<scp>EBNEO</scp> Commentary: Reassessing <scp>INSURE</scp> : Is Lung Recruitment Necessary?

Few therapies have impacted a field like surfactant has neonatology. Since its discovery in the 1980s, surfactant replacement therapy revolutionised the management of respiratory distress syndrome (RDS), reducing immediate associated mortality and subsequent development of bronchopulmonary dysplasia (BPD) [1]. Historically, surfactant was delivered via endotracheal tube, followed by a prolonged course of invasive mechanical ventilation (IMV). However, as the link between prolonged IMV and development of BPD became more apparent, research efforts shifted to novel delivery methods to minimise IMV exposure. The original IMV-sparing technique is the intubate-surfactant-extubate (INSURE) method, which called for the immediate removal of the endotracheal tube following surfactant administration [2]. While newer methods of surfactant administration avoid an endotracheal tube altogether, either by using a thin catheter or supraglottic airway, INSURE remains the most commonly used method of surfactant administration in the US [3-5]. This study from Gallini et al. presents the 2-year follow-up data from the IN-REC-SURE Trial, an unblinded, randomised control trial comparing the use of a recruitment manoeuvre prior to selective administration of surfactant to standard INSURE protocol [6]. The physiologic rationale for this study being that a “well-recruited” lung facilitates the homogenous distribution of surfactant and improves its efficacy [7]. Although the primary outcome did not show statistically significant differences between groups, the overall mortality benefit when including deaths during the NICU stay is striking (35.1% vs. 22.8%; p = 0.05) [6]. However, it is important to note that statistical significance was only met in the per-protocol analysis. Of the 6 patients excluded from the ITT analysis (3 for meeting exclusion criteria post-enrollment and 3 who did not receive the assigned recruitment manoeuvre; all in the IN-REC-SURE arm) 4 died during their NICU stay. Furthermore, nearly 70% of infants in the trial received at least one sustained inflation (SI) during initial delivery room resuscitation. It has since been shown that exposure to SI in the delivery room increases the risk of early mortality [8]. While the authors argued in the primary analysis of the IN-REC-SURE Trial [9] that this should not influence the results since infants in both groups received SI and there was no differential exposure, an increased baseline mortality risk may exaggerate the observed mortality benefit and may not be applicable to populations with lower baseline mortality risks. In considering the dissemination of this approach, clinicians must remain mindful of the technical demands, including the need for high-frequency ventilators and specific training to perform recruitment manoeuvres safely. Despite these challenges, the study provides encouraging safety data regarding the IN-REC-SURE procedure with a possible signal for improved mortality. Future investigations, such as the proposed IN-REC-LISA Trial [10], should compare IN-REC-SURE with other commonly used less invasive strategies to further elucidate the optimal balance between effective lung recruitment and the benefits of avoiding endotracheal intubation to improve the outcomes of extremely preterm infants. URL LINK: https://ebneo.org/ebneo-commentary-reassessing-insure-is-lung-recruitment-necessary/. Dr. Foglia discloses personal consulting fees for Chiesi USA. Dr. Foglia is the PI for a grant from Chiesi USA to her institution for research focused on Less Invasive Surfactant Administration.