DISCUSSION
In this open-label RCT, we compared the newer less invasive surfactant
administration technique with the traditional, more invasive method of
surfactant instillation, InSurE. The population included spontaneously
breathing preterm babies between 28 to 34 weeks of gestation with RDS
using NIPPV as a primary mode of ventilation. A less invasive approach
was proven to be equally effective with no significant difference in the
need for mechanical ventilation within 72hours of birth between the two
groups. We found insignificant statistical difference in duration of
ventilation, oxygen therapy, length of hospital stay, major
complications, adverse events, or mortality between the two groups.
InSurE has been the traditional method of surfactant administration.
However, a brief period of invasive ventilation in this technique may
also cause lung injury, so less invasive methods (LISA) came into the
field. Following an initial pilot trial by Verder et al.(24), several
variations have been conducted and published over years using different
types of catheters for intratracheal administration of surfactant with
or without Magill forceps(25–28). Over the years LISA has been
increasingly used in different parts of the world. Few studies have been
reported from India.
As with our study, several other trials(27–34) found no significant
difference between the InSurE and LISA groups about the need for
intubation within 72 hours of birth. Mohammadizadeh, et al.(28)
Conducted a multicentre RCT in Iran among 38 preterm babies below 34
weeks gestational age and found insignificant difference in the need for
intubation within first 72 hours of life. Similar findings were seen in
a single-centre RCT from china by Bao et al(27). However, various
studies(22,31,35,36) of similar design and meta-analysis(1,4,37,38) from
various countries in the world have reported a significant reduction in
the need for mechanical ventilation in the LISA group. Most of
studies(22,31,35,36) which found significant difference in the need of
MV in 72 h used nCPAP as their primary respiratory support. Evidence
from literature shows that NIPPV facilates better deliver of presure in
the alveoli to overcome the airway clog and leaks during catheterisation
by a thin intra-tracheal catheter(39). Also NIPPV prevents
intubation(18). Both these factors may explain the lack of difference
between LISA and InSurE groups in the primary outcome in our study.
In our study, we used NIPPV as a primary mode of respiratory support
whereas the majority of the studies which found a significant difference
in the need for intubation in the first 72h used nCPAP as their primary
mode of ventilation(2,31,35,36). Evidence from the literature supports
that NIPPV as the primary mode of respiratory support reduces the need
for mechanical ventilation(18). Multiple studies(17,40) and
meta-analysis (40,41) suggest that NIPPV works better than CPAP in
reducing the need for mechanical ventilation. The possible mechanism
explained is the inclusion of PIP above PEEP, thereby delivering higher
MAP, improving alveolar recruitment, and thus reducing the work of
breathing(17,40–43). This can explain the lack of difference in the
primary outcome among both the groups in our study. Other notable Indian
research by Gupta et al.(29) and Pareek et al.(34) using NIPPV showed no
significant difference in the need for intubation within the first 72h.
Similar findings were seen in a recent trial from Turkey by Akcay et
al.(30)
The study population included preterm babies of a wider gestational age
range (28-36weeks) with a mean gestational age of 31.4 weeks. It is
comparable with other studies(29,34). Most of the studies have included
preterms below 34 weeks of gestation(27,28,30,32,35,36,44). It is
uncertain whether difference in the study groups affected key endpoints.
There were insignificant statistical difference in the duration of MV/
NIPPV or supplemental oxygen and the incidence of BPD between the
groups.This could be attributed to similar rate of mechanical
ventilation in both the groups. Similar findings were reported from
other studies(27–30,33,34). We found no significant difference in other
major complications such as IVH, NEC, ROP, hsPDA, pneumothorax, and LOS
between the groups. Similar results were reported from other
studies(27,29,30,34,44). Our study did not show any significant
difference between the groups in the need for a second dose of
surfactant, as did most of the studies of similar design(27,29,34,36).
Continuous NIPPV support along with LISA gives a better pressure
effect(45), potential reason for less surfactant retreatment in our
study. There was no substantial difference in the rate of adverse events
such as transient bradycardia/desaturation during the procedure(12%
LISA &14.6% InSurE, p = 0.63), comparable with other
studies(27,29,36). In contrast, Olivier et al(46) and Mohamadizadeh et
al.(28) reported a statistically significant higher incidence of
desaturation/ bradycardia during the procedure, attributed to
premedication for sedation before the procedure or inadequate training.
Duration of hospital stay was also similar among the groups, comparable
to other studies(2,27,33). There was no statistically significant
difference in the survival outcome between the groups (RR: 1.06,
95%CI:0.76-1.57 (37,47). Gestational age stratified subgroup analysis
was done for all primary and secondary outcomes and findings did not
differ from main results..
Generalizability of the study: this study can be replicated in tertiary
level nicu of many LMICs, provided NIPPV facility should be available
Strength of the study : Our study is among the very few RCTs that has
compared the efficacy of LISA with InSurE using NIPPV as a primary mode
of respiratory support, carried out in a large public hospital in LMIC.
This study has large sample size with bigger and wider gestational age
compared to other studies.
LIMITATION: This study has some limitations. As both the groups included
different procedures; hence healthcare workers could not be blinded, but
the study analysis was done by a statistician not involved in this
research study. Our null hypothesis for primary outcome was true however
the hypothesis for secondary outcome that LISA would be better in
reducing rates of bpd in babies reqiring surfacatant administration was
not true.This could be due to the fact that our study was not adequately
powered for evaluating rates of bpd in babys recieving surfactant
therapy.
CONCLUSION: To conclude, our study found LISA to be equally effective
and safe compared to InSurE, as a method for surfactant administration
in spontaneously breathing preterm neonates using NIPPV as a primary
mode of respiratory support. We found insignificant statistical
difference in the need for intubation within 72hours of birth between
the two groups. The study is among very few trials comparing LISA with
InSurE using NIPPV in preterms with a wide range of gestation between
28-36 weeks.
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