LISA/MIST: Complex clinical problems almost never have easy solutions.

Over the last 10 years, new techniques to administer surfactant have been promoted, based on their presumed lesser invasiveness and they have been generally called LISA (less invasive surfactant administration). We believe that the clinical potential of LISA techniques is currently overestimated. LISA lacks biological and pathophysiological background justifying its potential benefits. Moreover, LISA has been investigated in clinical trials without previous translational data and these trials are affected by significant flaws. The available data from these trials only allow to conclude that LISA is better than prolonged, unrestricted invasive ventilation with loosely described parameters, a mode of respiratory support that should be anyway avoided in preterm infants. We urge the conduction of high-quality studies to understand how to choose and titrate analgesia/sedation and optimize surfactant administration in preterm neonates. We offer a comprehensive, evidence-based review of the clinical data on LISA, their biases and the lack of physiopathology background.