Surfactant administration methods for premature newborns: LISA vs. INSURE comparative analysis.

INTRODUCTION: Respiratory Distress Syndrome (RDS) is the most common respiratory disorder among premature infants. The use of surfactant has significantly reduced respiratory complications and mortality. There are two conventional methods for administering surfactant: Intubate-Surfactant-Extubate (INSURE) and Less Invasive Surfactant Administration (LISA). This study aims to compare the effects of surfactant administration using these two methods on the treatment outcomes of premature newborns. MATERIALS AND METHODS: In this retrospective cohort study, we included 100 premature newborns with RDS and spontaneous breathing who were admitted to the Neonatal Intensive Care Unit of Besat Hospital in Sanandaj city in 2021. Exclusion criteria comprised congenital anomalies and the needing for intubation for resuscitation at birth. The outcomes of epmericaly trated with two methods were compared: the LISA (50 neonates) and the INSURE (50 neonates). Our interesting outcomes were needing for mechanical ventilation, duration of ventilation, pneumothorax, pulmonary hemorrhage, severe retinopathy, CPAP duration, and bronchopulmonary dysplasia. Finally, we entered the data into STATA-14 statistical software and analyzed it using chi-square and t-tests. RESULTS: In this study, 69% of the neonates were boys. The LISA group exhibited significantly lower rates of need for mechanical ventilation (P = 0.003) and ventilation duration (P < 0.001) compared to the INSURE group. Conversely, there were no significant differences between the two groups (P > 0.05) in terms of pneumothorax, pulmonary hemorrhage, severe retinopathy, CPAP duration, and bronchopulmonary dysplasia rates. CONCLUSION: The results of this study suggest that the LISA method is a safe and non-invasive approach for surfactant administration. Notably, it resulted in a reduced need for mechanical ventilation and decreased ventilation duration compared to the INSURE method.

Less Invasive Surfactant Administration (LISA) Versus INSURE Method in Preterm Infants: a Retrospective Study.

Background: Respiratory distress syndrome (RDS) is a major cause of morbidity and mortality in preterm infants. Early nasal CPAP and selective administration of surfactant via the endotracheal tube are widely used in the treatment of RDS in preterm infants. Objective: The aim of this study was to compare the need for intubation and mechanical ventilation after surfactant delivery between LISA-treated and INSURE-treated premature infants with respiratory distress syndrome (RDS). Methods: Retrospective registry-based cohort study enrolled 36 newborns admitted to the neonatal intensive care unit of the "Santa Maria" Hospital of Terni between 2016 and 2023. As a primary outcome, we followed the need for intubation and mechanical ventilation within 72 hours of life, while the secondary outcomes were major neonatal morbidities and death before discharge. Results: The LISA group and the INSURE group included 13 and 23 newborns respectively. Demographic features showed no significant differences between the two groups. The need for mechanical ventilation in the first 72 hours of life was similar in both groups (p >0.99). There were no significant differences in morbidities. Conclusion: LISA and INSURE are equally effective modalities for surfactant administration for the treatment of RDS in preterm infants.

Less invasive surfactant administration versus intubation-surfactant-extubation in the treatment of neonatal respiratory distress syndrome: a systematic review and meta-analyses.

OBJECTIVES: To compare LISA with INSURE technique for surfactant administration in preterm with gestational age (GA) < 36 weeks with RDS in respect to the incidence of pneumothorax, bronchopulmonary dysplasia (BPD), need for mechanical ventilation (MV), regional cerebral oxygen saturation (rSO2), peri­intraventricular hemorrhage (PIVH) and mortality. METHODS: A systematic search in PubMed, Embase, Lilacs, CINAHL, SciELO databases, Brazilian Registry of Randomized Clinical Trials (ReBEC), Clinicaltrials.gov, and Cochrane Central Register of Controlled Trials (CENTRAL) was performed. RCTs evaluating the effects of the LISA technique versus INSURE in preterm infants with gestational age < 36 weeks and that had as outcomes evaluation of the rates of pneumothorax, BPD, need for MV, rSO2, PIVH, and mortality were included in the meta-analysis. Random effects and hazard ratio models were used to combine all study results. Inter-study heterogeneity was assessed using Cochrane Q statistics and Higgin's I2 statistics. RESULTS: Sixteen RCTs published between 2012 and 2020 met the inclusion criteria, a total of 1,944 preterms. Eleven studies showed a shorter duration of MV and CPAP in the LISA group than in INSURE group. Two studies evaluated rSO2 and suggested that LISA and INSURE transiently affect brain autoregulation during surfactant administration. INSURE group had a higher risk for MV in the first 72 h of life, pneumothorax, PIVH and mortality in comparison to the LISA group. CONCLUSION: This systematic review and meta-analyses provided evidence for the benefits of the LISA technique in the treatment of RDS, decreasing CPAP time, need for MV, BPD, pneumothorax, PIVH, and mortality when compared to INSURE.

