Discussion
hypoxic respiratory failure, RDS, APACHE-II, ARDS
ADVERSE EVENTS, NEONATAL RESPIRATORY DISTRESS SYNDROME, DISEASE, HYPOXIC RESPIRATORY FAILURE, SECONDARY, ARDS
This is a pilot, randomised, unblinded, two-centre, controlled study evaluating the feasibility, efficacy, and safety of delivering nebulized surfactant for COVID-19 patients with acute severe hypoxic respiratory failure. Breath synchronised exogenous surfactant delivery is feasible, and surfactant phospholipid composition was augmented following nebulizationAlthough surfactant replacement is established and effective in neonatal respiratory distress syndrome (RDS) so far, no adult studies demonstrated mortality benefitsRecently, several case series and observational studies have used exogenous surfactant replacement in COVID-19 patients and reported improved clinical outcomesIn this a small, pilot, phase 2, feasibility, two-centre trial, we have shown that nebulized synchronised natural bovine surfactant is feasible to deliver without any significant adverse events. However, in mechanically ventilated COVID-19 patients, natural bovine exogenous surfactant at doses of 540 mg or 1080 mg did not improve oxygenation or other secondary outcomes. Furthermore, the surfactant group had a trend towards increased mortality. However, this finding could be attributed to disease severity rather than the intervention. Although nonsignificant, the surfactant group had higher APACHE-II and SOFA scores. Moreover, the surfactant group had a considerably greater neutrophil-to-lymphocyte ratio and CRP on admission (more than twofold), indicating increased disease severityWhile it is biologically plausible that exogenous surfactant may improve clinical outcomes, or notwithstanding that surfactant therapy may be ineffective, this study raises several questions; (1) what is the correct patient group?; (2) what is the timing of surfactant treatment (early/late)?; (3) what the ideal surfactant for adults (natural/synthetic)?; (4) what the ideal dose (high dose/low dose) and delivery method (nebulized/intratracheal/bronchoscope)?; (5) What is the ideal interval between doses?; (6) why is there rapid surfactant turnover and how to minimise it?; (7) is high fractional inspired oxygen given to patients detrimental to surfactant function?.The strength of the study include: (1) this is the first study to utilise a novel breath synchronized nebulizer device in combination with photo defined aperture plate vibration mesh technology to deliver exogenous surfactant in mechanically ventilated adult patients; and (2) demonstration of augmentation of surfactant phospholipids following nebulization followed by a rapid turnover of surfactant phospholipidsIn neonates, natural surfactant is the preferred choice for supplementation. Due to the large surface area and the need for larger quantities of exogenous surfactant, most adult studies on ARDS patients were conducted with synthetic surfactant preparations. Moreover, natural surfactants are more costly than synthetic preparations. We chose a well-established natural surfactant, which has shown proven benefit in neonatal RDS