Table 3.

Randomized controlled trials evaluating LISA vs INSURE.

Study design	LISA vs INSURE threshold, method	Results
Kanmaz et al., 201230 Single center <32 weeks GA Poractant alfa, 100 mg/kg	FiO2 ≥40% within 2 HOL, CPAP 5–7 cm H2O LISA—only by experienced neonatologists 5 Fr Feeding tube, Take Care methoda No premedication	n = 200 ↓ Need for MV within 72 HOLd in the LISA group ↓ Duration of MV and CPAP in the LISA group ↔ BPD
Mirnia, 201348,49 3 centers 27–32 weeks GA Poractant alfa, 100 mg/kg	FiO2 >0.3, CPAP 8–10 cm H2O 5 Fr feeding tube, Take Care method Premedication with atropine 5 mcg/kg	n = 136 ↔ Need for MV within 72 HOL in the LISA group ↓ Mortality and NEC in the LISA group
Mohammadizadeh et al., 201549 2 centers <34 weeks GA 1000–1800 g Poractant alfa, 200 mg/kg	FiO2 >0.4, CPAP 6 cm H2O 4 Fr Feeding tube, Cologne methodb Premedication with atropine 25 mcg/kg	n = 38 ↔ Need for MV within 72 HOLd between groups
Bao et al., 201550 Single center, pilot 28–32 weeks GA Poractant alfa, 200 mg/kg	FiO2 ≥0.3 for 28–29 weeks GA, ≥0.35 for 30–32 weeks GA, CPAP ≥7 cm H2O Hobart methodc No premedication	n = 100 ↔ Need for MV within 72 HOL between groups ↔ Duration of MV between groups
Mosayebi et al., 201853 Single center 28–34 weeks GA Poractant alfa 200 mg/kg	FiO2 >0.4, CPAP 5–8 cm H2O 5 Fr feeding tube, Take Care method No premedication	n = 53 ↔MV within 72 HOLd between groups
Choupani et al., 201854 Single center No GA or weight criteria, Poractant alfa, 200 mg/kg	FiO2 >0.4, CPAP 6 cm H2O Hobart method No premedication	n = 104 ↔ MV within 72 HOLd between groups
Halim, 201955 Single center ≤34 weeks GA Beractant, 100 mg/kg	FiO2 ≥0.3, CPAP 5–7 cm H2O 6 Fr feeding tube, Take Care method No premedication or sedation	n = 100 ↓ Need for MV in the LISA group ↓ Duration of MV in the LISA group
Boskabadi et al., 201957 Single center <32 weeks GA Poractant alfa, 200 mg/kg	FiO2 >0.4, CPAP 5–8 cm H2O 5 Fr feeding tube, Take Care method No premedication	n = 40 ↓ MV within 72 HOL in the LISA group
Jena et al., 201958 3 centers ≤34 weeks GA Bovine lung extract, 135 mg/kg	FiO2 >0.3, CPAP 6 cm H2O Hobart method or 6 Fr feeding tube without Magill forceps No premedication	n = 350 ↓ MV within 72 HOLd in the LISA group ↓ BPD in the LISA group ↓ NEC in the LISA group
Yang et al., 202059 Single center 32–36 weeks GA Poractant alfa 200 mg/kg	FiO2 >0.4, CPAP 6 cm H2O, 6 Fr feeding tube, Cologne method (insertion depth: 2 cm for 32–34 weeks, 2.5 cm for 34–35 weeks GA) No premedication	n = 97 ↔ Procedural adverse events between two groups ↔ Need for MV or pneumothorax between groups
Han, 202060 8 centers 25–31 weeks GA Calf pulmonary surfactant, 70–100 mg/kg	FiO2 >0.4, CPAP 5-6 cm H2O 5 Fr feeding tube with ophthalmic forceps No premedication	n = 298 ↔ BPDd between the groups ↓ hsPDA in the LISA group
Gupta et al., 202061 Single center 28–34 weeks GA Poractant alfa 200 mg/kg	FiO2 >0.3, NIPPV PEEP 5–6 cm H2O 5 Fr feeding tube, Cologne method No premedication	n = 58 ↔MV within 72 HOLd between groups
Pareek et al., 202162,63 Single center 28–36 weeks GA Unspecified surfactant 100 mg/kg	NIPPV, Silverman Score ≥4, FiO2 >0.3 5 Fr Feeding tube, ± Magill forceps No premedication	n = 40 ↔ MV within 72 HOLd between two groups ↔ Difference adverse events between two groups

BPD bronchopulmonary dysplasia, HOL hours of life, hsPDA hemodynamically significant patent ductus arteriosus, NEC necrotizing enterocolitis, NIPPV non-invasive positive pressure ventilation.

^aTake Care method: insertion of a flexible catheter (i.e., feeding tube) below the vocal cords with direct laryngoscopy without using Magill forceps.

^bCologne method: insertion of a flexible catheter (i.e., feeding tube) below the vocal cords with direct laryngoscopy using Magill forceps.

^cHobart method: insertion of a stiff catheter (i.e., 16 G 5.25” vascular catheter) below the vocal cords with direct laryngoscopy.

^dPrimary outcome defined a priori.

↑ Higher, ↓ Lower, ↔ Not significantly different.