deMISTify: The Impact of Ventilator Pressure Levels During Minimally Invasive Surfactant Therapy on Lung Aeration in Preterm Infants

Infants born preterm (before 36 weeks' gestation age) have immature lungs and struggle to breathe on their own. They are supported via respiratory machines like ventilators, as well as pharmaceutical aids like exogenous surfactant. Exogenous surfactant is an established therapy for the treatment of respiratory distress syndrome and may reduce the risk of an infant developing bronchopulmonary dysplasia. Exogenous surfactant therapy can be administered via an endotracheal tube which is either permanent, or transiently placed, but can now also be administered via less-invasive techniques. Minimally Invasive Surfactant Therapy (MIST) uses a thin catheter that is passed through the vocal cords to deliver exogenous surfactant directly into the lungs when an infant is on non-invasive respiratory support. MIST is becoming increasing popular in neonatal practice as more infants are managed on non-invasive respiratory support, and it is considered lower-risk compared to techniques that transiently place an endotracheal tube for surfactant therapy as there is no risk of extubation failure. To further improve surfactant therapy, optimisations of delivery techniques have been explored. One optimisation that has been investigated with the transient endotracheal tube method of delivery surfactant is adding a lung recruitment manoeuvre (LRM) prior to surfactant delivery. This demonstrated a reduced need for mechanical ventilation within 72 hours following a LRM compared to infants which did not receive the LRM before surfactant via a transient endotracheal tube. By adding a lung recruitment component to MIST, the benefits of this more invasive method may be replicated without increasing risk of extubation failure. deMISTify is a blinded, randomised, controlled trial of preterm infants, 24-32 weeks' gestation, receiving continuous positive airway pressure (CPAP) respiratory support and MIST. The primary aim of the study is to investigate the impact of a LRM prior to MIST on the mean ventro-dorsal centre of ventilation. Infants will receive a transient increase in CPAP Positive End-Expiratory Pressure (PEEP) levels, known as a LRM, prior to the administration of MIST. Infants who do not receive a LRM will act as the control group. The primary outcome will be change in centre of ventilation (ventro-dorsal) from a pre-MIST baseline as a measure of air distribution in the lungs, 1 hour after MIST, assessed using electrical impedance tomography (EIT). Arm 1: Control - Patients randomised to Control will receive no LRM prior to MIST and no changes to baseline PEEP will be made. In all participating sites the standard PEEP level during CPAP is 7-8 cmH2O. Arm 2: Intervention \- PEEP will be transiently increased to 10 cmH2O 20 minutes before MIST is scheduled to occur. PEEP will remain at this setting for the duration of MIST. Following MIST, PEEP will be decreased to baseline.