Management of respiratory distress syndrome in moderate/late preterm neonates: A Delphi consensus.

INTRODUCTION: Respiratory distress syndrome (RDS) is the most frequent cause of respiratory distress in preterm neonates. In the management of RDS, surfactant plays a pivotal role, but there are no evidence-based recommendations for moderate/late preterm neonates (32-36 weeks). METHODS: A scientific committee developed a questionnaire with 53 questions addressing diagnosis, treatment, potential complications and future trends in RDS specifically focused on moderate and late preterm neonates. This was followed by the performance of a Delphi survey of expert neonatologists. RESULTS: Consensus was reached on 98 of the 109 items. The recommendations for the diagnosis of RDS included performing a lung ultrasound and including mild respiratory distress, transient tachypnoea of the newborn, congenital pneumonia and primary pulmonary hypertension in the differential diagnosis. Most panellists agreed on the need for studies that determine the benefit/harm balance, clinical profile and methods of surfactant administration in moderate/late preterm neonates. All respondents would use the MIST approach with devices specifically designed for surfactant administration. Regarding sedation measures during MIST, most participants agreed on the use of nonpharmacological interventions and, if these proved ineffective, an opioid. All respondents agreed that moderate/late preterm neonates are at increased risk of neonatal morbidity and mortality, particularly respiratory problems, and considered the need for more specialised monitoring in hospital follow-up visits in neonates with associated risk factors or a history of complications in the neonatal period. Finally, all respondents agreed that there is a lack of studies identifying risk factors and medium-term adverse outcomes in moderate/late preterm neonates. CONCLUSION: This expert consensus will help with the diagnosis and management of RDS and guide decision-making about surfactant administration in moderate/late preterm neonates.

Changes in practice of less-invasive surfactant administration (LISA) in United Kingdom neonatal units.

AIM: To determine whether the use of less-invasive surfactant administration (LISA) had changed between 2018 and 2024. METHODS: An online questionnaire was sent to all 191 neonatal units between June 2023 and May 2024. One consultant from each neonatal unit was randomly selected. Follow-up was done by telephone (middle-grade doctor grade and above or alternatively to Advanced Neonatal Nurse Practitioners) for the non-responders. RESULTS: Response rate was 100%from 191 units neonatal units. LISA was used in 134 (70%) neonatal units in 2024 compared to 35 (18.7%) units in 2018 (p < 0.001). The reason why LISA was not performed was lack of experience/training (51%) or not having a standardised practice/guideline (49%). LISA in the delivery suite (DS) had increased from 2% in 2018 to 16% in 2024, and the use of video laryngoscope for LISA is becoming standard of practice. The oxygen requirement criteria for the use of LISA in both the DS and on neonatal unit had reduced to FiO2 of 0.3 or more. CONCLUSION: The uptake of LISA had increased in the United Kingdom. There is greater use of LISA in the DS. Lack of training and expertise were the major limiting factors for LISA not being performed.

Influence of catheter thickness on respiratory physiology during less invasive surfactant administration in extremely preterm infants.

Introduction: Delivering surfactant via thin catheters (minimal-invasive surfactant therapy (MIST); less invasive surfactant administration (LISA)) has become a common procedure. However, the effect of tracheal obstruction caused by catheters of different sizes on tracheal resistance in extremely low gestational age newborns (ELGANs) is unknown. Methods: To investigate the effect of catheters size 3.5, 5 and 6 French on airway resistance in ELGANs of 23-28 weeks gestational age during LISA, we performed calculations based on Hagen-Poiseuille's law and compared these with a clinically and physically more accurate method: computational fluid dynamics (CFD) simulations of respiratory airflow, performed in 3D virtual airway models derived from MRI. Results: The presence of the above catheters decreased the cross-sectional area of the infants' tracheal entrance (the cricoid ring) by 13-53%. Hagen-Poiseuille's law predicted an increase in resistance by 1.5-4.5 times and 1.3-2.6 times in ELGANs born at 23 and 28 weeks, respectively. However, CFD simulations demonstrated an even higher increase in resistance of 3.4-85.1 and 1.1-3.5 times, respectively. The higher calculated resistances were due to the extremely narrow remaining lumen at the glottis and cricoid with the catheter inserted, resulting in a stronger glottal jet and turbulent airflow, which was not predicted by Hagen-Poiseuille. Conclusion: Catheter thickness can greatly increase tracheal resistance during LISA-procedures in ELGANs. Based on these models, it is recommended to use the thinnest catheter possible during LISA in ELGANs to avoid unnecessary increases in airway resistance in infants already experiencing dyspnea due to respiratory distress syndrome.