Ultrasound evaluation of diaphragm kinetics after minimally invasive surfactant administration.

PURPOSE: Concerns remain on different alveolar deposition of surfactant between LISA and INSURE methods. Ultrasound evaluation of diaphragm kinetics may provide clinical evidence on this issue, as indirect representation of the respiratory system compliance. METHODS: This was a prospective-observational pilot study. The inclusion criterion was CPAP-supported infants ≤ 32 weeks with RDS receiving surfactant via minimally invasive technique. 52 patients randomized for surfactant administration via LISA or INSURE methods were enrolled. Right diaphragm (RD) global mean peak velocity (MPV) by Pulsed-Wave Tissue Doppler Imaging (PTDI) was recorded before and two hours after surfactant administration with simultaneous measurements of oxygen saturation (SpO2)/fraction of inspired oxygen (FiO2) (SF ratio). Mechanical ventilation ≤ 72 h from birth represented treatment failure. RESULTS: LISA infants had significantly higher gestational age (p = 0.029) and birth weight (p = 0.030) with lower CRIB-II scores (p = 0.030) than INSURE infants. LISA infants showed higher median MPV at baseline RD-PTDI US assessment (p = 0.024), but post-surfactant median MPV and other the investigated variables were similar at the adjusted analysis for gestational age and sedation. 8/52 (15%) infants who failed treatment had a significantly lower SF ratio (p = 0.002) and higher median MPV at RD-PTDI US (p = 0.004) after surfactant administration, despite the higher CPAP support level before (p = 0.007) and after (p = 0.001) surfactant administration. A full course of antenatal steroids was protective against mechanical ventilation (p = 0.038). CONCLUSIONS: Different minimally invasive surfactant administration techniques do not appear to influence diaphragm kinetics evaluated by RD-PTDI US.

Less invasive surfactant administration versus intubation-surfactant-extubation in the treatment of neonatal respiratory distress syndrome: a systematic review and meta-analyses

Abstract Objectives To compare LISA with INSURE technique for surfactant administration in preterm with gestational age (GA) < 36 weeks with RDS in respect to the incidence of pneumothorax, bronchopulmonary dysplasia (BPD), need for mechanical ventilation (MV), regional cerebral oxygen saturation (rSO2), peri‑intraventricular hemorrhage (PIVH) and mortality. Methods A systematic search in PubMed, Embase, Lilacs, CINAHL, SciELO databases, Brazilian Registry of Randomized Clinical Trials (ReBEC), Clinicaltrials.gov, and Cochrane Central Register of Controlled Trials (CENTRAL) was performed. RCTs evaluating the effects of the LISA technique versus INSURE in preterm infants with gestational age < 36 weeks and that had as outcomes evaluation of the rates of pneumothorax, BPD, need for MV, rSO2, PIVH, and mortality were included in the meta-analysis. Random effects and hazard ratio models were used to combine all study results. Inter-study heterogeneity was assessed using Cochrane Q statistics and Higgin's I2 statistics. Results Sixteen RCTs published between 2012 and 2020 met the inclusion criteria, a total of 1,944 preterms. Eleven studies showed a shorter duration of MV and CPAP in the LISA group than in INSURE group. Two studies evaluated rSO2 and suggested that LISA and INSURE transiently affect brain autoregulation during surfactant administration. INSURE group had a higher risk for MV in the first 72 h of life, pneumothorax, PIVH and mortality in comparison to the LISA group. Conclusion This systematic review and meta-analyses provided evidence for the benefits of the LISA technique in the treatment of RDS, decreasing CPAP time, need for MV, BPD, pneumothorax, PIVH, and mortality when compared to INSURE.

