Surfactant delivery by aerosol inhalation – past, present, and future

Surfactant replacement therapy (SRT) by nebulization to spontaneously breathing patients has been regarded as the Holy Grail since surfactant deficiency was first identified as the cause for neonatal respiratory distress syndrome. It avoids neonatal endotracheal intubation, a procedure that is often difficult and occasionally harmful. Unapproved alternatives to endotracheal tube placement for liquid surfactant instillation, such as LISA (thin catheter intubation) and SALSA (supraglottic airway insertion) have significant merit but are still invasive, leaving nebulized SRT as the only truly non-invasive method. In the past 60 years, we have learned much about the potential - and limitations - of nebulized SRT. In this review, we examine the promises and pitfalls of nebulized SRT, discuss what we know about neonatal aerosol drug delivery and recap some of the most recent randomized clinical trials of nebulized SRT. We conclude with a discussion of what is known and the next steps needed if this type of SRT is to become a regular part of clinical care.