[Retracted] Surfactant without Endotracheal Tube Intubation (SurE) versus Intubation-Surfactant-Extubation (InSurE) in Neonatal Respiratory Distress Syndrome: A Systematic Review and Meta-Analysis

Table 1

Summary of the included articles in the meta-analysis.

Author	Country	Methods	Sample size	Study type	Gestational age (weeks)	Necessity or type of MV	Intervention	Current findings	Future recommendation/limitation/comments
Jena et al. 2019	India	Surfactant therapy	350	Original study	29–33	CPAP	SurE and InSurE	The need for MV in the first 72 hours of life was significantly lower in the SurE group. Similarly, duration of oxygen therapy, hospital stay, and BPD were significantly lower in the SurE group.	Studies with larger sample size are required along with a pain medication, which was absent in this study.
Gupta et al. 2020	India	Surfactant therapy	58	Original study	28–34	NIPPV	InSurE and MIST	No significant difference was found in need of IMV in first 72 h between MIST and InSurE (relative risk with MIST, 0.62; 95% confidence interval, 0.22 to 1.32).	Larger multicenter studies are needed.
Yang et al. 2020	China	Surfactant therapy	97	Observational study	32–36	CPAP	LISA and InSurE	LISA could be used to treat premature infants with RDS with stronger spontaneous breathing ability.	Further clinical studies are needed to determine the optimal strategy of LISA administration and the most suitable population of patients.
Aldana-Aguirre et al. 2017	Canada	Surfactant therapy	895	Review study	36	CPAP	LISA and endotracheal intubation	LISA for surfactant delivery resulted in less demand for MV in infants with RDS.	No data are provided for long-term neurodevelopmental outcomes.
Wang et al. 2019	China	Minimally invasive surfactant therapy	53	Original study	32	nCPAP	InSurE and MIST	MIST was feasible and safe, and it might reduce the composite outcome of death.	Single-center study
Kamaz et al. 2013	Turkey	Noninvasive surfactant therapy	200	Original randomized controlled trial	<32	nCPAP	Noninvasive SurE and InSurE	The Take Care technique was feasible for the treatment of respiratory distress syndrome in infants with very low birth weight. It significantly reduced both the need and duration of MV, as well as the BPD rate in preterm infants.	Further studies about the effect on BPD with sufficient power and meta-analysis are needed.
Kribs et al. 2015	Germany	Nonintubated surfactant therapy	211	Multicenter, randomized, clinical, parallel-group study	36	CPAP	LISA via a thin catheter and conventional treatment	LISA did not increase survival without BPD but was associated with increased survival without major complications.	LISA is a promising new therapy for extremely preterm infants with respiratory distress syndrome, but this requires further investigation.
Langhammer et al. 2018	Germany	Surfactant therapy	407	Observational cross-sectional multicenter study	26–29	nCPAP	LISA and intubation therapy	LISA-treated infants needed less MV and shorter duration with supplemental oxygen. It also required less analgesics and sedatives. SGA infants seem to have higher risks of LISA failure.	Further studies are needed to demonstrate that LISA-treated infants require shorter duration of supplemental oxygen and lower needs for analgesics and sedatives. Also, it needs to be confirmed whether there are fewer ROP infants in the LISA group.
Hartel et al. 2018	Germany	Less-invasive surfactant administration	7533	Original cohort study	22–28	NIPPV-CPAP	No surfactant, LISA, and ETT	LISA was superior to intubation for surfactant delivery for short-term outcomes. It was associated with focal intestinal perforation in the extremely preterm infants.	Whether “protective” or earlier intubation of extremely preterm infants with significant abdominal distension is beneficial, needs to be investigated further in clinical trials.
Tomar et al. 2017	India	Surfactant therapy	136	Single-center, prospective observational study	24–34	CPAP	MIST and InSurE	The modified MIST technique was an effective method for the treatment of RDS in preterm infants with better clinical efficacy than and comparable outcomes to the more invasive InSurE procedure	Further investigation with multicentric trials is needed.
