Gaseous nitric oxide to treat antibiotic resistant bacterial and fungal lung infections in patients with cystic fibrosis: a phase I clinical study, Infection
Fakhr, Fenza, Gianni, Wiegand, Miyazaki et al., Nitric oxide study investigators. Inhaled high dose nitric oxide is a safe and effective respiratory treatment in spontaneous breathing hospitalized patients with COVID-19 pneumonia, Nitric Oxide
Fakhr, Wiegand, Pinciroli, Gianni, Morais et al., High concentrations of nitric oxide inhalation therapy in pregnant patients with severe coronavirus disease 2019 (COVID-19), Obstet Gynecol
Gebistorf, Karam, Wetterslev, Afshari, Inhaled nitric oxide for acute respiratory distress syndrome (ARDS) in children and adults, Cochrane Database Syst Rev
Gianni, Morais, Larson, Ideation and assessment of a nitric oxide delivery system for spontaneously breathing subjects, Nitric Oxide
Ichinose, Roberts, Zapol, Inhaled nitric oxide: a selective pulmonary vasodilator: current uses and therapeutic potential, Circulation
Kacmarek, Ripple, Cockrill, Bloch, Zapol et al., Inhaled nitric oxide. A bronchodilator in mild asthmatics with methacholine-induced bronchospasm, Am J Respir Crit Care Med
Keyaerts, Vijgen, Chen, Inhibition of SARS-coronavirus infection in vitro by S-nitroso-N-acetylpenicillamine, a nitric oxide donor compound, Int J Infect Dis IJID Off Publ Int Soc Infect Dis
Kline, Hall, Jones, Puskarich, Mastouri et al., Randomized trial of inhaled nitric oxide to treat acute pulmonary embolism: the iNOPE trial, Am Heart J, doi:10.1016/j.ahj.2017.01.011
Kline, Hernandez, Garrett, Jones, Pilot study of a protocol to administer inhaled nitric oxide to treat severe acute submassive pulmonary embolism, Emerg Med J
Kline, Puskarich, Pike, Zagorski, Alves, Inhaled nitric oxide to control platelet hyper-reactivity in patients with acute submassive pulmonary embolism, Nitric Oxide
Miller, Mcmullin, Ghaffari, Gaseous nitric oxide bactericidal activity retained during intermittent high-dose short duration exposure, Nitric Oxide
Pepke-Zaba, Higenbottam, Dinh-Xuan, Stone, Wallwork, Inhaled nitric oxide as a cause of selective pulmonary vasodilatation in pulmonary hypertension, Lancet, doi:10.1016/0140-6736(91)92033-x
Regev-Shoshani, Vimalanathan, Mcmullin, Gaseous nitric oxide reduces influenza infectivity in vitro, Nitric Oxide
Samama, Diaby, Fellahi, Inhibition of platelet aggregation by inhaled nitric oxide in patients with acute respiratory distress syndrome, Anesthesiology
Late treatment
is less effective
Please send us corrections, updates, or comments. Vaccines and treatments are complementary. All practical, effective, and safe means should be used based on risk/benefit analysis. No treatment, vaccine, or intervention is 100% available and effective for all current and future variants. We do not provide medical advice. Before taking any medication, consult a qualified physician who can provide personalized advice and details of risks and benefits based on your medical history and situation. FLCCC and WCH provide treatment protocols.
  or use drag and drop