Predictors of CPAP failure after less-invasive surfactant administration in preterm infants.

Introduction: Less-invasive surfactant administration (LISA) is associated with better respiratory outcomes in preterm infants with respiratory distress syndrome. However, mechanical ventilation (MV) shortly after the LISA procedure has been related to lower survival. This study aimed to analyze the trends and main predictors of continuous positive airway pressure (CPAP) failure after LISA. Material and methods: Preterm infants born between 230 and 336 weeks gestational age (GA) in two level III neonatal units who received surfactant were included (2017-2022). Demographic data, lung ultrasound (LUS) scores, the saturation/fraction of inspired oxygen (SF) ratio, technique, time to surfactant administration, and the main neonatal outcomes were collected. Results: Over the study period, 289 inborn preterm infants received surfactant, 174 with the LISA method (60.2%). Patients who received surfactant after intubation in the delivery room (n = 56) were more immature and exhibited worse outcomes. Patients who received surfactant via an endotracheal tube in the neonatal intensive care unit (n = 59) had higher LUS scores and a lower SF ratio than those treated with LISA. The LISA method was associated with less death or bronchopulmonary dysplasia (BPD), with an adjusted odds ratio (aOR) = 0.37 [95% confidence interval (CI), 0.18-0.74, p = 0.006]. CPAP failure after LISA (defined as the need for intubation and MV in the first 72 h of life) occurred in 38 patients (21.8%), inversely proportional to GA (38.7% at 23-26 weeks, 26.3% at 27-30 weeks, and 7.9% at 30-33 weeks (p < 0.001). CPAP failure after LISA was significantly related to death, with an aOR = 12.0 (95% CI, 3.0-47.8, p < 0.001), and moderate to severe BPD, with an aOR = 2.9 (95% CI, 1.1-8.0, p = 0.035), when adjusting for GA. The best predictors of CPAP failure after LISA were GA, intrauterine growth restriction, temperature at admission, the SF ratio, and the LUS score, with a Nagelkerke's R 2 = 0.458 (p < 0.001). The predictive model showed an area under the curve = 0.84 (95% CI, 0.75-0.93, p < 0.001). Conclusions: CPAP failure after LISA is still common in extremely preterm infants, leading to an increase in death or disability. Clinicians must acknowledge the main risk factors of CPAP failure to choose wisely the right patient and the best technique. LUS and the SF ratio at admission can be useful when making these decisions.

Less Invasive Surfactant Administration for Preterm Infants - State of the Art.

BACKGROUND: Less invasive surfactant administration (LISA) has become the preferred method of surfactant administration for spontaneously breathing babies on continuous positive airway pressure (CPAP). SUMMARY: The development of LISA followed the need to combine CPAP and surfactant replacement as mainstay treatment options for respiratory distress syndrome, thereby avoided exposure to positive pressure ventilation. KEY MESSAGES: This review summarises the current knowns and unknowns of LISA including the physiological concept, its relevance for short-term and long-term outcomes and the challenges for practical implementation of LISA as part of a less invasive respiratory care bundle. Further, we provide an update of the evidence on alternatives to LISA, for example, nebulised surfactant administration, pharyngeal deposition of surfactant and delivery via supraglottic airway.

