Randomized Controlled Trial of Surfactant Delivery Via Laryngeal Mask Airway (LMA) Versus Endotracheal Intubation
Condition: Respiratory Distress Syndrome, Newborn
MeSH terms: Respiratory Distress Syndrome; Respiratory Distress Syndrome, Newborn; Syndrome
Study type: Interventional
Phase: Phase 4

Summary: 
      In this study, newborn babies with respiratory distress syndrome (RDS), receiving oxygen via
      nasal CPAP, and needing surfactant treatment will be randomized to standard delivery of
      surfactant via and endotracheal tube airway(inserted after pre-medication for pain), or to
      surfactant delivery via laryngeal mask airway (LMA). The intent is to remove the airways and
      return babies to nasal CPAP, after surfactant is given. The primary outcome measure is the
      rate of failure of initial surfactant therapy. Standardized failure criteria are reached: a)
      early, if the baby is unable to be placed back on CPAP (needs mechanical ventilation) or, b)
      late, if the baby requires retreatment with surfactant within 8 hours or more than 2 doses of
      surfactant.

      The objective of this protocol is to reduce the need for endotracheal intubation and
      mechanical ventilation in preterm neonates with RDS needing rescue surfactant therapy by
      instilling surfactant though an LMA, while achieving comparable efficacy of surfactant
      treatment.

      The hypothesis is that surfactant treatment through an LMA will decrease the proportion of
      babies with RDS who require mechanical ventilation or subsequent intubation, when compared
      with standard surfactant treatment following sedation and endotracheal intubation.
    

Detailed description: 
      Respiratory Distress Syndrome (RDS) due to deficiency of lung surfactant is common in preterm
      newborns. Early treatment with surfactant improves oxygenation, reduces the need for
      subsequent mechanical ventilation, decreases the incidence of pulmonary air leaks and chronic
      lung disease and it also reduces mortality in extremely premature newborns. Optimal treatment
      of RDS includes surfactant therapy and avoidance of invasive mechanical ventilation by using
      nasal continuous positive airway pressure (NCPAP). The current standard method of surfactant
      delivery requires tracheal intubation and at least brief positive-pressure ventilation.
      Tracheal intubation causes pain and leads to vagal-mediated physiologic instability in
      neonates; therefore, premedication with morphine and atropine is routinely practiced in our
      setting. However, premedication with morphine often increases respiratory depression,
      requiring sustained mechanical ventilation. The Laryngeal Mask Airway (LMA) is a commercially
      available, less invasive artificial airway that does not need to be inserted into the
      trachea; it is FDA-approved for use in neonates, and preliminary data suggest that it can be
      used for surfactant administration.

      The main objective of this study protocol is reduce the need for endotracheal intubation and
      mechanical ventilation in preterm neonates with mild to moderate RDS needing rescue
      surfactant therapy by instilling surfactant though an LMA. A second objective is to compare
      the efficacy of surfactant administered via LMA versus endotracheal tube (ETT) in decreasing
      the severity of RDS. Additionally, we will evaluate the safety of surfactant administration
      via LMA.

      The primary hypothesis is that surfactant treatment via the LMA approach will decrease the
      proportion of babies with RDS who require mechanical ventilation or subsequent intubation,
      when compared with standard surfactant as administered to the ETT group.

      This randomized controlled trial will include babies with mild-to-moderate RDS, between 4 to
      48 hours of age, with gestational age 29 0/7 to 36 6/7 weeks, treated with NCPAP ≥ 5 cm H2O
      and FiO2 between 0.30 and 0.60 for at least 2 hours to maintain SpO2 88-95%, and informed
      consent. Exclusion criteria are weight < 1000 g, airway anomalies, pulmonary air leaks, and
      craniofacial and cardiothoracic malformations.

      After informed consent is obtained, babies are randomly assigned (from sealed, opaque,
      consecutively numbered envelopes), to the "ETT" or "LMA". The "ETT" group is managed
      according to our current practice of surfactant therapy (endotracheal intubation following
      premedication with atropine + morphine), whereas the "LMA" group will be pre-medicated with
      atropine before LMA insertion for surfactant administration.

      Both groups will receive Infasurf (3mL/kg) instilled in 2 aliquots via their respective
      airway, followed by PPV for at least 5 minutes. The artificial airway will be removed and the
      patient returned to NCPAP by 15 minutes, if spontaneous respirations are adequate.
      Indications for surfactant re-dosing and mechanical ventilation will be equivalent for both
      groups.

      Babies will continue or initiate assisted ventilation via ETT if any of the following occurs:

        -  Persistent apnea;

        -  Severe retractions;

        -  Inability to wean FiO2 < 60%

      Criteria for re-dosing with surfactant:

        1. Within 8 hours after first dose of surfactant (early re-dosing):

             -  FiO2 20% higher than the baseline FiO2, after excluding other obvious causes of
                respiratory insufficiency such as pneumothorax.

           If early re-dosing of surfactant is needed in patients of either group, the dose will be
           administered via ETT (i.e., LMA patients will be intubated, and will receive the dose of
           surfactant via ETT)

        2. Beyond 8 hours of the first dose of surfactant (late re-dosing):

             -  FiO2 is ≥ 60%, or;

             -  FiO2is ≥ 30% associated with worsening clinical signs of RDS.

      If late re-dosing is needed in patients of the LMA group, use of the LMA is permitted for the
      second dose. In the ETT group, all doses are given via the ETT.

      Primary Outcome Measures:

      Rate of failure of early surfactant rescue therapy in the 2 groups, using the following
      criteria to differentiate early from late failure:

        -  Criteria for early failure (within 1 hour):

             1. The need of mechanical ventilation within 1 hour of surfactant therapy.

             2. Use of Narcan to avoid mechanical ventilation after surfactant therapy.

        -  Criteria for late failure (beyond 1 hour):

             1. Sustained FiO2 > 0.60 to maintain target SpO2

             2. Second dose of surfactant within 8 hours after the first dose.

             3. More than 2 doses of surfactant.

      Babies will have FiO2 adjusted to maintain SpO2 88-95%, per current practice. Other aspects
      of weaning ventilatory support will be managed by clinicians' preference.
    

Intervention name(s): Endotracheal tube insertion; Laryngeal mask airway insertion
Intervention type(s): Device; Device
Intervention description(s): Endotracheal tube insertion after premedication with atropine (0.02 mg/kg) and morphine (0.1 mg/kg); Laryngeal mask airway insertion after premedication with atropine (0.02 mg/kg)
Other intervention name(s): LMA North America
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Respiratory distress syndrome; Surfactant; Tracheal intubation; Laryngeal mask airway; Newborn