We hypothesize that the success rate for keeping babies extubated (without a breathing tube for assisted mechanical ventilation), defined as the proportion of infants remaining extubated for a minimum of 72 hours, will be equivalent among infants managed with nasal CPAP compared to humidified high flow nasal cannula (HHFNC).
Respiratory failure remains a common problem in the neonatal ICU. Among premature infants with respiratory failure the use of mechanical ventilation has been associated with increased risk for secondary lung injury and subsequent development of bronchopulmonary dysplasia (BPD). As reported by Avery et al and Van Marter et al, early application of nasal continuous positive airway pressure (nCPAP) has been shown as an effective non-invasive mode of respiratory support in this population.(1, 2) Additionally, in the premature sheep and baboon models of BPD, the early use of nCPAP is accompanied by significant improvement in subsequent lung development and alveolization.(3) In light of these findings, there has been a concerted effort in most NICU's to avoid prolonged ventilator support through the early application of nCPAP. Unfortunately, nCPAP systems are not always easily applied or tolerated in the preterm population. Difficulties with the application of nCPAP include bulky head wraps, positional problems, compression of the nose, marked dilation and tissue breakdown of the nares, and apparent agitation, often leading to the use of potentially neurotoxic medications.(4) Previous studies have suggested that NC flows at 1-2 lpm may also generate a positive pressure in the airway of preterm infants.(5) The use of NC flow to generate positive airway pressure would minimize many of the application issues of nCPAP. However, standard NC systems used in neonates routinely employ gas that is inadequately warmed and humidified, limiting the use of such flows due to increased risk of nasal mucosa injury, and possibly increasing the risk for nosocomial infection.(4, 6) The development of humidified high flow via nasal cannulas (HHFNC) systems may obviate these problems and provide a safe, effective alternative to nCPAP in the preterm infant. Unfortunately, HHFNC does not allow the measurement of distending pressure without an invasive process such as an esophageal pressure catheter. Two recent reports have suggested that HHFNC does not provide excessive distending pressure.(7, 8) The study by Saslow and colleagues found that work of breathing and lung compliance were improved in preterm infants on HHFNC up to a maximum of 5 lpm compared to nCPAP at 6 cm H2O.(7) In comparison to nCPAP, the maximum positive distending pressure measured was 4.8 cm H2O and was not significantly increased with HHFNC flows up to 5 lpm. Kubicka and colleagues also demonstrated that the maximum distending pressure measured during support with HHFNC up to 8 lpm was \< 5 cm H2O.(8) A recent publication has suggested that HHFNC can safely and effectively be applied in the non-invasive respiratory management of premature infants with respiratory dysfunction.(9) In this retrospective analysis evaluating over 1000 infants, Shoemaker et al reported a significant decrease in ventilator days among the group of infants managed with HHFNC compared to infants previously managed with nCPAP. Additionally, they found no increased adverse effects noted such as air leak, intraventricular hemorrhage, nosocomial infection or BPD. In a smaller prospective study, Campbell et al did not find a benefit from high-flow NC among a group 40 infants \< 1250 grams.(10) However, they did not use adequate humidification and the maximum "high-flow" applied was \< 2 lpm. The previously noted study by Woodhead et al demonstrated that HHFNC decreased respiratory work effort and was more effective at preventing reintubation than high-flow from a standard, non-heated, non-humidified nasal cannula.(4) Thus HHFNC, with flow rates as high as 8 lpm, is being used clinically in a large number of NICU's, including all of the units participating in this study, for management of a variety of neonatal respiratory problems. The introduction of HHFNC into clinical practice has not been accompanied by apparent changes in neonatal outcome, but this has not been systematically studied in a randomized, controlled approach. The purpose of this randomized controlled trial is to evaluate the clinical impact of applying HHFNC to that of nCPAP among a group of infants requiring continuing non-invasive respiratory support in the NICU.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
420
Infants randomized to the Standard nasal CPAP via "bubble" or ventilator support at levels of 4-8 cm H2O post extubation
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, United States
Wilford Hall Medical Center
Lackland Air Force Base, Texas, United States
McKay-Dee Medical Center
Ogden, Utah, United States
Utah Valley Regional Medical Center
Compare extubation success rate, defined as % infants remaining extubated for > 72 hrs, among infants managed with HHFNC versus nCPAP
Time frame: 72 hrs
Compare frequency of significant apnea after extubation to HHFNC v CPAP
Time frame: 7 days
Compare total duration of ventilator, positive pressure (CPAP and/or HHFNC), and oxygen use up to the time of discharge from the NICU
Time frame: 3 months
Compare incidence of potential adverse effects associated with the use of nasal CPAP and HHFNC including pulmonary air leaks, nasal deformities, feeding intolerance, necrotizing enterocolitis, intestinal perforation and BPD
Time frame: 3 months
Compare weight gain and the time to establish full enteral feeds (> 120 ml/kg/d) between infants on HHFNC v CPAP
Time frame: 3 months
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.
Provo, Utah, United States
Primary Children's Medical Center
Salt Lake City, Utah, United States
University Hospital
Salt Lake City, Utah, United States
Intermountain Medical Center
Salt Lake City, Utah, United States
Dixie Medical Center
St. George, Utah, United States
Hebei Provincial Children's Hospital
Shijiazhuang, China