Less Invasive Surfactant Administration in Preterm Infants in Tertiary Neonatal Intensive Care Units in Germany: A Survey.

INTRODUCTION: The European guideline for treatment of respiratory distress syndrome recommends less invasive surfactant administration (LISA) as the preferred method of surfactant administration in spontaneously breathing preterm infants. However, there is limited evidence on practical aspects such as sedation and catheter types, leading to considerable variability between centers. METHODS: An anonymous online survey (www.soscisurvey.de) was sent to 164 tertiary neonatal intensive care units (NICUs) in Germany including 43 questions on practical aspects of LISA. RESULTS: Of 122 (74%) participating NICUs, 117 (96%) reported experience with LISA with 82% of those reporting LISA as their preferred method of surfactant administration. Indications for surfactant administration differed widely between NICUs. Most (89%) used FiO2-thresholds only or in combination with other criteria, such as Silverman score/signs of dyspnea (41%) or lung ultrasound findings (3%). Prophylactic surfactant was administered by 42%. Differences in use of LISA in extremely immature infants were reported (e.g., 36% did not perform LISA in infants below 24-26 weeks). Preferred drugs for sedation were (Es-)Ketamine, followed by Propofol and Midazolam. Minimum time interval between subsequent LISA procedures was 4 (2-6) h. Catheters specifically designed for LISA were used by most NICUs (69%). CONCLUSION: This survey shows that LISA is common practice in German NICUs, but with considerable variability in practical aspects. These data may serve as a guidance for NICUs that have not yet implemented LISA and might be helpful design clinical trials with the aim to standardize and/or optimize LISA.

Effectiveness and safety profile of introducing less invasive surfactant administration in management of respiratory distress syndrome: A retrospective cohort study in a tertiary neonatal unit in Hong Kong.

BACKGROUND: The objective was to evaluate the efficacy of introducing less invasive surfactant administration (LISA) for management of preterm neonates with respiratory distress syndrome (RDS). METHODS: This was a retrospective cohort study identifying preterm neonates with RDS born between 2017 and 2022 in a tertiary neonatal unit, where LISA was introduced in January 2020. Time trend analysis comparing cohort of neonates born before (2017-2020) and after LISA introduction (2020-2022) was performed. The primary outcomes were incidence and severity of bronchopulmonary dysplasia (BPD). Multivariable regression models were used to estimate the association between introducing LISA to RDS management and health and safety outcomes. RESULTS: In total, 261 neonates with RDS were included (114 born after LISA was introduced). Neonates receiving invasive surfactant administration had lower gestational age, birth weight, lower Apgar scores, and higher oxygen requirement, compared to those receiving LISA. In the time trend analysis, introduction of LISA was associated with lower incidence of BPD (odds ratio (95% confidence interval) 0.34 (0.16, 0.72)), and lower severity of BPD (0.31 (0.16, 0.59)). Pre- and post-LISA period showed similar treatment safety profiles. CONCLUSION: Introduction of LISA was associated with improved prognosis in neonates with RDS in Hong Kong.

Lung ultrasound for prediction of surfactant requirement in Indian preterm neonates: a diagnostic accuracy study.

