A Single-centre, Randomized Pilot Study on the Effects of Different Premedication Treatments for Less Invasive Surfactant Administration (LISA) on Pain, Cerebral Tissue Oxygenation and Cortisol Levels in Preterm Infants

In the last decades, one of the most relevant interventions which have led to a significant increase in preterm infants survival rate is the introduction of surfactant replacement therapy.

Nowadays, given the trend towards the less invasive respiratory support also for low and extremely low gestational age infants, the use of intubation and prolonged mechanical ventilation has been minimized. In fact, bronchopulmonary dysplasia (BPD) has been proved to be closely related to prolonged intubation and it is one of the main problem clinicians must face with. This is the reason why the INSURE technique was introduced as a routine care procedure in neonatal units. In fact, INSURE is the acronym for INtubation - SURfactant administration-Extubation. This technique ensures the baby the positive effects of surfactant on respiratory mechanics minimizing the intubation length. However, the INSURE procedure still involves intubation, meaning that it is still invansive and some infants cannot be extubated immediately afterward. Thus, lately new technique for surfactant administration has been introduced. The most extensively studied are the so-called less invasive surfactant administration (LISA) and minimally invasive surfactant therapy (MIST). With these procedures, infants receive non-invasive continuous positive airway pressure (CPAP) treatment, while being given intratracheal surfactant via a feeding tube or small catheter. Although the paucity of literature available to date, for extremely preterm infants LISA has shown to be able to reduce the need for intubation, ventilation and supplemental oxygen when compared with the standard technique of rescue intubation and ventilation. In comparison with the INSURE procedure the less invasive surfactant administration was associated with a reduced need for ventilation and reduced risk of BPD.

Even if this technique can provide the gentlest treatment presently available in administering surfactant, it implies laryngoscopy and somewhat discomfort. The importance of proper care in managing preterm infants, especially during painful procedures, has been well demonstrated and all the caregivers have to be even more committed to this aspect.

Pain in neonates is usually assessed through pain scales and using clinical parameters such as pulse oximetry (SatO2) and Heart Rate (HR). Since pain scores are subject to caregivers' individual perception and parameters can be influenced by other clinical underlying condition, especially in preterm infants, determination of cortisol concentration could be a useful alternative.

Cortisol is the major glucocorticoid produced in the adrenal cortex. Cortisol production has a circadian rhythm, with levels peaking in the early morning and dropping to lowest values at night. Levels rise independently of circadian rhythm in response to stress.