Surfactant Administration Methods in Preterm Infants With RDS: A Swedish Cohort Study

Vastra Gotaland Region300 enrolled

Overview

The goal of this observational study is to evaluate different methods of surfactant administration in preterm infants with respiratory distress syndrome (RDS). Preterm infants often have immature lungs and a deficiency of surfactant, a substance that helps keep the lungs open and supports oxygen exchange.Surfactant can be delivered to the lungs using different techniques, including INSURE (brief intubation), LISA (via a thin catheter), SALSA (via a laryngeal mask airway), and traditional administration via endotracheal intubation followed by mechanical ventilation. The main question this study aims to answer is:Which method of surfactant administration is associated with better clinical outcomes in preterm infants with RDS?The study will prospectively collect clinical data on infants receiving surfactant as part of standard care, with long-term follow-up using data from the Swedish Neonatal Quality Register. The results are intended to be used to inform the design of a future randomized multicenter study.

Background Complications of preterm birth are the leading cause of child mortality worldwide, with respiratory distress syndrome (RDS) as a major contributor. RDS is primarily caused by surfactant deficiency due to immature lungs. Early surfactant therapy, in combination with antenatal corticosteroids and non-invasive respiratory support such as continuous positive airway pressure (CPAP), is central to treatment. However, mechanical ventilation is associated with an increased risk of lung injury and bronchopulmonary dysplasia (BPD), prompting the development of less invasive surfactant administration techniques. Surfactant Administration Methods Three main methods are currently used in spontaneously breathing preterm infants. The INSURE method involves transient intubation for surfactant delivery followed by extubation. Less Invasive Surfactant Administration (LISA) uses a thin catheter inserted below the vocal cords under laryngoscopy, allowing continued spontaneous breathing. LISA is recommended as first-line treatment in European guidelines due to improved outcomes compared to INSURE. However, both methods require laryngoscopy and are technically demanding, with potential adverse events. Surfactant Administration via Laryngeal or Supraglottic Airways (SALSA) is a newer, less invasive technique that delivers surfactant via a supraglottic airway without laryngoscopy or passage through the vocal cords. Preliminary studies suggest comparable effectiveness to INSURE and CPAP, with potential safety advantages. Historically, SALSA has been limited to larger infants due to lack of appropriately sized devices, but newly available CE-marked devices now enable its use in extremely preterm infants. Rationale Despite widespread use of INSURE, LISA, and SALSA, there are no direct comparisons between LISA and SALSA, and real-world data on their implementation, safety, and outcomes are limited. In Sweden, these methods are used variably across neonatal units, and their relative use and outcomes have not been systematically evaluated. The availability of smaller supraglottic airway devices now allows evaluation of SALSA in the most vulnerable population, including extremely preterm infants. Aim The primary aim is to prospectively evaluate and compare the feasibility, safety, clinical performance, and procedural characteristics of surfactant administration methods (SALSA, LISA, INSURE) in spontaneously breathing preterm infants in a real-world clinical setting. Secondary aims include comparison with infants receiving surfactant via intubation followed by mechanical ventilation, evaluation of short- and long-term clinical outcomes, and generation of data to inform the design of a future randomized multicentre trial. Study Design This is a prospective, multicentre, observational study conducted in neonatal intensive care units (NICUs) in Region Västra Götaland (VGR), Sweden. No interventions are introduced, and all treatment decisions are made according to local clinical guidelines. Study Population Eligible participants are preterm infants (37 weeks' gestation) receiving their first surfactant treatment within 48 hours of birth due to suspected or confirmed RDS. Infants are included regardless of administration method. Data Collection and Follow-up Data are collected from routine clinical documentation, structured procedure forms, clinician surveys, and the Swedish Neonatal Quality Register (SNQ). Variables include perinatal factors, procedural details, respiratory outcomes, and morbidity. Infants are followed until discharge and, where applicable, at 2 and 5.5 years of age using SNQ data. Outcomes The primary outcome is treatment failure, defined as the need for mechanical ventilation or repeat surfactant administration within 72 hours. Secondary outcomes include changes in oxygenation, need for respiratory support, adverse events, procedural characteristics, and short- and long-term morbidity and mortality. Clinician-reported feasibility and ease of use are also assessed. Statistical Considerations All eligible infants will be included over a three-year period, with an expected sample size of approximately 300 infants. Analyses will include descriptive statistics, unadjusted comparisons, and multivariable regression models, with propensity score matching to address confounding. Ethics Ethical approval has been granted by the Swedish Ethical Review Authority. Written informed consent is obtained from caregivers for participation and for permission to collect and analyse observational data. Participation is voluntary and does not affect the infant's clinical care. Significance This study will provide real-world evidence on the use, safety, and outcomes of different surfactant administration methods, including the implementation of SALSA in extremely preterm infants. The results will inform clinical practice and provide essential data for the design of a future large-scale randomized multicentre trial.

