Original Article

Journal of Perinatology (2003) 23, 195–199. doi:10.1038/sj.jp.7210904

Early Bubble CPAP and Outcomes in ELBW Preterm Infants

Vivek Narendran MD, MRCP (UK)1, Edward F Donovan MD1, Steven B Hoath MD1, Henry T Akinbi MD1, Jean J Steichen MD1 and Alan H Jobe MD, PhD1

1Division of Neonatology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA

Correspondence: Vivek Narendran, MD, MRCP (UK), Division of Neonatolgy, 231 Bethesda Avenue, Medical Sciences Building, ML 6158, Cincinnati, OH 45267-0541, USA



OBJECTIVE: To test whether the introduction of early bubble continuous positive airway pressure (CPAP) results in improved respiratory outcomes in extremely low birth-weight infants.

STUDY DESIGN: Outcomes of all infants between 401 and 1000 g born in a level 3 neonatal intensive care units (NICU) between July 2000 and October 2001 (period 2) were compared using historical controls (period 1). Early bubble (CPAP) was prospectively introduced in the NICU during period 1. Univariate and adjusted comparisons were made across time periods.

RESULTS: Delivery room intubations, days on mechanical ventilation and use of postnatal steroids decreased (p<0.001) in period 2, while mean days on CPAP, number of babies on CPAP at 24 hours (p<0.001) and mean weight at 36 weeks corrected gestation also increased (p<0.05) after introduction of early bubble CPAP.

CONCLUSIONS: Early bubble CPAP reduced delivery room intubations, days on mechanical ventilation, postnatal steroid use and was associated with increased postnatal weight gain with no increased complications.



In 1987, Avery et al.1 reported large site differences in the risk-adjusted incidence of bronchopulmonary dysplasia (BPD) in a group of 12 academic neonatal intensive care units (NICUs). This study first identified the Columbia approach of using "bubble continuous positive airway pressure (CPAP)" in the delivery room as a possible strategy to reduce the incidence of BPD.1 A recent comparison of outcomes between an NICU in Boston and the Columbia NICU, reinforced the apparent benefits of the Columbia approach.2

Chronic lung disease, which occurs primarily in infants less than 1000 g (the "new BPD"), is thought to have a qualitatively different pathogenesis than the traditional BPD described by Northway et al.3 Traditional BPD has a pathogenesis dominated by hyperoxic baro/volutrauma in surfactant deficient lungs, while the new BPD has a pathogenesis dominated by immaturity and alveolar hypoplasia. Recent evidence attributes these changes to prenatal (chorioamnionitis) and postnatal proinflammatory mediators (ventilator-induced lung injury), which are known to influence both lung development and lung injury.4

Several recent epidemiologic studies have demonstrated a decreased incidence of BPD by avoiding intubation in the delivery room and using early (CPAP).5,6 There is little experimental information as to the mechanism whereby CPAP might minimize lung injury in a preterm lung. There is one study demonstrating decreased indicators of acute lung injury using bubble CPAP in a preterm lamb model.7 Furthermore, there is a paucity of data regarding differences in gas exchange effectiveness between conventional and bubble CPAP systems. Bubble CPAP is a form of oscillatory pressure delivery in which mechanical vibrations are transmitted into the chest secondary to the nonuniform flow of gas bubbles across a downstream water seal. This system results in waveforms similar to those produced by high-frequency ventilation when recorded by a transducer attached to the infant's airway.8

At present, there are no definitive studies and no clinical consensus about the best approach to minimize ventilator-associated lung injury in extremely low birth-weight (ELBW) infants. Strategies vary from early delivery room surfactant administration and intermittent mandatory ventilation to early delivery room CPAP with or without pretreatment with surfactant.9

The primary objective of this study was to test whether the introduction of early bubble CPAP in the delivery room was safe and resulted in improved respiratory outcomes in ELBW. We defined safety as improved respiratory outcomes without an increase in mortality and nonpulmonary morbidities such as IVH and NEC. These outcomes along with growth parameters were monitored on a regular basis. Risk-adjusted comparisons of care and outcomes of infants during the two time periods were made.