Surfactant replacement for respiratory distress syndrome (RDS) is currently guided by oxygen (FiO2) requirement in preterm neonates. Lung ultrasound (LUS) has emerged as an important predictive tool; however, there is a paucity of evidence from developing countries. The objective of this study was to determine the diagnostic accuracy of the LUS score in comparison to standard criteria based on FiO2 requirement for prediction of surfactant requirement. In this prospective study, preterm neonates of < 34 weeks' gestation with RDS were included within 2 h of life. Surfactant was administered if the FiO2 requirement exceeded 30%. Baseline characteristics, respiratory parameters, and LUS clips were recorded soon after birth and compared between the surfactant and non-surfactant groups. LUS scoring was later performed by masked assessors which was not used in the management of neonates. Among 82 neonates (mean gestation 30.6 weeks and weight 1375 g) included in the study, 33 (40.2%) received surfactant. The surfactant group had a higher Silverman score, required higher FiO2 and mean airway pressure, and needed invasive ventilation more frequently. The mean (± SD) LUS score was significantly higher in the surfactant (9.4 ± 3.2) compared to the non-surfactant group (5.1 ± 2.1). The diagnostic accuracy of LUS scoring was determined by ROC curve analysis (AUC (95% CI): 0.83 (0.74-0.92), p < 0.01). A cutoff score of ≥ 8 for LUS was considered optimal for the prediction of surfactant requirement (sensitivity and specificity (95% CI) of 70% (51-84) and 80% (66-90), respectively).    Conclusion: Lung ultrasound is a valid diagnostic tool for the prediction of surfactant requirements in resource-limited settings. What is Known: • Lung ultrasound has a good diagnostic accuracy in predicting the need for surfactant administration in preterm neonates in developed countries, but its role in developing countries is unclear. What is New: • Lung ultrasound proved to be a valid diagnostic tool in predicting surfactant replacement therapy in resource-limited settings. • The diagnostic performance of lung ultrasound was better in neonates on non-invasive ventilation, compared to invasive ventilation.

Low incidence of acute kidney injury in VLBW infants with restrictive use of mechanical ventilation.

BACKGROUND: We assessed the incidence of and risk factors for acute kidney injury (AKI) in very low birthweight infants (VLBW) in a center with a specific neonatal management protocol focusing on avoidance of early mechanical ventilation (MV). METHODS: This retrospective single center analysis includes 128 infants born in 2020 with a gestational age ≥ 22 weeks who were screened for AKI using the nKDIGO criteria. RESULTS: AKI was identified in 25/128 patients (19.5%) with eight of them (6.3%) presenting with severe AKI. Low gestational age, birthweight and 10-minute Apgar score as well as high CRIB-1 score were all associated with incidence of AKI. Forty-five percent of the infants with MV developed AKI vs. 8.9% of those without MV (p < 0.001). Early onset of MV and administration of more than 3 dosages of NSAIDs for patent duct were identified as independent risk factors for AKI in a logistic regression analysis. CONCLUSIONS: We report a substantially lower frequency of AKI in VLBW infants as compared to previous studies, along with a very low rate of MV. A neonatal protocol focusing on avoidance of MV within the first days of life may be a key factor to decrease the risk of AKI in immature infants.

Experience of less invasive surfactant administration with a 5F infant feeding tube in a tertiary center of low- and middle-income countries.

BACKGROUND: Less invasive surfactant administration (LISA) results in less need for mechanical ventilation and a reduction in death, bronchopulmonary dysplasia, and intraventricular hemorrhage as outcomes. This study aimed to evaluate the efficacy and short-term outcomes of surfactant administration by the LISA method using an 5F infant feeding tube in preterm infants. METHODS: During the period from May, 2019 to August, 2022, we carried out a prospective observational study that included all premature infants with respiratory distress syndrome who were admitted to our neonatal intensive care unit. The study involved collecting and analyzing data on the procedural efficacy of LISA, vital parameters, and short-term outcomes. RESULTS: Our study included a total of 110 infants with an average gestational age of 30.9 ± 1.9 weeks and a mean birthweight of 1347.5 ± 354.1 g. Of these infants, two required intubation during the LISA procedure, whereas 11 infants required intubation within 72 h after LISA. Infants with a higher pre-surfactant fraction of inspired oxygen (Fi O2 ) requirement, an elevated Score for Neonatal Acute Physiology with Perinatal Extension (SNAPPE), and the presence of sepsis were associated with the need for intubation within the first 72 h of life. Thirty-one infants also experienced a drop in saturation of peripheral oxygen (SpO2 ) below 80% for more than 1 min. CONCLUSIONS: Less invasive surfactant administration was feasible and safe to administer via an orotracheally introduced 5F infant feeding tube in non-invasive ventilation to support spontaneously breathing infants between 28+0 and 33+6 weeks of gestation.

