Does high-dose inhaled nitric oxide improve respiratory function and outcomes among pregnant patients hospitalized with severe COVID-19 pneumonia?

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. 

Background

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.

Results

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.

Conclusions

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. 

Written by

Shanet Susan Alex

Shanet Susan Alex, a medical writer, based in Kerala, India, is a Doctor of Pharmacy graduate from Kerala University of Health Sciences. Her academic background is in clinical pharmacy and research, and she is passionate about medical writing. Shanet has published papers in the International Journal of Medical Science and Current Research (IJMSCR), the International Journal of Pharmacy (IJP), and the International Journal of Medical Science and Applied Research (IJMSAR). Apart from work, she enjoys listening to music and watching movies.