Nasal respiratory support through the nares: its time has come

Journal of Perinatology (2010) 30, S67–S72 r 2010 Nature America, Inc. All rights reserved. 0743-8346/10 www.nature.com/jp REVIEW Nasal respiratory support through the nares: its time has come R Ramanathan Division of Neonatal Medicine, Department of Pediatrics, Los Angeles County þ University of Southern California Medical Center and Childrens Hospital Los Angeles, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA Respiratory distress syndrome (RDS) is the most common respiratory morbidity in preterm infants. Surfactant therapy and invasive mechanical ventilation through the endotracheal tube (ETT) have been the cornerstones in RDS management. Despite improvements in the provision of mechanical ventilation, bronchopulmonary dysplasia (BPD), a multifactorial disease in which invasive mechanical ventilation is a known contributory factor, remains an important cause of morbidity among preterm infants. Barotrauma, volutrauma or oxygen-induced lung inflammation (oxy-trauma) contributes significantly to the development of BPD in neonates ventilated through an ETT. Recently, nasal respiratory support has been increasingly used in preterm infants in an attempt to decrease post-extubation failure and, perhaps, BPD, and for the treatment of apnea of prematurity in nonventilated neonates. Observational studies using noninvasive respiratory support, such as nasal continuous positive airway pressure (NCPAP), have shown a decrease in the incidence of BPD when used to avoid intubation or minimize the duration of invasive mechanical ventilation through the ETT. Moreover, synchronized as well as nonsynchronized nasal intermittent positive-pressure ventilation (NIPPV) have been shown to significantly decrease post-extubation failure compared with NCPAP and their use has been associated with a reduced risk of BPD in small randomized controlled clinical trials. More recently, early surfactant administration followed by extubation to NIPPV has been suggested to be synergistic in decreasing BPD. Although these findings are promising, additional studies evaluating different nasal interfaces, flow synchronization, synchronization using neurally adjusted ventilatory assist mode, and closed loop control of oxygen during nasal ventilation to minimize lung injury are needed in an attempt to further decrease the incidence of lung injury in preterm neonates requiring respiratory support. Journal of Perinatology (2010) 30, S67–S72; doi:10.1038/jp.2010.99 Keywords: mechanical ventilation; nasal ventilation; NCPAP; NIPPV; BPD Correspondence: Professor R Ramanathan, Division of Neonatal Medicine, Department of Pediatrics, Los Angeles County þ University of Southern California Medical Center and Childrens Hospital Los Angeles, Keck School of Medicine, University of Southern California, 1200, North State Street, IRD-Building-Room 820, Los Angeles, CA 90033, USA. E-mail: This paper resulted from the Evidence vs. Experience in Neonatal Practices Conference, 19 to 20 June 2009, sponsored by Dey LP. Introduction Respiratory failure requiring mechanical ventilation is a very frequent presentation in preterm infants admitted to the neonatal intensive care unit (NICU). Surfactant administration followed by invasive mechanical ventilation using an endotracheal tube (ETT) in preterm infants with respiratory distress syndrome (RDS) has become the standard of care. However, invasive ventilation through the ETT is independently associated with an increased risk for the development of bronchopulmonary dysplasia (BPD) in about one-third of very low birth weight infants (birth weight <1500 g). Indeed, the incidence of clinical BPD, defined as oxygen requirement at 36 weeks of postmenstrual age in preterm infants with a birth weight <1250 g, was about 35%, with large center to center variations.1 To standardize the definition of BPD and minimize center to center variations in the reported incidence of BPD among different centers, a physiological definition for BPD, based on a timed room air challenge at 36±1 weeks of gestation was proposed by Walsh et al.1 Incidence of physiological BPD was about 25% and use of this definition for BPD reduced the variation among centers. Despite the increased use of antenatal corticosteroids2,3 and improved invasive ventilation techniques, the incidence of BPD has not decreased. This is important, as BPD is associated with short- as well as long-term pulmonary and nonpulmonary morbidities. Injury to the developing lung results from the interaction between a susceptible host and a number of contributing factors, such as mechanical ventilation, oxygen toxicity and specific and nonspecific inflammation. Preterm infants are at greater risk because they have increased pulmonary epithelial and capillary permeability, immature antioxidant defenses and immune responses compared with term newborns. BPD is considered as an inflammatory lung disease in which the injury often is initiated at birth4 or even before birth in infants born to mothers with chorioamnionitis,5 and as mentioned above, is triggered by several factors, including positive-pressure ventilation through the ETT, supplemental oxygen and postnatal inflammation.6 Decreased production of anti-inflammatory cytokines, such as interleukin (IL)-10, and relative adrenal insufficiency have also been suggested to contribute to the prolonged proinflammatory state of preterm neonates who develop BPD. In addition to lung inflammation, the presence of Nasal ventilation in preterm infants R Ramanathan S68 a persistent patent ductus arteriosus has been associated with a higher incidence of BPD.7 The concept that the interplay between inflammation and patent ductus arteriosus contributes to the pathogenesis of BPD has been supported by the observation that the presence of IL-6 in tracheal aspirate at birth and persistent patent ductus arteriosus additively predict the risk of BPD.8 Invasive positive-pressure ventilation with its resultant barotrauma and volutrauma from using tidal volume ventilation has also been shown to be an important contributing factor. However, meta-analysis of studies comparing tidal ventilation versus nontidal volume ventilation showed no significant difference in BPD when an optimal lung volume strategy was used.9 On the basis of these data, targets for decreasing the incidence of BPD include reducing oxygen exposure, minimizing lung infection and inflammation, and avoiding ventilator-associated lung injury. Focus on decreasing the use of invasive mechanical ventilation through the ETT has led to a renewed interest in noninvasive, nasal ventilation in preterm infants. Nasal ventilation Nasal respiratory support through the nares has been in use since the early 1970s. Gregory et al.10 first reported the use of continuous positive airway pressure (CPAP) using the so-called Gregory box to treat RDS. Although CPAP gained a more widespread acceptance in the early 1980s, advances in (...truncated)