Comparison of mortality and short-term outcomes between classic, intubation-surfactant-extubation, and less invasive surfactant administration methods of surfactant replacement therapy.

Background: Intubation-Surfactant-Extubation (InSurE) and less invasive surfactant administration (LISA) are alternative surfactant replacement therapy methods for reducing the complications associated with invasive mechanical ventilation. This study aimed to compare the Classic, InSurE, and LISA methods in Very-Low-Birth-Weight infants (VLBWIs) in South Korea. Methods: The Korean Neonatal Network (KNN) enrolled VLBWIs born between January 1, 2019 and December 31, 2020. They were analyzed retrospectively to compare the duration of respiratory support, length of hospitalization, mortality, and short-term outcomes of the three groups. Results: The duration of invasive ventilator support was shorter in the following order: InSurE (3.99 ± 11.93 days), LISA (8.78 ± 29.32 days), and the Classic group (22.36 ± 29.94 days) (p = 0.014, p < 0.01) and InSurE had the shortest hospitalization (64.91 ± 24.07 days, p < 0.05) although the results couldn't adjust for confounding factor because of irregular distribution. InSurE had the lower risk of intraventricular hemorrhage (IVH) grade II-IV [odds ratio (OR) 0.524 [95% confidence interval (CI): 0.287-0.956], p = 0.035] than in the Classic group. Mortality was lower in the InSurE [OR 0.377 (95% CI: 0.146-0.978), p = 0.045] and LISA [OR 0.296 (95% CI: 0.102-0.862), p = 0.026] groups than in the Classic group. There was a reduced risk of moderate to severe bronchopulmonary dysplasia (BPD) [OR 0.691 (95% CI: 0.479-0.998, p = 0.049), OR 0.544 (95% CI: 0.355-0.831, p = 0.005), respectively], pulmonary hypertension [OR 0.350 (95% CI: 0.150-0.817, p = 0.015), OR 0.276 (95% CI: 0.107-0.713, p = 0.008), respectively], periventricular leukomalacia (PVL) [OR 0.382 (95% CI: 0.187-0.780, p = 0.008), OR 0.246 (95% CI: 0.096-0.627, p = 0.003), respectively], and patent ductus arteriosus (PDA) with treatment [OR 0.628 (95% CI: 0.454-0.868, p = 0.005), OR 0.467 (95% CI: 0.313-0.696, p < 0.001) respectively] in the InSurE and LISA groups compared to the Classic group. Conclusion: InSurE showed the lowest duration of invasive ventilator support, length of hospitalization. InSurE and LISA exhibited reduced mortality and decreased risks of moderate to severe BPD, pulmonary hypertension, PVL, and PDA with treatment compared to the Classic group.

Neonatal respiratory support strategies-short and long-term respiratory outcomes.

Mechanical ventilation (MV), although life-saving, is associated with chronic respiratory morbidity in both preterm and term born infants. New ventilation modes have been developed with the aim of minimising lung injury. These include invasive and non-invasive respiratory support strategies, techniques for less invasive surfactant administration (LISA) and closed-loop automated oxygen control (CLAC) systems. Increasingly, newborn infants with signs of respiratory distress are stabilised on continuous positive airway pressure (CPAP) and receive LISA. Early CPAP when compared to mechanical ventilation reduced the incidence of BPD and respiratory morbidity at 18 to 22 months corrected age. Nasal intermittent positive pressure ventilation reduced treatment failure rates compared to CPAP, but not bronchopulmonary dysplasia (BPD). LISA compared with intubation and surfactant delivery reduced BPD, but there is no evidence from randomised trials regarding long-term respiratory and neurodevelopmental outcomes. Synchronisation of positive pressure inflations with the infant's respiratory efforts used with volume targeting should be applied for infants requiring intubation as this strategy reduces BPD. A large RCT with long term follow up data demonstrated that prophylactic high frequency oscillatory ventilation (HFOV) improved respiratory and functional outcomes at school age, but those effects were not maintained after puberty. CLAC systems appear promising, but their effect on long term clinical outcomes has not yet been explored in randomised trials. Further studies are required to determine the role of newer ventilation modes such as neurally adjusted ventilator assist (NAVA). All such respiratory support strategies should be tested in randomised controlled trials powered to assess long-term outcomes.