The study population comprised all infants with birth weights between 401 and 1000 g, born at a neonatal tertiary care unit in Cincinnati, OH, between 1 July 2000 and 10th October 2001 (period 2). These infants were compared to historical controls (period 1) born between 1 January 1998 and 31st December 1999. The same group of neonatologists provided care in both periods. The neonatal unit was part of the NICHD Neonatal Research Network, and had extensive data collected prospectively throughout the two time periods.

The NICHD Neonatal Research Network is a consortium of tertiary neonatal centers.10 The network maintains a registry of all very low birth-weight (VLBW) infants (401–1500 g) born and/or admitted to participating centers within 14 days of birth. This registry was developed to describe the populations at each participating center, to survey neonatal practice, to assess morbidity and mortality rates, and to provide information for the planning of randomized clinical trials. Trained research nurses collect maternal demographic, pregnancy and delivery data soon after birth and infant data until 120 days, discharge, or death.

In period 1, infants were managed with intermittent positive pressure ventilation with bag and mask in the delivery room, early intubation, surfactant administration and intermittent mandatory ventilation for infants with moderate-to-severe respiratory distress syndrome. CPAP was not used in the delivery room and CPAP was rarely introduced in the early management of RDS compared to intubation and surfactant administration. FiO2 was adjusted based on transcutaneous PaO2 or arterial PaO2 from an indwelling arterial catheter. No new major technologies or clinical practice guidelines were introduced in the intensive care units during the two study periods.

In period 2, the neonatologists prospectively introduced routine, early, bubble nasal CPAP in the delivery room modeling closely the Columbia method. Hudson nasal prongs were used to initiate bubble CPAP immediately after the initial steps of drying and stimulation in all spontaneously breathing infants (Figure 1). The bubble CPAP circuit was very similar to conventional CPAP except that the expiratory seal is an 'underwater seal' in the former compared to a mechanical device in the latter (Figure 2). The depth of immersion (5 cm) of the expiratory limb in 25% acetic acid determined the level of CPAP provided (5 cm of water). This was maintained constant during the study.

Figure 1.
Figure 1 - Unfortunately we are unable to provide accessible alternative text for this. If you require assistance to access this image, please contact help@nature.com or the author

Premature infant in incubator on bubble CPAP.

Full figure and legend (156K)

Figure 2.
Figure 2 - Unfortunately we are unable to provide accessible alternative text for this. If you require assistance to access this image, please contact help@nature.com or the author

Schematic diagram of bubble CPAP circuit.

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Infants were electively intubated and given Survanta® (Ross Abbott Laboratories, OH), when FiO2 was greater than 60% to maintain saturations between 92 and 96%, pH <7.15, or PCO2 >65. FiO2 was commonly adjusted using pulse oximetry to maintain saturations between 92 and 96% and indwelling arterial catheters were used sparingly. Ventilated infants were weaned aggressively and extubated back to CPAP as early as possible. Infants were monitored for neonatal morbidities for a period of 120 days unless discharged or transferred to another hospital.

Statistical Analysis

Data were retrospectively analyzed by chi2-test and continuous t-test for comparisons between the two time periods and expressed as proportions. Results were considered to be statistically significant for p<0.05.



Demographic characteristics did not differ during the two study periods (Table 1). When compared to period 1, after initiation of early bubble CPAP, delivery room intubations, days on mechanical ventilation and postnatal steroid use decreased (Table 2). Infants on CPAP at 24 hours and number of days on CPAP also increased (Table 2). Mean weight at 36 weeks corrected gestational age increased (Table 1). Chronic lung disease defined as oxygen requirement at 36 weeks corrected gestational age tended to decrease but was not statistically significant. Mean length and head circumference at 36 weeks corrected gestational age tended to increase. Other nonpulmonary morbidities tended to decrease except PDA (Table 1). There were three infants with septal erosions, which resolved spontaneously and required no surgical intervention. No infant in period 2 developed a pneumothorax.



