. 2022 Aug 19;93(5):1188–1198. doi: 10.1038/s41390-022-02265-8

Table 4.

Meta-analyses of studies comparing LISA with surfactant administration via ETT.

Author	Results	Certainty of evidence according to GRADE
Abdel-Latif et al., 2021⁷³ 16 RCTs n = 1324 for death of BPD n = 1422 for MV <72 HOL n = 857 for severe IVH	Compared to ETT surfactant, LISA lead to • ↓ Death or BPD (RR 0.59 (95% CI 0.48–0.73), NNB 9 (95% CI 7–16) • ↓ BPD (RR 0.57, 95% CI 0.45–0.74), NNB 13 (95% CI 9–24) • ↓ MV within 72 h (RR 0.63, 95% CI 0.54–0.74), NNB 8 (95% CI 6–12) • ↓ Severe IVH (RR 0.63, 95% CI 0.42–0.96), NNB 22 (95% CI 12–193) • ↓ Mortality (RR 0.63, 95% CI 0.47–0.84), NNB 20 (95% CI 12–58) Compared to INSURE, LISA lead to • ↓ Death or BPD, (RR 0.52, 95% CI 0.4–0.68) NNB 9 (95% CI 6–15) • ↓ BPD (RR 0.57, 95% CI 0.44–0.75), NNB 14 (95% CI 9–28) • ↓ Mortality (RR 0.60, 95% CI 0.44–0.82), NNB 19 (95% CI 11–52) • ↓ MV within 72 h (RR 0.61, 95% CI 0.50–0.75), NNB 8 (95% CI 6–14)	Moderate Moderate Moderate Low Low
Barkhuff et al., 2019⁶⁴ 7 RCTs n = 940 for pneumothorax n = 895 for all other outcomes	Compared to ETT surfactant ± MV, LISA lead to • ↓ MV within 72 HOL, RR 0.74 (0.65–0.85) • ↓ Death or BPD, RR 0.74 (0.59–0.94), NNB: 14 • ↓ Pneumothorax 0.61 (0.37–1) Compared to INSURE, LISA lead to • ↓ MV within 72 h, RR 0.72 (0.53–0.97) • ↓ Death or BPD, RR 0.66 (0.46–0.93), NNB 11 (6–50)	–
Rigo et al., 2016⁶⁷ 6 RCTs n = 895 Subgroup: INSURE vs LISA-4 RCTs, n = 464	Compared with ETT surfactant ± MV, LISA lead to • ↓ Early CPAP failure, (RR 0.67, 95% CI 0.53–0.84) • ↓ MV requirements during NICU stay (RR 0.65, 95% CI 0.45–0.95) • ↓ Death/BPD (RR 0.74, 95% CI 0.58–0.94), NNB 15 Compared to INSURE, LISA lead to • ↓ Need for MV within 72 h (RR 0.71, 95% CI 0.53–0.96) • ↓ Death of BPD (RR 0.63, 95% CI 0.44–0.92)	–
Aldana-Aguirre et al., 2017⁶⁸ 6 RCTs n = 895	Compared to ETT surfactant ±MV, LISA lead to • ↓ Death/BPD with LISA; RR = 0.75 (0.59–0.94) • ↑ Surfactant reflux with LISA; RR = 2.52 (1.47–4.31)	–
Isayama, 2016⁶⁶ Network meta-analysis 30 RCTs Total n = 5598 LISA studies n = 637	Compared with MV, LISA group had • ↓ Death/BPD (OR 0.49, 95% CI 0.30–0.79) • ↓ BPD (OR 0.53, 95% CI 0.27–0.96) • ↓ Severe IVH (OR, 0.44, 95% CI 0.19–0.99) Compared with CPAP alone, LISA group had • ↓ Death/BPD (OR 0.58, 95% CI 0.35–0.93) • ↓ Air leak (OR 0.24, 95% CI 0.05–0.96)	Moderate Moderate Moderate Moderate Very low