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.

Comparison of Beractant Administration by Thin Catheter vs Intubation-Surfactant-Extubation (INSURE) in Preterm Infants Less than 34 Weeks Gestational Age with Respiratory Distress Syndrome - A Single Centre Experience.

BACKGROUND: Poractant administration with thin catheter is gradually gaining popularity compared to the INSURE technique. However, there is little evidence to use thin catheters for administration of beractant. With this background, we compared the effect of beractant administration with INSURE vs thin catheter in preterm infants less than 34 weeks with RDS on death/chronic lung disease (CLD). METHODS: This prospective cohort study was conducted in a tertiary NICU where inborn preterm infants≤34 weeks with RDS receiving beractant by INSURE or thin catheter were studied over two epochs- Epoch1- INSURE (Jan 2020-Oct 2020) & Epoch 2- Surfactant through thin catheter (Nov 2020-July 2021).The primary outcome was occurrence of death/CLD. Procedure related complications like transient bradycardia/desaturation, pneumothorax, failure of procedure, rates of other outcomes like failure of CPAP within 72hr, duration of invasive mechanical ventilation/ CPAP support, oxygen supplementation, other major neonatal morbidities & mortality were evaluated as secondary outcomes. RESULTS: The combined outcome of death/CLD was significantly lower in the thin catheter epoch (RR 0.56, 95% CI 0.34-0.90, p = 0.012). When analyzed independently for death/CLD, we found significantly lower number of deaths in the thin catheter epoch (RR 0.44, 95% CI 0.23-0.83, p = 0.008). Number of infants who failed CPAP within 72 hrs of life was lower in thin catheter epoch (RR 0.59, 95% CI 0.41-0.85, p = 0.003). Transient bradycardia/desaturation was higher during thin catheter technique (RR 4.17, 95% CI 2.22-7.69, p < 0.001). Incidence of severe IVH was lower with thin catheter technique (RR 0.13, 95% CI 0.02-0.98, p = 0.034). CONCLUSION: Beractant administration by thin catheter reduces combined outcome of death/CLD.

Efficacy and safety of surfactant administration by MIST and INSURE techniques in Neonates with Respiratory Distress Syndrome: A randomized controlled trial.

Objective: To measure the efficacy and safety of surfactant administered by MIST and INSURE to neonates with respiratory distress syndrome. Methods: A randomized controlled trial was conducted from June 2021 to August 2022 at the NICU of the University of Child Health Sciences, Lahore. Neonates meeting inclusion criteria i.e with RDS who worsened on nasal Continuous positive airway pressure (nCPAP) (fiO2 30%, pressure 6cmH2O) were enrolled in the study in both interventional arms (MIST, n=36 and INSURE, n=36) using simple random sampling. Data was analysed using SPSS 25. Results: The mean age of neonates in MIST was 1.27±0.40 days and 1.23±0.48 days in INSURE cohort. Neonates with MIST (n=8) required statistically significant reduced need for IMV than INSURE (n=17) technique (P-Value 0.047). This study could not achieve significant difference in duration of mechanical ventilation (1±1.67; 1.52±1.40 days, P=0.152) and duration of nCPAP (3.27±1.65;3.67±1.64 hrs, P=0.312) in MIST versus INSURE. The second dose of surfactant was administered in fewer cases in MIST (n=2) than INSURE (n=7) (P=0.075). Risk estimation, although not significant, determined less likelihood for the pulmonary haemorrhage (0.908 than 1.095), intraventricular hemorrhage (0.657 than 1.353), administration of the second dose of surfactant (0.412 than 1.690) and greater likelihood of discharge (1.082 than 0.270) at 95% confidence interval with MIST technique. Conclusion: Surfactant therapy through MIST is effective and there is significantly reduced need of IMV than in INSURE. Safety profile though could not achieve statistical significance yet determines less risk of complications associated with MIST than INSURE.RCT Registration Number: TCTR20210627001.

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.

Early Surfactant Therapy for Respiratory Distress Syndrome in Very Preterm Infants.