Assessment of Comfort during Less Invasive Surfactant Administration in Very Preterm Infants: A Multicenter Study.

INTRODUCTION: This study was set up to investigate if and to what extent non-pharmacological analgesia is able to provide comfort to very preterm infants (VPI) during less invasive surfactant administration (LISA). METHODS: This was a prospective non-randomized multicenter observational study performed in level IV NICUs. Inborn VPI with a gestational age between 220/7 and 316/7 weeks, signs of respiratory distress syndrome, and the need for surfactant replacement were included. Non-pharmacological analgesia was performed in all infants during LISA. In case of failure of the first LISA attempt, additional analgosedation could be administered. COMFORTneo scores during LISA were assessed. RESULTS: 113 VPI with a mean gestational age of 27 weeks (+/- 2.3 weeks) and mean birth weight of 946 g (+/- 33 g) were included. LISA was successful at the first laryngoscopy attempt in 81%. COMFORTneo scores were highest during laryngoscopy. At this time point, non-pharmacological analgesia provided adequate comfort in 61% of the infants. 74.4% of lower gestational aged infants (i.e., 220-266 weeks) were within the comfort zone during laryngoscopy compared to 51.6% of higher gestational aged infants (i.e., 270-320 weeks) (p = 0.016). The time point of surfactant administration did not influence the COMFORTneo scores during the LISA procedure. CONCLUSION: Non-pharmacological analgesia provided comfort in as much as 61% of the included VPI during LISA. Further research is needed to both develop strategies to identify infants who, despite receiving non-pharmacological analgesia, are at high risk for experiencing discomfort during LISA and define patient-tailored dosage and choice of analgosedative drugs.

Failure of early non-invasive ventilation in preterm infants with respiratory distress syndrome in current care practice in Spanish level-III neonatal intensive care units - a prospective observational study.

Introduction: Despite advances in respiratory distress syndrome (RDS) management over the past decade, non-invasive ventilation (NIV) failure is frequent and associated with adverse outcomes. There are insufficient data on the failure of different NIV strategies currently used in clinical practice in preterm infants. Methods: This was a prospective, multicenter, observational study of very preterm infants [gestational age (GA) <32 weeks] admitted to the neonatal intensive care unit for RDS that required NIV from the first 30 min after birth. The primary outcome was the incidence of NIV failure, defined as the need for mechanical ventilation for <72 h of life. Secondary outcomes were risk factors associated with NIV failure and complication rates. Results: The study included 173 preterm infants with a median GA of 28 (IQR 27-30) weeks and a median birth weight of 1,100 (IQR 800-1,333) g. The incidence of NIV failure was 15.6%. In the multivariate analysis, lower GA (OR, 0.728; 95% CI, 0.576-0.920) independently increased the risk of NIV failure. Compared to NIV success, NIV failure was associated with higher rates of unfavorable outcomes, including pneumothorax, intraventricular hemorrhage, periventricular leukomalacia, pulmonary hemorrhage, and a combined outcome of moderate-to-severe bronchopulmonary dysplasia or death. Conclusion: NIV failure occurred in 15.6% of the preterm neonates and was associated with adverse outcomes. The use of LISA and newer NIV modalities most likely accounts for the reduced failure rate. Gestational age remains the best predictor of NIV failure and is more reliable than the fraction of inspired oxygen during the first hour of life.

Less Invasive Surfactant Administration for the Treatment of Neonatal Respiratory Distress Syndrome Combined With Noninvasive Ventilation in Anhui Province, China: A Retrospective Cohort Study.

