Abstract: American Journal of Emergency Medicine 58 (2022) 5–8 Contents lists available at ScienceDirect American Journal of Emergency Medicine journal homepage: www.elsevier.com/locate/ajem Safety and practicality of high dose inhaled nitric oxide in emergency department COVID-19 patients Brian Strickland, MD a,1,⁎, Lorenzo Albala, MD a, El Centro Coffey, MD a, Ryan W. Carroll, MD, MPH b, Warren M. Zapol, MD c, Fumito Ichinose, MD, PhD d, Lorenzo Berra, MD d,e, N. Stuart Harris, MD, MFA a a Division of Wilderness Medicine, Department of Emergency Medicine, Massachusetts General Hospital, 55 Fruit Street, Boston, MA 02114, United States of America Department of Pediatrics, Massachusetts General Hospital, 55 Fruit Street, Boston, MA 02114, United States of America Anesthesia Center for Critical Care Research (ACCCR), Massachusetts General Hospital, 55 Fruit Street, Boston, MA 02114, United States of America d Respiratory Care Service, Patient Care Services, Massachusetts General Hospital, 55 Fruit Street, Boston, MA 02114, United States of America e Surgical Intensive Care Unit, Department of Anesthesia, Critical Care and Pain Medicine (DACCPM), Massachusetts General Hospital, 55 Fruit Street, Boston, MA 02114, United States of America b c a r t i c l e i n f o Article history: Received 25 October 2021 Received in revised form 5 April 2022 Accepted 29 April 2022 Keywords: Nitric oxide COVID-19 Emergency department a b s t r a c t 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...