BACKGROUND: It is currently considered that early initiation of nasal continuous positive airway pressure, using a less invasive exogenous surfactant administration and avoiding mechanical ventilation as much as possible to minimize lung damage, may reduce mortality and/or the risk of morbidities in preterm infants. The aim of our study was to quantify our experience and compare different strategies of surfactant administration, to investigate which method is associated with less morbidity. MATERIALS AND METHODS: A total of 135 preterm infants with early rescue surfactant administration for respiratory distress syndrome were included in the study. The infants were treated in an academic, Level III Neonatal Intensive Care Unit over a 3-year period between 1 December 2018 and 1 December 2021. Patients were separated into three groups: those with standard surfactant administration; those with Less Invasive Surfactant Administration-LISA; and those with Intubation Surfactant Administration Extubation-INSURE. As a primary outcome, we followed the need for intubation and mechanical ventilation within 72 h, while the secondary outcomes were major neonatal morbidities and death before discharge. RESULTS: The surfactant administration method was significantly associated with the need for mechanical ventilation within 72 h after the procedure (p < 0.001). LISA group infants needed less MV (OR = 0.538, p = 0.019) than INSURE group infants. We found less morbidities (OR = 0.492, p = 0.015) and deaths before discharge (OR = 0.640, p = 0.035) in the LISA group compared with the INSURE group. The analysis of morbidities found in infants who were given the surfactant by the LISA method compared with the INSURE method showed lower incidence of pneumothorax (3.9% vs. 8.8%), intraventricular hemorrhage (17.3% vs. 23.5%), intraventricular hemorrhage grade 3 and 4 (3.9% vs. 5.9%), sepsis/probable sepsis (11.5% vs. 17.7%) retinopathy of prematurity (16.7% vs. 26.7%) and deaths (3.9% vs. 5.9%). There were no significant differences between groups in frequencies of bronchopulmonary dysplasia, necrotizing enterocolitis and patent ductus arteriosus. CONCLUSIONS: Less invasive surfactant administration methods seem to have advantages regarding early need for mechanical ventilation, decreasing morbidities and death rate. In our opinion, the LISA procedure may be a good choice in spontaneously breathing infants regardless of gestational age.

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.

Implementation of Surfactant Administration through Laryngeal or Supraglottic Airways (SALSA): A Jordanian NICU's Journey to Improve Surfactant Administration.

Administration of liquid surfactant through an endotracheal tube for the treatment of respiratory distress syndrome has been the standard of care for decades. Surfactant administration through laryngeal or supraglottic airways (SALSA) is a simplified procedure for delivery of surfactant that is less invasive and better tolerated. The Al Bashir Maternity and Children's Hospital NICU in Amman, Jordan, implemented SALSA as a potentially better practice in 2019 with the objective to effectively and efficiently deliver surfactant in a minimally invasive way and to decrease the adverse events associated with intubation−surfactant−extubation (InSurE) and laryngoscopy. The quality improvement initiative was conducted from March 2019 to December 2019. All infants who weighed 750 g or more who required surfactant were eligible. As physicians were trained in the technique and use expanded, we were able to use plan−do−study−act cycles to observe differences between SALSA and InSurE. The primary aim was the optimization of non-invasive ventilation by the effective and efficient delivery of surfactant. Balancing measures included episodes of bradycardia while receiving surfactant or the need for a second dose of surfactant. We evaluated 220 infants who received surfactant by SALSA or InSurE with a mean gestational age of 32 weeks and a mean birth weight of 1.8 kg. The Respiratory Severity Score (RSS) prior to surfactant administration was 2.7 in the SALSA group compared to 2.9 in the InSurE group (p = 0.024). Those in the InSurE group had a lower mean heart rate during the procedure (p =< 0.0001) and were more likely to need a second dose of surfactant (p = 0.026) or require intubation for mechanical ventilation (p = 0.022). Both groups were effectively delivered surfactant as evidenced by improvement in their RSS over an 8 h period. SALSA was a more time efficient surfactant delivery method (93 vs. 111 secs, p =< 0.0001). Implementation of SALSA into the Al Bashir NICU was successful. We found that it was equally effective to InSurE, but was a more efficient method of delivery. Infants who received surfactant by this method tolerated it well.

Post-INSURE Administration of Heated Humidified High-Flow Therapy Versus Nasal Continuous Positive Airway Pressure in Preterm Infants More Than 28 Weeks Gestation with Respiratory Distress Syndrome: A Randomized Non-Inferiority Trial.