The less invasive surfactant application (LISA) technology has been widely used to manage breathing in premature infants. Premature infants with respiratory distress syndrome (RDS) were retrospectively analyzed and divided into 2 groups according to the drug delivery methods used: LISA versus traditional pulmonary surfactant injection (INSURE). The decrease of transcutaneous saturation (TcSO2) and heart rate during surfactant delivery in the LISA group was higher than that in the INSURE group (P < .05). Between the 2 groups, there was no significant difference in the change in partial pressure of oxygen/fraction of inspired oxygen value before and after drug delivery; second-use pulmonary surfactant; noninvasive ventilation (NIV) failure rate; incidence of some complications; duration of NIV use; hospitalization time; and mortality (P > .05). However, the incidence of bronchopulmonary dysplasia (BPD) in the LISA group was lower than that in the INSURE group (P < .05). The clinical efficacy of LISA combined with the NIV treatment in premature infants with RDS was clear, and this treatment could reduce the incidence of BPD.

Evaluation of methods of surfactant administration in the delivery suite?

Surfactant administered in the delivery suite might prevent or reduce the severity of subsequent respiratory distress syndrome. This review describes the evidence for surfactant delivery methods with relationship to their relevance in the delivery suite. The techniques include delivery using a thin catheter with the first breath, by the intubation-surfactant extubation procedure, less invasive surfactant administration (LISA) technique, using a laryngeal mask airway (LMA), or by nebulisation. There have been few randomised trials that have evaluated outcomes using these techniques in the delivery suite, and these were early trials. Currently, practitioners favour use of nasal continuous positive airway pressure with early rescue surfactant. Whether prophylactic surfactant given by the LISA technique or other techniques, such as via a LMA in the delivery suite, is more beneficial merits testing. This will require appropriately designed randomised trials with long-term outcomes.

Effects of less invasive surfactant administration versus intubation-surfactant-extubation on bronchopulmonary dysplasia in preterm infants with respiratory distress syndrome: a single-center, retrospective study from China.

BACKGROUND: This study evaluated the effects of less invasive surfactant administration (LISA) and intubation-surfactant-extubation (InSurE) on bronchopulmonary dysplasia (BPD) in preterm infants with respiratory distress syndrome (RDS). METHODS: Neonates with respiratory distress syndrome requiring surfactant, with gestational age < 32 weeks and birth weight < 1500 g admitted to our neonatal intensive care unit from January 2018 to December 2019, were retrospectively analyzed. LISA and InSurE were used independently. The incidence of BPD at 36 weeks postmenstrual age, pre-discharge mortality, and need for mechanical ventilation (MV) within 72 h of birth were compared between LISA and InSurE group. Secondary outcomes including necrotizing enterocolitis requiring surgery, retinopathy of prematurity ≥ stage 3, patent ductus arteriosus requiring medical therapy or surgery, and length of hospitalization were analyzed. RESULTS: Among the 148 included neonates, there were 46 and 102 infants in LISA group and InSurE group, respectively. There were no significant differences in BPD incidence, the severity of BPD at 36 weeks postmenstrual age, and the rate of MV within the first 72 h after birth between the two groups (P > 0.05, respectively). The incidences of necrotizing enterocolitis requiring surgery, retinopathy of prematurity ≥ stage 3, patent ductus arteriosus requiring medical therapy or surgery, and length of hospitalization did not differ significantly between the two groups (P > 0.05, respectively). CONCLUSIONS: For surfactant administration among preterm infants with respiratory distress syndrome, LISA did not decrease bronchopulmonary dysplasia and severity of BPD at 36 weeks postmenstrual age. The benefits of LISA would require further evaluations.

Health Economics of Selective Early Rescue Surfactant Administration and Standard Surfactant Administration for Newborns With Respiratory Distress Syndrome.

