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.