In preterm infants with respiratory distress syndrome (RDS), non-invasive ventilation (NIV) is usually provided using nasal continuous positive airway pressure (NCPAP) or non-invasive mechanical ventilation after surfactant administration by INtubation-SURfactant-Extubation (INSURE) method. Heated humidified high-flow nasal cannula (HHHFNC) is a mode of NIV with advantages of ease of application, less grades of nasal injury and easy handling. This study was done to compare the effectiveness of HHHFNC therapy administration as post-INSURE respiratory support in preterm infants as compared to NCPAP. The primary outcome was to compare the rate of treatment failure within 7 days of randomization to HHHFNC or NCPAP as a post-INSURE ventilatory modality. It was a pilot trial wherein all preterm infants more than 1 kg and more than 28 weeks gestational age with RDS who required surfactant were randomized to receive NCPAP or HHHFNC. Infants with an urgent need for intubation and mechanical ventilation were considered to have treatment failure. Thirty babies were enrolled-15 in each group. Baseline demographic characteristics were comparable. There was no significant difference in the primary outcome of early failure rate, i.e. mechanical ventilation rate within 7 days of starting treatment. There were no significant differences in other outcomes except nasal injury which was significantly lesser in the HHHFNC group. In conclusion, HHHFNC appears to be non-inferior to NCPAP when used in preterm infants more than 28 weeks gestation with RDS as a post-INSURE ventilatory modality.

Lung recruitment improves the efficacy of intubation-surfactant-extubation treatment for respiratory distress syndrome in preterm neonates, a randomized controlled trial.

BACKGROUND: Lung recruitment is a maneuver used to decrease the length of intubation in preterm neonates. This study aimed to compare the therapeutic efficacy of lung recruitment plus intubation-surfactant-extubation (INSURE) procedure and INSURE alone for the preterm neonates with respiratory distress syndrome. METHODS: From 2017 to 2019, 184 preterm neonates (gestational age 24-32 weeks) with respiratory distress syndrome were enrolled and randomized into the lung recruitment group receiving lung recruitment (25 cm H2O, 15 s) plus INSURE and the control group receiving INSURE only. The primary outcome was the need for mechanical ventilation (MV) within 72 h after extubation. The secondary outcomes included duration of MV, noninvasive ventilation, total oxygen therapy, hospitalization time, and complications. RESULTS: Compared to the control group, the lung recruitment group had a significantly lower proportion of preterm neonates requiring MV within 72 h after extubation (23% vs. 38%, P = 0.025) and pulmonary surfactant administration, as well as a shorter MV duration. There was no significant difference in the incidences of complications (all P > 0.05) and in-hospital mortality (2% vs. 4%, P = 0.4) between the lung recruitment group and control group. Multivariate logistic regression analysis demonstrated that the control group had a 2.17-time higher risk of requiring MV than the lung recruitment group (AOR: 2.17, 95% CI: 1.13-4.18; P = 0.021). Compared with infants with a normotensive mother, infants with a hypertensive mother have a 2.41-time higher risk of requiring MV (AOR: 2.41, 95% CI: 1.15-5.05; P = 0.020). CONCLUSION: Lung recruitment plus INSURE can reduce the need for MV within 72 h after extubation and did not increase the incidence of complications and mortality. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR1800020125 , retrospectively registered on December 15, 2018.

Comparison of minimally invasive surfactant therapy with intubation surfactant administration and extubation for treating preterm infants with respiratory distress syndrome: a randomized clinical trial.