OBJECTIVE: To quantify the effect of early rescue surfactant administration techniques for preterm infants with respiratory distress syndrome (RDS) from a health care delivery system perspective. METHODS: A cost-consequence model was developed based on previously published literature to compare the health economic impact of implementing early surfactant administration strategies vs standard surfactant administration via endotracheal intubation and mechanical ventilation (MV). RESULTS: Early rescue surfactant treatment strategies are associated with a decrease in the number of patients requiring MV, cumulative MV days, and rate of neonatal complications. Total annual surfactant costs are higher than standard surfactant administration, but this is offset by savings in total hospital and complication costs. CONCLUSIONS: This cost-consequence analysis suggests selective early rescue surfactant administration strategies are associated with a lower health care burden in premature infants with RDS.

Less Invasive Surfactant Administration: A Review of Current Evidence of Clinical Outcomes With Beractant.

Evidence supporting clinical recommendations or approval for less invasive surfactant administration (LISA) has primarily examined heterogeneous or small-volume (e.g., 1.25-2.5 mL/kg) animal-derived surfactant regimens. To address the evidence gap for larger-volume (e.g., 4-5 mL/kg) animal-derived surfactants, the aim of this review was to evaluate and summarize LISA literature for widely used larger-volume beractant. Surfactant treatment and the LISA technique were initially summarized. The available literature on beractant with LISA was thoroughly assessed and reviewed, including a recent systematic analysis, studies from regions where access or preferences may influence reliance on larger-volume surfactants, and investigations of short- and long-term outcomes. The available literature indicated improved short-term outcomes, including less need for mechanical ventilation, death, or bronchopulmonary dysplasia, and no negative long-term developmental outcomes when beractant was administered via LISA compared with older, more invasive techniques. The rates of short-term outcomes were similar to those previously observed in examinations of LISA with small-volume surfactants, including in populations reflecting very preterm infants. As uptake of LISA is expected to increase, future research directions for larger-volume surfactants include cost-effectiveness evaluations and robust examinations of repeat dosing and surfactant reflux to further inform clinical practice. This review provides a detailed assessment of the literature describing surfactant and LISA, with a focus on studies of beractant. Collectively, the available evidence supports the use of beractant with LISA based both on short-term and long-term outcomes relative to more invasive techniques and comparability of outcomes with small-volume surfactants and may be valuable in guiding clinical decision-making.

Device positioning with LISA vs. INSURE: a crossover randomized controlled manikin trial.

OBJECTIVE: We aimed to compare time of device positioning, success of procedure and operator's opinion with LISA vs. INSURE in a manikin simulating an extremely low birthweight infant. METHODS: A randomized controlled crossover (AB/BA) trial of surfactant administration with LISA vs. INSURE in a preterm manikin. Forty-two tertiary hospital consultants and pediatric residents with previous experience with LISA and INSURE participated. The primary outcome measure was the time of device positioning. The secondary outcome measures were: success of the first attempt, number of attempts, correct depth, and participant's opinion on difficulty in using the device. RESULTS: Median time of device positioning was shorter with LISA vs. INSURE (median difference -8 s, 95% confidence interval -16 to -1 s; p = .04). Success at first attempt was 35/40 with LISA (83%) and 31/40 with INSURE (74%) (p = .42). Median number of attempts was 1 (IQR 1-1) with LISA and 1 (IQR 1-2) with INSURE (p = .08). Correct depth was achieved in 30/40 with LISA (71%) and 37/40 with INSURE (88%) (p = .12). Participants found LISA easier to insert in the trachea (p = .002) but INSURE easier to place at the correct depth (p = .008). Handling the device (p = .43), visualizing the glottis (p = .17) and overall difficulty in using the device (p = .13) were not statistically different. CONCLUSIONS: In a preterm manikin model, positioning a thin catheter (LISA) was quicker and easier than a tracheal tube (INSURE), but the magnitude of the difference was unlikely to be clinically relevant and the tracheal tube was easier to place at the correct depth. REGISTRATION: clinicaltrial.gov NCT04944108.