In a recent article published in Obstetrics & Gynecology, researchers demonstrated that inhaled nitric oxide 200 (iNO200) enhances oxygenation in pregnant coronavirus disease 2019 (COVID-19) patients with severe pneumonia. 

Study: High-Dose Inhaled Nitric Oxide for the Treatment of Spontaneously Breathing Pregnant Patients With Severe Coronavirus Disease 2019 (COVID-19) Pneumonia. Image Credit: Pressmaster/Shutterstock
Study: High-Dose Inhaled Nitric Oxide for the Treatment of Spontaneously Breathing Pregnant Patients With Severe Coronavirus Disease 2019 (COVID-19) Pneumonia. Image Credit: Pressmaster/Shutterstock


Due to the increased oxygen requirements during pregnancy and the related immunological, physiological, and hormonal alterations, pregnant individuals are susceptible to developing hypoxic respiratory failure in COVID-19. Randomized clinical studies involving pregnant individuals with COVID-19 have not yet explored any respiratory therapy to adjunct supplementary oxygenation.

iNO is employed as a rescue treatment for severe hypoxemia among intubated patients suffering respiratory failure, including those associated with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Additionally, nitric oxide exhibits antiviral effects toward SARS-CoV-2.

The present study’s authors priorly treated six non-intubated pregnant COVID-19 patients with severe pneumonia hospitalized in Massachusetts General Hospital (MGH) during the first SARS-CoV-2 wave with about 200 ppm of iNO (iNO200) administered through a snug-fitting mask for half an hour, two times a day. The safe administration of 39 iNO200 treatments led to an improvement in systemic oxygenation and a reduction in respiratory rate. These findings led to the implementation of iNO200 at MGH as a therapy for COVID-19 pneumonia during pregnancy.

About the study

In the current work, the researchers assessed if iNO200 enhances respiratory function and outcomes in hospitalized pregnant patients with severe COVID-19 pneumonia to explore further the efficacy and safety of the iNO200 among pregnant SARS-CoV-2 patients.

The team used information from pregnant patients admitted at four academic hospitals from March 2020 to December 2021 for severe bilateral SARS-CoV-2 pneumonia. They established the Delivery of iNO network, also known as the DELFiNO network, involving four university hospitals in Boston, Massachusetts (Boston Medical Center, Beth Israel Deaconess Medical Center, Tufts Medical Center, and MGH).

Every DELFiNO network’s institutions have comparable access to modern methods for managing respiratory failure, such as extracorporeal membrane oxygenation (ECMO). Only one facility (MGH) had access to the unique, unlabeled usage of iNO therapy, known as iNO200 treatment. The researchers identified two groups: those getting the standard of care alone (SoC cohort) and those getting iNO200 for half an hour twice daily in conjunction with SoC alone (iNO200 group).

The predetermined primary outcome was the number of days without oxygen supplementation at 28 days after hospitalization. Secondary outcomes included duration of hospital stay, intubation rate, and length of stay in the intensive care unit (ICU). The multivariable-adjusted regression assessments considered the body mass index, age, gestational age, use of remdesivir, steroids, and the research center.


The study results indicated that 51 women in the SoC group and 20 women in the iNO200 arm were hospitalized with severe bilateral SARS-CoV-2 pneumonia, accounting for 71 pregnant patients.

The team demonstrated that inhaling iNO200 increased oxygenation and decreased tachypnea. Subjects treated with iNO200 exhibited more days without oxygen supplementation, on average 24 days ranging from 23 to 26 days, relative to patients receiving SoC alone, who had 22 days without oxygen supplementation varying from 14 to 24.

In the multivariable-adjusted studies, iNO200 was linked to 63.2% more days without oxygen supplementation, 59.7% shorter duration of ICU stay, and 63.6% shorter length of hospital stay. According to the current research, iNO200 was associated with a quicker recovery from respiratory assistance, such as rapid weaning of oxygen therapy.

Besides, no iNO200-linked adverse events were observed during the 144 treatments with iNO200. The maximum measured methemoglobin level was 5.3%, and it fell quickly following the treatment completion. Indeed, in the present investigation, the clinical and echocardiographic evaluation did not detect any proof of rebound pulmonary hypertension, cardiac failure, or hypotension, possibly because of the short, i.e., 30-minute exposure to iNO200 treatments.

Notably, according to the serum creatinine concentrations, none of the trial participants who received iNO200 showed signs of acute renal injury. Since they noticed no adverse obstetric or neonatal outcomes, the researchers believe that giving pregnant patients iNO200 for half an hour twice a day while closely monitoring them was a safe respiratory intervention in COVID-19-associated severe pneumonia.


Overall, the authors discovered that iNO200 was connected to better oxygenation and diminished dyspnea among pregnant SARS-CoV-2 patients with severe pneumonia in the present study. In addition, iNO200 was linked to a shorter duration of hospital and ICU stay and oxygen supplementation when compared to SoC alone. Among pregnant COVID-19 pneumonia patients, this novel respiratory intervention was viable, and both mothers and infants did not experience any adverse effects.

In sum, iNO200 could be an efficient respiratory therapy for hospitalized tachypneic and hypoxemic pregnant patients with severe bilateral SARS-CoV-2 pneumonia to increase oxygenation and reduce respiratory rate. Randomized controlled investigations are necessary to assess enhanced outcomes with iNO200, considering the current findings and the lack of therapeutic studies among pregnant severe pneumonic patients. 


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