In this study, authors compared the effectiveness between the LISA and the INSURE method for surfactant administration for RDS in preterm infants. The LISA and the INSURE were equally efficacious methods to improve respiratory acidosis and OSI, and there were no significant differences in morbidity and mortality. As an indicator of the effect of exogenous surfactant administration, pCO2 was decreased quickly in the INSURE group within 1 hour after surfactant administration, although there was no significance. In contrast, the LISA group showed no significant decrease in pCO2 within 1 hour after surfactant administration, but it fell rapidly after 2 hours. The results of repeated measure ANOVA showed that there was interaction between the surfactant administration methods and the time. These results imply that onset time of surfactant depends on the method of administration, and further investigation is needed.
The authors presumed that the distribution of the surfactant caused these differences. Using animal experiments, Niemarkt reported decreased surfactant distribution to the right upper lobe in the LISA method compared with the intubation method [18]. Surfactant distribution, which is affected by the volume of the administered surfactant, rate of installation, the position of the infant, and underline the status of the lung of the patient, is an essential factor of surfactant administration [19].
Efforts to reduce BPD have continued for many years. Various methods, such as prenatal or postnatal steroid, have been attempted, but the most effective method to reduce BPD is avoiding invasive mechanical ventilation. Caffeine is administered to decrease respiratory support [4, 7, 20]. Application of non-invasive mechanical ventilation and aggressive weaning of invasive mechanical ventilation are recommended to shorten the duration of invasive mechanical ventilation. However, despite these efforts, many premature infants still require invasive mechanical ventilation to achieve sufficient lung capacity for oxygenation, ventilation, and prevention of atelectasis.
RDS is one of the leading causes of invasive mechanical ventilation. RDS is a common respiratory disease for premature infants caused by an insufficient amount of surfactant and immaturity of the peripheral airway. Perinatal hypoxic insults, Cesarean section, and acidosis affect decreased production of surfactant, and the immature lung itself is unable to produce a sufficient amount of surfactant. RDS causes a vicious cycle of interrupted oxygenation and ventilation, respiratory acidosis and hypoxic insults, and reduced surfactant production. Therefore, surfactant replacement is crucial in the management of RDS
In Korea, an animal-derived surfactant, such as Surfactant-TA (Surfacten®), Korean bovine surfactant (Newfactan®), poractant alfa (Curosurf®), and calfactant (Infasurf®), is used. Surfactant-TA and Korean bovine surfactant are extracted from minced bovine lung and administered after diluting with normal saline. The disadvantage of these two surfactants is that the patients’ position should be changed during administration. Meanwhile, poractant alfa and calfactant have advantages in that there is no need to dilute the medication, and less position changes are needed.
Our center uses poractant alfa (Curosurf®) only due to higher efficacy and advantage of the reduced number of positioning changes, and there were no differences in instillation rate and position changes found in our study [21]. The authors presumed that the diameter of the catheter used for surfactant delivery and the method of respiratory support after surfactant administration affected the results. Hugo et al. 19 reported that the catheter diameter affected administration of surfactant in an animal experiment. Further investigation about the effect of administration methods in surfactant distribution is required to improve the efficacy of surfactant treatment.
Traditionally, the surfactant is administered through an endotracheal tube, and invasive mechanical ventilation is performed thereafter. However, to avoid ventilator-induced lung injury, various methods of non-invasive surfactant administration were studied since the 1990s. Currently, the surfactant can be delivered without mechanical ventilation through various non-invasive method such as INSURE and LISA method, thus decreasing the occurrence of BPD. Nebulized preparation and pharyngeal preparation have also been studied as feasible delivery method [22].
Some studies reported lower mortality in patients treated with the LISA than in patients treated with the INSURE method.12,13 More than half of the centers in Europe use the LISA method for the management of RDS, but there is a difference in the actual use by country. For example, less than 1% of centers in Poland manage RDS patients using the LISA method [23]. This difference may be caused by the difference in human and material resources and experiences. In our center, the surfactant is administered through the LISA method in more than half of the preterm RDS cases. With respect to staff resource, the LISA method is more convenient in that although it requires proper equipment, an experienced medical staff can perform the procedure. Meanwhile, the INSURE method should be performed by doctors experienced in endotracheal intubation.
However, because of the difficulty in the maneuver of a thin catheter, the LISA method needs more experience and skills. There are several methods of tracheal catheterization according to catheter type and guidance through vocal cord. In Cologne method, flexible nasogastric tube is used, and Magill’s forceps are used for guidance of the catheter to vocal cord. Semi-rigid vascular catheter is used in Hobart method, and flexible nasogastric tube is guided without forceps in the TAKE CARE method [7, 24]. The authors adopt the TAKE CARE method and modified it to introduce catheters using fine tip curved forceps.
In the case of the Cologne method, Magill forceps are used for inserting a catheter, which has an advantage in less probability of airway injury due to the blunt edge of the forceps. However, Magill forceps have disadvantages in difficulty in handling and preference of small-sized forceps suitable for extremely premature infants. Thus, fine-tip curved forceps are used instead of Magill forceps in our center.
A 4–5 Fr feeding tube is used for surfactant instillation. Although an angiocatheter is easier to operate due to its stiffness, there is also a higher risk of vocal cord injury. The difficulty in maneuverability of the feeding tube is compensated with the use of fine-tip curved forceps. In our center, these modifications have made it easier to perform LISA.
There are several limitations to this study. First, the number of cases was limited. Second, OSI was used to measure the severity of respiratory difficulty. The OSI of patients in whom surfactant administration was followed with heated high-flow nasal cannula may be less accurate than that of patients in whom mechanical ventilation was performed [25, 26]. Finally, although the number of days needed for respiratory support was evaluated, it was difficult to determine the cause of respiratory distress. There may have been undetected nosocomial respiratory infection. More frequent evaluation may be required for clinical deteriorations or difficulties in weaning of mechanical ventilation.