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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 c19early.org 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  
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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. Contact: brian.strickland@cuanschutz.edu.
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.
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Late treatment
is less effective
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