ABSTRACT
Introduction: Pregnant patients with a severe form of COVID-19 are at increased risk of maternal and fetal complications. Nitric Oxide (NO) gas is a selective pulmonary vasodilator currently approved to treat newborns with pulmonary hypertension. Inhaled NO has been safely used in patients with severe pneumonia and for cases of pregnant patients with pulmonary hypertension. The antimicrobial effect of NO has been confirmed against bacteria and viruses. In vitro study demonstrated a dose-dependent effect of NO against SARS-CoV-1 and 2. We hypothesize that breathing NO at 160-200 ppm twice daily for 30 minutes in spontaneously breathing pregnant patients might provide a safe and effective treatment for COVID-19. Methods: We retrospectively reviewed the data of 6 pregnant patients hospitalized for COVID-19 treated with inhaled NO. Nitric Oxide was delivered at 160- 200 ppm for 30 minutes twice daily until resolution of respiratory symptoms or negative RT-PCR for SARS-CoV- 2. Demographic and clinical data were collected to assess cardiopulmonary function and safety during the treatment. For safety, we focused on the values of blood methemoglobin (MetHb) and inhaled Nitrogen Dioxide (NO2). Data regarding newborn delivery and health, and 28 days outcomes of mothers and babies were collected. Results: Six pregnant patients were admitted with a severe (2 patients) or critical (4 patients) form of COVID-19 and received inhaled NO therapy between April and June 2020. Two pregnant patients were in the second trimester, while 4 were in the third trimester. A total of 39 treatments were administered. No adverse events were reported relating to NO administration. MetHb peaked at 2.5% (1.95%-3%, safety limit =5%) and inhaled NO2 remained below the safety limit of 2ppm. The patients remained hemodynamically stable;cardiac ultrasound performed in three patients did not detect any rebound pulmonary hypertension after NO interruption. Oxygen saturation improved in hypoxemic patients after the initiation of NO (Figure-1). All patients experienced a reduction in respiratory rate (by a median 4.5breaths/min after NO initiation). Three patients delivered a total of 4 babies (negative for SARS-CoV-2) while the other 3 remained pregnant after hospitalization (gestational age 22-26-33weeks) with normal follow-ups. Five mothers out of 6 tested negative for COVID-19 28 days after hospitalization. Conclusion: Nitric oxide gas at 160-200 ppm was safely administered to pregnant patients with severe-critical COVID-19, improved oxygenation and reduced respiratory rate in all 6 patients. The clinical effectiveness shown suggests inhaled high dose NO as a therapeutic novel therapy for COVID-19 in pregnancy.
ABSTRACT
INTRODUCTION: The prone position and protective lung ventilation are the only interventions to improve survival in Acute Respiratory Distress Syndrome (ARDS) patients. Due to early reports during the COVID-pandemic showing dramatic improvements in oxygenation, the use of prone position has been broadly adopted in intubated patients around the globe. However, it remains unclear on whether titration of ventilation should be reassessed when the patient is repositioned. Therefore, the objective of this study was to characterize the response of respiratory mechanics in supine and prone positions during a decremental end-expiratory positive pressure trial in COVID-19 related ARDS patients. METHODS: This is a retrospective analysis of patients with COVID-19 related ARDS under invasive mechanical ventilation in supine and prone positions. The study was approved by the Investigational Review Board at the Massachusetts General Hospital and by the Ethics and Research Committee at Heart Institute (InCor) from the University of São Paulo. Prone position was recommended based on hypoxia, measured as PaO2/FIO2 ratio (< 150 mmHg). Patients were sedated, and under volume-controlled ventilation (5-6 mL/Kg PBW). Airway pressure, flow, esophageal pressure and electrical impedance tomography (EIT) were recorded. A decremental PEEP trial was performed on supine and prone position. RESULTS: We included 10 patients with COVID-19 related ARDS. Median age was 62 years (range, 35-72), 5 patients (50%) were female, and BMI was 35 (range, 27-46). After 24 hours of intubation, median PaO2/FIO2 was 174 mmHg (IQR, 166-192), PEEP was 10 cmH2O (IQR, 10-14.5), and static compliance of respiratory system (CRS) was 28.5 mL/cmH2O (IQR, 24.2-35.7). The time interval between intubation and the supine-prone assessment was 7 days (IQR, 5-10). During the supine/prone assessment, a variety of CRS responses were observed among patients (Figure 1). Overall, the highest CRS was 44 mL/cmH2O (IQR, 29-57) in supine and 52 mL/cmH2O (IQR, 39-67) in prone position. At the highest CRS, from supine to prone position: lung compliance (CL) increased by 15 mL/cmH2O (IQR, 13-31), suggesting lung recruitment, and chest wall compliance (CCW) was reduced by 28 ml/cmH2O (IQR, 14-48) indicating external compression of the chest;and end-expiratory transpulmonary pressure (PLend-exp) increased from-3.4 cmH2O (IQR,-4.6 to-2.5) to 0.4 cmH2O (IQR, 0.1-3.0) suggesting decreased pleural pressure. CONCLUSION: Patients with COVID-19 related ARDS assessed in supine and prone positions revels a variety response to prone position on CRS during decremental PEEP trial, suggesting the necessity to reassess the PEEP when the patient is repositioned. (Table Presented).