DISCUSSION
The present study is, to the best of the author’s knowledge, the first
randomized controlled trial that compared the use of NIPPV during
neonatal intubation with the use of the standard procedure to reduce
physiological instability. In the present multicenter study, the rate of
successful intubation without physiological instability during all
intubation attempts was higher when NIPPV was implemented compared to
the implementation of standard care. The results regarding the heart
rate and the SpO2 level during the procedure were more
favorable with the use of NIPPV. In addition, NIPPV during intubation
was revealed to be more favorable when intubation performed by
practitioners with less experience.
NIPPV augments continuous positive airway pressure (CPAP) by providing
inflations to a set peak pressure by a nasal mask or nasal prongs. NIPPV
provides stabilization of the upper airways and the compliant preterm
chest wall and prevention of end-expiratory alveolar collapse, thus,
maintains functional residual capacity and reduces ventilation-
perfusion mismatch, which improves oxygenation and work of
breathing.14 NHF therapy was not designed originally
to deliver PEEP, but to washout the anatomical and physiological dead
space.15 NHF prongs are designed to avoid occlusion of
the nares; leak around the prongs serves to avoid excessive pressure
generation,16 therefore, the generated-pressure was
not measurable and could not be regulated.17 Some
studies reported NIPPV was more effective in decreasing the requirement
of mechanical ventilation and treatment failure than
NHF.18,19 NIPPV also reduces re-intubation, treatment
failure and air leaks compared to CPAP.10 In light of
this information and because NIPPV is one of the most commonly used
non-invasive ventilation modes, we preferred to use NIPPV during
intubation in this study. We concluded that the improvement in
oxygenation and work of breathing due to the multiple physiological
mechanisms of NIPPV mentioned above improved the primary outcome.
Severe desaturation, bradycardia, and tracheal intubation-associated
events may occur during neonatal intubation.6,7,11,12Tracheal intubation-associated events, including bradycardia and severe
oxygen desaturation, increase substantially with the number of
intubation attempts.20-22 In the case of multiple
attempts (≥3), the risk of severe oxygen desaturation increases 6-fold
compared to that on the first attempt.20 Multiple
intubation attempts are more common in newborns than in children and
adults, and also when the practitioners are pediatric residents rather
than experienced ones.3,20 Among newborns, multiple
intubation attempts are reportedly more common in neonates <32
weeks corrected gestation and <1500 g at the time of
intubation.3 The rate of successful intubation on the
first attempt for newborns is 64% when the practitioner is experienced,
while the lowest success rates are reported for cases handled by
pediatric residents (20%–26%).23 Severe oxygen
desaturation is more common in resident airway practitioners compared to
the fellows and attendings.4 Physiologic instability,
including oxygen desaturation, is the most common reason for
unsuccessful intubation.24 In a recent study conducted
on a small number of newborn infants, Foran et al.7noted that physiological instability appeared to increase with the
increase in the number of intubation attempts, particularly when
inexperienced practitioners were involved. In the present study, it was
demonstrated that the rate of successful intubation without
physiological instability during all intubation attempts was
significantly higher in the NIPPV group (64%) compared to the standard
care group (47%). Moreover, this difference was statistically
significant only when inexperienced clinicians were involved. Hodgson et
al.6 compared NHF during intubation with standard care
in preterm infants and reported that successful intubation on the first
attempt without physiological instability was achieved in 50.0% of the
cases of intubations in the NHF group and 31.5% of the cases of
intubations in the control group, with the difference between the two
groups being significant. While this finding was similar to that
observed in the present study, the aforementioned study did not involve
evaluating NHF beyond the first intubation attempt. The rate of
successful intubation on the first attempt without physiological
instability was also evaluated in the present study, and while this rate
was higher in the NIPPV group (50%) compared to the control group
(37%), significance was not reached. These percentiles were, however,
similar to those reported by Hodgson et al.,6 who
suggested a greater benefit of using NHF when the intubations were
performed by inexperienced operators (<20 previous intubations).
Similarly, in the present study, the rate of successful intubation
without physiological instability during all intubation attempts was
noted to be lower when NIPPV was implemented by inexperienced
practitioners (<36 previous intubations).
Severe oxygen desaturation is reported to occur in 29% to 69% of
intubations, while bradycardia is reported in 24% of intubations during
procedure in NICU.11,12 Hodgson et
al.6 reported that the rate of severe desaturation
during neonatal intubation was significantly lower in the NHF group
(28.2%) compared to the control group (39.4%). These authors also
stated that the median oxygen saturation was higher, and the time to
desaturation was longer in the intervention group during the first
attempt. However, the bradycardia rate was similar (<100 bpm) in
both groups (8.9% in the NHF group and 12.6% in the control group) in
their study. However, the authors did not report any significant
difference in the duration of severe desaturation and time to
bradycardia between the groups. In the present study, consistent with
the findings reported by Hodgson et al.,6 the rate of
severe desaturation was noted to be significantly lower, while the
lowest SpO2 level was significantly higher in the NIPPV
group. However, in contrast to the findings of Hodgson et
al.,6 the bradycardia rate was noted to be higher, and
the duration of severe desaturation was longer in the control group in
the present study. All of the findings reported by Hodgson et
al.6 were noted for the first intubation attempt,
while the findings of the present study are for all intubation attempts.
This difference in the number of intubation attempts included could be
the reason for the different findings between the two studies. In a
recent meta-analysis that included eight randomized controlled trials,
Fuchs et al.25 evaluated the efficacy and
effectiveness of apnoeic oxygenation (low-flow oxygen or high-flow nasal
oxygen) during laryngoscopy conducted for tracheal intubation in
newborns and children. The meta-analysis confirmed that apnoeic
oxygenation during intubation significantly increases the success rate
of first-pass intubation and reduces the incidence of hypoxia
(SpO2 <90%). The meta-analysis also revealed
that the lowest SpO2 level was higher when apnoeic
oxygenation was applied. Therefore, it was inferred that apnoeic
oxygenation facilitates stable physiological conditions by maintaining
oxygen saturation within the normal range.25 However,
in the same study, no reduction was noted in the incidence of
bradycardia when apnoeic oxygenation was applied.25Consistent with the findings of the afore-stated meta-analysis, lower
incidences of hypoxia and the lowest SpO2 level were
recorded for the intervention group during the procedure in the present
study.
The incidence of intubation-associated adverse events ranged from 22%
to 39%.4,12 Two studies showed that nasal high-flow
oxygen or continuous gas flow via the endotracheal tube during
intubation did not increase the risk of unexpected adverse events in
neonates compared to the control group.6,8 In line
with these previous studies,6,8,12 no difference was
noted between the groups in the present study in terms of the incidence
of non-severe and severe adverse events.
The present study also has certain limitations. The first limitation is
that a nasal cannula was not used for the control group during the
procedure, which could have led to bias in the outcomes. However, to
reduce this bias, an independent reviewer performed a video review. So
our study was not blinded. Another limitation arose because the accuracy
of the pulse oximeter decreases at extremely low saturation levels
(<70%). In addition, video-laryngoscopy was not performed due
to its unavailability at the NICU of our hospital. This could be a
limitation as video-laryngoscope reportedly improves intubation success
and reduces adverse events.11,22 Finally, since the
study was conducted only in the NICU, the generalization of the findings
to the delivery room and operating room may be limited.
In conclusion, NIPPV implementation during oral endotracheal intubation
increases the rate of successful intubation without physiological
instability during all intubation attempts in newborn infants. This
difference is particularly significant in inexperienced practitioners.
In addition, the procedure is associated with lower incidences of
hypoxemia and bradycardia.