BACKGROUND: Respiratory distress syndrome (RDS) is a common cause of hospitalization and death in preterm infants who require surfactant treatment and respiratory support. PURPOSE: This study aimed to compare the clinical outcomes of minimally invasive surfactant therapy (MIST) and the INtubation, SURfactant administration, and Extubation (INSURE) technique in preterm infants with RDS. METHODS: In this clinical trial, 112 preterm infants born at 28-36 weeks of gestation and diagnosed with RDS randomly received 200-mg/kg surfactant by MIST or the INSURE method. In the MIST group, surfactant was administered using a thin catheter (5F feeding tube); in the INSURE group, surfactant was administered after intubation using a feeding tube and the tracheal tube was removed after positive pressure ventilation was started. Nasal continuous positive airway pressure was applied in both groups for respiratory support and the postprocedure clinical outcomes were compared. RESULTS: The mean hospitalization time was shorter for infants in the MIST group than for those in the INSURE group (9.19± 1.72 days vs. 10.21±2.15 days, P=0.006). Patent ductus arteriosus was less frequent in the MIST group (14.3% vs. 30.4%, P=0.041). Desaturation during surfactant administration occurred less commonly in the MIST group (19.6% vs. 39.3%, P=0.023). There were no significant intergroup differences in other early or late complications. CONCLUSION: These results suggest that surfactant administration using MIST could be a good replacement for INSURE in preterm infants with RDS since its use reduced the hospitalization time and the number of side effects.

Minimally invasive surfactant therapy versus intubation for surfactant delivery in preterm infant with RDS: evaluation of safety and efficacy.

BACKGROUND: Minimally invasive surfactant therapy (MIST) is a promising mode of administration that offers the potential to limit barotrauma and prevent lung injury in preterm infants with respiratory distress syndrome (RDS). OBJECTIVE: This study assessed the effects of the implementation of MIST on safety and efficacy in infants who met criteria for surfactant administration and were treated by MIST as compared with a historical control group treated with surfactant via an endotracheal tube during mechanical ventilation. METHODS: This retrospective study included infants born between 2012 and 2017 who met the following inclusion criteria: gestational age 23-36 + 6 weeks, a diagnosis of RDS requiring at least 30% oxygen with or without nasal continuous positive airway pressure (nCPAP). MIST was introduced in 2014 and a comparison was made between the study group who received MIST and the control group who met similar criteria and received surfactant via an endotracheal tube during mechanical ventilation. RESULTS: No significant differences were found between the groups in baseline and demographic data. Severity of initial disease, assessed by the CRIB II score, was similar in the two groups (control 4.6 ± 2.8, MIST 4.4 ± 2.4, p=.995). The requirement for oxygen during the first 3 d of life was significantly lower (area under the curve [AUC]: p=.001) in the MIST group as assessed by the AUC. Likewise, the mean days of oxygen requirement were significantly lower in the MIST group (Control: 10.3 d, MIST: 5.9 d, p=.04). Only six infants in the MIST group (13%) subsequently required intubation for mechanical ventilation, only one of whom adjacent to the procedure. A modest reduction in duration of ventilation was also noted. Duration of admission was 32 ± 23 d in the control group and 26 ± 21 d in the MIST group, p=.061. No significant differences were found between the groups in the incidence of major morbidities or mortality. No major adverse events related to the procedure were observed. CONCLUSIONS: Transition to MIST was associated with significantly reduced need for oxygen, mechanical ventilation and surfactant, and a borderline shortened NICU admission.

Early risk factors for the failure of the INSURE strategy in premature infants with respiratory distress syndrome / 中国新生儿科杂志

Objective:To study the early risk factors for the failure of INtubation-SURfactant-Extubation (INSURE) strategy in preterm infants with respiratory distress syndrome (RDS).Methods:From November 2016 to October 2020, preterm infants with gestational age (GA) <34 weeks admitted to our hospital were enrolled in this study. Infants required invasive ventilation within 72 hours after extubation were assigned into INSURE failure group and other infants INSURE success group. SPSS 25.0 was used to compare the clinical data of the two groups and Logistic regression analysis was used to analyze the independent risk factors of INSURE failure.Results:The incidence of INSURE strategy failure was 25.0% (34/136). The antenatal dexamethasone use, GA, birth weight, 1 min Apgar score, 5 min Apgar score, respiratory index (PaO 2/FiO 2) and mean hemoglobin (Hb) in INSURE failure group were significantly lower than INSURE success group ( P<0.05). INSURE failure group had significantly delayed use of first-time pulmonary surfactant (PS), longer duration of positive pressure ventilation resuscitation, higher respiratory score in Apgar, higher procalcitonin (PCT) level, more placental chorioamnionitis and more RDS radiological grade ≥3 cases than INSURE success group ( P<0.05). Logistic regression analysis showed that respiratory score ≥8 ( OR=10.609, 95% CI 2.630~42.797, P=0.001), RDS radiological grade ≥ 3 ( OR=8.813, 95% CI 2.022~38.423, P=0.004) and Hb<145 g/L ( OR=9.074, 95% CI 1.771~46.147, P=0.008) were independent risk factors for INSURE failure. And antenatal dexamethasone use ( OR=0.270, 95% CI 0.075~0.978, P=0.046) was a protective factor for INSURE failure. Conclusions:Respiratory score ≥8 in Apgar, RDS radiological grade ≥3, Hb<145 g/L and the insufficient use of antenatal dexamethasone are independent risk factors for INSURE failure.