Author

Results

Certainty of evidence according to GRADE

Abdel-Latif et al., 2021⁷³

16 RCTs

n = 1324 for death of BPD

n = 1422 for MV <72 HOL

n = 857 for severe IVH

Compared to ETT surfactant, LISA lead to

• ↓ Death or BPD (RR 0.59 (95% CI 0.48–0.73), NNB 9 (95% CI 7–16)

• ↓ BPD (RR 0.57, 95% CI 0.45–0.74), NNB 13 (95% CI 9–24)

• ↓ MV within 72 h (RR 0.63, 95% CI 0.54–0.74), NNB 8 (95% CI 6–12)

• ↓ Severe IVH (RR 0.63, 95% CI 0.42–0.96), NNB 22 (95% CI 12–193)

• ↓ Mortality (RR 0.63, 95% CI 0.47–0.84), NNB 20 (95% CI 12–58)

Compared to INSURE, LISA lead to

• ↓ Death or BPD, (RR 0.52, 95% CI 0.4–0.68) NNB 9 (95% CI 6–15)

• ↓ BPD (RR 0.57, 95% CI 0.44–0.75), NNB 14 (95% CI 9–28)

• ↓ Mortality (RR 0.60, 95% CI 0.44–0.82), NNB 19 (95% CI 11–52)

• ↓ MV within 72 h (RR 0.61, 95% CI 0.50–0.75), NNB 8 (95% CI 6–14)

Moderate

Low

Barkhuff et al., 2019⁶⁴

7 RCTs

n = 940 for pneumothorax

n = 895 for all other outcomes

Compared to ETT surfactant ± MV, LISA lead to

• ↓ MV within 72 HOL, RR 0.74 (0.65–0.85)

• ↓ Death or BPD, RR 0.74 (0.59–0.94), NNB: 14

• ↓ Pneumothorax 0.61 (0.37–1)

Compared to INSURE, LISA lead to

• ↓ MV within 72 h, RR 0.72 (0.53–0.97)

• ↓ Death or BPD, RR 0.66 (0.46–0.93), NNB 11 (6–50)

–

Rigo et al., 2016⁶⁷

6 RCTs

n = 895

Subgroup: INSURE vs LISA-4 RCTs, n = 464

Compared with ETT surfactant ± MV, LISA lead to

• ↓ Early CPAP failure, (RR 0.67, 95% CI 0.53–0.84)

• ↓ MV requirements during NICU stay (RR 0.65, 95% CI 0.45–0.95)

• ↓ Death/BPD (RR 0.74, 95% CI 0.58–0.94), NNB 15

Compared to INSURE, LISA lead to

• ↓ Need for MV within 72 h (RR 0.71, 95% CI 0.53–0.96)

• ↓ Death of BPD (RR 0.63, 95% CI 0.44–0.92)

–

Aldana-Aguirre et al., 2017⁶⁸

6 RCTs

n = 895

Compared to ETT surfactant ±MV, LISA lead to

• ↓ Death/BPD with LISA; RR = 0.75 (0.59–0.94)

• ↑ Surfactant reflux with LISA; RR = 2.52 (1.47–4.31)

–

Isayama, 2016⁶⁶

Network meta-analysis

30 RCTs

Total n = 5598

LISA studies n = 637

Compared with MV, LISA group had

• ↓ Death/BPD (OR 0.49, 95% CI 0.30–0.79)

• ↓ BPD (OR 0.53, 95% CI 0.27–0.96)

• ↓ Severe IVH (OR, 0.44, 95% CI 0.19–0.99)

Compared with CPAP alone, LISA group had

• ↓ Death/BPD (OR 0.58, 95% CI 0.35–0.93)

• ↓ Air leak (OR 0.24, 95% CI 0.05–0.96)

Moderate

Very low

CI confidence interval, NNB number needed for treatment benefit, OR odds ratio, RR typical risk ratio.