Severe COVID-19 ARDS Treated by Bronchoalveolar Lavage with Diluted Exogenous Pulmonary Surfactant as Salvage Therapy: In Pursuit of the Holy Grail?

Abstract

Background: Severe pneumonia caused by coronavirus disease 2019 (COVID-19) is characterized by inflammatory lung injury, progressive parenchymal stiffening and consolidation, alveolar and airway collapse, altered vascular permeability, diffuse alveolar damage, and surfactant deficiency. COVID-19 causes both pneumonia and acute respiratory distress syndrome (COVID-19 ARDS). COVID-19 ARDS is characterized by severe refractory hypoxemia and high mortality. Despite extensive research, the treatment of COVID-19 ARDS is far from satisfactory. Some treatments are recommended for exhibiting some clinically positive impacts on COVID-19 patients although there are already several drugs in clinical trials, some of which are already demonstrating promising results in addressing COVID-19. Few studies have demonstrated beneficial effects in non-COVID-19 ARDS treatment of exogenous surfactant, and there is no evidence-based, proven method for the procedure of surfactant administration.

Aim: The aim of this work is to underline the key role of ATII cells and reduced surfactant levels in COVID-19 ARDS and to emphasize the rational basis for exogenous surfactant therapy in COVID-19 ARDS, providing insights for future research.

Methods: In this article, we describe and support via the literature the decision to administer large volumes of surfactant to two patients via bronchoalveolar lavage to maximize its distribution in the respiratory tract.

Results: In this study, we report on two cases of COVID-19 ARDS in patients who have been successfully treated with diluted surfactants by bronchoalveolar lavage, followed by a low-dose bolus of surfactant.

Conclusion: Combining the administration of diluted, exogenous pulmonary surfactant via bronchoalveolar lavage along with the standard therapy for SARS-CoV-2-induced ARDS may be a promising way of improving the management of ARDS.

Keywords: COVID-19; acute respiratory distress syndrome (ARDS); coronavirus disease; non-invasive respiratory support (NIRS); respiratory failure; surfactant.

Figure 1

Graphic presentation of the surfactant administration protocol. A total of 10 vials of Curosurf (each one containing 3 mL of 80 mg/mL surfactant solution, for a total amount of 2400 mg) were diluted with 500 mL of Ringer solution (for a final phospholipid concentration 4.8 mg/mL). The first 250 mL were instilled into the right main bronchus in 5 aliquots of 50 mL during bronchoscopy, and suction was applied after administration. This procedure was repeated 5 times and took about 10 min, while the patient was supine. The left lung was then treated similarly; 207 mL were recovered from both lungs (41.4% of the administered volume). After the lavage procedure, a further bolus of 600 mg of Curosurf was delivered into each main bronchus, and no suctioning was performed after this instillation.

Figure 2

(A) Axial High Resolution CT image at baseline in a 60-year-old man (patient n.1) with severe COVID-19 pneumonia, showing bilateral diffuse areas of ground-glass opacities (GGO) and consolidations with peripheral and peribronchovascular distribution. (B) A follow-up CT scan 3 months after hospital discharge shows the complete resolution of consolidations, with residual, bilateral, low-density GGO, bronchial dilatation, distortion in the lingula, and diffuse subpleural curvilinear opacities. (C) A follow-up CT scan after a further 9 months, demonstrates the complete resolution of GGO and minimal residual, subpleural curvilinear opacities.