According to a research group led by Massachusetts General Hospital (MGH). In a study published in Obstetrics and gynecologyAdding nitrous oxide twice a day to standard oxygen therapy reduced the breathing rate of pregnant women with low blood oxygenation without causing any side effects, researchers at four Boston hospitals reported.
“To date, very few airway therapies have been tested that complement supplemental oxygenation in pregnant patients with COVID-19,” says senior author Lorenzo Berra, MD, of MGH’s Department of Anesthesia, Critical Care, and Analgesia. “Researchers from all four medical centers participating in our study agreed that the administration of high-dose nitric oxide through a tight-fitting mask has tremendous potential as a novel therapeutic strategy for pregnant patients with COVID-19.”
Pneumonia caused by COVID-19 poses a particular threat to pregnant women because it can rapidly progress to insufficient oxygen in the body’s blood and tissues, a condition known as hypoxemia, which requires hospitalization and cardiopulmonary care. “Compared to non-pregnant patients with COVID-19, pregnant women are three times more likely to require intensive care unit admission, mechanical ventilation or extended life support, and four times more likely to die,” notes Carla Valsecchi, MD , lead author in the Department of Anesthesia, Intensive Care and Analgesia, MGH. “They also face a greater risk of obstetric complications such as pre-eclampsia, premature birth and stillbirth.”
Nitrous oxide is a therapeutic gas that was originally approved by the US Food and Drug Administration in 1999 for the inhalation treatment of intubated and ventilated neonates with hypoxic respiratory failure. Thanks to MGH leading much of the early research, iNO at high concentrations has also shown efficacy as an antimicrobial agent to reduce the replication of SARS-CoV-1 and, more recently, SARS Co-V-2, the virus that causes COVID-19. During the first wave of COVID-19, MGH treated six non-intubated pregnant patients with iNO at high doses up to 200 parts per million (ppm). The findings of a more favorable outcome for iNO led MGH clinicians to offer this treatment to other pregnant patients and to design an ongoing study to determine the safety and efficacy of iNO200 for COVID-19 pneumonia in pregnancy.
To that end, a collaborative network of four medical centers in the Boston area was created. In addition to MGH, it included Tufts Medical Center, Deaconess Beth Israel Medical Center, and Boston Medical Center. Researchers and clinicians from a variety of departments, including critical care, respiratory care, and maternal-fetal medicine, studied 71 pregnant patients with severe COVID-19 pneumonia admitted to these hospitals, 20 of whom received iNO200 twice daily. The study found that iNO therapy at this dosage, compared with standard treatment, resulted in a reduction in the need for supplemental oxygen and the length of hospital and intensive care stays. No adverse effects related to the intervention were reported in either the mothers or their children.
“Being able to wean patients off respiratory support more quickly could have other significant consequences, including reducing stress for women and their families, reducing the risk of hospital-acquired infections, and reducing the burden on the health care system,” notes Bera. “Overall, our study confirms the safety of high-dose nitric oxide for pregnant women, and we hope that more doctors will consider including it in carefully controlled treatment regimens.”
Bera is an assistant professor of anesthesia at Harvard Medical School (HMS) and medical director of respiratory care at MGH. Valsecchi is a postdoctoral fellow and researcher in the Department of Anesthesia, MGH. Co-authors include William Barth, Jr., MD, vice chair of the Department of Obstetrics, MGH, and assistant professor of Obstetrics, Gynecology and Reproductive Biology, HMS; Ayris Collier, MD, researcher and instructor of obstetrics, gynecology and reproductive biology at Beth Israel Deaconess Medical Center; Ala Nozari, professor of anesthesiology at Boston Medical Center; Jamel Artoleva, MD, assistant professor of anesthesiology at Tufts School of Medicine and cardiothoracic anesthesiologist and critical care physician at Tufts Medical Center; and Anjail Kaimal, MD, Chief, Maternal-Fetal Medicine, MGH, and Associate Professor, Department of Obstetrics, Gynecology, and Reproductive Biology, HMS.