Less Invasive Surfactant Administration (LISA) vs. Intubation Surfactant Extubation (InSurE) in Preterm Infants with Respiratory Distress Syndrome: A Pilot Randomized Controlled Trial.

OBJECTIVE: There has been an endeavor in recent years, to administer surfactant by minimally invasive techniques to neonates with surfactant deficiency. The objective of this study was to compare the need for intubation and mechanical ventilation after surfactant delivery, using Less Invasive Surfactant Administration (LISA) technique and Intubation SURfactant Extubation (InSurE), in preterm infants with respiratory distress syndrome (RDS). METHODS: We conducted a pilot randomized control trial (RCT) at a tertiary care center over a period of 18 months. Preterm neonates with RDS (gestational age 28-36 weeks) were randomized to receive surfactant within 6 h of birth by InSurE or LISA. The primary outcome was need for intubation and mechanical ventilation within 72 h of birth. Infants were followed until discharge for adverse events and complications. RESULTS: A total of 40 infants were analyzed (20 in each group). There was no difference in the need for intubation and mechanical ventilation within 72 h of birth between the two groups [InSurE, 6 (30%) and LISA, 6 (30%), relative risk 1.0, 95% confidence interval 0.51-1.97]. About 15% of infants in both groups had adverse events during the procedure. There was no statistically significant difference in the rates of major complications or duration of respiratory support, hospital stay and mortality. CONCLUSION: We found LISA to be feasible and equally effective as InSurE for surfactant administration in the treatment of RDS in preterm infants. Future larger RCTs are required to compare the efficacy and long-term outcomes of LISA with the standard invasive methods of surfactant administration.

Examining Variations in Surfactant Administration (ENVISION): A Neonatology Insights Pilot Project.

Variability in neonatal clinical practice is well recognized. Respiratory management involves interdisciplinary care and often is protocol driven. The most recent published guidelines for management of respiratory distress syndrome and surfactant administration were published in 2014 and may not reflect current clinical practice in the United States. The goal of this project was to better understand variability in surfactant administration through conduct of health care provider (HCP) interviews. Questions focused on known practice variations included: use of premedication, decisions to treat, technique of surfactant administration and use of guidelines. Data were analyzed for trends and results were communicated with participants. A total of 54 HCPs participated from June to September 2020. In almost all settings, neonatologists or nurse practitioners intubated the infant and respiratory therapists administered surfactant. The INSURE (INtubation-SURrfactant-Extubation) technique was practiced by 83% of participants. Premedication prior to intubation was used by 76% of HCPs. An FiO2 ≥ 30% was the most common threshold for surfactant administration (48%). In conclusion, clinical practice variations exist in respiratory management and surfactant administration and do not seem to be specific to NICU level or institution type. It is unknown what effects the variability in clinical practice might have on clinical outcomes.

LISA/MIST: Complex clinical problems almost never have easy solutions.

Over the last 10 years, new techniques to administer surfactant have been promoted, based on their presumed lesser invasiveness and they have been generally called LISA (less invasive surfactant administration). We believe that the clinical potential of LISA techniques is currently overestimated. LISA lacks biological and pathophysiological background justifying its potential benefits. Moreover, LISA has been investigated in clinical trials without previous translational data and these trials are affected by significant flaws. The available data from these trials only allow to conclude that LISA is better than prolonged, unrestricted invasive ventilation with loosely described parameters, a mode of respiratory support that should be anyway avoided in preterm infants. We urge the conduction of high-quality studies to understand how to choose and titrate analgesia/sedation and optimize surfactant administration in preterm neonates. We offer a comprehensive, evidence-based review of the clinical data on LISA, their biases and the lack of physiopathology background.