Table 1: Characteristics of the included studies.

Author Kind of studyInclusion criteria INSUREExclusion criteria INSUREDefinition of intubation conditionsDefinition of INSURE failurePredefined side effects

Ancora et al. [26]Retrospective case control studyFiO2 requirement > 0.40 on nCPAP > 30 min to maintain SpO2 values 85–93% in presence of radiological signs of RDSNot reportedNot definedFiO2 > 0.40 on nCPAP, intractable apnea (>4 episodes of apnea/hour or >2 episodes of apnea/hour requiring bag and mask ventilation) or severe respiratory acidosis (pH < 7.2 and pCO2 > 70 mmHg) within 7 days from extubationNot defined
Van den Berg et al. [22]Prospective cohort studyNot reportedNot reportedNot definedNot definedNot defined
Bohlin et al. [23] Retrospective descriptive studyPreterm with RDS on nCPAP with a/A ratio ≤ 0.22Infants requiring intubation as part of resuscitation at birthNot definedNeed for mechanical ventilation in the first week after surfactant treatment. Need for MV: PaCO2 ≥ 8.5 kPa, FiO2 ≥ 0.60, signs of severe respiratory distress or apneasNot defined
Cherif et al. [20]Retrospective case studyGA > 27 weeks, a/A ratio ≤ 0.25 on nCPAP Not reportedNot definedNeed for MV during 72 hours after surfactant treatment. Criteria for MV: > 3 episodes of apnea in 3-hour unresponsive stimulation or caffeine treatment, arterial pH < 7.20, arterial pCO2 > 65 mmHg, a/APO2 < 0.15, metabolic acidosis not responsive to treatmentNot defined
Gizzi et al. [25]Retrospective case studyFiO2 requirement > 0.40 on nCPAP > 30 min to maintain SpO2 values 85–93% in the presence of radiologic signs of RDSNot reportedNot reportedFiO2 > 0.40 to maintain SpO2 85–93%, significant apnea defined as >4 episodes of apnea/hour or >2 episodes of apnea/hour requiring bag and mask ventilation, respiratory acidosis (pCO2 > 65 mmHg and pH < 7.20) Not reported
Flor-de-Lima et al. [18]Retrospective case control studyFiO2 > 0.40 with respiratory distress and/or arterial pCO2 > 65 mmHg and pH < 7.20 on nCPAPNot reportedNot definedNot definedNot defined
Leone et al. [27]Case control studyPreterm with RDS on nCPAP with a/A ratio ≤ 0.22 Infants requiring intubation as part of resuscitation at birth or later as part of respiratory failureNeed for MV during admission to the NICU. Criteria for MV: PaCO2 ≥ 8.5 kPa, FiO2 ≥ 0.60, signs of severe respiratory distress or apneas
Sandri et al. [24]RCTGA 28–32 weeks, inborn, FiO2 on nCPAP > 0.40 for more than 30 minutes to maintain SpO2 93–96% and radiographic signs of RDSNeed for MV during first week of life. Criteria for MV: FiO2 > 0.40 to maintain SpO2 85–93%, significant apnea defined >4 episodes of apnea/hour or >2 episodes of apnea/hour requiring bag and mask ventilation, respiratory acidosis (pCO2 > 65 mmHg and pH < 7.20), FiO2 rapidly increasing above 0.80
Verder et al. 1994 [19]RCTGA 25–35 weeks, clinical and radiologic findings of RDS, age 2–72 hours, requirement for nCPAP with PEEP ≥ 6 cmH2O, a/A ratio ≤ 0.22Apgar score < 3 at 5 minutes, rupture of membranes > 14 days, severe malformations, pneumonia, pneumothoraxNot definedNot definedNot defined
Verder et al. 1999 [21]RCTGA < 30 weeks, postnatal age 2–72 hours, treated with nCPAP ≥ 6 cmH2O for RDS, a/A ratio 0.35–0.22 decreasing over a period of >30 minApgar score ≤ 2 at 5 min, prolonged rupture of membranes > 3 weeks, lethal malformations, pneumonia, incompletely treated pneumothoraxNot definedNeed for MV within 7 days of birth. Criteria for MV: a/A values < 0.15 decreasing further over a period of >30 min, severe apnea defined as >4 episodes per hour or need for mask ventilation > 2 times per hour, or inability to extubation within 1 hour after INSURENot defined
Welzing et al. 2010 [17]Prospective cohort studyGA 29–32 weeks, postnatal age < 8 hours, moderate to severe respiratory distress (FiO2 ≥ 0.30 on nCPAP to reach postductal SpO2 ≥ 88% OR Silvermanscore ≥ 6)Any kind of disease not allowing early extubationScore of 0–2 on items coughing, breathing, and limb movements. Excellent conditions: score ≤ 1. Good conditions: score 2-3. Inacceptable conditions: score > 3 or distinct coughing or limb movementsNot reportedHypotension
Welzing et al. 2009Prospective cohort studyGA 29–32 weeks, postnatal age <8 hours, moderate to severe respiratory distress (FiO2 ≥ 0.30 on nCPAP to reach postductal SpO2 ≥ 88% OR Silvermanscore ≥ 6)Any kind of disease not allowing early extubationScore of 0–2 on items coughing, breathing, and limb movements. Excellent conditions: score ≤ 1. Good conditions: score 2-3. Inacceptable conditions: score > 3 or distinct coughing or limb movements Not reportedHypotension
Bradycardia
Chest rigidity

a/A ratio: arterial to alveolar oxygen tension ratio; FiO2: fraction of inspired oxygen; GA: gestational age; MV: mechanical ventilation; nCPAP: nasal continuous positive airway pressure; pCO2: partial pressure of carbon dioxide; RCT: randomized controlled trial; SpO2: transcutaneous oxygen saturation.