Regular articleThe potential of non-invasive ventilation to decrease BPD
Introduction
Bronchopulmonary dysplasia (BPD) is the most common chronic lung disease in infancy.1., 2. While a variety of genetic and environmental factors interact in the pathogenesis of BPD, one critical factor is prematurity.1., 2. For the purposes of this review, BPD has been defined using the National Institutes of Health (NIH) consensus definition, which requires for infants <32 weeks of gestation to have needed supplemental oxygen for at least 28 days, and assessment at 36 weeks corrected postmenstrual age (or discharge, if earlier) for the need for supplemental oxygen and/or positive pressure support.1., 2. BPD is associated with significant long-term complications including repeated hospitalizations, neurodevelopmental impairment and abnormal pulmonary function tests extending across childhood to adulthood.1., 2. These translate to significant healthcare costs.3., 4. Since there is no preventive and/or specific effective therapy available for BPD, efforts have focused on modifying environmental factors to decrease and/or ameliorate the severity of the disease. One such approach has been avoiding the use of invasive ventilation. Nasal continuous positive airway pressure (NCPAP) has been extensively studied in multiple randomized controlled trials (RCT) with equivocal results.5 Over the last decade, use of nasal intermittent positive pressure ventilation (NIPPV) in premature neonates has increased considerably.6 This review focuses on studies of NCPAP and NIPPV published in the last 5 years, with the primary outcome of BPD.
Section snippets
NCPAP and BPD
Anecdotal evidence and small RCTs have suggested that early NCPAP use could lead to a decreased incidence of BPD.7., 8. However, this has not been borne out by 2 recent large RCTs that compared extremely preterm neonates randomized to NCPAP or intubation at birth.9., 10. In the first study, in infants born at 25–28 weeks gestation (n = 610), early NCPAP did not significantly reduce the rate of BPD/death, as compared with the infants who were intubated at birth.9 In addition, the NCPAP group of
NCPAP with surfactant and BPD
The failure of only providing early NCPAP to decrease BPD has brought up the notion that denying early surfactant to these premature infants may be contributing to such results.5 The experience with the INtubation SURfactant Extubation (INSURE) procedure has suggested that this technique may diminish the development of BPD.11 A meta-analysis concluded that early surfactant-replacement therapy with extubation to NCPAP within 1 h, compared with later selective surfactant replacement and continued
NIPPV nomenclature
NIPPV is essentially a mode of providing intermittent mandatory ventilation (IMV) using nasal prongs.28 When it is synchronized, it is referred to as synchronized NIPPV or SNIPPV. The primary mode of NIPPV refers to its use soon after birth with or without a short period (≤2 h) of intubation for surfactant delivery, followed by extubation.28 The secondary mode refers to its use following a longer period (>2 h to days to weeks) of intubation.28
NIPPV technique
The pre-surfactant era experience with NIPPV was complicated by increased gastrointestinal perforations29; hence, in the post-surfactant period, investigators used SNIPPV in the first 3 RCTs.21., 22., 23. All used the Infant Star® ventilator with the StarSync® (CareFusion, San Diego, CA) module to provide SNIPPV. Subsequent SNIPPV studies in neonates have also mostly used the same ventilator.30., 31., 32., 33., 34., 35., 36.