Outcomes

Primary Outcomes

Mechanical ventilation or repeat surfactant within 72 hours after first surfactant treatment delivered by LISA, SALSA or INSURE method

Categorical variable (Yes/No). Decision to initiate mechanical ventilation via intubation will be made at the discretion of the treating physician, guided by the local NICU criteria for mechanical ventilation. Data is extracted from medical records.

Time frame: Within 72 hours after first surfactant treatment

Secondary Outcomes

Bradycardia <100 bpm (any duration)

Categorical variable (Yes/No). Measured by pulse oximetry and noted by team performing procedure.

Time frame: During the procedure, an average of 5-10 minutes

Oesophageal/upper airway injury

Categorical (Yes/No). Observations of infant during and post-procedure. Details provided if present.

Time frame: During and within an hour from procedure.

Bradycardia <60 bpm (any duration)

Categorical variable (Yes/No). Measured by pulse oximetry and noted by team performing procedure.

Time frame: During the procedure, an average of 5-10 minutes

Desaturation to SpO₂ <80% lasting ≥30 seconds (single episode)

Categorical variable (Yes/No). Measured by pulse oximetry and noted by team performing procedure.

Time frame: During the procedure, an average of 5-10 minutes

Duration of bradycardia <100 and <60 bpm

Continous variable. Measured by pulse oximetry.

Time frame: During the procedure, an average of 5-10 minutes

Duration of desaturation <80%, <60% and <40%

Continuous variable (seconds). Measured by pulse oximetry.

Time frame: During the procedure, an average of 5-10 minutes

Surfactant-like content in gastric aspirate

Continous variable, ml.

Time frame: Directly after first surfactant administration

Proportion of administered surfactant recovered in gastric aspirate

Continuous variable (%). Fraction (calculated from residual aspirated surfactant and total dose (mL). Observed by clinical team during procedure and noted in CRF.

Time frame: Directly after first surfactant administration

Surfactant reflux

Categorical variable (Yes/No). Clinical reflux of surfactant during procedure.

Time frame: Directly after first surfactant administration

Δ-FiO₂: Hourly change in FiO₂ from pre-procedure to 12 hours post-procedure

Continuous variable.

Time frame: Within 15 minutes before the procedure to 12 hours after first surfactant administration

Δ-SpO2/FiO2-ratio: Change in SpO₂/FiO₂ ratio from pre-procedure to 4 hours post-procedure

Continuous variable.

Time frame: Within 15 minutes before the procedure to 4 hours after first surfactant administration

Early failure: Mechanical ventilation within 1 hour of first surfactant administration

Categorical variable (Yes/no).

Time frame: Within 1 hour after first surfactant administration

Mechanical ventilation within 72 hours of first surfactant administration

Time frame: Within 72 hours after first surfactant administration

Repeat surfactant within 72 hours of first surfactant administration

Categorical variable (Yes/No). Decision to repeat surfactant will be made at the discretion of the treating physician, guided by the local NICU guideline. Data is extracted from medical records. When

Time frame: Within 72 hours after first surfactant administration

Documented reason for mechanical ventilation

Categorical (Nominal).

Time frame: Within 72 hours after first surfactant administration

Documented reason for repeat surfactant

Categorical (nominal).

Time frame: Within 72 hours after first surfactant administration

FiO2 requirement at time of intubation

Numerical variable.

Time frame: Within 72 hours after first surfactant administration

Mechanical ventilation at any time during admission and duration