Klebermass-Schrehof et al. 2013	Austria	Surfactant therapy	224	Single-center original study	23–27	CPAP	LISA	LISA resulted in significant improvement in MV, intraventricular hemorrhage, leukomalacia, PDA, and ROP.	Need for a retrospective design and a randomized control group.
Dargaville et al. 2014	Australia	Surfactant therapy	156	Open feasibility study	25–28	CPAP	MIST and InSurE	Surfactant was successfully administered via MIST in all cases, with a rapid and sustained reduction in FiO2 thereafter.	Further investigation with clinical trials is needed.
Mirnia et al. 2013	Iran	Surfactant administration	136	Multicenter randomized clinical trial study	27–32	CPAP	TEC and InSurE	TEC method was effective in treating RDS, NEC, and BPD. Mortality was significantly decreased in the TEC group.	TEC procedure is a new method of surfactant administration, and there are few studies on it. Thus, there is a need for more studies to fully understand this procedure.
Li et al. 2016	China	Surfactant therapy	44	Original study	28–30	nCPAP	LISA and InSurE	Both InSurE and LISA caused a transient impairment in cerebral autoregulation of RDS infants. LISA was superior to InSurE in terms of the effect duration.	Further evaluation of neurological functions of RDS is required.
Gopel et al. 2011	Germany	Surfactant therapy	220	Parallel-group, randomized group trial	26–28	Oxygen supplementation + CPAP	SurE and InSurE	Surfactant administered via a thin catheter to spontaneously breathing preterm infants in addition to CPAP reduced the need for MV.	In the future, surfactant given to spontaneously breathing preterm infants via a thin catheter might be included for individualized and gentler care for preterm infants.
Bao et al. 2015	China	Surfactant therapy	90	Original study	28–32	nCPAP	LISA and InSurE	LISA in spontaneously breathing infants on nCPAP was an alternative therapy for PS delivery, avoiding intubation with an endotracheal tube.	Further clinical trials are required.
Mohammadizadeh et al. 2015	Iran	Surfactant therapy	38	Original study	<35	nCPAP	Surfactant administration via thin intratracheal catheter vs. endotracheal tube	Both methods had similar efficacy, feasibility, and safety.	N/A
Abdel-Latif et al. 2021	Australia	Surfactant therapy	2164	Analytical study	<37	CPAP and rescue surfactant administration	Surfactant administration via thin catheter and via ETT tube	Administration of surfactant via thin catheter was compared with administration via an ETT. The former approach was associated with reduced risk of death or BPD, less intubation in the first 72 hours, incidence of major complications, and in-hospital mortality.	Further well-designed studies with adequate size and power are needed to clarify whether surfactant therapy via thin tracheal catheter provides benefits over continuation of noninvasive respiratory support without surfactant. Moreover, uncertainties related to special subgroups and the role of sedation need to be addressed.
More et al. 2014	Canada	Surfactant therapy	3081	Narrative review	<35	CPAP	MIST	Surfactant administration via a thin catheter might be an efficacious and potentially safe method.	Further investigations are recommended for better surfactant administration.
Dekker et al. 2016	Netherlands	Surfactant therapy	38	Original study	25–36	--	MIST	Preterm infants receiving MIST were more comfortable when sedation was given.	Neonates required more ventilation.
Panza et al. 2020	Italy	Surfactant therapy	4926	Analytical study	20–36	CPAP and nCPAP	SurE, Take Care, LISA, MIST, and InSurE	Compared with InSurE to deliver surfactant to newborn preterm infants with RDS, using thin catheters was associated with a reduced incidence of BPD and less need for MV.	More evidence on premedication, the dose of surfactant, use of caffeine, and use of high flow are needed. In addition, information about pain level, physiological responses, and implementation protocols are required in the future studies.

MV : mechanical ventilation; N/A : not applicable; SurE : surfactant without endotracheal tube intubation; InSurE : intubation, surfactant, and extubation; MIST : minimally invasive surfactant therapy; CPAP : continuous positive airway pressure; nCPAP: nasal continuous positive airway pressure; LISA : less invasive surfactant administration; ETT: endotracheal tube; BPD : bronchopulmonary dysplasia; NEC: necrotizing enterocolitis; TEC: thin endotracheal catheter; NIPPV: noninvasive positive pressure ventilation.