The SNIPPV mode of ventilation as recommended by us28 is different from
SNIPPV studies and extubation
Initial studies focused on SNIPPV used in the secondary mode (refers to its use following a period of intubation of >2 h to days to weeks).28 The main outcome measure was the duration of staying extubated. Successful extubation was defined as not requiring intubation within 72 h. A meta-analysis of the first 3 studies in the secondary mode21., 22., 23. concluded that SNIPPV was more effective than NCPAP in preventing failure of extubation [RR 0.21, 95% CI 0.10, 0.45; number needed to treat (NNT)
NIPPV studies and extubation
In one RCT using NIPPV in the secondary mode, infants were randomized to either NIPPV or NCPAP after extubation. There were no differences in the primary outcome (re-intubation within 7 days) or treatment-related complications.43 This RCT had some important limitations. Infants randomized to NIPPV had lower birth weights and body weights at time of extubation, had fewer males but more respiratory distress syndrome (RDS) and exposure to antenatal steroids. Also, infants on NIPPV were kept on the
SNIPPV studies and BPD
While the initial SNIPPV studies focused on the duration of successful extubation, some of them also reported on rates of BPD as secondary outcomes. In the largest of the 3 SNIPPV studies, the incidence of BPD was lower in the SNIPPV group, but not significantly so (53% vs. 35%; NCPAP vs. SNIPPV groups; p = 0.21).21 Similarly, in the next largest study in terms of sample size, the rates of BPD were lower in the SNIPPV group (56% vs. 44%; NCPAP vs. SNIPPV groups), but not statistically
NIPPV studies and BPD
In a RCT, infants treated initially with primary mode NIPPV (n = 43) required less invasive mechanical ventilation than infants treated with NCPAP (n = 41; 25% vs. 49%, p < 0.05). Infants in the NIPPV group had a significantly lower incidence of BPD compared with the NCPAP group (2% vs. 17%, p < 0.05, and 5% vs. 33%, p < 0.05, for infants with birth weight <1500 g).37 However, in a meta-analysis of 3 NIPPV studies (which included the study mentioned above37), there was no difference between
SNIPPV vs. NIPPV
As mentioned earlier, the phasing out of the Infant Star® ventilator (CareFusion, San Diego, CA) led to re-emergence of NIPPV. There were legitimate concerns, given the pre-surfactant experience with NIPPV, that there may be an increased rate of complications and/or impact on clinical outcomes. However, despite the loss of synchronization, use of NIPPV as per our suggested guidelines6., 28., 47. appears to continue to be beneficial to neonates. In a retrospective study, after adjusting for
Type of respiratory support and timing of extubation and BPD
In an interesting study, the mode of respiratory support (ETT, NIPPV or NCPAP) in the first week of life was correlated with the outcome of BPD/death.35 There was no difference in the mean gestational age and birth weight in the 3 groups: ETT (n = 65; 26.7 weeks; 909 g), NIPPV (n = 66; 27.1 weeks; 948 g), and NCPAP (n = 33; 27.4 weeks; 976 g). In a multivariate analysis, when compared with ETT, NIPPV (p < 0.02) and NCPAP (p < 0.01) groups were less likely to have BPD/death. Infants on ETT (n = 97)
Strategizing NIPPV use
If a specific neonatal intensive care unit practices prophylactic surfactant administration, it would appear that an early extubation to NIPPV, within 2 h if possible, would be preferred. For those centers that initiate NCPAP at birth, the data would suggest that early surfactant be administered as clinically indicated,12., 14. and subsequently the infant be extubated to NIPPV as early as possible. The data would also suggest that delaying surfactant administration by escalating the therapy (for
High flow nasal cannula (HFNC) and BPD
HFNC may be as effective as NCPAP at improving respiratory mechanics, but probably only at flow rates ≥2 L/min.49 In a recent meta-analysis, there was insufficient evidence to establish the safety or effectiveness of HFNC as a form of respiratory support in preterm infants.50 HFNC use may be associated with a higher rate of re-intubation, when compared with NCPAP.50 There was no difference in rates of BPD [RR 0.34, 95% CI 0.01–8.13].50 Additional studies are needed for improved understanding of
Nasal high frequency ventilation (NHFV)
In a small study, 14 very low-birth-weight infants, who were stable on NCPAP, were placed on NHFV (using the Infant Star®) for 2 h.51 Mean airway pressure was set to equal the previous level of NCPAP and amplitude was adjusted to obtain chest wall vibration. The investigators noted that NHFV was effective in decreasing pCO2.51 These results are similar to an earlier report.52 A significant amount of additional research needs to be done to determine the clinical utility of this technique, if any,
Conclusions
Based on the studies discussed in this article, the data favor NIPPV over NCPAP as the preferred mode of non-invasive ventilation following extubation, in neonates. It is important to realize that the efficacy of this technique can be significantly decreased if lower ventilator parameters are used.43 Given the marked variation in the ventilator settings being utilized for delivering NIPPV in various centers worldwide,25., 53., 46. use of the published guidelines is recommended.6., 28., 47.
While
Acknowledgment
The author would like to thank Mark Mercurio, MD for his critical appraisal of the manuscript.
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