CPAP has been used primarily to treat surfactant deficiency in preterm infants for many years.11 Particular interest in CPAP focuses on its potential role to reduce ventilator-induced lung injury and BPD. The mechanisms responsible for the possible effects of CPAP to decrease BPD have not yet been evaluated. One postulated mechanism is the avoidance of aggressive initiation of intermittent positive pressure ventilation with high tidal volumes and inadvertent hyperventilation/under ventilation that occurs in ventilated infants.12 CPAP also protects the airway from mechanical injury and bacterial colonization related to the endotracheal tube.

CPAP putatively increases both functional residual capacity and endogenous respiratory drive leading to decreased delivery room intubations, reintubations and days on mechanical ventilation.12,13 CPAP has been associated with decreased BPD in several clinical reports.14,15,16 Multivariate regression analysis has shown intubation and mechanical ventilation of preterm infants to be the single most important predictor of subsequent BPD.2

The controversy of early vs delayed CPAP continues as many of the trials favoring early CPAP were carried out in the larger infants prior to routine use of antenatal steroids and postnatal surfactant.17 The evidence suggesting decreased mechanical ventilation and increased exogenous surfactant use with early CPAP and brief ventilation in ELBW is from one small randomized clinical trial.18 There are no studies as yet comparing the role of early surfactant administration with brief ventilation and extubation to nasal CPAP vs selective surfactant use with continued mechanical ventilation for ELBW preterm infants at risk for RDS. Additional randomized trials are needed and are underway.19

There are practical concerns regarding the implementation of early CPAP in the delivery room. Preterm infants allowed to breathe spontaneously with nasal prongs will not 'pink up' as rapidly and PCO2 values will be higher than tolerated by most clinicians previously. The decision point of when to intervene is imprecise and depends on experience and constant vigilance. Secondly, the safety of permissive hypercapnia has to be accepted.20 Although high PCO2 levels may decrease lung injury,21 safe upper values for PCO2 have not been determined for preterm infants. Long-term follow-up of infants treated with permissive hypercapnia are now being reported and appear to be safe.22 Thirdly, the prolonged use of CPAP delivered by nasal prongs can lead to nasal septal erosions and abnormal head molding that can complicate clinical management.

In this study, we evaluated early delivery room CPAP on babies at highest risk for developing BPD; that is, infants with birth weight less than 1000 g. Two time periods were compared where the only change in the later period was the introduction of early bubble CPAP. We compared respiratory outcomes using bubble CPAP to test if results from Columbia were reproducible and if their success in reducing the incidence of BPD was related to their use of 'bubble CPAP'. We used a similar system as used by Dr. Jen-Tien Wung at Columbia.23

The clinical population studied was demographically stable and well defined. A single group of neonatologists cared for these infants during both periods. Our data were collected prospectively as part of the NIH Neonatal Network to monitor safety. Drawbacks of the study were that it was not a randomized controlled trial and used historical controls.

In this study, the use of early bubble CPAP significantly decreased delivery room intubations, use of postnatal steroids and days on mechanical ventilation. Similar results were reported in larger infants (1000–1499 g) from the group in South Auckland, New Zealand24 after starting nasal CPAP closely modeled after the Columbia method. When compared to historical controls, the number of infants ventilated (65 vs 14%), median days of ventilation (6 vs 2 days) and chronic lung disease at 28 days of life (11 vs 0%) decreased. However, when CLD was defined as any form of respiratory support at 36 weeks gestation there was no difference between the groups. Nonrespiratory outcomes such as NEC, time to full feeds, and the average length of stay tended to decrease, without any additional morbidity.

The role of bubble CPAP in decreasing postnatal steroid use is unclear. Whether this represents a true causal effect or an association is unclear. Emerging literature during the time frame of the study increasingly linked postnatal steroids with poor neurodevelopmental outcome, which could have changed clinical practice.

Opponents of bubble CPAP suggest that infants may not gain weight adequately in a relatively 'hypercarbic' environment. In addition, nonrespiratory outcomes such as weight, height and head circumference at 36 weeks corrected gestation have not been previously reported for infants managed with bubble CPAP. In our study, infants exhibited significantly increased weight gain following institution of early bubble CPAP.

In summary, we found that early bubble CPAP when begun in the delivery room was safe, inexpensive and an effective way to avoid intubations in the delivery room. Randomized control trials are needed to definitely demonstrate beneficial effects on BPD and neurodevelopmental outcomes.



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